Elevated thrombin generation levels in the left atrial appendage in patients with atrial fibrillation.

Background: Atrial Fibrillation (AF) is the most common sustained tachi-arrhythmia. Thrombus formation in the left atrial appendage (LAA) increases the risk of stroke and systemic embolism in patients with AF. Objectives: The aim of this study was to compare thrombin generation in the LAA to the LA among patients with AF. Methods: A cross-sectional study of consecutive patients with AF undergoing pulmonary veins catheter ablation. Blood samples from the femoral vein (FV), right atrium (RA), left atrium (LA), and LAA were collected during the catheter ablation procedures. Thrombin generation was assessed by a Calibrated Automated Thrombogram. The LAA-calibrated automated thrombogram parameters were compared with the RA, LA, and FV. Results: A total of 47 consecutive patients were enrolled in the study. The endogenous thrombin potential and peak height were significantly higher in the LAA compared with the LA, the mean differences and 95% CI between the LA and LAA were -378.9 (-680.5, -77.2) (nM∗min) and -66.7 (-119.6, -13.8) (nM) in the endogenous thrombin potential and peak height respectively. Conclusion: In patients with AF undergoing catheter ablation, the LAA demonstrated increased thrombin generation compared with the LA. This finding might contribute to the understanding of why the LAA is more predisposed to thrombus formation than the LA. Clinical Trials Registration: NCT03795883.

Role of a thrombin generation assay in the prediction of infection severity.

Thrombin plays a central role in sepsis pathophysiology. The correlation of thrombin generation (TG) assays with infection severity and prognosis, and whether it can be used as a clinical tool, have been poorly explored and are the subjects of our research. We recruited 130 patients with systemic infection between 2016 and 2019. Patients were divided according to infection severity by using the sequential organ failure assessment (SOFA) and quickSOFA (qSOFA) scores. The hemostatic state was analyzed by Calibrated Automated Thrombogram. The primary end points were TG values and the secondary end point was in-hospital mortality. Patients with qSOFA ≥ 2 had a longer lag time (5.6 vs. 4.6 min) and time to peak (8 vs. 6.9 min) than those with lower scores (p = 0.014 and 0.01, respectively). SOFA ≥ 2 had a longer lag time (5.2 vs. 4.3 min), time to peak (7.5 vs. 6.7 min) and lower endogenous thrombin potential (ETP) (1834 vs. 2015 nM*min), p = 0.008, 0.019, and 0.048, respectively. Patients who died (11) had lower ETP (1648 vs. 1928 nM*min) and peak height (284 vs. 345 nM), p = 0.034 and 0.012, respectively. In conclusion TG assays may be a valuable tool in predicting infection severity and prognosis.

Thrombin generation's role in predicting coronary disease severity.

BACKGROUND: Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity. METHODS: In this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography. RESULTS: From April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively). CONCLUSION: In patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity.

Low venous thromboembolism incidence in high risk medical patients in an Israeli hospital. Can risk assessment be extrapolated to different populations?

BACKGROUND: Guidelines recommend venous thromboembolism (VTE) prophylaxis in hospitalized medical patients with Padua prediction score (PPS) ≥4 points. This recommendation is based on the high risk of symptomatic VTE observed among these patients in the Italian PPS derivation study, and the fivefold risk reduction with VTE-prophylaxis. This study aims to assess the incidence of VTE in high risk medical patients in a medium sized hospital in Israel. METHOD: In this retrospective cohort study, data was collected of all medical patients hospitalized between January and June 2014. Patients were classified into low and high risk groups according to their PPS score, and according to whether they received anticoagulant thromboprophylaxis for VTE. Patients were further randomly selected to compare high risk patients that did or did not receive anticoagulant thromboprophylaxis. We further compared VTE incidence in high and low risk patients not treated with thromboprophylaxis. A search was conducted for diagnoses of venous thromboembolism and death during hospitalization and the following 90 days. RESULTS: 568 high risk patients (PPS ≥4 points) were included, 284 treated with prophylactic anticoagulation and 284 not. There were no VTE events in either group. There was no difference in mortality. A total of 642 non anticoagulated patients were randomly selected, 474 low risk and 168 high risk. There were no VTE events in either group. CONCLUSIONS: The risk of VTE appears to be very low in our study, suggesting that among medical patients with PPS ≥4, the risk of VTE may differ dramatically between populations.

