Pitfalls and technical errors in the first approach to neonates with anorectal malformations in a non-specialist context: can we do any better? A review from three Eastern African Centres

Introduction: In sub-Saharan Africa, Anorectal malformations (ARM) are the most frequent cause of neonatal obstruc- tion. Referral to a Pediatric Surgeon is frequently delayed. The first treatment is often delivered at not specialist level and mismanagement may result. Aim: To study ARM patients referred beyond neonatal period and managed at a non-specialist level. Materials and Methods: One hundred and thirty patients were included (M/F ratio 63/67) among 144 admitted to three Eastern African Hospitals with Pediatric Surgical facilities. Demographics, type of anomaly, delay on referral, previous man- agement, most commonly observed errors are reported. Results: The Mean age at referral was 23 months (range five weeks – 23 years). Colostomy was the most frequent surgery (92 cases). Stomas often did not follow the recommended criteria. Ten per cent were not on the sigmoid, and 35% were not divided. "Loop" or "double-barrel" colostomies did not exclude the distal loop. Inverted (10,5%), prolapsed stomas (7,5%), short distal loop (16%) were observed. Twenty-four cases (26%) needed redo. Primary perineal exploration in eight patients resulted in incontinence. Conclusions: Investments on training practitioners, acting at District/Rural level, and closer links with tertiary centres are recommended to avoid ARM mismanagement and delayed referral to a Specialist. Keywords: Ano rectal malformations; neonate; low resources context.

A randomized clinical trial evaluating the short-term results of ureteral stent encrustation in urolithiasis patients undergoing ureteroscopy: micro-computed tomography evaluation

Although many ureteral stents are commercially available, the actuality of encrustation is yet to be elucidated in humans. This study compared the Tria Ureteral Stent with PercuShield and the Polaris Ultra Ureteral Stent with HydroPlus Coating for short-term encrustation formation. Eighty-four patients, who required ureteral stent placement after ureteroscopy, were randomized into two stent groups. After stent removal on postoperative day 14, the encrustation volume on the stent surface was measured by micro-computed tomography. The primary outcome was the inner luminal encrustation volume. Secondary outcomes were encrustation volume on the outer or total surfaces and occurrence of adverse events. Clinical factors related to encrustation were also assessed as a post-hoc analysis. Finally, of the 82 patients analyzed, 75 (91.5%) had encrustation in the inner lumen of the stent. The difference in median inner encrustation volume between the Tria and Polaris Ultra stents was comparable (0.56 vs. 0.37 mm3, P = 0.183). There was no difference observed in the encrustation volume on the outer/total surfaces and stent-related adverse events. In both ureteral stents, the shaft body showed significant inner luminal encrustation compared to the proximal or distal loop (all, P < 0.05). Dyslipidemia (P = 0.027), elevated urine pH (P = 0.046), and crystalluria (P = 0.010) were associated with encrustation formation. The Tria and Polaris Ultra stents had similar efficacy for preventing encrustation in the short-term. Further studies are required to compare their long-term patency.

A case report of endorectal displacement of a right ureteral stent following radiochemotherapy and Bevacizumab

Background The angiogenesis inhibitor monoclonal antibody Bevacizumab is presently the standard treatment for numerous neoplasms but particular toxicities are emerging, such as hypertension, haemorrhage, thromboembolism, gastrointestinal perforation, fistulae, and delayed wound healing. The addition of Bevacizumab to radio and chemotherapy has improved the overall survival rate in patients with metastatic, persistent or recurrent cervical carcinoma. However an increased risk of enteric or urinary fistula formation has been documented, related to hypoxia which is induced by the inhibition of angiogenesis. Moreover, previous pelvic surgery, repeated ureteral stenting and radiation are additional risk factors. Case presentation We describe the remarkable case of a right ureteral stent displacement inside the rectum lumen in a patient treated with Bevacizumab for pelvic recurrence of cervical cancer. The patient was referred to our Urology Department with urinary sepsis and bilateral hydronephrosis. Right ureteral stent substitution was planned; at cystoscopy the distal loop of the stent was not visualized inside the bladder. The presence of the distal loop of the right ureteral inside the rectum was clearly demonstrated with a CT scan. Conclusions Since Bevacizumab is increasingly used in the treatment of gynaecological neoplasms and indwelling ureteral stents are often required to treat or prevent ureteral compressions, similar cases are likely to be diagnosed and this complication should be considered in the management of advanced pelvic cancers.

Structure of PINK1 and mechanisms of Parkinson's disease-associated mutations

Mutations in the human kinase PINK1 (hPINK1) are associated with autosomal recessive early-onset Parkinson's disease (PD). hPINK1 activates Parkin E3 ligase activity, involving phosphorylation of ubiquitin and the Parkin ubiquitin-like (Ubl) domain via as yet poorly understood mechanisms. hPINK1 is unusual amongst kinases due to the presence of three loop insertions of unknown function. We report the structure of Tribolium castaneum PINK1 (TcPINK1), revealing several unique extensions to the canonical protein kinase fold. The third insertion, together with autophosphorylation at residue Ser205, contributes to formation of a bowl-shaped binding site for ubiquitin. We also define a novel structural element within the second insertion that is held together by a distal loop that is critical for TcPINK1 activity. The structure of TcPINK1 explains how PD-linked mutations that lie within the kinase domain result in hPINK1 loss-of-function and provides a platform for the exploration of small molecule modulators of hPINK1.