Treatment of external genital warts in men with imiquimod 2% in cream. A placebo-controlled, double-blind study

OBJECTIVE: The purpose of this double-blind, placebo-controlled study was to evaluate the safety, clinical efficacy and tolerability of imiquimod (2%) in cream to cure external genital warts in males. METHODS: Preselected male patients (n=60) ranging between 18 and 50 years of age (mean 24.2) harbouring 558 lesions (mean 9.3) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient was allocated a precoded 25g tube, and instructions on how to apply the trial medication to their lesions at home once daily for three consecutive days per week (max. 12 application in 4 weeks). To evaluate the safety, clinical efficacy and tolerance, patients were exa-mined on a weekly basis. Cure was defined as the total elimination of treated warts with PCR, and Southern blot hybridization confirmed negative HPV DNA. RESULTS: By the end of the treatment, 40% (24/60) patients and 49.8% (278/558) warts were cured. Breaking the code revealed that imiquimod cream had cured 70% (21/30) patients and 86.8% of warts, while placebo healed three subjects and 28 warts (P=0.0001). Eleven patients (18.3%), predominantly in the imiquimod cream group, experienced mild to moderate, non-objective, drug-related side effects with no dropouts. The study was followed up for 18 months from the first day of the treatment, and among the 26 cured patients, one in the imiquimod cream group and two in the placebo had a relapse after 14 months. CONCLUSION: The study demonstrated that 2% imiquimod in cream with mild non-objective side effects is safe, tolerable and significantly more effective than placebo in curing external genital warts in males.     

Application of transcatheter valves for aortic valve replacement in pediatric patients: A case series

• Diabetic patients are frequently affected by coronary artery disease (CAD) and are at increased risk of CAD‐related adverse events, even after drug‐eluting stent (DES) implantation. If currently available DES have similar safety and efficacy in diabetic and nondiabetic patients is still debated.
• This prospective, multicenter registry showed similar 3‐year outcome in patients undergoing different DES implantation, although diabetic patients, especially those requiring insulin treatment, had significantly higher risk of adverse events than nondiabetic patients.
• Specific efforts to improve the performance of DES in diabetic patients are mandatory to adequately address the unsolved issue of diabetic patients affected by CAD.

     

The Treatment of Cholangiocarcinoma: a Hepatologist’s Perspective

Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered.     

The role of endoscopy after upper gastrointestinal bleeding in sub-Saharan Africa: A prospective observational cohort study

BackgroundUpper gastrointestinal (UGI) bleed is a common surgical disease in sub-Saharan Africa where there is often a lack of diagnostic and interventional adjuncts such as endoscopy. This study sought to characterize the role of endoscopy in management of acute UGI bleeding.Materials and MethodsThis is a prospective observational analysis of adults presenting with an UGI bleed to a tertiary center in Lilongwe, Malawi, over two years. Patients were classified as having no endoscopy, diagnostic endoscopy, or endoscopy with variceal banding. Bivariate, survival analysis, and logistic regression analyses were used to compare intervention cohorts.Results293 patients were included with 49 patients (16.7%) receiving endoscopy with banding, 65 (22.2%) patients receiving diagnostic endoscopy only, and 179 (61.1%) receiving no endoscopy. Upon survival analysis comparing to the no endoscopy group, cox hazard modelling showed an adjusted hazard ratio over 30 days of 0.12 (95% CI 0.02, 0.88, p=0.038) for the endoscopic banding group and a hazard ratio of 0.39 (95% CI 0.13, 1.16, p=0.090) for the diagnostic endoscopy only group. Physical exam findings consistent with cirrhosis and decreasing age were independent predictors of an endoscopic diagnosis of variceal bleeding.ConclusionEsophagogastric varices are a common cause of UGI bleeding in sub-Saharan Africa and can be predicted with age and physical exam findings. Endoscopy with variceal banding has a survival benefit for patients presenting with acute UGI bleed even with relatively low utilization. Appropriately triaging patients with likely variceal bleeding and improving endoscopy capacity would likely have a significant impact on mortality.     

A bi-functional hepatitis B virus core antigen (HBcAg) chimera activates HBcAg-specific T cells and preS1-specific antibodies

A major problem in chronic hepatitis B virus (HBV) infection is that treatment with specific antivirals is life-long since they rarely induce a sustained response. An attractive option is therefore to combine antiviral therapy with some type of immune stimulator, such as a therapeutic vaccine. Several lines of evidence suggest that a key target for the cellular immune response is the HBV core antigen (HBcAg). However, it may also be of advantage to simultaneously improve the neutralizing antibody response to the surface (S) region of HBV. We therefore generated chimeric HBcAg particles expressing preS1 residues 1-42 at the tip of the spike region. We could show that this chimeric HBcAg-preS1 protein primed both HBcAg-specific T cells and antibodies to preS1. This strongly suggests that this may be a viable approach to develop an effective bi-functional therapeutic vaccine as an add-on for the treatment of chronic HBV infections.     

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.     

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.