Citations

BACKGROUND: Patients with functioning pituitary adenomas (FPA) require a multidisciplinary team-based approach to select best medical, surgical, and radiation treatments, including stereotactic radiosurgery (SRS). OBJECTIVE: The aim of this study was to provide evidence-based recommendations on the use of SRS for adult patients with FPA. METHODS: PubMed and Embase were searched from data base inception to June 8, 2021. Full-text articles were then screened using published exclusion/inclusion criteria. Evidence tables were developing based on data extraction from the full-text reviews, and evidence-based recommendations were finalized. RESULTS: Of the total 1842 abstracts pertinent to this topic, 343 full articles met eligibility. Of these, 21 met entry criteria and were included in the evidence tables. The provided Class III evidence supported 2 Level III recommendations: 1. SRS, hypofractionated SRS, fractionated (>5 fractions) radiotherapy, and conventional radiation therapy provide excellent radiographic control with variable hormonal reduction and endocrine remission rates. For SRS and fractionated radiotherapy hormonal reduction may continue for up to 10 years after treatment. 2. Clinicians may continue to administer endocrine suppressive medical treatment before SRS as this may not affect radiographic control. CONCLUSION: This systematic review provides evidence-based recommendations to guide providers caring for adult patients with FPA when making decisions pertinent to radiosurgery. The CNS Guidelines Committee will continue to pursue timely updates to further improve the care of patients with this diagnosis.

Despite improvements in kidney transplantation rates, the shortage of donor kidneys remains a critical issue, exacerbated by non-utilization of recovered kidneys due to quality concerns, necessitating advancements in perfusion methods to enhance graft outcomes and usage. Although static cold storage remains the default standard for kidney preservation, newer methods like hypothermic machine perfusion have shown improved outcomes, including reduced delayed graft function and better survival rates. Hypothermic oxygenated machine perfusion and normothermic machine perfusion offer some potential clinical benefits but studies to date have demonstrated mixed results. In the United States, LifePort and the XVIVO’s Kidney Assist Transport are the most popular hypothermic perfusion devices, with NMP devices mostly in trials. Combining perfusion with biomarkers such as mitochondrial flavin mononucleotide, neutrophil gelatinase-associated lipocalin, and osteopontin shows promise in assessing kidney viability and predicting post-transplant outcomes, though further research is also needed. Emphasis on repair biomarkers, such as uromodulin and osteopontin, aims to better predict graft outcomes and develop new therapies. While notable advancements have been made in the use of machine perfusion and viability testing for liver transplantation, additional research with larger sample sizes is essential to substantiate these results and enhance kidney transplantation outcomes.

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 109 PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.

Key Points Significant heterogeneity in patient characteristics, urine metabolic studies, and kidney outcomes exist among enteric hyperoxaluria patients from diverse etiologies. Structurally induced malabsorption and exocrine pancreatic insufficiency have the highest kidney stone event rates. Patients with structurally induced malabsorption have up to 18% ESKD incidence at 5 years. Background Enteric hyperoxaluria (EH) is a risk factor for calcium oxalate nephrolithiasis and kidney disease. The study compares patient characteristics and urine metabolic profiles at the time of EH diagnosis and kidney stones and ESKD events during follow-up in a cohort with diverse causes of EH. Methods Adult patients with newly documented elevated urinary oxalate excretion >40 mg/24 h between January 1, 2010, and October 10, 2023, and a known enteric diagnosis including inflammatory bowel disease, exocrine pancreatic insufficiency (EPI), celiac disease, structural intestinal malabsorption (SIM), or malabsorptive bariatric surgery (Bariatric) were identified. Event rates and cumulative incidence of kidney stones and ESKD were assessed. Results Among 814 identified patients, the most common enteric etiology was Bariatric ( n =524, 64%). Patients with ulcerative colitis had the highest prevalence of kidney stones at EH diagnosis (93.6%) compared with other enteric etiologies ( P = 0.002). Patients with SIM had the highest urinary oxalate, lower urinary citrate, and volume, compared with other enteric etiologies ( P < 0.05). Calcium oxalate supersaturation was similar among the enteric groups ( P = 0.67). Median stone event rate for the overall cohort was 0.70 stone events/year during a mean (SD) follow-up of 5.0 (3.9) years. The SIM and EPI groups experienced the highest stone events (median [IQR] 1.24 [0.28–2.40] and 1.20 [0.41–1.99] events/year, respectively) while the Bariatric group had the lowest event rates (median [IQR] 0.45 [0.00–1.66 events/year]; P < 0.001). The SIM group had the highest ESKD incidence (17.8% 5 years postdiagnosis; log-rank test P < 0.001). Conclusions We describe a large EH cohort from diverse enteric etiologies. Significant heterogeneity exists in patient characteristics, urine metabolic risk factors, and adverse kidney outcomes. Patients with SIM and EPI experienced the highest kidney stone events and patients with SIM had the highest ESKD incidence. This study highlights the urgent need for more granular information regarding the natural history and risk factors for kidney complications for patients with EH to support interventional trials to improve outcomes.

