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BACKGROUND: Cholera has harmful effects on the fetus but safety data on the oral cholera vaccine in pregnant women are controversial. OBJECTIVES: We conducted the first meta-analysis of studies in pregnant women comparing the effect of oral cholera vaccination on pregnancy outcomes with unvaccinated women. Outcomes of interest were adverse pregnancy outcome, miscarriage, stillbirth, preterm delivery, low birthweight, abortion and malformation. SEARCH STRATEGY: The search was run in MEDLINE/PubMed, SCOPUS and Embase databases from inception up to December 2019. SELECTION CRITERIA: Inclusion criteria were: (1) studies that investigated the association between oral cholera vaccines and adverse pregnancy outcomes; (2) studies that reported outcomes with appropriate estimates; and (3) studies that contained an unvaccinated control group. DATA COLLECTION AND ANALYSIS: A random-effects model (DerSimonian and Laird) was run to evaluate the overall treatment effect (relative risk, RR). The PRISMA statement was followed in reporting this meta-analysis. MAIN RESULTS: Five studies included in meta-analysis with 5584 women (2920 exposed and 2664 not exposed). No significant increase in adverse pregnancy outcome (RR 1.03, 95% CI 0.79-1.34), miscarriage (RR 1.15, 95% CI 0.84-1.57) or stillbirth (RR 1.11, 95% CI 0.69-1.80) following cholera vaccine administration was found compared with control group. There was also no association with an increased risk of preterm delivery (RR 0.61, 95% CI 0.35-1.06) low birthweight (RR 0.84, 95% CI 0.56- 1.26), accidental abortion (RR 1.02, 95% CI 0.77-1.35) or malformation (RR 0.70, 95% CI 0.22-2.25). CONCLUSIONS: This study shows no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm. TWEETABLE ABSTRACT: There is no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm.

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PURPOSE: Breast cancer is a leading cause of cancer mortality in developed countries. We performed a meta-analysis of randomized clinical trials to investigate the effect of metformin on biomarkers associated with breast cancer outcomes and to explore the dose-response relationship. METHODS: A systematic search was performed from onset of the database to January 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane library to identify randomized clinical trials investigating the impact of metformin on insulin, glucose, CRP, leptin, body mass indices (BMI), cholesterol, Ki-67, and Homeostatic Model Assessment for Insulin-Resistance (HOMA-IR). Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI) using a random-effects models. RESULTS: Nine studies providing 1,363 participants were included in the meta-analysis. Pooled results showed a significant reduction in insulin (WMD: - 0.99 U/ml, 95% CI - 1.66, - 0.33), glucose (WMD: - 1.78 ml/dl, 95% CI - 2.96, - 0.60), CRP (WMD: - 0.60 mg/l, 95% CI - 0.88, - 0.33), HOMA-IR (WMD: - 0.45, 95% CI - 0.77, - 0.11), leptin (WMD: - 2.44 ng/ml, 95% CI - 3.28, - 1.61), BMI (WMD: - 0.55 kg/m2, 95% CI - 1.00, - 0.11), and Ki-67 (WMD: - 4.06, 95% CI - 7.59, - 0.54). Results of the subgroup analyses showed that insulin, glucose, and BMI decreased more significantly when the duration of administering metformin intervention was above 4 weeks. We did not observe non-linear changes in the dose-response relationship between metformin and biomarkers as outcomes. CONCLUSIONS: Breast cancer patients receiving metformin as treatment for diabetes showed significant reduction in levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67.

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BACKGROUND AND AIM: Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP). METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to October 2018 in the following databases: PubMed, Scopus, and Cochrane. RCTs that investigated the effect of folate on CRP were included in the present study. Data were combined with the use of generic inverse-variance random-effects models. Statistical heterogeneity between studies was evaluated using Cochran's Q-test. Ten RCTs (1179 subjects) were included in the present meta-analysis. Pooled analysis results showed that folate supplementation significantly lowered the serum CRP level (weighted mean difference (WMD): -0.685 mg/l, 95% CI: -1.053, -0.318, p < 0.001). However, heterogeneity was significant (I2 = 96.7%, p = 0.000). Stratified analyses indicated that sex, intervention period, and type of study population were sources of heterogeneity. Following analysis, results revealed that the greatest impact was observed in women (WMD: -0.967 mg/l, 95% CI: -1.101, -0.833, p = 0.000), patients with type 2 diabetes mellitus (WMD: -1.764 mg/l, 95% CI: -2.002, -1.526, p = 0.000), and intervention period less than 12 weeks (WMD: -0.742 mg/l, 95% CI: -0.834, -0.650, p = 0.000). CONCLUSION: This meta-analysis suggested that folic acid supplementation could significantly lower the serum CRP level. Folic acid leads to greater CRP lowering effect in women, patients with T2DM, and those with less than 12-week intervention.

