Unravel the distinct effects of adiposity at different life stages on COVID-19 susceptibility and severity: A life-course Mendelian randomization study.

Childhood obesity is widely recognized as a risk factor for numerous health conditions, particularly cardiovascular disease. However, it remains unclear whether childhood adiposity directly affects the risk of COVID-19 in later life. We aimed to investigate the causal effects of early life adiposity on COVID-19 susceptibility and severity. We used genetic instruments from large-scale genome-wide association studies to examine the relationships between birth weight, childhood and adulthood adiposity indicators (including body mass index [BMI], obesity, and body size), and COVID-19 outcomes. Univariable and multivariable Mendelian randomization (MR) analyses were used to obtain the causal estimates. Univariable MR analyses found that childhood BMI and obesity were positively associated with COVID-19 risk and severity in adulthood, however, the significant associations were attenuated to null after further adjusting for adulthood adiposity indicators in multivariable MR analyses. In contrast, our analysis revealed strong evidence of a genetically predicted effect of childhood obesity on COVID-19 hospitalization (OR 1.08, 95% CI: 1.01-1.15, p = 2.12E-2), which remained robust even after adjusting for adulthood obesity and potential lifestyle confounders. Our results highlight the importance of promoting healthy weight management throughout life to reduce the risk of COVID-19.

A comparative study of two α-L-rhamnosidases with high sequence identity.

The GH78 α-L-rhamnosidase from Aspergillus tubingensis (AT-Rha) was proved to be a new clade of Aspergillus α-L-rhamnosidases in the previous study. A putative α-L-rhamnosidase from A. kawachii IFO 4308 (AK-Rha) has 92 % identity in amino acid sequence with AT-Rha. In this study, AK-Rha was expressed in P. pastoris and characterized. Similar to AT-rRha, the recombinant AK-Rha (AK-rRha) showed a narrow substrate specificity to naringin. Interestingly, the enzyme activity of AK-rRha was 0.816 U/mg toward naringin, significantly lower than 125.142 U/mg of AT-rRha. Their large differences in catalytic efficiency was mainly due to their differences in kcat values between AK-rRha (0.67 s-1) and AT-rRha (4.89 × 104 s-1). The molecular dynamics simulation exhibited that the overall conformation of AK-Rha was rigid and that of AT-Rha was flexible; the Loop Y-L located above the catalytic domain formed different steric hindrances to naringin, and interacted with the flavonoid matrices at different strengths. The polar solvation energy analysis implied that the glycosidic bond was more easily hydrolysed in AT-Rha. The comparative study verified that the main feature of AK-Rha and AT-Rha represented Aspergillus α-L-rhamnosidase was the narrow substrate specificity toward naringin, and provided an insight of the relationships between their catalytic abilities and structures.

Spontaneous gallbladder perforation and colon fistula in hypertriglyceridemia-related severe acute pancreatitis: A case report.

BACKGROUND: Gallbladder perforation and gastrointestinal fistula are rare but serious complications of severe acute pancreatitis (SAP). However, neither spontaneous gallbladder perforation nor cholecysto-colonic fistula has been reported in acalculous acute pancreatitis patients. CASE SUMMARY: A 31-year-old male presenting with epigastric pain was diagnosed with hypertriglyceridemia-related SAP. He suffered from multiorgan failure and was able to leave the intensive care unit on day 20. Three percutaneous drainage tubes were placed for profound exudation in the peripancreatic region and left paracolic sulcus. He developed spontaneous gallbladder perforation with symptoms of fever and right upper quadrant pain 1 mo after SAP onset and was stabilized by percutaneous drainage. Peripancreatic infection appeared 1 mo later and was treated with antibiotics but without satisfactory results. Then multiple colon fistulas, including a cholecysto-colonic fistula and a descending colon fistula, emerged 3 mo after the onset of SAP. Nephroscopy-assisted peripancreatic debridement and ileostomy were carried out immediately. The fistulas achieved spontaneous closure 7 mo later, and the patient recovered after cholecystectomy and ileostomy reduction. We presume that the causes of gallbladder perforation are poor bile drainage due to external pressure, pancreatic enzyme erosion, and ischemia. The possible causes of colon fistulas are pancreatic enzymes or infected necrosis erosion, ischemia, and iatrogenic injury. According to our experience, localized gallbladder perforation can be stabilized by percutaneous drainage. Pancreatic debridement and proximal colostomy followed by cholecystectomy are feasible and valid treatment options for cholecysto-colonic fistulas. CONCLUSION: Gallbladder perforation and cholecysto-colonic fistula should be considered in acalculous SAP patients.

