Intravenous doxycycline, azithromycin, or both for severe scrub typhus

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of −13.3 percentage points (95% confidence interval [CI], (21.6 to −5.1; P=0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of −14.8 percentage points (95% CI, −23.1 to −6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, −7.0 to 10.0; P=0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry–India number, CTRI/2018/08/015159.

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Tanakaea radicans Franch. et Savat.

原著和名: イハユキノシタ科名: ユキノシタ科 = Saxifragaceae採集地: 静岡県 静岡市 真富士山麓 (駿河 静岡市 真富士山麓)採集日: 1986/7/10採集者: 萩庭丈壽整理番号: JH036719国立科学博物館整理番号: TNS-VS-98671

Additional file 3: Table S3. of Consensus computational network analysis for identifying candidate outer membrane proteins from Borrelia spirochetes

Orthologous clusters. List of predicted orthologous clusters utilized to generate heat maps. (XLSX 667 kb

Additional file 5: Table S4. of Consensus computational network analysis for identifying candidate outer membrane proteins from Borrelia spirochetes

Servers utilized in this study. List of all servers utilized in the study as well as URLs and references for each server. (DOCX 14 kb

Minimally Invasive Left Ventricular Assist Device Implantation: A Comparative Study

Left ventricular assist device (LVAD) is now a routine therapy for advanced heart failure. Minimally invasive approach via thoracotomy for LVAD implantation is getting popular due to its potential advantage over the conventional sternotomy approach in terms of reduced risk at re-operation due to sternal sparing. We compared the approaches (thoracotomy and sternotomy) to determine the superiority. Minimally invasive approach involved fitting of the LVAD inflow cannula into left ventricle apex via left anterior thoracotomy and anastomosis of outflow graft to ascending aorta via right anterior thoracotomy. In the sternotomy approach, both the procedures were performed via sternotomy. Outcomes in patients after LVAD implantation were compared depending on these approaches for the surgery. Two hundred and five continuous flow LVAD implantations performed between July 2006 and June 2015 at a single center were divided based on surgical approach, that is, sternotomy (n = 180) and thoracotomy (n = 25) groups. There was no significant difference between the groups in relation to patient demographics, preoperative hemodynamic parameters, laboratory markers, or risk factors. There was no significant difference between the groups in terms of postoperative hemodynamic parameters, laboratory markers, bleeding and requirement of blood products, intensive care unit, and hospital stay or complications of LVAD surgery. There were no significant differences in terms of long-term survival (Log-Rank P = 0.953), however, thoracotomy, compared to sternotomy approach, incurred significantly less requirement of temporary right ventricular assist (4 vs. 19.4%, P = 0.041). Minimally invasive bilateral thoracotomy approach for LVAD implantation in addition to benefits of sternal sparing avoids dilatation of right ventricle and reduces chances of right ventricular failure requiring temporary right ventricular assist

The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes

Aims/hypothesis: We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes. Methods: A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as ‘high-risk’ for future albuminuria and the lower two tertiles were deemed ‘low-risk’. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1–Q5) for associations with log10 ACR and ACR risk groups. Results: Greater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2–Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1–Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control. Conclusions/interpretation: Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications