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Purpose of review This review explores the transformative advancement, potential application, and impact of artificial intelligence (AI), particularly machine learning (ML) and large language models (LLMs), on critical care nephrology. Recent findings AI algorithms have demonstrated the ability to enhance early detection, improve risk prediction, personalize treatment strategies, and support clinical decision-making processes in acute kidney injury (AKI) management. ML models can predict AKI up to 24–48 h before changes in serum creatinine levels, and AI has the potential to identify AKI sub-phenotypes with distinct clinical characteristics and outcomes for targeted interventions. LLMs and generative AI offer opportunities for automated clinical note generation and provide valuable patient education materials, empowering patients to understand their condition and treatment options better. To fully capitalize on its potential in critical care nephrology, it is essential to confront the limitations and challenges of AI implementation, including issues of data quality, ethical considerations, and the necessity for rigorous validation. Summary The integration of AI in critical care nephrology has the potential to revolutionize the management of AKI and continuous renal replacement therapy. While AI holds immense promise for improving patient outcomes, its successful implementation requires ongoing training, education, and collaboration among nephrologists, intensivists, and AI experts.

Background Debridement, antibiotics, and implant retention (DAIR) is used to manage acute periprosthetic joint infections (PJIs) after total joint arthroplasty (TJA). Given the uncertain success of single or multiple DAIR attempts and possible long-term deleterious effects this treatment can create when trying to treat persistent infection, it is important to understand the frequency with which surgeons in the United States are attempting multiple debridements for PJI and whether those procedures are achieving the desired goal. Question/purposes In the context of the American Joint Replacement Registry (AJRR), we asked: (1) What proportion of patients who undergo DAIR have only one DAIR, and what percentage of those patients have more than one? (2) Of the patients who undergo one or more DAIR procedures, what is the proportion who progress to additional surgical procedures? (3) What is the cumulative incidence of medical or surgical endpoints related to infection on the affected leg (other than additional DAIR procedures)? Methods DAIR procedures to treat PJI, defined by ICD-9/10 and CPT (Current Procedural Technology) codes, reported to the AJRR from 2012 to 2020 were merged with Centers for Medicare and Medicaid Services (CMS) data from 2012 to 2020 to determine the incidence of patients aged 65 and older who underwent additional PJI-related procedures on the same joint. Linking to CMS ensures no loss to follow-up or patient migration to a non-AJRR site. As of 2021, the AJRR captures roughly 35% of all arthroplasty procedures performed in the United States. Of the total 2.2 million procedures in the AJRR, only 0.2% of the procedures were eligible based on our inclusion criteria. Additionally, 61% of the total population is Medicare eligible, and thus, these patients are linked to CMS. Of the 5029 DAIR attempts after a TKA, 46% (2318) were performed in female patients. Similarly, there were a total of 798 DAIR attempts after a THA, and 50% (398) were performed in female patients. For the purposes of decreasing confounding factors, bilateral THAs and TKAs were excluded from the study population. When querying for eligible procedures from 2012 to 2020, the patient population was limited to those 65 years and older, and a subsequent reoperation for infection had to be reported after a primary TJA. This limited the patient population as most infections reported to AJRR resulted in a revision, and we were searching for DAIRs. Although 5827 TJAs were identified as a primary TJA with a subsequent infectious event, more than 65% (3788) of that population did not have a reported event. The following conditions were queried as secondary outcomes after the first DAIR: sepsis, cellulitis, postoperative infection, endocarditis, amputation, knee fusion, resection, drainage, arthrotomy, and debridement. To answer our first and second study questions, we used frequency testing from the available AJRR data. Because of competing risks and issues with incomplete data, we used the cumulative incidence function to evaluate the outcomes specific to study question 3. Results Of the patients who underwent DAIR, 93% (5406 of 5827) had one DAIR and 8% (421 of 5827) had more than one. Among the DAIR population, at least 35% of TKAs and 38% of THAs were identified as having experienced an additional PJI-related event (an additional surgical procedure on the same joint, sustained an infectious endpoint in the linked CMS-AJRR dataset, or they had died). The cumulative incidence of developing a further medical or surgical condition related to the joint that had the initial DAIR were as follows: 48% (95% CI 42% to 54%) at 8 years after a DAIR following a TKA and 42% (95% CI 37% to 46%) at 4 years after a DAIR following a THA. The timepoints for TKA and THA are different because there are more longitudinal procedure data available for TKAs regarding DAIR procedures than for THAs. Conclusion In this study, we used data from the AJRR to assess the incidences of single and multiple DAIR attempts and additional surgical- and infection-related sequalae. Continued investigation is required to determine the fate of infected joints that undergo DAIR with regard to ultimate patient outcome. Future cross-sectional studies using large datasets are necessary to assess functional outcomes and determine the risk of persistent infection after DAIR more precisely. Level of Evidence Level III, therapeutic study.

