Effect of the alveolar recruitment maneuver during laparoscopic colorectal surgery on postoperative pulmonary complications: A randomized controlled trial.

Intraoperative lung-protective ventilation, including low tidal volume and positive end-expiratory pressure, reduces postoperative pulmonary complications. However, the effect and specific alveolar recruitment maneuver method are controversial. We investigated whether the intraoperative intermittent recruitment maneuver further reduced postoperative pulmonary complications while using a lung-protective ventilation strategy. Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to the recruitment or control groups. Intraoperative ventilation was adjusted to maintain a tidal volume of 6-8 mL kg-1 and positive end-expiratory pressure of 5 cmH2O in both groups. The alveolar recruitment maneuver was applied at three time points (at the start and end of the pneumoperitoneum, and immediately before extubation) by maintaining a continuous pressure of 30 cmH2O for 30 s in the recruitment group. Clinical and radiological evidence of postoperative pulmonary complications was investigated within 7 days postoperatively. A total of 125 patients were included in the analysis. The overall incidence of postoperative pulmonary complications was not significantly different between the recruitment and control groups (28.1% vs. 31.1%, P = 0.711), while the mean ±â€…standard deviation intraoperative peak inspiratory pressure was significantly lower in the recruitment group (10.7 ±â€…3.2 vs. 13.5 ±â€…3.0 cmH2O at the time of CO2 gas-out, P < 0.001; 9.8 ±â€…2.3 vs. 12.5 ±â€…3.0 cmH2O at the time of recovery, P < 0.001). The alveolar recruitment maneuver with a pressure of 30 cmH2O for 30 s did not further reduce postoperative pulmonary complications when a low tidal volume and 5 cmH2O positive end-expiratory pressure were applied to patients undergoing laparoscopic colorectal surgery and was not associated with any significant adverse events. However, the alveolar recruitment maneuver significantly reduced intraoperative peak inspiratory pressure. Further study is needed to validate the beneficial effect of the alveolar recruitment maneuver in patients at increased risk of postoperative pulmonary complications. Trial registration: Clinicaltrials.gov (NCT03681236).

Intraoperative lung protection: strategies and their impact on outcomes.

PURPOSE OF REVIEW: The present review summarizes the current knowledge and the barriers encountered when implementing tailoring lung-protective ventilation strategies to individual patients based on advanced monitoring systems. RECENT FINDINGS: Lung-protective ventilation has become a pivotal component of perioperative care, aiming to enhance patient outcomes and reduce the incidence of postoperative pulmonary complications (PPCs). High-quality research has established the benefits of strategies such as low tidal volume ventilation and low driving pressures. Debate is still ongoing on the most suitable levels of positive end-expiratory pressure (PEEP) and the role of recruitment maneuvers. Adapting PEEP according to patient-specific factors offers potential benefits in maintaining ventilation distribution uniformity, especially in challenging scenarios like pneumoperitoneum and steep Trendelenburg positions. Advanced monitoring systems, which continuously assess patient responses and enable the fine-tuning of ventilation parameters, offer real-time data analytics to predict and prevent impending lung complications. However, their impact on postoperative outcomes, particularly PPCs, is an ongoing area of research. SUMMARY: Refining protective lung ventilation is crucial to provide patients with the best possible care during surgery, reduce the incidence of PPCs, and improve their overall surgical journey.

Protective effects of inhaled antioxidants against air pollution-induced pathological responses.

As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease.

An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol.

BACKGROUND: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. METHODS: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. DISCUSSION: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. TRIAL REGISTRATION: ClinicalTrial.gov NCT04108130.

Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Spine Surgery Patients' Perceptions of Postoperative Pulmonary Complications.

Postoperative pulmonary complications (PPCs) are associated with poor patient outcomes, increased costs and prolonged hospitalizations. Incentive spirometry (IS) reduces PPC incidence, but patient IS adherence is often suboptimal. Thus, the purpose of this study was to explore patients' beliefs about, and knowledge of PPCs and IS. We observed IS technique and conducted interviews guided by qualitative descriptive methodologies and the Health Belief Model. Verbatim transcripts of interviews were analyzed using inductive and deductive content analytic methods. Twenty postoperative spinal surgery patients at a single tertiary hospital were enrolled. Five categories related to PPC and IS beliefs and knowledge were identified: (1) social support, (2) preventing a PPC, (3) learning about PPCs, (4) reminders, and (5) lack of IS knowledge. Understanding why patients do not adhere to IS protocols is crucial for minimizing the risk of iatrogenic PPCs and developing strategies to improve adherence to IS.

