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OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD. ispartof: JOURNAL OF PEDIATRICS vol:199 pages:22-+ ispartof: location:United States status: published

Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disease with a severe phenotype often presenting prenatally or in early childhood. With its obligate renal and hepatic involvement, ARPKD is one of the most important indications for liver and/or kidney transplantation in childhood. Marked phenotypic variability is observed, the genetic basis of which is largely unknown. Treatment is symptomatic and largely empiric as evidence-based guidelines are lacking. Therapeutic initiatives for ARPKD face the problem of highly variable cohorts and lack of clinical or biochemical risk markers without clear-cut clinical end points. ARegPKD is an international, multicenter, retro- and prospective, observational study to deeply phenotype patients with the clinical diagnosis of ARPKD. Initiated in 2013 as a web-based registry (www.aregpkd.org), ARegPKD enrolls patients across large parts of Europe and neighboring countries. By January 2017, more than 400 patients from 17 mostly European countries have been registered in the ARPKD registry study with significant follow-up data. Due to comprehensive retro- and prospective data collection and associated biobanking, ARegPKD will generate a unique ARPKD cohort with detailed longitudinal clinical characterization providing a basis for future clinical trials as well as translational research. Hence, ARegPKD is hoped to contribute to the pathophysiological understanding of the disease and to the improvement of clinical management. ispartof: Frontiers in Pediatrics vol:5 pages:18- ispartof: location:Switzerland status: published

To evaluate the influences of the XRCC1 gene polymorphisms on the risk of sporadic breast cancer and the response to adjuvant treatment, a case-control study was conducted in 185 patients with breast cancer and 205 female controls. Our results suggested that the polymorphisms of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women. Background: The XRCC1 gene encoding the X-ray cross-complementing group 1 protein (XRCC1) is involved in the base excision repair (BER) pathway. Methods: The aim of this study was to investigate an association of the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene with a risk of breast cancer occurrence and the response to adjuvant treatment among Polish women. Overall survival (OS) and disease-free survival (DFS) were investigated in groups of patients with breast cancer treated with (1) all types of adjuvant therapy, (2) concomitant radiotherapy and chemotherapy, (3) chemotherapy alone, or (4) radiotherapy alone. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to evaluate the genotype distribution of the XRCC1 gene among 185 patients with breast cancer and 205 female controls. Results: We showed a higher risk of breast cancer occurrence for the Trp allele and the Arg194Trp genotype of the XRCC1 gene. However there was no significant difference in distribution of the Arg399Gln genotype of XRCC1 between patients and the control group. In the patient subgroup treated with adjuvant therapy, Kaplan-Meier survival analysis showed a significantly higher OS as well as DFS for carriers of the Gln399Gln genotype when compared with carriers of the Arg399Gln and Arg399Arg genotypes. The Gln399Gln genotype was associated with a significantly higher DFS in the subgroup of patients treated with chemotherapy alone or with concomitant radiotherapy and chemotherapy. Conclusion: We suggest that the polymorphism of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women.

Methotrexate (MTX) and 6-mercaptopurine (6MP) are the most commonly used drugs in the therapy of childhood acute lymphoblastic leukaemia (ALL). The main genotoxic effect of MTX resulting from inhibition of thymidylate synthase is mis-incorporation of uracil into DNA, which is considered essential for the effectiveness of the Protocol M in ALL IC BFM 2002/EURO LB 2002 regimens. In this study, we investigated the level of basal and induced DNA damage as well as the effectiveness of DNA repair in lymphocytes of children with ALL at four time-points during therapy with MTX and 6MP. To assess DNA damage and the efficacy of DNA repair we used the modified alkaline comet assay with uracil DNA glycosylase (Udg) and endonuclease III (EndoIII). In addition, we examined the induction of apoptosis in the lymphocytes of the patients during treatment. Finally, we compared the activity of base-excision repair (BER), involved in removal of both uracil and oxidized bases from DNA in lymphocytes of children with ALL and lymphocytes of healthy children. BER efficiency was estimated in an in vitro assay with cellular extracts and plasmid substrates of heteroduplex DNA with an AP-site. Our results indicate that there is a significant decrease in the efficacy of DNA repair associated with an increased level of uracil in DNA and induction of apoptosis during therapy. Moreover, it was found that the BER capacity was decreased in the lymphocytes of ALL patients in contrast to that in lymphocytes of healthy children. Thus, we suggest that an impairment of the BER pathway may play a role in the pathogenesis and therapy of childhood ALL.

