Investigative Radiology,https://journals.lww.com/investigativeradiology/pages/default.aspx

7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How ...

7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How Does Spatial Resolution Affect the Detectability of...

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the...

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted

Reduction of Metal Artifacts and Improvement in Dose Efficiency Using...

Reduction of Metal Artifacts and Improvement in Dose Efficiency Using Photon-Counting Detector Computed Tomography and Tin...

April 2019: Val M. Runge, MD, a note from the Editor

This issue of the journal, as always, has many outstanding articles, representing cutting edge research and technology in diagnostic imaging. A study at 7 T demonstrates the utility at that field strength for increased spatial resolution in spectroscopy for the evaluation of multiple sclerosis lesions. A second excellent article explores visualization of the glymphatic system (CSF microcirculation) on MR following IV administration of gadolinium-based contrast agents. A third article describes advances in reduction of metal artifacts and improvement in dose efficiency using photon-counting detector CT in combination with tin filtration. The remaining papers explore important advances in tomoelastography, prostate imaging (specifically DWI), and T1- and T2*-mapping, as well as assessing robustness and reproducibility in Radiomics and adverse events with gadolinium chelate administration.

Current Issue Highlights

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A Structured Survey on Adverse Events Occurring Within 24 Hours After Intravenous Exposure to Gadodiamide or Gadoterate Meglumine: A Controlled Prospective Comparison Study

Parillo, Marco; Sapienza, Martina; Arpaia, Francesco; More

Investigative Radiology. 54(4):191-197, April 2019.

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Objective

This study compares the incidence of new-onset symptoms within 24 hours after enhanced magnetic resonance imaging (eMRI) with intravenous administration of gadodiamide or gadoterate meglumine compared with a control group undergoing unenhanced MRI (uMRI).

Materials and Methods

A prospective cohort study (n = 1088 patients) was designed to assess the incidence of symptoms within 24 hours after administration of gadodiamide or gadoterate meglumine. The participants underwent a structured questionnaire by phone call before and 24 hours after the MRI scan to check for symptoms that were not present before the scan. The questionnaire included a list of active questions aimed to test the prevalence of symptoms that have been proposed in the debated definition of gadolinium deposition disease (GDD) and that we recorded in this study as GDD-like. In particular, the following symptoms and signs were tested: central torso pain, arm or leg pain, bone pain, headache, skin redness (any site of the body), fatigue, and mental confusion.

Fisher exact test was used to test differences between groups with significance threshold set at P < 0.05.

Results

Within the 24 hours after the MRI scan, 8.3% of patients reported at least one new-onset symptom in the uMRI group versus 17.4% in the gadodiamide eMRI versus 17.8% in the gadoterate meglumine eMRI group. The difference between the eMRI and the uMRI group was statistically significant ( P < 0.001 for gadodiamide and P < 0.001 for gadoterate meglumine). There was not a different incidence of symptoms between the gadodiamide and the gadoterate meglumine eMRI groups. For gadodiamide, fatigue ( P < 0.05) and dizziness ( P < 0.05) were symptoms significantly more frequent than uMRI group; for gadoterate meglumine, fatigue ( P < 0.01), mental confusion ( P < 0.01), and diarrhea ( P < 0.01) were significantly more frequent than uMRI group.

Conclusions

We found that the onset of new symptoms within 24 hours after exposure to gadolinium-based contrast agent was more frequent than after uMRI. Among GDD-like symptoms, fatigue and mental confusion were the most frequent symptoms reported after eMRI. The other GDD-like symptoms were not overreported after eMRI versus uMRI. Thus, these results are questioning the term GDD.

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Tomoelastography for the Evaluation of Pediatric Nonalcoholic Fatty Liver Disease

Hudert, Christian A.; Tzschätzsch, Heiko; Rudolph, Birgit; More

Investigative Radiology. 54(4):198-203, April 2019.

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Objectives

Today, nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults alike. Yet, the noninvasive evaluation of disease severity remains a diagnostic challenge. In this study, we apply multifrequency magnetic resonance elastography (mMRE) for the quantification of liver steatosis and fibrosis in adolescents with NAFLD.

Methods

Fifty adolescents (age range, 10–17 years; mean BMI, 33.9 kg/m 2 ; range, 21.4–42.1 kg/m 2 ) with biopsy-proven NAFLD were included in this prospective study. Multifrequency magnetic resonance elastography was performed using external multifrequency vibrations of 30 to 60 Hz and tomoelastography postprocessing, resulting in penetration rate ( a ) and shear wave speed ( c ). Hepatic fat fraction was determined using Dixon method. The diagnostic accuracy of mMRE in grading liver steatosis and staging liver fibrosis was assessed by receiver operating characteristic curve analysis.

Results

Multifrequency magnetic resonance elastography parameters c and a were independently sensitive to fibrosis and steatosis, respectively, providing area under the receiver operating characteristic values of 0.79 (95% confidence interval [CI], 0.66–0.92), 0.91 (95% CI, 0.83–0.99), and 0.90 (95% CI, 0.80–0.99) for the detection of any (≥F1), moderate (≥F2), and advanced (≥F3) fibrosis, and 0.87 (95% CI, 0.76–0.97) and 0.87 (95% CI, 0.77–0.96) for the detection of moderate (≥S2) and severe (S3) steatosis.

Conclusions

One mMRE measurement provides 2 independent parameters with very good diagnostic accuracy in detecting moderate and advanced fibrosis as well as moderate and severe steatosis in pediatric NAFLD.

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SDC

Reduction of Metal Artifacts and Improvement in Dose Efficiency Using Photon-Counting Detector Computed Tomography and Tin Filtration

Zhou, Wei; Bartlett, David J.; Diehn, Felix E.; More

Investigative Radiology. 54(4):204-211, April 2019.

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Objectives

The aim of this study was to investigate the impact on metal artifacts and dose efficiency of using a tin filter in combination with high-energy threshold (TH) images of a photon-counting detector (PCD) computed tomography (CT) system.

Materials and Methods

A 3D-printed spine with pedicle screws was scanned on a PCD-CT system with and without tin filtration. Image noise and severity of artifacts were measured for low-energy threshold (TL) and TH images. In a prospective, institutional review board–approved, Health Insurance Portability and Accountability Act-compliant study, 20 patients having a clinical energy-integrating detector (EID) CT were scanned on a PCD-CT system using tin filtration. Images were reviewed by 3 radiologists to evaluate visualization of anatomic structures, diagnostic confidence, and image preference. Artifact severity and image noise were measured. Wilcoxon signed rank was used to test differences between PCD-CT TH and EID-CT images.

Results

Phantom TH images with tin filtration reduced metal artifacts and had comparable noise (32 HU) to TL images (29 HU) acquired without tin filtration. Visualization scores for the cortex, trabeculae, and implant-trabecular interface from PCD-CT TH images (4.4 ± 0.9, 4.4 ± 1.0, and 4.4 ± 1.0) were significantly higher ( P < 0.0001) than EID-CT images (3.3 ± 1.3, 3.3 ± 1.2, and 3.3 ± 1.6). A strong preference was shown for PCD-CT TH images due to improved diagnostic confidence and decreased artifact severity. Noise in PCD-CT TH images (93 ± 41 HU) was significantly lower than that in EID-CT images (133 ± 92 HU, P < 0.05).

Conclusions

Threshold high images acquired with tin filtration on PCD-CT demonstrated a substantial decrease in metal artifacts and an increase in dose efficiency compared with EID-CT.

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SDC

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties: A Phantom MRI Study

Bachmann, Elias; Rosskopf, Andrea B.; Götschi, Tobias; More

Investigative Radiology. 54(4):212-220, April 2019.

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Objectives

The aim of this study was to quantitatively assess changes in collagen structure using MR T1- and T2*-mapping in a novel controlled ex vivo tendon model setup.

Materials and Methods

Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*- and T1-mapping, respectively. Standard T1- and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis.

Results

T1- and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties ( r = −0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons.

Conclusions

T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology.

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Robustness and Reproducibility of Radiomics in Magnetic Resonance Imaging: A Phantom Study

Baeßler, Bettina; Weiss, Kilian; Pinto dos Santos, Daniel

Investigative Radiology. 54(4):221-228, April 2019.

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Objectives

The aim of this study was to investigate the robustness and reproducibility of radiomic features in different magnetic resonance imaging sequences.

Materials and Methods

A phantom was scanned on a clinical 3 T system using fluid-attenuated inversion recovery (FLAIR), T1-weighted (T1w), and T2-weighted (T2w) sequences with low and high matrix size. For retest data, scans were repeated after repositioning of the phantom. Test and retest datasets were segmented using a semiautomated approach. Intraobserver and interobserver comparison was performed. Radiomic features were extracted after standardized preprocessing of images. Test-retest robustness was assessed using concordance correlation coefficients, dynamic range, and Bland-Altman analyses. Reproducibility was assessed by intraclass correlation coefficients.

Results

The number of robust features (concordance correlation coefficient and dynamic range ≥ 0.90) was higher for features calculated from FLAIR than from T1w and T2w images. High-resolution FLAIR images provided the highest percentage of robust features (n = 37/45, 81%). No considerable difference in the number of robust features was observed between low- and high-resolution T1w and T2w images (T1w low: n = 26/45, 56%; T1w high: n = 25/45, 54%; T2 low: n = 21/45, 46%; T2 high: n = 24/45, 52%). A total of 15 (33%) of 45 features showed excellent robustness across all sequences and demonstrated excellent intraobserver and interobserver reproducibility (intraclass correlation coefficient ≥ 0.75).

Conclusions

FLAIR delivers the most robust substrate for radiomic analyses. Only 15 of 45 features showed excellent robustness and reproducibility across all sequences. Care must be taken in the interpretation of clinical studies using nonrobust features.

