Background:Knowing the prevalence of patent foramen ovale (PFO) and the increasing number of people who inject drugs (PWID) with right-sided infective endocarditis (RSIE), we aimed to better characterize the syndrome of injection drug use, RSIE, and PFO with systemic embolic events. Method:A systematic search across multiple databases was independently screened using predefined criteria (from inception until September 2025). Published cases of adult PWID diagnosed with RSIE and ischemic stroke or other systemic embolic event were included, provided they had PFO assessment. Individuals were excluded if they had cardiac implantable electronic device (CIED) infections or any other conditions associated with systemic or paradoxical embolism. Results:The review identified 13 studies with 14 young patients, mostly without comorbidities, predominantly infected with Staphylococcus aureus. In most cases, echocardiography revealed large tricuspid valve vegetations. Neuroimaging confirmed multiple ischemic infarcts, while 5 patients showed emboli outside the central nervous system (4 of them as the only systemic embolism). At least 11 (79%) patients had echocardiographic evidence of right-to-left shunting. Management included cardiac surgery in 6 cases that involved valve replacement or repair, percutaneous PFO closure in 2 cases, and percutaneous mechanical aspiration in 1 case. Three patients (21%) died during hospitalization, and only 27.3% patients had outpatient follow-up. Conclusions:RSIE with systemic embolism in PWID with PFO has rarely been reported, affects younger patients without sex predominance, and was usually due to S. aureus with large tricuspid vegetations. Right-to-left shunting was characteristic, and outcomes were poor despite combined medical, surgical, and interventional therapies.

Isolated pulmonary valve endocarditis (PV-IE) is a rare condition. Its epidemiology, clinical profile, and management remain poorly characterized. A systematic review was conducted to provide a contemporary characterization (2020–2025) of adult cases with isolated PV-IE. Individuals with previous cardiac surgeries, cardiac implantable electronic devices (CIEDs), or long-term venous catheters were excluded. Of 1902 citations identified, 72 studies were selected with 79 eligible cases, mostly case reports. Patients were predominantly male (78.5%) with a median age of 43 years. Congenital heart disease (CHD) and injection drug use (IDU) were risk factors in 30.4% and 27.8% of cases, respectively, while 41.8% had neither (No-CHD/IDU group). Staphylococcus aureus was the leading pathogen (39%), followed by streptococci (16.5%) and Enterococcus faecalis (8.9%). Vegetations were large (median, 19.5 mm), and pulmonary septic emboli highly prevalent (~93% of cases). More than half (54.4%) of patients underwent surgery. Hospital mortality was low (7.6%). Differences across risk factor subgroups were observed, with higher median age in No-CHD/IDU patients and more staphylococcal etiology in patients with IDU, although treatment approaches and mortality did not differ. This review highlights distinct characteristics and the overall favorable short-term prognosis of isolated PV-IE, underscoring the need for larger, systematically collected datasets.

BACKGROUND AND IMPORTANCE:Rapid sequence intubation in emergency settings may involve opioid pretreatment to blunt hemodynamic responses during laryngoscopy and intubation; however, opioids may lead to postintubation hypotension, increasing morbidity and mortality. Global clinical practice varies significantly, reflecting uncertainty about opioids' benefits and risks. OBJECTIVE:Our goal was to evaluate the association between opioid pretreatment and hemodynamic instability, focusing on postintubation hypotension in adult patients undergoing emergency intubation. DESIGN, SETTINGS, AND PARTICIPANTS:We performed a systematic review of randomized controlled trials and observational studies comparing opioid administration vs. no opioids before adult emergency intubations. Searches included Cochrane, Embase, Medline, Scopus, and Web of Science databases until November 2024. Elective intubations were excluded. Eight (6708 patients) studies met criteria. OUTCOMES MEASURE AND ANALYSIS:The primary outcome was postintubation hypotension, variably defined across studies. Secondary outcomes included hypoxemia, first-attempt success, cardiac arrest, and vasopressor use. Independent reviewers conducted data extraction, risk-of-bias assessments, and certainty evaluation. Results were qualitatively synthesized. MAIN RESULTS:Among 6708 (2757 opioids and 3951 controls) patients, postintubation hypotension incidence varied widely (risk differences: -12.5% favoring opioids to +13.2% favoring controls). The single low-risk randomized study reported opioids increased hypotension (risk difference: 13%, odds ratio: 2.15, 95% confidence interval: 1.22-3.78). Observational studies yielded inconsistent results. Secondary outcomes showed no consistent differences. Evidence certainty was very low because of risk of bias, inconsistency, and imprecision. CONCLUSIONS:Current evidence regarding opioid pretreatment effect on postintubation hypotension risk during emergency intubation is limited and conflicting.

