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Abstract A 14‐year‐old male tiger developed anorexia with elevated blood urea nitrogen and creatinine levels. The patient had a palpable abdominal mass and demonstrated neutrophilic leukocytosis and anaemia. Leukocytes, yeast and bacteria were present in the urine. The animal was non‐responsive to therapy and was subsequently euthanised. Extensive acute renal papillary necrosis (RPN) with pyelonephritis, chronic nephritis and polycystic renal disease were evident during gross and microscopic pathology examinations. The histologic occurrence of fungal spores and pseudohyphae morphologically consistent with Candida species were observed within the necrotic papillary regions of the kidney and within multiple foci of mild parakeratotic hyperkeratosis present in the gingiva and tongue. Candida albicans along with a slight growth of Escherichia coli were recovered from kidney cultures. Possible contributory factors for the renal candidiasis and associated RPN include predisposing oral candidiasis, polycystic renal disease, ischaemic nephrosclerosis, age‐associated or other forms of immunodeficiency and therapy with meloxicam, a non‐steroidal anti‐inflammatory drug. The absence of apparent lower urinary tract involvement coupled with the presence of intravascular renal ‘Candida emboli’ suggest that chronic oral candidiasis was the probable source of the kidney infection.

Our systematic review and meta-analysis of 40 studies ( n = 3,905,559) identified gastric acid suppressants, recent hospitalization, antibiotic exposure, and certain comorbidities as independent predictors of healthcare-associated Clostridioides difficile infection (HA-CDI) among adult inpatients. Targeted antibiotic stewardship and judicious use of gastric acid suppressants can reduce the incidence of HA-CDI., Competing Interests: A.D. has received research support from Clorox and Seres Therapeutics not related to this study., (© The Author(s) 2024.)

Background: Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long-term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression-a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers., Objective: To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings., Methods: We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer-reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected., Results: We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting-state, while others investigated a sensory modality using an evoked or event-related paradigm with a total of 35 cohort and 3 case studies. Thirty-two studies focused exclusively on migraine, while the rest reported other primary headache disorders., Conclusion: The findings show an evolution of MEG from a 7- to a 306-channel system and analysis evolving from sensor-level evoked responses to more advanced source-level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case-control studies, which could have led to false-positive findings. More studies are needed to investigate the affective-cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Introduction: Silicone breast implants are widely prevalent. An increasing group of patients detail self-reported somatic and psychological symptoms that have been ascribed as breast implant illness (BII) and seek capsulectomy and implant removal. To guide consultations and shared decision making, more outcome data relating to this intervention are required., Aim: To present a multicentre study of patient-centred (n = 100) outcome data, following total capsulectomy with implant removal for BII., Method: A questionnaire survey was cross-referenced with medical records. Collected data included demographics, operation details, pre- and postoperative symptom scores, overall self-perceived percentage improvement in BII symptoms and breast shape satisfaction ratings after explantation., Results: The 10 most frequently self-reported symptoms were fatigue (81%), pains/aches (72%), brain/memory fog (56%), mood disturbances (36%), neuropathic pain (28%), hair loss (28%), headaches (25%), gastric symptoms/intolerances (24%), eczema/rash (18%) and vision disturbance (17%). A high proportion of patients (98%) experienced a 62 ± 4% average symptom improvement; most self-reported symptoms (21/28) improved significantly after explantation with total capsulectomy (p < 0.05). Furthermore, patients had high overall self-perceived BII percentage improvement (76 ± 3%) and satisfaction with breast shape numerical rating score (8 ± 0.30) postoperatively., Conclusion: Despite BII not being a defined disease entity, symptom association with silicone breast implants continues for a growing number of patients. It is important to recognise that in this patient group, capsulectomy and implant removal may not be curative, however we have demonstrated that symptom improvement can occur. It is very difficult to prove a causal link between breast implants and BII; to do so will require extensive prospective data collection., (Copyright © 2024. Published by Elsevier Ltd.)

Right ventricle-pulmonary artery (RV-PA) coupling describes the energetic relationship between RV contractility and its afterload. The gold standard for assessment of this relationship requires invasive pressure-volume (PV) loop measurements. Non-invasive surrogates of RV-PA coupling have been developed, such as the echocardiographic tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP), but their performance has not been systematically assessed. We sought to assess performance of TAPSE/PASP ratio compared to PV loop-defined RV-PA coupling. A systematic search was conducted. Studies were included if PV loop derived RV-PA coupling metrics were compared to echocardiographic or magnetic resonance imaging surrogates. We conducted a meta-analysis of TAPSE/PASP correlation to PV loop-defined RV-PA coupling. 1452 studies were identified in the initial search, of which ten met inclusion criteria. Five studies allowed for pooled analysis of TAPSE/PASP to Ees/Ea correlation ( r  = 0.52, 95% confidence interval 0.36-0.65). There was moderate heterogeneity across the pooled studies. Despite the common use of Non-invasive surrogates of RV-PA coupling, there is only moderate correlation with gold standard measurements. These metrics do not inform on the individual components of RV-PA coupling, limiting their use in the management of patients with RV dysfunction., Competing Interests: ART has participated in advisory boards for Janssen and Merck. All other authors have no relevant financial conflicts of interest to disclose., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Objective: This review aimed to examine the impact of patient suicide on health care professionals (HCPs), assess available support resources, and evaluate postvention (i.e., activities designed to support HCPs after a patient suicide) efforts., Methods: An integrative systematic review was conducted to evaluate the prevalence of patient suicide and its emotional and professional impacts on HCPs. Searches were conducted in MEDLINE, Embase, CINAHL Plus, and the Cochrane Library in October 2021 and August 2022. Index terms and keywords were related to suicide, patients, and clinicians. Each article was assessed for quality with the Mixed Methods Appraisal Tool., Results: Sixty-six relevant articles were identified. Across studies, the mean±SD percentage of HCPs who experienced a patient suicide was 51%±<1%. Fifty-eight (88%) articles reported on the emotional impact of patient suicide, and 50 (76%) reported on the professional impact of patient suicide. Thirty-three articles described a change in practice habits, which occurred for 51%-100% of professionals in these samples. Perceptions of support ranged widely, with 11%-87% of HCPs feeling that they received sufficient support. HCPs wanted formal support, including referral to counseling (12%-82%), more suicide prevention or postvention training (4%-70%), debriefing or supervision (41%-75%), formal case review (18%-20%), time off (12%), and legal assistance (4%)., Conclusions: HCPs can be affected by patient suicide, regardless of practice setting. More information is needed to better understand the implementation of postvention services after patient suicide and to create practical and universally deliverable support services to meet HCPs' needs., Competing Interests: The authors report no financial relationships with commercial interests.

Purpose: The Ventral Hernia Working Group (VHWG) proposed a ventral hernia grading guideline, primarily supported by expert opinion, recommending biologic mesh placement in high-risk patients. We investigated the relationship between this industry-sponsored guideline and discourse around ventral hernia repair (VHR)., Methods: Medline platform from Web of Science's database identified publications "pre-VHWG"(1999-01-01 to 2009-12-31), and "post-VHWG"(2010-01-01 to 2020-12-31) describing VHR and complications or recurrence of VHR with the following comorbidities: COPD, smoking, diabetes, immunosuppression, or obesity. Poisson regression analyzed keyword frequency over time using logarithmically transformed data., Results: Of 1291 VHR publications identified pre-VHWG and 3041 publications identified post-VHWG, 172 (13.3%) and 642 (21.1%) publications respectively included prespecified keywords. The keyword groups "biologic"(IRR 3.39,95%CI1.34-11.4,p = 0.022) and "comorbid"(IRR 1.95, 95%CI1.09-3.74,p = 0.033) significantly increased with frequency after publication of the VHWG., Conclusion: The VHWG publication likely contributed to a focus on comorbidities and biologic mesh in the ensuing literature within the field of VHR., (© 2024. The Author(s).)

Background: Cerebral microbleeds (CMBs) have been described in critically ill patients with respiratory failure, acute respiratory distress syndrome (ARDS), or sepsis. This scoping review aimed to systematically summarize existing literature on critical illness-associated CMBs., Methods: Studies reporting on adults admitted to the intensive care unit for respiratory failure, ARDS, or sepsis with evidence of CMBs on magnetic resonance imaging were included for review following a systematic search across five databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science) and a two-stage screening process. Studies were excluded if patients' CMBs were clearly explained by another process of neurological injury., Results: Forty-eight studies reporting on 216 critically ill patients (mean age 57.9, 18.4% female) with CMBs were included. Of 216, 197 (91.2%) patients developed respiratory failure or ARDS, five (2.3%) patients developed sepsis, and 14 (6.5%) patients developed both respiratory failure and sepsis. Of 211 patients with respiratory failure, 160 (75.8%) patients had coronavirus disease 2019. The prevalence of CMBs among critically ill patients with respiratory failure or ARDS was 30.0% (111 of 370 patients in cohort studies). The corpus callosum and juxtacortical area were the most frequently involved sites for CMBs (64.8% and 41.7% of all 216 patients, respectively). Functional outcomes were only reported in 48 patients, among whom 31 (64.6%) were independent at discharge, four (8.3%) were dependent at discharge, and 13 (27.1%) did not survive until discharge. Cognitive outcomes were only reported in 11 of 216 patients (5.1%), all of whom showed cognitive deficits (nine patients with executive dysfunction and two patients with memory deficits)., Conclusions: Cerebral microbleeds are commonly reported in patients with critical illness due to respiratory failure, ARDS, or sepsis. CMBs had a predilection for the corpus callosum and juxtacortical area, which may be specific to critical illness-associated CMBs. Functional and cognitive outcomes of these lesions are largely unknown., (© 2024. The Author(s).)

Introduction: Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, imposes a significant economic burden because of its high prevalence and the chronic nature of its symptoms. IBS currently has 7 United States Food and Drug Administration-approved treatments. Despite efforts to improve diversity in randomized controlled trials' participation, significant disparities remain in various medical fields; yet, these have not been thoroughly examined within the context of IBS. We aimed to investigate the demographic, socioeconomic, educational, and geographic disparities in IBS drug trials., Methods: We conducted a systematic review of phase 3 randomized controlled trials on United States Food and Drug Administration-approved drugs for the treatment of IBS with constipation and IBS with diarrhea in the United States. Data on participant demographics and trial site locations were extracted and analyzed to identify disparities., Results: Our analysis included 17 studies encompassing 21 trials with 17,428 participants. Approximately 77.3% of participants were female, with a mean age of 45.4 years. Race was reported in 95% of the trials, but only 35% disclosed ethnicity. White participants constituted the majority at 79.3%. Hispanics accounted for only 5.9%. Counties without trial sites had smaller average population sizes compared with trial and trial-adjacent counties. Socioeconomic indicators such as poverty rates, median household income, educational attainment, and broadband internet access were lower in counties without trial sites, with higher average Area Deprivation Index scores indicating greater deprivation., Discussion: The findings highlight significant disparities in IBS trial participation across race, ethnicity, gender, and socioeconomic backgrounds. This raises potential concerns about generalizability of trial outcomes and underscores the need for strategies to enhance inclusivity in clinical research., (Copyright © 2024 by The American College of Gastroenterology.)

