Evaluation of quality and quantity of randomized controlled trials in hepatobiliary surgery: A scoping/mapping review.

AIM: To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. METHODS: A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. RESULTS: The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. CONCLUSION: The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.

Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). METHODS: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-ß expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. RESULTS: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. CONCLUSION: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).

Four-week experimental plus 1-week taper period using live high train low does not alter muscle glycogen content.

This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80-200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day-1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition.

Using training impulse and monotony methods to monitor aerobic training load in rats.

This study is the first to apply training impulse (TRIMP) and Training Monotony (TM) methodologies, within the realm of sport science, in animal model studies. Rats were divided into Sedentary (SED, n=10) and Training (TR, n=13). TR performed a four-week moderate-intensity interval training with load progression. Lactate kinetics, lactate training impulse (TRIMPLac), maximal speed training impulse (TRIMPSmax) and TM were utilized to develop and monitor training protocol. TR showed an 11.9% increase in time to exhaustion at the second maximum incremental test and a 17.5% increase at the third test. External work was increased by 17.8% at the second test and 30.3% at the third. There was a 10.6% increase in external work at the third test compared to the second for TR. No difference in TRIMPLac between the 1st week (94±9 A.U) and 3rdweek (83±10 A.U) were seen. TRIMPSmax was 2400 A.U. in the 1st week, 2760 A.U. in the 2nd and 3rd weeks, and 3120 A.U. in the 4th week. The TM remained at 1.24 A.U throughout the protocol and there was no dropouts. TRIMPLac and TRIMPSmax contributed to the development and monitoring loads, demonstrating their potential to improve the accuracy of training protocols in animal model research.

Volatile Organic Compounds from Offspring of Stingless Bee Sacrificed in Hygienic Behavior Test.

This study shows the profile of volatile organic compounds (VOCs) from pupae and larvae of Melipona quadrifasciata anthidioides Lepeletier subjected to three death induction techniques for hygienic behavior (HB) studies: freezing in liquid nitrogen (LN2), freezing in a freezer (FRZ) and piercing of offspring with an entomological pin (PIN). The VOCs from larvae and pupae were obtained through headspace solid-phase microextraction and characterized using gas chromatography coupled to mass spectrometry. In addition, an HB test was performed on the colonies. The main classes of VOCs were hydrocarbons, terpenes and alcohols. Multivariate analysis was applied and showed that there was a separation in the compound profiles between the different treatments. The HB test in the colonies showed that 24 hours after the application of the techniques, the bees removed more dead larvae in LN2 treatment (83.5 %), while after 48 hours more larvae were removed in the LN2 and FRZ treatments (92.3 %). When compared to pupae removal, larvae removal was significantly faster in LN2.

Implementation and Results of a Dedicated Telemedicine Program (TeleTrachea) for Patients with Tracheal Diseases.

Background: Central airway diseases requiring frequent outpatient visits to a specialized medical center due to tracheal devices. Many of these patients have mobility and cognition restrictions or require specialized transport due to the need for supplemental oxygen. This study describes the implementation and results of a telemedicine program dedicated to patients with central airway diseases based in a Brazilian public health system. Methods: A retrospective study of telemedicine consultation for patients with central airway diseases referred to a public academic hospital between August 1, 2020 and August 1, 2022. The consultations occurred in a telemedicine department using the hospital's proprietary platform. Data retrieved consisted of demographics, disease characteristics, and the treatment modalities of the patients. The analysis included the savings in kilometers not traveled, the carbon footprint based on reducing CO2 emissions, and the cost savings in transportation. Results: A total of 1,153 telemedicine visits conducted in 516 patients (median age of 31.5 years). Two hundred ninety patients (56.2%) had a tracheal device (129 silicone T-Tube, 128 tracheostomy, and 33 endoprosthesis) and 159 patients (30.8%) had difficulties in transportation to the specialized medical center. Patients were served from 147 Brazilian cities from 22 states. The savings in kilometers traveled was 1,224,108.54 km, corresponding to a 250.14 ton reduction in CO2 emissions. The costs savings in transportation for the municipalities was BRL$ 1,272,283.78. Conclusions: Telemedicine consultations for patients with central airway diseases are feasible and safe. Cost savings and the possibility of disseminating specialized care make telemedicine a fundamental tool in current medical practice.

Understanding seasonal variations in As and Pb river fluxes and their regulatory mechanisms through monitoring data.

