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Intensive Care Unit Liberation After Complete Left Anterior Descending Artery Occlusion: Unexpected Neurologic Recovery After a 53-Minute Cardiac Arrest
No full textOut-of-hospital cardiac arrest (OHCA) is associated with low survival and neurologic recovery rates, especially when return of spontaneous circulation exceeds 45 minutes. Additionally, neurologic prognostic indicators, such as absent brainstem reflexes and presence of alpha coma electroencephalogram (EEG) patterns, are typically associated with poor outcomes. This report outlines the case of a 48-year-old woman with a history of hypertension, dyslipidemia, and tobacco use who suffered an OHCA due to an acute left anterior descending artery occlusion. She experienced a total downtime of 53 minutes and required multiple rounds of defibrillation and advanced cardiac life support. Following successful percutaneous coronary intervention, her initial neurologic examination remained poor with absent brainstem reflexes, nonreactive pupils, and EEG findings consistent with severe encephalopathy. After 22 days in the hospital with minimal neurologic improvement, she was discharged to long-term care with a tracheostomy and percutaneous endoscopic gastrostomy tube. Two months after initial discharge, the patient unexpectedly returned to the hospital, demonstrating signs of cognitive recovery. During this second hospital stay, she was alert, followed commands, was able to communicate using a voice modulator, and passed a swallow study. This case illustrates a rare example of survival after prolonged OHCA and subsequent neurologic improvement following an initially guarded prognosis
Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial
No full textIMPORTANCE: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.
OBJECTIVE: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.
DESIGN, SETTING, AND PARTICIPANTS: Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteremia who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibacterial therapy were included. Participants were excluded if they had central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immune compromise.
INTERVENTIONS: Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or antistaphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant).
MAIN OUTCOMES AND MEASURES: The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was \u3e50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety.
RESULTS: Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. Participants without a day 70 efficacy assessment were treated as clinical failures in the analyses. The probability of a more desirable day 70 outcome with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, -11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups.
CONCLUSIONS AND RELEVANCE: Among adult participants with complicated S aureus bacteremia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking. When considered with other efficacy and safety outcomes these findings may help inform use of dalbavancin in clinical practice.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04775953
Efficacy and Safety of Linaclotide as an Adjunct to Polyethylene Glycol in Bowel Preparation: A Meta-Analysis
No full textOBJECTIVES: Linaclotide, a guanylyl cyclase-C agonist, may enhance efficacy and tolerability when combined with polyethylene glycol (PEG) for bowel preparation. This meta-analysis evaluated linaclotide plus PEG versus PEG alone for bowel preparation prior to colonoscopy.
METHODS: Randomized controlled trials (RCTs) including adults undergoing colonoscopy that compared linaclotide plus PEG with PEG alone for bowel preparation were identified via database search up to March 2024. Statistical analysis was performed in RevMan Web using random-effects models.
RESULTS: Eleven RCTs were analyzed. Adequate bowel preparation rate was comparable (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.98-1.04; I(2) = 23%), as was cecal intubation rate (RR 1.01, 95% CI 1.00-1.01). Subgroup analyses showed that compared with 3-L PEG alone, 2-L PEG plus linaclotide was non-inferior, while 3-L PEG plus linaclotide was superior regarding bowel preparation adequacy (RR 1.11, 95% CI 1.01-1.23) and total Boston Bowel Preparation Scale (BBPS) score (mean difference 0.44, 95% CI 0.04-0.85). Right and left colon BBPS scores were also higher with linaclotide. Polyp detection rate improved significantly in the 3-L PEG plus linaclotide subgroup (RR 1.78, 95% CI 1.32-2.40), whereas adenoma detection rate and withdrawal time were comparable. Linaclotide reduced abdominal pain, bloating, nausea, and sleep disturbance, and increased willingness to repeat colonoscopy.
