COVID-19 pandemic changed the way medical research is published, possibly forever. As the need for rapidity led to the rise of preprint servers, the undeniable drop in the overall quality of ...scientific publications requires an in-depth review of all available evidence. The present manuscript aims to identify and summarize all treatments which have been reported to reduce mortality in randomized trials in hospitalized COVID-19 patients.
Independent investigators searched MEDLINE/PubMed, Scopus, and Embase databases to identify all randomized trials of any intervention influencing mortality in hospitalized COVID-19 patients up to August 18
, 2022. Articles were selected only when they fulfilled all the following: randomized trial design; dealing with any kind of interventions in adult hospitalized COVID-19 patients; and statistically significant reduction in mortality.
We identified 28 interventions (42 manuscripts) reducing mortality in hospitalized COVID-19 patients. About 60% of the studies (26/42) were multicentric, for a total of 1140 centers involved worldwide. Several of these studies were published in high-ranked, peer-reviewed journals. Interventions with randomized evidence of mortality reduction in hospitalized COVID-19 patients belonged to 5 domains: corticosteroids, immunomodulators, antimicrobials, supportive therapies, and other drugs.
Many interventions have the potential to reduce mortality in COVID-19 hospitalized patients. The correct treatment of future pandemics relies on large, multicentric randomized clinical trials for further evaluation of these promising strategies.
Percutaneous dilation tracheostomy is an aerosol-generating procedure carrying a documented infectious risk during respiratory virus pandemics. For this reason, during the COVID-19 outbreak, surgical ...tracheostomy was preferred to the percutaneous one, despite the technique related complications increased risk.
We describe a new sequence for percutaneous dilation tracheostomy procedure that could be considered safe both for patients and healthcare personnel. A fiberscope was connected to a video unit to allow bronchoscopy. Guidewire positioning was performed as usual. While the established standard procedure continues with the creation of the stoma without any change in mechanical ventilation, we retracted the bronchoscope until immediately after the access valve in the mount tube, allowing normal ventilation. After 3 minutes of ventilation with 100% oxygen, mechanical ventilation was stopped without disconnecting the circuit. During apnea, the stoma was created by dilating the trachea and the tracheostomy cannula was inserted. Ventilation was then resumed. We evaluated the safeness of the procedure by recording any severe desaturation and by performing serological tests to all personnel.
Thirty-six patients (38%) of 96 underwent tracheostomy; 22 (23%) percutaneous dilation tracheostomies with the new approach were performed without any desaturation. All personnel (150 operators) were evaluated for serological testing: 9 (6%) had positive serology but none of them had participated in tracheostomy procedures.
This newly described percutaneous dilation tracheostomy technique was not related to severe desaturation events and we did not observe any positive serological test in health workers who performed the tracheostomies.
BACKGROUND: Glucocorticoids reduce mortality in hospitalized patients with severe and critical coronavirus disease 2019 (Covid-19), although a possible harm was documented in patients with Covid-19 ...not requiring oxygen. METHODS: We searched Embase, BioMed Central, medRxiv, bioRxiv, PubMed, and the Cochrane Central Register of Controlled Trials for any randomized trial or matched study ever performed on adult patients with Covid-19 not receiving oxygen therapy treated with intravenous or oral glucocorticoids versus any comparator (standard therapy or placebo); there were no restrictions on dose or time of administration. The primary end point was all-cause mortality at the longest available follow-up. RESULTS: Five randomized trials and one propensity-matched study involving 6634 hospitalized patients not on oxygen were finally included (3704 received glucocorticoids and 2930 received standard treatment). The overall mortality of patients treated with glucocorticoids was significantly higher than the mortality of patients in the control group (509 of 3704 14% in the glucocorticoid group vs. 294 of 2930 10% in the control group; odds ratio, 1.56 95% confidence interval, 1.27 to 1.92, with three articles reporting mortality events and contributing to the combined odds ratio; P<0.001; number needed to harm=27). CONCLUSIONS: Glucocorticoid use likely increases mortality in hospitalized patients with Covid-19 not receiving oxygen, with a number needed to harm of 27. (PROSPERO number CRD42022342996.)
