Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival.

Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.

Stemless reverse total shoulder arthroplasty: a systematic review of contemporary literature.

PURPOSE: Reverse shoulder prostheses are increasingly used for treatment of rotator cuff tear arthropathy and other degenerative shoulder diseases. In recent years, aiming for bone stock preservation has led to the design of metaphyseal humeral components without a stem. The aims of this study were to evaluate the complication and reintervention rates, as well as the clinical and radiographic outcomes in patients who underwent reverse shoulder arthroplasty (RSA) with stemless implants. METHODS: A systematic review of the literature was completed until May 2020 using PubMed, EMBASE, CINAHL and Cochrane databases, according to PRISMA guidelines. RESULTS: The literature search revealed 2942 studies, of which 13 were included in this review, with a total of 517 patients and a mean follow-up between 6.4 and 101.6 months. The total complication rate was 6.5%, while 3.3% were humeral associated complications. Finally, the rate of shoulders that underwent a reintervention was 6.7%, with 1.4% relating to a humeral component reason. Stemless RSA led to substantial improvements in patient reported outcome measures and range of motion across all studies. Scapular notching was reported in 15.2%, and lucencies around humeral component were reported in 0.8% of shoulders. CONCLUSION: Stemless RSA resulted in low complication and reintervention rates at the mid-term follow-up. The reported clinical and radiological outcomes showed that these prostheses have at least equivalent outcomes with their stemmed counterparts. Further studies are required to investigate the long-term longevity and performance of the stemless humeral implants. LEVEL OF EVIDENCE: Level IV; Systematic Review.

Ovarian hyperstimulation syndrome and heterotopic pregnancy after IVF.

We report a case of Severe OHSS combined with Heterotopic pregnancy. During the treatment of OHSS the patient underwent transvaginal paracentesis for the ascites but no sign of blood was noticed into the fluid. The ultrasound control in the 8th week had shown a normal intrauterine pregnancy without any suspicion for heterotopic pregnancy. The diagnosis for heterotopic pregnancy became possible at 10 Weeks of gestation by Ultrasound. Laparotomy with partial tubal resection was performed. The intrauterine pregnancy is still ongoing without complications.