Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC. PATIENTS AND METHODS: Patients who progressed on androgen deprivation therapy, one or more ARPIs, and taxane chemotherapy (unless declined/ineligible) were enrolled. The study included dose escalation (part A) and expansion (part B) of BMS-986365 up to 900 mg twice daily. Primary objectives were safety and tolerability, and to define maximum tolerated dose and/or recommended phase II dose. Key secondary endpoints included decline in prostate-specific antigen ≥50% (PSA50) and radiographic progression-free survival (rPFS). RESULTS: Parts A and B enrolled 27 and 68 patients, respectively. In part B, the median number of prior therapies was 4 (range 2-11). The most common treatment-related adverse events were asymptomatic prolonged corrected QT interval (47%) and bradycardia (34%). Part A maximum tolerated dose was not reached and recommended phase II dose selection is ongoing. Across part B three highest doses (400-900 mg twice daily, n = 60), PSA50 was 32% (n = 19), including 50% (n = 10/20) at 900 mg; median rPFS (95% confidence interval) was 6.3 months (5.3-12.6 months), including 8.3 months (3.8-16.6 months) at 900 mg; and rPFS was longer in patients without versus with prior chemotherapy: 16.5 months (5.5 months-not evaluable) versus 5.5 months (2.7-8.3 months), respectively. Efficacy was observed in patients with mCRPC with AR ligand binding domain (LBD) WT or with AR LBD mutations. CONCLUSIONS: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with potentially higher benefit in chemotherapy-naive patients. These data show the potential of BMS-986365 to overcome resistance to current ARPIs, regardless of AR LBD mutation status.

Nutritional Management in Children and Adolescents with Severe Neurological Impairment-Who Cares? A Web-Based Survey Among Pediatric Specialists in Germany.

BACKGROUND: Nutritional management of children and adolescents with severe neurological impairment (SNI) is challenging. A web-based survey was distributed to identify the present situation and the knowledge of the involved medical professionals in Germany. METHODS: The survey was created with LimeSurvey, and access data were distributed by several medical societies. Eighty-three questions covered four topics: "general information," "gastro- and jejunostomy procedure," "handling of gastrostomies and feeding tubes," and "nutritional management and follow-up of children and adolescents with SNI." A descriptive analysis was performed with Microsoft Excel. RESULTS: A total of 156 participated (65 completed and 91 partially), 27% being pediatric gastroenterologists, 23% pediatric neurologists, and 10% pediatric surgeons. The most common indications for gastrostomy and tube feeding were oropharyngeal dysfunction and failure to thrive. Many patients were still underweight after some months of enteral feeding. The procedure of gastrostomy and handling recommendations varied broadly. Frequently, standard operating procedures (SOPs) and written local guidelines did not exist, and there was a considerable request for training. Only 53% of participants were aware of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition position paper published in 2017, even fewer (38%) followed the guidelines. The recommended measures to assess a nutritional status were often not respected. CONCLUSION: Nutritional management of children and adolescents with SNI in Germany is still strongly deficient. Despite the international guideline of 2017, few colleagues are aware of and adhere to the recommendations. This could be improved by interdisciplinary teaching and evaluation of the reasons for noncompliance. The procedure of gastrostomy and the patients' follow-up vary widely. Therefore, modified SOPs should be developed.

Outcome of percutaneous transhepatic biliary interventions in the management of biliary enteric anastomotic strictures with hepatolithiasis.

AIM: To evaluate percutaneous transhepatic biliary interventions (PTBI) using the ADDFREE (Access-Drain-Dilate-Flush-REpeat periodically-Evaluate and remove) technique and its outcomes in patients with biliary enteric anastomotic strictures (BEAS) and hepatolithiasis. MATERIAL AND METHODS: A retrospective review was undertaken of patients having hepatolithiasis with BEAS who underwent PTBI with a therapeutic intent (from January 2010 to January 2021) was performed. The technical and clinical successes of PTBI were analysed. Technical success was divided into duct access, crossing of BEAS, stricture resolution, and calculi clearance. Improvement of liver function tests, resolution of leucocytosis and presenting complaints were considered as clinical success. The patients were followed-up for a minimum duration of 6-months. RESULTS: Eighteen patients received PTBI in form of the ADDFREE technique. Hepatolithiasis was bilobar (44.4%), unilobar in multiple ducts (unilobar-m; 27.8%) and unilobar in a single duct (unilobar-s; 27.8%) along with anastomotic stricture. The average number of sessions of stone clearance for bilobar, unilobar-m, and unilobar-s was 4.4 (±1.6), 3.6 (±2.4), and 1.5 (±0.5), respectively. Clinical success was observed in 14 (77.8%), while one patient had recurrence of calculi and received repeat treatment. Bile culture was positive for bacterial organisms in 17 (94.4%) patients. No major complication were seen while minor complication were seen in five patients consisting of self-limiting haemobilia (n=1), per-catheter bile leak (n=2) and aggravation of cholangitis (n=2). CONCLUSION: PTBI, consisting of bile duct access, cholangioplasty, and calculi clearance, is a safe and effective technique for the treatment of patients having hepatolithiasis secondary to BEAS.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Can honey improve the quality of cryopreserved cross bred ram semen added to tris egg yolk extender?