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SDC

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted

Deike-Hofmann, Katerina; Reuter, Julia; Haase, Robert; More

Investigative Radiology. 54(4):229-237, April 2019.

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Background

The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo.

Methods

Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system.

Findings

Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown.

Interpretation

Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

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Accelerated Segmented Diffusion-Weighted Prostate Imaging for Higher Resolution, Higher Geometric Fidelity, and Multi-b Perfusion Estimation

Aksit Ciris, Pelin; Chiou, Jr-yuan George; Glazer, Daniel I.; More

Investigative Radiology. 54(4):238-246, April 2019.

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Purpose

The aim of this study was to improve the geometric fidelity and spatial resolution of multi-b diffusion-weighted magnetic resonance imaging of the prostate.

Materials and Methods

An accelerated segmented diffusion imaging sequence was developed and evaluated in 25 patients undergoing multiparametric magnetic resonance imaging examinations of the prostate. A reduced field of view was acquired using an endorectal coil. The number of sampled diffusion weightings, or b -factors, was increased to allow estimation of tissue perfusion based on the intravoxel incoherent motion (IVIM) model. Apparent diffusion coefficients measured with the proposed segmented method were compared with those obtained with conventional single-shot echo-planar imaging (EPI).

Results

Compared with single-shot EPI, the segmented method resulted in faster acquisition with 2-fold improvement in spatial resolution and a greater than 3-fold improvement in geometric fidelity. Apparent diffusion coefficient values measured with the novel sequence demonstrated excellent agreement with those obtained from the conventional scan ( R 2 = 0.91 for b max = 500 s/mm 2 and R 2 = 0.89 for b max = 1400 s/mm 2 ). The IVIM perfusion fraction was 4.0% ± 2.7% for normal peripheral zone, 6.6% ± 3.6% for normal transition zone, and 4.4% ± 2.9% for suspected tumor lesions.

Conclusions

The proposed accelerated segmented prostate diffusion imaging sequence achieved improvements in both spatial resolution and geometric fidelity, along with concurrent quantification of IVIM perfusion.

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7 T Magnetic Resonance Spectroscopic Imaging in Multiple Sclerosis: How Does Spatial Resolution Affect the Detectability of Metabolic Changes in Brain Lesions?

Heckova, Eva; Strasser, Bernhard; Hangel, Gilbert J.; More

Investigative Radiology. 54(4):247-254, April 2019.

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Objectives

The aim of this study was to assess the utility of increased spatial resolution of magnetic resonance spectroscopic imaging (MRSI) at 7 T for the detection of neurochemical changes in multiple sclerosis (MS)–related brain lesions.

Materials and Methods

This prospective, institutional review board–approved study was performed in 20 relapsing-remitting MS patients (9 women/11 men; mean age ± standard deviation, 30.8 ± 7.7 years) after receiving written informed consent. Metabolic patterns in MS lesions were compared at 3 different spatial resolutions of free induction decay MRSI with implemented parallel imaging acceleration: 2.2 × 2.2 × 8 mm 3 ; 3.4 × 3.4 × 8 mm 3 ; and 6.8 × 6.8 × 8 mm 3 voxel volumes, that is, matrix sizes of 100 × 100, 64 × 64, and 32 × 32, respectively. The quality of data was assessed by signal-to-noise ratio and Cramér-Rao lower bounds. Statistical analysis was performed using Wilcoxon signed-rank tests with correction for multiple testing.

Results

Seventy-seven T2-hyperintense MS lesions were investigated (median volume, 155.7 mm 3 ; range, 10.8–747.0 mm 3 ). The mean metabolic ratios in lesions differed significantly between the 3 MRSI resolutions (ie, 100 × 100 vs 64 × 64, 100 × 100 vs 32 × 32, and 64 × 64 vs 32 × 32; P < 0.001). With the ultra-high resolution (100 × 100), we obtained 40% to 80% higher mean metabolic ratios and 100% to 150% increase in maximum metabolic ratios in the MS lesions compared with the lowest resolution (32 × 32), while maintaining good spectral quality (signal-to-noise ratio >12, Cramér-Rao lower bounds <20%) and measurement time of 6 minutes. There were 83% of MS lesions that showed increased myo -inositol/ N -acetylaspartate with the 100 × 100 resolution, but only 66% were distinguishable with the 64 × 64 resolution and 35% with the 32 × 32 resolution.

Conclusions

Ultra-high-resolution MRSI (~2 × 2 × 8 mm 3 voxel volume) can detect metabolic alterations in MS, which cannot be recognized by conventional MRSI resolutions, within clinically acceptable time.

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SDC

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Rapid Diffusion-Weighted Magnetic Resonance Imaging of the Brain Without Susceptibility Artifacts: Single-Shot STEAM With Radial Undersampling and Iterative Reconstruction: Erratum

Investigative Radiology. 54(4):255, April 2019.

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Cancer

What's new at the Indian Journal of Cancer? Indian Journal of Cancer 2019 56(1):1-1

Testing alternate biochemotherapy combinations in recurrent/metastatic head and neck cancer - Putting the best foot forward HS Darling Indian Journal of Cancer 2019 56(1):2-3

Biweekly cetuximab in combination with platinum and 5-fluorouracil in metastatic head and neck carcinoma Zeki G Surmeli, Ahmet Ozveren, Cagatay Arslan, Mustafa Degirmenci, Burcak Karaca, Ruchan Uslu Indian Journal of Cancer 2019 56(1):4-8 Background and Aim: The combination of cetuximab with platinum and 5-fluorouracil (5-FU) chemotherapy prolongs survival in patients with metastatic or recurrent squamous-cell carcinoma of the head and neck (SCCHN). Biweekly (once in 2 weeks) administration of cetuximab requires fewer hospital visits and decreases treatment costs; therefore, it is more convenient both for the patients and for the healthcare providers. Here, we assessed the efficacy, safety, and tolerability of an alternative biweekly regimen of cetuximab in combination with platinum and 5-FU chemotherapy as a first-line treatment for these patients. Methods and Materials: Medical records of patients with metastatic or recurrent non-nasopharyngeal SCCHN who were treated with a biweekly regimen of cetuximab (500 mg/m2 on day 1), cisplatin (40 mg/m2 on day 1) or carboplatin (target area under the curve 3.5 mg/ml × min on day 1), folinic acid (400 mg/m2 on day 1), and 5-FU (400 mg/m2 bolus on day 1 followed by continuous infusion of 2,400 mg/m2 5-FU over 46 h) were retrospectively reviewed. Survival estimates were calculated with the Kaplan–Meier method. Results: In total, 60 patients were included. The median age of the patients was 60.5. The objective response rate was 53.3% (95% confidence interval [CI] = 40.7–65.9). The median progression-free survival duration was 6.8 months (95% CI = 5.5–8.1) and the median overall survival duration was 13.3 months (95% CI = 8.4–18.2). The most common grade 3 or 4 adverse events were neutropenia (28.3%) and leucopenia (13.3%). Grade 3 or 4 rash was observed in 3.3% of the patients. Conclusion: Biweekly administration of cetuximab, cisplatin, and 5-FU is an effective regimen with a favorable toxicity profile for the first-line treatment of metastatic or recurrent SCCHN. These results warrant further evaluation of this regimen in prospective trials.

Oncological outcome following TORS in HPV negative supraglottic carcinoma Surender Dabas, Karan Gupta, Reetesh Ranjan, Ashwani K Sharma, Himanshu Shukla Indian Journal of Cancer 2019 56(1):9-14 Objective: The aim of this study was to determine the oncological and functional outcomes following transoral robotic surgery (TORS) in human papilloma virus negative supraglottic cancers. Study Design: A prospective observational study at a tertiary cancer care center, New Delhi, India. Materials and Methods: From February, 2013 to December, 2015, 45 patients with supraglottic lesions underwent TORS using the da Vinci® surgical system. Results: Forty-five patients underwent TORS for supraglottic laryngectomy (SGL), with all patients undergoing bilateral neck dissection. The most common site was Ary-epiglottic fold. 47.9% were cT1 and 52.1% were cT2. Average robotic set-up time was 8.8 min and average robotic operative time was 42.9 min. A positive or close margin was seen in 12 patients (26.7%) on frozen, which were revised intraoperatively. On final histology, 3 (6.7%) patients had a margin of <5 mm. The average closest margin was 5.7 mm. Patients tolerated oral feeds within 2 weeks of procedure. All patients were HPV negative. Postoperatively, all patients had adequate swallowing and speech. Follow-up ranged from 24 to 58 months. Thirty-eight (84.4%) patients were alive and disease free. Conclusion: TORS is a safe, feasible, minimally invasive, and oncologically safe procedure in patients with early HPV supraglottic cancers. It has less morbidity and offers benefits in terms of early airway and feeding rehabilitation and avoids complications resulting from radiation therapy for these patients.

Prevalence of oromucosal lesions in relation to tobacco habit among a Western Maharashtra population KA Kamala, S Sankethguddad, Ajay G Nayak, Abhijeet R Sanade, SR Ashwini Rani Indian Journal of Cancer 2019 56(1):15-18 OBJECTIVES: This study was conducted to determine the number and types of oromucosal lesions (OMLs) in relation to tobacco habits in patients who attended the outpatient department. METHODOLOGY: A total of 1730 patients visiting the Department of Oral Medicine and Radiology were interviewed and screened for tobacco habits (smoking and smokeless). Clinical oral examination was conducted with diagnostic instruments using the Color Atlas of Common Oral Diseases as a guide for diagnosis. When clinical features were not diagnostic, a biopsy was done. RESULTS: Of the 1730 outpatients, 975 (56.3% ) individuals used tobacco in one or other forms and 687 (70.4%) of these had OMLs. CONCLUSION: The results of this study provide important information on the prevalence of OMLs in patients seeking dental care. This provides baseline data for future studies on the prevalence of oral lesions in the general population.

