Severe intracranial infection caused by community-acquired hypervirulent Klebsiella pneumoniae: A case report.

Hypervirulent Klebsiella pneumoniae (HvKp) is a dynamic pathotype characterized by heightened mucoviscosity and virulence, typically afflicting individuals within the community, who commonly exhibit good health. We presented a case study of a 65-year-old male with diabetes who developed community acquired pneumonia, septic shock, and intracranial infection. The diagnosis was established through cranial magnetic resonance imaging (MRI), typical clinical presentation, and biological culture. The presence of HvKp infection was confirmed by cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) and blood culture. Treatment consisted of Amikacin 0.8 g qd in combination with meropenem 2.0 g q8h, based on drug sensitivity testing. The patient experienced symptom relief, with the CSF becoming clear and the elimination of the pathogen, ultimately resulting in a successful recovery. The clinical data, diagnosis, and treatment of the patient were documented, and a review of the literature was conducted to offer clinical guidance regarding the intracranial infection resulting from community-acquired HvKp.

Clinical efficacy and safety of high-flow nasal cannula (HFNC) in acute hypoxaemic patients with COVID-19: a protocol for a systematic review and meta-analysis.

INTRODUCTION: When COVID-19 patients develop hypoxaemic respiratory failure, they often undergo early intubation. Such a potentially aerosol-generating approach places caregivers at increased risk of contracting COVID-19. This protocol aims to evaluate the clinical efficacy and safety of a high-flow nasal cannula (HFNC) for the treatment of COVID-19 patients with acute hypoxaemic respiratory failure. METHODS AND ANALYSIS: We intend to search MEDLINE, Embase, Web of Science and Cochrane Library to identify all randomised controlled trials (RCTs) on the use of HFNC in COVID-19 patients with acute respiratory failure. We will screen the RCTs against eligibility criteria for inclusion in our review. Two reviewers will independently undertake RCT selection, data extraction and risk of bias assessment. Primary outcome will be the rate of intubation, and secondary outcomes will be intensive care unit (ICU)/hospital mortality, ICU/hospital length of stay and risks of infection transmission. We will conduct meta-analyses to determine the risk ratio for dichotomous data and the mean difference (MD) or standardised MD for continuous data. Subgroup analyses will be performed based on the different quality of studies, different levels of disease severity, and the age and sex of participants. ETHICS AND DISSEMINATION: Ethical approval is not required for this study considering this is a systematic review protocol that uses only published data. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021236519.

Long Non-coding RNA H19 Augments Hypoxia/Reoxygenation-Induced Renal Tubular Epithelial Cell Apoptosis and Injury by the miR-130a/BCL2L11 Pathway.

Acute kidney injury (AKI) is a severe kidney disease defined by partial or abrupt loss of renal function. Emerging evidence indicates that non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), function as essential regulators in AKI development. Here we aimed to explore the underlying molecular mechanism of the lncRNA H19/miR-130a axis for the regulation of inflammation, proliferation, and apoptosis in kidney epithelial cells. Human renal proximal tubular cells (HK-2) were induced by hypoxia/reoxygenation to replicate the AKI model in vitro. After treatment, the effects of LncRNA H19 and miR-130a on proliferation and apoptosis of HK-2 cells were investigated by CCK-8 and flow cytometry. Meanwhile, the expressions of LncRNA H19, miR-130a, and inflammatory cytokines were detected by qRT-PCR, western blot, and ELISA assays. The results showed that downregulation of LncRNA H19 could promote cell proliferation, inhibit cell apoptosis, and suppress multiple inflammatory cytokine expressions in HK-2 cells by modulating the miR-130a/BCL2L11 pathway. Taken together, our findings indicated that LncRNA H19 and miR-130a might represent novel therapeutic targets and early diagnostic biomarkers for the treatment of AKI.

Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets.

