The unbound fraction (ƒ ) of ceftriaxone was 44%, and total CL was 1.27 L/h, 25-30% higher than the CL reported in septic critically ill patients not receiving renal replacement therapies, and dependent on albumin concentration and weight. Despite this increment in ƒ and CL, Monte-Carlo simulations showed that a dose of 1 g once-daily ceftriaxone is sufficient to achieve a 100% ƒ T for MICs ≤2 mg/L for any range of weight and albumin concentration. Once-daily 1 g ceftriaxone provides optimal exposure in critically ill patients with septic shock and hypoalbuminemia receiving CVVHDF.Once-daily 1 g ceftriaxone provides optimal exposure in critically ill patients with septic shock and hypoalbuminemia receiving CVVHDF.The respiratory microbiome has been less explored than the gut microbiome. Despite the speculated importance of dysbiosis of the microbiome in ventilator-associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS), only few studies have been performed in invasively ventilated ICU patients. And only the results of small cohorts have been published. An overlap exists between bacterial populations observed in the lower respiratory tract and the oropharyngeal tract. The bacterial microbiota is characterized by relatively abundant bacteria difficult to cultivate by standard methods. Under mechanical ventilation, a dysbiosis occurs with a drop overtime in diversity. During VAP development, lung dysbiosis is characterized by a shift towards a dominant bacterial pathogen (mostly Proteobacteria) whereas enrichment of gut-associated bacteria mainly Enterobacteriaceae is the specific feature discriminating ARDS patients. However, the role of this dysbiosis in VAP and ARDS pathogenesis is not yet fully understood. A more in-depth analysis of the interplay between bacteria, virus and fungi and a better understanding of the host-microbiome interaction could provide a more comprehensive view of the role of the microbiome in VAP and ARDS pathogenesis. Priority should be given to validate a consensual and robust methodology for respiratory microbiome research and to conduct longitudinal studies. A deeper understanding of microbial interplay should be a valuable guide for care of ARDS and VAP preventive/therapeutic strategies. We present a review on the current knowledge and expose perspectives and potential clinical applications of respiratory microbiome research in mechanically ventilated patients.Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Rituximab Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.Bisphosphonates are the first-choice treatment of osteoporosis and Paget's disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget's disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations. Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes. The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85years and HbA 48-69mmol/mol (6.5-8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 11 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24.