Wednesday, February 2, 2022

Artemisinin resistance: an important emerging clinical problem in tropical medicine

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Int J Physiol Pathophysiol Pharmacol. 2021 Dec 15;13(6):152-157. eCollection 2021.

ABSTRACT

Artemisinin is an important antimalarial drug which is originated and developed from Chinese traditional herbal regimen. At present, artemisinin is used as an antimalarial drug for treatment of drug resistant malarial infection. The effectiveness of artemisinin is clinically accepted. Hence, artemisinin is currently used as main drug for malaria treatment in many tropical countries. Artemisinin resistance is a new emerging clinical problem in tropical medicine. New mutation can result in artemisinin resistance and the resistance becomes important new emerging problem in clinical malariology. It is necessary to control of artemisinin use and searching for new effective drug against artemisinin resistant malaria. In this article, the authors summarizes on important updated information regarding artemisinin resistance.

PMID:35103097 | PMC:PMC8784654

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Trends in Positive Surgical Margins in cT1‐T2 Oral Cavity Squamous Cell Carcinoma

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Objectives/Hypothesis

To evaluate trends in contemporary positive surgical margin incidence in cT1-T2 oral cavity squamous cell carcinoma and to evaluate factors associated with surgical margin status.

Study Design

Retrospective analysis of large dataset.

Methods

Retrospective analysis of the National Cancer Database.

Results

Between 2004 and 2016, 39,818 patients with cT1 or cT2 oral cavity squamous cell carcinoma received primary curative-intent surgery. Positive surgical margins were present in 7.95% of patients, and univariable adjusted probability of positive surgical margins over the study period declined by 1% per year (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98–1.0; P = .049). Multivariable regression revealed the annual rate of positive surgical margins declined significantly (OR, 0.95 per year; 95% CI, 0.92–0.97; P < .001). Factors associated with increased odds of positive surgical margins included cT2 disease, subsite, understaged disease, lymphovascular invasion, tumor grade, and positive lymph nodes. Race and socioeconomic status were not associated with surgical margin status. Treatment at an academic center was associated with increased time to definitive surgery (median 35 days IQR 22–50 vs. median 27 days IQR 14–42; P&nb sp;< .001) and a 20% reduction in positive surgical margin rate (OR, 0.80; 95% CI, 0.71–0.90; P < .001). Treatment at high-volume centers was less likely to be associated with positive surgical margins (OR, 0.85; 95% CI, 0.74–0.98; P = .02).

Conclusion

Surgical subsite, clinical T and N category, presence of lymphovascular invasion, and histologic grade were independent predictors of positive surgical margins. Patients are increasingly being treated at high-volume and academic centers. Overall, the rate of positive surgical margins in cT1-T2 oral cavity squamous cell carcinoma is decreasing.

Level of Evidence

4 Laryngoscope, 2022

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Evaluation of different setting configurations with a new developed telemedical interface of a parallel kinematic robotic system ‐ an experimental development study

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ABSTRACT

Background

For development of a minimally invasive intracorporal micromanipulator, a master-slave telemanipulation system was required.

Methods

Different input positions for a tablet-based input device with a heads-up centered screen were evaluated. Personal preference was assessed using a questionnaire. Then, the most ergonomic and intuitive position was compared to a surgical reference position based on laparoscopic sigmoid resection.

Results

After comparing a 45°, 75° (pitch) and 60°/20° (pitch/yaw) to a 60° reference position no significant differences in processing time and number of failures could be demonstrated. Study participants indicated the 60°/20° position as the most comfortable in the questionnaire. This was therefore compared with the laparoscopic reference position, both sitting and standing. Here, the laparoscopic sitting position was perceived to be the most ergonomic.

Conclusions

The developed input device offers a maximum of flexibility and individualization to reach ergonomic and intuitive conditions. General recommendations regarding an optimal setting cannot be given, based on our results.

This article is protected by copyright. All rights reserved.

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Effects of oral screen exercise on orofacial and pharyngeal activity: An exploratory study using videofluoroscopy and surface electromyography in healthy adults

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Clin Exp Dent Res. 2022 Feb 1. doi: 10.1002/cre2.538. Online ahead of print.

ABSTRACT

OBJECTIVE: The oral screen is a device commonly used for treatment of orofacial disorders. The objective of this exploratory study was to examine the effect of oral screen exercise on the muscle activity in the lips, submental complex, masseter muscle, and kinematic activity of the tongue base, soft palate, pharynx, and larynx in healthy adults. This was compared with the kinematic activity during a dry swallow. It was hypothesized that not only the lip musculature but also other structures in the oral and pharyngeal cavities are activated while using an oral screen device.

METHOD: Ten healthy subjects used an oral screen during examination with videofluoroscopy and surface electromyography (EMG). Three different instructions for oral screen application and a dry swallow were examined.