Frozen section is not cost beneficial for the assessment of margins in oral cancer Sourav Datta, Aseem Mishra, Pankaj Chaturvedi, Munita Bal, Deepa Nair, Yogesh More, Pranav Ingole, Sandeep Sawakare, Jai Prakash Agarwal, Shubhada V Kane, Poonam Joshi, Sudhir Nair, Anil D'Cruz Indian Journal of Cancer 2019 56(1):19-23 BACKGROUND: Routine use of frozen section (FS) is a costly procedure and sparsely available in resource poor countries. A proper cost benefit analysis may help to reduce its routine use and would empower surgeons to perform oral cancer surgeries without having FS facility. FS is performed to identify microscopic spread beyond gross disease that cannot be assessed clinically. OBJECTIVE: Our primary aim was to determine the cost benefit analysis of FS in the assessment of margins in oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Retrospective study of prospectively collected data of 1311 consecutive patients who were operated between January 2012 and October 2013. The gross and microscopic margin status of each patient was extracted from the patient's chart. The cost estimates were performed to calculate the financial burden of FS as well as expenses incurred on adjuvant treatment resulting from inadequate margins. RESULT: Microscopic spread changed the gross margin status in 5.2% (65/1237) patients. Of this entire cohort of 1237 patients, FS helped 29 (2.3%) patients to achieve tumor free margin, and it changed the adjuvant treatment plan in 9 (0.7%) patients. The cost of FS for each patient was INR 11052. The cost-benefit ratio of FS was 12:1. Gross examination alone could have identified majority of the inadequate margins. CONCLUSION: Frozen section for assessment of margin status bears poor cost-benefit ratio. Meticulous gross examination of the entire surgical specimen is sufficient to identify majority of inadequate margins.

Multiple logistic regression analysis predicts cancer risk among tobacco usage with glutathione S-transferase p1 genotyping in patients with head and neck cancer Argi Anuradha, Veerathu L Kalpana, Natukula Kirmani Indian Journal of Cancer 2019 56(1):24-28 INTRODUCTION: Numerous studies have been investigated to understand the association between glutathione S-transferase P1 (GSTP1) polymorphism and risk of head and neck cancer (HNC) but yielded contradictory results, and no studies could confirm polymorphism in GSTP1 and that tobacco usage increases the risk of HNCs. Therefore, this study aimed to understand the association of GSTP1 Ile105Val polymorphism with or without tobacco usage in carcinogenesis and clinicopathological characteristics of patients with HNC. MATERIALS AND METHODS: Binary logistic regression analysis was performed to predict HNC risk with tobacco use and GSTP1 genotyping. Five predictor variables such as gender, age, tobacco usage, familial, and GSTP1 genotypes were included in the model. RESULTS: The results of the logistic regression analysis show that the full model which considered all the five independent variables together was statistically significant, log-likelihood = −111.820, and all slopes are zero: G = 74.297, degree of freedom (DF) = 5, P = 0.000. The strongest predictor in this model is tobacco usage (odds ratio = Z = −5.16, P = 0.000). CONCLUSION: The study concludes that multiple logistic regression analysis model could predict the risk factors in case–control studies where control samples are compromised.

Second primary malignancies in laryngeal carcinoma patients treated with definitive radiotherapy Yurday Ozdemir, Erkan Topkan Indian Journal of Cancer 2019 56(1):29-34 INTRODUCTION: Second primary malignancy (SPM) is associated with decreased overall survival (OS) in laryngeal carcinomas (LC). METHODS: One hundred eighty three LC patients were analyzed retrospectively. The primary and secondary endpoints were the incidence of SPM and the OS difference between patients with and without SPM. RESULTS: SPM developed in 22 (12.0%) patients at median 52 months (range, 4–131 months), with a yearly 2.8% incidence, of which 19 (10.4%) and 3 (1.6%) were metachronous and synchronous, respectively. Lung was the commonest SPM (72.7%). Of 47 deaths, 12 (25.5%) were SPM related. Comparatively SPM patients had significantly shorter median OS (68.0 months vs. median not reached; P = 0.005), with lower 5-year (67.0% vs. 78.9%) and 8-year (32.6 vs. 69.8%) survival rates. CONCLUSION: The present findings suggested the SPM as a competing risk factor for death in index LC patients with its annual incidence rate of 2.8% and for accounting one of every four deaths in this patients group. Emergence of lung carcinoma as the most frequent type of SPM and the ability to treat >50% of them with an estimated long-term outcomes emphasizes the importance of early diagnosis and curative treatment of SPMs.

Second primary malignancies in patients with radiotherapy-treated laryngeal carcinoma - A commentary Deepti Sharma, Neha Sharma, Vineeta Goel Indian Journal of Cancer 2019 56(1):35-36

Neoadjuvant concurrent chemoradiation in male breast cancer: Experience from a tertiary cancer center Priya Iyer, Ananthi Balasubramanian, Ganesarajah Selvaluxmy, V Sridevi, Arvind Krishnamurthy, Venkatraman Radhakrishnan Indian Journal of Cancer 2019 56(1):37-40 BACKGROUND: Male breast cancers (MBC) account for 1% of all breast cancers. Neoadjuvant concurrent chemoradiation (CTRT) is not the standard of care for treating breast cancer. However, in our center, it has been routinely used in patients with locally advanced breast cancer to downsize the tumor and make it amenable to surgery. AIM: This study was conducted to examine the clinical and pathological profile and outcomes of patients with MBC treated at our institute with neoadjuvant CTRT. SETTINGS AND DESIGN: The study was conducted at a tertiary cancer center and was retrospective in nature. MATERIALS AND METHODS: All MBC patients treated with neoadjuvant CTRT at our center between 2001 and 2016 were enrolled in the study. Data were retrospectively extracted from the patients' case records. STATISTICAL ANALYSIS: Kaplan–Meier method was used for survival analysis and the outcome variables were compared using the log-rank test. RESULTS: Thirty-one MBC patients who received neoadjuvant CTRT were analyzed in this study. The median age of the patients was 53 years. Stage IIB disease was observed in 8/31 (26%) patients, stage III in 20/31 (64%), and stage IV in 3/31 (10%) patients. There was no grade 3 or 4 toxicity due to CTRT. Surgery was performed in 29/31 (94%) patients and none of the patients had a pathological complete response. The median duration of follow-up was 95.3 months. The 8-year event-free survival and overall survival for stage IIB, III, and IV were 75%, 50%, and 0% and 87.5%, 69%, and 0%, respectively. CONCLUSION: This is the first study to report on the use of neoadjuvant CTRT in MBC. Prospective evidence from phase-3 randomized controlled trials on the safety and efficacy of CTRT in breast cancer is required before its routine use can be recommended.

Anaesthesia

The subcostal nerve as the target for nerve stimulator–guided transversus abdominis plane blocks - Commentary Sumitra G Bakshi Indian Journal of Anaesthesia 2019 63(4):255-256

Radiological evaluation of airway – What an anaesthesiologist needs to know! Kinshuki Jain, Nishkarsh Gupta, Mukesh Yadav, Sanjay Thulkar, Sushma Bhatnagar Indian Journal of Anaesthesia 2019 63(4):257-264 Airway management forms the foundation of any anaesthetic management. However, unanticipated difficult airway (DA) and its sequelae continue to dread any anaesthesiologist. In spite of development of various clinical parameters to judge DA, no single parameter has proved to be accurate in predicting it. Radiological evaluation may help assess the aspects of patient's airway not visualised through the naked eye. Starting from traditional roentgenogram to ultramodern three-dimensional printing, imaging may assist the anaesthesiologists in predicting DA and formulate plan for its management. Right from predicting DA, it has been used for estimating endotracheal tube sizes, assessing airway pathologies in paediatric patients and planning extubation strategies. This article attempts to provide exhaustive overview on radiological parameters which can be utilised by anaesthesiologists for prediction of DA.

The subcostal nerve as the target for nerve stimulator guided transverse abdominis plane blocks – A feasibility study Prasanna Vadhanan, Mohammed Hussain, Revathy Prakash Indian Journal of Anaesthesia 2019 63(4):265-269 Background and Aims: Transverse Abdominis Plane (TAP) block was originally described as a landmark-based technique. Peripheral nerve stimulator (PNS) guided blocks are still widely performed, where ultrasound is unavailable. Methods: Cadaveric dissections were performed which showed the subcostal nerve following a predictable course at the lateral abdominal wall in the TAP. The subcostal nerve was identified by ultrasound in three volunteers. Stimulation of the subcostal nerve was performed using PNS and landmarks as guidance in and 20 patients. Twitches of the anterior abdominal wall muscles were elicited, and needle position and drug dispersion were confirmed using ultrasound. Results: Out of 32 attempts made, the drug dispersion was appropriate in 24, not appropriate on four insertions and twitches were not elicited in 4 attempts. Conclusion: Nerve stimulator can be used as a guidance for TAP blocks where the availability of ultrasound is limited.

Reliability of the thyromental height test for prediction of difficult visualisation of the larynx: A prospective external validation Shizuha Yabuki, Satoka Iwaoka, Mamoru Murakami, Hiroko Miura Indian Journal of Anaesthesia 2019 63(4):270-276 Background and Aims: Thyromental height (TMH) has been reported to be useful for prediction of difficult visualisation of the larynx (DVL), defined as Cormack--Lehane (C&L) grade III or IV. The aim of this study was to compare the diagnostic accuracy of the TMH test for DVL with that of other clinically used tests in Japanese patients. Methods: Six hundred and nine surgical patients undergoing endotracheal intubation under general anaesthesia were enrolled in this prospective observational study. TMH, thyromental distance (TMD), and Samsoon and Young's modified Mallampati (MMT) tests were performed in all patients. The C&L grades for the laryngoscopic view with and without external backward, upward, rightward pressure (BURP) were determined by designated airway assessors. The cutoff value for the TMH test was calculated using receiver-operating characteristic (ROC) curve analysis. The sensitivity, specificity, positive predictive value, accuracy, positive likelihood ratio, and area under the ROC curve (AUROC) for each predictive test were calculated and compared. Results: ROC curve analysis indicated that 54 mm is the optimal cutoff value for the TMH test. However, both this value and the conventional cutoff value of 50 mm, which has been reported as having good diagnostic accuracy in the literature, had poor diagnostic accuracy. The AUROC for the TMH test was 0.631 without BURP and 0.592 with BURP; these values were not superior to those for the TMD test or MMT. Conclusion: The TMH test is not a good predictor of DVL in Japanese patients.