Analgesic Effectiveness of Dinalbuphine Sebacate in Video-Assisted Thoracoscopic Wedge Resection and Its Effect on Reducing Postoperative Pulmonary Complications: A Retrospective Cohort Study.

BACKGROUND: Inadequate postoperative analgesia may cause postoperative complications, such as pulmonary complications. This study evaluated the analgesic effectiveness of a single preoperative injection of dinalbuphine sebacate (DS) in patients undergoing video-assisted thoracoscopic wedge resection and assessed whether it can reduce the incidence of postoperative pulmonary complications (PPCs). METHODS: In this study, the data of 757 patients who underwent VATS wedge resection at a medical center were retrospectively reviewed. The patients were divided into the DS group and the conventional analgesia (CA) group. The following parameters were analyzed: analgesic consumption during hospitalization, the incidence of PPCs, and the postoperative use of oxygen therapy. RESULTS: Compared with the CA group, the DS group had lower nalbuphine, tramadol, parecoxib, acetaminophen, diclofenac, and utraphen consumption during the postoperative period; higher morphine and ketorolac consumption; and comparable fentanyl consumption. Nonetheless, the frequency of requesting pain relief was significantly lower in the DS group. No significant between-group differences were noted in the incidence of PPCs. However, the DS group had fewer requirements for oxygen therapy in the ward, early removal of chest tubes, and shorter length of hospital stay. CONCLUSION: A single preoperative injection of DS reduced the frequency of salvage analgesic administration and total consumption of certain postoperative analgesics, suggesting the effective pain relief of DS, and it did not increase the incidence of PPCs. Additionally, it reduced the need for postoperative oxygen therapy, which may suggest a better prognosis and smoother postoperative pulmonary recovery for patients.

AZTEC-azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes.

BACKGROUND: The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described. METHODS AND DESIGN: A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks' gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks' postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks' PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up. RESULTS: Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect. CONCLUSION: We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment. TRIAL REGISTRATION: ISRCTN registry ISRCTN11650227. Registered on 31 July 2018.

Effects of Driving Pressure-Guided Ventilation on Postoperative Pulmonary Complications in Prone-Positioned Patients Undergoing Spinal Surgery: A Randomized Controlled Clinical Trial.

BACKGROUND: Prolonged spinal surgery in the prone position may lead to postoperative pulmonary complications (PPCs). We aimed to compare the effects of driving pressure-guided ventilation versus conventional protective ventilation on postoperative pulmonary complications in patients undergoing spinal surgery in the prone position. We hypothesized that driving pressure-guided ventilation would be associated with a decreased incidence of PPC. METHODS: We enrolled 78 patients into this single-center, double-blind, randomized controlled trial. The driving pressure (DP) group (n = 40) received a tidal volume of 6 ml/kg of predicted body weight, individualized positive end-expiratory pressure (PEEP) which produced the lowest driving pressure (plateau pressure-PEEP), and a recruitment maneuver. The protective ventilation (PV) group (n = 38) received the same tidal volume and recruitment maneuver but with a fixed PEEP of 5 cm H2O. Our primary outcome was postoperative pulmonary complications based on Lung Ultrasound Scores (LUS) at the end of the surgery and the simplified Clinical Pulmonary Infection Score (sCPIS) on postoperative days (POD) 1 and 3. RESULTS: DP patients had lower LUS and POD1 sCPIS than the PV group (p < 0.01). DP patients had lower driving pressure during the surgery than PV patients (p < 0.01). Perioperative arterial blood gases and hemodynamic parameters were comparable between the two groups (p > 0.05). The visual pain score (VAS) in postoperative days, drainage, and lengths of stay (LOS) were also similar between the two groups (p > 0.05). CONCLUSIONS: Driving pressure-guided ventilation during spinal surgery with a prolonged prone patient position may reduce the incidence of early postoperative pulmonary complications, compared with conventional protective ventilation.

Biopsy-tract haemocoagulase injection reduces major complications after CT-guided percutaneous transthoracic lung biopsy.

AIM: To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB). MATERIALS AND METHODS: A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications. RESULTS: A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results. CONCLUSION: Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB.

The National Heart Lung and Blood Institute Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Alliance.