New volumetric capnography-derived parameter: a potentially valuable tool for detecting hyperventilation during cardiopulmonary resuscitation in a porcine model.

BACKGROUND: Volumetric capnography is increasingly being applied in cardiopulmonary resuscitation. However, during cardiopulmonary resuscitation, the abnormal ventilation state affects the monitoring effect of the most commonly used capnography-derived parameter, the partial carbon dioxide end-tidal pressure (PetCO2). In this study, we evaluated the ability of a new volumetric capnography-derived parameter, the ratio between the PetCO2 and the volume of carbon dioxide (CO2) eliminated per min and per kilogram of body weight, for detecting hyperventilation during cardiopulmonary resuscitation. METHODS: We used 12 porcine models of primary ventricular fibrillation-induced cardiac arrest. Ventricular fibrillation was induced and left untreated for 4 min. Standardized chest compressions were performed throughout the experiment using mechanical cardiopulmonary resuscitation. Following 5 min of normal ventilation as a washout period, each animal underwent 4 types of ventilation. The main outcome measures were the PetCO2, the ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight with each ventilation type. RESULTS: Different ventilation types had a significant effect on the volumetric capnography-derived parameters. The PetCO2 and ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight values during cardiopulmonary resuscitation was significantly higher in non-hyperventilating than in hyperventilating animals. The ratio reflected hyperventilation accurately and immediately, with an area under the curve (AUC) of 0.98. The optimal cut-off point of the ratio for discriminating hyperventilation from non-hyperventilation was 6.36, with a sensitivity and specificity of 0.99 and 0.89, respectively. CONCLUSIONS: The ratio between the PetCO2 and the volume of CO2 eliminated per min and per kilogram of body weight showed good performance in discriminating hyperventilation from non-hyperventilation and was sensitive to changes in ventilation status. This ratio may be a valuable clinical indicator for monitoring the ventilation status during cardiopulmonary resuscitation.

Can bag-valve mask ventilation with positive end-expiratory pressure reduce hypoxia during intubation? A prospective, randomized, double-blind trial.

BACKGROUND: Hypoxia is one of the life-threatening complications of endotracheal intubation. Supplemental oxygen and ventilation play a vital role in preventing hypoxia. Bag-valve mask (BVM) ventilation is frequently used before intubation, and its ability to improve oxygenation was recently confirmed. It is still unclear if positive end-expiratory pressure (PEEP) added to BVM ventilation can further reduce hypoxia during intubation. METHODS: This will be a prospective, randomized, double-blind trial to determine if PEEP combined with BVM ventilation can reduce the incidence of hypoxia during intubation compared with conventional BVM ventilation. The lowest oxygen saturation and incidence of complications will be compiled to verify the comparative effectiveness and safety of the two groups. DISCUSSION: BMV ventilation with PEEP is hoped to further reduce the incidence of hypoxia during intubation. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000035156 . Registered on August 2, 2020. It had begun enrollment after passing ethical review but before registration.

Klebsiella pneumoniae pneumonia in patients with rheumatic autoimmune diseases: clinical characteristics, antimicrobial resistance and factors associated with extended-spectrum ß-lactamase production.

