Monday, February 13, 2023

Triple Dufourmentel hexagonal flap for scalp reconstruction

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Abstract

Transposition flaps are some of the most commonly used flaps for reconstructing scalp defects. Limberg first described his rhomboid transposition flap in 1946. Dufourmentel flap was an improved version of the Limberg flap published in 1962 in which the base of the flap is widened to improve vascularisation.

Transposition flaps are one of the best known and most widely used transposition flaps in reconstructive surgery. They has proven successful in different types of reconstructive and aesthetic situations as a full-thickness random transposition flap.

Combination of three Dufourmentel flaps to reconstruct hexagonal defects has not been reported in the literature. It is a modification of the triple Limberg flap, in which, after removing a hexagonal defect, we reconstruct the primary defect with a triple Dufourmentel flap.

This flap is very useful for reconstructing large scalp defects as it provides a large amount of skin tissue with high viability; however, given its versatility, it could be used in other anatomical areas1, 2, 3.

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A systematic comparison of pan‐Trk immunohistochemistry assays across multiple cancer types

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A systematic comparison of pan-Trk immunohistochemistry assays across multiple cancer types


Aims

NTRK-rearranged tumours are rare but can be successfully treated using anti-TRK–targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool in many laboratories. Unfortunately, the choice of antibodies and IHC protocols to investigate biomarkers is not standardized. In this study, we compared the performance of four pan-Trk IHC methods, using three different clones, primarily in NTRK- fusion positive tumours.

Method

We studied the performance of four pan-Trk IHC methods, using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam), A7H6R (Cell Signaling) in 22 molecularly confirmed NTRK-rearranged tumours. Additionally, selected NTRK-fusion negative tumours were further included: NTRK mutated (n=8) and amplified (N=15) tumours as well as NTRK-fusion negative tumours driven by other gene fusions such as ALK, ROS1 and BCOR (n=20) as well as salivary gland tumours (n=16). Interrater agreement of three pathologist was additionally calculated, including H-score.

Result

With clone EPR17341 (Abcam in house and ready to use Ventana protocol) all molecularly confirmed NTRK 1-3 rearranged tumours were positively detected by immunohistochemistry, while the other clones missed NTRK2-3-rearranged tumours. For the fusion negative cohort we found the best performance (least false positive cases) using the clone A7H6R (Cell Signalling).

Conclusion

Given the therapeutic importance, testing for NTRK rearrangements in daily practice has become necessary and despite IHC being a fast and affordable tool, using it in routine diagnostics is complicated and requires a high level of expertise.

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Combined proliferation and apoptosis index provides better risk stratification in breast cancer

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Combined proliferation and apoptosis index provides better risk stratification in breast cancer


Introduction

Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in vivo growth rate measure and a precise prognostic predictor.

Methods and Results

Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour including high grade, high pleomorphism score, and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BC patients with a high combined AI and MI had the shortest survival. Replacing the mitosis score with the mitosis-apoptosis index, in the Nottingham grading system, revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio.

Conclusion

Apoptotic figures count provides additional prognostic value in BC when combined with MI, such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC.

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Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon [Report]

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Transfer RNA fragments are proposed to regulate numerous processes in eukaryotes, including translation inhibition, epigenetic inheritance and cancer. In the bacterium Salmonella enterica serovar Typhimurium, 5' tRNA halves ending in 2', 3' cyclic phosphate are proposed to bind the RtcR transcriptional activator, resulting in transcription of an RNA repair operon. However, since 5' and 3' tRNA halves can remain base paired after cleavage, the 5' tRNA halves could potentially bind RtcR as nicked tRNAs. Here we report that nicked tRNAs are ligands for RtcR. By isolating RNA from bacteria under conditions that preserve base pairing, we show that many tRNA halves are in the form of nicked tRNAs. Using a circularly permuted tRNA that mimics a nicked tRNA, we show that nicked tRNA ending in 2', 3' cyclic phosphate is a better ligand for RtcR than the corresponding 5' tRNA half. In human cells, we show that some tRNA halves similarly remain base paired as nicked tR NAs following cleavage by anticodon nucleases. Our work supports a role for the RNA repair operon in repairing nicked tRNAs and has implications for the functions proposed for tRNA fragments in eukaryotes.