BACKGROUND: Severe asthma is a chronic disease contributing to disproportionate disease morbidity and mortality. From the year of 2007, many genome-wide association studies (GWAS) have documented a large number of asthma-associated genetic variants and related genes. Nevertheless, the molecular mechanism of these identified variants involved in asthma or severe asthma risk remains largely unknown. METHODS: In the current study, we systematically integrated 3 independent expression quantitative trait loci (eQTL) data (N = 1977) and a large-scale GWAS summary data of moderate-to-severe asthma (N = 30,810) by using the Sherlock Bayesian analysis to identify whether expression-related variants contribute risk to severe asthma. Furthermore, we performed various bioinformatics analyses, including pathway enrichment analysis, PPI network enrichment analysis, in silico permutation analysis, DEG analysis and co-expression analysis, to prioritize important genes associated with severe asthma. RESULTS: In the discovery stage, we identified 1129 significant genes associated with moderate-to-severe asthma by using the Sherlock Bayesian analysis. Two hundred twenty-eight genes were prominently replicated by using MAGMA gene-based analysis. These 228 replicated genes were enriched in 17 biological pathways including antigen processing and presentation (Corrected P = 4.30 × 10- 6), type I diabetes mellitus (Corrected P = 7.09 × 10- 5), and asthma (Corrected P = 1.72 × 10- 3). With the use of a series of bioinformatics analyses, we highlighted 11 important genes such as GNGT2, TLR6, and TTC19 as authentic risk genes associated with moderate-to-severe/severe asthma. With respect to GNGT2, there were 3 eSNPs of rs17637472 (PeQTL = 2.98 × 10- 8 and PGWAS = 3.40 × 10- 8), rs11265180 (PeQTL = 6.0 × 10- 6 and PGWAS = 1.99 × 10- 3), and rs1867087 (PeQTL = 1.0 × 10- 4 and PGWAS = 1.84 × 10- 5) identified. In addition, GNGT2 is significantly expressed in severe asthma compared with mild-moderate asthma (P = 0.045), and Gngt2 shows significantly distinct expression patterns between vehicle and various glucocorticoids (Anova P = 1.55 × 10- 6). CONCLUSIONS: Our current study provides multiple lines of evidence to support that these 11 identified genes as important candidates implicated in the pathogenesis of severe asthma.

Adherence to Guidelines on Nutritional Support by Medical Residents in an Intensive Care Unit in China: A Prospective Observational Study.

BACKGROUND The use of evidence-based clinical practice guidelines improves the quality of patient medical care. Although the implementation of clinical guidelines can be a challenge, nutritional support is important for critically ill patients. This prospective observational study aimed to investigate the attention to and implementation of guidelines for nutritional support in an Intensive Care Unit (ICU) in China and to identify factors that determine attention to these guidelines. MATERIAL AND METHODS The study included 16 medical residents who were interviewed while working in an emergency Intensive Care Unit (ICU) during one month. A structured interview questionnaire on attention to patient nutritional guidelines was used. Interviews were conducted daily after an early ICU ward round, and residents were asked questions regarding each patient. RESULTS The response rate from medical residents was 99.6% (455/457). The rate of attention to and implementation of nutritional support guidelines was 57.1% (260/455) and 73.1% (334/457), respectively. Multivariate logistic regression analysis showed that weekdays and weekends (OR, 0.59; 95% CI, 0.38-0.91), medical groups (OR, 0.67; 95% CI, 0.46-0.98), and the numbers of patients admitted (OR, 0.91; 95% CI, 0.85-0.97) were independently associated with attention to nutritional support guidelines by the residents. CONCLUSIONS Nutritional guidelines for patients in the ICU were not fully paid attention to by medical residents or implemented. The reasons included high work demands and lack of standardized training. Further studies are needed to determine whether measures to reduce workload and improve medical training can improve adherence to nutritional support guidelines in the ICU.

Challenges in diagnosing community-acquired carbapenem-susceptible Acinetobacter baumannii enterogenic sepsis: A case report.

INTRODUCTION: Community-acquired (CA) carbapenem-susceptible Acinetobacter baumannii (CSAB) enterogenic sepsis is very rare but has a high mortality. Although CA A. baumannii bloodstream infections have been known to develop from respiratory tract, urinary tract, and intravenous device-related infections, CA A. baumannii bloodstream infections from the gastrointestinal tract have not yet been reported. PATIENT CONCERNS: A 73-year-old male with the chief presentation of gastrointestinal symptoms was initially diagnosed with acute gastroenteritis and showed poor clinical response to empirical antibiotic therapy. DIAGNOSES: The diagnosis of CSAB enterogenic sepsis was established based on results of blood culture, elevated serum procalcitonin level, and specific hemodynamic changes related to septic shock. INTERVENTIONS: The patient initially received empirical antibiotic treatment (cefodizime 2.0 q12 hours plus moxifloxacin 0.4 qd); then, treatment was changed to the conventional dose of carbapenem (imipenem 0.5 q6 hour). OUTCOMES: Finally, CSAB was eliminated from the bloodstream, and the patient was discharged. LESSONS: Although severe, CA CSAB enterogenic sepsis is often misdiagnosed because of its clinical rarity. Early diagnosis and appropriate initial empirical antibiotic therapy are crucial for treating such cases.

