Balanced crystalloids versus isotonic saline in pediatric sepsis: a comprehensive systematic review and meta-analysis.

Purpose: We conducted a comprehensive meta-analysis to compare the effects of balanced crystalloids (BC) and isotonic saline (IS) in pediatric sepsis. Methods: A systematic search was performed for studies comparing BC and IS in pediatric sepsis. Outcomes included mortality, acute kidney injury (AKI), need for renal replacement therapy (RRT), hospital length of stay (LOS), and pediatric intensive care unit (PICU) LOS. A random-effect models was used to calculated pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CIs). Results: The analysis included six studies with 8753 children. BC demonstrated significant reductions in overall mortality (OR 0.84, 95% CI 0.71 to 0.98, P = 0.03, I2 = 0%) and AKI (OR 0.74, 95% CI 0.57 to 0.96, P = 0.03, I2 = 37%) compared to IS. RRT need was similar between the BC and IS groups (OR 0.79, 95% CI 0.60 to 1.02, P = 0.07, I2 = 0%). Hospital and PICU LOS did not differ significantly. However, subgroup analysis of randomized controlled trials revealed significantly shorter hospital LOS in the BC group (mean difference -0.66 days, 95% CI -1.10 to -0.23, P = 0.003, I2 = 0%). Conclusion: Our meta-analysis demonstrates that using BC in pediatric sepsis is associated with reduced mortality, AKI, and hyperchloremia rates compared to IS, while maintaining similar hospital and PICU LOS. Large-scale randomized controlled trials are needed to validate these findings.

Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Atypical Gradenigo Syndrome in an Elderly Man Resolved with Mastoidectomy and Petrous Apicectomy.

Gradenigo syndrome (GS) was described primarily in the paediatric population, especially in the pre-antibiotic era. GS is rarely reported in the elderly population, especially in the post-antibiotic era. We present the rare case of a 67-year-old man who presented with an incomplete triad of symptoms (without abducens nerve palsy) of GS that failed medical therapy and was successfully treated with surgical intervention (mastoidectomy and petrous apicectomy). Physicians should be familiar with atypical presenting symptoms of GS as it can lead to life-threatening complications, especially in the elderly. GS cases resistant to medical therapy may require prompt appropriate imaging studies and surgical intervention. LEARNING POINTS: Gradenigo syndrome may present with an incomplete triad (without abducens nerve palsy), especially in the post-antibiotic era.Gradenigo syndrome can rarely affect immunocompromised elderly patients.Gradenigo syndrome cases resistant to medical therapy may require prompt appropriate imaging studies and surgical intervention (mastoidectomy and petrous apicectomy).

Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis.

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.

High-Flow Nasal Cannula Versus Noninvasive Ventilation in Patients With COVID-19.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen and noninvasive ventilation (NIV) have been widely used in patients with acute hypoxic respiratory failure (AHRF) due to COVID-19. However, the impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. Therefore, we performed this meta-analysis to evaluate the effect of HFNC versus NIV in COVID-19-related AHRF. METHODS: Several electronic databases were searched through February 10, 2022, for eligible studies comparing HFNC and NIV in COVID-19-related AHRF. Our primary outcome was intubation. The secondary outcomes were mortality, hospital length of stay (LOS), and PaO2 /FIO2 changes. Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% CI were obtained using a random-effect model. Prediction intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future. RESULTS: Nineteen studies involving 3,606 subjects (1,880 received HFNC and 1,726 received NIV) were included. There were no differences in intubation (RR 1.01 [95% CI 0.85-1.20], P = .89) or LOS (MD 0.38 d [95% CI -0.61 to 1.37], P = .45) between groups, with consistent results on the subgroup of randomized controlled trials (RCTs). Mortality was lower in NIV (RR 0.81 [95% CI 0.66-0.98], P = .03). However, the prediction interval was 0.41-1.59, and subgroup analysis of RCTs showed no difference in mortality between groups. There was a greater improvement in PaO2 /FIO2 with NIV (MD 22.80 [95% CI 5.30-40.31], P = .01). CONCLUSIONS: Our study showed that despite the greater improvement in PaO2 /FIO2 with NIV, intubation rates and LOS were similar between HFNC and NIV. Although mortality was lower with HFNC than NIV, the prediction interval included the null value, and there was no difference in mortality between HFNC and NIV on a subgroup of RCTs. Future large-scale RCTs are necessary to support our findings.

Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

BACKGROUND AND AIMS: Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19. METHODS: We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model. RESULTS: We identified 26 studies (10 randomized controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62-1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56-5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49-1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32-0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, -0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60-1.03, P = 0.08). CONCLUSIONS: Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.

Lung ultrasound-guided management to reduce hospitalization in chronic heart failure: a systematic review and meta-analysis.

Pulmonary edema is a leading cause of hospital admissions, morbidity, and mortality in heart failure (HF) patients. A point-of-care lung ultrasound (LUS) is a useful tool to detect subclinical pulmonary edema. We performed a comprehensive literature search of multiple databases for studies that evaluated the clinical utility of LUS-guided management versus standard care for HF patients in the outpatient setting. The primary outcome of interest was HF hospitalization. The secondary outcomes were all-cause mortality, urgent visits for HF worsening, acute kidney injury (AKI), and hypokalemia rates. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random-effect model meta-analysis. A total of 3 randomized controlled trials including 493 HF patients managed in the outpatient setting (251 managed with LUS plus physical examination (PE)-guided therapy vs. 242 managed with PE-guided therapy alone) were included in the final analysis. The mean follow-up period was 5 months. There was no significant difference in HF hospitalization rate between the two groups (RR 0.65; 95% CI 0.34-1.22; P = 0.18). Similarly, there was no significant difference in all-cause mortality (RR 1.39; 95% CI 0.68-2.82; P = 0.37), AKI (RR 1.27; 95% CI 0.60-2.69; P = 0.52), and hypokalemia (RR 0.72; 95% CI 0.21-2.44; P = 0.59). However, LUS-guided therapy was associated with a lower rate for urgent care visits (RR 0.32; 95% CI 0.18-0.59; P = 0.0002). Our study demonstrated that outpatient LUS-guided diuretic therapy of pulmonary congestion reduces urgent visits for worsening symptoms of HF. Further studies are needed to evaluate LUS utility in the outpatient treatment of HF.

Efficacy and Safety of Intravascular Lithotripsy in Calcified Coronary Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: Intravascular lithotripsy (IVL) is a recently introduced therapeutic modality in the management of calcified coronary lesions (CCAD). IVL delivers sonic pressure waves to modulate calcium, hence promote vessel compliance and optimize stent deployment. METHODS: We performed a comprehensive literature search for studies that evaluated the utility of adjunctive IVL. The primary outcomes of our study were the clinical success, defined as the ability of IVL to produce residual diameter stenosis <50% (RDS < 50%) after stenting with no evidence of in-hospital major adverse cardiac events, and the angiographic success, defined as success in facilitating stent delivery with RDS < 50% and without serious angiographic complications. The secondary outcomes included post-IVL and post-stenting changes in lumen area, calcium angle, and the maximum calcium thickness. Proportional analysis was used for binary data and mean difference was used for continuous data. All meta-analyses were conducted using a random-effect model and 95% confidence intervals (CIs) were included. RESULTS: A total of eight single-arm observational studies, including 980 patients (1011 lesions), were included. 48.8% of the patients presented with acute coronary syndrome. Severe calcifications were present in 97% of lesions. Clinical success was achieved in 95.4% of patients (95%CI:92.9%-97.9%). Angiographic success was achieved in 97% of patients (95%CI:95%-99%). There was an overall increase in postprocedural lumen area as well as significant reduction of calcium angle and maximum calcium thickness. CONCLUSIONS: IVL seems to have excellent efficacy and safety in the management of CCAD. However, adequately powered RCTs are needed to evaluate IVL compared to other calcium/plaque modifying techniques.

Efficacy of remote physiological monitoring-guided care for chronic heart failure: an updated meta-analysis.