INTRODUCTION:Current guidelines recommend endoscopic surveillance of Barrett's esophagus (BE) but do not account for competing mortality unrelated to esophageal cancer (EC). We conducted a systematic review and meta-analysis to estimate EC and non-EC mortality risk in BE patients. METHODS:We searched multiple databases for studies reporting mortality in BE. We included population-based studies providing standardized mortality ratio (SMR). The primary outcome was SMR from all causes and EC and non-EC etiologies. SMR was calculated by dividing the observed mortality over the expected mortality. Logarithmic form of SMRs was pooled using random-effects model. RESULTS:Our search yielded 2,826 articles, of which 7 studies (n = 34,454) were included. All-cause mortality was elevated in BE patients compared with population controls (pooled SMR 1.24, 95% confident interval [CI] 1.01-1.53) driven in part by increased EC mortality risk (SMR 8.98, 95 CI 5.12-15.77). The mortality risk was still increased but attenuated after excluding EC mortality (SMR 1.21, 95% CI 1-1.46). There was no increased mortality risk of non-EC malignancies (SMR 1.22, 95% CI 0.82-1.82) or mortality due to noncancer etiologies (SMR 1.13, 95% CI 0.90-1.43). Death due to cardiovascular diseases was higher in BE (SMR 1.16, 95% CI 1.02-1.33). BE patients were 10 times more likely to die from noncancer etiologies than EC (risk ratio 10.71, 95% CI 5.98-19.16). Subgroup analysis of studies that excluded prevalent EC at baseline (3 studies) also showed increased all-cause (SMR 1.12, 95% CI 1.07-1.18) and EC mortality (SMR 4.7, 95% CI 3.58-6.17) among BE patients. DISCUSSION:BE patients exhibit a higher all-cause mortality, driven in part by risk of EC mortality. A personalized approach to surveillance, mitigating risk of EC while recognizing the broader mortality risks, is warranted.

BACKGROUND:Esophageal-pericardial fistula (EPF) is rare with an incidence of 0.016%-0.04%. With novel procedures involving intracardiac or esophageal instrumentation in the last few decades, including atrial fibrillation (AF) ablation, further understanding of this unique entity is warranted. In this systematic review, we summarize the etiology, diagnostic features, management, and outcomes of EPF. METHODS:A librarian conducted a systematic literature review of case reports/series describing adults diagnosed with EPF through 7 major databases/registries from inception to 7/30/2024. RESULTS:One hundred twenty patients from 115 papers met the inclusion criteria. Median age(IQR) was 57(44-67) years, with a male predominance (73.7%). The primary etiology of EPF shifted from benign esophageal diseases before 2000 to AF ablation on/after 2000. Median time(IQR) from AF ablation to EPF presentation/diagnosis was 17(13-23) days. Chest pain (70.8%) and pneumopericardium (90.0%) were, respectively, the most common presenting symptom and pericardial finding. Water-soluble contrast esophagram (WSCE) had the highest diagnostic sensitivity (82.8%). Management included surgery (47.5%), stent placement (22.5%), combined surgery/stenting (19.2%), and conservative (10.8%). Overall mortality was 37.5%; median(IQR) time to death was 20(9-41) days. EPF from malignancy had poorer survival than those from benign esophageal causes (HR 2.65 [1.36-5.17]; p = 0.004) and cardiac ablation (HR 5.74 [2.41-13.65]; p < 0.0001). Patients who received any intervention (HR 0.28 [0.13-0.57]; p = 0.0005) or had confirmed EPF resolution (HR 0.27 [0.12-0.59]; p = 0.0009) demonstrated better survival. There was no difference in survival between surgery and stenting alone (p = 0.91). CONCLUSIONS:AF ablation is now the leading etiology of EPF. Given its high mortality, a high degree of clinical suspicion is essential in those presenting with key signs/symptoms following AF ablation to enable urgent diagnosis and multi-disciplinary management. WSCE may be the diagnostic modality to perform, given its high sensitivity. Future studies are warranted to investigate whether stenting should be the primary management given possible non-inferiority to surgery.

