Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial

RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7% vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hematocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea-resistant or intolerant patients with polycythemia vera. This trial was registered at clinicaltrials.gov identifier: 01243944.     

Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group

Purposes

Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity.

Methods

Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay?<?48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification.

Results

Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1–2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15–1.27, p?<?0.001]; maximum lactate level day 1–2: (HR 1.07, 95% CI 1.02–1.12, p?=?0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23–3.03, p?=?0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15–0.50, p?<?0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68–10.54, p?=?0.003), in patients?≥?65 years old (HR 2.59, 95% CI 1.56–4.28, <?0.001) and in those with body mass index (BMI)?<?25 kg/m² (HR 2.11, 95% CI 1.10–4.06, p?=?0.025).

Conclusions

Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged?≥?65 years and with BMI?<?25 kg/m².

     

In Vitro and In Vivo Evaluation of the Thermal Patterns and Lesions of Catheter Ablation with a Microwave Monopole Antenna

BACKGROUND: Radiofrequency (RF) catheter ablation is an effective treatment for supraventricular tachycardia. The effectiveness of the technique is at times limited by the small lesion size produced by RF energy delivery. Previous reports have indicated that microwave energy is capable of producing a larger volume of heated tissue than radiofrequency energy, raising the possibility that microwave energy may offer a potential alternative energy source to radiofrequency for the substrate ablation of certain arrhythmias such as ventricular tachycardia or atrial flutter. METHODS: The present study evaluated the thermal profiles of a monopole microwave antenna delivering energy at 2.45 GHz frequency in a phantom tissue-equivalent material with dielectric and thermal properties similar to myocardium. In addition, microwave catheter ablations were performed in vivo in the ventricles of goats prior to the examination of the lesions. RESULTS: The measured thermal profiles in the phantom revealed that the antenna is capable of producing heating to a temperature associated with myocardial necrosis to a controllable depth that can be more than 8 mm, while the endocardial temperature is maintained relatively low. The ablation volume is significantly reduced but is still effective when there is only a partial contact between the antenna and the tissue surface. In vivo studies on goat models confirmed that the monopole antenna can produce a deep transmural lesion in the left ventricle without causing coagulation or charring on the endocardial surface.     

Understanding breastfeeding behavior: rates and shifts in patterns in Québec.

The study objective was to measure breastfeeding rates and patterns in the Montérégie region of Québec. A survey of 632 mothers of 6-month-old infants was performed, of which 80% initiated breastfeeding, and 68% exclusively breastfed at birth. Breastfeeding rates progressively decreased with time: 63%, 56%, 51%, 44%, 39%, and 32% of mothers breastfed at 1, 2, 3, 4, 5, and 6 months, respectively. Among mothers breastfeeding at a given period, 62%, 57%, 48%, 35%, and 10% of women exclusively breastfed since birth for 1, 2, 3, 4, and 5 months, respectively. Exclusive breastfeeding for 6 months among the 200 women still breastfeeding was practically nonexistent. Introduction of nonhuman milk or solids was primarily responsible for the shift in patterns from exclusive to complementary feeding without passing through predominant breastfeeding. These findings confirm the need to prioritize effective hospital-based and community-based interventions to increase breastfeeding duration and exclusivity in the region.     

Effect of an Enterococcus faecium probiotic on specific IgA following live Salmonella Enteritidis vaccination of layer chickens

Probiotics and immunization are being widely adopted by the poultry industry with the goal of controlling Salmonella enterica. However, the interaction between these two management protocols has been sparsely studied. The present study aimed to understand the role of an Enterococcus faecium probiotic in the production of salmonella-specific IgA in layers immunized with a live vaccine. Four groups were used: “Control” (no vaccine or probiotic); “Probiotic” (which received an E. faecium product); “Vaccine” (immunized with two doses of a live attenuated S. Enteritidis vaccine); and “Vaccine?+?probiotic”. Faecal salmonella-specific IgA was analysed 7 and 20 days post-vaccination (dpv) boost. At 7 dpv, the “Vaccine” and “Vaccine?+?probiotic” groups had similar IgA levels. However, at 20 dpv, IgA levels were two times higher in the “Vaccine?+?probiotic” group compared to the “Vaccine” group. To understand the role of the intestinal microbiota in this finding, bacterial diversity in faeces was analysed by 16S rRNA gene sequencing. The improvement in IgA production in probiotic-treated birds was accompanied by marked changes in the faecal microbiome. Some of the main differences between the “Vaccine” and “Vaccine?+?probiotic” groups included reduction of Escherichia-Shigella and increases in Blautia, Anaerotruncus and Lactobacillus in the latter group. Although no direct causal link can be established from this study design, it is possible that the E. faecium probiotic induces improved antibody production following vaccination via modulation of the intestinal microbiota.