A New Prognostic Index PDPI for the Risk of Pneumonia Among Patients With Diabetes.

Objective: Risk factors for the development of pneumonia among patients with diabetes mellitus are unclear. The aim of our study was to elucidate the potential risk factors and attempt to predict the probability of pneumonia based on the history of diabetes. Methods: We performed a population-based, prospective multicenter cohort study of 1,043 adult patients with diabetes in China during 2017-2019. Demographic information, comorbidities, or laboratory examinations were collected. Results: The study included 417 diabetic patients with pneumonia and 626 no-pneumonia-onset diabetic patients. The predictive risk factors were chosen on the basis of a multivariate logistic regression model to predict pneumonia among patients with diabetes including male sex [odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.27-2.33, p < 0.001], age ≥ 75 years (OR = 2.31, 95% CI: 1.61-3.31, p < 0.001), body mass index < 25 (OR = 2.59, 95% CI: 1.92-3.50, p < 0.001), chronic obstructive pulmonary disease (OR = 6.58, 95% CI: 2.09-20.7, p = 0.001), hypertension (OR = 4.27, 95% CI: 3.12-5.85, p < 0.001), coronary heart disease (OR = 2.98, 95% CI: 1.61-5.52, p < 0.001), renal failure (OR = 1.82, 95% CI: 1.002-3.29, p = 0.049), cancer (OR = 3.57, 95% CI: 1.80-7.06, p < 0.001), use of insulin (OR = 2.28, 95% CI: 1.60-3.25, p < 0.001), and hemoglobin A1c ≥ 9% (OR = 2.70, 95% CI: 1.89-3.85, p < 0.001). A predictive nomogram was established. This model showed c-statistics of 0.811, and sensitivity and specificity were 0.717 and 0.780, respectively, under cut-off of 125 score. Conclusion: We designed a clinically predictive tool for assessing the risk of pneumonia among adult patients with diabetes. This tool stratifies patients into relevant risk categories and may provide a basis for individually tailored intervention for the purpose of early prevention.

A Potential High-Risk Clone of Pseudomonas aeruginosa ST463.

Pseudomonas aeruginosa is one of the most common opportunistic pathogens, which causes severe nosocomial infections because of its well-known multidrug-resistance and hypervirulence. It is critical to curate routinely the epidemic P. aeruginosa clones encountered in the clinic. The aim of the present study was to investigate the connection between virulence factors and antimicrobial resistance profiles in epidemic clones. Herein, we found that ST463 (O4), ST1212 (O11), and ST244 (O5) were prevalent in 30 isolates derived from non-cystic fibrosis patients, based on multilocus sequence type (MLST) and serotype analysis. All isolates were multidrug-resistant (MDR) and each was resistance to at least three classes of antibiotics in antimicrobial susceptibility tests, which was consistent with the presence of the abundant resistance genes, such as bla OXA-50, bla PAO, aph(3'), catB7, fosA, crpP, and bla KPC-2. Notably, all bla KPC-2 genes were located between ISKpn6-like and ISKpn8-like mobile genetic elements. In addition, classical exotoxins encoded by exoU, exoS, and pldA were present in 43.44% (13/40), 83.33% (25/30), and 70% (21/30) of the isolates, respectively. The expression of phz operons encoding the typical toxin, pyocyanin, was observed in 60% of isolates (18/30) and was quantified using triple quadrupole liquid chromatograph mass (LC/MS) assays. Interestingly, compared with other MLST types, all ST463 isolates harbored exoU, exoS and pldA, and produced pyocyanin ranging from 0.2 to 3.2 µg/mL. Finally, we evaluated the potential toxicity of these isolates using hemolysis tests and Galleria mellonella larvae infection models. The results showed that ST463 isolates were more virulent than other isolates. In conclusion, pyocyanin-producing ST463 P. aeruginosa, carrying diverse virulence genes, is a potential high-risk clone.

Increased Antimicrobial Resistance among Sputum Pathogens from Patients with Hyperglycemia.

BACKGROUND: Glucose management is of great significance. Infection and hyperglycemia are a vicious circle. This study was conducted to describe distribution and antimicrobial resistance of bacteria isolated from patients with normoglycemia, hyperglycemia, or diabetes on admission. METHODS: A retrospective study was conducted in a teaching hospital from January 2015 to March 2017. Bacteria were identified by the Vitek 2 automated system and antimicrobial susceptibility determined. RESULTS: A total of 1,163 patients were included: 582 with normoglycemia, 292 with hyperglycemia and 289 with diabetes. Enterobacter, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium were the main species isolated from these patients, with 1,616 unduplicated isolates from sputum samples. Patients with hyperglycemia were more prone to carry more than one species, and the rate of multidrug-resistant K. pneumoniae and methicillin-resistant S. aureus was higher in this group. K. pneumoniae from hyperglycemia patients demonstrated increased resistance to carbapenems, especially imipenem (p=0.002) and meropenem (p=0.003), than those isolated from patients with normoglycemia or diabetes. No significance was detected for K. pneumoniae, A. baumannii, or P. aeruginosa between nondiabetes and diabetes patients. In addition, hyperglycemia patients had a higher rate of ICU admission (p=0.035) and a lower survival rate (p<0.001). CONCLUSION: Patients with hyperglycemia were more prone to carry bacteria, especially multidrug-resistant K. pneumoniae and methicillin-resistant S. aureus. Assessing glucose on admission is of great significance in predicting bacterial carriage and antimicrobial resistance.