OBJECTIVE:To determine whether hyperangulated videolaryngoscopy (HAVL) improves first-attempt success (FAS) in adult orotracheal intubations compared to standard-geometry videolaryngoscopy (SGVL), with a focus on emergency settings. METHODS:We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and comparative observational studies evaluating HAVL versus SGVL in adult tracheal intubations. Comprehensive searches were performed in Ovid MEDLINE, Embase, Cochrane, Scopus, and web of science from inception through November 2024. Risk of bias was assessed using RoB2 and Newcastle-Ottawa tools, and certainty of evidence was rated using GRADE. Both emergency and operating room intubations were included; most emergency data derived from large cohort studies. RESULTS:Of 4445 screened records, 25 studies (17 RCTs, 8 observational; 38,597 patients) were included. HAVL was associated with lower FAS overall (87.2 % vs 91.0 %; pooled RR 0.96, 95 % CI 0.94-0.99; p = 0.002). In emergency intubations (8 studies; n = 34,927), HAVL yielded reduced FAS (RR 0.97, 95 % CI 0.95-0.99; p = 0.003). There was no significant difference in difficult airways (RR 0.98, 95 % CI 0.92-1.05; p = 0.57). HAVL was linked to higher rates of airway trauma (7.5 % vs 2.9 %; RR 1.88, 95 % CI 1.01-3.49; p = 0.046) and numerically more adverse events. Certainty of evidence was low due to risk of bias and heterogeneity. CONCLUSIONS:In emergency intubations, HAVL was associated with lower first-attempt success and increased airway trauma compared to SGVL. These findings support prioritizing SGVL for emergency airway management, with careful operator training if HAVL is used.

BACKGROUND:β-Lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of β-lactam antibiotics. OBJECTIVE:This systematic review and meta-analysis aimed to identify sex- and gender-based differences in the prevalence of immediate β-lactam allergy. METHODS:We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013 and 2023. Patients with a documented β-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in β-lactam allergy with meta-analysis. RESULTS:We included 69 primary studies assessing 53,989 participants from outpatient and inpatient cohorts. A total of 7,558 patients had a confirmed β-lactam allergy. There was no difference in the prevalence of positive β-lactam allergy test between males and females. Subgroup analysis of studies that performed oral challenges showed a higher risk of β-lactam allergy in females compared with males (relative risk = 1.40; 95% CI, 1.18-1.66; P < .001; I2 = 77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in β-lactam allergy studies. CONCLUSIONS:Our findings suggest both sex-based and gender-based differences in the prevalence of immediate β-lactam allergy. Biological factors such as sex hormones and gender-based behaviors including increased health care use may contribute to higher rates of β-lactam allergy diagnosis in females.