Appetite and ghrelin levels in iron deficiency anemia and the effect of parenteral iron therapy: A longitudinal study.

BACKGROUND: Iron deficiency anemia (IDA) is associated with decreased appetite. The ghrelin hormone is one of the major regulators of appetite. OBJECTIVES: To evaluate appetite and ghrelin levels in patients with IDA, and to investigate the change in appetite and ghrelin following intravenous iron therapy. METHODS: A total of 56 IDA patients and 51 controls were included in the study. Both appetite and ghrelin were assessed at baseline and following intravenous iron therapy. These were assessed at corresponding time intervals in the control group. Appetite was assessed by the SNAQ score (Simplified Nutritional Appetite Questionnaire) and fasting ghrelin levels were assessed by acylated ghrelin (AG), unacylated ghrelin (UAG) and their respective ratio AG/UAG. RESULTS: IDA patients had significantly lower SNAQ scores, yet higher AG levels and higher AG/UAG ratios compared to healthy controls; the mean SNAQ scores were 12.56 ± 3.45 and 16.1 ± 2, respectively (P<0.01); the median AG levels were 57.5 pg/ml and 43 pg/ml respectively (P = 0.007); and the median AG/UAG ratios were 0.48 and 0.25 respectively (P = 0.04). On multivariate linear regression analysis, IDA remained independently associated with decreased SNAQ score (ß = -0.524, P<0.001) and increased acylated ghrelin (ß = 0.289, P = 0.013). After IDA was treated, SNAQ scores increased significantly by a mean of 2 points. AG and AG/UAG ratios decreased significantly by a mean of -18.44 pg/ml and -0.2 respectively. The control group showed no significant change in SNAQ scores or ghrelin at corresponding time intervals. CONCLUSIONS: IDA patients have a reduced appetite and paradoxically elevated ghrelin hormone activity compared to healthy controls. Treating IDA enhances appetite and lowers ghrelin levels. Future studies are needed to explore the mechanism of this paradoxical ghrelin activity.

Does infection prolong the QT interval?

BACKGROUND: The corrected QT (QTc) interval is a strong predictor of ischaemic heart disease and cardiovascular mortality. It may trigger lethal arrhythmias and sudden death. Risk factors include electrolyte disorders, medications, prior cardiovascular disease and genetic predisposition. We previously demonstrated that QTc intervals are prolonged in patients hospitalised with pneumonia, regardless which antibiotics were given. It is unclear whether QTc prolongation is associated with pneumonia itself or whether it occurs with other infections. AIMS: To investigate any association between hospitalisation for infection and QTc prolongation. METHODS: We enrolled 169 patients, 160 of whom were used for analysis. QTc was measured in seconds by routine electrocardiogram (ECG) on admission. Subsequently, daily ECG were performed for 3 days, or until discharge (whichever occurred sooner). When clinically significant QTc prolongation was detected, possible causes were investigated. RESULTS: Clinically significant prolongation was not observed in any patient. The QTc was slightly longer in patients hospitalised for pneumonia or upper respiratory tract infections on admission. It was also prolonged in men, in patients with ischaemic heart disease, hypertension, history of cerebrovascular accident or cancer. A very slight trend for prolongation was observed between the first and second day of monitoring, however it later returned to baseline levels. Nearly 54% of study participants had positive systemic inflammatory response syndrome scores, however no association was detected between their score and baseline QTc, or any subsequent prolongation. CONCLUSIONS: We found no association between hospitalisation due to infection and prolongation of the QTc interval.

Role of thrombin generation assays in the diagnosis of acute myocarditis and non-ST myocardial infarction.