Context: Tendinopathy is a disease state characterized by tendon disorder with pain or decreased function that can cause significant disability. Multiple treatment modalities exist; however, no single treatment is superior. Ultrasound-guided percutaneous needle tenotomy (PNT) and TENEX are emerging as promising treatment options for tendinopathy., Objective: To review the current literature of reported outcomes for PNT, TENEX, and TENJET, for the treatment of tendinopathy, including pain relief, change in function, and patient-reported outcomes., Data Sources: A comprehensive search was conducted from database inception to September 2023 in Ovid Medline, Ovid Embase, and Cochrane Library., Study Selection: Keywords and index terms related to tendon injury, ultrasound, and tenotomy were used in combination to identify relevant literature that included ultrasound-guidance, treatment of tendinopathy, and treatment with PNT, TENEX, or TENJET. Covidence Systematic Review Software used to screen for relevant studies. Only English-language studies were included., Study Design: Systematic Review using PICO framework as defined and registered with the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42022321307)., Level of Evidence: Level 4 (evidence from a systematic review graded to the lowest level of study included)., Data Extraction: Articles meeting the inclusion criteria were reviewed. Type and region of tendinopathy studied, outcome measures, and complications were recorded. Clinical and self-reported outcomes data were compared across studies., Results: A total of 10 studies, representing 11 tendon sites, were included. The studies overall report improvements in pain, function, and quality of life after undergoing PNT or TENEX, with minimal adverse effects. Mean risk of bias assessment scores were 8.35 out of 10 assessing internal and external validity for included studies., Conclusion: PNT and TENEX are safe, beneficial, and minimally invasive treatment option for patients, especially for conditions refractory to more conservative treatments options., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC 50  < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Global health (GH) education is offered in post-graduate medical education (PGME) programs and local experiences are desired by trainees and educators. This scoping review aimed to map the literature on local GH education in PGME, to describe curricular components, factors facilitating successes, and challenges to implementation using a validated education intervention checklist and inclusion of seven components of local GH programming., Methods: A decolonization conceptual framework informed a 5-step scoping review. In May 2022, eight databases and MedEdPORTAL were searched using key words describing local GH education curricula., Results: Sixty-eight full-text articles described local GH education programs in residencies ( n  = 52; 76.4%) and fellowships ( n  = 10; 14.7%) spanning multiple specialties, predominantly in North America (90%). Successful programs included faculty mentoring, community-based partnerships, and a multidisciplinary component. Scheduling challenges, cultural and linguistic differences, and trainee workload contributed to implementation difficulties. Only four programs included all seven local GH health equity/decolonization components., Conclusions: Local GH curricula vary widely in clinical experiences, didactic sessions, and inclusion of mentorship and partnerships. Local populations within the communities of these training programs could benefit from standardized inclusion of components for local global health education with careful consideration of health equity.

