Management of Congenital Diaphragmatic Hernia (CDH): role of molecular genetics

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery

Closure of cutaneous incision after thyroid surgery: A comparison between metal clips and cutaneous octyl-2-cyanoacrylate adhesive. A prospective randomized clinical trial

Octyl-2-cyanoacrylate (Dermabond, Ethicon Inc.) has been introduced in clinical practice as an ideal system of closure of wounds, but no studies have confirmed the advantages of wound closure performed with Dermabond compared to skin staples (Proximate, Ethicon Inc.) in thyroid surgery. The objective of this study is to evaluate the short- and long-term results of wound closure in thyroid surgery performed with Dermabond (DERM) versus Proximate (PROX). Seventy patients after thyroidectomy were randomly assigned into the two groups (DERM vs PROX). The postoperative and the long-term outcomes were clinically evaluated by physicians, and the Stony Brook scar evaluation scale has also been used. The patients' satisfaction with the early postoperative management and with the cosmetic outcomes has been assessed by a numerical scale ranging from 0 to 10. Results were compared using appropriate statistical tests. Thirty-two patients used DERM, while 38 patients used PROX. Immediate results showed difficult application in two cases DERM (6.2%) and hyperemia in one case DERM (3.1%). Early results showed edema in eight cases DERM (25%) vs two cases PROX (5.2%; p<0.05); patients' satisfaction: optimum judgement in 100% DERM vs 15.7% PROX (p< 0.001); patients' self aesthetic evaluation: PROX higher percentage of excellent results vs DERM (p<0.005). After one month, results showed edema in nine cases DERM (28.8%) vs two cases PROX (5.2%; p<0.01), while after 6 months, DERM had lesser symptoms than PROX (p< 0.01). Octyl-2-cyanoacrylate has proven to be effective and reliable in the skin closure of cervical incision similar to suture with staples and yields similar final cosmetic outcomes. Because Dermabond offers the advantage of better management in the early postoperative phase, the patients' satisfaction is clearly better. © Springer-Verlag 2010

An Overview of Short-Bowel Syndrome in Pediatric Patients: Focus on Clinical Management and Prevention of Complications

Short-bowel syndrome (SBS) in pediatric age is defined as a malabsorptive state, resulting from congenital malformations, significant small intestine surgical resection or disease-associated loss of absorption. SBS is the leading cause of intestinal failure in children and the underlying cause in 50% of patients on home parental nutrition. It is a life-altering and life-threatening disease due to the inability of the residual intestinal function to maintain nutritional homeostasis of protein, fluid, electrolyte or micronutrient without parenteral or enteral supplementation. The use of parenteral nutrition (PN) has improved medical care in SBS, decreasing mortality and improving the overall prognosis. However, the long-term use of PN is associated with the incidence of many complications, including liver disease and catheter-associated malfunction and bloodstream infections (CRBSIs). This manuscript is a narrative review of the current available evidence on the management of SBS in the pediatric population, focusing on prognostic factors and outcome. The literature review showed that in recent years, the standardization of management has demonstrated to improve the quality of life in these complex patients. Moreover, the development of knowledge in clinical practice has led to a reduction in mortality and morbidity. Diagnostic and therapeutic decisions should be made by a multidisciplinary team that includes neonatologists, pediatric surgeons, gastroenterologists, pediatricians, nutritionists and nurses. A significant improvement in prognosis can occur through the careful monitoring of nutritional status, avoiding dependence on PN and favoring an early introduction of enteral nutrition, and through the prevention, diagnosis and aggressive treatment of CRSBIs and SIBO. Multicenter initiatives, such as research consortium or data registries, are mandatory in order to personalize the management of these patients, improve their quality of life and reduce the cost of care

Clinical impact and disease evolution of SARS-CoV-2 infection in familial Mediterranean fever

The innate immune system is critically involved in the pathogenesis of familial Mediterranean fever (FMF), characterized by dysregulated inflammasome activity and recurrent inflammatory attacks: this is the most common among monogenic autoinflammatory diseases, which shares some biochemical pathways with the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In this short review we explore the overlap in the pathophysiology of FMF and SARS-CoV-2 infection, discussing how to understand better the interaction between the two diseases and optimize management. A poorer outcome of SARS-CoV-2 infection seems not to be present in infected FMF patients in terms of hospitalization time, need for oxygen support, need for intensive care, rate of complications and exitus. Long-term surveillance will confirm the relatively low risk of a worse prognosis observed so far in SARS-CoV-2-infected people with FMF. In these patients COVID-19 vaccines are recommended and their safety profile is expected to be similar to the general population

Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery

Leak after sleeve gastrectomy. How long do we have to be worried?

Currently, laparoscopic sleeve gastrectomy (LSG) is the most popular procedure for the treatment of morbid obesity in USA and Europe. Minor complications have an overall incidence of 11 % while major l complications constitute about 5 % in large series. The mean incidence of leak is 2.1 % . According to the time of onset, Csendes et al. classified leakage as early when diagnosed within 4 days posteratively, intermediate within days 5–9 and late when occurring after the 10th postoperative day. Leak is the second most common cause of death with an overall reported mortality rate of 0.4 %. It remains unusual and unexplainable to see very late leaks occurring several months after LSG (6-7- months) as those reported in this paper

Adenocarcinoma of the ileal pouch mucosa. A new diagnostic challenge

.Dear editor, We read with interest the manuscript recently published by O’Mahoney et al. entitled “Adenocarcinoma of the ileal pouch mucosa: case report and literature review” [1]. The authors well presented a case of adenocarcinoma of ileal pouch mucosa diagnosed after 13 years of pouch creation. They reviewed literature for true pouch adenocarcinoma, and a total of 27 patients have been described around the world. Of these, 63 % (17/27) had neoplasia in their original proctocolectomy specimen. Mean time of adenocarcinoma development was 8.9 years. Five-year survival after excision of the pouch was 70 %. In our experience of 112 ileal pouch anastomosis, we had one case of true pouch adenocarcinoma. A 71-year-old man was diagnosed of ulcerative colitis for 30 years; he underwent a total colectomy 26 years ago (on 1985). Patient course was complicated by chronic pouchitis medically treated. After 11 years of follow-up, primary sclerosing cholangitis diagnosis was done. During annual endoscopic control, a polypectomy was performed. At pathology, a wide area of high-grade dysplasia with a minute focus of adenocarcinoma polyp was observed. A magnetic resonance imaging was performed, and a mucosal thickening was observed. Considering oncological indication to remove the pouch, patient age, and technical difficulty to restore intestinal continuity, the patient underwent ileal pouch excision with end ileostomy. After 34 months of follow-up, the patient is alive with no local or systemic recurrence. In our experience, mean age at surgery was 37 years old with a mean follow-up of 123 months ..

[Factors associated with ileal-pouch related fistulas in 100 consecutives patients who underwent restorative proctocolectomy].

The pouch-related fistulas range in literature from 2% to 16% and they can be cause of failure of the intervention of restorative proctocolectomy. Aim of this study was to examine factors associated with theirs development and to identify theirs possible etiology and pathogenesis. Retrospective study focusing on 100 consecutive patients who underwent restorative proctocolectomy with pouch-anal anastomosis (IPAA). Patients with fistula and patients without fistula have been identified and the fistula type, the time from surgery and the site relative to IPAA have been recorded. Patients' demographics, co-morbidity or related medical history, clinical indication for treatment, surgical method, histological diagnosis, length of follow-up, early and late postoperative complications have been reviewed, and data collected have been compared among the two groups through univariate analysis. The overall incidence of fistulas was of 10% (10 cases); 8 cases had pouch-vaginal fistulas, involving the distal tract of the vagina, and associated with pouch-perineal fistulas in 2 cases; 1 case had pouch-vulval fistula; 1 case had a complex pouch-perineal fistula. Three fistulas were precocious, all associated with an IPAA leak; 2 of these cases also had pelvic sepsis while the third had delayed diagnosis of Crohn s disease. Seven fistulas had a late development. Four fistulas occurred at the level of the IPAA; 5 fistulas were located below the IPAA, and 1 fistula originated above and below the IPAA. When the two groups of patients were compared we found that there was an higher percentage of perineal or anal disease (40.0% vs 2.2%; p <0.001), of extraintestinal manifestations of inflammatory bowel disease (IBD) (40.0% vs 3.3%, p <0.001), and of leak of the IPAA (40.0% vs 11.1%; p <0.05) in the group with fistula vs the group without fistula. A direct link with the leak of the IPAA appears in all the early fistulas, while the cryptoglandular infection was suggested as a possible cause of the late fistulas located below the IPAA; the association with the extraintestinal manifestations of IBD could show a correlation between the fistulas and an higher specific activity of the underlying chronic inflammatory disease