Myocarditis and myocardial infarction share a common clinical characteristics despite significant differences in etiology and pathogenesis. Current guidelines recommend using cardiac magnetic resonance imaging (MRI) or endocardial biopsy for a definite diagnosis; however, these guidelines are not fully implemented due to the high cost and low availability. We used a thrombin generation assay and simple blood test to characterize both diseases. We conducted a cross-sectional study from April to December 2018. Patients with initial clinical suspicions of non-ST elevation myocardial infarction (NSTEMI) or myocarditis were eligible. All patients were recruited prior to anticoagulant treatment. Patients in both groups underwent acceptable standard clinical evaluation. Twenty-eight patients were enrolled; 12 patients in the NSTEMI group and 16 in the myocarditis group. Patients in the NSTEMI group were significantly older than those in the myocarditis group (64.25 ± 9.67 vs. 37.94 ± 19.66 years, p < 0.01, respectively) with a higher prevalence of hyperlipidemia, diabetes mellitus, and ischemic heart disease (p < 0.01 for all). There was no difference between the groups regarding INR, PT, aPTT, and serum levels of creatinine, urea, CPK, troponin, and fibrinogen. Endogenous thrombin potential (ETP), which represents the total thrombin concentration in the plasma, was significantly higher in the myocarditis group than in the NSTEMI group (2091.88 ± 336.41 vs. 1860.75 ± 438.02 nM × min, p < 0.03). Myocarditis and myocardial infarction have a different pattern of thrombin generation Thrombogram. The myocarditis group had significantly higher plasma ETP than the NSTEMI group. This finding requires further evaluation to define a numerical threshold, thus avoiding invasive or expensive assessment of myocarditis.

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia: A Rare Case Report from Nephrology.

BACKGROUND Tumor lysis syndrome is common in hematological malignancy, but less frequent in chronic and solid tumors. Almost always it is observed after chemotherapy or radiotherapy initiation, but rarely occurs spontaneously. CASE REPORT A 89-year-old female with stable chronic lymphocytic leukemia was admitted to the hospital because of worsening dyspnea and dry cough. Her vital signs were normal, except for sinus tachycardia. On physical examination, she appeared distressed, dyspneic, sweaty but afebrile, anxious, but alert and well oriented. Lung examination revealed reduced air entry with bibasilar crackles. No peripheral edema was seen, pulses were normal, and no signs of deep vein thrombosis were observed. Laboratory analysis revealed leukocytosis; but normal hematological and biochemical parameters. Intravenous (IV) furosemide and antibiotics (IV ceftriaxone and orally azithromycin) were started along with steroid therapy (methylprednisolone 62.5 mg, IV). The treatment with steroids lasted for 1 day only, and in the following day, the patient was switched to prednisone (20 mg/day orally) for only 1 additional day. White blood cell count increased on day 1, 2 and 3 after admission, along development of hyperuricemia, hyperphosphatemia, hyperkalemia, acute renal failure and elevated troponin levels. Hemodiafiltration/hemodialysis was initiated, and the patient was discharged after serum concentrations of these electrolytes and kidney function were restored. One month after discharge, the patient denied any malaise and was at stable condition. CONCLUSIONS Herein, we present a case of a patient with stable chronic lymphocytic leukemia, who developed spontaneous tumor lysis syndrome after short low dose of steroid therapy. This case highlights the importance of including spontaneous tumor lysis syndrome in the differential diagnosis of any acute renal failure in the constellation of any malignancy.

Calibrated Automated Thrombogram During Pregnancy in Unexplained Recurrent Miscarriages: A Pilot Study.

BACKGROUND: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia. OBJECTIVES: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages. METHODS: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia. RESULTS: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05). CONCLUSIONS: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Enhanced thrombin generation in patients with arterial hypertension.