Diaphragmatic palsy after lung transplantation has been reported infrequently. Given the role of the diaphragm in respiration, the palsy may play a significant role in the post-surgical recovery as well as morbidity and mortality. This review summarises the current literature to better understand diaphragmatic palsy in the post lung-transplant setting among adults. A thorough literature search was conducted through multiple databases and 91 publications were identified that fit the research question. The review aimed to report the burden of this problem, explore different modalities of diagnosis reported, the effect of various clinical factors and treatment modalities, as well as their effects on outcomes. Additionally, it aimed to highlight the variability, limitations of reported data, and the absence of a standardised approach. This review emphasises the crucial need for more dedicated research to better address this clinical challenge., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Objective: The current standards of postoperative respiratory monitoring on medical-surgical floors involve spot-pulse oximetry checks every 4-8 h, which can miss the opportunity to detect prolonged hypoxia and acute hypercapnia. Continuous respiratory monitoring can recognize acute respiratory depression episodes; however, the existing evidence is limited. We sought to review the current evidence on the effectiveness of continuous pulse oximetry (CPOX) with and without capnography versus routine monitoring and their effectiveness for detecting postoperative respiratory failure, opioid-induced respiratory depression, and preventing downstream adverse events., Methods: We performed a systematic literature search on Ovid Medline, Embase, and Cochrane Library databases for articles published between 1990 and April 2023. The study protocol was registered in Prospero (ID: 439467), and PRISMA guidelines were followed. The NIH quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using the software R version 4.1.1 and the package meta. The stability of the results was assessed using sensitivity analysis., Design: Systematic Review and Meta-Analysis., Setting: Postoperative recovery area., Patients: 56,538 patients, ASA class II to IV, non-invasive respiratory monitoring, and post-operative respiratory depression., Interventions: Continuous pulse oximetry with or without capnography versus routine monitoring., Measurements: Respiratory rate, oxygen saturation, adverse events, and rescue events., Results: 23 studies (17 examined CPOX without capnography and 5 examined CPOX with capnography) were included in this systematic review. CPOX was better at recognizing desaturation (SpO 2  < 90%) OR: 11.94 (95% CI: 6.85, 20.82; p < 0.01) compared to standard monitoring. No significant differences were reported for ICU transfer, reintubation, and non-invasive ventilation between the two groups., Conclusions: Oxygen desaturation was the only outcome better detected with CPOX in postoperative patients in hospital wards. These comparisons were limited by the small number of studies that could be pooled for each outcome and the heterogeneity between the studies., Competing Interests: Declaration of competing interest Roop Kaw consults for Medtronic. Ashish K. Khanna consults for Medtronic, Edwards Life Sciences, Philips Research North America, Baxter, GE Healthcare, Potrero Medical, Retia Medical and Caretaker Medical. He is also funded with a Clinical and Translational Science Institute (CTSI) NIH/NCTAS KL2 TR001421 award for a trial on continuous postoperative hemodynamic and saturation monitoring. The Department of Anesthesiology at Wake Forest School of Medicine is supported by Edwards Lifesciences under a master clinical trial agreement and receives grant funding from Masimo and Medtronic. All other authors have no relevant conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Many clinicians consider thermodilution (TD) as a means to measure cardiac output (CO) to be unreliable in patients with tricuspid regurgitation (TR). No systematic appraisals of this clinical issue have been conducted. We hypothesized that the level of inaccuracy of using TD in patients with TR, compared to the direct Fick (DF) method, to determine CO, is overstated., Methods: We performed a systematic search of 6 major literature databases for the period from 1946 to July 2023. Studies were included if they included CO measurements determined with both TD and the DF method in patients with vs without TR. Meta-analysis of the correlation between the measurements determined by TD vs the DF method was performed, stratified by the presence of TR., Results: A total of 1064 studies were identified, of which 8 met the inclusion criteria. Four of the studies were included in the pooled analysis. The presence of TR did not affect the correlation between CO measurements determined by TD vs the DF method (moderate-to-severe TR: r  = 0.90, 95% confidence interval 0.76, 0.96; mild or no TR, r  = 0.86, 95% confidence interval 0.71, 0.93). Many studies had high levels of heterogeneity and risk of bias., Conclusions: The accuracy of CO measurements made using TD, compared to the gold-standard DF method, may not be meaningfully affected by the presence of moderate-to-severe TR. Given the high levels of heterogeneity and risk of bias of the included studies, these findings should be replicated in a modern cohort., (© 2024 The Authors.)

