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Introduction: The Critical Area Perfusion Score (CAPS) predicts functional outcomes in vertebrobasilar thrombectomy patients based on computed tomography perfusion (CTP) hypoperfusion. We compared CAPS to the clinical-radiographic Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS)., Methods: Acute basilar thrombosis patients from January 2017-December 2021 were included in this retrospective analysis from a health system's stroke registry. Inter-rater reliability was assessed for 6 CAPS raters. A logistic regression with CAPS and CLEOS as predictors was performed to predict 90-day modified Rankin Scale (mRS) score 4-6. Area under the curve (AUC) analyses were performed to evaluate prognostic ability., Results: 55 patients, mean age 65.8 (± 13.1) years and median NIHSS score 15.5 5-24 , were included. Light's kappa among 6 raters for favorable versus unfavorable CAPS was 0.633 (95% CI 0.497-0.785). Increased CLEOS was associated with elevated odds of a poor outcome (odds ratio (OR) 1.0010, 95% CI 1.0007-1.0014, p<0.01), though CAPS was not (OR 1.0028, 95% CI 0.9420-1.0676, p=0.93). An overall favorable trend was observed for CLEOS (AUC 0.69, 95% CI 0.54-0.84) versus CAPS (AUC 0.49, 95% CI 0.34-0.64; p=0.051). Among 85.5% of patients with endovascular reperfusion, CLEOS had a statistically higher sensitivity than CAPS at identifying poor 90-day outcomes (71% versus 21%, p=0.003)., Conclusions: CLEOS demonstrated better predictive ability than CAPS for poor outcomes overall and in patients achieving reperfusion after basilar thrombectomy., Competing Interests: Declaration of Competing Interest Dr. Joe Bernard declares stock/stock options from Viz.Ai and personal fees from Stryker, Terumo, and Rapid AI. Dr. Jeremy Heit is a consultant for Medtronic and MicroVention and a member of the Scientific and Advisory Board for iSchemaView. Dr. Gregory Albers is a consultant for Genentech, iSchemaView, and Biogen and has equity interest in iSchemaView. All other authors report no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Piriformis syndrome is described as a neuromuscular condition which occurs when the sciatic nerve is compressed and/or irritated by the piriformis muscle. It is characterized by acute tenderness in the buttock with sciatica-like pain radiating into the posterior aspect of the thigh, leg, and foot. The neurogenic leg and foot pain experienced with this condition is consistent with involvement of the sciatic nerve. However, the posterior thigh pain associated with piriformis syndrome is due to involvement of the posterior femoral cutaneous nerve (i.e., posterior cutaneous nerve of the thigh), which is a branch of the sacral plexus independent of the sciatic nerve. This nerve is rarely mentioned relative to piriformis syndrome even though posterior thigh pain is more prevalent in patients than leg and foot pain. In the few instances when the posterior femoral cutaneous nerve is referenced relative to piriformis syndrome the neuralgic signs associated with it are attributed to compression by piriformis. Yet, given the dramatic size difference between the sciatic and posterior femoral cutaneous nerves one would expect direct piriformis compression to impact the sciatic nerve first and produce leg/foot pain at a far greater frequency than posterior thigh pain. However, the opposite is seen in the literature, which raises the question, what underlying mechanism is responsible for this phenomenon? It is hypothesized that the prevalence of posterior femoral cutaneous nerve involvement in piriformis syndrome is due to compression of the inferior gluteal vein by a hypertrophied piriformis muscle., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cancer-cachexia (CC) is a wasting condition directly responsible for 20-40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the postcachectic state and do not examine progression of the condition. We recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations before wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Lewis lung carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wk of age with tumor allowed to develop for 1, 2, 3, or 4 wk and compared with PBS-injected control. Muscle wasting was evident at 4 wk LLC. RNA sequencing of gastrocnemius muscle samples showed widespread alterations in LLC compared with PBS animals with largest differences seen in 4 wk LLC, suggesting extensive transcriptomic alterations concurrent to muscle wasting. Commonly altered pathways included: mitochondrial dysfunction and protein ubiquitination, along with other less studied processes in this condition regulating transcription/translation and cytoskeletal structure. Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.