Introduction Individuals ascending to elevations above 2500 m are at risk of developing altitude illness. We sought to establish the incidence and to determine what risk factors, if any, increased the likelihood of developing acute mountain sickness (AMS) in adolescents at Philmont Scout Ranch (PSR) in Cimarron, New Mexico. PSR, with elevations ranging from 2011 to 3792 m, attracts thousands of adolescent participants each year, many of whom arrive from lower elevations with little or no experience ascending to high altitude. Methods We conducted a prospective observational study of adolescent participants aged 14 to 19 years who ascended to a minimum of 3000 m while trekking from June to July 2021. Prior to the start of each participant's trek, pretrek survey data were obtained at PSR's basecamp (2011 m). During the trek at 3048 m, the Lake Louise AMS score was used to diagnose AMS. Results The incidence of AMS in our study was 13.7%. Participants reporting a history of daily headaches had more than four times the risk of developing AMS. A history of gastrointestinal problems carried three times the risk of developing AMS, and a prior history of AMS increased the risk of developing AMS by 44%. Conclusions Our findings enhance our understanding of AMS risk in adolescents and may provide guidance to youth for developing AMS. For individuals with a history of headaches or gastrointestinal problems or a prior history of AMS, there may be an opportunity to reduce the risk of developing AMS.

Abstract Objective To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Background Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene–related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head‐to‐head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. Methods An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000‐305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9–12 in the base case analysis; weeks 1–12 and 9–12 for atogepant and during weeks 9–12 for rimegepant in the scenario analyses). Results In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9–74.5) for atogepant and 51.8% (95% CI, 42.9–60.6) for rimegepant, compared to 44.1% (95% CI, 39.4–49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1–9.0) for atogepant compared to 13.0 (95% CI, 5.9–75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079–$29,516) for atogepant compared to $73,029 (95% CI, $32,901–$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Conclusions Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials.

Pre-analytical variability significantly impacts the reproducibility of liquid biopsy research, which is critical for precision medicine and biomedical research. This report highlights the challenges and variability in the pre-analytical processes of liquid biopsies, especially regarding extracellular vesicles (EVs), which are crucial for diagnostics in oncology. The MIBlood-EV initiative aims to standardize the reporting of pre-analytical variables and the quality control of plasma and serum samples to enhance reproducibility in EV research. By providing a comprehensive and flexible reporting framework, MIBlood-EV seeks to improve the reliability of EV studies and facilitate the development of evidence-based protocols, ultimately advancing the field of liquid biopsy research.