CONCLUSIONS: Linaclotide with PEG provides comparable overall bowel cleansing to PEG alone while reducing adverse events and improving patient acceptance. Importantly, 2-L PEG plus linaclotide was non-inferior compared with 3-L PEG, whereas 3-L PEG plus linaclotide showed superiority over 3-L PEG alone, supporting its use in low-volume bowel preparation strategies
Esophageal Hematoma Following Transcatheter Edge-to-Edge Repair of the Mitral Valve: A Rare Complication of Transesophageal Echocardiography
No full textTransesophageal echocardiography is commonly used to guide structural cardiac interventions but carries a risk of esophageal injury. We present a 79-year-old woman who underwent a Transcatheter Edge-to-Edge Repair of the mitral valve and developed an esophageal hematoma. Clinical course was complicated by intractable gastrointestinal bleeding and sepsis due to acute cholecystitis. She did not survive despite aggressive measures. Our case demonstrates the potential severity of transesophageal echocardiography-related complications, especially in patients with predisposing factors such as esophageal diverticula and anticoagulation use
Diagnostic accuracy of discovery NM 530c CZT SPECT for myocardial perfusion imaging in coronary artery disease: a systematic review and meta-analysis
No full textCoronary artery disease (CAD) is the leading cause of cardiovascular mortality (CVD), accounting for 1 in 5 CVD-related deaths. The advent of non-invasive imaging modalities has driven the use of myocardial perfusion imaging (MPI) to enhance diagnostic accuracy and improve clinical outcomes in CAD. Building on the role of myocardial perfusion imaging (MPI), this meta-analysis assesses the diagnostic accuracy of the Discovery NM 530c CZT SPECT for CAD compared with invasive coronary angiography (ICA ± FFR) and noninvasive modalities, including PET, MRI, and coronary CT angiography. A systematic search of six databases was conducted to identify studies evaluating the diagnostic accuracy of the NM 530c CZT-SPECT for detecting CAD. Comparator modalities included ICA ± FFR, PET, MRI, or coronary CTA performed within 90 days. Diagnostic performance was assessed using pooled sensitivity, specificity, summary receiver operating characteristic (SROC) curves, and diagnostic odds ratio (DOR), using R (v2024.12.0 + 467) with the meta and mada packages. A bivariate meta-analysis of 11 studies showed a pooled sensitivity of 83.5% (95% CI: 77.3-88.3%) and specificity of 75.8% (95% CI: 67.8-82.3%), with an AUC of 0.858 and diagnostic odds ratio (DOR) of 15.9. Likelihood ratios were 3.45 (positive) and 0.22 (negative). The SSS ≥ 4 subgroup showed the highest sensitivity (0.881) and DOR (19.21). The univariate random-effects model yielded a pooled sensitivity of 83% and specificity of 77%. Heterogeneity was moderate, and Deeks\u27 test showed no publication bias (p = 0.83). This meta-analysis establishes the Discovery NM 530c CZT SPECT as a reliable and clinically effective non-invasive modality for detecting coronary artery disease (CAD), with a pooled sensitivity of 0.835, specificity of 0.758, and AUC of 0.858, supporting its diagnostic utility across diverse clinical settings
Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson\u27s Disease
No full textParkinson\u27s Disease (PD) is a neurodegenerative disorder characterized by α-synuclein accumulation and aggregation, leading to disrupted cellular homeostasis, impaired mitochondrial function, and neuroinflammation, ultimately causing neuronal death. Recent biomarker studies reveal elevated serum levels of L-ornithine-derived polyamines correlating with PD progression and clinical subtypes, though their precise role in PD pathology remains unclear. We investigated the impact of polyamine-interconversion enzymes (PAIEs) on α-synucleinopathy in a Drosophila melanogaster model of PD, evaluating key degenerative features such as lifespan, locomotor function, tissue integrity, and α-synuclein accumulation. Knockdown of ornithine decarboxylase 1 (ODC1), spermidine synthase (SRM), and spermine oxidase (SMOX) reduced α-synuclein toxicity, while suppression of spermidine/spermine N1-acetyltransferase 1 (SAT1) and spermine synthase (SMS) exacerbated it. Conversely, overexpressing SAT1 or SMOX significantly reduced α-synuclein toxicity, highlighting their potential role in PD. These findings underscore the critical role of polyamine pathways in modulating α-synuclein toxicity, offering novel therapeutic targets for PD
Immune-responsive gene 1: The mitochondrial key to Th17 cell pathogenicity in CNS autoimmunity
No full textPathogenic Th17 cells play crucial roles in CNS autoimmune diseases such as multiple sclerosis (MS), but their regulation by endogenous mechanisms remains unknown. Through RNA-seq analysis of primary brain glial cells, we identified immune-responsive gene 1 (Irg1) as one of the highly upregulated genes under inflammatory conditions. Validation in the spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), a preclinical MS model, confirmed elevated Irg1 levels in myeloid, CD4, and B cells in the EAE group, raising concerns as to whether Irg1 is detrimental or protective. Irg1 knockout (KO) mice exhibited severe EAE disease, increased mononuclear cell infiltration, and increased levels of triple-positive CD4+ T cells expressing IL17a, GM-CSF, and IFNγ. Adoptive transfer in Rag-1 KO and single-cell RNA sequencing highlighted the crucial role of Irg1 in shaping pathogenic Th17 cells. A lack of Irg1 in macrophages elevates Class II expression, promoting the polarization of myelin-primed CD4+ T cells into pathogenic Th17 cells via the NLRP3/IL-1β axis. Moreover, bone marrow chimeras revealed that immune cells lacking Irg1 maintained pathogenic and inflammatory phenotypes, suggesting its protective role in autoimmune diseases, including MS
Maxillary Sinus Antrochoanal Polyp Recurrence Following Surgery in Adults: A Systematic Review
No full textOBJECTIVE: Antrochoanal polyps (ACPs) are cystic non-neoplastic lesions that most commonly originate from the maxillary sinus and may extend posteriorly through the choana. Transnasal endoscopic removal is preferred for symptomatic ACPs. ACPs can recur after surgical removal, and while a 15% recurrence rate was published in a systematic review on pediatric ACPs, this has not been well-established in adults. The purpose of this systematic review was to determine the recurrence rate of maxillary sinus ACPs following surgical resection in adults.