Background: Prevalence of Type 2 Diabetes Mellitus (T2DM) has reached pandemic levels in the Western societies. T2DM begins with the development of peripheral insulin resistance which prior research suggests may commonly originate within the skeletal muscle. A number of mechanisms have been proposed for the development of muscle insulin resistance including those of classical glucose handling, and also other cellular derangements observed in this disease which include mitochondrial degeneration, alterations in muscle protein turnover and early evidences for dysregulation of the microRNAs. The purpose of the current review is to examine the current findings on these latter aspects of mitochondrial maintenance, protein turnover and microRNA dysregulation along with the potential implications for these derangements in the development of insulin resistance and hence T2DM. We summarize multiple evidences for the degeneration of mitochondria and known elements of the processes regulating mitochondrial quality. Subsequently, we examine current findings of the alterations in muscle protein synthesis and autophagic protein degradation in T2DM and potential feedback of these systems onto canonical insulin signaling. Finally, evidences have emerged for the dysregulation of microRNAs in muscle insulin resistance. Of note early data point to several microRNAs altered by the insulin resistant state which exhibit relations to classic insulin signaling and the other processes discussed here., Conclusion: Considering that T2DM may be initiated with muscle insulin resistance, improved understanding of the dysregulation of these metabolic parameters of skeletal muscle in the pathogenesis of T2DM may be key to developing efficacious therapeutic modalities to prevent and treat this condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia. Therefore, our purpose was to determine if mitochondrial degeneration precedes cancer-induced muscle wasting in tumour-bearing mice., Methods: First, weight-stable (MinStable) and cachectic (MinCC) Apc Min/+ mice were compared with C57Bl6/J controls for mRNA contents of mitochondrial quality regulators in quadriceps muscle. Next, Lewis lung carcinoma (LLC) cells or PBS (control) were injected into the hind flank of C57Bl6/J mice at 8 week age, and tumour allowed to develop for 1, 2, 3, or 4 weeks to examine time course of cachectic development. Succinate dehydrogenase stain was used to measure oxidative phenotype in tibialis anterior muscle. Mitochondrial quality and function were assessed using the reporter MitoTimer by transfection to flexor digitorum brevis and mitochondrial function/ROS emission in permeabilized adult myofibres from plantaris. RT-qPCR and immunoblot measured the expression of mitochondrial quality control and antioxidant proteins. Data were analysed by one-way ANOVA with Student-Newman-Kuels post hoc test., Results: MinStable mice displayed ~50% lower Pgc-1α, Pparα, and Mfn2 compared with C57Bl6/J controls, whereas MinCC exhibited 10-fold greater Bnip3 content compared with C57Bl6/J controls. In LLC, cachectic muscle loss was evident only at 4 weeks post-tumour implantation. Oxidative capacity and mitochondrial content decreased by ~40% 4 weeks post-tumour implantation. Mitochondrial function decreased by ~25% by 3 weeks after tumour implantation. Mitochondrial degeneration was evident by 2 week LLC compared with PBS control, indicated by MitoTimer red/green ratio and number of pure red puncta. Mitochondrial ROS production was elevated by ~50 to ~100% when compared with PBS at 1-3 weeks post-tumour implantation. Mitochondrial quality control was dysregulated throughout the progression of cancer cachexia in tumour-bearing mice. In contrast, antioxidant proteins were not altered in cachectic muscle wasting., Conclusions: Functional mitochondrial degeneration is evident in LLC tumour-bearing mice prior to muscle atrophy. Contents of mitochondrial quality regulators across Apc Min/+ and LLC mice suggest impaired mitochondrial quality control as a commonality among pre-clinical models of cancer cachexia. Our data provide novel evidence for impaired mitochondrial health prior to cachectic muscle loss and provide a potential therapeutic target to prevent cancer cachexia., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

