A Retrospective Study of Dexamethasone, Remdesivir, and Baricitinib in Severe COVID-19.

Purpose: RECOVERY, ACTT-1, and ACTT-2 trials have demonstrated that utilization of dexamethasone, remdesivir, or a combination of remdesivir with baricitinib leads to mortality benefit and faster time to recovery, respectively. However, no studies have investigated the benefit of triple therapy of dexamethasone, remdesivir, and baricitinib. We investigate the benefits of triple therapy compared to dual therapy of dexamethasone with remdesivir in patients with severe COVID-19 on HFNC. Materials and Methods: A retrospective data analysis was performed on patients with severe COVID-19 requiring HFNC and evaluated for hospital discharge status, requirement of mechanical ventilation, length of stay, and days on HFNC. Results: Among 191 patients with severe COVID-19, 81 patients received dexamethasone, remdesivir, and baricitinib. Patients receiving triple therapy had a significant survival benefit (HR 0.52; P=0.042). Treatment with triple therapy vs. dual therapy also trended towards less requirement of mechanical ventilation (OR 0.66; P=0.26). There was no significant change in length of stay (mean 13.74 vs. 13.31; P=0.74) or days on HFNC (mean 8.95 vs. 7.28 days, P=0.16). Conclusions: The use of dexamethasone, remdesivir, and baricitinib in patients with severe COVID-19 requiring HFNC was associated with a significant survival benefit in comparison to dual therapy of dexamethasone with remdesivir.

Radiographic changes in ribs following clipping of patent ductus arteriosus in preterm infants.

Objectives: There are no published reports on the rib abnormalities on the plain chest radiograph in preterm infants following surgical clipping of isolated patent ductus arteriosus. The purpose of this study was to describe changes in the ribs on the plain chest radiograph following surgical clipping of patent ductus arteriosus (surgery groups) in preterm infants compared to non-surgical closure of patent ductus arteriosus (control group). Methods: Data from preterm infants with patent ductus arteriosus clipping (surgery) via a left postero-lateral thoracotomy were compared with infants in whom the patent ductus arteriosus closed: spontaneously, with medications or use of an occlusive device (controls). Serial pre- and post-closure plain chest radiographs were randomly reviewed by a reader blinded to the route of closure and up to 1 year following the patent ductus arteriosus closure. Results: Of the total of 196 cases included in the study: 45 of the patent ductus arteriosus closed following treatment with medications, 8 cases closed with an occlusion device, 38 were closed surgically, and in 105 cases, the patent ductus arteriosus closed spontaneously. Compared to the pre-operative period, 36/38 (95%) infants in the surgery group had one or more of the following rib abnormalities: ipsilateral fourth and fifth rib fusion, narrowing of the ipsilateral fifth intercostal space, thinning of the ipsilateral fourth or fifth rib, or a combination of the above on the chest radiograph compared to 0% in the control group (p < 0.001). Conclusion: Radiographic rib abnormalities are common and appear in infancy following surgical clipping of patent ductus arteriosus in preterm infants. Further studies are needed to clarify the natural history of these abnormalities on thoracic cage and cardiopulmonary functions.

Diagnostic yield of electromagnetic navigational bronchoscopy in a low volume center when performed by community pulmonologists.

INTRODUCTION: Electromagnetic navigational bronchoscopy (ENB) may be used for evaluation of pulmonary nodules. The purpose of this study was to determine the yield of ENB at a low volume center (0-4 cases per month), where the cases were performed by community pulmonologists neither trained in interventional pulmonology nor an expert in electromagnetic navigational bronchoscopy. The primary endpoint was to find the diagnostic yield of ENB at our center. A safety analysis was also performed to evaluate complications during the procedures. MATERIALS AND METHODS: A retrospective chart review of all the patients who had undergone ENB from January 2019 to January 2021 was performed. A total of 29 ENB procedures were performed during that time frame. Four ENB procedures were performed for fiducial placement and were not included in the study. RESULTS: Diagnosis was made in 72% of patients (18 cases out of 25 cases). With the exception of a single pneumothorax, no other complications were found. CONCLUSIONS: In conclusion our study shows that ENB, performed at low volume center by physicians not formally trained in interventional pulmonology or considered as experts in the procedure, has a high diagnostic yield and a good safety profile. This study shows that ENB may be performed by community pulmonologists at low volume center with a diagnostic yield comparable to high volume centers. This will be help improve access of ENB to more patients.