BACKGROUND: Honey can improve the quality of cryopreserved ram semen because of its multinutrient and cryoprotective nature added to standard tris egg yolk extender. OBJECTIVE: Different concentrations of honey were added to the standard tris egg yolk extender to improve the post-thaw quality of crossbred ram semen. METHOD: Thirty six (36) ejaculates from eight healthy cross bred rams were pooled and divided into four aliquots. Standard tris egg yolk extender without any alteration acted as Control (C) and was supplemented with different concentrations of honey, viz. T1 (honey 1.5%), T2 (2.5%), and T3 (3.5%). RESULTS: The percent (mean ± S.E.M) sperm motility at pre-freeze was significantly (P < 0.05) higher in Group T2 and at post-thaw in Group T3 in comparison to T1 and C treatment groups. The percent (mean ± S.E.M) HOST reacted spermatozoa at post-thaw was significantly (P < 0.05) higher in Group C and at pre-freeze the value was significantly (P < 0.05) higher in the same treatment group than Group T1. The mean MDA level (mean ± S.E.M) at post thaw was significantly (P < 0.05) lower in Group T3 than the treatment groups C and Group T1. CONCLUSION: From this study it is concluded that the addition of 3.5% honey to the standard tris egg yolk extender provides better protection to ram semen than the addition of 1.5% honey (i.e., Control). doi.org/10.54680/fr22610110212.

Changes in pain catastrophization and neuropathic pain following operative stabilisation for patellofemoral instability: a prospective study with twelve month follow-up.

PURPOSE: To determine the prevalence and change in neuropathic pain or pain catastrophizing before and 12 months following patellar stabilisation surgery for patellofemoral instability. METHODS: We conducted a prospective clinical audit within a UK NHS orthopaedic surgical centre. Data from 84 patients with patellofemoral instability requiring stabilisation were analysed. Fifty percent (42/84) underwent MPFL reconstruction alone, and 16% (13/84) had both trochleoplasty and MPFL reconstruction. Neuropathic pain was assessed using painDETECT score. Pain catastrophizing was assessed using the Pain Catastrophizing Score. The Norwich Patellar Instability (NPI) Score and Kujala Patellofemoral Disorder Score were also routinely collected pre-operatively and one year post-operatively. RESULTS: At 12 months post-operatively there was a statistically significant reduction in mean Pain Catastrophizing Scores (18.9-15.7; p < 0.02), but no change in mean painDETECT scores (7.3-7.8; p = 0.72). There was a statistically significant improvement in NPI scores (90.2-61.9; p < 0.01) and Kujala Patellofemoral Disorder Scores (48.7-58.1; p = 0.01). The prevalence of pain catastrophizing decreased from 31% pre-operatively to 24% post-operatively, whereas the prevalence of neuropathic pain remained consisted (10-11%). CONCLUSIONS: Neuropathic pain and catastrophizing symptoms are not commonly reported and did not significantly change following patellofemoral stabilisation surgery. Whilst low, for those affected, there remains a need to intervene to improve outcomes following PFI surgery.

In vitro Assessment of Tris Egg Yolk and Soybean Lecithin Based Extenders for Cryopreservation of Crossbred Ram Semen.

BACKGROUND: The replacement of egg yolk with alternative plant-derived soybean lecithin is gaining interest in both animal and human sperm cryopreservation owing to biosecurity issues with egg yolk based extenders. OBJECTIVE: To evaluate the comparative effect of egg yolk and soyabean lecithin based extenders on the quality of cryopreserved crossbred ram semen. METHODS: Pooled ejaculates (total ejaculates = 36) were divided into two aliquots and extended with Tris egg yolk extender (Tris extender) and soybean lecithin based commercial extender (Ovixcell) RESULTS: Among the two extenders, Ovixcell showed better sperm quality both at the pre-freeze (Sperm motility) and post-thaw stages. Lower malondialdehyde (MDA) level (nmol/mL) was observed in Ovixcell as compared to Tris extender. Both sperm quality and MDA level decreased significantly (P < 0.05) from pre-freeze to post-thaw in both the extenders. CONCLUSION: The findings of the present study indicate that Ovixcell is a comparable alternative to Tris extender for the cryopreservation of crossbred ram semen.

