Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

Disruption of central and peripheral circadian clocks and circadian controlled estrogen receptor rhythms in night shift nurses in working environments.

Chronic disruption of circadian rhythms by night shift work is associated with an increased breast cancer risk. However, little is known about the impact of night shift on peripheral circadian genes (CGs) and circadian-controlled genes (CCGs) associated with breast cancer. Hence, we assessed central clock markers (melatonin and cortisol) in plasma, and peripheral CGs (PER1, PER2, PER3, and BMAL1) and CCGs (ESR1 and ESR2) in peripheral blood mononuclear cells (PBMCs). In day shift nurses (n = 12), 24-h rhythms of cortisol and melatonin were aligned with day shift-oriented light/dark schedules. The mRNA expression of PER2, PER3, BMAL1, and ESR2 showed 24-h rhythms with peak values in the morning. In contrast, night shift nurses (n = 10) lost 24-h rhythmicity of cortisol with a suppressed morning surge but retained normal rhythmic patterns of melatonin, leading to misalignment between cortisol and melatonin. Moreover, night shift nurses showed disruption of rhythmic expressions of PER2, PER3, BMAL1, and ESR2 genes, resulting in an impaired inverse correlation between PER2 and BMAL1 compared to day shift nurses. The observed trends of disrupted circadian markers were recapitulated in additional day (n = 20) and night (n = 19) shift nurses by measurement at early night and midnight time points. Taken together, this study demonstrated the misalignment of cortisol and melatonin, associated disruption of PER2 and ESR2 circadian expressions, and internal misalignment in peripheral circadian network in night shift nurses. Morning plasma cortisol and PER2, BMAL1, and ESR2 expressions in PBMCs may therefore be useful biomarkers of circadian disruption in shift workers.

Generation of an Armcx1 Conditional Knockout Mouse.

Armadillo repeat-containing X-linked protein-1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo, we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for ß-actin and Six3, in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1-deficient neurons to degeneration in the setting of additional heritable or environmental stressors.

Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome.

Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50-96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature.

A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

BACKGROUND: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. MATERIALS AND METHODS: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. RESULTS: Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). CONCLUSION: OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Universally Quantitative Band-Selective Pure Shift NMR Spectroscopy.

NMR spectroscopy is often described as a quantitative analytical technique. Strictly, only the simple pulse-acquire experiment is universally quantitative, but the poor signal resolution of the 1H NMR pulse-acquie experiment frequently complicates quantitative analysis. Pure shift NMR techniques provide higher resolution, by reducing signal overlap, but they are susceptible to a variety of sources of site-dependent signal loss. Here, we introduce a new method that corrects for signal loss from such sources in band-selective pure shift NMR experiments, by performing different numbers of iterations of the same pulse sequence elements before acquisition to allow extrapolation back to the loss-free signal. We apply this method to both interferogram and semi-realtime acquisition modes, obtaining integrals within 1% of those acquired from a pulse-acquire experiment for a three-component mixture.

Babesiosis in immunosuppressed hosts: pathogenesis, diagnosis and management.

PURPOSE OF REVIEW: This review provides the most recent evidence of the challenges that occur in the management of babesiosis in immunocompromised hosts. RECENT FINDINGS: The epidemiology of babesiosis is affected by climate change leading to increasing numbers of cases as well as increasing areas of endemicity. Immunosuppressed hosts, especially with asplenia or B-cell defects, are at high risk of having severe disease as well as persistent and relapsed infection. Resistance to the primary therapies azithromycin and atovaquone can develop leading to further challenges in treating persistent or relapsed disease in the immunocompromised host. SUMMARY: Babesiosis is likely to become a more frequent infectious complication in immunosuppressed hosts as the areas of endemicity expand. Reduced efficacy of standard therapies is likely to continue emerging so more effort needs to be placed on methods of assessing resistance in vitro and developing more reliable treatments for resistant infections.

Evolution of functional antibodies following acute Epstein-Barr virus infection.