OBJECTIVE:Extracorporeal cardiopulmonary resuscitation (ECPR) utilizes veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in cardiac arrest patients to reduce the risk of mortality and multiorgan dysfunction from systemic hypoperfusion. We aimed to compare clinical outcomes of patients receiving ECPR versus conventional cardiopulmonary resuscitation (CCPR) for refractory cardiac arrest. DATA SOURCES:This was a systematic review and meta-analysis. A librarian searched the main databases, Ovid MEDLINE (including epub ahead of print, in-process & other non-indexed citations), Ovid EMBASE and Ovid Cochrane Central Register of Controlled Trials from inception through July 2024. STUDY SELECTION:We included randomized controlled trials and observational studies that compared the outcomes of ECPR to CCPR in cardiac arrest patients. Primary outcomes were neurological sequelae and survival. DATA EXTRACTION:We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened articles, extracted data on selected articles and performed risk of bias assessments using ROBINS-I for non-randomized controlled trials and the revised Cochrane risk of bias tool for randomized controlled trials with disagreements settled by a third independent reviewer. DATA SYNTHESIS:Out of 3458 studies identified and screened, 28 studies including 304,360 cardiac arrest patients met eligibility criteria and were included. Survival at hospital discharge was 20% for ECPR versus 3.3% for CCPR (OR 0.48 [CI 0.27, 0.84]). Favorable neurological outcome at hospital discharge was 11.8% for ECPR versus 1.9% for CCPR (OR 0.41 [CI 0.17, 1.01]). Complications from bleeding were ten times higher in the ECPR group (35.3% vs 3.7%; OR 0.08 [0.03, 0.24]). CONCLUSIONS:ECPR appeared to be superior to CCPR for improved neurological outcome and survival in cardiac arrest patients, although bleeding was increased. There was large heterogeneity in the included studies and outcomes reported. Future prospective studies may improve the identification of subgroups of patients that will benefit most from ECPR.Systematic review and meta-analysis registration: PROSPERO - CRD42023394128.

To evaluate the efficacy of physical therapy (PT) to alleviate symptomatic thoracic radiculopathy (TR) without the use of invasive procedures. Database search was conducted by an experienced medical librarian from inception until January 27, 2023, in EBSCO CINAHL with Full Text, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection. Inclusion criteria included studies that involved adult patients (age≥18) who had a magnetic resonance imaging-confirmed TR and underwent a structured, supervised PT program of any length. All types of studies were included. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. A total of 1,491 studies were screened and 7 studies met inclusion criteria, 5 case studies and 2 cohort studies. All studies showed improvement or resolution of the TR with PT. Quantitative improvements were not noted in most studies and PT regimens were sparsely described. Overall quality assessment demonstrated 3 studies had “good,” 1 “fair,” and 3 “poor” quality evidence. Certainty of evidence was “low” due to risk of bias. A dedicated PT program may help to alleviate symptomatic TR; however due to limited evidence, risk of bias, and low certainty in evidence, the data is too weak to support a definite conclusion.

In 1928, Alexander Fleming (1881-1955) identified penicillin, the world's first antibiotic. It was a chance discovery that could have easily been missed had Fleming not taken a second look at a contaminated Petri dish. The discovery of penicillin marked a profound turning point in history as it was the first time deadly infections such as bacterial pneumonia, sepsis, diphtheria, meningitis, and puerperal fever after childbirth could be cured, and it paved the way for the development of additional antibiotics. The Alexander Fleming Laboratory Museum, one of several London Museums of Health and Medicine, is a reconstruction of Fleming’s laboratory in its original location at St. Mary’s Hospital. As if stepping back in time, visitors gain a glimpse into the man, his bacteriology work, and the events surrounding this important finding. For those unable to travel to London, this article provides a brief narrative of the fascinating story.

