COG6-CDG: Novel variants and novel malformation.

BACKGROUND: Deficiency of Conserved Oligomeric Golgi (COG) subunits (COG1-8) is characterized by both N- and O-protein glycosylation defects associated with destabilization and mislocalization of Golgi glycosylation machinery components (COG-CDG). Patients with COG defects present with neurological and multisystem involvement and possible malformation occurrence. Eighteen patients with COG6-CDG (COG6 mutations) were reported to date. We describe a patient with COG6-CDG with novel variants and a novel clinical feature namely a congenital recto-vaginal fistula. METHODS: In-depth serum N- and O-glycosylation structural analyses were conducted by MALDI-TOF mass spectrometry. COG6 variants were identified by a gene panel and confirmed by Sanger sequencing. RESULTS: This female newborn presented with facial dysmorphism, distal arthrogryposis and recurrent stool discharges per vaginam. A double-contrast barium-enema X-ray study revealed a dehiscence (approximately 5 mm) at the anterior wall of the rectal ampoule communicating with the vagina consistent with a recto-vaginal fistula. She had developmental delay, corpus callosum dysgenesis, liver and gastrointestinal involvement, hyperthermia episodes and early demise. Serum N- and O-glycosylation analyses pointed to a profound Golgi disarrangement. We identified two novel variants in COG6: a deletion of 1 bp mutation c.823delA creating a shift in the reading frame and a premature stop codon and a 3 bp deletion (c.1141_1143delCTC) producing an in-frame deletion of 1 amino acid. CONCLUSION: The congenital recto-vaginal fistula is a rare type of anorectal malformation that, to our knowledge, has not been reported in patients with a COG6 defect nor in patients with other COG defects. This study broadens COG6-CDG genetic landscape and spectrum of malformations.

Robotic Right Colectomy with Modified Complete Mesocolic Excision: Long-Term Oncologic Outcomes.

BACKGROUND: A modified complete mesocolic excision (mCME) technique for the treatment of right-sided colon cancer recently was shown by Hohenberger and colleagues to provide impressive long-term oncologic outcomes. This report aims to describe the authors' experience with robotic right colectomy using mCME. The safety, feasibility, and efficacy of this procedure are measured by complications, conversion rates, and 4-year oncologic outcomes. METHODS: A retrospective study analyzed 100 consecutive patients who underwent robotic right colectomy with mCME and intracorporeal anastomosis at the authors' institution between November 2005 and November 2013. Intra- and postoperative clinical outcomes, pathologic data, and survival were analyzed. RESULTS: Robotic right colectomy with mCME was successfully performed for all the patients. No conversions or intraoperative complications occurred. The major complication rate (Dindo 3 or 4) was 4 %. During a median follow-up period of 48.5 months (range 24-114 months), the survival rates were 94.5 % for disease-specific survival, 91.4 % for disease-free survival, and 90.3 % for overall survival. CONCLUSIONS: The authors' experience confirms the feasibility and safety of mCME for the treatment of right-sided colon cancer. This technique provided satisfying short-term outcomes with promising 4-year oncologic results. However, the real benefits of the CME technique should be evaluated further by well-conducted randomized studies before its adoption in routine practice is recommended.

Cardiac catheterization and postoperative acute kidney failure in congenital heart pediatric patients.

BACKGROUND: Acute renal failure (ARF) is a severe complication of cardiac operations in pediatric patients. Angiography with the exposure to contrast media is a risk factor for ARF. In the present study, we explored the association between timing of angiography, dose of contrast media, and the incidence of ARF after cardiac operations in pediatric patients. METHODS: We performed a retrospective analysis of prospectively collected data. Angiographic data and other covariates were collected in 277 patients aged ≤12 years receiving angiography and cardiac operations during the same hospital stay. Renal outcome was assessed according to the pediatric Risk, Injury, Failure, Loss of function, End stage score (pRIFLE). RESULTS: One hundred seventy-seven (64%) patients suffered some degree of postoperative renal dysfunction, and 55 (20%) had ARF (pRIFLE stage Failure). Patients with ARF received a significantly (P < 0.001) larger dose of iodine contrast media (4.6 ± 2.6 g/kg) with respect to the other patients (2.8 ± 2.2 g/kg), with a relative risk increase for ARF of 31% per each incremental iodine dose of 1 g/kg at the univariate analysis. A multivariable risk model demonstrated that the risk for ARF is 20 times higher in patients aged younger than 2 years and 3 times higher in case of postoperative low cardiac output. Within this model, the iodine dose on angiography is confirmed as an independent risk factor for ARF, with a relative risk increase for ARF of 16% per each incremental iodine dose of 1 g/kg. CONCLUSIONS: Angiography before cardiac surgery is an important risk factor for ARF in pediatric patients. Being a modifiable risk factor, the contrast media dose should be limited to the lowest possible value, avoiding large doses of iodine which, together with other factors (age and postoperative low cardiac output), concur in the determinism of postoperative ARF.

Fat and esophageal sensitivity to acid.

The hypothesis that fat increases esophageal sensitivity to acid was tested in eight patients with gastroesophageal reflux disease and 11 healthy subjects. Protocol 1 included randomized intragastric infusions of saline or Lipofundin S 20% (306 kcal) on two separate days, followed after 30 and 90 min by an 8 ml/min intraesophageal infusion of 0.1 N HCl. The time to the onset of heartburn and the maximum heartburn score by visual analog scale during the acid infusion were similar after intragastric saline (2 min and 29.5 mm, medians) and fat (2 min and 20.5 mm). Protocol 2 included two 8 ml/min intraesophageal infusions of 0.2 N HCI diluted in an equal volume of saline or Lipofundin S 20% at a time interval of 10 min in randomized order. The time to the onset of heartburn and the maximum heartburn score were unaffected by the presence of fat in the esophageal infusate (2.5 min and 53 mm without vs 1.5 min and 49 mm with fat). We conclude that fat does not increase esophageal sensitivity to acid.