Global macroeconomic burden of epilepsy and the role for neurosurgery: a modelling study based upon the 2016 Global Burden of Disease data.

BACKGROUND AND PURPOSE: Although the significant morbidity and mortality burden associated with epilepsy is well understood, associated economic consequences are yet to be estimated on a global scale. We sought to: (i) estimate the value of lost economic welfare attributable to epilepsy among countries included in the 2016 Global Burden of Disease study, (ii) evaluate differences in disease burden between countries of varied income classification and location, and (iii) understand the proportion of this burden that requires neurosurgical consultation and intervention. METHODS: Publicly available morbidity and mortality data were incorporated into a 'full-income' model to generate estimates of the cumulative value of lost economic welfare (VLW) related to epilepsy. Results from a survey of neurosurgeons were then used to estimate the VLW attributable to the proportion of disease requiring neurosurgical consultation and intervention. RESULTS: A total of 195 countries and territories were included in this analysis. We estimate that the cumulative VLW related to epilepsy was $647.37 billion [2016 US dollars (USD), purchasing power parity (PPP)]. Economic welfare losses were equivalent to a mean of 1.45% (±1.00%) of gross domestic product. The value of economic losses attributable to the proportion of the burden necessitating neurosurgical consultation and intervention was $258.95 billion (2016 USD, PPP) and $155.37 billion (2016 USD, PPP) respectively. CONCLUSIONS: Our results indicate that the economic consequences of epilepsy-related morbidity and mortality are substantial. When considered with evidence supporting the cost-effectiveness of various interventions for improved epilepsy diagnosis and management, our findings suggest that the implementation of simple and affordable measures may avert significant economic loss.

Disentangling the evolutionary and biogeographical history of the freshwater fish trematode genus Creptotrema (Digenea: Allocreadiidae) using an integrative taxonomy approach: the case of Creptotrema agonostomi in Middle American mountain mullets.

Species of the allocreadiid genus Creptotrema are parasites of freshwater fishes in the Americas. Species in the genus possess one pair of muscular oral lobes on the oral sucker. Currently, the genus contains eight species, six distributed in South America, one in Middle America and one in North America. Genetic data are only available for the North American species, Creptotrema funduli, a parasite of fundulids originally described from Oneida Lake, New York State. In this study, we obtained 28S ribosomal DNA sequences of trematodes morphologically similar to Creptotrema agonostomi from the mountain mullet, Dajaus monticola, across a wide geographical range in Middle America. Our molecular phylogenetic analyses showed that (1) the genus Creptotrema, as currently conceived, is not monophyletic; (2) the allocreadiids in mountain mullets should be re-allocated in the genus Pseudoparacreptotrema; and (3) the allocreadiid trematodes from D. monticola across Middle America represent four morphologically similar species, three of which can be distinguished genetically. These three new species are described herein using an integrative taxonomy approach. We contend that accurate estimates of species diversity and phylogenetic relationships among allocreadiids, and most likely other species of trematodes, necessarily require an integrative taxonomy approach that should consider at least DNA sequences and scanning electron microscopy.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

Parasites of freshwater fishes and the Great American Biotic Interchange: a bridge too far?

We examine the extent to which adult helminths of freshwater fishes have been part of the Great American Biotic Interchange (GABI), by integrating information in published studies and new data from Panama with fish biogeography and Earth history of Middle America. The review illustrates the following: (1) the helminth fauna south of the Trans-Mexican Volcanic Belt, and especially south of the Isthmus of Tehuantepec, shows strong Neotropical affinities; (2) host-parasite associations follow principles of the 'biogeographic core fauna' in which host-lineage specificity is pronounced; (3) phylogenetic analysis of the widespread freshwater trematode family Allocreadiidae reveals a complex history of host-shifting and co-diversification involving mainly cyprinodontiforms and characids; (4) allocreadiids, monogeneans and spiruridan nematodes of Middle American cyprinodontiforms may provide clues to the evolutionary history of their hosts; and (5) phylogenetic analyses of cryptogonimid trematodes may reveal whether or how cichlids interacted with marine or brackish-water environments during their colonization history. The review shows that 'interchange' is limited and asymmetrical, but simple narratives of northward isthmian dispersal will likely prove inadequate to explain the historical biogeography of many host-parasite associations in tropical Middle America, particularly those involving poeciliids. Finally, our study highlights the urgent need for targeted survey work across Middle America, focused sampling in river drainages of Colombia and Venezuela, and deeper strategic sampling in other parts of South America, in order to develop and test robust hypotheses about fish-parasite associations in Middle America.

