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.     

Intestinal microbiota and its association with colon cancer and red/processed meat consumption

The human colon harbors a high number of microorganisms that were reported to play a crucial role in colorectal carcinogenesis. In the recent decade, molecular detection and metabolomic techniques have expanded our knowledge on the role of specific microbial species in promoting tumorigenesis. In this study, we reviewed the association between microbial dysbiosis and colorectal carcinoma (CRC). Various microbial species and their association with colorectal tumorigenesis and red/processed meat consumption have been reviewed. The literature demonstrated a significant abundance of Fusobacterium nucleatum, Streptococcus bovis/gallolyticus, Escherichia coli, and Bacteroides fragilis in patients with adenoma or adenocarcinoma compared to healthy individuals. The mechanisms in which each organism was postulated to promote colon carcinogenesis were collated and summarized in this review. These include the microorganisms' ability to adhere to colon cells; modulate the inhibition of tumor suppressor genes, the activations of oncogenes, and genotoxicity; and activate downstream targets responsible for angiogenesis. The role of these microorganisms in conjugation with meat components including N‐nitroso compounds, heterocyclic amines, and heme was also evident in multiple studies. The outcome of this review supports the role of red meat consumption in modulating CRC progression and the possibility of gut microbiome influencing the relationship between CRC and diet. The study also demonstrates that microbiota analysis could potentially complement existing screening methods when detecting colonic lesions.     

【In Press】 Optical coherence tomography changes following vitrectomy for long standing premacular hemorrhage in Valsalva retinopathy

Letter to the editor     

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.     

Prevention of Kernicterus in South Asia: Role of Neonatal G6PD Deficiency and its Identification

Extreme hyperbilirubinemia (EHB) caused by neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency is strongly associated with mortality and long-term neurodevelopmental impairment, yet there are limited national strategies to reduce this burden in South Asia. Current known and predicted prevalence of G6PD deficiency in Afghanistan, Bangladesh, Bhutan, India, Nepal, and Pakistan ranges from 3.8 to 15 %, with regional “hot spots” exceeding 22 %. Annually, 3.14 million infants are born at risk for this condition. In 2010, South Asian countries reported 37 million (27 %) of world-wide livebirths ≥ 32 wk gestational-age and G6PD deficiency accounted for > 33 % of the global EHB burden, in contrast to 2.2 % for those born in high-income nations. Traditional national approach includes universal newborn screening in malaria-endemic countries or those with prevalence >3.5 %. However, screening implementation should be best optimized using timely quantitative enzyme assay and identification of at-risk female newborns. Furthermore, economic and social constraints, in context of sub-regional variances, call for flexible problem-solving methods in anticipation of changing community demographics. Thus, incremental and need-based newborn screening programs could be the most optimal approach. A human-centered design (HCD) approach, as an alternate pathway, could build the evidence to translate the complex biology of G6PD deficiency and the biodesign of affordable technologies, allowing facilitation of access to knowledge and services, in order to deliver on a long-term public health mandate. Key steps would encompass the initiation of local inquiry of both quantitative and qualitative data to identify at-risk communities and to prospectively design for local innovative solutions.