OBJECTIVE: To describe the National Heart Lung and Blood Institute (NHLBI) sponsored Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease (DECIPHeR) Alliance to support late-stage implementation research aimed at reducing disparities in communities with high burdens of cardiovascular and/or pulmonary disease. STUDY SETTING: NHBLI funded seven DECIPHeR studies and a Coordinating Center. Projects target high-risk diverse populations including racial and ethnic minorities, urban, rural, and low-income communities, disadvantaged children, and persons with serious mental illness. Two projects address multiple cardiovascular risk factors, three focus on hypertension, one on tobacco use, and one on pediatric asthma. STUDY DESIGN: The initial phase supports planning activities for sustainable uptake of evidence-based interventions in targeted communities. The second phase tests late-stage evidence-based implementation strategies. DATA COLLECTION/EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: We provide an overview of the DECIPHeR Alliance and individual study designs, populations, and settings, implementation strategies, interventions, and outcomes. We describe the Alliance's organizational structure, designed to promote cross-center partnership and collaboration. CONCLUSIONS: The DECIPHeR Alliance represents an ambitious national effort to develop sustainable implementation of interventions to achieve cardiovascular and pulmonary health equity.

Grape Phytochemicals and Vitamin D in the Alleviation of Lung Disorders.

BACKGROUND: Typical lung diseases are pneumonia, asthma, sleep apnea syndrome (SA), interstitial pneumonia (IP), lung cancer, and chronic obstructive pulmonary disease (COPD). Coronavirus disease 2019 (COVID-19) is a type of viral pneumonia. Many researchers have reported that phytochemicals (chemical compounds produced by plants) and vitamin D are useful in stimulating our immunity. This review discusses the alleviation of lung diseases by grape phytochemicals and vitamin D. DISCUSSION: Pneumonia is an acute inflammation caused by the infection of pathogens; the worst case is a fatal cytokine storm in the lung. In asthma, allergens, tobacco smoke, or air pollution may cause seizures. Lung diseases caused by lung fibrosis may manifest chronic inflammation, progress into alveolar fibrosis, and cause respiratory malfunction. SA is a lifestyle disease related to obesity and metabolic syndrome. To alleviate these symptoms, changing the eating habit is one of the strategies. Improvement in the daily lifestyle reduces the risk of lung cancer. Self-management, including nutritional management and exercise, is very important for COPD patients in addition to pharmacotherapy. CONCLUSION: The intake of grape phytochemicals and vitamin D prevents the progress of lung diseases. Both phytochemicals and vitamin D prevent the production of proinflammatory cytokine, TNF-α, that is responsible for inflammation and lung diseases. Daily intake of grape phytochemicals is important. The optimum vitamin D level in serum is > 30 ng/mL. For the prevention of lung diseases, upregulating immunity and maintaining good gut microbiota are important because gut microbiota change depending on what we eat.

Protective role of crocin against sepsis-induced injury in the liver, kidney and lungs via inhibition of p38 MAPK/NF-κB and Bax/Bcl-2 signalling pathways.

CONTEXT: Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown. OBJECTIVE: We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action. MATERIALS AND METHODS: Five experimental groups (n = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated. RESULTS: Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1ß, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation. DISCUSSION AND CONCLUSIONS: Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.

Perinatal Outcomes after Fetal Endoscopic Tracheal Occlusion for Isolated Congenital Diaphragmatic Hernia: Rapid Review / Resultados perinatais após oclusão traqueal endoscópica fetal por hérnia diafragmática congênita isolada: Revisão rápida

Abstract Objective To compare the perinatal outcomes of fetuses with isolated congenital diaphragmatic hernia after fetal endoscopic tracheal occlusion (FETO) and antenatal expectant management. Data sources In this rapid review, searches were conducted in the MEDLINE, PMC, EMBASE and CENTRAL databases between August 10th and September 4th, 2020. Randomized controlled trials (RCTs), quasi-RCTs or cluster-RCTs published in English in the past ten years were included. Study selection We retrieved 203 publications; 180 studies were screened by abstract. Full-text selection was performed for eight studies, and 1 single center RCTmet the inclusion criteria (41 randomized women; 20 in the FETO group, and 21 in the control group). Data collection Data collection was performed independently, by both authors, in two steps (title and abstract and full-text reading). Data synthesis There were no cases of maternal mortality. The mean gestational age at delivery was of 35.6±2.4 weeks in the intervention group, and of 37.4±1.9 weeks among the controls (p<0.01). Survival until 6 months of age was reported in 50% of the intervention group, and in 5.8% of the controls (p<0.01; relative risk: 10.5; 95% confidence interval [95%CI]: 1.5-74.7). Severe postnatal pulmonary hypertension was found in 50% of the infants in the intervention group, and in 85.7% of controls (p=0.02; relative risk: 0.6; 95%CI: 0.4-0.9). An analysis of the study indicated some concerns of risk of bias. The quality of evidence was considered moderate to low. Conclusion Current evidence is limited but suggests that FETO may be an effective intervention to improve perinatal outcomes.