AbstractBackgroundTrauma remains the leading cause of pediatric mortality in the United States. Although use of massive transfusion protocols (MTPs) in this population is widespread, optimal pediatric resuscitation is not well established. We sought to assess contemporary pediatric MTP practice in the United States.Study Design and MethodsA web‐based survey was designed by the Association for the Advancement of Blood & Biotherapies (AABB) Pediatric Transfusion Medicine Subsection and distributed to select American College of Surgeons (ACS) Level I Verified pediatric trauma centers. The survey assessed current MTP policy, implementation, and recent changes in practice.ResultsResponse rate was 55% (22/40). Almost half of the respondents were from the South. The median RBC:plasma ratio was 1 (interquartile range 1–1.5). Protocolized fibrinogen supplementation was common while integration of antifibrinolytic therapy into MTPs was infrequent. Viscoelastic testing (VET) was available at most sites, 71% (15/21, one site did not respond), and was generally utilized on an ad‐hoc basis. Roughly, a third of sites had changed their MTP in the past 3 years due to blood supply issues, and about a third reported having group O Whole Blood on‐site.ConclusionMTP practice is similar throughout the United States. Though fibrinogen supplementation is common—other emerging interventions such as antifibrinolytic therapy or utilization of routine viscoelastic testing—are not widespread. Pediatric transfusion medicine experts must continue to follow practice change, as contemporary large trials begin to characterize new supportive modalities to optimize resuscitation in pediatric trauma patients.

Background and Objectives: Proteomics encompasses the exploration of protein composition, regulation, function, and pathways. Its influence spans diverse clinical fields and holds promise in addressing various women’s health conditions, including cancers, osteoporosis, and cardiovascular disorders. However, no comprehensive summary of proteomics and menopausal health exists. Our objective was to summarize proteomic profiles associated with diseases and disorders in peri- and postmenopausal women. Materials and Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, the Cochrane database, Elsevier, and ScienceDirect until 2022. A total of 253 studies were identified, and 41 studies met the inclusion criteria to identify data of interest. These included the study design, disease, and proteomics/proteins of significance, as described by the authors. Results: The 41 studies covered diverse areas, including bone disorders (10 studies), cardiovascular diseases (5 studies), oncological malignancies (10 studies), and various conditions, such as obesity, nonalcoholic liver disease, the effects of hormone replacement therapy, and neurological diseases (16 studies). The results of our study indicate that proteomic profiles correlate with heart disease in peri- and postmenopausal women, with distinct sex differences. Furthermore, proteomic profiles significantly differ between women with and without osteoporosis. Additionally, patients with breast, ovarian, and endometrial cancer exhibit notable variations in proteomic profiles compared to those without these conditions. Conclusions: Proteomics has the potential to enhance risk assessment and disease monitoring in peri- and postmenopausal women. By analyzing unique protein profiles, clinicians can identify individuals with heightened susceptibility to specific diseases or those already affected by established conditions. This review suggests that there is sufficient preliminary data related to proteomics in peri- and postmenopausal women for early identification of cardiovascular disease, osteoporosis, and cancers, disease monitoring, and tailoring individualized therapies. Rigorous validation studies involving large populations are essential before drawing definitive conclusions regarding the clinical applicability of proteomic findings.

Context.— Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare, and lesions may resemble conventional bowel polyps. Objective.— To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture. Design.— The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin–stained slides. Results.— The patients were 13 men and 2 women aged 26–80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, rectosigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2–2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically, the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass. Conclusions.— Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.

AbstractBackgroundThe psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member’s cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first‐degree relatives and spouses of patients affected by cancer.MethodsThis retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first‐degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer. The Utah Population Database was used and familial linkage was determined. Follow‐up included 1‐, 3‐, and 5‐year intervals. Patients residing outside of Utah and first‐degree relatives and spouses with psychological or cardiovascular disease diagnosed before a family member’s cancer diagnosis were excluded.ResultsA total of 49,284 patients with a genitourinary cancer were identified with 77,938 first‐degree relatives and spouses. A matched control group included 246,775 patients with 81,022 first‐degree relatives and spouses. Via Cox proportional hazards models, a 10% increased risk of developing a psychological illness (hazard ratio [HR], 1.10; 95% CI, 1.00–1.20) and a 28% increased risk of developing cardiovascular disease (HR, 1.28; 95% CI, 1.17–1.41) at 1 year after a family member’s cancer diagnosis were found.ConclusionsThis study provides population‐level evidence to support the hypothesis that cancer diagnoses will lead to adverse health outcomes for family members of patients with cancer. Increased clinical attention and support are needed to reduce the harm to families caused by cancer.