Background
Male patients with COVID‐19 have been found with reduced serum total testosterone (tT) levels and with more severe clinical outcomes.
Objectives
To assess total testosterone (tT) levels ...and the probability of recovering eugonadal tT levels during a minimum 12‐month timespan in a cohort of men who have been followed over time after the recovery from laboratory‐confirmed COVID‐19.
Materials and methods
Demographic, clinical and hormonal values were collected for the overall cohort. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index was used to score health‐significant comorbidities. Descriptive statistics was used to compare hormonal levels at baseline versus 7‐month (FU1) versus 12‐month (FU2) follow‐up, respectively. Multivariate cox proportional hazards regression model was used to identify the potential predictors of eugonadism recovery over time among patients with hypogonadism at the time of infection.
Results
Of the original cohort of 286 patients, follow‐up data were available for 121 (42.3%) at FU1 and 63 (22%) patients at FU2, respectively. Higher median interquartile range (IQR) tT levels were detected at FU2 (13.8 (12.3–15.3) nmol/L) versus FU1 (10.2 9.3–10.9 nmol/L) and versus baseline (3.6 3.02–4.02 nmol/L) (all p < 0.0001), whilst both LH and E2 levels significantly decreased over the same time frame (all p ≤ 0.01). Circulating IL‐6 levels further decreased at FU2 compared to FU1 levels (19.3 vs. 72.8 pg/ml) (p = 0.02). At multivariable cox regression analyses, baseline tT level (HR 1.19; p = 0.03 1.02–1.4) was independently associated with the probability of tT level normalization over time, after adjusting for potential confounders.
Conclusions
Circulating tT levels keep increasing over time in men after COVID‐19. Still, almost 30% of men who recovered from COVID‐19 had low circulating T levels suggestive for a condition of hypogonadism at a minimum 12‐month follow‐up.
Objective Because at present no pharmacologic prevention or treatment of acute kidney injury seems to be available, the authors updated a meta-analysis to investigate the effects of fenoldopam in ...reducing acute kidney injury in patients undergoing cardiac surgery, focusing on randomized placebo-controlled studies only. Design A meta-analysis of randomized, placebo-controlled trials. Setting Hospitals. Participants A total of 440 patients from 6 studies were included in the analysis. Interventions None. The ability of fenoldopam to reduce acute kidney injury in the perioperative period when compared with placebo was investigated. Measurements and Main Results Google Scholar and PubMed were searched (updated January 1, 2012). Authors and external experts were contacted. Pooled estimates showed that fenoldopam consistently and significantly reduced the risk of acute kidney injury (odds ratio OR = 0.41; 95% confidence interval CI, 0.23-0.74; p = 0.003), with a higher rate of hypotensive episodes and/or use of vasopressors (30/109 27.5% v 21/112 18.8%; OR = 2.09; 95% CI, 0.98-4.47; p = 0.06) and no effect on renal replacement therapy, survival, and length of intensive care unit or hospital stay. Conclusions This analysis suggests that fenoldopam reduces acute kidney injury in patients undergoing cardiac surgery. Because the number of the enrolled patients was small and there was no effect on renal replacement therapy or survival, a large, multicenter, and appropriately powered trial is needed to confirm these promising results.
Purpose
Left atrial appendage (LAA) closure is an interventional procedure increasingly used to prevent stroke in patients with permanent atrial fibrillation and contraindications to anticoagulation ...therapy. As this procedure requires a relatively immobile patient and performance of continuous and prolonged transesophageal echocardiography (TEE), it is usually performed under general anesthesia. In this case series, we describe the feasibility of prolonged TEE for percutaneous LAA closure using a new noninvasive ventilation device that can avoid the need for endotracheal intubation and general anesthesia.