Resumo Objetivo Comparar os resultados perinatais de fetos com hérnia diafragmática congênita após oclusão traqueal endoscópica fetal (OTEF) e conduta expectante pré-natal. Fontes dos dados Nesta revisão rápida, pesquisas foram conduzidas nas bases de dados MEDLINE, PMC, EMBASE e CENTRAL entre 10 de agosto de 2020 e 4 de setembro de 2020. Ensaios clínicos randomizados (ECRs), quase-ECRs e ECRs em cluster publicados em inglês nos últimos dez anos foram incluídos. Seleção dos estudos Foram recuperadas 203 publicações; 180 destas foram triadas pelo resumo. Fez-se a leitura do texto completo de 8 estudos, e 1 ECR cumpriu os critérios de inclusão (41 mulheres aleatorizadas; 20 no grupo OTEF e 21 no grupo de controle). Coleta de dados A coleta de dados realizada independentemente pelos dois autores, em duas etapas (título e resumo, e leitura do texto completo). Síntese dos dados Não houve casos de mortematerna. A idade gestacionalmédia no parto foi de 35,6±2,4 semanas no grupo de intervenção, e de 37,4±1,9 semanas entre os controles (p<0,01). A sobrevida até 6 meses de idade foi relatada em 50% do grupo de intervenção, e em 5,8% dos controles (p<0,01; risco relativo: 10,5; intervalo de confiança de 95% [IC95%]: 1,5-74,7). Hipertensão pulmonar grave ocorreu em 50% dos lactentes do grupo de intervenção, e em 85,7% dos controles (p = 0.02; risco relativo: 0,6; IC95%: 0,4-0,9). Uma análise do estudo indicou algumas preocupações quanto ao risco de viés. A qualidade da evidência foi considerada de moderada a baixa. Conclusão As evidências atuais são limitadas,mas sugeremque a OTEF pode ser uma intervenção eficaz para melhorar resultados perinatais.

Amelioration of cyclophosphamide toxicity via modulation of metabolizing enzymes by avocado (Persea americana) extract.

OBJECTIVES: Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity. METHODS: Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity. KEY FINDINGS: CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats. CONCLUSIONS: AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity.

Outer Membrane Vesicles Displaying a Heterologous PcrV-HitA Fusion Antigen Promote Protection against Pulmonary Pseudomonas aeruginosa Infection.

Along with surging threats and antibiotic resistance of Pseudomonas aeruginosa in health care settings, it is imperative to develop effective vaccines against P. aeruginosa infection. In this study, we used an Asd (aspartate-semialdehyde dehydrogenase)-based balanced-lethal host-vector system of a recombinant Yersinia pseudotuberculosis mutant to produce self-adjuvanting outer membrane vesicles (OMVs). The OMVs were used as a carrier to deliver the heterologous PcrV-HitAT (PH) fusion antigen of P. aeruginosa for vaccine evaluation. Intramuscular vaccination with OMVs carrying the PH antigen (referred to rOMV-PH) afforded 73% protection against intranasal challenge with 5 × 106 (25 50% lethal doses) of the cytotoxic PA103 strain and complete protection against a noncytotoxic PAO1 strain. In contrast, vaccination with the PH-deficient OMVs or PH antigen alone failed to offer effective protection against the same challenge. Immune analysis showed that the rOMV-PH vaccination induced potent humoral and Th1/Th17 responses compared to the PH vaccination. The rOMV-PH vaccination rapidly cleared P. aeruginosa burdens with coordinated production of proinflammatory cytokines in mice. Moreover, antigen-specific CD4+ and CD8+ T cells and their producing cytokines (tumor necrosis factor alpha and interleukin-17A), rather than antibodies, were essential for protection against pneumonic P. aeruginosa infection. Our studies demonstrated that the recombinant Y. pseudotuberculosis OMVs delivering heterologous P. aeruginosa antigens could be a new promising vaccine candidate for preventing the spread of drug-resistant P. aeruginosa. IMPORTANCE Hospital- and community-acquired infections with Pseudomonas aeruginosa cause a high rate of morbidity and mortality in patients who have underlying medical conditions. The spread of multidrug-resistant P. aeruginosa strains is becoming a great challenge for treatment using antibiotics. Thus, a vaccine as one of the alternative strategies is urgently required to prevent P. aeruginosa infection.

