Updates on the Applications of Spectral Computed Tomography for Musculoskeletal Imaging.

Spectral CT represents a novel imaging approach that can noninvasively visualize, quantify, and characterize many musculoskeletal pathologies. This modality has revolutionized the field of radiology by capturing CT attenuation data across multiple energy levels and offering superior tissue characterization while potentially minimizing radiation exposure compared to traditional enhanced CT scans. Despite MRI being the preferred imaging method for many musculoskeletal conditions, it is not viable for some patients. Moreover, this technique is time-consuming, costly, and has limited availability in many healthcare settings. Thus, spectral CT has a considerable role in improving the diagnosis, characterization, and treatment of gout, inflammatory arthropathies, degenerative disc disease, osteoporosis, occult fractures, malignancies, ligamentous injuries, and other bone-marrow pathologies. This comprehensive review will delve into the diverse capabilities of dual-energy CT, a subset of spectral CT, in addressing these musculoskeletal conditions and explore potential future avenues for its integration into clinical practice.

Detecting androgen receptor (AR), AR variant 7 (AR-V7), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA) gene expression in CTCs and plasma exosome-derived cfRNA in patients with metastatic castration-resistant prostate cancer (mCRPC) by integrating the VTX-1 CTC isolation system with the QIAGEN AdnaTest.

BACKGROUND: Therapies for metastatic castration-resistant prostate cancer (mCRPC) include targeting the androgen receptor (AR) with androgen receptor inhibitors (ARIs) and prostate-specific membrane antigen (PSMA). Having the ability to detect AR, AR splice variant 7 (AR-V7), or PSMA in circulating tumor cells (CTCs) or circulating exosomal cell-free RNA (cfRNA) could be helpful to guide selection of the appropriate therapy for each individual patient. The Vortex Biosciences VTX-1 system is a label-free CTC isolation system that enables the detection of the expression of multiple genes in both CTCs and exosomal cfRNA from the same blood sample in patients with mCRPC. Detection of both AR-V7 and PSMA gene expression in both CTCs and cfRNA simultaneously has not yet been reported. METHODS: To characterize the combined VTX-1-AdnaDetect workflow, 22Rv1 cancer cells were spiked into blood from healthy donors and processed with the VTX-1 to mimic patient samples and assess performances (capture efficiency, purity, AR and AR-V7 expression). Then, we collected 19 blood samples from 16 patients with mCRPC and therapeutic resistance to androgen receptor inhibitors (ARIs). Plasma was separated and the plasma-depleted blood was processed further with the VTX-1 to collect CTCs. Both plasma exosomal cfRNA and CTCs were subsequently analyzed for AR, AR-V7, PSMA, and prostate-specific antigen (PSA) mRNA expression using the AdnaTest ProstateCancerPanel AR-V7 assay. RESULTS: AR-V7 expression could be detected in 22Rv1 cells spiked into blood from healthy volunteers as well as in CTCs and plasma-derived exosomal cfRNA from patients with mCRPC by processing blood with the VTX-1 CTC isolation system followed by the AdnaTest ProstateCancerPanel AR-V7 assay. 94.7% of patient blood samples (18/19) had detectable AR expression in either CTCs or exosomal cfRNA (16 in CTCs, 12 in cfRNA). 15.8% of the 19 patient blood samples (3/19) were found to have AR-V7-positive (AR-V7+) CTCs, one of which was also AR-V7+ in the exosomal cfRNA analysis. 42.1% of patient blood samples (8/19) were found to be PSMA positive (PSMA+): 26.3% (5/19) were PSMA+ in the CTC analysis and 31.6% (6/19) were PSMA+ in the exosomal cfRNA analysis. Of those 8 PSMA+ samples, 2 had detectable PSMA only in CTCs, and 3 had detectable PSMA only in exosomal cfRNA. CONCLUSION: VTX-1 enables isolation of CTCs and plasma exosomes from a single blood draw and can be used for detecting AR-V7 and PSMA mRNA in both CTCs and cfRNA in patients with mCRPC and resistance to ARIs. This technology facilitates combining RNA measurements in CTCs and exosomal cfRNA for future studies to develop potentially clinically relevant cancer biomarker detection in blood.