Correlation between bispectral index, end-tidal anaesthetic gas concentration and difference in inspired–end-tidal oxygen concentration as measures of anaesthetic depth in paediatric patients posted for short surgical procedures Raylene Dias, Nandini Dave, Barkha Agrawal, Aarti Baghele Indian Journal of Anaesthesia 2019 63(4):277-283 Background and Aims: Measurement of end-tidal anaesthetic gas concentrations (ETAG) is currently a pragmatic indicator for monitoring anaesthetic depth. We aimed to assess the performance of ETAG for sevoflurane (ETAG-sevo) with bispectral index (BIS) and difference between inspired and end-tidal oxygen concentration (Fi−Et)O2% in measuring anaesthetic depth in toddlers and preschool children. Primary outcome was to correlate BIS with ETAG-sevo. Secondary outcome was to correlate (Fi−Et)O2% with ETAG-sevo and to derive cut-off value of (Fi−Et)O2%which corresponds with light planes of anaesthesia [minimum alveolar concentration (MAC <0.6)]. Methods: Thirty patients between 1 and 5 years of age undergoing short procedures were included. ETAG, MAC, BIS and (Fi−Et)O2% were measured at intubation, maintenance phase, last 15 min of surgery, end of surgery, extubation, recovery. Pearson's correlation coefficient was used to measure correlation. Receiver operating characteristic (ROC) curves were used to derive cut-off value of (Fi−Et)O2% which corresponded with MAC <0.6. Results: BIS correlated poorly with ETAG at all time intervals. Significant correlation was seen between (Fi−Et)O2% and ETAG at intubation (P = 0.042), last 15 min of surgery (P = 0.019) and end of surgery (P = 0.001). Cut-off value >7 was obtained for (Fi−Et)O2% corresponding to MAC <0.6 at extubation with area under ROC curve0.955 (95% confidence interval 0.811–0.997), with sensitivity 0.8571 and specificity 1.00. Conclusion: BIS was an unreliable measure of anaesthetic depth. (Fi−Et)O2% values >7 corresponded with light planes of anaesthesia.

Evaluation of performance of C-MAC® video laryngoscope Miller blade size zero for endotracheal intubation in preterm and ex-preterm infants: A retrospective analysis Renu Sinha, Kanil Ranjith Kumar, Ram Kumar Kalaiyarasan, Puneet Khanna, Bikash Ranjan Ray, Ravinder Kumar Pandey, Jyotsna Punj, Vanlal Darlong Indian Journal of Anaesthesia 2019 63(4):284-288 Background and Aims: The preterm and ex-preterm babies form a separate group among the paediatric population with unique airway anatomy. The utility of C-MAC® Video laryngoscope (VL) for routine intubation of preterm babies has not been evaluated. The purpose of this study is to report the performance of C-MAC® VL Miller blade size-0 for endotracheal intubation in preterm babies at our institute. Methods: After Institute Ethics Committee approval, a retrospective study was designed to evaluate the performance of C-MAC® VL for intubation in preterm and ex-preterm babies. The medical files, and video recordings of preterm babies up to 60 weeks of post-gestational age who had undergone surgery for retinopathy of prematurity from January 2014 to April 2016 were reviewed. All babies were intubated with C-MAC® Miller blade size-0. Demographic parameters, time to best glottic view (TTGV), time to intubate (TTI), ease and number of intubation attempts were assessed. Episodes of desaturation and complications related to intubation were recorded. Results: Data of 37 preterm and ex-preterm babies were analysed. The mean age and weight at the time of surgery were 40.5 (±4.9) weeks and 2532 (±879) grams respectively. The median TTGV and TTI were 11.0 and 22.0 seconds. A total of 32 babies (86.5%) were intubated on initial attempt and five were intubated on second attempt. Stylet was used to facilitate intubation in all infants. There was no incidence of desaturation, mucosal injury or bleeding. Conclusion: C-MAC video laryngoscope Miller blade size 0 is suitable for endotracheal intubation in preterm and ex-preterm infants.

Comparing the efficacy of aprepitant and ondansetron for the prevention of postoperative nausea and vomiting (PONV): A double blinded, randomised control trial in patients undergoing breast and thyroid surgeries Salome Jeyabalan, Suma Mary Thampi, Reka Karuppusami, Kunder Samuel Indian Journal of Anaesthesia 2019 63(4):289-294 Background and Aims: Aprepitant, a Neurokinin-1 receptor antagonist, has been evaluated in abdominal and neurosurgeries, but its effect is less clear in breast and thyroid surgeries, which are also known to be high risk for post-operative nausea and vomiting (PONV). This study was done to compare the antiemetic efficacy of ondansetron and aprepitant in women undergoing mastectomy and thyroidectomy. Methods: One hundred and twenty-five ASA I and II, female patients, aged between 18 and 65 years were randomly assigned into Group I (ondansetron group, n = 62) or Group II (aprepitant group, n = 63), by computer-generated random sequencing. Per protocol analysis was done to assess the incidence and severity of PONV, use of rescue antiemetics, and patient satisfaction with PONV control between the two groups, till 24 h post-surgery. Results: In the immediate postoperative period, 79.7% of patients in Group I and 85.2% in Group II were free of emesis (P value: 0.49). In Group I, the first episode of vomiting occurred within a median duration 90 min (IQR 2575: 45-147) postoperatively, whereas the median duration in Group II was 160 min (IQR 25-75: 26-490), with request for rescue antiemetic at 60 min in Group I (IQR 25-75: 27-360) and 147 min in Group II (IQR 25-75: 11-457). Conclusion: A single dose of oral aprepitant has comparable effects to injection ondansetron administered eighth hourly in preventing PONV, the severity of nausea, number of rescue antiemetics, and the time to first emetic episode in the 24-h postoperative period. CTRI Reg No: REF/2017/06/014637.

Comparison of Full Outline of UnResponsiveness (FOUR) score and the conventional scores in predicting outcome in aneurysmal subarachnoid haemorrhage patients Rajeeb Kumar Mishra, Charu Mahajan, Indu Kapoor, Hemanshu Prabhakar, Parmod Kumar Bithal Indian Journal of Anaesthesia 2019 63(4):295-299 Background and Aims: Full Outline of UnResponsiveness (FOUR) score is a more comprehensive score used to assess eye response, motor response, brainstem reflexes, and respiration that was introduced to overcome the drawbacks of Glasgow coma scale (GCS) score. Our aim was to assess which score best predicts mortality and poor outcome in aneurysmal subarachnoid haemorrhage (aSAH) patients. Methods: This cohort study, prospectively evaluated the use of FOUR score to assess the mortality and outcome in aSAH patients during the period from November 2015 to November 2016. For each patient of aSAH, GCS, FOUR score, Hunt and Hess (HH) score and World Federation of Neurological Surgeons (WFNS) score were determined at the time of admission to neurosurgical intensive care unit. All patients were followed till 28 days post-SAH and their outcome were assessed by Glasgow outcome scale (GOS). We calculated the sensitivity (Sn) and specificity (Sp) for each of these scores. We generated the receiver operating characteristic curve (ROC), quantified the accuracy by the area under curve (AUC), and also calculated their 95% confidence interval (95% CI). Results: A total of 75 aSAH patients were enrolled for the study. The mortality was 24/75 (32%) with 23 in-hospital deaths. FOUR score was highly specific (86.27%) and sensitive (75%) for the prediction of mortality. However, for predicting 28-day outcome, WFNS and HH grade were most specific (92.5%), whereas FOUR and HH score was moderately specific (68.57%). Conclusion: FOUR score is among the most specific and moderately sensitive tool for prediction of mortality. However, WFNS and HH grade are more specific in predicting the 28-day outcome.

Assessment of predisposing factors in myofascial pain syndrome and the analgesic effect of trigger point injections - A primary therapeutic interventional clinical trial S Parthasarathy, Siyam Sundar, Gayatri Mishra Indian Journal of Anaesthesia 2019 63(4):300-303 Background and Aims: Myofascial pain syndrome (MPS) is a common cause of chronic musculoskeletal pain, characterised by myofascial trigger points (TPs). TP injection is an established technique for management of MPS. In this study, we analysed the efficacy of myofascial TP injection of lignocaine and the influencing biomechanical factors on MPS. Methods: After obtaining ethical committee approval, we included the first 100 adult patients of MPS with failed physical therapy aged above 18 years, and with TPs in the trapezius, infraspinatus, and/or the levator scapulae muscles and Visual analog scale (VAS) >4. TP injection of 2% (2 ml) lignocaine was performed. Visual analogue scale (VAS) scores were recorded immediately and after 1 month. Number of repeat TP injections and use of oral analgesic in one month was noted. Results were analysed with the analysis of variance test. Results: The mean VAS reduced significantly both immediately and 1 month after therapeutic injections (8.57 ± 0.77, 2.67 ± 1.43 and 2.82 ± 1.4, respectively, P < 0.01). Keeping the palm below the head during sleep was the major contributing factor for myofascial TP, followed by slanting the neck to use mobile phones. Repeat TP injection was used in 4% of cases. Conclusion: TP injection of 2 ml of 2% lignocaine along with correction of predisposing biomechanical factors provided significant pain relief for MPS in patients with failed physical therapy without any side effects.