Lung Ultrasound Combined With Procalcitonin for a Diagnosis of Ventilator-Associated Pneumonia.

BACKGROUND: Lung ultrasound is a valuable imaging tool in the diagnosis of community-acquired pneumonia. However, its diagnostic accuracy in ventilator-associated pneumonia (VAP) has not been fully investigated. The aim of this study was to evaluate the diagnostic performance of the combination of a lung ultrasound with procalcitonin (PCT) in mechanically ventilated subjects with symptoms suggestive of pneumonia. METHODS: A prospective study of 124 subjects with suspected VAP in 2 multidisciplinary ICUs was conducted between December 2016 and October 2017. Lower respiratory tract specimens were collected from all the subjects at enrollment and on the following 3 d. PCT assays were performed within 1 h of enrollment. Lung ultrasound and then computed tomography of the chest were performed within 24 h to detect lung consolidations. The subjects were divided into VAP and non-VAP groups according to the results of a computed tomography of the chest and semi-quantitative culture of the lower respiratory tract sample. RESULTS: A total of 124 subjects were included (48 in the VAP group and 76 in the non-VAP group). A positive lung ultrasound result combined with PCT of ≥0.25 ng/mL diagnosed VAP, with a sensitivity and specificity of 81.3 and 85.5%, respectively. The area under the receiver operating characteristic curve was significantly higher for lung ultrasound combined with PCT than for a white blood cell count, PCT, C-reactive protein, or Clinical Pulmonary Infection Score alone. CONCLUSIONS: A combination of lung ultrasound and PCT was accurate in the diagnosis of VAP. Lung ultrasound is a useful lung-imaging tool to assist VAP diagnosis.

Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad­spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti­inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation­induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase­3, B­cell lymphoma­2 (Bcl­2) family proteins, total­Akt and phospho­Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase­3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl­2, Bcl­extra large and Bcl­associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI­induced anti­apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.

[Risk factors analysis of renal replacement therapy after liver transplantation and prognosis effect of initial treatment time].