Heat shock protein 27 in the pathogenesis of COVID-19 and non-COVID acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure in intensive care units that has increased dramatically as a result of the COVID-19 pandemic. In both COVID-19 and non-COVID ARDS, the pathogenesis of lung injury involves local (pulmonary) and systemic inflammation, leading to impaired gas exchange, requirement for mechanical ventilation, and a high risk of mortality. Heat shock protein 27 (HSP27) is a chaperone protein expressed in times of cell stress with roles in modulation of systemic inflammation via the NF-κB pathway. Given its important role as a modulator of inflammation, we sought to investigate the role of HSP27 and its associated auto-antibodies in ARDS caused by both SARS-CoV-2 and non-COVID etiologies. A total of 68 patients admitted to the intensive care unit with ARDS requiring mechanical ventilation were enrolled in a prospective, observational study that included 22 non-COVID-19 and 46 COVID-19 patients. Blood plasma levels of HSP27, anti-HSP27 auto-antibody (AAB), and cytokine profiles were measured on days 1 and 3 of ICU admission along with clinical outcome measures. Patients with COVID-19 ARDS displayed significantly higher levels of HSP27 in plasma, and a higher ratio of HSP27:AAB on both day 1 and day 3 of ICU admission. In patients with COVID-19, higher levels of circulating HSP27 and HSP27:AAB ratio were associated with a more severe systemic inflammatory response and adverse clinical outcomes including more severe hypoxemic respiratory failure. These findings implicate HSP27 as a marker of advanced pathogenesis of disease contributing to the dysregulated systemic inflammation and worse clinical outcomes in COVID-19 ARDS, and therefore may represent a potential therapeutic target.

Variability in Reporting eGFR at Dialysis Initiation in Canada: A Research Letter.

Background: Estimated glomerular filtration rate (eGFR) at dialysis initiation is increasingly recognized as a key quality indicator (QI) for patients with end-stage kidney disease (ESKD). Specifically, guidelines recommend assessing deferral of dialysis initiation until symptoms arise or if the eGFR is ≤6 mL/min/1.73 m2. Despite the recognition of the importance of this QI, how eGFR at the time of dialysis initiation is defined, collected, and tracked at dialysis centers across Canada remains unknown. Objectives: To identify how provincial renal programs define eGFR at dialysis initiation, to compare practice across Canadian provinces, and to determine if there is a consistent benchmark for deferred dialysis start. Design: Cross-sectional survey distributed to the medical leads of each provincial renal program, administered from July 2021 to November 2021. Quebec was not included given it did not yet participate in Canadian Organ Replacement Register (CORR) data submission. Setting: The survey was designed and distributed by the Canadian Society of Nephrology Quality Improvement & Implementation Science Committee (CSN-QUIS) Indicator Working Group. Methods: The survey asked respondents on how eGFR is defined, collected, reported, and perceived barriers to QI data collection. The National Senior Renal Leaders Forum helped identify the key provincial medical leads to disseminate the survey for completion. Results: Surveys were distributed to the medical leads of the 9 provincial renal programs that participate in CORR. In total, there were 8 responses. Five provinces submit eGFR for all new dialysis starts and 3 provinces only submit this information for chronic patients. There is variation in determining when a patient with acute kidney injury requiring dialysis is classified as a chronic patient. Four provinces use a 30-day trigger, 3 provinces use a 90-day trigger, and the patient's nephrologist makes this determination in 1 province. The creatinine used for the eGFR at dialysis initiation was the value measured on the first dialysis session (ie, day 0) for 5 provinces; the last outpatient clinic creatinine value in 2 provinces, and 1 province did not have a standard definition. Three provinces did not have a benchmark target for eGFR at dialysis initiation, 1 province had a target of <9.5 mL/min/1.73 m2, 3 provinces had a target of <10 mL/min/1.73 m2, 1 province had a target of <15 mL/min/1.73 m2. All 8 responding provincial medical leads support the establishment of a national benchmark for this measure. Limitations: This survey was restricted to provincial medical leads and therefore is unable to determine practice at individual dialysis sites. The survey was not anonymous, so it may be subject to conformity bias. Conclusions: There is wide variability in how eGFR at dialysis initiation is measured and reported across Canada. Additionally, there is no consensus on a benchmark target for an intent-to-defer dialysis strategy. Standardization of target eGFR at dialysis initiation may facilitate national reporting and quality improvement initiatives.