Magnesium sulphate optimises surgical field without attenuation of the stapaedius reflex in paediatric cochlear implant surgery Wahba Z Bakhet, Hassan A Wahba, Lobna M El Fiky, Hossam Debis Indian Journal of Anaesthesia 2019 63(4):304-309 Background and Aims: The anaesthesia technique for paediatric cochlear implantation should be modified to achieve an optimised surgical field and allow neuromonitoring. Total intravenous anaesthesia (TIVA) provides good surgical condition without affecting intraoperative electrical stapaedial reflex threshold (ESRT). Though magnesium sulphate (MgSO4) is a cheap, readily available drug for controlled hypotension, it can decrease the amplitude of motor-evoked potentials. This study aimed to evaluate the effect of MgSO4 infusion on quality of surgical field, intraoperative ESRT, and anaesthetic requirements in paediatric cochlear implant surgery performed under TIVA. Methods: In this randomised controlled trial, 66 children (1-6 years) undergoing cochlear implant under TIVA were randomly assigned to control group or MgSO4 group. The primary outcome was quality of surgical field, and the secondary outcomes were mean arterial blood pressure (MAP), heart rate (HR), ESRT, and the intraoperative anaesthetic requirements. The incidence of adverse events was recorded as well. Results: The quality of surgical field was better in group M than group C, P < 0.02. The number of children who achieved optimum surgical conditions (scores ≤2) was significantly better in the group M (n = 23/33, 70%) compared with group C (n = 13/33, 39%), P < 0.001. MAP, HR, and anaesthetic requirements were significantly lower in group M, P < 0.05. There were no differences between both groups regarding ESRT response. Conclusion: Magnesium sulphate IV infusion optimised surgical field and decreased anaesthetic requirements without attenuating the ESRT in paediatric cochlear implant surgery performed under TIVA.

Urology

New treatment modalities with vaccine therapy in renal cell carcinoma Mehmet Giray Sönmez, Leyla Öztürk Sönmez Urology Annals 2019 11(2):119-125 The aim of implementing vaccine therapy is to activate immune response against malignant cells by overcoming the tolerance triggered by the tumor. These treatments are effective using the immune response against cancer. Not every type of cancer is suitable for vaccine therapies. For a vaccine therapy to be implemented, cancer should be immunogenic and contain tissue-specific proteins, should have a slow progression, and treatments should be feasible. For that reason, studies regarding urological cancers are mostly focused on the kidneys and the prostate. Vaccine therapies used in renal cell carcinoma (RCC) can be categorized under the following titles: autologous tumor cells, dendritic cells, genetically modified tumor cells, and protein/peptide. Although there are old studies on the implementation of vaccine therapies in RCC, researches have only been intensified recently. In addition to their effective potential for lengthening general survival, decreasing tumor burden and cancer development in long term, vaccine treatments are especially effective in metastatic RCC patients. We think that vaccine treatments would be applied more in near future since RCC are immunogenic. In this compilation, we will discuss vaccine therapies used in RCC, which urologists are not so familiar with, in the light of the up-to-date literature.

Guideline on writing a case report Basim Saleh Alsaywid, Nada Mansour Abdulhaq Urology Annals 2019 11(2):126-131 Research is an important competency that should be mastered by medical professionals. It provides an opportunity for physicians to develop numerous skills including communication, collaboration, time management, and teamwork. Case report, as a research design, describes important scientific observations that are encountered in a clinical setting to expand our knowledge base. Preparing a case report is far easier than conducting any other elaborative research design. Case report, with its main components, should be focused and delivers a clear message. In this article, the key components of a case report were described with the aim of providing guidance to novice authors to improve the quality of their reporting.

Lower urinary tract symptoms and feeling of incomplete emptying in Saudi Arabian men and its correlation with postvoid residual urine Reem Aldamanhori Urology Annals 2019 11(2):132-134 Purpose: This study was conducted to assess the clinical value of postvoid residual (PVR) urine measurement and associate it with the feeling of incomplete emptying in men with lower urinary tract symptoms. Methods: Two hundred men were surveyed in the King Fahd Hospital of the University. Patients who had previous urological surgery and patients who are currently on urology treatment were excluded. Information from the remaining 181 patients was analyzed. International Prostate Symptom Score (IPSS) sheets were filed, and then, the PVR was measured. Results: Data from IPSS sheets were evaluated: 45 patients (24.8%) were characterized as experiencing no symptoms (Score: 0 and 1), 87 (48%) as mild-to-moderate symptoms (Score: 2 and 3), and 49 (27%) as severe symptoms (Score: 4 and 5). The PVR measurement showed no statistical difference in all three categories (being 10, 13, and 12, respectively). Feeling of incomplete emptying despite little PVR was frequently observed. Conclusion: The study concluded that the feeling of incomplete emptying was poorly correlated with PVR urine volume measurement. This feeling was significantly associated with worsening of both voiding and storage symptoms.

Incidence of prostate cancer among patients with prostate-related urinary symptoms: A single institution series in 10 years Khalid M Alotaibi Urology Annals 2019 11(2):135-138 Purpose: The aim of the study is to correlate between the value of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and transrectal ultrasound (TRUS) as predictors for diagnosing prostate cancer in patients with voiding symptoms. Materials and Methods: A total of 1610 male patients seen over a period of 10 years in a single institution had prostate-related voiding problems. Routine studies including DRE and serum PSA were done to all patients. TRUS and TRUS biopsy were performed for patients with suspected prostatic cancer based on abnormal DRE findings and/or serum PSA levels. Results: TRUS biopsy revealed prostate cancer in 206 out of 1610 patients with prostate-related voiding problems (13%), 40% had abnormal PSA and 28% had abnormal DRE. Combined abnormal PSA and DRE revealed cancer in 63% of patients. This percentage increased to 90% when TRUS was also abnormal, but dropped to 54% when TRUS was normal. Conclusions: DRE together with serum PSA and TRUS have the highest predictable values for diagnosis of prostate cancer among patients with voiding symptoms. In the absence of abnormal TRUS, PSA and DRE together are more predictable than either alone. Serum PSA alone is more predictable than DRE. Random prostate biopsies should be performed in the presence of high serum PSA, and/or abnormal findings by DRE in male patients with urinary symptoms suggestive of the prostate disease.

Pain and anxiety assessment during cystourethroscopy in males using voiding instruction: A prospective, randomized controlled study Debansu Sarkar, Kunal Kapoor, Dilip Kumar Pal Urology Annals 2019 11(2):139-142 Introduction: Office cystourethroscopy is one of the common and most frequent urological procedures. Pain and anxiety during the procedure might lead to noncompliance and incomplete cystoscopic examination. Negotiating cystoscope through external sphincter is the most painful and uncomfortable distressing part of cystoscopy. To overcome this, manual compression of irrigation bag during cystoscopy has been used and found to be helpful. Numerous other methods were also studied. Despite these, cystoscopy is still painful and causes anxiety in patients. External sphincter gets relaxed naturally during the act of micturition. Based on this principle, pain and anxiety were studied with voiding instruction during cystourethroscopy. Objective: To study the effect of voiding instruction on anxiety and pain during cystourethroscopy using the Hamilton Anxiety Rating Scale (HAM-A) and visual analogue scale (VAS), in a well-matched Eastern Indian male patient population in a prospective, randomized pattern. Methods: A total of 100 male patients were recruited from those who underwent cystourethroscopy examination in SSKM Hospital and were prospectively randomized into two groups: cystoscopy with or without voiding instruction. Pre- and postprocedure HAM-A score and postprocedure VAS score were recorded. Results: The mean postprocedural pain (VAS) score between voiding instructed and noninstructed groups reached statistical significance: 3.06 ± 1.98 (Range, 2–5) and 5.16 ± 2.86 (Range, 4–8), respectively (P < 0.001). Preprocedure HAM-A score was similar between both groups. Postprocedure median HAM-A score was statistically significantly lower (mean 17.86 ± 2.8 vs. 19.76 ± 3.12; P < 0.001) in voiding instructed group. Conclusion: Pain and anxiety level during cystourethroscopy examination in males can be significantly reduced when the patient is instructed to void during cystourethroscopy examination.

Effectiveness of bladder tumor antigen quantitative test in the diagnosis of bladder carcinoma in a schistosoma endemic area Abubakar Sadiq Muhammad, Ismaila Arzika Mungadi, Nnaemeka Ndodo Darlington, Garba Diffa Kalayi Urology Annals 2019 11(2):143-148 Introduction: Bladder carcinoma is the most common male cancer in our environment due to endemicity of schistosomiasis. Squamous-cell carcinoma is the most common histological type and patients present at an advanced stage. The objective of this study is to compare the sensitivity, specificity, and predictive values of the bladder tumor antigen quantitative test (BTA TRAK) and urine cytology in the diagnosis of bladder carcinoma in a schistosoma endemic area. Materials and Methods: This is a 12-month cross-sectional study of 88 patients, 52 of them with features of bladder carcinoma as study group, and 36 of them with hematuria from other urologic conditions, and benign urologic conditions and healthy volunteers as control group (CG). The mean ages of patients in the study and CGs were 47.17 ± 17.00 and 44.19 ± 18.89 years, respectively (P = 0.412). Bladder tumor antigen was assayed using enzyme-linked immunosorbent assay. Data were analyzed using SPSS version 20.0 for Windows. Results: The sensitivity of urine cytology and BTA TRAK in the study was 29.1% and 98.8%, respectively. The specificity of urine cytology and BTA TRAK was 95.5% and 13.6%, respectively (P = 0.05). The positive predictive values of urine cytology and BTA TRAK in the study were 96.2% and 81.7%, respectively. The negative predictive values were 25.0% and 75.0% for urine cytology and BTA TRAK, respectively. Conclusion: BTA TRAK is more sensitive but poorly specific as compared to that of the urine cytology for bladder cell carcinoma detection in a schistosoma endemic area.