BACKGROUND AND AIMS:Although gastroesophageal reflux disease (GERD) symptoms are an essential criterion for Barrett's esophagus (BE) screening in most gastroenterology society guidelines, a significant proportion of BE and esophageal adenocarcinoma (EAC) cases do not endorse them. In a systematic review and meta-analysis, we aimed to study the prevalence of BE/EAC in those with and without GERD. METHODS:A systematic search was conducted through 5 major databases for studies reporting prevalence of BE/EAC in patients with and without GERD. Pooled proportions and odds ratios (ORs) of BE, long-segment BE, short-segment BE, dysplasia, and EAC in patients with and without GERD were synthesized. RESULTS:Forty-three articles (12,883 patients with GERD; 51,350 patients without GERD) were included in the final analysis. BE prevalence was 7% (95% confidence interval [CI], 5.8%-8.5%) and 2.2% (95% CI, 1.6%-3%) among individuals with and without GERD, respectively. EAC prevalence was 0.6% (95% CI, 0.4%-1%) and 0.1% (95% CI, 0%-0.2%) in those with and without GERD, respectively. The overall risks for BE (OR, 2.91; 95% CI, 2.06-4.11) and long-segment BE (OR,4.17; 95% CI, 1.78-9.77) were higher in patients with GERD, but the risk for short-segment BE (OR, 1.77; 95% CI, 0.89-3.52) did not differ between the two groups. In 9 population-based high-quality studies (2244 patients with GERD; 3724 patients without GERD), BE prevalence in patients without GERD was 4.9% (95% CI, 2.6%-9%). BE prevalence was highest in North American studies (10.6% [GERD] and 4.8% [non-GERD]). CONCLUSIONS:BE prevalence in those without GERD is substantial, particularly in large high-quality population-based studies. These data are important to factor in future BE/EAC early detection guidelines.

Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.

Pulmonary auscultation is essential for detecting abnormal lung sounds during physical assessments, but its reliability depends on the operator. Machine learning (ML) models offer an alternative by automatically classifying lung sounds. ML models require substantial data, and public databases aim to address this limitation. This systematic review compares characteristics, diagnostic accuracy, concerns, and data sources of existing models in the literature. Papers published from five major databases between 1990 and 2022 were assessed. Quality assessment was accomplished with a modified QUADAS-2 tool. The review encompassed 62 studies utilizing ML models and public-access databases for lung sound classification. Artificial neural networks (ANN) and support vector machines (SVM) were frequently employed in the ML classifiers. The accuracy ranged from 49.43% to 100% for discriminating abnormal sound types and 69.40% to 99.62% for disease class classification. Seventeen public databases were identified, with the ICBHI 2017 database being the most used (66%). The majority of studies exhibited a high risk of bias and concerns related to patient selection and reference standards. Summarizing, ML models can effectively classify abnormal lung sounds using publicly available data sources. Nevertheless, inconsistent reporting and methodologies pose limitations to advancing the field, and therefore, public databases should adhere to standardized recording and labeling procedures.

BACKGROUND & AIMS: Alcohol is one of the leading causes of hepatocellular carcinoma (HCC). However, pooled estimates of HCC incidence in alcohol-associated cirrhosis have not been evaluated systematically. We performed a pooled analysis of time-to-event data to provide robust estimates for the incidence of HCC in alcohol-associated cirrhosis. METHODS: Medline, Embase, Cochrane Central Register, Scopus, and Web of Science were searched from inception to August 2021. Individual patient data were reconstructed from published Kaplan-Meier curves, and a pooled analysis of cumulative HCC incidence was performed using a random-effects model. RESULTS: We screened 5022 articles and included 18 studies (148,333 patients). In the pooled analysis, the cumulative incidence of HCC in alcohol-associated cirrhosis at 1, 5, and 10 years among studies that accounted for the competing risk of death without HCC was 1%, 3%, and 9%, respectively. A secondary analysis by traditional meta-analysis determined that the HCC incidence rate was higher in cohorts enrolled in a HCC surveillance program (18.6 vs 4.8 per 1000 person-years; P [ .001) vs those who were not enrolled in a surveillance program. Meta-regression showed that diabetes, smoking, variceal bleeding, and hepatic decompensation were associated with a higher risk of HCC. CONCLUSIONS: Our analysis determined that the 5- and 10-year cumulative risk of HCC in alcohol-associated cirrhosis was 3% and 9%, respectively, with a higher incidence in cohorts that were enrolled in a HCC surveillance program. These data should be validated further in large prospective studies, and may have important implications for HCC screening and surveillance among pa-tients with alcohol-associated cirrhosis.