Contexte: Le débit de filtration glomérulaire estimé (DFGe) à l'amorce de la dialyse est de plus en plus reconnu comme un indicateur clé de la qualité (IQ) chez les patients atteints d'insuffisance rénale terminale (IRT). Plus précisément, les lignes directrices recommandent d'évaluer la possibilité de reporter l'initiation de la dialyse jusqu'à l'apparition des symptômes ou l'atteinte d'un DFGe égal ou inférieur à 6 ml/min/1,73 m2. Bien qu'on reconnaisse l'importance de cet IQ, on ignore encore comment le DFGe est défini, mesuré et suivi au moment de l'initiation de la dialyse dans les centres de dialyse canadiens. Objectifs: Déterminer la façon dont les programmes rénaux provinciaux définissent le DFGe à l'initiation de la dialyse, comparer les pratiques en cours dans les différentes provinces canadiennes et déterminer s'il existe une cible de référence commune pour une initiation différée de la dialyse. Conception: Un sondage transversal distribué entre juillet et novembre 2021 aux directeurs médicaux de chaque programme provincial de soins rénaux. Le Québec n'a pas été inclus puisque la province n'a pas encore participé au Registre canadien des insuffisances et des transplantations d'organes (RCITO). Cadre: Le sondage a été conçu et distribué par le Groupe de travail sur les indicateurs du Quality Improvement & Implementation Science Committee de la Société canadienne de néphrologie (CSN-QUIS). Méthodologie: Les répondants au sondage devaient décrire la façon dont le DFGe est défini, mesuré et rapporté, ainsi que les obstacles perçus à la collecte de données sur les IQ. Le sondage a été distribué aux directeurs médicaux provinciaux identifiés par le biais du National Senior Renal leaders Forum. Résultats: Le sondage a été distribué aux directeurs médicaux des neuf programmes provinciaux de soins rénaux participant au RCITO; huit ont répondu. Cinq provinces soumettent le DFGe pour toute nouvelle initiation d'un traitement de dialyse; trois provinces ne soumettent cette information que pour les patients atteints d'insuffisance rénale chronique. Il existe des différences entre les provinces dans la détermination du moment où un patient passe de l'insuffisance rénale aiguë nécessitant une dialyse à l'insuffisance rénale chronique. Quatre provinces utilisent un délai de 30 jours, trois provinces utilisent un délai de 90 jours et dans la dernière province, cette détermination est faite par le néphrologue du patient. Dans cinq des huit provinces sondées, le taux de créatinine utilisé pour établir le DFGe à l'initiation de la dialyse est la valeur mesurée à la première séance de dialyse (au jour 0); deux provinces utilisent la valeur de créatinine mesurée lors de la dernière visite en ambulatoire, et une province n'a pas de définition normalisée. Trois provinces n'ont pas de cible de référence pour le DFGe à l'initiation de la dialyse; cette cible est de moins de 9,5 ml/min/1,73 m2 dans une province, de moins de 10 ml/min/1,73 m2 dans trois provinces, et de moins de 15 ml/min/1,73 m2 dans une province. Les huit responsables médicaux provinciaux ayant répondu au sondage appuient l'établissement d'une valeur de référence nationale pour cette mesure. Limites: Ce sondage n'a été envoyé qu'aux directions médicales provinciales, par conséquent, il ne permet pas de déterminer les pratiques en cours dans chaque site de dialyse. Le sondage n'étant pas anonyme, il pourrait comporter un biais de conformité. Conclusion: Il existe une grande variabilité au Canada dans la façon dont le DFGe est mesuré et rapporté au début de la dialyse. On observe en outre une absence de consensus quant à une cible de référence pour une stratégie d'initiation différée de la dialyse. La normalisation de la valeur cible de DFGe au début de la dialyse pourrait faciliter les initiatives nationales de déclaration et d'amélioration de la qualité.

The rare case of double valve surgery in a patient with factor VII deficiency.

Performing cardiac surgery on patients with bleeding diatheses poses significant challenges since these patients are at an increased risk for complications secondary to excessive bleeding. Despite its rarity, patients with factor VII (FVII) deficiency may require invasive procedures such as cardiac surgery. However, we lack guidelines on their pre-, peri-, and post-operative management. As FVII deficiency is rare, it seems unlikely to design and learn from large clinical studies. Instead, we need to base our clinical decision-making on single reported cases and registry data. Herein, we present the rare case of a patient with FVII deficiency who underwent double valve surgery. Pre-operatively, activated recombinant FVII (rFVIIa) was administered to reduce the risk of bleeding. Nevertheless, the patient experienced major bleeding. This case highlights the significance of FVII deficiency in patients undergoing cardiac surgery and emphasizes the importance of adequate and appropriate transfusion of blood products for these patients.

Glucagon-like peptide 1 receptor agonists in end-staged kidney disease and kidney transplantation: A narrative review.

AIMS: Glucagon-like peptide 1 receptor agonists (GLP-1RA) improve glycemic control and promote weight loss in type 2 diabetes (DM2) and obesity. We identified studies describing the metabolic benefits of GLP-1RA in end-staged kidney disease (ESKD) and kidney transplantation. DATA SYNTHESIS: We searched for randomized controlled trials (RCTs) and observational studies that investigated the metabolic benefits of GLP-1RA in ESKD and kidney transplantation. We summarized the effect of GLP-1RA on measures of obesity and glycemic control, examined adverse events, and explored adherence with therapy. In small RCTs of patients with DM2 on dialysis, liraglutide for up to 12 weeks lowered HbA1c by 0.8%, reduced time in hyperglycemia by ∼2%, lowered blood glucose by 2 mmol/L and reduced weight by 1-2 kg, compared with placebo. In prospective studies inclusive of ESKD, 12 months of semaglutide reduced HbA1c by 0.8%, and contributed to weight losses of 8 kg. In retrospective cohort studies in DM2 and kidney transplantation, 12 months of GLP-1RA lowered HbA1c by 2%, and fasting glucose by ∼3 mmol/L compared with non-use, and in some reports, weight losses of up to 4 kg were described. Gastrointestinal (GI) side effects were most commonly reported, with hypoglycemia described with GLP-1RA in hemodialysis, particularly in those using insulin. CONCLUSIONS: GLP-1RA are growing in popularity in those with DM2 and obesity. In small RCTs and observational cohort studies modest glycemic and weight benefits have been described in ESKD and transplantation, but GI side effects may limit adherence. Larger and longer term studies of GLP-1RA remain important.