Investigation of the reasons for withdrawal from long-term treatment with mirabegron of treatment-naïve Japanese female patients with overactive bladder in the real-world clinical setting Yoshinori Tanaka, Yasushi Tanuma, Naoya Masumori, Hirofumi Ohnishi Urology Annals 2019 11(2):149-154 Purpose: The persistence of treatment with mirabegron and the reasons for withdrawal from the treatment among treatment-naïve Japanese female patients with overactive bladder (OAB) were prospectively investigated for 3 years in the real-world clinical setting. Materials and Methods: A total of 62 treatment-native Japanese female patients clinically diagnosed with OAB were treated with mirabegron and prospectively followed for 3 years. The persistence rate was estimated using the Kaplan-Meier method. If mirabegron had to be terminated or a patient did not come to the hospital to receive a prescription, the reasons for withdrawal from treatment were determined. Results: The 6-month, 1-year, 2-year, and 3-year persistence rates were 51.6%, 38.7%, 32.3%, and 25.8%, respectively. The most frequent reasons for withdrawal from treatment with mirabegron were symptom resolution (38.7%), deterioration of comorbidity unrelated to OAB (12.9%), lack of efficacy (8.1%), and adverse events (4.8%). Conclusions: The persistence rate of treatment with mirabegron among treatment-naïve Japanese female patients with OAB is low for 3 years in the real-world clinical setting. Many patients discontinue the treatment for various reasons, the most frequent of which is symptom resolution. These findings provide important considerations for clinicians whose patients are continuing medication for OAB.

Evaluation of response in patients of metastatic castration resistant prostate cancer undergoing systemic radiotherapy with lutetium177-prostate-specific membrane antigen: A comparison between response evaluation criteria in solid tumors, positron-emission tomography response criteria in solid tumors, European organization for research and treatment of cancer, and MDA criteria assessed by gallium 68-prostate-specific membrane antigen positron-emission tomography-computed tomography Manoj Gupta, Partha Sarathi Choudhury, Sudhir Rawal, Harish Chandra Goel, Shriram Avinash Rao Urology Annals 2019 11(2):155-162 Introduction: We evaluated various morphological and molecular response criteria in metastatic castration-resistant prostate cancer (PCa) patient undergoing peptide receptor radioligand therapy (PRLT) with Lutetium177-prostate-specific membrane antigen (PSMA) by using Gallium 68-PSMA positron-emission tomography-computed tomography (Ga68-PSMA PET-CT). Methods: A total of 46 pre- and 8–12 weeks' post-PRLT Ga68-PSMA PET-CT studies were reanalyzed (23 comparisons). Prostate-specific antigen drop of ≥50% and ≥25% increase was considered as partial response (PR) and progressive disease (PD), respectively, for biochemical response (BR) while change in-between was considered as stable disease (SD). Response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson (MDA) criteria for morphological response while PET response criteria in solid tumors 1.0 (PERCIST 1.0) and European organization for research and treatment of cancer (EORTC) criteria for molecular response were used. Kappa coefficient was derived to see the level of agreement. Results: The proportion of PD, PR, and SD by BR and RECIST criteria was 9 (39.13%), 3 (13.04%), and 11 (47.83%) and 5 (21.74%), 2 (8.70%), and 16 (69.57%), respectively. The proportion of PD, PR, and SD was same by PERCIST and EORTC criteria and which were 8 (34.78%), 5 (21.74%), and 10 (43.48%). The proportion of PD, PR, and SD by MDA criteria was 1 (4.35%), 1 (4.35%), and 21 (91.30%), respectively. Poor agreement between BR and both morphological criteria while a statistically significant agreement with both molecular criteria seen. Conclusion: We concluded that molecular criteria performed better than morphological criteria in response assessment by Ga68-PSMA PET-CT in metastatic castration resistant PCa patients undergoing PRLT.

Effects of fluid absorption following percutaneous nephrolithotomy: Changes in blood cell indices and electrolytes Dipti Saxena, Divyangna Sapra, Atul Dixit, Saurabh Chipde, Santosh Agarwal Urology Annals 2019 11(2):163-167 Background and Aims: Effects of fluid absorption on hematological profile in the immediate postoperative period in patients undergoing percutaneous nephrolithotomy (PCNL) have not been given due importance. Considering the limited number of studies available, we conducted this study to evaluate the changes in hemodynamics, complete blood count (CBC), and electrolytes in patients undergoing PCNL using normal saline for irrigation in the prone position. Furthermore, we evaluated the common factors known to affect the absorption. Materials and Methods: Forty American Society of Anesthesiologist Class I or II patients aged 18–65 years were recruited who underwent PCNL under general anesthesia. Heart rate, blood pressure (BP), CBC, and serum electrolytes were recorded preoperatively and just before extubation and compared using the Student's t-test. Correlation of these changes with height and total volume of irrigating fluid, total time of irrigation, duration of operation, and total intravenous fluids administered intraoperatively were performed using the Pearson's correlation coefficient. Results: There was a statistically significant fall in mean hemoglobin (12.5 g/dL to 11.5 g/dL), packed cell volume (38.6%–35.6%), platelet count (2.9 × 105 cells/μL to 2.5 × 105 cells/μL), and sodium ion concentration (Na+) (138.9 meq/L to 137.7 meq/L) in the immediate postoperative period as compared to that of the preoperative values. Rest of the blood indices and electrolytes did not show any significant change. There was a significant rise in postoperative heart rate and BP. Postoperative systolic BP showed a significant positive correlation with the total volume of irrigating fluid. No significant correlation was observed with height and total time of irrigation. Conclusion: This study reveals that there is a significant fall in hemoglobin and Na+ during PCNL in the immediate postoperative period. Only, total volume of irrigating fluid and total duration of surgery had a significant correlation with blood cell indices.

Practice patterns in ordering a voiding cystourethrogram for pediatric patients among different specialties in a Middle Eastern Tertiary care center Mohammad Hout, Bilal Aoun, Lamya Ann Atweh, Ali Merhe, Yaser El-Hout Urology Annals 2019 11(2):168-170 Introduction: Voiding cystourethrogram (VCUG) is a very popular test performed to evaluate genitourinary tract anomalies. Nevertheless, this test can be overused and can lead to unnecessary patient discomfort, radiation exposure, and cost. We sought to study the practice patterns in ordering a VCUG in a Middle Eastern tertiary care center. Methods: Over a period of 3 years, a retrospective analysis of all VCUG images done for pediatric patients in a single center was made. Further clinical details were extracted from the electronic health records. The specialty of an ordering physician and the reported indication for the procedure were noted. Indications for VCUG were recorded based on the AAP 2011 guidelines, NICE guidelines 2007, and ACR 2011 guidelines. Based on these criteria, patients were analyzed. Results: A total of 92 VCUGs were evaluated. Of all VCUGs done, pediatricians ordered the most VCUGs (50/92), followed by pediatric infectious disease (16/92), pediatric nephrology (9/92), pediatric urology (7/92), adult urology (5/92), pediatric surgery (3/92), obstetrician-gynecologist (1/92), and emergency medicine (1/92). Properly indicated VCUGs were 50% by general pediatrics, 55% by pediatric infectious disease, 45% by pediatric nephrology, 40% by adult urology, 33% by pediatric surgery, and 100% by pediatric urology. Conclusion: VCUG is utilized differently by different specialties. In some centers, adult specialties may order a pediatric VCUG. General pediatricians order VCUG the most with a tendency for misuse in up to 50%. Pediatric urology is not the most ordering specialty of VCUG; however, it utilizes it most appropriately. The noted practice patterns may be improved with awareness of the indications and limitations of the study and with proper referral.

Neurotherapeutic potential of erythropoietin after ischemic injury

 of the central nervous system
Florian Simon, Nicolaos Floros, Wiebke Ibing, Hubert Schelzig, Artis Knapsis

Neural Regeneration Research 2019 14(8):1309-1312

Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30&#37; and improvement of neurobehavioral outcome by nearly 40&#37;. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors. 

Hypertension and sleep duration and water intake

Association between hypertension and sleep duration and water intake in Indian young adults
Umeshwar Pandey, Tanu Midha, Yashwant Kumar Rao

Journal of Clinical and Preventive Cardiology 2019 8(2):50-55

Context: The prevalence of hypertension is on the rise in developing countries like India. Physiological parameters such as sleep duration and water intake may be associated with hypertension in young adults. Aims: The aim is to study the association between hypertension and day and nighttime sleep duration and water intake among young adults. Setting and Design: The study was a cross-sectional study, conducted among 596 students of Government Medical College, Kannauj, aged between 17 and 22 years. Materials and Methods: Participants were classified using the diagnostic criteria of the American Heart Association. Data were recorded on a pre-designed and pretested questionnaire. Data analysis was performed using SPSS 22.0. Receiver operator characteristic curve analysis and multiple logistic regression analysis were applied. Results: The prevalence of hypertension was 34.9&#37;, 35.9&#37; among boys, and 33.5&#37; among girls, respectively. Less water intake and shorter sleep duration at nighttime were found to be independent predictors of hypertension. Cutoff of sleep duration at nighttime for predicting hypertension was &#8804;7.6 h among boys and &#8804;7.1 h among girls. The sensitivity and specificity of the cutoff for sleep duration at night time in boys was 79.3&#37; and 74.2&#37;, respectively, and that in girls was 81.5&#37; and 75.6&#37;, respectively. The cutoff for water intake for predicting hypertension was &#8804;2.1 L for boys and &#8804;1.5 L for girls, respectively. The sensitivity and specificity of the cutoff for water intake in boys was 74.8&#37; and 70.3&#37;, and in girls was 78.3&#37; and 71.5&#37;, respectively. Conclusions: Young adults with longer duration of sleep during night time and more water intake had a lesser risk of hypertension. 

Ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease

Utility of ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease: A study from major center in Northeastern India
Farhin Iqbal, Amol Vasantrao Patil, Jogesh Chandra Barkataki

Journal of Clinical and Preventive Cardiology 2019 8(2):44-49

Background: Studies have shown that carotid intima-media thickness (CIMT) and ankle&#8211;brachial pressure index (ABI) can be used as surrogate markers of coronary artery disease (CAD). However, whether studying the ratio of ABI and CIMT has any added value in predicting CAD when compared to either of them alone, has not been studied. Aims: The aim of the study is to compare CIMT and ABI as surrogate markers for the presence and extent of CAD and to investigate whether studying the ratio of ABI and CIMT has any incremental value in predicting CAD than either of them. Methods: We prospectively enrolled 235 stable, non-ACS patients who underwent CIMT and ABI measurements followed by diagnostic coronary angiography. Results: The mean age of the study population was 56.32 &#177; 10.14 years. CIMT was significantly higher in the CAD group compared to non-CAD group (0.91 &#177; 0.22 vs. 0.66 &#177; 0.15, P &#8804; 0.0001). ABI was significantly lower in the CAD group compared to non-CAD group (1.07 &#177; 0.19 vs. 1.18 &#177; 0.14, P &#8804; 0.0001). At an optimal cutoff value of &#8805;0.75 mm, CIMT showed better predictive values (sensitivity and specificity &#8211;72.3&#37; and 79&#37;, respectively) compared to ABI &#8804;0.9 (sensitivity and specificity &#8211; 21.53&#37; and 96.19&#37;, respectively). CIMT was the strongest independent predictor of CAD (P &#60; 0.0001) followed by ABI (P &#61; 0.006) by multiple regression. ABI/CIMT ratio of &#8804;1.55 had better predictive value (sensitivity and specificity &#8211;75.4&#37; and 78.1&#37;, respectively) and stronger correlation with CAD severity (R &#61; 0.42), than either of them. Conclusion: CIMT is a better surrogate marker of CAD compared to ABI. Studying ABI/CIMT ratio has an incremental value in predicting CAD. 

Neural Regeneration Research

Tandem pore TWIK-related potassium channels and neuroprotection J Antonio Lamas, Diego Fernández-Fernández Neural Regeneration Research 2019 14(8):1293-1308 TWIK-related potassium channels (TREK) belong to a subfamily of the two-pore domain potassium channels family with three members, TREK1, TREK2 and TWIK-related arachidonic acid-activated potassium channels. The two-pore domain potassium channels is the last big family of channels being discovered, therefore it is not surprising that most of the information we know about TREK channels predominantly comes from the study of heterologously expressed channels. Notwithstanding, in this review we pay special attention to the limited amount of information available on native TREK-like channels and real neurons in relation to neuroprotection. Mainly we focus on the role of free fatty acids, lysophospholipids and other neuroprotective agents like riluzole in the modulation of TREK channels, emphasizing on how important this modulation may be for the development of new therapies against neuropathic pain, depression, schizophrenia, epilepsy, ischemia and cardiac complications.

Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system Florian Simon, Nicolaos Floros, Wiebke Ibing, Hubert Schelzig, Artis Knapsis Neural Regeneration Research 2019 14(8):1309-1312 Erythropoietin (EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors.

Dendritic shrinkage after injury: a cellular killer or a necessity for axonal regeneration? An Beckers, Lieve Moons Neural Regeneration Research 2019 14(8):1313-1316 Dendrites form an essential component of the neuronal circuit have been largely overlooked in regenerative research. Nevertheless, subtle changes in the dendritic arbors of neurons are one of the first stages of various neurodegenerative diseases, leading to dysfunctional neuronal networks and ultimately cellular death. Maintaining dendrites is therefore considered an essential neuroprotective strategy. This mini-review aims to discuss an intriguing hypothesis, which postulates that dendritic shrinkage is an important stimulant to boost axonal regeneration, and thus that preserving dendrites might not be the ideal therapeutic method to regain a full functional network upon central nervous system damage. Indeed, our study in zebrafish, a versatile animal model with robust regenerative capacity recently unraveled that dendritic retraction is evoked prior to axonal regrowth after optic nerve injury. Strikingly, inhibiting dendritic pruning upon damage perturbed axonal regeneration. This constraining effect of dendrites on axonal regrowth has sporadically been proposed in literature, as summarized in this short narrative. In addition, the review discusses a plausible underlying mechanism for the observed antagonistic axon-dendrite interplay, which is based on energy restriction inside neurons. Axonal injury indeed leads to a high local energy demand in which efficient axonal energy supply is fundamental to ensure regrowth. At the same time, axonal lesion is known to induce mitochondrial depolarization, causing energy depletion in the axonal compartment of damaged neurons. Mitochondria, however, become mostly stationary after development, which has been proposed as a potential underlying reason for the low regenerative capacity of adult mammals. Per contra, upon reduced neuronal activity, mitochondrial mobility enhances. In this view, dendritic shrinkage after axonal injury in zebrafish could result in less synaptic input and hence, a release of mitochondria within the soma-dendrite compartment that then translocate to the axonal growth cone to stimulate axonal regeneration. If this hypothesis proofs to be correct, i.e. dendritic remodeling serving as fuel for axonal regeneration, we envision a major shift in the research focus within the neuroregenerative field and in the potential uncovering of various novel therapeutic targets.

Regenerative biomarkers for Duchenne muscular dystrophy Simon Guiraud, Kay E Davies Neural Regeneration Research 2019 14(8):1317-1320 Skeletal muscle has an extraordinary capacity to regenerate after injury and trauma. The muscle repair mechanism is a complex process orchestrated by multiple steps. In neuromuscular disorders such as Duchenne muscular dystrophy (DMD), the pathological consequences of the lack of dystrophin and the loss of the dystrophin-associated protein complex are dramatic, with a progressive cascade of events, such as continual influx of inflammation, repeated cycles of degeneration and impaired regeneration. Thus, muscle regeneration is a hallmark of the disease and careful monitoring of regenerative processes with robust markers should provide useful information to the field. Since decades, several indices of regeneration such as centronucleation and fibre size have been commonly used. In the present review, we discuss the impaired regenerative process in DMD, the common and new indices of regeneration and their associated methodologies. We notably highlight the regenerative marker embryonic myosin as a robust indicator of muscle regeneration. We also describe new quantitative methodologies offering the possibility of using a panel of translational regenerative biomarkers to obtain a more complete view of the regeneration processes. Upregulation of utrophin, an autosomal and functional paralogue of dystrophin, is one of the most promising therapeutic strategies as it targets the primary cause of the disease and is applicable to all DMD patients regardless their genetic defects. As utrophin is a regeneration associated protein increased in dystrophic muscle, we discuss the correlation of utrophin levels after drug treatment with regeneration markers. The recent advances in technologies and complementary markers of muscle regeneration described in this review, provide an unprecedented opportunity to develop more robust utrophin DMD based strategies for all DMD patients.

Exploring the efficacy of natural products in alleviating Alzheimer's disease Prajakta Deshpande, Neha Gogia, Amit Singh Neural Regeneration Research 2019 14(8):1321-1329 Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD.

Involvement of insulin receptor substrates in cognitive impairment and Alzheimer's disease Daisuke Tanokashira, Wataru Fukuokaya, Akiko Taguchi Neural Regeneration Research 2019 14(8):1330-1334 Type 2 diabetes—associated with impaired insulin/insulin-like growth factor-1 (IGF1) signaling (IIS)—is a risk factor for cognitive impairment and dementia including Alzheimer’s disease (AD). The insulin receptor substrate (IRS) proteins are major components of IIS, which transmit upstream signals via the insulin receptor and/or IGF1 receptor to multiple intracellular signaling pathways, including AKT/protein kinase B and extracellular-signal-regulated kinase cascades. Of the four IRS proteins in mammals, IRS1 and IRS2 play key roles in regulating growth and survival, metabolism, and aging. Meanwhile, the roles of IRS1 and IRS2 in the central nervous system with respect to cognitive abilities remain to be clarified. In contrast to IRS2 in peripheral tissues, inactivation of neural IRS2 exerts beneficial effects, resulting in the reduction of amyloid β accumulation and premature mortality in AD mouse models. On the other hand, the increased phosphorylation of IRS1 at several serine sites is observed in the brains from patients with AD and animal models of AD or cognitive impairment induced by type 2 diabetes. However, these serine sites are also activated in a mouse model of type 2 diabetes, in which the diabetes drug metformin improves memory impairment. Because IRS1 and IRS2 signaling pathways are regulated through complex mechanisms including positive and negative feedback loops, whether the elevated phosphorylation of IRS1 at specific serine sites found in AD brains is a primary response to cognitive dysfunction remains unknown. Here, we examine the associations between IRS1/IRS2-mediated signaling in the central nervous system and cognitive decline.

Role of macrophages in peripheral nerve injury and repair Ping Liu, Jiang Peng, Gong-Hai Han, Xiao Ding, Shuai Wei, Gang Gao, Kun Huang, Feng Chang, Yu Wang Neural Regeneration Research 2019 14(8):1335-1342 Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory (M1) and anti-inflammatory (M2) actions, and M2 macrophages have four subtypes. The co-action of M1 and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.

Therapeutic strategies for peripheral nerve injury: decellularized nerve conduits and Schwann cell transplantation Gong-Hai Han, Jiang Peng, Ping Liu, Xiao Ding, Shuai Wei, Sheng Lu, Yu Wang Neural Regeneration Research 2019 14(8):1343-1351 In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury.