The Doce River Basin (DRB) suffers with the adverse impacts of mining activities, due to its high level of urbanization and numerous industrial operations. In this study, we present novel insights into contaminant flow dynamics, seasonal variations, and the primary factors driving concentration levels within the region. We conducted an extensive analysis using a database sourced from the literature, which contained data on the contamination of arsenic (As) and lead (Pb) in the Doce River. Our primary aim was to investigate the patterns of As and Pb flow throughout the entire basin, their response to seasonal fluctuations, and the key parameters influencing their concentration levels. The results showed significant seasonal fluctuations in As and Pb fluxes, peaking during the rainy season. The 2015 Fundão dam breach in the DRB led to notable changes, elevating elemental concentrations, particularly As and Pb, which were subsequently transported to the Atlantic Ocean. These increased concentrations were primarily associated with iron and manganese oxides, hydroxides, and sulfates, rather than precipitation, as evidenced by regressions with low R2 values for both As (R2 = 0.07) and Pb (R2 < 0.001), concerning precipitation. The PCA analysis further supports the connection between these elements and the oxides and hydroxides of Fe and Mn. The approach employed in this study has proven to be highly effective in comprehending biogeochemical phenomena by leveraging data from the literature and could be a model for optimizing resources by capitalizing on existing information to provide valuable insights for drainage basin management, particularly during crises.

Is self-reported 7-day point prevalence abstinence an useful measure for smoking cessation effectiveness among individuals with mental disorders?

Smoking rates among individuals with mental disorders are higher compared to general population. We aimed to investigate the effectiveness of a smoking cessation treatment among individuals with and without mental disorders. Self-report 7-day point prevalence was used to assess abstinence status among 'intention to treat' (n = 1,213) and 'completers-only' (n = 578) samples. Participants were distributed in (1) ND-only; (2) ND and other substance use disorder (ND-SUD); (3) ND associated with mental disorder but no other SUD (ND-MD); and (4) co-morbid ND, SUD and MD (ND-SUMD). The treatment program was composed by six weeks of group Cognitive Behavioral Therapy (CBT) and medical consultations. Multivariate logistic regression models were applied. Rates of abstinence between ND-only and both ND-MD and ND-SUMD differed in the 'intention-to-treat' sample, with the former group showing the best rate (62.5%, 48% and 45.4% respectively). ND-SUD had the second-best rate of abstinence (56.1%). Differences between groups were not observed among 'completers-only'. Self-report 7-day point prevalence abstinence is economical and reliable to be used in low to middle-income countries. In this study, it showed that the 6-week smoking cessation treatment had a positive effect among completers, which supports the importance of investing in treatment to decrease smoking prevalence in this population.

Use of Inter-Effort Recovery Hypoxia as a New Approach to Improve Anaerobic Capacity and Time to Exhaustion.

Putti, Germano Marcolino, Gabriel Peinado Costa, Matheus Silva Norberto, Carlos Dellavechia de Carvalho, Rômulo Cássio de Moraes Bertuzzi, and Marcelo Papoti. Use of inter-effort recovery hypoxia as a new approach to improve anaerobic capacity and time to exhaustion. High Alt Med Biol. 25:68-76, 2024. Background: Although adding hypoxia to high-intensity training may offer some benefits, a significant problem of this training model is the diminished quality of the training session when performing efforts in hypoxia. The purpose of this study was to investigate the effects of training and tapering combined with inter-effort recovery hypoxia (IEH) on anaerobic capacity, as estimated by alternative maximum accumulated oxygen deficit (MAODALT) and time to exhaustion (TTE). Methods: Twenty-four amateur runners performed, for 5 weeks, 3 sessions per week of training consisted of ten 1-minute bouts at 120% (weeks 1-3) and 130% (weeks 4 and 5) of maximum velocity (VMAX) obtained in graded exercise test, separated by a 2-minute interval in IEH (IEH, n = 11, FIO2 = 0.136) or normoxia (NOR, n = 13, fraction of inspired oxygen = 0.209). Before training, after training, and after 1 week of tapering, a graded exercise test and a maximal effort to exhaustion at 120% of VMAX were performed to determine TTE and MAODALT. The results were analyzed using generalized linear mixed models, and a clinical analysis was also realized by the smallest worthwhile change. Results: MAODALT increased only in IEH after training (0.8 ± 0.5 eq.lO2) and tapering (0.8 ± 0.5 eq.lO2), with time x group interaction. TTE increased for the pooled groups after taper (23 ± 11 seconds) and only for IEH alone (29 ± 16 seconds). Clinical analysis revealed a small size increase for NOR and a moderate size increase for IEH. Conclusions: Although the effects should be investigated in other populations, it can be concluded that IEH is a promising model for improving anaerobic performance and capacity. World Health Organization Universal Trial Number: U1111-1295-9954. University's ethics committee registration number: CAAE: 32220020.0.0000.5659.

Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study.

Background: Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. Methods: This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Results: Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Conclusion: Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

Identification and characterization of plastic debris in the gastrointestinal tract of Guiana dolphins (Sotalia guianensis) from Espírito Santo coast, Brazil.

The Guiana dolphin (Sotalia guianensis) is categorized as vulnerable in the Brazilian list of endangered animals, and its populations suffer from several anthropological threats. In this study, we analyzed the presence of macro, meso, and microplastics (MPs) in Guiana dolphins (n = 12) in Brazil Southeastern coast by analysing their gastrointestinal tract. The MP extractions were carried out with H2O2 (35 %) to remove organic matter. Four specimens ingested meso and macroplastics, including an item of polypropylene of 19.22 cm that was produced about 943 km from the place in which the animal was found stranded. All the specimens analyzed had fragment-type microplastics in their intestines. Blue was the prevailing color, followed by black, green, and red. We highlight the contamination by microplastics in the species, still little investigated, especially the need to understand the contamination by microplastics along trophic levels.

Promising Results of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Perihilar Cholangiocarcinoma in a Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

Analysing chemical composition and antimicrobial activity of geopropolis from Melipona scutellaris: HPLC-DAD and in vitro/in silico investigations.

This study evaluated the chemical profile, antimicrobial activity, and the presence of potentially toxic elements in geopropolis extracts produced by Melipona scutellaris in the Recôncavo region of Bahia, Brazil. It was found that the major chemical compounds belong to the class of phenolic compounds, with emphasis on the presence of gallic acid. In this study, no potentially toxic elements were found in the analysed geopropolis. Regarding the antimicrobial potential, gram-positive bacteria were susceptible to the action of geopropolis extract at concentrations of 0.25 to 2.5 mg.mL-1, highlighting its microbiological activity against Streptococcus mitis (ATCC 00456) and Candida albicans (CCMB 251). Thus, this geopropolis extract can be used as a bacteriostatic rather than a bactericide. Our results suggest the potential for the economic and therapeutic use of M. scutellaris geopropolis, adding value to one of the meliponiculture products.

Differences of ventilatory muscle recruitment and work of breathing in COPD and interstitial lung disease during exercise: a comprehensive evaluation.

Introduction: COPD and interstitial lung disease (ILD) are significant chronic respiratory disorders, impacting quality of life. Respiratory muscle roles and differences remain not entirely clear. The objective of the present study was to evaluate the degree of recruitment of the respiratory muscles and the work of breathing in COPD and ILD during exercise. Methods: We compared the sensory-mechanical relationships in COPD, ILD and healthy controls (n=20 each). They performed pulmonary function, noninvasive and invasive respiratory muscle strength, surface electromyography and work-of-breathing assessments. Results: COPD and ILD did not show lower static muscle strength compared to controls, but did show poor performance in the exercise test with increased transdiaphragmatic pressure (P di). In ILD, there was a higher increase in oesophageal pressure and a lower gastric pressure (P ga) on inspiration; in COPD, there was a significant increase in P ga on inspiration. In ILD, there is greater recruitment of accessory inspiratory muscles, whereas in COPD, there is marked use of both inspiratory and expiratory muscles. The neuromechanical inefficiency (increased neural respiratory drive without the corresponding tidal volume) was found in both diseases. In COPD, there is a considerable increase in elastic work to overcome intrinsic positive end-expiratory pressure (PEEPi) and expiratory work of breathing, whereas in ILD, non-PEEPi elastic work of breathing is the highest part of the total work of breathing. Conclusions: Early and increased activity of the respiratory muscles and work-of-breathing components significantly contribute to dyspnoea, exercise intolerance and neuromechanical inefficiency of ventilation in COPD and ILD. The mechanisms of P di generation were different between diseases.

Chitosan-based nanocomposite films with carnauba wax, rosin resin, and zinc oxide nanoparticles.