OBJECTIVE: To analyze the risk factors of renal replacement therapy (RRT) in acute kidney injury (AKI) patients after liver transplantation, and to investigate the prognosis effect of initial RRT treatment time. METHODS: Clinical data of 132 recipients undergoing organ donation for cardiac death (DCD) allograft orthotopic liver transplantation admitted to Ningbo Medical Center Lihuili Hospital and Ningbo Medical Center Lihuili Eastern Hospital from July 2014 to July 2018 was retrospectively analyzed. AKI was defined and staged by the criteria of Kidney Disease Improving Global Outcomes (KDIGO) guideline in the first 7 days. According to the implementation of RRT, the patients were divided into non-RRT group and RRT group. The differences in gender, age, body mass index (BMI), model for end-stage liver disease with serum sodium (MELD-Na) score, serum creatinine (SCr), and intraoperative norepinephrine (NE) dose, blood loss, fluid infusion, anhepatic phase time, duration of operation between two groups were compared. The statistically significant risk factors of AKI found by univariate analysis were selected and analyzed to find independent risk factors of RRT in AKI patients after liver transplantation with multivariate Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the test efficiency of all risk factors of RRT implementation. According to the implementation of RRT on KDIGO stage-2, all the patients on KDIGO stage-2 and stage-3 were divided into early group (initial RRT on KDIGO stage-2) and delayed group (including self-improvement without RRT on KDIGO stage-2 and initial RRT on KDIGO stage-3). The duration of mechanical ventilation, the length of intensive care unit (ICU) stay, AKI duration, incidence of catheter related bloodstream infection (CRBSI) and 28-day mortality were compared between the two groups. RESULTS: All 132 receptors were enrolled in the final analysis, and 77 patients developed AKI, accounting for 58.3%, among which 52 cases were in RRT group (67.5%) and 25 were in non-RRT group (32.5%). As shown by univariate analysis, the MELD-Na score (21.6±4.4 vs. 18.0±4.3), intraoperative NE dose (µg×kg-1×h-1: 7.5±1.2 vs. 5.2±1.7), blood loss [mL: 3 000 (2 200, 4 000) vs. 2 600 (1 800, 3 200)], fluid infusion [mL: 6 400 (4 500, 7 800) vs. 5 600 (4 200, 6 800)], and anhepatic period (minutes: 65.6±4.5 vs. 63.0±5.0) were significantly increased in RRT group as compared with those in non-RRT group (all P < 0.05). There was no significant difference in gender, age, BMI, SCr before operation or the duration of operation. It was shown by multivariate Logistic regression analysis that MELD-Na score before operation [odds ratio (OR) = 1.398, 95% confidence interval (95%CI) = 1.062-1.841, P = 0.017], intraoperative NE dose (OR = 4.724, 95%CI = 2.036-10.961, P = 0.000) and fluid infusion (OR = 1.002, 95%CI = 1.001-1.004, P = 0.010) were independent risk factors of RRT implementation in AKI patients after liver transplantation. It was shown by ROC curve analysis that the area under the ROC curve (AUC) of MELD-Na score, NE dose and fluid infusion for predicting the implementation of RRT in AKI patients after liver transplantation was 0.719, 0.867, and 0.670, respectively, which suggesting that NE dose had moderate predictive value, but MELD-Na score and fluid infusion had low predicative value. When the optimal cut-off value of NE dose was 6.5 µg×kg-1×h-1, the sensitivity was 84.6% and the specificity was 80.0%. The 28-day mortality was both 0 in early group (n = 25) and delayed group (n = 39). Compared with the early group, the duration of mechanical ventilation (hours: 41.0±1.0 vs. 35.8±6.7) and the length of ICU stay (hours: 98.8±6.6 vs. 94.2±7.3) were significantly increased in delayed group (both P < 0.05), there was no significant difference in AKI duration (days: 11.8±4.2 vs. 10.6±4.9) or the incidence of CRBSI [5.1% (2/39) vs. 4.0% (1/25), both P > 0.05]. CONCLUSIONS: MELD-Na score, intraoperative NE dose and fluid infusion were the independent risk factors of RRT implementation in AKI patients after liver transplantation. NE dose had moderate predictive value, but MELD-Na score and fluid infusion had low predicative value. Initial RRT on KDIGO stage-2 could reduce the duration of mechanical ventilation and the length of ICU stay.

Delayed cerebellar infarction after a slight electric injury.

Electrical injury causes direct damage to nerves. It may manifest as peripheral nerve injury, spinal cord damage, cerebellar ataxia, hypoxic encephalopathy, or intracerebral hemorrhage. Various factors determine the severity of electric injury, including type of current, amperage, voltage, tissue resistance, pathway of the current, and duration of contact with the body. However, the severity of the electrical injury is not proportional to the source voltage, visible burns, loss of consciousness, or neuroimaging findings. While most neurologic aftereffects due to electric injuries are immediate and transient, delayed and permanent manifestations are also known. We report a case of a middle-aged man who accidentally sustained cerebellar infarction without burns, which occurred 4 days after a slight electrical injury. Magnetic resonance imaging of the brain showed an acute infarct in the bilateral cerebellar and left occipital regions. The exact mechanism of the delayed cerebellar infarction after a slight electric injury still remains unknown. The initial electrical injury might result in a transient neurapraxia-like situation, but progressive cellular damage and death accounts for the evolution of delayed-onset symptoms. We learned from this case that we should not underestimate any potential risk of electrical injury; continuous observation should be made in case of subsequent neurologic dysfunction.

CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer--Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects.

BACKGROUND: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. MATERIALS AND METHODS: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. RESULTS: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). CONCLUSIONS: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.