Objectives: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients., Data Sources: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords., Study Selection: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms., Data Extraction: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool., Data Synthesis: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes., Conclusions: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change., Competing Interests: Dr. Khanna consults for Edwards Lifesciences, Medtronic, Potrero Medical, GE Healthcare, Philips North America, Caretaker Medical, and Retia Medical. He is funded by an National Institutes of Health/National Center for Advancing Translational Sciences KL2 award for assessment of blood pressure and oxygenation in postoperative patients and a Wake Forest Hypertension and Vascular Research award for studying the relationship between serum renin and outcomes in patients with septic shock. Dr. Duggal consults for ALung Technologies and receives funding from National Heart, Lung, and Blood Institute U grant for the Prevention and Early Treatment of Acute Lung Injury (PETAL) network to study prevention and treatment of acute lung injury. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Despite the growing use of immune checkpoint inhibitors (ICI) in cancer treatment, data regarding ICI-associated pericardial disease are primarily derived from case reports and case series. ICI related pericardial disease can be difficult to diagnose and is associated with significant morbidity. We conducted a systematic review to further characterize the epidemiology, clinical presentation, and outcomes of this patient population., Methods: A search of four databases resulted in 31 studies meeting inclusion criteria. Patients > 18 years old who presented with ICI mediated pericardial disease were included. Intervention was medical + surgical therapy and outcomes were development of cardiac tamponade, morbidity, and mortality., Results: Thirty- eight patients across 31 cases were included. Patients were majority male (72%) with a median age of 63. Common symptoms included dyspnea (59%) and chest pain (32%), with 41% presenting with cardiac tamponade. Lung cancer (81%) was the most prevalent, and nivolumab (61%) and pembrolizumab (34%) were the most used ICIs. Pericardiocentesis was performed in 68% of patients, and 92% experienced symptom improvement upon ICI cessation. Overall mortality was 16%., Discussion: This study provides the most comprehensive analysis of ICI-mediated pericardial disease to date. Patients affected were most commonly male with lung cancer treated with either Nivolumab or Pembrolizumab. Diagnosis may be challenging in the setting of occult presentation with normal EKG and physical exam as well as delayed onset from therapy initiation. ICI-associated pericardial disease demonstrates high morbidity and mortality, as evidenced by a majority of patients requiring pericardiocentesis., (© 2024. The Author(s).)

Background: Malignant pericardial effusion (Eff) is often asymptomatic and has an unknown prevalence, due to its occult presentation. The condition often is identified postmortem on autopsy, and it is associated with a poor prognosis. Given the late presentation of malignant pericardial Effs, a minimal volume of literature has examined the epidemiology, clinical characteristics, and outcomes of these complex patients. We conducted a systematic review to advance present understanding of this condition., Methods: A search of 4 databases resulted in 41 case reports meeting criteria. Inclusion criteria were being a patient aged > 18 years who presented with pericardial Eff in the setting of malignancy. Intervention was medical and/or surgical therapy, and the outcome was mortality., Results: For the 41 patients included, the median age was 54 years, and the majority were male patients (58%). Dyspnea was the leading symptom (90%), and cardiac tamponade was present in 78% of cases. Common cancers included lung, gastrointestinal, and renal neoplasms (59%). Pericardiocentesis occurred in 98% of cases, with a median fluid extraction volume of 1000 mL. Death occurred in 44%, primarily due to disease progression and/or metastasis., Conclusions: This study presents the largest systematic review on malignancy-induced pericardial Effs to date. Notably, solid tumours, and specifically lung adenocarcinomas, are common culprits. Malignant pericardial Effs are often severe, with a majority of patients presenting with cardiac tamponade. Overall, treatment options are limited, and the associated mortality rate is high., (© 2024 The Authors.)

Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in a significant increase in morbidity and mortality in hospitalized patients. We aimed to analyze the impact of applying 10% povidone iodine (PI) twice daily to both nares in addition to chlorhexidine (CHG) bathing on nosocomial (MRSA) bacteremia in critically ill patients. A quality improvement study was completed with pre and post-design. The study period was from January 2018 until February 2020 and February 2021 and June 2021. The control period (from January 2018 to May 2019) consisted of CHG bathing alone, and in the intervention period, we added 10% PI to the nares of critically ill patients. Our primary outcome is rates of nosocomial MRSA bacteremia, and our secondary outcome is central line associated blood stream infection (CLABSI) and potential cost savings. There were no significant differences in rates of MRSA bacteremia in critically ill patients. Nosocomial MRSA bacteremia was significantly lower during the intervention period on medical/surgical areas (MSA). CLABSIs were significantly lower during the intervention period in critically ill patients. There were no Staphylococcus aureus CLABSIs in critical care area (CCA)during the intervention period. The intervention showed potential significant cost savings. The application of 10% povidone iodine twice a day in addition to CHG bathing resulted in a significant decrease in CLABSIs in critically ill patients and a reduction in nosocomial MRSA in the non-intervention areas. Further trials are needed to tease out individual patients who will benefit from the intervention.