While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses over the course of EBV infection and to gain a better understanding of the potential contribution of antibody (Ab) function to viral control, we comprehensively profiled Ab specificities and Fc-functionalities using systems serology and VirScan. Ab functions against latent (EBNA1), early (p47/54) and two late (gp350/220 and VCA-p18) EBV proteins were overall modest and/or short-lived, differing from humoral responses induced during acute infection by other viruses such as HIV. In the first year post infection, only p18 elicited robust IgM-driven complement deposition and IgG-driven neutrophil phagocytosis while responses against EBNA-1 were largely Fc-functionally silent and only matured during chronic infection to drive phagocytosis. In contrast, Abs against Influenza virus readily mediated broad Fc-activity in all participants. These data suggest that EBV evades the induction of robust Fc-functional Abs, potentially due to the virus' life cycle, switching from lytic to latent stages during infection.

Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells.

The maintenance of immune homeostasis requires regulatory T cells (Treg cells). Here we found that Treg cell­specific ablation of Ubc13, a Lys63 (K63)-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect the survival of Treg cells or expression of the transcription factor Foxp3, it impaired the in vivo suppressive function of Treg cells and rendered them sensitive to the acquisition of T helper type 1 (TH1) cell­ and interleukin 17 (IL-17)-producing helper T (TH17) cell­like effector phenotypes. This function of Ubc13 involved its downstream target, the kinase IKK. The Ubc13-IKK signaling axis controlled the expression of specific Treg cell effector molecules, including IL-10 and SOCS1. Collectively, our findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains Treg cell function and prevents Treg cells from acquiring inflammatory phenotypes.

Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) Staging Manual has been updated and improved to ensure the highest degree of clinical relevance and to improve its utility for patient evaluation and clinical research. Major changes include: 1) pathologically organ-confined disease is now considered pT2 and is no longer subclassified by extent of involvement or laterality, 2) tumor grading now includes both the Gleason score (as in the seventh edition criteria) and the grade group (introduced in the eighth edition criteria), 3) prognostic stage group III includes select, organ-confined disease based on prostate-specific antigen and Gleason/grade group status, and 4) 2 statistical prediction models are included in the staging manual. The AJCC will continue to critically analyze emerging prostate cancer biomarkers and tools for their ability to prognosticate and guide treatment decision making with the highest level of accuracy and confidence for patients and physicians. CA Cancer J Clin 2017;67:245-253. © 2017 American Cancer Society.

A synthetic genetic edge detection program.

Edge detection is a signal processing algorithm common in artificial intelligence and image recognition programs. We have constructed a genetically encoded edge detection algorithm that programs an isogenic community of E. coli to sense an image of light, communicate to identify the light-dark edges, and visually present the result of the computation. The algorithm is implemented using multiple genetic circuits. An engineered light sensor enables cells to distinguish between light and dark regions. In the dark, cells produce a diffusible chemical signal that diffuses into light regions. Genetic logic gates are used so that only cells that sense light and the diffusible signal produce a positive output. A mathematical model constructed from first principles and parameterized with experimental measurements of the component circuits predicts the performance of the complete program. Quantitatively accurate models will facilitate the engineering of more complex biological behaviors and inform bottom-up studies of natural genetic regulatory networks.

Factors Associated with Urgent Amputation Status and Its Impact on Mortality.