Effects of continuous positive airway pressure therapy on glycaemic control, insulin sensitivity and body mass index in patients with obstructive sleep apnoea and type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that 15-30% of individuals with obstructive sleep apnoea (OSA) have type 2 diabetes mellitus (T2DM), and that OSA is an independent risk factor for T2DM. There is considerable interest in ascertaining whether OSA treatment improves glycaemic control and insulin sensitivity in patients with OSA and T2DM. AIMS: To assess the effects of continuous positive airway pressure (CPAP) therapy on glycosylated haemoglobin (HbA1c) level, insulin sensitivity and body mass index (BMI) in patients with OSA and T2DM. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched to identify prospective studies involving patients with OSA and T2DM who had received CPAP, and data on primary outcome (change in HbA1c) and/or secondary outcomes (changes in insulin sensitivity and BMI) were reported. All relevant studies published before 31 January 2014 were included. RESULTS: Six studies were included in the systematic review and meta-analysis. The numbers of patients ranged from 9 to 44 (total=128), and mean age ranged from 50.7 to 66.1 years. For the change in HbA1c (six studies, 128 patients), the combined standardised paired difference revealed no significant effect of CPAP (-0.071, 95% confidence interval (CI)=-0.245, 0.103; P=0.421). Similarly, there was no significant effect of CPAP on the change in BMI (-0.102, 95% CI=-0.296, 0.092; P=0.302; five studies, 103 patients). In contrast, there was a significant effect of CPAP on the change (improvement) in insulin sensitivity (0.330, 95% CI=0.001, 0.658; P=0.049; three studies, 39 patients). CONCLUSION: The limited available evidence from randomised controlled trials and prospective observational studies suggests that CPAP does not decrease HbA1c level or BMI in patients with OSA and T2DM but may improve insulin sensitivity.

Passive leg raising as an indicator of fluid responsiveness in patients with severe sepsis.

BACKGROUND: In the management of critically ill patients, the assessment of volume responsiveness and the decision to administer a fluid bolus constitute a common dilemma for physicians. Static indices of cardiac preload are poor predictors of volume responsiveness. Passive leg raising (PLR) mimics an endogenous volume expansion (VE) that can be used to predict fluid responsiveness. This study was to assess the changes in stroke volume index (SVI) induced by PLR as an indicator of fluid responsiveness in mechanically ventilated patients with severe sepsis. METHODS: This was a prospective study. Thirty-two mechanically ventilated patients with severe sepsis were admitted for VE in ICU of the First Affiliated Hospital, Zhejiang University School of Medicine and Ningbo Medical Treatment Center Lihuili Hospital from May 2010 to December 2011. Patients with non-sinus rhythm or arrhythmia, parturients, and amputation of the lower limbs were excluded. Measurements of SVI were obtained in a semi-recumbent position (baseline) and during PLR by the technique of pulse indicator continuous cardiac output (PiCCO) system prior to VE. Measurements were repeated after VE (500 mL 6% hydroxyethyl starch infusion within 30 minutes) to classify patients as either volume responders or non-responders based on their changes in stroke volume index (ΔSVI) over 15%. Heart rate (HR), systolic artery blood pressure (ABPs), diastolic artery blood pressure (ABPd), mean arterial blood pressure (ABPm), mean central venous pressure (CVPm) and cardiac index (CI) were compared between the two groups. The changes of ABPs, ABPm, CVPm, and SVI after PLR and VE were compared with the indices at the baseline. The ROC curve was drawn to evaluate the value of ΔSVI and the change of CVPm (ΔCVPm) in predicting volume responsiveness. SPSS 17.0 software was used for statistical analysis. RESULTS: Among the 32 patients, 22 were responders and 10 were non-responders. After PLR among the responders, some hemodynamic variables (including ABPs, ABPd, ABPm and CVPm) were significantly elevated (101.2±17.6 vs.118.6±23.7, P=0.03; 52.8±10.7 vs. 64.8±10.7, P=0.006; 68.3±11.7 vs. 81.9±14.4, P=0.008; 6.8±3.2 vs. 11.9±4.0, P=0.001). After PLR, the area under curve (AUC) and the ROC curve of ΔSVI and ΔCVPm for predicting the responsiveness after VE were 0.882±0.061 (95%CI 0.759-1.000) and 0.805±0.079 (95%CI 0.650-0.959) when the cut-off levels of ΔSVI and ΔCVPm were 8.8% and 12.7%, the sensitivities were 72.7% and 72.7%, and the specificities were 80% and 80%. CONCLUSION: Changes in ΔSVI and ΔCVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.