A New Perspective to Longstanding Challenges with Outpatient Hyperkalemia: A Narrative Review.

Purpose of Review: Outpatient hyperkalemia is a common problem with potentially deadly consequences. Potassium level thresholds to treat outpatient hyperkalemia are unstandardized and variable, leaving health care providers to rely on their own clinical judgment. This narrative review highlights the challenges of outpatient hyperkalemia management and includes recommendations for future studies that may standardize treatment, improve patient outcomes, and optimize health care utilization. Sources of Information: PubMed, Google Scholar, and the reference lists of identified articles were used to include English, peer-reviewed studies and guidelines for this review. Methods: This narrative review examines outpatient hyperkalemia from both a laboratory and clinical perspective. In addition to peer-reviewed literature, guidelines and expert consensus statements were included to highlight the inconsistencies and paucity of evidence that health care providers rely on to make clinical decisions. Key Findings: There are multiple reasons why outpatient hyperkalemia management is both challenging and sub-optimal. Clinicians must discern if the potassium level result is accurate and, if so, does the result warrant referral to the emergency department. Factitious hyperkalemia, or falsely elevated potassium level results due to analytical errors, occurs frequently, but there are no ways to identify it other than for hemolyzed samples. Additionally, guidelines and expert panels are inconsistent on the thresholds for treatment and the management of hyperkalemia. Finally, there are inconsistencies between laboratories as to when and how providers are notified of results, and the suggested thresholds for urgent management. A study that integrates the expertise of clinical biochemists and clinicians is needed to inform evidence-based guidelines for the management of outpatient hyperkalemia. Limitations: This was a comprehensive review of what is known and what still needs to be understood for the management of outpatient hyperkalemia. A formal tool to assess the quality of the included studies was not used and selection bias may have occurred.

Raison de la revue: L'hyperkaliémie ambulatoire est fréquente et peut avoir des conséquences mortelles. Les seuils de potassium justifiant le traitement de l'hyperkaliémie ambulatoire varient et ne sont pas normalisés; les professionnels de la santé doivent par conséquent s'en remettre à leur propre jugement clinique. Cette revue narrative met en évidence les défis liés à la prise en charge de l'hyperkaliémie ambulatoire et comprend des recommandations pour de futures études pour standardiser le traitement, améliorer les résultats des patients et optimiser l'utilisation des soins de santé. Sources d'information: PubMed, Google Scholar et les listes de références des articles répertoriés ont été utilisés pour inclure les études évaluées par les pairs et les lignes directrices rédigées en anglais. Méthodologie: Cette revue narrative examine la prise en charge de l'hyperkaliémie ambulatoire du point de vue clinique et paraclinique. En plus des articles évalués par les pairs, on a inclus des lignes directrices et des déclarations de consensus d'experts afin de mettre en évidence les incohérences et la rareté des données probantes sur lesquelles s'appuient les prestataires de soins de santé pour prendre des décisions cliniques. Principaux resultants: Plusieurs raisons peuvent expliquer pourquoi la prise en charge de l'hyperkaliémie ambulatoire est à la fois difficile et sous-optimale. Les cliniciens doivent juger eux-mêmes si le résultat du potassium est exact et, dans l'affirmative, déterminer s'il justifie l'aiguillage du patient vers les urgences. L'hyperkaliémie factice, soit des taux de potassium faussement élevés en raison d'erreurs analytiques, est fréquente, mais il n'existe aucun moyen de l'établir à l'exception des échantillons hémolysés. Aussi, les lignes directrices et les groupes d'experts ne s'entendent pas sur les seuils de traitement et de prise en charge de l'hyperkaliémie. Enfin, on observe des incohérences entre les laboratoires quant au moment et à la façon dont les prestataires sont informés des résultats, de même qu'en ce qui concerne les seuils suggérés pour une prise en charge urgente. Une étude intégrant l'expertise des biochimistes cliniques et des cliniciens est nécessaire pour éclairer des lignes directrices fondées sur des données probantes pour la prise en charge de l'hyperkaliémie ambulatoire. Limites: Il s'agit d'un examen complet de ce que l'on connaît et de ce qui doit encore être compris au sujet de la prise en charge de l'hyperkaliémie ambulatoire. Des biais de sélection pourraient s'être introduits puisqu'aucun outil formel n'a été utilisé pour évaluer les études incluses.

Radiodensity Analysis of Lateral Column Superconstruct Fixation Sites in Midfoot Charcot Neuroarthropathy.