RESULTS: The lip muscles showed the highest activity during oral screen exercise. The other muscle groups were activated to a lesser degree. The pattern of activation differed between individuals. Compared with a dry swallow, the range of motion of the tongue base, posterior pharyngeal wall, and the larynx was significantly smaller during oral screen activation. No major differences were found between three different instructions.

CONCLUSION: This study indicates that the lips and submental complex and, to a lesser degree, oral, pharyngeal, and laryngeal structures are activa ted with the oral screen, but the pattern of activation varied between individuals. In comparison to the activity during a dry swallow, range of motion during oral screen exercise is small.

PMID:35106972 | DOI:10.1002/cre2.538

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Drug-drug interactions of tyrosine kinase inhibitors in treatment of non-small-cell lung carcinoma

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Bull Cancer. 2022 Jan 29:S0007-4551(22)00010-8. doi: 10.1016/j.bulcan.2021.11.019. Online ahead of print.

ABSTRACT

The development of tyrosine kinase inhibitors has revolutionized the treatment strategy in patients with non-small cell lung cancer with activating EGFR mutations, ALK or ROS-1 gene rearrangements. The Food and Drug Administration and European Medicines Agency have approved several inhibitors for the treatment of non-small cell lung cancer : five tyrosine kinase inhibitors targeting EGFR (erlotinib, gefitinib, afatinib, osimertinib and dacomitinib) and six tyrosine kinase inhibitors targeting ALK (crizotinib, céritinib, alectinib, brigatinib, lorlatinib and entrectinib). Interestingly, these tyrosine kinase inhibitor treatments are administered orally. While this route of administration improves the treatment flexibility and provides a comfortable and preferable option for patients, it also increases the risk of drug-drug interactions. The latter may result in changes in pharmacokinetics or pharmacodynamics of the tyrosine kinase inhibitors or their concomitant treatments, with subsequent risks of increasing their toxicity and/or reducing their effectiveness. This review provides an overview of drug-drug interactions with tyrosine kinase inhibitors targeting EGFR and ALK, as well as practical recommendations to guide oncologists and clinical pharmacists in the process of managing drug-drug interactions during the treatment of non-small cell lung cancer with tyrosine kinase inhibitors.

PMID:35105467 | DOI:10.1016/j.bulcan.2021.11.019

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The 'hyperdense basivertebral vein' sign: another marker of a CSF-venous fistula

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Neuroradiology. 2022 Feb 1. doi: 10.1007/s00234-022-02908-x. Online ahead of print.

ABSTRACT

CSF-venous fistulas - initially described in 2014 - are a significant cause of spontaneous intracranial hypotension. Dynamic lateral decubitus digital subtraction and/or CT myelography typically show a hyperdense paraspinal vein. In case of a central drainage toward the internal vertebral venous plexus, it is the "hyperdense basivertebral vein" which should be searched for carefully.

PMID:35106631 | DOI:10.1007/s00234-022-02908-x

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Rituximab added to standard chemotherapy and its effect on minimal residual disease during induction in CD20 positive pediatric acute lymphoblastic leukemia: a pilot RCT

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Am J Blood Res. 2021 Dec 15;11(6):571-579. eCollection 2021.

ABSTRACT

The use of rituximab in the treatment of pediatric acute lymphoblastic leukemia (ALL) has been evaluated but mostly this has been done in the setting of a relapsed or refractory disease. Addition of rituximab to the initial treatment regimen improves the outcomes in adult CD20 positive ALL. This study was done to study its effect on newly diagnosed CD20 positive pediatric ALL patients. Twenty pediatric patients with CD20 positive ALL were randomly assigned to receive rituximab along with standard-chemotherapy [Intervention-arm (IA)] or standard-chemotherapy alone [Standard-arm (SA)]. The absolute blast count (ABC) on day 8, flowcytometry-MRD levels in the peripheral blood (PB) on day-8, day-15 and in the bone marrow (BM) at end of induction (EOI) were the outcome variables. Baseline characteristics were comparable between the IA (n=10) and SA (n=10). Significantly lo wer day-8 ABC was seen in the IA (P=0.005). The day-8 PB-MRD showed lower values for the IA but the difference wasn't significant (P=0.22). There was no difference between the IA and SA for day-15 PB-MRD and EOI BM-MRD. There was no difference in the incidence of adverse effects. Rituximab added to standard-chemotherapy lead to lower day-8 ABC and lower day-8 PB-MRD in CD20 positive pediatric ALL patients. Rituximab may be beneficial in pediatric ALL treatment. Studies with larger sample size are needed for more evidence.

PMID:35103111 | PMC:PMC8784647

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Effects of transfusion of stored blood in patients with transfusion-dependent thalassemia

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Am J Blood Res. 2021 Dec 15;11(6):592-599. eCollection 2021.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the hematological and biochemical effects of stored blood transfusion on patients with transfusion-dependent thalassemia (TDT).