BACKGROUND: Thirty-day mortality is higher after urgent major lower extremity amputations compared to elective lower extremity amputations. This study aims to identify factors associated with urgent amputations and to examine their impact on perioperative outcomes and long-term mortality. METHODS: Patients undergoing major lower limb amputation from 2013 to 2020 in the Vascular Quality Initiative were included. Urgent amputation was defined as occurring within 72 hr of admission. Associations with sociodemographic characteristics, comorbidities, and outcomes including postoperative complication, inpatient death, and long-term survival were compared using univariable tests and multivariable logistic regression. Long-term survival between groups was compared using Kaplan-Meier analysis. RESULTS: Of the 12,874 patients included, 4,850 (37.7%) had urgent and 8,024 (62.3%) had elective amputations. Non-White patients required urgent amputation more often than White patients (39.8% vs. 37.9%, P = 0.03). A higher proportion of Medicaid and self-pay patients presented urgently (Medicaid: 13.0% vs. 11.0%; self-pay: 3.4% vs. 2.5%, P < 0.001). Patients requiring urgent amputation were less often taking aspirin (55.6% vs. 60.1%, P < 0.001) or statin (62.2% vs. 67.2%, P < 0.001), had fewer prior revascularization procedures (41.0% vs. 48.8%, P < 0.001), and were of higher American Society of Anesthesiologists (ASA) class 4-5 (50.9% vs. 40.1%, P < 0.001). Urgent amputations were more commonly for uncontrolled infection (48.1% vs. 29.4%, P < 0.001) or acute limb ischemia (14.3% vs. 6.2%, P < 0.001). Postoperative complications were higher after urgent amputations (34.7% vs. 16.6%, P < 0.001), including need for return to operating room (23.8% vs. 8.4%, P < 0.001) and need for higher revision (15.2% vs. 4.5%, P < 0.001). Inpatient mortality was higher after urgent amputation (8.9% vs. 5.4%, P < 0.001). Multivariable analysis revealed non-White race, self-pay, homelessness, current smoking, ASA class 4-5, and amputations for uncontrolled infection or acute limb ischemia were associated with urgent status, whereas living in a nursing home or prior revascularization were protective. Furthermore, urgent amputation was associated with an increased odds of postoperative complication or death (odds ratio 1.86 [1.69-2.04], P < 0.001) as well as long-term mortality (odds ratio: 1.24 [1.13-1.35], P < 0.001). Kaplan-Meier analysis corroborated that elective status was associated with improvement of long-term survival. CONCLUSIONS: Patients requiring urgent amputations are more often non-White, uninsured, and less frequently had prior revascularization procedures, revealing disparities in access to care. Urgency was associated with a higher postoperative complication rate, as well as increased long-term mortality. Efforts should be directed toward reducing these disparities to improve outcomes following amputation.

Mitigating the Prozone-Like Effect in HLA Antibody Testing: A Case Report of Therapeutic Plasma Exchange for Antibody-Mediated Rejection Post-Heart Transplantation.

Therapeutic plasma exchange (TPE) is a cornerstone treatment for antibody-mediated rejection (AMR) post-organ transplantation, aiming to eliminate pathogenic donor-specific HLA antibodies (DSA). However, limitations in HLA antibody interpretation due to the prozone-like effect (PLE) can lead to inaccurate assessment of treatment efficacy. We present a case of a heart transplant recipient with suspected AMR, where an unexpected increase in DSA levels post-TPE prompted investigation into PLE. Solid-phase Luminex assays were employed to detect HLA antibodies. Serum was run neat as well as after treatment with ethylenediaminetetraacetic acid (EDTA). Nephelometry was used to detect complement levels. Laboratory analysis of pre-TPE serum revealed higher DSA levels with EDTA treatment, characteristic of PLE. Complement measurements supported complement-mediated interference in the pre-TPE sample. This case underscores the importance of being aware that PLE can occur in HLA testing and can impact the interpretation of TPE efficacy for AMR.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience.

BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

Evaluating the feasibility of implementing the Sup-ER protocol for infants with brachial plexus birth injury.

BACKGROUND: The Sup-ER protocol involves a repositioning program for infants with brachial plexus birth injury to position the shoulder in external rotation (ER) to address progressive loss in passive range of motion (PROM). The British Columbia Children's Hospital (BCCH) eligibility criteria for this protocol are infants aged 4-8 weeks with decreased shoulder ER PROM and/or Active Movement Scale (AMS) shoulder ER and/or supination scores ≤2. The resources needed to implement this protocol in large clinics have not been studied. PURPOSE: This study aims to evaluate the BCCH criteria that are used to identify appropriate candidates for the Sup-ER protocol. STUDY DESIGN: A retrospective cohort study was conducted to identify the percentage of infants who would have been recommended the Sup-ER protocol based on their PROM and AMS scores between 4 and 8 weeks of age. METHODS: A sensitivity and specificity evaluation was used to describe the BCCH criteria's ability to identify infants in this historical cohort who went on to have incomplete shoulder function (ie, true positive) vs infants who had functional shoulder outcome at 9 months of age (ie, false positive). RESULTS: At a mean of 5.8 weeks (95% confidence interval [CI] 5.3, 6.3), 46 of the 87 (53%) infants satisfied the BCCH Sup-ER protocol criteria. Forty-four (51%) were female, half (n = 45) were left side affected, and 88% had upper plexus injury. The BCCH Sup-ER protocol criteria had sensitivity of 100% and specificity of 71% to identify infants with incomplete shoulder function. Removing the AMS supination ≤2 score criterion from the criteria improves the specificity to 84%, while sensitivity remains high (97%). CONCLUSIONS: Modifying the BCCH criteria to all infants aged 4-8 weeks with AMS shoulder ER ≤2 and/or decreased shoulder ER PROM improves the precision of identifying infants who would benefit from the Sup-ER protocol.