This work aimed to develop edible emulsion-based barriers in the form of chitosan composite films, with a focus on assessing the impacts of carnauba wax, rosin resin, and zinc oxide nanoparticles on their properties. Six films were produced by casting using chitosan as polymer base and glycerol as plasticizer. Acetic acid and polysorbate 80 were also used to facilitate the dissolution and mixing of the components. The six filmogenic solutions contained chitosan at 1.2% w/v, wax or resin content with 0 or 0.6% m/v and ZnO with 0 or 0.05% m/v. The dried films were characterized according to their chemical, barrier, mechanical, thermal and optical properties. All treatments resulted in flexible films. Chitosan films appeared smoother and more uniform under SEM imaging, while carnauba wax films displayed roughness due to their hydrophobic nature. Wax and resin films were less transparent and water soluble than the chitosan-only films. On the other hand, the addition of ZnO in the formulations increased the solubility of the films. The sorption degree was in line with the solubility results, i.e., films with ZnO presented higher sorption degree and solubility values. All treatments showed low or non-light UV transmission, indicating that the films provide good barrier to UV light. In the visible light region, films of resin with ZnO showed the lowest transmittance values, hence offering a good barrier to visible light. Among the evaluated films, chitosan, and resin films with ZnO nanoparticles were more rigid and resistant to deformation. Overall, films produced with rosin resin and ZnO nanoparticles showed potential improvements in barrier, mechanical, thermal, and optical properties, mainly due to their low water solubility, good UV protection and low permeability to water vapor and oxygen, which are suitable for using in formulations, intended to produce edible films and coatings.

Effects of acute consumption of a beverage based on extruded whole-grain pearl millet flour on glycemic and insulinemic control, food intake, and appetite sensation in eutrophic adults: A randomized cross-over clinical trial.

OBJECTIVES: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults. METHODS: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session. RESULTS: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage. CONCLUSIONS: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects.

Chemical composition and in vitro iron bioavailability of extruded and open-pan cooked germinated and ungerminated pearl whole millet "Pennisetum glaucum (L.) R. Br."

This study aimed to evaluate the effect of extrusion and of open-pan cooking on whole germinated and non-germinated grains of pearl millet (Pennisetum glaucum L. R. Br.), on its chemical-nutritional composition and in vitro iron bioavailability. The experimental design consisted of three flours: non-germination open-pan cooked millet flour (NGOPCMF), germination open-pan cooked millet flour (GOPCMF), and extrusion cooked millet flour (ECMF). The ECMF increased the carbohydrates, iron, manganese, diosmin, and cyanidin and decreased the total dietary fiber, resistant starch, lipids, and total vitamin E, in relation to NGOPCMF. The GOPCMF increased the lysine and vitamin C and decreased the phytate, lipids, total phenolic, total vitamin E, and riboflavin concentration, in relation to NGOPCMF. Furthermore, germinated cooked millet flour and extruded millet flour improved iron availability in vitro compared to non-germinated cooked millet flour. GOPCMF and ECMF generally preserved the chemical-nutritional composition of pearl millet and improved in vitro iron bioavailability; therefore, they are nutritionally equivalent and can be used to develop pearl millet-based products.

Temporal trends of severity and outcomes of critically ill patients with COVID-19 after the emergence of variants of concern: A comparison of two waves.

BACKGROUND: The emergence of SARS-CoV-2 variants led to subsequent waves of COVID-19 worldwide. In many countries, the second wave of COVID-19 was marked by record deaths, raising the concern that variants associated with that wave might be more deadly. Our aim was to compare outcomes of critically-ill patients of the first two waves of COVID-19. METHODS: This retrospective cohort included critically-ill patients admitted between March-June 2020 and April-July 2021 in the largest academic hospital in Brazil, which has free-access universal health care system. We compared admission characteristics and hospital outcomes. The main outcome was 60-day survival and we built multivariable Cox model based on a conceptual causal diagram in the format of directed acyclic graph (DAG). RESULTS: We included 1583 patients (1315 in the first and 268 in the second wave). Patients in the second wave were younger, had lower severity scores, used prone and non-invasive ventilatory support more often, and fewer patients required mechanical ventilation (70% vs 80%, p<0.001), vasopressors (60 vs 74%, p<0.001), and dialysis (22% vs 37%, p<0.001). Survival was higher in the second wave (HR 0.61, 95%CI 0.50-0.76). In the multivariable model, admission during the second wave, adjusted for age, SAPS3 and vaccination, was not associated with survival (aHR 0.85, 95%CI 0.65-1.12). CONCLUSIONS: In this cohort study, patients with COVID-19 admitted to the ICU in the second wave were younger and had better prognostic scores. Adjusted survival was similar in the two waves, contrasting with record number of hospitalizations, daily deaths and health system collapse seen across the country in the second wave. Our findings suggest that the combination of the burden of severe cases and factors such as resource allocation and health disparities may have had an impact in the excess mortality found in many countries in the second wave.

Impact of extended lung protection during mechanical ventilation on lung recovery in patients with COVID-19 ARDS: a phase II randomized controlled trial.

BACKGROUND: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. METHODS: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. RESULTS: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. CONCLUSIONS: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

A comprehensive physical functional assessment of survivors of critical care unit stay due to COVID-19.

OBJECTIVE: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. METHODS: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). RESULTS: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. CONCLUSION: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.