Lateral column deterioration and subsequent loss of function poses a challenge for limb preservation in patients with Charcot neuroarthropathy (CN). Application of "superconstructs" provides stability and clinical improvement to an often-ulcerated lateral foot. This study examines radiodensity in Hounsfield units (HU) to compare bone quality of lateral column fixation targets using computed tomography (CT) scans between patients with and without midfoot CN. A retrospective chart review identified control (nondiabetic, non-CN; n = 29) and midfoot CN (n = 21) groups. Patient demographics and medical history were collected. Two reviewers measured the mean HU of circular regions of interest centered on the fourth and fifth metatarsal heads as well as the anterior, middle, and posterior thirds of the calcaneus. Radiodensity was compared between groups, among calcaneal locations, Eichenholtz stages and Brodsky types. A p value ≤.05 was considered statistically significant. Age and body mass index were not significantly different between groups. The CN group exhibited greater HU than the control group at the metatarsal head and calcaneus (p < .001). The anterior calcaneus exhibited greater HU than the posterior calcaneus in the CN group (p = .02). The difference in HU was not statistically significant between Stages 0-1 and Stages 2-3 or midfoot Brodsky Types. Indirect bone density analysis revealed an increased density in CN compared to control patients with no significant difference between midfoot CN stages or types. The anterior calcaneus was the densest rearfoot bone among the CN patients, a result that may have implications in surgical fixation.

Recognition of Obesity and Perceptions of Weight Loss Management in Patients With Chronic Kidney Disease: A Retrospective Cross-Sectional Study.

Background: Obesity is, directly and indirectly, linked to the progression of chronic kidney disease (CKD). However, nephrologists' recognition of obesity and willingness to address and manage obesity are unknown. Objectives: The aim of this article is to investigate if obesity is recognized and documented in the clinical encounter and to examine nephrologists' perceptions of obesity and comfort with weight loss management. Design: We conducted a 2-part study. Part I used a retrospective chart review and part II used an anonymous online survey of practicing nephrologists (n = 14) in our center. Setting: The study took place in the Multi-care Kidney Clinic (MCKC) at London Health Sciences Centre in London, Ontario, Canada. Patients: In part I, we conducted a retrospective chart review of 10 random patients with advanced CKD and obesity (body mass index [BMI] > 30 kg/m2) from each of the nephrologists between January and December 2019. Methods: In part I, charts were assessed for documentation of obesity and/or a treatment plan (lifestyle counseling, pharmacologic intervention, and specialist referral). In part II, a survey completed by the nephrologists explored their current experience and perceptions of obesity and comfort with weight loss management. Responses were ranked on a 5-point Likert scale. Results: In all, 140 patient charts were reviewed. The median age was 69 (interquartile range [IQR] = 60-77) years, estimated glomerular filtration rate (eGFR) was 17 (IQR = 12-20) ml/min/1.73 m2, weight was 99 (IQR = 90-116) kg, and BMI was 36 (IQR = 33-40) kg/m2. Obesity with a BMI was documented in 36 (26%) charts, and only 2 (1%) documented a weight loss plan, which only included non-pharmacologic strategies. There were 13 survey responses (93% response rate). All nephrologists agreed that obesity negatively affects the health of patients with CKD. Twelve (92%) reported discussing obesity with patients, but none felt that they had time to treat it. All reported discussions of obesity would evoke a negative patient response, while 5 (38%) thought patients actually want to discuss obesity. Regarding treatment, 8 (62%) nephrologists felt comfortable with non-pharmacologic treatment, but only 1 respondent was comfortable with pharmacologic treatments. Twelve (92%) nephrologists thought patients should be referred to a specialist. Limitations: There was limited generalizability as this was a single center study. The BMI may reflect hypervolemia rather than body mass. Conclusion: In our study, nephrologists rarely document and manage obesity in patients with advanced CKD, despite their perception of treatment benefits. Improved outcomes of obesity management for patients with CKD will require increased knowledge and clinical tools to efficiently address obesity with patients.