Adverse Cardiovascular and Pulmonary Events Associated With Chimeric Antigen Receptor T-Cell Therapy.

BACKGROUND: Pivotal trials of chimeric antigen receptor T-cell (CAR-T) have identified common toxicities but may have been underpowered to detect cardiovascular and pulmonary adverse events (CPAEs). OBJECTIVES: This study sought to investigate CPAEs associated with commercial CD19-directed CAR-T therapy. METHODS: In this retrospective, pharmacovigilance study, the authors used the Food and Drug Administration adverse event reporting system to identify CPAEs associated with axicabtagene-ciloleucel and tisagenlecleucel. The authors evaluated disproportionate reporting by the reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025 >0 is deemed significant). Significant associations were further adjusted to age and sex (adj.ROR). RESULTS: The authors identified CAR-T reports of 2,657 patients, including 546 CPAEs (20.5%). CPAEs overlapped with cytokine release syndrome in 68.3% (373 of 546) of the reports. Compared with the full database, CAR-T was associated with overreporting of tachyarrhythmias (n = 74 [2.8%], adj.ROR = 2.78 [95% CI: 2.21-3.51]), cardiomyopathy (n = 69 [2.6%], adj.ROR = 3.51 [2.42-5.09]), pleural disorders (n = 46 [1.7%], adj.ROR = 3.91 [2.92-5.23]), and pericardial diseases (n = 11 [0.4%], adj.ROR = 2.26 [1.25-4.09], all IC025 >0). Venous thromboembolic events (VTEs) were associated only with axicabtagene-ciloleucel therapy (n = 28 [1.6%], adj.ROR = 1.80 [1.24-2.62], IC025 >0). Atrial fibrillation (n = 55) was the leading tachyarrhythmia, followed by ventricular arrhythmias (n = 14). Tachyarrhythmias and VTEs were reported more often following axicabtagene-ciloleucel than tisagenlecleucel in an age- and sex-adjusted model (adj.ROR = 1.82 [1.04-3.18] and adj.ROR = 2.86 [1.18-6.93], respectively). Finally, the fatality rate of CPAEs was 30.9%. CONCLUSIONS: In this largest post-marketing study to date, the authors identified an association between CAR-T and various CPAEs, including tachyarrhythmias, cardiomyopathy, pericardial and pleural disorders, and VTEs. These findings should be considered in the multidisciplinary assessment for and monitoring of CAR-T therapy recipients.

Hemodynamic, renal and hormonal effects of lung protective ventilation during robot-assisted radical prostatectomy, analysis of secondary outcomes from a randomized controlled trial.

BACKGROUND: Lung protective ventilation with low tidal volume (TV) and increased positive end-expiratory pressure (PEEP) can have unfavorable effects on the cardiovascular system. We aimed to investigate whether lung protective ventilation has adverse impact on hemodynamic, renal and hormonal variables. METHODS: In this randomized, single-blinded, placebo-controlled study, 24 patients scheduled for robot-assisted radical prostatectomy were included. Patients were equally randomized to receive either ventilation with a TV of 6 ml/IBW and PEEP of 10 cm H2O (LTV-h.PEEP) or ventilation with a TV of 10 ml/IBW and PEEP of 4 cm H2O (HTV-l.PEEP). Before, during and after surgery, hemodynamic variables were measured, and blood and urine samples were collected. Blood samples were analyzed for plasma concentrations of electrolytes and vasoactive hormones. Urine samples were analyzed for excretions of electrolytes and markers of nephrotoxicity. RESULTS: Comparable variables were found among the two groups, except for significantly higher postoperative levels of plasma brain natriuretic peptide (p = 0.033), albumin excretion (p = 0.012) and excretion of epithelial sodium channel (p = 0.045) in the LTV-h.PEEP ventilation group compared to the HTV-l.PEEP ventilation group. In the combined cohort, we found a significant decrease in creatinine clearance (112.0 [83.4;126.7] ml/min at baseline vs. 45.1 [25.4;84.3] ml/min during surgery) and a significant increase in plasma concentrations of renin, angiotensin II, and aldosterone. CONCLUSION: Lung protective ventilation was associated with minor adverse hemodynamic and renal effects postoperatively. All patients showed a substantial but transient reduction in renal function accompanied by activation of the renin-angiotensin-aldosterone system. TRIAL REGISTRATION: ClinicalTrials, NCT02551341 . Registered 13 September 2015.