Previous studies have reported contradictory findings on the utility of remote physiological monitoring (RPM)-guided management of patients with chronic heart failure (HF). Multiple databases were searched for studies that evaluated the clinical efficacy of RPM-guided management versus standard of care (SOC) for HF patients. The primary outcome was HF-related hospitalization (HFH). The secondary outcomes were all-cause mortality, cardiovascular-related (CV) mortality, and emergency department (ED) visits. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using a random-effects model. A total of 16 randomized controlled trials, including 8679 HF patients (4574 managed with RPM-guided therapy vs. 4105 managed with SOC), were included in the final analysis. The average follow-up period was 15.2 months. There was no significant difference in HFH rate between the two groups (RR: 0.94; 95% CI: 0.84-1.07; P = 0.36). Similarly, there were no significant differences in CV mortality (RR 0.86, 95% CI 0.73-1.02, P = 0.08) or in ED visits (RR 0.80, 95% CI 0.59-1.08, P = 0.14). However, RPM-guided therapy was associated with a borderline statistically significant reduction in all-cause mortality (RR: 0.88; 95% CI: 0.78-1.00; P = 0.05). Subgroup analysis based on the strategy of RPM showed that both hemodynamic and arrhythmia telemonitoring-guided management can reduce the risk of HFH (RR: 0.79; 95% CI: 0.64-0.97; P = 0.02) and (RR: 0.79; 95% CI: 0.67-0.94; P = 0.008) respectively. Our study demonstrated that RPM-guided diuretic therapy of HF patients did not reduce the risk of HFH but can improve survival. Hemodynamic and arrhythmia telemonitoring-guided management could reduce the risk of HF-related hospitalizations.

Effect of Prone Positioning on Clinical Outcomes of Non-Intubated Subjects With COVID-19.

BACKGROUND: Awake prone positioning (APP) has been recently proposed as an adjunctive treatment for non-intubated coronavirus disease 2019 (COVID-19) patients requiring oxygen therapy to improve oxygenation and reduce the risk of intubation. However, the magnitude of the effect of APP on clinical outcomes in these patients remains uncertain. We performed a comparative systematic review and meta-analysis to evaluate the effectiveness of APP to improve the clinical outcomes in non-intubated subjects with COVID-19. METHODS: The primary outcomes were the need for endotracheal intubation and mortality. The secondary outcome was hospital length of stay. Pooled risk ratio (RR) and mean difference with the corresponding 95% CI were obtained by the Mantel-Haenszel method within a random-effect model. RESULTS: A total of 14 studies (5 randomized controlled trials [RCTs] and 9 observational studies) involving 3,324 subjects (1,495 received APP and 1,829 did not) were included. There was a significant reduction in the mortality rate in APP group compared to control (RR 0.68 [95% CI 0.51-0.90]; P = .008, I2 = 52%) with no significant effect on intubation (RR 0.85 [95% CI 0.66-1.08]; P = .17, I2 = 63%) or hospital length of stay (mean difference -3.09 d [95% CI-10.14-3.96]; P = .39, I2 = 97%). Subgroup analysis of RCTs showed significant reduction in intubation rate (RR 0.83 [95% CI 0.72-0.97]; P = .02, I2 = 0%). CONCLUSIONS: APP has the potential to reduce the in-hospital mortality rate in COVID-19 subjects with hypoxemia without a significant effect on the need for intubation or length of hospital stay. However, there was a significant decrease in the need for intubation on subgroup analysis of RCTs. More large-scale trials with a standardized protocol for prone positioning are needed to better evaluate its effectiveness in this select population.

Hybrid convergent ablation versus endocardial catheter ablation for atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Endocardial catheter ablation (ECA) for atrial fibrillation (AF) has limited efficacy. Hybrid convergent procedure (HCP) with both epicardial and endocardial ablation is a novel strategy for AF treatment. In this meta-analysis, we aimed to evaluate the efficacy and safety of HCP in AF ablation. METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of HCP compared with ECA for AF. The primary outcome was freedom of atrial arrhythmia (AA). The secondary outcome was the periprocedural complication rate. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: A total of eight studies, including 797 AF patients (mean age: 60.7 ± 9.8 years, 366 patients with HCP vs. 431 patients with ECA alone), were included. HCP showed a higher rate of freedom of AA compared with ECA (RR: 1.48, 95% CI: 1.13-1.94, p = .004). However, HCP was associated with higher rates of periprocedural complications (RR: 3.64, 95% CI: 2.06-6.43; p = .00001). Moreover, the HCP had a longer procedure time and postprocedural hospital stay. CONCLUSIONS: Although hybrid ablation was associated with a higher success rate, this should be judged for increased periprocedural adverse events and extended hospital stay. Prospective large-scale randomized trials are needed to validate these results.