Role and prospects of regenerative biomaterials in the repair of spinal cord injury Shuo Liu, Yuan-Yuan Xie, Bin Wang Neural Regeneration Research 2019 14(8):1352-1363 Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.

The "Brain Stress Timing" phenomenon and other misinterpretations of randomized clinical trial on aneurysmal subarachnoid hemorrhage Rafael Martinez-Perez, Natalia Rayo, Agustín Montivero, Jorge Marcelo Mura Neural Regeneration Research 2019 14(8):1364-1366 Clipping and coiling are currently the two alternatives in treatment of ruptured cerebral aneurysms. In spite of some meritorious analysis, further discussion is helpful to understand the actual state of art. Retreatment and rebleeding rates clearly favors clipping, although short-term functional outcome seems to be beneficial for clipping, while this different is not such if we perform the comparison at a longer follow up. Long-term follow ups and cost analysis are mandatory to have a clear view of the current picture in treatment of subarachnoid hemorrhage. Treatment strategy should be made by a multi-disciplinary team in accredited centers with proficient experience in both techniques.

Clinical and Preventive Cardiology

Editor's page April 2019 Ravi R Kasliwal Journal of Clinical and Preventive Cardiology 2019 8(2):43-43

Utility of ankle–brachial pressure index/carotid intima-media thickness ratio in predicting presence and severity of coronary artery disease: A study from major center in Northeastern India Farhin Iqbal, Amol Vasantrao Patil, Jogesh Chandra Barkataki Journal of Clinical and Preventive Cardiology 2019 8(2):44-49 Background: Studies have shown that carotid intima-media thickness (CIMT) and ankle–brachial pressure index (ABI) can be used as surrogate markers of coronary artery disease (CAD). However, whether studying the ratio of ABI and CIMT has any added value in predicting CAD when compared to either of them alone, has not been studied. Aims: The aim of the study is to compare CIMT and ABI as surrogate markers for the presence and extent of CAD and to investigate whether studying the ratio of ABI and CIMT has any incremental value in predicting CAD than either of them. Methods: We prospectively enrolled 235 stable, non-ACS patients who underwent CIMT and ABI measurements followed by diagnostic coronary angiography. Results: The mean age of the study population was 56.32 ± 10.14 years. CIMT was significantly higher in the CAD group compared to non-CAD group (0.91 ± 0.22 vs. 0.66 ± 0.15, P ≤ 0.0001). ABI was significantly lower in the CAD group compared to non-CAD group (1.07 ± 0.19 vs. 1.18 ± 0.14, P ≤ 0.0001). At an optimal cutoff value of ≥0.75 mm, CIMT showed better predictive values (sensitivity and specificity –72.3% and 79%, respectively) compared to ABI ≤0.9 (sensitivity and specificity – 21.53% and 96.19%, respectively). CIMT was the strongest independent predictor of CAD (P < 0.0001) followed by ABI (P = 0.006) by multiple regression. ABI/CIMT ratio of ≤1.55 had better predictive value (sensitivity and specificity –75.4% and 78.1%, respectively) and stronger correlation with CAD severity (R = 0.42), than either of them. Conclusion: CIMT is a better surrogate marker of CAD compared to ABI. Studying ABI/CIMT ratio has an incremental value in predicting CAD.

Association between hypertension and sleep duration and water intake in Indian young adults Umeshwar Pandey, Tanu Midha, Yashwant Kumar Rao Journal of Clinical and Preventive Cardiology 2019 8(2):50-55 Context: The prevalence of hypertension is on the rise in developing countries like India. Physiological parameters such as sleep duration and water intake may be associated with hypertension in young adults. Aims: The aim is to study the association between hypertension and day and nighttime sleep duration and water intake among young adults. Setting and Design: The study was a cross-sectional study, conducted among 596 students of Government Medical College, Kannauj, aged between 17 and 22 years. Materials and Methods: Participants were classified using the diagnostic criteria of the American Heart Association. Data were recorded on a pre-designed and pretested questionnaire. Data analysis was performed using SPSS 22.0. Receiver operator characteristic curve analysis and multiple logistic regression analysis were applied. Results: The prevalence of hypertension was 34.9%, 35.9% among boys, and 33.5% among girls, respectively. Less water intake and shorter sleep duration at nighttime were found to be independent predictors of hypertension. Cutoff of sleep duration at nighttime for predicting hypertension was ≤7.6 h among boys and ≤7.1 h among girls. The sensitivity and specificity of the cutoff for sleep duration at night time in boys was 79.3% and 74.2%, respectively, and that in girls was 81.5% and 75.6%, respectively. The cutoff for water intake for predicting hypertension was ≤2.1 L for boys and ≤1.5 L for girls, respectively. The sensitivity and specificity of the cutoff for water intake in boys was 74.8% and 70.3%, and in girls was 78.3% and 71.5%, respectively. Conclusions: Young adults with longer duration of sleep during night time and more water intake had a lesser risk of hypertension.

Clinical presentation and 2-year mortality outcomes in acute heart failure in a tertiary care hospital in South India: A retrospective cohort study Vengatesh Munusamy, Luxitaa Goenka, Masum Sharma, Thilagavathi Ramamoorthy, Durga Jha, S Solaipriya, VE Dhandapani, Melvin George Journal of Clinical and Preventive Cardiology 2019 8(2):56-63 Background: Heart failure (HF) is one of the leading causes of mortality and morbidity worldwide. We sought to describe the clinical epidemiology of HF from a representative sample in a tertiary care setting and to evaluate the factors which could increase the mortality risk in the study patients. Methods: This retrospective cohort study was carried out among patients who had been admitted with a diagnosis of acute HF from 2013 to 2017. Demographic data, history, laboratory investigations, data on medication clinical variables, and in-hospital outcomes were obtained from the patient's hospital records. The patients were assessed through the telephonic interview for mortality outcomes. Data were analyzed using SPSS software version 16.0 (SPSS Inc., Chicago, IL) and all values of P < 0.05 was considered as statistically significant. Results: A total of 355 acute heart failure (AHF) patients were included in the study with a mean age of 57.78 ± 12.78 years. The most common etiologies among the study patients were ischemic heart disease (58%) and Dilated Cardiomyopathy (24.79%). The in-hospital and 2-year mortality was found to be 104 (29.3%) and 179 (50.4%), respectively. The 2-year mortality was significantly higher in patients with ischemic HF than that of nonischemic HF (119 [57.8%] vs. 58 [39.5%], P = 0.003). Multivariate Cox proportional hazard analysis demonstrated that elderly age, the presence of diastolic dysfunction and higher levels of total leukocyte count (TLC) were independent predictors of mortality. Conclusion: The mortality rate in AHF is higher among ischemic HF than nonischemic HF. The major factors contributing to the 2-year mortality rate among AHF were elderly age, diastolic dysfunction, and high-TLC.

Stress echocardiography in aortic stenosis Nitin Burkule Journal of Clinical and Preventive Cardiology 2019 8(2):64-70 In apparently asymptomatic severe aortic stenosis (AS) group, stress echocardiography objectively identifies symptomatic, high-risk AS patients requiring early aortic valve replacement (AVR). The low-flow, low-gradient AS is well-characterized clinical entity with distinct diagnostic, management, and clinical outcome challenges. A comprehensive two-dimensional transthoracic echocardiography (2D echo) and Doppler and low-dose dobutamine stress echocardiography are of paramount importance for accurate diagnosis and timely decision of AVR. However, clinicians and imaging experts should be aware of the pitfalls and inaccuracies inherent in 2D echo/Doppler measurements and the effects of pathophysiological factors which impact the stroke volume and transvalvular gradient measurements. In appropriate clinical situations, clinicians should take additional help of cardiac computational tomography, cardiac magnetic resonance imaging, and biomarkers.

QT interval – Its measurement and clinical significance Sita Ram Mittal Journal of Clinical and Preventive Cardiology 2019 8(2):71-79 QT interval extends from the beginning of QRS complex to the end of T wave. Thus, it includes the duration of ventricular depolarization (QRS) and repolarization (J point to end of T wave). It corresponds to the duration of cellular action potential. “long-” and “short”-QT intervals are considered as risk markers for cardiac arrhythmias and sudden death. In the last decade, there have been significant advances in our understanding about measurement and significance of QT interval. We have made an attempt to review the literature to find the limitations and queries surrounding the present status of measurement of QT interval and its significance as a risk marker for cardiac arrhythmias and sudden death.

Republication- Indian academy of echocardiography guidelines and manual for performance of stress echocardiography in coronary artery disease Nitin Burkule, Manish Bansal Journal of Clinical and Preventive Cardiology 2019 8(2):80-112 Stress echocardiography is one of the most useful non-invasive diagnostic modalities for detection and evaluation of coronary artery disease (CAD). It is also very useful for assessment of cardiac response to hemodynamic stress in a variety of other cardiac and non-cardiac disorders. Given its cost-effectiveness, stress echocardiography is particularly suited for Indian scenario where the incidence of CAD is rising at an alarming rate and the astronomical expenditure required for its management is borne largely by the patients themselves. However, despite its unequivocal diagnostic value, stress echocardiography remains underutilized, particularly in India, due to the lack of adequate exposure and training in this modality. Unfortunately, while there is extensive literature available to document diagnostic accuracy of stress echocardiography, there are very few texts that actually describe how to perform stress echocardiography in real life. This Indian Academy of Echocardiography guideline document aims to fill this very void. This is a comprehensive 'how to do' document prepared with the objective of providing detailed description of the steps involved in performance and interpretation of stress echocardiography so that there is increased adoption of this important and clinically useful diagnostic modality in daily clinical practice. However, while stress echocardiography has several clinical applications, the present document is restricted to its main application, which is evaluation of CAD. Republished with permission from: Dr. Satish Govind, Editor-in-chief (Journal of the Indian Academy of Echocardiography & Cardiovascular Imaging).