Proton Pump Inhibitors Versus Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients: A Meta-analysis and Trial Sequential Analysis.

GOALS AND BACKGROUND: Stress ulcer prophylaxis has been shown to lower gastrointestinal bleeding (GIB) rates. Various agents have been studied, and the optimal strategy continues to be contested. This study evaluates the efficacy between proton pump inhibitors (PPIs) and histamine-2-receptor antagonists. Small sample sizes and methodology flaws limited prior studies. STUDY: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science, and ClinicalTrials.gov for randomized controlled trials reporting the use of PPI and histamine-2-receptor antagonist reporting rates of GIB and standardized intensive care outcomes. Risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). A trial sequential analysis was performed to guard against errors. RESULTS: A total of 14 randomized controlled trials of 28,526 patients with a mean age of 57.83±17.35 years and 30.82% females. In our pooled analysis, PPI outperformed its comparator (RR: 0.68; 95% CI: 0.57-0.82) in clinically significant GIB. PPI re-demonstrated significant reduction in overt GIB (RR: 0.61; 95% CI: 0.39-0.97). No differences between groups was noted toward all-cause mortality (RR: 1.05; 95% CI: 1.00-1.10) or incidence of pneumonia (RR: 1.11; 95% CI: 0.82-1.51). Duration of stay (SMD: 0.07; 95% CI: -0.04-0.17) and ventilator days (SMD: 0.01; 95% CI: -0.01-0.04) were indifferent between the groups. CONCLUSIONS: Among critically ill patients, PPI was associated with reduced clinically significant or overt GIB. No differences in pneumonia were seen with the use of either agent. Trial sequential analysis for clinically significant GIB ruled out the risk for false-positive results, and thereby it is unlikely that future trials will affect our conclusions.

Artificial intelligence (AI) real-time detection vs. routine colonoscopy for colorectal neoplasia: a meta-analysis and trial sequential analysis.

GOALS AND BACKGROUND: Studies analyzing artificial intelligence (AI) in colonoscopies have reported improvements in detecting colorectal cancer (CRC) lesions, however its utility in the realworld remains limited. In this systematic review and meta-analysis, we evaluate the efficacy of AI-assisted colonoscopies against routine colonoscopy (RC). STUDY: We performed an extensive search of major databases (through January 2021) for randomized controlled trials (RCTs) reporting adenoma and polyp detection rates. Odds ratio (OR) and standardized mean differences (SMD) with 95% confidence intervals (CIs) were reported. Additionally, trial sequential analysis (TSA) was performed to guard against errors. RESULTS: Six RCTs were included (4996 participants). The mean age (SD) was 51.99 (4.43) years, and 49% were females. Detection rates favored AI over RC for adenomas (OR 1.77; 95% CI: 1.570-2.08) and polyps (OR 1.91; 95% CI: 1.68-2.16). Secondary outcomes including mean number of adenomas (SMD 0.23; 95% CI: 0.18-0.29) and polyps (SMD 0.23; 95% CI: 0.17-0.29) detected per procedure favored AI. However, RC outperformed AI in detecting pedunculated polyps. Withdrawal times (WTs) favored AI when biopsies were included, while WTs without biopsies, cecal intubation times, and bowel preparation adequacy were similar. CONCLUSIONS: Colonoscopies equipped with AI detection algorithms could significantly detect previously missed adenomas and polyps while retaining the ability to self-assess and improve periodically. More effective clearance of diminutive adenomas may allow lengthening in surveillance intervals, reducing the burden of surveillance colonoscopies, and increasing its accessibility to those at higher risk. TSA ruled out the risk for false-positive results and confirmed a sufficient sample size to detect the observed effect. Currently, these findings suggest that AI-assisted colonoscopy can serve as a useful proxy to address critical gaps in CRC identification.

