Alexander Fleming: a second look.

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.

Prevalence of Barrett's Esophagus and Esophageal Adenocarcinoma With and Without Gastroesophageal Reflux: A Systematic Review and Meta-analysis.

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.

Preoperative Epidural Steroid Injections and Postoperative Infections After Lumbar or Cervical Spine Surgery: A Systematic Review and Meta-Analysis.

Objective: To determine the risk difference and 95% prediction intervals (PIs) for postoperative infections (POIs) associated with preoperative epidural steroid injections (ESIs) in adults undergoing lumbar or cervical spine surgery. Methods: Comprehensive database searches were conducted from inception dates through December 2023. Inclusion criteria included all study designs involving adults receiving a preoperative ESI before lumbar or cervical decompression or fusion spine surgery. Risk of bias was assessed using a modified tool developed for uncontrolled studies. The summary estimates of risk difference and the corresponding PIs were reported. Results: A total of 12 studies were included in the systematic review, of which 9 were included in the meta-analysis. Preoperative ESIs within 1 month of lumbar spine decompression or fusion surgery were associated with a 0.6% and 2.31% greater risk of a POI, respectively. In adults ≥65 years of age, ESIs within 1 or 1-3 months of lumbar spine decompression or fusion surgery were associated with a 1.3% and 0.6% greater risk of a POI, respectively. Preoperative ESIs within 3 months of cervical spine fusion were not associated with an increased risk of a POI. The bounds of all corresponding 95% PIs were nonsignificant. Conclusion: The observations of this study provide summary estimates of risk difference and 95% PIs, which could be used to support shared decision-making about the use of ESIs before cervical or lumbar spine surgery.

Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis.

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 patients with alcohol-associated cirrhosis.

A clinical profile of infective endocarditis in patients with recent COVID-19: A systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients. METHODS: Our search was conducted in 8 databases for all published reports of probable or definite IE in patients with a prior COVID-19 confirmed diagnosis. After ensuring an appropriate inclusion of the articles, we extracted data related to clinical characteristics, modified duke criteria, microbiology, outcomes, and procedures. RESULTS: Searches generated a total of 323 published reports, and 20 articles met our inclusion criteria. The mean age of patients was 52.2 ± 16.9 years and 76.2% were males. Staphylococcus aureus was isolated in 8 (38.1%) patients, Enterococcus faecalis in 3 patients (14.3%) and Streptococcus mitis/oralis in 2 (9.5%) patients. The mean time interval between COVID-19 and IE diagnoses was 16.7 ± 15 days. Six (28.6%) patients required critical care due to IE, 7 patients (33.3%) underwent IE-related cardiac surgery and 5 patients (23.8%) died during their IE hospitalization. CONCLUSIONS: Our systematic review provides a profile of clinical features and outcomes of patients with a prior COVID-19 infection diagnosis who subsequently developed IE. Due to the ongoing COVID-19 pandemic, it is essential that clinicians appreciate the possibility of IE as a unique complication of COVID-19 infection.

Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset.

BACKGROUND: The objective was to systematically evaluate the sensitivity of diffusion-weighted magnetic resonance imaging (DW-MRI) for transient global amnesia (TGA) across various time frames compared to the reference-standard clinical criteria. METHODS: All indexed publications related to TGA and MRI through June 2020 were retrieved by a medical librarian. Two independent reviewers identified original research studies of adults with a clinical diagnosis of TGA using Caplan and Hodges and Warlow criteria (reference standard) who were evaluated with DW-MRI. Pooled estimates and its 95% confidence intervals (CI) for the proportion of acute TGA patients with positive DW-MRI (i.e., sensitivity) were obtained using random-effects meta-analysis for various time frames. Quality assessment was performed using the revised Quality of Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: After screening 665 reports, we identified 81 potentially relevant studies. Twenty-three studies representing 1688 patients met eligibility criteria, but not all studies had data available for meta-analysis. The pooled sensitivity (also described as positivity rate) of DW-MRI was 15.6% (95% CI = 2.6%-35.0%) between 0 and 12 h from symptom onset, 23.1% (95% CI = 6.1%-45.7%) at 0-24 h, 72.8% (95% CI = 40.8%-96.3) at 12-24 h, 68.8% (95% CI = 44.8%-88.8%) at 24-36 h, 72.4% (95% CI = 59.8%-83.5%) at 36-48 h, 82.8% (95% CI = 54.7%-99.6%) at 48-60 h, 66.9% (95% CI = 47.5%-83.9%) at 60-72 h, and 72.0% (95% CI = 30.1%-100.0%) at 72-96 h. There was significant concern for risk of bias in the QUADAS-2 domains of patient selection and index test, yielding a low level of certainty in the pooled estimates. CONCLUSION: DW-MRI lesions are uncommon in patients with TGA early after symptom onset, but the sensitivity (i.e., positivity rate) of DW-MRI increases with time. Despite the limited quality of existing evidence, obtaining an early DW-MRI in patients with clinical diagnosis of TGA in the acute setting is likely a low-yield test.