New Findings: What is the central question of this study? What are the individual and combined effects of muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) overexpression and physical activity during high-fat feeding on glucose and exercise tolerance? What is the main finding and its importance? Our main finding is that muscle-specific PGC-1α overexpression provides no protection against lipid-overload pathologies nor does it enhance exercise adaptations. Instead, physical activity, regardless of PGC-1α content, protects against high-fat diet-induced detriments. Activation of muscle autophagy was correlated with exercise protection, suggesting that autophagy might be a mediating factor for exercise-induced protection from lipid overload. The prevalence of glucose intolerance is alarmingly high. Efforts to promote mitochondrial biogenesis through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) to mitigate glucose intolerance have been controversial. However, physical activity remains a primary means to alleviate the condition. The aim of this study was to determine the combined effects of muscle-specific overexpression of PGC-1α and physical activity on glucose handling during diet-induced obesity. Wild-type (WT, ∼20) and PGC-1α muscle transgenic (MCK-PGC-1α, ∼20) mice were given a Western diet (WD) at 8 weeks age and allowed to consume food ab libitum throughout the study. At 12 weeks of age, all animals were divided into sedentary (SED) or voluntary wheel running (VWR) interventions. At 7, 11 and 15 weeks of age, animals underwent glucose tolerance tests (GTT) and graded exercise tests (GXT). At 16 weeks of age, tissues were collected. At 11 weeks, the MCK-PGC-1α animals had 50% greater glucose tolerance integrated area under the curve compared with WT. However, at 15 weeks, SED animals also had greater GTT integrated area under the curve compared with VWR, regardless of genotype; furthermore, SED animals demonstrated reduced exercise capacity compared with earlier time points, which was not seen in VWR animals. Voluntary distance run per day was correlated with GTT in VWR-WT, but not VWR-MCK-PGC-1α mice. Voluntary wheel running and genotype independently resulted in a greater LC3II/LC3I ratio, suggesting enhanced autophagosome formation, which was correlated with exercise-induced improvements in GTT. In conclusion, artificially increasing mitochondrial content does not protect from lipid-induced pathologies nor does it augment exercise adaptations. Physical activity ameliorates the effects of lipid overload-induced glucose intolerance, an effect that appears to be related to enhanced activation of autophagy., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

Aim: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass., Methods: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined., Results: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA., Conclusion: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions., (© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia., (Copyright © 2017 the American Physiological Society.)

When it struck the US Gulf Coast in 2005, Hurricane Katrina severely disrupted many graduate medical education residency/fellowship programs in the region and the training of hundreds of residents/fellows. Despite the work of the Accreditation Council for Graduate Medical Education in responding to this natural disaster and facilitating communication and transfer of residents/fellows to other unaffected training programs, the storm exposed the gaps in the existing system. Subsequently, the Accreditation Council for Graduate Medical Education, with the aid of its member organizations, including the American Medical Association, developed a new disaster recovery plan to allow for a more rapid, effective response to future catastrophic events. These policies were instrumental in the rapid relocation of 597 residents/fellows from the University of Texas Medical Branch at Galveston after the landfall of Hurricane Ike in September 2008. As a further accommodation to affected trainees, medical certification boards should be as flexible as possible in waiving continuity requirements in the event of a disaster that affects residency/fellowship programs.

A renewed emphasis on clinical competence and its assessment has grown out of public concerns about the safety, efficacy, and accountability of health care in the United States. Medical schools and residency training programs are paying increased attention to teaching and evaluating basic clinical skills, stimulated in part by these concerns and the responding initiatives of accrediting, certifying, and licensing bodies. This paper, from the Residency Review Committee for Internal Medicine of the Accreditation Council for Graduate Medical Education, proposes a new outcomes-based accreditation strategy for residency training programs in internal medicine. It shifts residency program accreditation from external audit of educational process to continuous assessment and improvement of trainee clinical competence.

One of the most important challenges in resident education is to train residents how to function in relation to managed care companies and systems so as to enhance the quality, accessibility, and efficiency of health care. Since 1996, The University of Texas Medical Branch in Galveston has presented an annual half-day seminar on managed care to new residents. The format involves training sessions and didactic presentations aimed at small groups (led by faculty physicians and nonphysicians from throughout the medical and managed care establishments). Problem-based learning sessions conducted in these groups focus on topics such as the organization of managed care systems, access, network, admit versus observation, inpatient status, denials, avoidable hospital days, concurrent reviews, gatekeepers, referrals, behavioral health, disease management programs, and financial considerations. Pretests and posttests are given to those participating to gauge the effectiveness of the program. In addition, participants complete evaluation forms that can be used by program coordinators to assess resident satisfaction with the learning format and to determine what improvements can be made in the process. For the 1999 and 2000 seminars, posttest results were significantly higher than pretest results for the new residents who participated in the seminar. Each year, seminar evaluations show that the small-group format is well received. We conclude that the small-group learning format is effective and enjoyable for the residents and their leaders. The format necessitates the training of 30 group leaders to increase their knowledge of managed care systems.