Prehabilitation exercise therapy before elective abdominal aortic aneurysm repair.

BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal dilation in the diameter of the abdominal aorta of 50% or more of the normal diameter or greater than 3 cm in total. The risk of rupture increases with the diameter of the aneurysm, particularly above a diameter of approximately 5.5 cm. Perioperative and postoperative morbidity is common following elective repair in people with AAA. Prehabilitation or preoperative exercise is the process of enhancing an individual's functional capacity before surgery to improve postoperative outcomes. Studies have evaluated exercise interventions for people waiting for AAA repair, but the results of these studies are conflicting. OBJECTIVES: To assess the effects of exercise programmes on perioperative and postoperative morbidity and mortality associated with elective abdominal aortic aneurysm repair. SEARCH METHODS: We searched the Cochrane Vascular Specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Physiotherapy Evidence Database (PEDro) databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 6 July 2020. We also examined the included study reports' bibliographies to identify other relevant articles. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) examining exercise interventions compared with usual care (no exercise; participants maintained normal physical activity) for people waiting for AAA repair. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed the included studies, extracted data and resolved disagreements by discussion. We assessed the methodological quality of studies using the Cochrane risk of bias tool and collected results related to the outcomes of interest: post-AAA repair mortality; perioperative and postoperative complications; length of intensive care unit (ICU) stay; length of hospital stay; number of days on a ventilator; change in aneurysm size pre- and post-exercise; and quality of life. We used GRADE to evaluate certainty of the evidence. For dichotomous outcomes, we calculated the risk ratio (RR) with the corresponding 95% confidence interval (CI). MAIN RESULTS: This review identified four RCTs with a total of 232 participants with clinically diagnosed AAA deemed suitable for elective intervention, comparing prehabilitation exercise therapy with usual care (no exercise). The prehabilitation exercise therapy was supervised and hospital-based in three of the four included trials, and in the remaining trial the first session was supervised in hospital, but subsequent sessions were completed unsupervised in the participants' homes. The dose and schedule of the prehabilitation exercise therapy varied across the trials with three to six sessions per week and a duration of one hour per session for a period of one to six weeks. The types of exercise therapy included circuit training, moderate-intensity continuous exercise and high-intensity interval training. All trials were at a high risk of bias. The certainty of the evidence for each of our outcomes was low to very low. We downgraded the certainty of the evidence because of risk of bias and imprecision (small sample sizes). Overall, we are uncertain whether prehabilitation exercise compared to usual care (no exercise) reduces the occurrence of 30-day (or longer if reported) mortality post-AAA repair (RR 1.33, 95% CI 0.31 to 5.77; 3 trials, 192 participants; very low-certainty evidence). Compared to usual care (no exercise), prehabilitation exercise may decrease the occurrence of cardiac complications (RR 0.36, 95% CI 0.14 to 0.92; 1 trial, 124 participants; low-certainty evidence) and the occurrence of renal complications (RR 0.31, 95% CI 0.11 to 0.88; 1 trial, 124 participants; low-certainty evidence). We are uncertain whether prehabilitation exercise, compared to usual care (no exercise), decreases the occurrence of pulmonary complications (RR 0.49, 95% 0.26 to 0.92; 2 trials, 144 participants; very low-certainty evidence), decreases the need for re-intervention (RR 1.29, 95% 0.33 to 4.96; 2 trials, 144 participants; very low-certainty evidence) or decreases postoperative bleeding (RR 0.57, 95% CI 0.18 to 1.80; 1 trial, 124 participants; very low-certainty evidence). There was little or no difference between the exercise and usual care (no exercise) groups in length of ICU stay, length of hospital stay and quality of life. None of the studies reported data for the number of days on a ventilator and change in aneurysm size pre- and post-exercise outcomes. AUTHORS' CONCLUSIONS: Due to very low-certainty evidence, we are uncertain whether prehabilitation exercise therapy reduces 30-day mortality, pulmonary complications, need for re-intervention or postoperative bleeding. Prehabilitation exercise therapy might slightly reduce cardiac and renal complications compared with usual care (no exercise). More RCTs of high methodological quality, with large sample sizes and long-term follow-up, are needed. Important questions should include the type and cost-effectiveness of exercise programmes, the minimum number of sessions and programme duration needed to effect clinically important benefits, and which groups of participants and types of repair benefit most.

Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial.

BACKGROUND: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. METHODS: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6-8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. RESULTS: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. CONCLUSIONS: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. TRIAL REGISTRATION: registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.