Contexte: L'obésité est directement et indirectement liée à la progression de l'insuffisance rénale chronique (IRC). La reconnaissance de l'obésité par les néphrologues et leur volonté de la prendre en charge demeurent toutefois mal connues. Objectifs: Vérifier si l'obésité est reconnue et documentée lors de la rencontre clinique. Examiner les perceptions des néphrologues quant à l'obésité et leur confort face à la gestion du poids. Conception: Notre étude était constituée de deux parties. La première consistait en un examen rétrospectif des dossiers et la deuxième en un sondage anonyme mené en ligne auprès des néphrologues praticiens (n = 14) de notre centre. Cadre: La clinique multidisciplinaire en santé rénale (CMSR) du London Health Sciences Centre de London, en Ontario (Canada). Sujets: Dans la première partie, nous avons examiné rétrospectivement les dossiers de dix patients aléatoires atteints d'IRC de stade avancé et jugés obèses (IMC > 30 kg/m2) pour chacun des néphrologues participants entre janvier et décembre 2019. Méthodologie: Dans la première partie, les dossiers ont été examinés à la recherche d'une mention de l'obésité et/ou d'un plan de traitement (conseils sur le mode de vie, intervention pharmacologique, aiguillage vers un spécialiste). Dans la deuxième partie, un sondage réalisé auprès des néphrologues a exploré leur expérience et leurs perceptions actuelles sur l'obésité et leur confort quant à la gestion de la perte de poids. Les réponses ont été classées sur une échelle Likert de 5 points. Résultats: En tout, 140 dossiers patients ont été examinés. L'âge médian s'établissait à 69 ans (ÉIQ: 60-77), le DFGe médian à 17 ml/min/1,73 m2 (ÉIQ: 12-20), le poids médian à 99 kg (ÉIQ: 90-116) et l'IMC médian à 36 kg/m2 (ÉIQ: 33-40). L'obésité avec IMC était documentée dans 36 dossiers (26%) et seulement deux dossiers (1%) comportaient un plan de perte de poids, lequel ne comprenait que des stratégies non pharmacologiques. Treize néphrologues ont répondu au sondage (taux de réponse: 93%). Tous ont convenu que l'obésité affecte négativement la santé des patients atteints d'IRC; douze (92%) ont mentionné discuter d'obésité avec leurs patients, mais aucun ne pensait avoir le temps de la traiter. Tous les répondants ont indiqué que les discussions abordant l'obésité recevaient un accueil négatif de la part du patient; seuls 5 néphrologues (38%) étaient d'avis que les patients sont réellement ouverts à discuter d'obésité. Quant à son traitement, huit néphrologues (62%) se sont dits à l'aise avec un traitement non pharmacologique; un seul répondant était à l'aise avec les traitements pharmacologiques. Selon douze répondants (92%), les patients devraient être dirigés vers un spécialiste. Limites: Étude dans un seul centre, ce qui limite la généralisabilité. L'IMC pourrait refléter une hypervolémie plutôt que la masse corporelle. Conclusion: Dans notre étude, les néphrologues ont rarement documenté et pris en charge l'obésité de leurs patients atteints d'IRC de stade avancé, et ce, bien qu'ils croient aux avantages de son traitement. Pour améliorer la prise en charge de l'obésité chez les patients atteints d'IRC, il faudra améliorer les connaissances et les outils cliniques permettant de la traiter efficacement chez ces patients.

The Curious Case of a Missing Gallbladder: An Unusual Presentation of a Cholecystoduodenal Fistula.

Large gallstones could erode through gallbladder wall to nearby structures, causing fistulas, gastric outlet obstruction and gallstone ileus. They typically occur in elderly patients with comorbidities carrying therapeutic challenges. We present a case of a middle-aged woman who was thought to have symptomatic cholelithiasis. Extensive adhesions precluded safe cholecystectomy. While hepatobiliary iminodiacetic acid scan and magnetic resonance imaging with cholangiopancreatography (MRI-MRCP) failed to visualize the gallbladder, computed tomography (CT) was consistent with cholecystoduodenal fistula. A very large gallstone was seen endoscopically in the duodenum, which was broken down into pieces using a large stiff snare.

Late Stent Thrombosis in a Patient with Endovascular Aortic Repair for Blunt Thoracic Aortic Injury.

Blunt thoracic aortic injury (BTAI) is associated with high mortality and morbidity. Thoracic endovascular aortic repair has become the recommended treatment modality given improved short-term results compared to open repair. We present a case of a 19-year-old male who presented with acute paralysis and multiorgan dysfunction from acute TEVAR thrombosis. Systemic thrombolysis, catheter-directed thrombolysis followed by aspiration thrombectomy, and angioplasty were initially successful in restoring perfusion. However, he developed progressive multiorgan failure related to prompt reocclusion within 48 hours. This case is the first to describe thrombolysis and angioplasty as a management strategy for acute TEVAR thrombosis. We also review the literature surrounding this uncommon complication.

Radiodensity Analysis of Medial Column Superconstruct Fixation Sites in Midfoot Charcot Neuroarthropathy.

Charcot neuroarthropathy (CN) is a highly destructive, pathologic process with devastating consequences to foot structure and viability. The use of intramedullary fixation "superconstructs" allows for "re-bar" support of compromised bone and allows for some dynamic fixation. This study examines radiodensity in Hounsfield units (HU) to compare bone quality of medial column fixation targets using computed tomography scans between patients with and without midfoot CN. A retrospective chart review identified control (nondiabetic, non-CN; n = 29) and midfoot CN (n = 21) groups. Patient demographics and medical history were collected. Two reviewers measured the mean HU of a circular region of interest centered on the first metatarsal head and the anterior, middle, and posterior thirds of the talar body. Radiodensity was compared between groups, and among talar locations, Eichenholtz stages and Brodsky types, with statistical significance set at p ≤ .05. Age and body mass index were not significantly different between groups. The CN group maintained greater mean HU than the control group at the metatarsal head (p < .001), and talar body locations (p < .019). The difference in mean HU of these bones was not statistically significant between Stages 0 to 1 and Stages 2 to 3 or Brodsky Types 1 and 2. Mean HU differences among talus positions were not statistically significant. Indirect bone density analysis using HU showed an increased density in CN patients with no significant difference among talar body locations or midfoot Charcot stages and types. These results may assist in optimizing fixation length. Future studies may examine these densities in ankle CN.