Roux-en-Y gastric bypass (RYGBP) is a mainstay of bariatric surgical therapy. Gastro-gastric fistula (GGF) is an infrequent but potentially serious complication of gastric bypass, and diagnosis may be difficult. We report two patients who underwent RYGBP complicated by development of GGF who nevertheless achieved excellent, durable weight loss. The pathogenesis, diagnosis, prevention and management of GGF after RYGBP is reviewed. GGF may not result in poor weight loss after RYGBP and is not an absolute indication for surgical revision.

Background: Surgical intervention is currently indicated for patients with BMI >40 or >35 with life-threatening comorbidities. Patients with BMI 32-40 without these comorbidities not only have the increased propensity to develop them but also suffer from similar psychosocioeconomic consequences. These patients may not respond to non-surgical treatment of obesity any better than those with BMI>40. The question has been raised whether to offer them surgical intervention. Methods: A study was carried out to determine outcome of surgery on patients with BMI >32 but

Background: No bariatric operation has been documented to effect adequate weight loss in all patients. Patients with inadequate weight loss or significant weight regain with an anatomically intact short-limb gastric bypass, of which the Fobi pouch operation (FPO) for obesity is a modification, are usually revised to a distal Roux-en-Y gastric bypass (DRYGBP) to enhance weight loss. Method: A retrospective review of the charts of all patients who had a revision to a DRYGBP at our Center during an 8-year period was carried out and the findings analyzed. Results: 65 patients who had the FPO had a revision to the DRYGBP.Most were super obese patients who, even though they had lost significant weight, were still morbidly obese. Some were patients who had not lost adequate weight or

Background The effect of transecting vs. stapling the stomach in continuity in the banded gastric bypass (GBP) operation was studied. Method 50 patients, 25 in each group, were enrolled into a prospective study to determine if transecting the stomach vs. stapling it in continuity in performing GBP for obesity decreases the incidence of gastro-gastric fistula formation without increased morbidity. Results The patient profiles in the 2 groups were very similar. The peri-operative complications included 1 splenic capsular injury in each group, controlled without a splenectomy. There was 1 anastomotic leak in the stapled and 1 bleeding from the cut edge of the bypassed stomach in the transected group, both requiring re-operations in the immediate postoperative period. There was no peri-operative mortality. The percent follow-up after 6 years was 80% and 88% in the stapled and transected groups respectively. The incidence of late complications of solid food intolerance, ventral incisional hernia, cholelithiasis and small bowel obstruction was similar in both groups. There were 8 gastro-gastric fistulas in the stapled group and 1 in the transected group. The reduction in body mass index and percent excess weight loss (66%) were similar in both groups. Conclusion The incidence of gastro-gastric fistula may be reduced in GBP procedures by transecting the stomach as opposed to stapling it in continuity, without an increase in morbidity or mortality or any loss in the effectiveness of the operation.

Background: Many patients who qualify for obesity surgery have a moderate to large panniculus (grade 1-5). They can benefit from panniculectomy done concurrently with gastric bypass (GBP) or subsequently after significant weight reduction, usually 18 months after the GBP. Method: Over the last 8 years, 2,231 bariatric operations were performed at the Center. 577 panniculectomies were done, with 428 (74.2%) concurrent with the GBP and 149 (25.8%) subsequent to the GBP. Results:The redundant pannus weighed from 5 to 54.5 kg. Wound problems occured in 15.1% of panniculectomies. Transfusion was necessary in 1.9%. Hospital stay was 4 to 5 days, and was no greater than in patients that underwent the GBP alone. Those with grades 3-5 suffer more back-pain and problems of hygiene resulting from panniculitis. Conclusion: A very redundant panniculus compounds the patient's physical, social and emotional problems. Where cardiopulmonary and other medical status are satisfactory,a panniculectomy may be offered to patients with a symptomatic panniculus at the time of bariatric surgery, as a physically beneficial and cost-effective adjuvant.