BACKGROUND: Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum ß-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department. METHODS: We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected. RESULTS: Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing. CONCLUSIONS: K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

Efficacy of prophylactic methylprednisolone on reducing the risk of post-extubation stridor in patients after an emergency intubation: study protocol for a randomized controlled trial.

BACKGROUND: Post-extubation stridor (PES) is one of the most common complications of invasive respiratory support, with severe cases leading to possible extubation failure (reintubation within 48 h) and increased mortality. Previous studies confirmed that prophylactic corticosteroids play an important role in reducing the risk of PES and extubation failure. However, few studies have looked at the efficacy of corticosteroids on preventing PES in patients after an emergency intubation. AIM: To evaluate whether a single dose of methylprednisolone given over a set timeframe before extubation is effective in preventing PES in patients after an emergency intubation. METHODS: A multicenter, randomized, placebo-controlled trial will be performed in an emergency department (ED) setting. The trial will include 132 patients who fail a cuff-leak test (CLT) prior to the intervention. Patients will be randomly assigned to either intravenous methylprednisolone (40 mg) or placebo 4 h prior to extubation. Other eligible patients who pass the CLT will be included in a non-intervention (observation) group. The primary endpoint is the incidence of PES within 48 h after extubation. Secondary endpoints include oxygen therapy, respiratory support requirements, reintubation secondary to PES, adverse effects within 48 h after extubation, hospital length of stay, and hospital mortality. DISCUSSION: Patients who are intubated on an emergency basis have a higher risk of intubation-related complications. Previous studies have examined treatment regimens involving more than 10 different variations on corticosteroid treatments for PES prevention, while for ED therapy, only a simple and effective treatment would be appropriate. Corticosteroid administration is usually accompanied by adverse effects; thus, this study will be important for further risk stratification among intubated ED patients. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2000030349 . Registered on 29 February 2020.

Pulse rate as an alternative, real-time feedback indicator for chest compression rate: a porcine model of cardiac arrest.

Feedback indicators can improve chest compression quality during cardiopulmonary resuscitation (CPR). However, the application of feedback indicators in the clinic practice is rare. Pulse oximetry has been widely used and reported to correlate spontaneous circulation restoration during CPR. However, it is unclear if pulse oximetry can monitor the quality of chest compression. We hypothesized that pulse rate monitored by pulse oximetry can be used as a feedback indicator of the chest compression rate during CPR in a porcine model of cardiac arrest. Seven domestic male pigs (30-35 kg) were utilized in this study. Eighteen intermittent chest compression periods of 2 min were performed on each animal. Chest compression and pulse oximetry plethysmographic waveforms were recorded simultaneously. Chest compression and pulse rates were calculated based on both waveforms. Compression interruption and synchronous pulse interruption times were also measured. Agreement was analyzed between pulse rates and synchronous chest compression rates, as well as between compression interruption times and synchronous pulse interruption times. A total of 126 compression periods of 2 min were performed on seven animals. Interclass correlation coefficients and Bland-Altman analysis revealed reliable agreement between pulse rates and synchronous chest compression rates. Similarly, compression interruption and synchronous pulse interruption times obtained also showed high agreement. Pulse rate can be used as an alternative indicator of chest compression rate during CPR in a porcine model of cardiac arrest. Pulse interruption time also can be used to reflect compression interruption time precisely in this model.

Therapeutic and immunoregulatory effect of GATA-binding protein-3/T-box expressed in T-cells ratio of astragalus polysaccharides on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats.

OBJECTIVE: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides (APS) treatment. METHODS: Thirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS (0.5 g•kg-1•day-1, once daily) or prednisone (1.0 mg•kg-1•day-1, once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase (MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3) were determined by immunohistochemistry analysis and western blot. RESULTS: Both macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity (P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio (P=0.025). APS administration enhanced the expression of T-bet (P=0.04) and GATA-3 (P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio. CONCLUSIONS: These results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1 (Th1) and T helper cell 2 (Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis.