A New α1-Globin Variant, Hb Ormylia [HBA1:c.63C > G; p.His21Gln]. Report of Eleven Cases in Northern Greece.

The first identification of a novel α1-Globin variant, Hb Ormylia in 11 Greeks originating from a small village, Ormylia, Chalkidiki, Greece is reported. The new genetic variant leads to the production of a hemoglobin variant that can be identified and quantified by High-Performance Liquid Chromatography. Capillary and classic electrophoresis were not informative. Direct DNA sequencing revealed a new mutation C > G mutation at codon 21 of α1 gene (His > Gln). The new variant has been named Hb Ormylia and this is the first description of this genetic variant of α1 gene in the literature.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Antifungal agents and the kidney: pharmacokinetics, clinical nephrotoxicity, and interactions.

INTRODUCTION: Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades have seen a considerable expansion in antifungal drug research, resulting in the clinical development of different classes of antifungal agents with different pharmacologic properties. Among drug-specific characteristics of antifungal agents, renal disposition and nephrotoxicity are important clinical considerations as many patients requiring antifungal therapy have compromised organ functions or are receiving other potentially nephrotoxic medications. AREAS COVERED: The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies. EXPERT OPINION: Based on the available data amphotericin B deoxycholate has the highest relative potential for nephrotoxicity, followed by the lipid formulations of amphotericin B, and, to a much lesser extent and by indirect mechanisms, the antifungal triazoles.

Prevention of Anastomotic Leakage in Gastrointestinal Tract: A Brief Literature Review.

Anastomotic leakage and its consequences in gastrointestinal tract surgery, especially in low anterior resection, is a day major complication affecting morbidity and mortality rate. Early detection and prevention is crucial in order for sepsis to be avoided. There are well-defined risk factors influencing anastomosis healing. The patient’s status and operative conditions including surgical technique have been incriminated for dehiscence. The correct application of conventional operative principles is important. The outcome of anastomosis either handsewn or stapled is deemed to have no major difference. Novel compression anastomotic instruments have been proposed as an alternative option, yet without wide broad application and enough experience. There are innovative staple line reinforcement materials. Some topics such as proximal defunctioning stoma, pelvic tubes or the recently proposed transanal drainage tube are in debate for routine or selective use. Protective transverse colostomy does not affect the risk of leakage, but it reduces the septic consequences. Laparoscopic procedures have similar anastomotic leakage rate with open operations. There is no consensus on whether covering anastomosis with great omentum is necessary as protection or for mechanical bowel preparation. Novel promising perspectives exist as well as commonly accepted aspects. The combination of conventional techniques (handsewn or stapled anastomosis performance) with modern techniques may be proved effective in reducing anastomotic leakage rates.

Brief Useful Comments on Laparoscopic Surgery in Acute Abdomen.

The use of laparoscopic surgery tends to become more and more popular, nowadays. It has also been extended in the management of acute abdominal disease as a diagnostic and as a therapeutic tool. However, its therapeutic use requires special experience and appropriate instrumentation, in addition to a reliable definite diagnosis. Based on randomized, controlled trials, it can be postulated that laparoscopic surgery in acute abdomen is feasible, safe and effective in acute cholecystitis, acute appendicitis and gastroduodenal ulcer perforation. There are still conflicting aspects in perforated diverticular disease and small bowel obstruction. In case of purulent peritonitis attention must be paid in order to avoid residual abscess formation and sepsis by thorough irrigation of the peritoneal cavity and on time antibiotic therapy. The proper indication for each case under the certain emergency circumstances is crucial.