Current practices of partner notification among MSM with HIV, gonorrhoea and syphilis in the Netherlands: an urgent need for improvement

ABSTRACT: BACKGROUND: Partner notification (PN) among individuals newly diagnosed with HIV/STI is seen as a vital tool to identify others at risk of infection. However, hardly any data are available on the effectiveness of PN on HIV/STI transmission in the Netherlands. This study aims to fill this gap by assessing current PN practices, case-finding effectiveness, and determinants of being notified among men having sex with men (MSM) in the Netherlands. METHODS: Nurses from five STI centers participated in a prospective pilot study on PN outcomes (partners being: at risk, notifiable, notified, and tested) for HIV/STI, by completing a newly developed PN registration form (PN database). PN outcomes including case-finding effectiveness (number of newly diagnosed cases in partners/number of partners being tested) for HIV, syphilis, and gonorrhoea were studied among MSM. Furthermore, the national STI database was analyzed to identify determinants of being notified. The number of infections that remained undetected was estimated based on these two databases. RESULTS: In total 105 MSM, newly diagnosed with HIV/STI, reported 612 sexual partners at risk of whom 41% were notifiable and 31% were notified. Patient referral was the predominant PN method (90%). The overall case-finding percentage was 36% (HIV: 15-33%, gonorrhoea: 17- 50% and syphilis: 4-11%). Case-finding percentages were lower in the national STI database: 21% (5%, 28%, 12%). Persons with one or more sexual partners, known HIV positives, and IDU were more likely to be notified to the STI clinic. Notified clients were more likely to have HIV/STI than unnotified clients (OR 1.7-2.5). Based on these two databases, an estimated 75 to 133 infections remained undetected (HIV: 12-90; gonorrhoea: 28-97; syphilis: 5-12 infections). CONCLUSIONS: Partner notification among MSM in the Netherlands is suboptimal; an extensive number of STI/HIV infections remained undetected mainly due to unnotifiable partners. To enhance PN practices, combined and innovative PN interventions such as Internet-based PN will be implemented for hard-to-reach MSM and other risk groups.     

Uterine Remnants and Pelvic Pain in Females with Mayer-Rokitansky-Küster-Hauser Syndrome

ObjectiveTo assess the association between pelvic pain and uterine remnants and review the management of pelvic pain in females with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.DesignRetrospective cohort.SettingDepartment of Obstetrics and Gynecology at a tertiary referring medical center.PatientsForty-eight females with MRKH presenting from 1997 to 2011 with anatomy confirmed by magnetic resonance imaging (MRI).InterventionsNone.Main Outcome MeasurePrevalence Of uterine remnants and the association of uterine remnants with pelvic pain in females with MRKH.ResultsOf the 48 females with MRKH, 23 (48%) had uterine remnants and 22 (46%) had pelvic pain. Presence of endometrium was associated with pelvic pain (RR = 2.3; 95% CI = 1.2-4.7) in females with MRKH. Of the females with MKRH and pain, 9/22 had laparoscopy, with endometriosis seen in 5/9 of the uterine remnants at stages higher than are usually seen in teenagers (56%). Nine patients with pain and uterine remnants (8 with endometrium, 1 without) had laparoscopic removal of uterine remnants with resolution of pain.ConclusionsGiven the high prevalence of uterine remnants in females with MRKH, anatomic evaluation with MRI should be considered when assessing the etiology of pelvic pain. Presence of endometrium within uterine remnants, and subsequent endometriosis, in females with MRKH may be associated with pelvic pain necessitating surgical or medical management.     

Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration

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A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

BackgroundOur aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature.MethodsWe performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature.ResultsOur patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0‐54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity.ConclusionThe first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.     

Targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden

The membrane-anchored serine proteases are a unique group of trypsin-like serine proteases that are tethered to the cell surface via transmembrane domains or glycosyl-phosphatidylinositol-anchors. Overexpressed in tumors, with pro-tumorigenic properties, they are attractive targets for protease-activated prodrug-like anti-tumor therapies. Here, we sought to engineer anthrax toxin protective antigen (PrAg), which is proteolytically activated on the cell surface by the proprotein convertase furin to instead be activated by tumor cell-expressed membrane-anchored serine proteases to function as a tumoricidal agent. PrAg''s native activation sequence was mutated to a sequence derived from protein C inhibitor (PCI) that can be cleaved by membrane-anchored serine proteases, to generate the mutant protein PrAg-PCIS. PrAg-PCIS was resistant to furin cleavage in vitro, yet cytotoxic to multiple human tumor cell lines when combined with FP59, a chimeric anthrax toxin lethal factor-Pseudomonas exotoxin fusion protein. Molecular analyses showed that PrAg-PCIS can be cleaved in vitro by several serine proteases including the membrane-anchored serine protease testisin, and mediates increased killing of testisin-expressing tumor cells. Treatment with PrAg-PCIS also potently attenuated the growth of testisin-expressing xenograft tumors in mice. The data indicates PrAg can be engineered to target tumor cell-expressed membrane-anchored serine proteases to function as a potent tumoricidal agent.     

Role of robotic-assisted pancreatic surgery:lessons learned from our initial experience

BACKGROUND:Minimally invasive surgery has achieved worldwide acceptance in various fields, however, pancreatic surgery remains one of the most challenging abdominal pro-cedures. In fact, the indication for robotic surgery in pancre-atic disease has been controversial. The present study aimed to assess the safety and feasibility of robotic pancreatic resec-tion. METHODS: We retrospectively reviewed our experience of robotic pancreatic resection done in Sanchinarro University Hospital. Clinicopathologic characteristics, and perioperative and postoperative outcomes were recorded and analyzed. RESULTS: From October 2010 to April 2016, 50 patients underwent robotic-assisted surgery for different pancreatic pathologies. All procedures were performed using the da Vinci robotic system. Of the 50 patients, 26 were male and 24 female. The average age of all patients was 62 years. Operative time was 370minutes. Among the procedures performed were 16 pancreaticoduodenectomies (PD), 23 distal pan-createctomies (DP), 11tumor enucleations (TE). The mean hospital stay was 17.6 days in PD group, 9.0 days in DP group and 8.4 days in TE group. Pancreatic fistula occurred in 10 cases (20%), 2 after PD, 3 after DP, and 5 after TE. Four pa-tients had postoperativetransfusion in PD group and one in DP group. Conversion to open laparotomy occurred in four patients (8%). No serious intraoperative complications were observed. CONCLUSIONS:From our early experience, robotic pancre-atic surgery is a safe and feasible procedure. Further experi-ence and follow-up are required to confirm the role of robotic approach in pancreatic surgery.