Background: Wernicke's encephalopathy (WE) is a serious neurological disorder that is underdiagnosed. Despite limited clinical guidelines, the standard use of intravenous (IV) thiamine is underutilized and remains an area of research deserving much attention., Objectives: We conducted a systematic review using Medline, Embase, and CENTRAL databases to identify and summarize the literature on IV thiamine treatment in WE. Human studies with WE patients who received ≥100 mg of thiamine IV met inclusion criteria. Randomized controlled trials, cross-sectional studies, and case reports were included., Results: A total of 27 studies were included: 20 case reports, five retrospective studies, one prospective study and one randomized control trial. Of the case reports, 11 (55%) cases were female, and the average age of all cases was 45 years (SD = 15). The other seven studies included 688 patients; the average age was 52 years (SD = 9), and 266 (38.7%) were female. Among the case reports, neurological and clinical findings were used to diagnose WE in 16 (80%) cases. MRI was utilized to diagnose 15 (75%) cases. 500 mg IV thiamine TID was reported in 12 case reports (60%). 18 (90%) of case reports had partial or complete resolution of symptoms following IV thiamine., Conclusion: IV thiamine can alleviate neurological symptoms, cognitive dysfunction, and brain imaging lesions associated with WE. We found key limitations in the evidence for IV thiamine and diagnostic standards for WE. Future targeted research should establish clear diagnostic and treatment guidelines for WE to prevent this serious condition from being underdiagnosed or undertreated., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids., Data Sources: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022., Study Selection and Data Extraction: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use., Data Synthesis: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs., Relevance to Patient Care and Clinical Practice: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline., Conclusion and Relevance: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.D. reports he is on the Advisory Committee for ALung Technologies, Inc. All other authors report no conflicts of interest. The other authors declare no conflicts to disclose.

Objective: Coronary artery bypass grafting (CABG) is an established revascularisation strategy for multivessel and left main coronary artery disease. Although aspirin is routinely recommended for patients with CABG, the optimal antiplatelet regimen after CABG remains unclear. We evaluated the efficacies and risks of different antiplatelet regimens (dual (DAPT) versus single (SAPT), and dual with clopidogrel (DAPT-C) versus dual with ticagrelor or prasugrel (DAPT-T/P)) after CABG., Methods: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and performed a comprehensive literature search using PubMed, Ovid Medline, Ovid Embase and Cochrane Central Register of Controlled Trials. Data were extracted and pooled using random-effects models and Review Manager (V.5.4)., Results: Among the 2970 article abstracts screened, 215 full-text articles were reviewed and 38 studies totaling 77 447 CABG patients were included for analyses. DAPT compared with SAPT was associated with significantly lower all-cause mortality (OR 0.65 with 95% CI 0.50 to 0.86; p=0.002), cardiovascular mortality (OR 0.53, 95% CI 0.33 to 0.84; p=0.008), and major adverse cardiac and cerebrovascular events (MACCE) (OR 0.68, 95% CI 0.51 to 0.91; p=0.01), but higher rates of major (OR 1.30, 95% CI 1.08 to 1.56; p=0.007) and minor bleeding (OR 1.87, 95% CI 1.28 to 2.74; p=0.001) after CABG. DAPT-T/P compared with DAPT-C was associated with significantly lower all-cause (OR 0.43, 95% CI 0.29 to 0.65; p≤0.0001) and cardiovascular mortality (OR 0.44, 95% CI 0.24 to 0.80; p=0.008), and no differences on other cardiovascular or bleeding outcomes after CABG., Conclusion: In patients with CABG, DAPT compared with SAPT and DAPT-T/P compared with DAPT-C were associated with reduction in all-cause and cardiovascular mortality, especially in patients with acute coronary syndrome. Additionally, DAPT was associated with reduction in MACCE, but higher rates of major and minor bleeding. An individualised approach to choosing antiplatelet regimen is necessary for patients with CABG based on ischaemic and bleeding risks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility-onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years)., Background: CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain., Methods: Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST., Results: Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias., Conclusion: The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.