Prevalence and predictors of elbow flexion contractures during early childhood following brachial plexus birth injury.

BACKGROUND: Elbow flexion contracture development in school-age children with a brachial plexus birth injury (BPBI) is common. Reports indicate onset between 2 and 4 years; however, little is known about early childhood prevalence, development, and trajectory of these contractures. PURPOSE: To determine the prevalence and predictors of BPBI elbow flexion contractures during early childhood. STUDY DESIGN: A retrospective cross-sectional study. METHODS: Demographic, diagnostic, treatment, and elbow contracture data were collected for children with a BPBI <4 years between 2015 and 2019 from a prospectively collected database. Spinal root motor contributions and injury were determined using Active Movement Scale (AMS) scores at 6 weeks of age and used to predict contracture development. RESULTS: Of the 171 children that met inclusion criteria, 87% (n = 149) had upper plexus injuries. The mean age at the time of evaluation for an elbow contracture was 21.4 ± 12.7 months. The prevalence of elbow flexion contractures was 22% (n = 38), with mean onset at 13.4 ± 11.0 months. Mean contracture degree was -10.8 ± -6.9 degrees with 76% (n = 29) <-10 degrees. AMS shoulder abduction, flexion, and external rotation; elbow flexion; forearm supination; and wrist extension scores at a mean 2.3 ± 1.4 months were significantly lower in children who developed elbow flexion contractures (p < 0.001). Logistic regression found that low AMS elbow flexion with high elbow extension scores were a significant (p < 0.003) predictor of elbow contracture development. CONCLUSIONS: The prevalence of elbow flexion contractures in early childhood is greater than previously understood. These findings indicate that C5-C6 injury affecting elbow flexion with relative preservation of elbow extension is a predictor of contracture development. Further research is needed to investigate the nature and sequelae of C5-C6 injury and its effects on elbow flexion contracture development.

Body composition and mortality in men receiving prostate radiotherapy: A pooled analysis of NRG/RTOG 9406 and NRG/RTOG 0126.

PURPOSE: To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality. MATERIALS AND METHODS: Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death. RESULTS: Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area. CONCLUSIONS: This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.

Clinical recommendations for posttransplant assessment of anti-HLA (Human Leukocyte Antigen) donor-specific antibodies: A Sensitization in Transplantation: Assessment of Risk consensus document.

Although anti-HLA (Human Leukocyte Antigen) donor-specific antibodies (DSAs) are commonly measured in clinical practice and their relationship with transplant outcome is well established, clinical recommendations for anti-HLA antibody assessment are sparse. Supported by a careful and critical review of the current literature performed by the Sensitization in Transplantation: Assessment of Risk 2022 working group, this consensus report provides clinical practice recommendations in kidney, heart, lung, and liver transplantation based on expert assessment of quality and strength of evidence. The recommendations address 3 major clinical problems in transplantation and include guidance regarding posttransplant DSA assessment and application to diagnostics, prognostics, and therapeutics: (1) the clinical implications of positive posttransplant DSA detection according to DSA status (ie, preformed or de novo), (2) the relevance of posttransplant DSA assessment for precision diagnosis of antibody-mediated rejection and for treatment management, and (3) the relevance of posttransplant DSA for allograft prognosis and risk stratification. This consensus report also highlights gaps in current knowledge and provides directions for clinical investigations and trials in the future that will further refine the clinical utility of posttransplant DSA assessment, leading to improved transplant management and patient care.

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.