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Strength-based rehabilitation on clinical outcomes in patients post-partial meniscectomy: a systematic review and meta-analysis

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Objective To determine the effect of strength-based rehabilitation programs on patients who underwent partial meniscectomy procedures Design Three databases MEDLINE, PubMed and EMBASE were searched from inception to May 9th, 2022. Data on functional outcomes such as quadriceps and hamstring strengths, as well as patient-reported outcomes such as Knee Osteoarthritis and Outcome Score (KOOS) and Visual-Analogue Scale (VAS) were recorded. Results A total of nine studies comprising 417 patients were included in this review. There were no significant differences in quadriceps or hamstring strength measures between pre and post-intervention for both groups. KOOS scores significantly increased from pre and post-intervention in both control and exercise groups. VAS scores changed from 5.0 cm to 1.4 cm in the exercise arm and 3.1 cm to 1.9 cm in the control arm. Conclusion Strength-based exercise programs for patients post-partial meniscectomy did not result in significantly different improvements in quadriceps or hamstring strength compared to control programs. However, strength-based exercise programs resulted in significantly higher KOOS scores and a greater decrease in VAS scores. Further studies, specifically well-designed systematic randomized controlled trials are necessary in order to elucidate the specifics behind what type of exercises to use in addition to load progression and frequency of training. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
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Atypical Cause for Back Pain and Sciatica in a 35-year-old Female with Fibromyalgia

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Spinal and extra-pelvic lesions causing sciatic symptoms are well recognized in clinical research and practice.1–5 We present a 35-yr-old woman with a history of axial back pain and fibromyalgia who presented with episodes of radicular type pain down her legs and associated bilateral tingling in her feet. Medicinal and therapeutic interventions for traditional sciatica etiologies failed to provide relief. Lumbar magnetic resonance imaging showed mild multilevel degenerative changes and partially visualized fibroids, but no other significant spinal pathology was appreciated. Subsequent pelvic magnetic resonance imaging revealed an enlarged retroverted uterus with multiple fibroid lesions. The patient elected for laparoscopic myomectomy, which improved her likelihood of fertility while drastically alleviatin g her axial spine and lower extremity symptomology. This case reinforces the importance of keeping a broad differential that includes intrapelvic etiologies when traditional workup and treatment for sciatic neuropathy fails. To our knowledge, this is the first reported case of sciatic neuropathy secondary to uterine fibroids treated with the intent of both fertility improvement and pain relief. Spinal and extra-pelvic lesions causing sciatic symptoms are well recognized in clinical research and practice.1–5 We present a 35-yr-old woman with a history of axial back pain and fibromyalgia who presented with episodes of radicular type pain down her legs and associated bilateral tingling in her feet. Medicinal and therapeutic interventions for traditional sciatica etiologies failed to provide relief. Lumbar magnetic resonance imaging showed mild multilevel degenerative changes and partially visualized fibroids, but no other significant spinal pathology was appreciated. Subsequent pelvic magnetic resonance imaging revealed an enlarged retroverted uterus with multiple fibroid lesions. The patient elected for laparoscopic myomectomy, which improved her likelihood of fertility while drastically alleviating her axial spine and lower extremity symptomology. This case reinforces the importance of keeping a broad differential that includes intrapelvic etiologies when traditional worku p and treatment for sciatic neuropathy fails. To our knowledge, this is the first reported case of sciatic neuropathy secondary to uterine fibroids treated with the intent of both fertility improvement and pain relief. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
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Key Modifiable Factors in Community Participation among Adults with Lower-Limb Amputation

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Objective To identify factors that may predict community participation among adults with lower-limb amputation (LLA). Design This study is a secondary analysis of a cross-sectional dataset, including 126 community-dwelling adults, ≥1 year after unilateral transfemoral- (n = 44; mean age = 59 ± 14 years) or transtibial-level amputation (n = 82; mean age = 59 ± 14 years) seen in an outpatient limb loss clinic. Participation was assessed with the Community Integration Questionnaire (CIQ). Factors, i.e., demographics, comorbidities, prosthesis-use per the Houghton Scale, Socket Comfort Score, assistive device use, falls history, and activity level per General Practice Physical Activity Questionnaire were evaluated. Moreover, balance-confidence per the Activities-Specific Balance Confidence Scale, mobility per the Locomotor Capabilities Index, fast and self-selected gait speed per 10-meter Walk Tests, and functional mobility via Timed Up and Go, were also included. Results Community participation was correlated with several factors (p ≤ 0.050). Stepwise regression of correlated factors found absence of peripheral neuropathy and greater self-reported physical activity, balance-confidence, and prosthesis use, as the strongest correlates, collectively explaining 50.1% of the variance in community participation post-LLA. Conclusions Findings identify key modifiable factors for consideration in future prospective research seeking to enhance community reintegration and participation among adults living with a unilateral transfemoral- or transtibial-level amputation. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
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Improving trunk postural control facilitates walking in children with cerebral palsy: a pilot study