Lidocaine for postoperative pain after cardiac surgery: a systematic review.

OBJECTIVE: Lidocaine is one of the most widely used local anesthetics with well-known pharmacological properties. The purpose of this systematic review is to investigate the effects of lidocaine on postoperative pain scores and recovery after cardiac surgery. METHODS: A comprehensive database search was conducted by a reference librarian for randomized clinical trials (RCT) from January 1, 1980 to September 1, 2019. Eligible study designs included randomized controlled trials of lidocaine for postoperative pain management in adults undergoing cardiac surgery. After removal of duplicates, 947 records were screened for eligibility and 3 RCTs met inclusion criteria. RESULTS: Sources of bias were identified in 2 of 3 RCTs. Lidocaine was administered intravenously, topically, and intrapleurally. Key findings included [1] 2% lidocaine placed topically on chest tube prior to intraoperative insertion was associated with significantly lower pain scores and lower cumulative doses of fentanyl; and [2] 2% lidocaine administered intrapleurally was associated with significantly lower pain scores and significant improvements in pulmonary mechanics. Lidocaine infusions were not associated with significant changes in pain scores or measures of recovery. No significant associations were observed between lidocaine and overall mortality, hospital length of stay or ICU length of stay. No data were reported for postoperative nausea and vomiting or arrhythmias. CONCLUSIONS: Due to the favorable risk profile of topical lidocaine and the need for further advancements in the postoperative care of adults after cardiac surgery, topically administered lidocaine could be considered for incorporation into established postoperative recovery protocols.

Risk factors for delirium among older adults in the emergency department: a systematic review protocol.

INTRODUCTION: Delirium is commonly missed in older adults presenting to the emergency department (ED). Although current recommendations for active screening of delirium in the ED, this might not be feasible or practical. Identifying patients at high risk for prevalent and incident delirium in the ED will help to improve the screening process and to build interventions. There is currently scattered synthesis of evidence on risk factors associated with delirium in the ED. To address this gap, we are conducting a systematic review to describe the risk factors (patient vulnerability factors and precipitating factors) for delirium in the ED. METHODS AND ANALYSIS: A literature search was performed from inception to March 2020 in Ovid EBM Reviews, Ovid EMBASE, Ovid MEDLINE, Scopus and Web of Science. We will include original research studies that report a quantitative relationship between at least one risk factor and delirium in the ED setting. Two investigators will use eligibility criteria from this protocol to independently screen titles and abstracts, and select studies based on full-text review of potentially eligible studies. After arriving at a final set of included studies, two investigators will extract data using a standardised data collection form. If appropriate, data regarding each risk factor will be pooled through a random-effect meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to evaluate the overall quality of evidence. ETHICS AND DISSEMINATION: To our knowledge, this will be the first systematic review evaluating risk factors for prevalent and incident delirium specifically related to the ED setting. Results of this study will aid in the identification of older adults at risk for delirium in the ED. We aim to publish the results of this systematic review in a peer-reviewed journal with good visibility for the fields of emergency medicine and geriatrics.PROSPERO registration numberCDR42020175261.