Experimental evidences suggest that hyperglycaemia-induced overproduction of reactive oxygen species and subsequent damage to proteins, lipids and DNA may play a key role in the development of distal symmetric polyneuropathy (DSPN)—the most common complication of diabetes mellitus. The study population consisted of 51 individuals aged 52–82 years classified into 3 groups: 16 patients diagnosed with type 2 diabetes mellitus (T2DM) with DSPN, 16 T2DM patients without DSPN and 19 control subjects without diabetes and neuropathy. The study was conducted to determine the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant status (TAS) in the examined groups. An alkaline comet assay was used to determine the extent of DNA damage of oxidized purines as glicosylo-formamidoglicosylase (Fpg) sites, and oxidized pyrimidines as endonuclease III (Nth) sites. A significant decrease of SOD (P 0.05), and TAS status (P > 0.05) were seen in T2DM patients with neuropathy compared to T2DM patients as well as controls. T2DM patients with or without neuropathy revealed significantly lower (P

Banded gastric bypass is a modification which enhances the restrictive component of the gastric bypass operation. A reinforced stoma is created by placing a band around the pouch, as in the vertical banded or silastic ring vertical gastroplasty. The gastroenterostomy (GE) is made just distal to the band. This GE is made at least 2 cm wide since – unlike in the non-banded gastric bypass – the banded stoma, not the gastroenterostomy, controls the outflow from the pouch. The stabilized and reinforced stoma has been documented to effect more weight loss even in the super obese and better weight loss maintenance in more patients than the non-banded gastric bypass. The stoma created in the banded gastric bypass is larger than in the gastroplasty operations. The perioperative and long-term complications are as reported with the short-limb gastric bypass. Since the gastroenterostomy is made wider there is a lesser incidence of outlet stenosis requiring endoscopic dilation, but there is a 2% incidence of band erosion. Eroded bands can be treated expectantly or can be removed with an endoscope. In patients with an intact operation but inadequate weight loss or some weight regain the bypass can be modified to a banded distal Roux-en-Y gastric bypass (BDRYGB).

Primary open-angle glaucoma (POAG) is the leading cause of blindness in the industrial countries. It is reported that oxidative stress might be an important risk factor in the pathogenesis of POAG. Forty subjects including 20 patients with open-angle glaucoma (9 men and 12 women, mean age 61.8±12.1yr) and 20 controls without glaucoma symptoms (9 men and 12 women, mean age 58.1±17.7yr) were enrolled in our study. The main aim of the work was to evaluate oxidative stress markers in the pathogenesis of open-angle glaucoma. In our work the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the total antioxidant status (TAS) was estimated. An alkaline comet assay was used to measure DNA damage of strand breaks (SB), oxidized purines as glicosylo-formamido-glicosylase (Fpg) sites, and oxidized pirmidines as endonuclease III (Nth) sites. We measured endogenous as well as exogenous DNA damage after 10μM hydrogen peroxide treatment (H(2)O(2)). We did not observe any statistical changes of DNA strand break lesion in examined POAG patients according to healthy subjects (P0.05). However, either endogenous (P0.01) or exogenous (P0.001) levels of oxidative DNA damage in POAG patients were found to be statistically higher than controls. A significant decrease of antioxidant enzymes: CAT (P0.001), SOD (P0.05), and GPX (P0.001) and a non-statistical decrease of TAS status (P0.05) in glaucoma patients according to controls were also indicated. In conclusion our data revealed that oxidative stress had a pathogenic role in primary open-angle glaucoma. Therefore, we suggested that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.

Background: Morbid obesity is one of the major risk factors for gallbladder disease, and this risk is even greater following rapid weight loss. Because of this, prophylactic cholecystectomy has been offered to our patients undergoing the transected silastic ring vertical Roux-en-Y gastric bypass (TSRVRYGBP). A study was undertaken to determine the incidence of pathologic gallbladders in patients undergoing this prophylactic cholecystectomy. Method: The records of all patients who underwent TSRVRYGBP from June 1999 through December 2000 were reviewed. Pathologic findings of the gallbladder were documented as cholelithiasis, cholecystitis, cholesterolosis, polyps or normal. Results: 761 patients underwent the operation. 178 patients (23%) had cholecystectomy before the surgery. 154 (20%) had gallstones documented by ultrasound and had cholecystectomy at the time of the surgery. 324 of the 429 patients with negative preoperative findings by ultrasound had pathologic evidence of gallbladder disease. Conclusion: Because of the high incidence of gallbladder disease even with negative preoperative findings in morbidly obese patients and the lack of significant morbidity with cholecystectomy in experienced hands, routine cholecystectomy at the time of the weight loss operation is justified.