Clinical characteristics and outcomes of coronavirus disease 2019 infections among diabetics: A retrospective and multicenter study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged in December 2019 and has spread globally. Diabetics are at increased risk of infections caused by a variety of pathogens including viruses. The present research aims to describe clinical characteristics and outcomes of COVID-19 patients with diabetes. METHODS: A retrospective multicenter study of COVID-19 patients with diabetes was conducted in four hospitals in Wuhan, Shanghai, and Anhui Province. Reverse transcription polymerase chain reaction or next-generation sequencing was carried out to confirm the existence of severe acute respiratory syndrome coronavirus 2 from respiratory specimens. RESULTS: A total of 54 diabetics (10.36%) were recruited from among 521 COVID-19 patients, with a median age of 63 (interquartile range, 52-70) years. Among them, 51 had been previously diagnosed with diabetes and 3 had been newly diagnosed based on glycosylated hemoglobin over 6.5%. For COVID-19, 47 of the 54 patients had an exposure history. Fever (47/54, 87.04%), dry cough (36/54, 66.67%), and expectoration (21/53, 39.62%) were among the top three symptoms. Lung infiltration was bilateral (46/52, 88.46%) and multilobe (47/52, 90.38%), and ground-glass opacity (36/37, 97.30%) was the most common pattern in radiological images. Moreover, COVID-19 patients with diabetes were prone to be classified as severe or critical cases (46.30%, 25/54) and had complications such as acute lung injury, acute respiratory distress syndrome, and acute kidney injury. The proportions of intensive care unit (ICU) admissions and deaths among the COVID-19 diabetics were 14.81% (8/54) and 12.96% (7/54), respectively. CONCLUSIONS: With older age, diabetics diagnosed as having COVID-19 were prone to develop into severe cases and exhibited a high rate of ICU admission and mortality.

A randomized controlled trial on ambulatory blood pressure lowering effect of CPAP in patients with obstructive sleep apnea and nocturnal hypertension.

Objective: In a randomised controlled trial, we investigated the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in patients with moderate-severe obstructive sleep apnoea syndrome (OSAS, an apnoea-hypopnoea index, AHI of 15 or higher) and nocturnal hypertension (night-time systolic/diastolic BP ≥120/70 mmHg).Methods: Sixty patients were randomly assigned to CPAP or sham CPAP, while maintaining their antihypertensive treatment. Ambulatory BP monitoring was performed at baseline (first run-in visit) and the end of follow-up. Clinic and home BP were measured at baseline and each of the monthly follow-up visits.Results: Of the 60 patients, 47 completed the 3-month study. CPAP (n = 26), compared with sham CPAP (n = 21), slightly and non-significantly reduced 24-h systolic/diastolic BP by -2.8/-2.5 mmHg (p ≥ 0.27), with a slightly greater between-group difference in the daytime (-4.0/-2.8 mmHg, p ≥ 0.29) than night-time (-0.2/-1.5 mmHg, p ≥ 0.50). The CPAP treatment did not significantly influence clinic or home BP during follow-up (p ≥ 0.27). Nonetheless, simple and partial correlation analyses showed that the ambulatory BP lowering effect was dependent on the daytime pulse rate at baseline (r ≥ 0.47, p ≤ 0.01). In patients with a daytime pulse rate greater than 85 beats/min, the mean changes in daytime systolic BP were significantly greater in the CPAP (n = 10) than sham CPAP group (n = 11), with a between-group mean difference of -10.1 mmHg (p = 0.048).Conclusions: The CPAP treatment did not show significant ambulatory BP lowering effect in patients with moderate-severe OSAS and nocturnal hypertension. However, it may be effective in lowering daytime BP in patients with a faster pulse rate.

Legionella pneumophila as Cause of Severe Community-Acquired Pneumonia, China.

We report a case of community-acquired pneumonia in a patient in China. We verified Legionella pneumophila infection through next-generation sequencing of blood, sputum, and pleural effusion samples. Our results show the usefulness of next-generation sequencing and of testing different samples early in the course of illness to identify this bacterium.

Antimicrobial resistance and risk factors for mortality of pneumonia caused by Klebsiella pneumoniae among diabetics: a retrospective study conducted in Shanghai, China.