Abstract The link between regional tau load and clinical manifestation of Alzheimer’s disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicentres. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression. In this large-scale, multicentre study across 14 international sites, we included cross-sectional tau-PET data from 320 individuals with atypical AD (n = 139 posterior cortical atrophy/PCA-AD; n = 103 logopenic variant primary progressive aphasia/lvPPA-AD; n = 35 behavioural variant AD/bvAD; n = 43 corticobasal syndrome/CBS-AD), with a subset of individuals (n = 78) having longitudinal tau-PET data. Additionally, as an independent sample, we included regional post-mortem tau stainings from 93 atypical AD patients from two sites (n = 19 PCA-AD, n = 32 lvPPA-AD, n = 23 bvAD, n = 19 CBS-AD). Gaussian mixture modelling was used to harmonize different tau-PET tracers by transforming tau-PET standardized uptake value ratios to tau positivity probabilities (a uniform scale ranging from 0% to 100%). Using linear regression, we assessed whether brain regions with stronger resting-state functional MRI-based functional connectivity, derived from healthy elderly controls in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showed greater covariance in cross-sectional and longitudinal tau-PET and post-mortem tau pathology. Furthermore, we examined whether functional connectivity of tau-PET epicentres (i.e. the top 5% of regions with the highest baseline tau load) and tau-PET accumulation epicentres (i.e. the top 5% of regions with the highest tau accumulation rates) was associated with cross-sectional and longitudinal tau patterns. Our findings show that tau-PET epicentres aligned with clinical variants, e.g. a visual network predominant pattern in PCA-AD (‘visual AD’) and left-hemispheric temporal predominance, particularly within the language network, in lvPPA-AD (‘language AD’). Moreover, more strongly functionally connected regions showed correlated concurrent tau-PET levels (confirmed with post-mortem data) and tau-PET accumulation rates. The functional connectivity profile of tau-PET epicentres and accumulation epicentres corresponded to tau-PET progression patterns, with higher tau-PET levels and accumulation rates in functionally close regions, and lower tau-PET levels and accumulation rates in functionally distant regions. Our data are consistent with the hypothesis that tau propagation occurs along functional connections originating from local epicentres, across all AD clinical variants. Since tau proteinopathy is a major driver of neurodegeneration and cognitive decline, this finding may advance personalized medicine and participant-specific end points in clinical trials.

Abstract The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post–CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy (22 patients; overall response rate [ORR], 40%), pirtobrutinib (17 patients; ORR, 36%), and bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (&lt;3 vs 3-6 vs &gt;6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.

Abstract Anterior shoulder instability is a common cause of shoulder pain and dysfunction in young patients and may be associated with concomitant bony and soft tissue pathology. Humeral avulsion of the glenohumeral ligament (HAGL) and rotator cuff tears are often seen in the setting of traumatic anterior shoulder instability events, especially in patients over 40 years of age, and portend poor postoperative outcomes if not addressed appropriately. While arthroscopic repair of rotator cuff tears is standard of care, both arthroscopic and open approaches for HAGL repair have been described and are associated with good clinical outcomes. Open HAGL repair affords the ability to address additional pathologies, including subscapularis tears and biceps tendon tears/SLAP tears with open subpectoral tenodesis, with direct visualization of the tear, while affording protection of the neurovascular structures. In this Technical Note, the authors describe their preferred technique for combined arthroscopic rotator cuff tear and open HAGL repair. Technique Video video See video under supplementary data.

Abstract Purpose : While it’s commonplace in medical education to train learners using simulated patient encounters, task trainers, or by practicing skills on healthy volunteers, little is known about how well learning and skills transfer to patient care. The purpose of this research is to quantify Point-of-Care Ultrasound (POCUS) skill transfer to patient care through performance assessment. Method : A quantitative analysis of aggregated data consisting of image quality of student-performed POCUS examinations from one midwestern Physician Assistant program was performed. Probabilities for scores of 1-2, 3, 4, and 5 were estimated using a multivariable cumulative logit model. Results : Forty-six PA students were included in the study. A total of 6,218 POCUS examinations were included; 4,506 on non-patients, and 1,712 on patients. When evaluating skill transfer from non-patients to patients, the probability of obtaining a high-quality examination decreases significantly, with a more substantial decrease in performance on more complex skills. The probability of a high-quality examination on the twenty-fifth examination was the highest when learning transfer happened earlier. Conclusion : While training medical providers using non-patient experiences is common, educators must understand the significant loss of quality upon skills transfer to patient care. More complex or higher risk skills likely require close monitoring at the point of skill transfer, to support the learner and ensure patient safety. Based on the findings of this research, earlier skill transfer is associated with worse immediate performance but better long-term re-learning outcomes. Increased deliberate practice prior to skill transfer is associated with better first-time performance on actual patients.

This study aimed to determine if extended infusion (EI; over > 3 hr) beta-lactam therapy increased IV access requirements compared with traditional dosing (TD; over 30 min). Eighty-six adult ICU patients treated with TD anti-pseudomonal beta-lactams who underwent therapeutic drug monitoring (TDM) were included. Patients who transitioned from TD to EI after TDM (EI group) were matched 1:1 to patients who remained on TD. In the primary analysis, the median (interquartile range) total number of lumens in the 24 hours before TDM compared with the 48 hours after TDM were similar between groups (pre: TD 3 [2–5] vs. EI 4 [3–5]; p = 0.22 and post: TD 3 [2–4] vs. EI 4 [3–5]; p = 0.05). Delivery of beta-lactams via EI was not associated with a need for more IV access. Practical challenges such as access should not limit use of EI beta-lactams when indicated.