Treatment of craniofacial hyperhidrosis currently consists of thoracic sympathectomy, which is not widely available. Oral anticholinergic agents and beta-blockers may be effective but also carry significant side effects. We describe a healthy, active 27-year-old male resident physician who had excessive facial sweating with minimal exertion or stress. The sweating was especially pronounced on the forehead, nose, and upper lip. Daily topical application of a 0.5% glycopyrrolate solution to the face and forehead was offered. After the first treatment, facial sweating was significantly reduced and was well controlled under stressful situations, without any discomfort to the skin. No loss of efficacy was seen after multiple face washings. Facial hyperhidrosis recurred after withdrawal of the glycopyrrolate for 2 days, confirming its therapeutic effect. Two years later, he continues to use glycopyrrolate as needed. We conclude that topical glycopyrrolate is effective in treating craniofacial hyperhidrosis and is associated with few adverse effects.

Study Objective: To determine the usefulness of screening reviews of the cardiopulmonary and gastrointestinal systems during medical admissions., Design: Case series., Setting: General internal medicine ward of a university hospital., Patients: 550 consecutive medical patients were initially screened at admission. The authors excluded 265 patients with life-limiting medical conditions, and they studied 98 patients with no known cardiopulmonary disease and 207 patients with no known gastrointestinal disease., Interventions: Positive responses to screening systems review questions were evaluated using a standardized testing algorithm., Main Outcome Measures: Numbers of new diagnoses; potential for patient benefit., Main Results: The authors made 26 new diagnoses for 25 patients (95% confidence limits, 16 to 37 patients), two of whom may have gained years of life as a result., Conclusions: The absolute yield of the screening cardiopulmonary and gastrointestinal reviews of systems of 550 patients admitted to an internal medicine service of a university hospital was a new diagnosis in about 5% of patients. An estimate of the cost-effectiveness compares favorably with those of other accepted screening practices.

The primary goal of medical education is to foster development of clinical competence in trainees at all levels. Variable clinical experience, inconsistent methods of instruction, and ambiguous evaluation criteria undermine this goal. Standardized patients, trained to consistently portray a wide variety of clinical cases, can help overcome many of these educational problems. This article describes the development and application of standardized patients throughout medical training at The University of Texas Medical Branch, Galveston, in the freshman interviewing course, the second-year physical diagnosis course, third-year clerkships, a fourth-year final exercise, and residency training. Development of this program is discussed in the context of a broader literature in medical education, and investigation of variables affecting standardized patient and student performance is reported. Future directions for use of standardized patients in monitoring and promoting the development of clinical competence are discussed.

Clinical performance of residents should be assessed as reliably and validly as possible. This study investigated the reliability and validity of an objective structured clinical examination (OSCE) for assessing clinical performance of internal medicine residents. Residents were required to take a 17-patient OSCE in their first and second year. Reliability of the OSCE was 0.40. Validity studies indicated second-year students were significantly better than third-year students for five of six OSCE skill scores; first-year students were significantly better for three scores. Resident's scores for diagnosis, plan, and total significantly increased on their second OSCE. Generally faculty overall ratings of residents' clinical performance did not correlate with OSCE scores. American Board of Internal Medicine certifying examination scores were consistently positively correlated only with diagnosis. This 17-case OSCE is a feasible method for obtaining moderately reliable, valid data not available from other sources about the clinical performance of residents. More cases should be added to increase its reliability.

Studies repeatedly have shown the clinical performance of students and residents to be less than expected by faculty. Because evaluation methods substantially influence education, poor performance can be improved with better clinical evaluation methods. This study evaluated a standardized method to measure clinical performance in which trained actual and simulated patients were organized in a multiple-station format for efficient testing of examinees on 17 cases in less than four hours. Specific checklists completed by patients and predetermined scoring protocols yielded reliable data and reduced faculty time. Data from 204 students in three clerkships were consistent with previous research showing case specificity and substantial case-to-case variability. As a group however, the students' overall total scores were very similar. This suggests that clinical education is inconsistent and that a profile of an examinee's performance is more accurate than a single overall score. Validity of this standardized clinical examination was supported by significant but moderate correlations with faculty ratings of ward performance and the medicine subtest of the National Board of Medical Examiners test, part II. Direct per-student costs were $21.00. This standardized objective examination of clinical skills is feasible for use in training programs and will provide reliable and valid data on clinical performance not available through typical methods.