The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study

PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.     

Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore

Background To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.Methods We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.Results RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.Conclusions Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.Subject terms: Breast cancer, Breast cancer, Chemotherapy     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Nivolumab as adjuvant treatment for a spinal melanocytoma: A case report

Rationale:Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy.Patient concerns:A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia.Diagnoses:A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis.Interventions:The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area.Outcomes:Disease progression finally led to the patient''s death 3 years after diagnosis.Lessons:This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.     

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade

Heart Failure Reviews - An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after...     

Temporal and Spatial Compartmentalization of Drug-Resistant Cytomegalovirus (CMV) in a Child with CMV Meningoencephalitis: Implications for Sampling in Molecular Diagnosis

We describe a case of antiviral-resistant cytomegalovirus meningoencephalitis occurring after hematopoietic stem cell transplantation. Antiviral-resistant cytomegalovirus was identified in blood 16 months earlier. However, wild-type cytomegalovirus was evidenced in blood when the meningoencephalitis was diagnosed. Treatment of meningoencephalitis should be adapted to all previously identified resistance mutations in any compartment.     

Peri-implant bone preservation of a novel,self-cutting,and fully tapered implant in the healed crestal ridge of minipigs: submerged vs. transgingival healing

Clinical Oral Investigations - The aim of this study was to assess the influence of transgingival compared with submerged healing on peri-implant bone maintenance around a novel, fully tapered...