The Two-bag System for Intravenous Fluid Management of Children with Diabetic Ketoacidosis: Experience from a Community-Based Hospital.

Objectives: Intravenous fluid (IVF) administration using the two-bag system compared with the one-bag system in children with diabetic ketoacidosis (DKA) admitted between January 1, 2015 and December 31, 2016. Design: Retrospective cohort study. Setting: Community-based hospital. Results: A total of 109 patients were enrolled with a mean age of 13.24 years. The 2 groups had comparable demographics. Initial laboratory results were similar except for initial PH and Sodium. The two bag system had significantly less number of calls compared to one bag system (25.2 vs 5.2 P = .0001). One bag system had fewer hypoglycemia <60 mg/dl (4 vs 12 P = .049). No statistically significant observations noted in regards to glucose drop rate, number of intravenous fluid bags used, amount of fluid boluses given, hospital stay and Pediatric ICU stay. Conclusions: The two-bag system has less resource utilization and slower blood glucose drop rate, but higher hypoglycemic events.

Management of stable coronary artery disease and atrial fibrillation with anti-thrombotic therapy: A systematic review and meta-analysis.

INTRODUCTION: Long term management of patients with stable coronary artery disease of >1 year after myocardial infarction (MI) or percutaneous coronary intervention and atrial fibrillation is unclear. Current guidelines recommend using oral anti-coagulation (OAC) alone although the recommendation is weak and there is low quality evidence. Two new randomized control trials (RCTs) were published recently. We conducted an updated meta-analysis to evaluate the effect of these studies on patient outcomes. OBJECTIVE: To conduct a systematic review and meta-analysis of published RCTs and observational studies to compare OAC alone versus OAC plus single anti-platelet therapy. METHODS: Electronic searches were conducted using appropriate terms from 3 databases. Relevant studies included. Data extracted and analysis were performed using STATA. MEASUREMENTS: Summary statistics were pooled and measured for primary and secondary outcomes of both treatment arms. MAIN RESULTS: Eight studies involving 10,120 patients were included for the analysis. Five thousand two hundred thirty-seven patients were on combination therapy while 4883 were on OAC alone. There was no statistically significant difference in the primary outcome of major adverse cardiac events (hazard ratio [HR] 1.067; 95% confidence interval [CI] 0.912-1.249; P value .417). There was no statistically significant difference even in the measured secondary outcomes namely all cause mortality (HR 1.048; 95% CI 0.830-1.323; P value .695), cardiovascular mortality (HR 0.863; 95% CI 0.593-1.254; P value .439). However, we found statistically significant difference between the 2 groups in the incidence of MI with higher incidence in mono therapy group (HR 1.229; 95% CI 1.011-1.495; P value .039) and higher incidence of major bleeding in the combination therapy group in the subgroup analysis (HR 0.649; 95% CI 0.464-0.907; P value .011). CONCLUSION: We found no reduction of major adverse cardiac event between combination therapy and mono therapy. Although mono therapy showed increased risk of major bleeding overall, subgroup analysis of the RCTs showed increased risk of major bleeding in the combination therapy group. MI was higher in the mono therapy group compared to the combination therapy group, however this outcome was not reproducible in the subgroup analysis of the RCTs.

Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES: To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS: We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS: Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. CONCLUSIONS: Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Comparison of Coronary Artery Bypass Grafting and Drug-Eluting Stents in Patients with Left Main Coronary Artery Disease and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of left main coronary artery disease (LMCAD) in patients with chronic kidney disease (CKD) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. Therefore, we performed a meta-analysis to evaluate the optimal choice of therapy when treating LMCAD in patients with CKD. METHOD: We performed an electronic database search of Pubmed, Embase, and Cochrane Library for all studies that compared PCI with CABG when treating LMCAD in the setting of CKD. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included myocardial infarction (MI), cerebrovascular events, all-cause mortality, and repeat revascularization. RESULTS: Our analysis included 5 studies (2 randomized controlled trial and 3 retrospective) representing a total of 1212 patients. Mean follow up was 3.4 ±â€¯1.3 years. Our study demonstrated a significant reduction in MACCE for patients treated with CABG compared with PCI (odd ratio [OR] 0.72; 95% confidence interval [CI] 0.55-0.95, P = 0.02, I2 = 0%). We also found a significant reduction in both MI (OR 0.55; 95% CI 0.34-0.87; P = 0.01; I2 = 0%) and repeat revascularization (OR 0.22; 95% CI 0.10-0.51; P < 0.001, I2 = 63%) in the CABG group. However, CABG was associated with increased risks of cerebrovascular disease events compared with PCI (OR 2.04; 95% CI 1.02-4.08; P = 0.04, I2 = 0%). CONCLUSION: In patients with CKD requiring LMCAD intervention, CABG is associated with a lower risk of MACCE, MI, and repeat revascularization, however it was associated with an increased risk of cerebrovascular accidents when compared to patients who received PCI therapy. Further RCTs with sufficient power are required to confirm these findings.