Promoting FAIR Data Through Community-driven Agile Design: the Open Data Commons for Spinal Cord Injury (odc-sci.org).

The past decade has seen accelerating movement from data protectionism in publishing toward open data sharing to improve reproducibility and translation of biomedical research. Developing data sharing infrastructures to meet these new demands remains a challenge. One model for data sharing involves simply attaching data, irrespective of its type, to publisher websites or general use repositories. However, some argue this creates a 'data dump' that does not promote the goals of making data Findable, Accessible, Interoperable and Reusable (FAIR). Specialized data sharing communities offer an alternative model where data are curated by domain experts to make it both open and FAIR. We report on our experiences developing one such data-sharing ecosystem focusing on 'long-tail' preclinical data, the Open Data Commons for Spinal Cord Injury (odc-sci.org). ODC-SCI was developed with community-based agile design requirements directly pulled from a series of workshops with multiple stakeholders (researchers, consumers, non-profit funders, governmental agencies, journals, and industry members). ODC-SCI focuses on heterogeneous tabular data collected by preclinical researchers including bio-behaviour, histopathology findings and molecular endpoints. This has led to an example of a specialized neurocommons that is well-embraced by the community it aims to serve. In the present paper, we provide a review of the community-based design template and describe the adoption by the community including a high-level review of current data assets, publicly released datasets, and web analytics. Although odc-sci.org is in its late beta stage of development, it represents a successful example of a specialized data commons that may serve as a model for other fields.

Corrigendum to "Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis".

[This corrects the article DOI: 10.1155/2021/6695967.].

Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis.

Acetaminophen overdose is one of the most common causes of acute hepatic failure in the developed world. There is strong evidence for N-acetylcysteine (NAC) as a safe and effective antidote for acetaminophen toxicity. However, there is less clarity in the management of massive overdoses (acute, single ingestions > 500 mg/kg with 4-hour equivalent concentrations ~6000 µmol/L) which are often associated with metabolic acidosis and multiorgan dysfunction. In such ingestions, the role of adjuvant treatments such as fomepizole and extracorporeal removal is unclear. We present a case of a 20-year-old female presenting with an acute ingestion of over 120 grams (1764.7 mg/kg) and an acetaminophen concentration of 5880 µmol/L who developed refractory shock, decreased level of consciousness, and metabolic acidosis requiring mechanical ventilation and vasopressor support. She was treated with gastric decontamination with activated charcoal, IV NAC, fomepizole, and hemodialysis. The patient had complete clearance of acetaminophen by 32 hours after presentation and normalization of her acid base and hemodynamic status without any organ failure. This case highlights the potential benefit of a triple strategy of NAC, fomepizole, and early hemodialysis in massive acetaminophen overdose, potentially sparing complications of prolonged intubation and ICU hospitalization.

Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias.

Cardiac tachyarrhythmias are a major cause of morbidity and mortality. Treatments for these tachyarrhythmias include antiarrhythmic drugs, catheter ablation, surgical ablation, cardiac implantable electronic devices, and cardiac transplantation. Each of these treatment approaches is effective in some patients but there is considerable room for improvement, particularly with respect to the most common of the tachydysrhythmias, atrial fibrillation, and the most dangerous of the tachydysrhythmias, ventricular tachycardia (VT) or ventricular fibrillation. Noninvasive stereotactic ablative radiation therapy is emerging as an effective treatment for refractory tachyarrhythmias. Animal models have shown successful ablation of arrhythmogenic myocardial substrates with minimal short-term complications. Studies of stereotactic radioablation involving patients with refractory VT have shown a reduction in VT recurrence and promising early safety data. In this review, we provide the background for the application of stereotactic arrhythmia radioablation therapy along with promising results from early applications of the technology.

