Different Pharmaceutical Products Need Similar Terminology

In the last decade, discussions on the development of the regulatory framework of generic versions of complex drugs such as biologicals and non-biological complex drugs have attracted broad attention. The terminology used is far from harmonized and can lead to multiple interpretations of legal texts, reflection papers, and guidance documents regarding market introduction as well as reimbursement. This article describes the meaning of relevant terms in different global regions (Europe, USA, WHO) and offers a proposal for a globally accepted terminology regarding (non-) biological complex drugs.     

Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

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Prompt Repair of Post Cholecystectomy Bile Duct Transection Recognized Intraoperatively and Referred Early: Experience from a Tertiary Care Teaching Unit

Postcholecystectomy bile duct injuries are a cause of significant morbidity and occasional mortality. Intraoperative recognition and repair of complete biliary transection with hepaticojejunostomy is the recommended treatment; however, it is possible only in few patients as either the injury is not recognized intraoperatively or the center is not geared up to perform an urgent hepaticojejunostomy in these patients with a nondilated duct. Retrospective analysis of data from a tertiary care referral center over a period of 10 years from January 2000 to December 2009 to report the feasibility and outcomes of prompt repair was done (defined as repair within 72 h of index operation) of postcholecystectomy bile duct injury. Ten patients of postcholecystectomy bile duct injury detected intraoperatively and referred early underwent prompt repair. All patients had a complete transection of the bile duct (type of injuries as per Strasberg classification: Type E V: 1, Type E III: 5, Type E II: 3 and Type E I: 1). The mean duration between injury and bile duct repair in the form of Roux-en-Y hepaticojejunostomy (RYHJ) was 22.7 (range 5–42) hours. The mean diameter of the anastomosis was 1.63 (range1–2.1) cm, and the anastomosis was stented in 7 patients. The mean duration of surgery was 4.6 +1.7 h. One patient developed bile leak on the first postoperative day, which settled by day 5. The mean duration of hospital stay was 5.1 (range 4–8) days. With a mean follow-up of 42 (range 24–110) months, all patients had excellent (70 %) or good outcome (30 %). Prompt RYHJ (within first 72 h) for postcholecystectomy biliary transection is an effective treatment and potentially limits the morbidity to the patient.     

Role of insulin resistance indices in predicting new‐onset diabetes after kidney transplantation

New‐onset diabetes mellitus (NODAT) is a serious complication following renal transplantation. In this cohort study, we studied 118 nondiabetic renal transplant recipients to examine whether indices of insulin resistance and secretion calculated before transplantation and at 3 months post‐transplantation are associated with the development of NODAT within 1 year. We also analysed the long‐term impact of early diagnosed NODAT. Insulin indices were calculated using homeostasis model assessment (HOMA) and McAuley's Index. NODAT was diagnosed using fasting plasma glucose. Median follow‐up was 11 years. The cumulative incidence of NODAT at 1 year was 37%. By logistic regression, recipient age (per year) was the only significant pretransplant predictor of NODAT (OR 1.04, CI 1.009–1.072), while age (OR 1.04, CI 1.005–1.084) and impaired fasting glucose (OR 2.97, CI 1.009–8.733) were significant predictors at 3 months. Pretransplant and 3‐month insulin resistance and secretion indices did not predict NODAT. All‐cause mortality was significantly higher in recipients developing NODAT within 1 year compared with those remaining nondiabetic (44% vs. 22%, log‐rank P = 0.008). By Cox's regression analysis, age (HR 1.075, CI 1.042–1.110), 1‐year creatinine (HR 1.007, CI 1.004–1.010) and NODAT within 3 months (HR 2.4, CI 1.2–4.9) were independent predictors of death. In conclusion, NODAT developing early after renal transplantation was associated with poor long‐term patient survival. Insulin indices calculated pretransplantation using HOMA and McAuley's Index did not predict NODAT.     

Interatrial Block in the Modern Era

Interatrial block (IAB; P-wave duration ≥ 110 ms), which represents a delay in the conduction between the atria, is a pandemic conduction abnormality that is frequently underappreciated in clinical practice. Despite its comprehensive documentation in the medical literature, it has still not received adequate attention and also not adequately described and discussed in most cardiology textbooks. IAB can be of varying degrees and classified based on the degree of P-duration and its morphology. It can transform into a higher degree block and can also manifest transiently. IAB may be a preceding or causative risk factor for various atrial arrhythmias (esp. atrial fibrillation) and also be associated with various other clinical abnormalities ranging from left atrial dilation and thromboembolism including embolic stroke and mesenteric ischemia. IAB certainly deserves more attention and prospective studies are needed to formulate a standard consensus regarding appropriate management strategies.     

End-Capped α-Helices as Modulators of Protein Function

Examination of complexes of proteins with other biomolecules reveals that proteins tend to interact with partners via folded sub-domains, in which the backbone possesses secondary structure. α-Helices, the largest class of protein secondary structures, play fundamental roles in a multitude of highly specific protein-protein and protein-nucleic acids interactions. Herein, we describe the potential of a helix nucleation strategy to afford modulators of protein-protein interactions.