Clinical features
Percutaneous LAA closure was performed under deep sedation in three elderly patients with permanent atrial fibrillation. Sedation was obtained with a combination of midazolam, propofol, and remifentanil. Continuous intraoperative TEE was performed through the port of the newly available Janus mask (Biomedical Srl; Florence, Italy), allowing for noninvasive ventilation (pressure support = 12-16 cm H
2
O; positive end-expiratory pressure = 7 cm H
2
O; F
i
O
2
= 0.3) in these spontaneously breathing patients. The total procedure times ranged from 75-90 min. The patients reported excellent satisfaction with the sedation received in terms of discomfort experienced during the procedure, capacity to recall the procedure, and comfort with the mask. The operators also rated the procedural conditions as excellent.
Conclusion
Deep sedation with noninvasive ventilation may be a reasonable and safe alternative to general endotracheal anesthesia in patients requiring prolonged TEE for noninvasive cardiac procedures, including LAA closure.
Although meningococcal disease has a low incidence in Italy, it is a public health concern owing to its high lethality rate and high frequency of transitory and/or permanent sequelae among survivors. ...The highest incidence rates are recorded in infants, children and adolescents, and most of the cases are due to Neisseria meningitidis B. In Italy, anti-meningococcal B (anti-MenB) vaccination is free for infants but, despite the considerable disease burden in adolescents, no national recommendation to vaccinate in this age-group is currently available. The aim of this study was to assess the main available scientific evidence to support the Italian health authorities in implementing a program of free anti-MenB vaccination for adolescents. We conducted an overview of the scientific literature on epidemiology, disease burden, immunogenicity and safety of available vaccines, and economic evaluations of vaccination strategies. Each case of invasive meningococcal disease generates a considerable health burden (lethality rate: 9%; up to 60% of patients experience at least one sequela) in terms of impaired quality of life for survivors and high direct and indirect costs (the mean overall cost of acute phase for a single case amounts to about EUR 13,952; the costs for post-acute and the long-term phases may vary widely depending of the type of sequela, reaching an annual cost of about EUR 100,000 in cases of severe neurological damage). Furthermore, vaccination against meningococcus B in adolescence proved cost-effective. The study highlights the need to actively offer the anti-MenB vaccination during adolescence at a national level. This would make it possible to avoid premature deaths and reduce the high costs borne by the National Health Service and by society of supporting survivors who suffer temporary and/or permanent sequelae.
Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological ...cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal.
To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery.
Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twenty-three patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area.
Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10 ± 6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38 ± 9%. In VHD patients, fibrosis was also present in the lateral wall (9 ± 4%) and in the septum (9 ± 6%).
Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.
Objective The authors conducted a review of randomized controlled trials to identify advantages in clinically relevant outcomes in patients undergoing cardiac surgery with remifentanil. Design ...Meta-analysis. Setting Hospitals. Participants A total of 1,473 patients from 16 randomized trials. Interventions None. Measurements and Main Result PubMed, BioMedCentral, and conference proceedings were searched (updated May 2010) for randomized trials that compared remifentanil with fentanyl or sufentanil in cardiac anesthesia. Four independent reviewers performed data extraction, with divergences resolved by consensus. Overall analysis showed that the use of remifentanil was associated with a significant reduction in postoperative mechanical ventilation (WMD = −139 min −244, −32, p for effect = 0.01, p for heterogeneity < 0.001, I2 = 89%); length of hospital stay (WMD = −1.08 days −1.60, −0.57, p for effect < 0.0001, p for heterogeneity = 0.004, I2 = 71%); and cardiac troponin-I release (WMD = −2.08 ng/mL −3.93, −0.24, p for effect = 0.03, p for heterogeneity < 0.02, I2 = 74%). No difference was noted in mortality (3/344 0.87% in the remifentanil group vs 1.06% the control group, OR 0.76 0.17-3.38, p for effect = 0.72, p for heterogeneity = 0.35, I2 = 5%). Conclusions Remifentanil reduces cardiac troponin release, time of mechanical ventilation, and length of hospital stay in patients undergoing cardiac surgery.
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