BACKGROUND: Arterial hypertension is associated with greater risk of cardiovascular diseases and thrombotic complications, suggesting that hypertension is a prothrombotic state. OBJECTIVES: To investigate the relationship between arterial hypertension and thrombin generation, and between blood pressure level and thrombin generation in hypertensive patients. METHODS: A total of 165 hypertensive patients and 47 healthy adults controls were include in the study. Thrombin generation was assessed in both groups by the Calibrated Automated Thrombogram (CAT) method. Ambulatory blood pressure monitoring (ABPM) was also performed for all patients in the hypertensive group. RESULTS: Hypertensive patients had significantly higher levels of ETP and peak heights compared to healthy controls; means of ETP 1720.6 ±â€¯267 and 1544.7 ±â€¯302, respectively (P < 0.001) and means of peak height were 297.26 ±â€¯48 and, 273 ±â€¯53, respectively (P < 0.001). On multivariate linear regression analysis, hypertension remained independently associated with increased ETP (ß = 0.185, P = 0.047). Analysis restricted to the hypertensive group with ABPM measurement showed statistically significant correlations between all measures of diastolic blood pressure (DBP) and ETP, and multivariate analysis showed that awake DBP was significantly associated with ETP (ß = 0.194 for each 1-mm Hg increase in awake DBP, P = 0.012). Furthermore, hypertensive patients with cardiovascular complications had statistically elevated levels of peak height compared to hypertensive patients without cardiovascular complications. CONCLUSIONS: Hypertensive patients possess enhanced thrombin generation compared healthy controls. Diastolic blood pressure level is independently correlated with increased thrombin generation in hypertensive patients. These findings suggest that arterial hypertension is a prothrombotic state.

Intravenous iron treatment reduces coagulability in patients with iron deficiency anaemia: a longitudinal study.

Although many case reports and observational studies have reported a correlation between iron deficiency anaemia (IDA) and thrombotic events, the mechanism for this is poorly understood. To evaluate this, we examined the change in coagulability in patients receiving treatment for IDA. Adult patients with IDA were recruited for this study and treated with intravenous iron. The change in coagulability was assessed by thrombin generation using the calibrated automated thrombogram method. The change in factor VIII (FVIII) activity was later examined as a possible link. Forty-eight participants received intravenous iron and were included in this study. After treatment with intravenous iron, endogenous thrombin potential and peak height decreased in IDA patients by a mean of 122·4 nmol/l/min (95% confidence interval [CI]: 17·9-227, P = 0·023) and 51·9 (95% CI: 26·6-77·2, P < 0·001) respectively. Time to peak (peak time) increased by a mean of 23·6 s (95% CI: 5·4-41·9, P = 0·012). FVIII activity was reduced by a mean of 9·6% (95% CI: 2·54-16·7, P = 0·009). In conclusion, treating IDA reduces the blood's coagulability, as evidenced by the change in thrombin generation and FVIII activity levels. No correlation was found between the degree of iron deficiency correction and thrombogram parameters.

The Prevalence of Thrombophilia in Women With Recurrent Fetal Loss and Outcome of Anticoagulation Therapy for the Prevention of Miscarriages.

OBJECTIVE: To estimate the prevalence of thrombophilia in women with recurrent miscarriages and to assess the effect of antithrombotic therapy. DESIGN: A retrospective cohort study between the years 2004 and 2010. SETTING: A hypercoagulation community clinic in northern Israel. PATIENTS: Four hundred ninety pregnant women referred for thrombophilia screening. MAIN OUTCOME MEASURES: Screening results for thrombophilia and antithrombotic treatment with enoxaparin, aspirin, or both and pregnancy outcomes. RESULTS: The most common thrombophilia in our study group was factor V Leiden mutation with a prevalence of 20.9% followed by protein S deficiency with a prevalence of 19%. Live birth rate was higher in the group of women who received enoxaparin regardless of whether a specific thrombophilia could be found. This finding was more pronounced in women who had ≥4 miscarriages. CONCLUSION: The prevalence of thrombophilia was higher in our study group than in the general population. Furthermore, treatment with enoxaparin might improve the rate of live births in women with or without evidence of thrombophilia, especially in women with ≥4 miscarriages.

Portal Vein Thrombosis and Thrombocytopenia in Eosinophilic Granulomatosis with Polyangiitis: A Paradox?