Isolated myxoid degeneration of aortic valve: diagnostic dilemma.

Myxoid degeneration of the aortic valve as a cause of acute aortic valve regurgitation in young age is uncommon. We report a 39-year-old African-American man with a history of epilepsy and hypertension who presented with a 1-month history of worsening shortness of breath. He was diagnosed with acute pulmonary oedema. Transoesophageal echocardiogram showed normal ejection fraction but severe aortic valve insufficiency with small masses on the ventricular side of the right and non-coronary cusps, small vegetations cannot be ruled out but other valves were normal. Subsequent cultures were negative for endocarditis. Myocardial positron emission tomography (PET) scan was strongly suggestive of cardiac sarcoidosis. However, this diagnosis was ruled out as well when he underwent aortic valve replacement with bioprosthetic valve as he did not want to take long-term anticoagulation. Histological examination of the aortic valve showed myxoid degeneration. The patient was doing very well 1 year after the surgery.

Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials.

Objective: We aimed to perform a meta-analysis evaluating the efficacy and safety of dupilumab in patients with uncontrolled asthma. Data source: A search of electronic databases was performed using PubMed, Cochrane library and Embase. Study selection: The literature search was conducted independently by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and dupilumab in patients with uncontrolled asthma were included in this analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous data, respectively. Results: A total of four RCTs representing 2,992 patients were included. Pooled analysis showed significant reductions of the annualized rate of severe asthma exacerbation in the dupilumab group compared with placebo (RR 0.44; 95% CI 0.35-0.055; P < 0.01; I2 = 42%). In addition, the absolute forced expiratory volume at 1 s (FEV1) changes were significantly increased for the dupilumab group (MD 0.14; 95% CI: 0.12-0.17; P < 0.01; I2 = 0%). Finally, there were no significant differences between both groups in the development of any adverse event, serious adverse events, adverse events leading to death, discontinuation of medication due to adverse event or the occurrence of upper respiratory tract, influenza or bronchitis infections. However, dupilumab was associated with an increased risk of injection site reactions compared with placebo (RR 1.91; 95% CI 1.41, 2.59; P < 0.01; I2 = 24%). Conclusion: Among patients with uncontrolled asthma, the addition of dupilumab was associated with a reduced risk of severe asthma exacerbations and improvement in FEV1 without an increased risk of adverse events apart from injection site reactions with dupilumab.

My tummy hurts - a case report of abdominal pain and macrocytic anemia caused by hypothyroidism.

A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity. LEARNING POINTS: Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.In pediatric population, treatment of hypothyroidism varies depending on patients' weight and age.Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.

Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis.