Les tachyarythmies cardiaques sont une cause importante de morbidité et de mortalité. Les traitements employés comprennent des antiarythmiques, l'ablation par cathéter, l'ablation par chirurgie, l'implantation de dispositifs cardiaques électroniques et la transplantation cardiaque. Toutes ces démarches thérapeutiques sont efficaces dans certains cas, mais les traitements peuvent encore être largement améliorés, en particulier en ce qui concerne la fibrillation auriculaire, qui est la tachyarythmie la plus fréquente, et la tachycardie ventriculaire (TV, aussi appelée fibrillation ventriculaire), qui est la tachyarythmie la plus dangereuse. La radiochirurgie stéréotaxique non invasive se démarque de plus en plus comme traitement efficace des tachyarythmies réfractaires. Des substrats myocardiques arythmogènes ont pu être réséqués avec succès sur des modèles animaux, l'intervention n'ayant entraîné que des complications minimales de courte durée. Dans le cadre d'études menées auprès de patients présentant une TV réfractaire, la radiochirurgie stéréotaxique a permis de réduire le risque de récurrence de la TV, et les premières données sur l'innocuité du traitement sont encourageantes. Dans notre revue, nous précisons le cadre d'application de la radiochirurgie stéréotaxique visant à réséquer le tissu responsable de l'arythmie, et nous présentons les résultats prometteurs des premières applications de la technologie à cette fin.

Appropriateness of Long-Term Acute Care Hospital Transfer: A Multicenter Study of Medicare ACO Beneficiaries.

OBJECTIVES: There is wide variation in long-term acute care hospital (LTACH) use nationwide, the most intensive and expensive post-acute care setting, although appropriateness of use is uncertain. Therefore, we examined the appropriateness and reasons for transfer in a high-use region, and how Medicare criteria for LTACH payment identifies appropriate transfers. DESIGN: Multicenter retrospective observational cohort. SETTING AND PARTICIPANTS: Consecutive hospitalized Medicare beneficiaries transferred to an LTACH from 2017 to 2018 from an accountable care organization in Texas. METHODS: The primary outcome was clinical appropriateness of transfer ascertained by 2 physician reviewers. We abstracted patients' characteristics and primary reasons for transfer. We examined the positive predictive value (PPV) of meeting Medicare criteria for full LTACH payment [preceding intensive care unit (ICU) stay ≥3 days or prolonged mechanical ventilation] for identifying appropriate transfers, and how this differed if Medicare adopted an 8-day minimum ICU stay criterion recommended by the Medicare Payment Advisory Commission (MedPAC). RESULTS: Of 105 LTACH transfers, 33 (31.4%) were clinically appropriate. The most common reason among appropriate transfers was respiratory care (58%), but 42% had other indications. Inappropriate transfers most commonly were for wound care (28%), intravenous medication infusions (28%), or patient (17%) and physician preference (26%). The PPV for meeting Medicare LTACH payment criteria was 55%. The PPV improved to 77% if Medicare adopted the 8-day minimum ICU stay criterion, with only a modest absolute increase in appropriate transfers not meeting the more stringent criteria (12% to 17%). CONCLUSIONS AND IMPLICATIONS: Two-thirds of LTACH transfers in a high-LTACH-use region are clinically inappropriate, and are most commonly transferred for wound care, intravenous infusions, or patient and physician preference. Medicare payment criteria modestly distinguished between appropriate and inappropriate transfers. Adoption of MedPAC's recommended 8-day minimum ICU stay criterion could safely reduce inappropriate transfers, although generalizability to low LTACH-use regions is uncertain.

Detection of EGFR Mutations in cfDNA and CTCs, and Comparison to Tumor Tissue in Non-Small-Cell-Lung-Cancer (NSCLC) Patients.

Lung cancer is the leading cause of cancer-related mortality worldwide. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapies, based on the evaluation of EGFR mutations, have shown dramatic clinical benefits. EGFR mutation assays are mainly performed on tumor biopsies, which carry risks, are not always successful and give results relevant to the timepoint of the assay. To detect secondary EGFR mutations, which cause resistance to 1st and 2nd generation TKIs and lead to the administration of a 3rd generation drug, effective and non-invasive monitoring of EGFR mutation status is needed. Liquid biopsy analytes, such as circulating tumor cells (CTCs) and circulating tumor DNA (cfDNA), allow such monitoring over the course of the therapy. The aim of this study was to develop and optimize a workflow for the evaluation of cfDNA and CTCs in NSCLC patients all from one blood sample. Using Vortex technology and EntroGen ctEGFR assay, EGFR mutations were identified at 0.5 ng of DNA (∼83 cells), with a sensitivity ranging from 0.1 to 2.0% for a total DNA varying from 25 ng (∼4 CTCs among 4000 white blood cells, WBCs) to 1 ng (∼4 CTCs among 200 WBCs). The processing of plasma-depleted-blood provided comparable capture recovery as whole blood, confirming the possibility of a multimodality liquid biopsy analysis (cfDNA and CTC DNA) from a single tube of blood. Different anticoagulants were evaluated and compared in terms of respective performance. Blood samples from 24 NSCLC patients and 6 age-matched healthy donors were analyzed with this combined workflow to minimize blood volume needed and sample-to-sample bias, and the EGFR mutation profile detected from CTCs and cfDNA was compared to matched tumor tissues. Despite the limited size of the patient cohort, results from this non-invasive EGFR mutation analysis are encouraging and this combined workflow represents a valuable means for informing therapy selection and for monitoring treatment of patients with NSCLC.