A 36-year-old woman with eosinophilic granulomatosis with polyangiitis (EGPA) presented with necrotic skin lesions and pulmonary infiltrates. There was eosinophilic vasculitis on skin biopsy, and substantial tissue eosinophilia in her bone marrow. She had unexplained worsening thrombocytopenia, which prompted a thrombophilia work-up. However, abnormalities in liver enzymes led to the extraordinary finding of portal vein thrombosis. Thrombocytopenia resolved with treatment with low molecular weight heparin. This case highlights the risk of hypercoagulability in eosinophilia specifically, and in EGPA. We suggest that thrombosis should be ruled out in all cases of EGPA. LEARNING POINTS: Eosinophilia is a hypercoagulable state.Thrombocytopenia is not part of eosinophilic granulomatosis with polyangiitis (EGPA) and may herald thrombosis.Thromboembolism should be ruled out in the setting of EGPA with eosinophilia.Prompt diagnosis can prevent unnecessary procedures.

Pattern of Blood Pressure Response in Patients With Severe Asymptomatic Hypertension Treated in the Emergency Department.

Severe asymptomatic hypertension (SAH) is a common cause of emergency department (ED) visits. Despite recommendations against using short-acting blood pressure (BP)-lowering drugs in the ED, it is still a common practice. The authors characterized BP response in the ED utilizing 24-hour ambulatory BP monitoring (ABPM). Patients with SAH who were not admitted to the hospital were recruited. All patients underwent 24-hour ABPM. A total of 21 patients (14 females) with a mean age of 58±16 years were studied. BP decreased from 199±16/101±17 mm Hg to 154±34/83±23 mm Hg after 5 hours but then rose to 174±25/94±17 mm Hg after 19 hours. In 17 patients, systolic BP was ≥180 mm Hg after 6.7±5.3 hours. Two patients experienced severe hypotension (systolic BP <90 mm Hg). Thus, data from a single site in Israel support the current recommendations for management of SAH in the ED.

Role of antibiotics for treatment of inflammatory bowel disease.

Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.

Could a Coagulation Nurse Liaison Improve Compliance With Venous Thromboembolism Prophylaxis in Medical Patients?

Medical patients worldwide are undertreated with venous thromboembolism prophylaxis. Our hypothesis was that the rate of prophylactic anticoagulation therapy for high-risk patients would improve with the use of a coagulation nurse liaison. Six months after appointing a nurse for this role, prophylaxis rates significantly improved, and patients were more likely to receive appropriate thromboprophylaxis. A coagulation nurse liaison substantially improves thromboprophylaxis in a medical ward.

The Effect of Vitamin D Supplementation on Thrombin Generation Assessed by the Calibrated Automated Thrombogram.

Observational and in vitro studies suggest that vitamin D may have antithrombotic activity. This study aimed to examine the relationship between vitamin D supplementation and thrombin generation. Serum 25-hydroxyvitamin D (25(OH)D) and thrombin generation parameters were measured in 73 healthy volunteers. Participants with serum 25(OH)D <50 nmol/L (n = 53) were treated with vitamin D3and tested for 25(OH)D and thrombin generation at the end of treatment. Lag time and time to peak decreased after treatment by a mean of -0.49 ± 0.51 minute (P< .001) and -0.76 ± 0.70 minute (P< .001), respectively, whereas endogenous thrombin potential and peak height increased after treatment by a mean of 170.1 ± 339.8 nmol/L minute (P= .001) and 34.2 ± 47.8 nmol/L (P< .001), respectively. Treatment with vitamin D supplementation seems to have prothrombotic effect in patients with vitamin D insufficiency. These findings should be interpreted with caution and need to be replicated in future studies.

Azithromycin is not associated with QT prolongation in hospitalized patients with community-acquired pneumonia.