OBJECTIVES: Intravenous fluids are one of the most used medical therapy for patients, especially critically ill patients. We conducted a meta-analysis comparing between balanced crystalloids and normal saline in critically ill patients and its effect on various clinical outcomes. DESIGN: Meta-analysis and systematic review of randomized clinical trials (RCTs). METHODS AND DATA SOURCE: Electronic search was performed using PubMed, Cochrane library, and clinical trials.gov from inception through March 1, 2018, with inclusion of prospective studies that investigated one of the primary outcomes which were acute kidney injury (AKI) and in-hospital mortality while secondary outcomes were intensive care unit (ICU) mortality and new renal replacement therapy (RRT). RESULTS: Six RCTs were included. Total of 19,332 patients were included in the final analysis. There was no significant difference in in-hospital mortality (11.5% vs 12.2%; OR 0.92; 95% CI 0.85-1.01; P = 0.09; I2 = 0%), incidence of AKI (12% vs 12.7%, OR 0.92; 95% CI 0.84-1.01; P = 0.1; I2 = 0), overall ICU mortality (OR 0.9, 95% CI 0.81-1.01, P = 0.08, I2 = 0%), or need for new RRT (OR 0.92, 95% CI 0.67-1.28, P = 0.65, I2 = 38%) between balanced crystalloids and isotonic saline in critically ill patients. CONCLUSION: Balanced crystalloids and isotonic saline have no difference on various clinical outcomes including in-hospital mortality, AKI, overall ICU mortality, and new RRT. Further powerful clinical trials are required to determine the relationship between crystalloid fluid type and clinical outcomes.

Acute Appendicitis in Young Children: A Persistent Diagnostic Challenge for Clinicians.

Acute appendicitis is a grave and life-threatening condition in children, accounting for one to two cases per 10,000 in children less than four years' old. Prompt diagnosis and management are imperative to prevent serious complications, such as abscess formation, perforation, bowel obstruction, peritonitis, and sepsis. In young children, however, the diagnosis of this condition is challenging. The delayed utilization of imaging may further delay the diagnosis due to concerns of exposure to ionizing radiation. Even with a prompt diagnosis, controversy persists regarding medical versus operative management in these young patients. We report a case of a 21-month-old female who presented with fever, non-bilious, non-bloody emesis, and decreased tolerance for liquids and solids. The initial physical exam and imaging were suggestive of non-obstructive bowel distention. The patient was admitted to the pediatric floor. Overnight, the patient's condition deteriorated severely and became septic. Repeat imaging revealed a 9-cm appendicular mass and a ruptured appendix. Antibiotic coverage was then broadened and the patient was transferred to the critical care unit for more intensive management. The patient's septic condition improved over the upcoming few days and the parents elected to perform an elective appendectomy following resolution of the condition. Atypical presentations are common in this population. The difficulty in obtaining a reliable history and physical examination findings makes the diagnosis even more challenging. Moreover, concerns with radiation exposure may delay the diagnosis and increase the risk of perforation and peritonitis. Thus, clinicians should have a high index of suspicion for acute appendicitis, particularly in young children, as this condition is commonly missed on initial presentation.

How an Elevated Creatinine Level Can Deter the Diagnosis of Acute Aortic Dissection.

Acute aortic dissection (AAD) classically manifests with sudden, severe chest pain radiating to the back or abdomen, often described as ripping or tearing sensation. Considering its abrupt onset, the diagnosis requires a high index of suspicion prompting immediate imaging using computed tomography (CT) with contrast. However, the use of contrast is a relative contraindication in the patients with renal compromise and acute care physicians are often deterred from contrast use in these patients. Herein, we present an unusual case of hematuria as the presenting symptom of a developing the Stanford type-A AAD. A 65-year-old female presented with sudden, severe chest pain radiating to her lower back. She reported that her urine color was 'pink' on the previous day and was becoming more 'red-colored' as the day progressed. The next morning, she began feeling a 10/10 crushing-type chest pain that was relieved when she lay on her left side and was associated with nausea, vomiting, and diaphoresis. The urine analysis revealed gross hematuria. The laboratory findings revealed a creatinine of 1.3. Due to her elevated creatine levels and possible acute kidney injury, a computed tomography (CT) without contrast was performed initially, which did not reveal an AAD. However, the index of suspicion was still high for the AAD, after prompt discussions about the risk of using contrast and contrast nephropathy versus the risks of potential complications, if AAD was missed. Further evaluation with CT of the chest and abdomen, with contrast, was obtained with the patients' consent, which revealed a Stanford type-A AAD starting proximally from the aortic arch and extending to the common iliac. In conclusion, the clinical presentations of AAD are more heterogeneous. Hematuria in the presence of high index of suspicion and symptoms of AAD could indicate the extension of the involvement of the renal arteries. Prompt CT with contrast may be indicated despite relative contraindications from the laboratory findings.