METHODS: In this quasi-experimental study, 20-patients with TDT were enrolled. Each participant received on first visit, freshly collected red cell concentrate (RCC) (<2-days storage) and 15-days later on second visit, 7-days stored blood. Blood samples were obtained immediately before and 24-hours after each transfusion. Differences in the Complete blood counts, bilirubin, LDH, C-Reactive protein, ferritin, and iron levels in the pre- and post-transfusion samples were compared between the first and second transfusion.

RESULTS: Fresh blood transfusion resulted in a higher (but non-significant) increase in hemoglobin and other red cell parameters. Notably, a significant incre ase in white cell counts (WCC) was seen in 7-days stored blood vs fresh blood (1.82×109/l vs 1.01×109/l, P=0.002). No statistically significant difference was found in LDH, direct and indirect bilirubin, creatinine, blood glucose, serum uric acid, serum ferritin, and serum Iron levels. There was a statistically significant rise in C-reactive protein levels in stored (6.43±7.46 mg/dl) versus fresh RCC (1.89±2.38 mg/dl), p-value =0.012.

CONCLUSIONS: We show that in patients with chronic TDT, an increase in inflammation-associated markers (WCC and CRP) is observed. Further studies to assess the extent and duration of this increase are needed.

PMID:35103113 | PMC:PMC8784645

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An analysis of hematological, coagulation and biochemical markers in COVID-19 disease and their association with clinical severity and mortality: an Indian outlook

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Am J Blood Res. 2021 Dec 15;11(6):580-591. eCollection 2021.

ABSTRACT

BACKGROUND: The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness which can be controlled only with timely intervention. There is an urgent need to identify laboratory markers of disease progression for optimum allocation of resources in developing countries like India.

METHODS: A cross-sectional study was conducted on 100 COVID-19 positive patients over two months. The cases were sub-classified based on disease severity into mild to moderate (n=61), severe (n=26) and very severe (n=13) and into survivors (n=85) and non-survivors (n=15) based on survivor status. These patients were tested for hematological parameters (total blood lymphocyte counts, NLR, PLR, platelet indices etc.), coagulation markers (D-dimer, fibrin degradation products (FDP), fibrinogen etc.) and biochemical markers (LDH, ferritin, IL-6, procalcitonin, hs-CRP).

RESU LTS: Statistically significant differences were observed in hematological variables (ANC, NLR and ESR), coagulation parameters (D-dimer, FDP, fibrinogen and thrombin time) and biochemical markers (LDH, ferritin, IL-6, procalcitonin and hs-CRP) with regard to subcategories based of disease severity as well as survivor status. There was strong correlation between NLR, D-dimer, IL-6, procalcitonin and ferritin. IL-6 emerged as the single best marker of disease severity (AUC: 0.997, P=0.00), however procalcitonin, LDH, D-dimer, FDP and NLR could also predict severe disease with a good sensitivity and specificity.

CONCLUSION: To conclude, study demonstrates a plethora of biomarkers which could be utilized to accurately identify the hyperinflammation and tissue damage reminiscent of cytokine storm in COVID-19 patients so that timely, safe, and effective therapies can be administered to prevent progression and potentially reduce mortality.

PMID:35103112 | PMC:PMC8784646

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A review of neoplasms with MITF/MiT family translocations

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Histol Histopathol. 2022 Feb 2:18426. doi: 10.14670/HH-18-426. Online ahead of print.

ABSTRACT

Microphthalmia-associated transcription factor (MITF/MiT) family is a group of basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors including TFE3 (TFEA), TFEB, TFEC and MITF. The first renal neoplasms involving MITF family translocation were renal cell carcinomas with chromosome translocations involving ASPL-TFE3/t(X;17)(p11.23;q25) or MALAT1-TFEB/t(6;11)(p21.1;q12), and now it is known as MiT family translocation RCC in 2016 WHO classification. Translocations involving MITF family genes also are found in other tumor types, such as perivascular epithelioid cell neoplasm (PEComa), Alveolar soft part sarcoma (ASPS), epithelioid hemangioendothelioma, ossifying fibromyxoid tumor (OFMT), and clear cell tumor with melanocytic differentiation and ACTIN-MITF translocation. In this review, we summarize the features of different types of neoplasms with MITF family translocations.

PMID:35107169 | DOI:10.14670/HH-18-426

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Adenoid stones, an unknown culprit in pediatric throat pain

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Ear Nose Throat J. 2022 Feb 2:1455613221074139. doi: 10.1177/01455613221074139. Online ahead of print.

ABSTRACT

We present a case of a 12-year-old male who presented with complaints of nasal congestion, intermittent throat pain, and odynophagia. He was taken to the operating room for inferior turbinate reduction and adenoidectomy and found to have stones within adenoid crypts. Adenoidectomy resulted in resolution of the patient's throat pain and pain with swallowing. Not pre viously described in the literature, adenoid stones may represent an unrecognized etiology of odynophagia and throat pain in the pediatric population. Adenoidectomy should be considered for patients symptomatic from adenoid stones.

PMID:35107383 | DOI:10.1177/01455613221074139

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