PURPOSE: Large data-based studies have reported excess cardiovascular mortality in high-risk patients treated with azithromycin, but whether or not azithromycin causes QT prolongation remains controversial. The purpose of this study was to examine the association of azithromycin treatment on QT prolongation in a cohort of patients hospitalized with community-acquired pneumonia (CAP) METHODS: One-hundred twenty-two hospitalized patients with CAP were enrolled in the study. We compared the baseline QTc, with daily post antibiotic QTc. Other risk factors for QT prolongation such as medication or electrolyte abnormalities were recorded. RESULTS: Ninety (73.8%) patients were treated with azithromycin (usually in combination with ceftriaxone), and 32 (26.2%) patients with other antibiotics (ampicillin-clavulanate, chloramphenicol, doxcycline, or ceftriaxone); 72.1% (88) of the cohort experienced QT lengthening; 72.7% with QT lengthening had a normal baseline QTc. Azithromycin was not associated with the post-antibiotic QTc. Wide (pathological) post-antibiotic QTc was associated with the pneumonia score. Every 10-point increase in the pneumonia score raised the risk for a pathological post antibiotic QTc by 1.249 (95%CI: 1.050-1.486). Analysis of patients with non-pathological baseline QTc revealed that pathological post-antibiotic QTc was only associated with previous stroke and not with the type of antibiotic. CONCLUSIONS: Azithromycin treatment was not associated with QT prolongation in patients with severe CAP. Nonetheless, in a large majority of hospitalized CAP patients, QT prolongation and pathological QTc develop regardless of the antibiotic used, especially in patients with previous stroke or a higher pneumonia score.

Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management.

Urinary tract infections are more common, more severe, and carry worse outcomes in patients with type 2 diabetes mellitus. They are also more often caused by resistant pathogens. Various impairments in the immune system, poor metabolic control, and incomplete bladder emptying due to autonomic neuropathy may all contribute to the enhanced risk of urinary tract infections in these patients. The new anti-diabetic sodium glucose cotransporter 2 inhibitors have not been found to significantly increase the risk of symptomatic urinary tract infections. Symptoms of urinary tract infection are similar to patients without diabetes, though some patients with diabetic neuropathy may have altered clinical signs. Treatment depends on several factors, including: presence of symptoms, severity of systemic symptoms, if infection is localized in the bladder or also involves the kidney, presence of urologic abnormalities, accompanying metabolic alterations, and renal function. There is no indication to treat diabetic patients with asymptomatic bacteriuria. Further studies are needed to improve the treatment of patients with type 2 diabetes and urinary tract infections.

The association between red cell distribution width and stroke in patients with atrial fibrillation.

OBJECTIVE: Red cell distribution width is associated with increased risk of cardiovascular morbidity and mortality. We aimed to assess its association with stroke in patients with atrial fibrillation. METHODS: By using the computerized database of the largest Health Maintenance Organization in Israel, we identified a cohort of adults with atrial fibrillation diagnosed before January 1, 2012. Eligible subjects were not taking anticoagulants at baseline and had at least 1 blood cell count performed in 2011 (41,140 subjects). The cohort was followed for the first occurrence of stroke until December 31, 2012. RESULTS: Overall, 1692 subjects developed stroke during 38,024 person-years of follow-up (stroke rate, 4.45 per 100 person-years). Stroke incidence rate increased across red cell distribution width quartiles: 3.26, 3.71, 5.01, and 6.05 per 100 person-years in the lowest (≤ 13.4%), second (13.4%-14.1%), third (14.1%-15.0%), and highest (>15%) red cell distribution width quartiles, respectively. On multivariate analysis adjusting for Congestive heart failure, Hypertension, Age ≥ 75, Diabetes, and Prior Stroke or TIA (doubled) (CHADS2) score risk factors, the hazard ratio for stroke was 1.29 (95% confidence interval, 1.17-1.42) in subjects with red cell distribution width >14.5% compared with those with values ≤ 14.5% and was similar in subjects with and without anemia. When analyzed as quartiles, the hazard ratio for stroke was 1.33 (confidence interval, 1.15-1.53) in the highest quartile compared with the lowest quartile and was similar in subjects with and without anemia. The area under the receiver operating characteristic curve was 0.598 for (CHADS2) score and increased to 0.618 when red cell distribution width was included in the model (P < .001). CONCLUSIONS: Red cell distribution width is directly associated with the risk of stroke regardless of anemia status and improves the predictive accuracy for stroke in patients with atrial fibrillation.