DATA SOURCES: A systematic review was conducted on ACP resection using Medline, Embase, and Web of Science databases from 1946 to July 2025.
REVIEW METHODS: After excluding duplicate and non-English articles, 395 abstracts were screened, and 63 articles were selected for full-text review. Articles were included if they were original studies that reported recurrence rates after surgical resection of maxillary sinus ACPs in patients ≥ 16 years old. Articles were excluded if study populations had minimum follow-up of less than 6 months or mean follow-up of less than 12 months.
RESULTS: After full-text review, 16 studies met inclusion criteria with 439 patients being utilized for analyses. Mean age was 33.8 years and 39.7% were female. Endoscopic middle meatal antrostomy with ACP removal was performed in 80.8% of cases. Following surgery, patients experienced an overall recurrence rate of 9% (95% CI: 6%-14%), with a mean follow-up of 36.8 months.
CONCLUSION: ACPs recurred in about 9% of adults following surgical resection. Further research is needed to determine whether certain patient factors and surgical techniques are associated with ACP recurrence
Overlapping Morphologic and Immunophenotypic Features of Plasmacytoid Urothelial Carcinoma and Urothelial Carcinoma With Osteoclast-Like Giant Cells
No full textOsteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is an uncommon tumor currently classified under poorly differentiated urothelial carcinoma subtype composed of osteoclast-like giant cells intermixed with abundant mononuclear cells. Not infrequently, the mononuclear component exhibits eccentric nuclear localization reminiscent of plasmacytoid urothelial carcinoma. Given an index tumor where the mononuclear component of UCOGC showed prominent plasmacytoid histology and concomitant plasmacytoid urothelial carcinoma immunophenotype (aberrant loss of membranous E-cadherin with cytoplasmic p120 expression), herein we explore E-cadherin/p120 immunoreactivity in 14 UCOGC with sequencing performed on 4 tumors. Plasmacytoid histology in the mononuclear was identified in all 14 (100%) UCOGC, extent ranging from 20% to 70% (mean = 40%). In 13 of 14 UCOGCs, the mononuclear component showed loss of membranous E-cadherin while strong cytoplasmic p120 staining was present in all 14 tumors. Four UCOGCs also contained separate elements of plasmacytoid subtype urothelial carcinoma, all exhibiting aberrant loss of membranous E-cadherin with cytoplasmic p120 expression. NGS testing showed no evidence of E-cadherin mutations in 4 tested UCOGCs. Although both plasmacytoid UC and UCOGC are associated with poor outcomes, given the established clinicopathologic and molecular features of plasmacytoid urothelial carcinoma, it is prudent to avoid misclassifying UCOGC as plasmacytoid urothelial carcinoma based on the shared aberrant immunoprofile of the mononuclear (loss of membranous E-cadherin with cytoplasmic p120 expression). Recognition of the intimately admixed osteoclast-like giant cells characteristic of UCOGC (often overlooked when sparse and/or in a small biopsy setting) is key for accurate diagnosis
Developing a Protocol for Therapeutic Plasma Exchange in Tandem With Continuous Renal Replacement Therapy (CRRT) and ExtraCorporeal Membrane Oxygenation (ECMO) in Pediatric Patients
No full textTherapeutic plasma exchange (TPE) in pediatric patients presents many challenges, including management of a large extracorporeal volume (ECV) and calcium replacement for patients who may not be able to express signs of hypocalcemia or other associated adverse events with a large ECV. Pediatric patients who are critically ill on continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO) may have indications for TPE, such as sepsis or liver failure anticipating transplant. It may be difficult or clinically detrimental to take the patient off the CRRT or ECMO circuit to perform TPE. Connecting the TPE device into the preexisting circuit is feasible with the understanding of the principles of the circuit flow set up and monitoring to mitigate adverse events. Effective communication among clinical teams managing distinct extracorporeal circuits is critical to ensuring coordinated patient care