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Objective The aim of this study was to determine the effects of bilateral trunk support during walking on trunk and leg kinematics and neuromuscular responses in children with cerebral palsy (CP). Design Fourteen children with spastic CP (GMFCS level I to III) participated in this study. Children walked on a treadmill under 4 different conditions, i.e., without support (BASELINE), with bilateral support applied to the upper trunk (UTS), the lower trunk (LTS), and combined upper and lower trunk (CTS). The trunk and leg kinematics and muscle activity were recorded. Results Providing bilateral support to the trunk had a significant impact on the displacement of the pelvis and trunk (p
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Accurate Detection of α‐Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort

AlexandrosSfakianakis shared this article with you from Inoreader
Accurate Detection of α-Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort


ABSTRACT

Background

Misfolded α-synuclein (αSyn) aggregates (αSyn-seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn-seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD).

Objectives

The objective of this study was to determine the accuracy of the αSyn–seed amplification assay (αS-SAA) in a comprehensively characterized cohort with a high proportion of PD and iRBD CSF samples collected at baseline.

Methods

We used a high-throughput αS-SAA to analyze 233 blinded CSF samples from 206 participants of the DeNovo Parkinson Cohort (DeNoPa) (113 de novo PD, 64 healthy controls, 29 iRBD confirmed by video polysomnography). Results were compared with the final diagnosis, which was determined after up to 10 years of longitudinal clinical evaluations, including dopamine-transporter–single-photon emission computed tomography (DAT-SPECT) at baseline, CSF proteins, Movement Disorder Society–Unified Parkinson's Disease Rating Scale, and various cognitive and nonmotor scales.

Results

αS-SAA detected αSyn-seeds in baseline PD-CSF with 98% accuracy. αSyn-seeds were detected in 93% of the iRBD cases. αS-SAA results showed higher agreement with the final than the initial diagnosis, as 14 patients were rediagnosed as non-αSyn aggregation disorder. For synucleinopathies, αS-SAA showed higher concordance with the final diagnosis than DAT-SPECT. Statistically significant correlations were found between assay parameters and disease progression.

Conclusions

Our results confirm αS-SAA accuracy at the first clinical evaluation when a definite diagnosis is most consequential. αS-SAA conditions reported here are highly sensitive, enabling the detection of αSyn-seeds in CSF from iRBD just months after the first symptoms, suggesting that αSyn-seeds are present in the very early prodromal phase of synucleinopathies. Therefore, αSyn-seeds are clear risk markers for synuclein-related disorders, but not for time of phenoconversion. © 2023 International Parkinson and Movement Disorder Society.

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Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

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Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

Plasma neurofilament light chain (NfL) is a promising biomarker of progressive supranuclear palsy (PSP) to assist in PSP diagnosis and differential diagnosis from Parkinson's disease (PD) and to monitor disease severity. Pending replication in independent cohorts, plasma glial fibrillary acidic protein (GFAP) holds promise for a PSP diagnosis and a differential diagnosis with multiple system atrophy with predominant parkinsonism (MSA-P) and for detecting brainstem atrophy and tau deposition in PSP.


ABSTRACT

Background

Development of disease-modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers.

Objectives

The objectives of this study were to explore the utility of plasma biomarkers in the diagnosis, differential diagnosis, and assessment of disease severity, brain atrophy, and tau deposition in PSP.

Methods

Plasma biomarkers were measured using a single-molecule array in a cohort composed of patients with PSP, Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P), and healthy controls (HCs).

Results

Plasma neurofilament light chain (NfL) outperformed other plasma makers (ie, glial fibrillary acidic protein [GFAP], phosphorylated-tau 181 [p-tau181], amyloid-β 1–40, amyloid-β 1–42) in identifying PSP from HC (area under the curve [AUC] = 0.904) and from MSA-P (AUC = 0.711). Plasma GFAP aided in distinguishing PSP from HC (AUC = 0.774) and from MSA-P (AUC = 0.832). It correlated with brainstem atrophy and higher regional tau accumulation. However, plasma p-tau181 neither helped in diagnosis nor was it associated with clinical or neuroimaging measures.

Conclusions

Plasma NfL and GFAP showed different values in differentiating PSP from HC or controls with other forms of neurodegenerative parkinsonism and detecting disease severity, brain atrophy, or tau deposition in PSP. © 2023 International Parkinson and Movement Disorder Society.

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