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OBJECTIVE: The aim of this multicentre prospective study was to analyse microbial pathogens cultured from an infected wound. METHODS: The study was performed in the emergency rooms of 10 public hospitals. All adult patients with a clinical diagnosis of cellulitis after a wound in the upper or lower extremities were included. Cultures were obtained with swabs from infected lesions. Micro-organisms cultured were identified by the usual methods and susceptibility testing was performed. RESULTS: The study population consisted of 214 patients, 153 men and 61 women, with a mean (SD) age of 40 (10) years. Wound cultures remained sterile in 28 cases and infected with micro-organisms in 186 cases. Of the 186 positive cultures, three were not identified. Of the 183 remaining cultures, one micro-organism was present in 132 patients (62%) and several micro-organisms in 51 patients (24%). A total of 248 micro-organisms were isolated in 183 patients. Staphylococcus and streptococcus were the most frequently isolated micro-organisms (56% and 21% respectively) followed by Gram negative bacilli (18%). Determination of the susceptibility to the antibiotics commonly used to treat wound infections showed resistance in some cases. CONCLUSION: These results support the need always to take culture specimens from infected wounds for microbiological evaluation and antibiotic susceptibility determination, so that adapted chemotherapy can be prescribed.

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Circuits on mechanical ventilators with cascade humidifiers are routinely changed every day or every other day, although humidifying cascades have been considered unlikely to increase the risk of respiratory infection because they do not generate aerosols. Moreover, changing ventilator tubings every 24 rather than every 48 h increases the risk of ventilator-associated pneumonia. To study the effects of ventilator circuit changes on the rate of nosocomial pneumonia and on patient and circuit colonization, 73 consecutive patients requiring continuous mechanical ventilation for more than 48 h were randomly assigned to either ventilator circuit changes every 48 h (Group 1, n = 38) or no change (Group 2, n = 35). Patients dying or being weaned before 96 h were not analyzed (Group 1 n = 3; Group 2 n = 7; leaving Group 1 n = 35 and Group 2 n = 28; p = 0.13). Ventilator-associated pneumonia was defined as the occurrence during mechanical ventilation or within 48 h after weaning of a new and persistent infiltrate on chest X-ray, purulent tracheal secretions, and a positive culture of a protected brush specimen (greater than or equal to 10(3) cfu/ml). Bacterial colonization was assessed every 48 h by quantitative cultures of pharyngeal swab, tracheal aspirate, humidifying cascade, and expiratory tubing trap. The two groups were similar in terms of age, indication for and duration of ventilation, and severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)

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The specific ECG characteristics of metabolic acidosis have not been satisfactorily defined in man. We addressed this question by prospectively studying 14 consecutive patients admitted with metabolic acidosis and without hyperkalemia. Arterial blood gas analysis and serum potassium determinations were performed during acidosis and after its correction. ECGs were recorded at the same times. Mean pHa increased from 7.11 +/- 0.05 to 7.40 +/- 0.01 (p less than .001) in response to an increase in total CO2 content from 6.8 +/- 1.4 to 21.2 +/- 0.7 mmol/L (p less than .001). Serum potassium concentration decreased only slightly after correction of the acidosis from 4.2 +/- 0.1 to 3.9 +/- 0.14 mmol/L (p less than .05). T waves were taller during acidosis than after correction (0.68 +/- 0.1 vs. 0.28 +/- 0.04 mV, p less than .001 and 0.64 +/- 0.08 vs. 0.38 +/- 0.04, p less than .005, in precordial leads V2 and V3, respectively). Moreover, the amplitude of T waves in V2 was correlated positively with the arterial concentration of H+ (r = .786, p less than .001) and negatively with the arterial total CO2 content (r = -.71, p less than .005). In addition to their augmented amplitude, T waves were peaked and symmetrical with a narrow base ("tent-shaped"). Thus, metabolic acidosis may be accompanied by an increase in the amplitude of T waves, even in the absence of hyperkalemia.

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The mechanism of hyponatremia associated with pneumonia has not been definitely established. Moreover, renal water excretion was never systematically investigated in cases of pneumonia without hyponatremia. We therefore studied nine consecutive patients breathing spontaneously (nasal oxygen in five), with acute infectious pneumonia and normal plasma sodium concentration. All the patients were previously healthy. Water loads were administered during illness and after recovery. Extracellular fluid volume, arterial blood pressure, PaO2, and PaCO2 were identical during and after pneumonia. By contrast, renal water excretion was markedly impaired during pneumonia and returned to normal values after recovery. This was attested to by a significant decrease in minimum urine osmolality together with significant increases in the percentage of the excreted water load and the maximum free water clearance, after resolution of the pneumonia. Plasma arginine vasopressin values were significantly higher during pneumonia than after recovery despite similar plasma sodium concentrations, both before and after water load. A positive correlation between plasma arginine vasopressin and minimum urine osmolality was found during pneumonia. Thus, impairment in renal water excretion appeared to be due to resetting of the vasopressin osmostat and could not be attributed to any recognized nonosmotic stimulus for vasopressin secretion. On the other hand, these defects varied in severity depending on the extent of the pneumonia and persisted until clearing of alveolar opacities, accounting for their protracted course in some patients. We conclude that water excretion is impaired in most if not in all patients with acute infectious pneumonia (especially if extended), and that the administration of hypotonic solutions should be avoided in these patients.

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