Purpose: To investigate antimicrobial resistance and risk factors for mortality of Klebsiella pneumoniae (KP) pneumonia in diabetics and nondiabetics. Patients and methods: A retrospective study was conducted among inpatients of KP pneumonia via electronic medical records in a territory hospital between January 2016 and June 2018. Antimicrobial resistance in KP pneumonia was compared between diabetics and nondiabetics. Independent risk factors for mortality in KP pneumonia were identified by univariate and multivariate logistic regression among diabetics and nondiabetics separately. Results: In this study, 456 patients with KP pneumonia were included. There were 156 cases with diabetes and 300 without diabetes. KP showed a lower antimicrobial resistance to a multitude of antimicrobials in pneumonia among diabetics than nondiabetics, namely aztreonam, cefotetan, sulperazone, meropenem, amikacin, tobramycin, sulfamethoxazole, and fosfomycin. In addition, carbapenem-resistant Klebsiella pneumoniae (CRKP) was more prevalent among nondiabetics than diabetics who were admitted to intensive care unit (ICU) (63.0% vs 45.1%, P = 0.038). Multivariable analysis showed that independent risk factors for in-hospital mortality (IHM) in KP pneumonia among diabetics differed from that among nondiabetics as well. Independent predictors for IHM of KP pneumonia among diabetics were male (OR: 5.89, 95% CI: 1.34-25.93, P = 0.019), albumin (ALB) < 35 g/L (OR: 7.00, 95% CI: 2.02-24.28, P = 0.002), bloodstream infection (BSI) (OR: 21.14, 95% CI: 3.18-140.72, P = 0.002), and invasive ventilation during hospitalization (OR: 8.00, 95% CI: 2.99-21.42, P < 0.001). In nondiabetics, independent predictors were higher CURB-65 score (OR: 1.92, 95% CI: 1.29-2.86, P = 0.001), CRKP (OR: 2.72, 95% CI: 1.07-6.90, P = 0.035), BSI (OR: 4.98, 95% CI: 1.34-18.50, P = 0.017), and ICU admission (OR: 4.06, 95% CI: 1.57-10.47, P = 0.004). Conclusion: In KP pneumonia, diabetics showed lower antimicrobial resistance and different independent risk factors for mortality compared with nondiabetics, in line with previous studies. Importantly, further attention should be paid on rational and effective antibiotic and supportive treatments in order to reduce mortality without aggravating antimicrobial resistance and metabolic damage among diabetics.

Glucagon-like peptide-1 receptor (GLP-1R) signaling ameliorates dysfunctional immunity in COPD patients.

BACKGROUND: The glucagon-like peptide-1 receptor (GLP-1R) agonist - liraglutide (LIR) - is an insulin secretagogue for the treatment of diabetes and has been proven to have therapeutic potential in the treatment of COPD. Evidence suggested that activating GLP-1R signaling might have immunomodulating and anti-inflammatory effects. COPD is characterized by dysregulation of immunity, oxidative stress, and excessive inflammation responses. The aim of this study was to investigate whether GLP-1R signaling had a regulatory role in COPD immunity. PATIENTS AND METHODS: Fifty-seven COPD patients in a stable condition and 51 age-, sex-, and smoking history-matched non-COPD subjects provided blood samples for isolation of peripheral blood mononuclear cells (PBMCs). GLP-1R expression was measured, and its association with clinical parameters and plasma cytokines was analyzed. T cell function was assessed at baseline and after regulating GLP-1R expression. RESULTS: GLP-1R expression decreased in circulating PBMCs of COPD patients, which was associated with decreased interferon (IFN)-γ expression. Reduced IFN-γ production stimulated by phytohemagglutinin (PHA) and increased programmed cell death protein 1 (PD-1) expression on T cells were observed in COPD patients compared with non-COPD subjects. Treatment with LIR could upregulate the GLP-1R expression, and this was observed to restore the antigen-stimulated IFN-γ production and downregulate PD-1 expression in T cells. CONCLUSION: PBMCs of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities that could be rescued by LIR treatment.

PERK/eIF2α contributes to changes of insulin signaling in HepG2 cell induced by intermittent hypoxia.

AIMS: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with abnormal glucose metabolism. Nowadays, endoplasmic reticulum (ER) stress emerges as an important mechanism underlying the development of type 2 diabetes mellitus (T2DM). However, it remains unclear that intermittent hypoxia (IH) could induce ER stress, resulting in abnormality of glucose metabolism. Thus, in the current study we explore the changes of insulin signaling under IH and the role of ER stress underlying these changes. MAIN METHODS: HepG2 cells were exposed to room air (RA) or IH for 8h, 16h and 24h respectively. Oxygen concentration in IH groups was in a dynamic cycle from 21% to 1% every 5min, while it remained at 21% in RA groups. Insulin was added into cell culture medium for AKT and p-AKT measurement. In another experiment set, HepG2 cells were pre-cultured with 4-PBA prior to IH or RA exposure. Expression of AKT, p-AKT, p-JNK, p-IRE1, p-PERK and p-eIF2α was examined by Western Blot. KEY FINDINGS: Compared with RA, p-AKT expression in HepG2 cells under IH for 24h was significantly lower even with insulin treatment. Expression of p-JNK, p-IRE1, ATF6, p-PERK and p-eIF2α were upregulated. p-AKT level in HepG2 with 4-PBA preculture under IH was restored. p-PERK and p-eIF2α expression in HepG2 cells in IH groups with 4-PBA preculture were inhibited while levels of p-JNK and p-IRE1 remained unchanged. SIGNIFICANCE: IH, the hallmarker of OSAHS, could disturb insulin signaling via activating PERK/eIF2α.