Expression of miR-210 in relation to other measures of hypoxia and prediction of benefit from hypoxia modification in patients with bladder cancer.

BACKGROUND: The addition of hypoxia modifiers carbogen and nicotinamide (CON) to radiotherapy (RT) improved overall survival (OS) in bladder cancer patients in the BCON phase III clinical trial. We investigate whether expression of hsa-miR-210 in BCON patient samples reflects hypoxia and predicts benefit from hypoxia modification. METHODS: In all, 183 T1-T4a bladder cancer samples were available for miR-210 analysis. A total of 86 received RT+CON and 97 received RT alone. TaqMan qPCR plates were used to assess miR-210 expression. Patients were classified as low (

Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer.

BACKGROUND: Pre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer. PATIENTS AND METHODS: Seventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable. RESULTS: An absolute lymphocyte count of 1.5 × 10(9)/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0-2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5-0.87; P = 0.003). CONCLUSION: Pre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.

Comparison between retrograde and transeptal approach in radiofrequency catheter ablation of left accessory pathways.

To study a series of patients submitted to radiofrequency catheter ablation (RFA) of left accessory pathways (AP) using the transeptal approach (TSA) as compared to the conventional retrograde arterial approach (RAA). Sixty consecutive patients (44 male; mean age of 35.60±11.63 years) with 60 left APs (39 overt and 21 concealed) underwent catheter ablation using the TS method (30 patients) and the RAA method (30 patients) in an alternate fashion. The analysis was performed according to the intention-to-treat principle. The transeptal puncture was successfully performed in 29 patients (96%). This access allowed primary success in the ablation in all the patients without any complication. When we compared this approach with the RAA there was no difference as regards the primary success (p=0.103), fluoroscopy time (p=0.565) and total time (p=0.1917). Three patients in the RAA group presented a vascular complication. The TSA allowed shorter ablation times (p=0.006) and smaller number of radiofrequency applications (p=0.042) as compared to the conventional RAA. The patients who had unsuccessful ablation in the first session in each approach underwent with the opposite technique (cross-over), with a final ablation success rate of 100%.The TS and RA approaches showed similar efficacy and safety for the ablation of left accessory pathways. The TSA allowed shorter ablation times and smaller number of radiofrequency applications. When the techniques were used in a complementary fashion, they increased the final efficacy of the ablation.

Study of Commonest Variety of Sinonasal Malignancy and Its Sex Wise Distribution.

This study was done to find the commonest variety of sinonasal malignancy and its association with sex.This cross-sectional study was conducted in the Department of Otolaryngology - Head & Neck Surgery Department, Dhaka Medical College & Hospital and in the Department of Otolaryngology - Head & Neck Surgery Department, Bangabandhu Sheikh Mujib Medical University between January 2009 and December 2009. A total of 146 cases of sinonasal malignancy were consecutively included in the study. The diagnosis was confirmed by histopathology. The mean age was 47.8 years (range: 22-75 years). Over three-quarters (77%) of the patients were male with male to female ratio being 3:1. Nearly one-third (30.8%) of the patients was farmer and over one-third (36.3%) was illiterate. The right sinonasal region was involved in 48.6% cases, left sinonasal region in 39% and both sinonasal region in 12.4% cases. Histopathological diagnosis of sinonasal malignancy revealed that squamous cell carcinoma accounted for 82.9% of sinonasal malignancies, 9.6% adenocarcinoma and the rest were olfactory neuroblastoma, adenoid cystic carcinoma and mucoepidermoid carcinoma. About 96.6% of the tumours involved nasal cavity, 97.9% maxillary sinuses, 17.8% frontal sinuses, 48.6% ethmoidal sinuses and 13% sphenoid sinuses. Over 80% of patients were smoker. Exposure to wood dust was found in 26% of cases. Lather tanning in 4.8% of cases and welding in 4.1% of cases. T staging shows that nearly half (48.6%) of the patients lesion was T2, 29.5% T3, 19.9% T4 and 2.1% T1. None of the patients exhibited lymph node involvement or distant metastasis. Males tend to develop squamous cell carcinoma significantly more than the females with risk of acquiring squamous cell carcinoma being nearly 3(1.1-7.1) times higher in male than that in female (p=0.022). The study concludes that the most common histopathological variety of sinonasal malignancy is squamous cell carcinoma and males are prone to develop this malignancy more frequently than the females.

Knowledge and practices of mothers on childhood diarrhoea and its management attended at a tertiary hospital in bangladesh.

This descriptive cross sectional study was conducted in Pediatric out Patient Department (OPD) of Mymensingh Medical College Hospital (MMCH) from March 2014 to August 2014 to assess the knowledge and practices of the mothers in acute diarrhoeal diseases in children under-five years of age regarding use of oral rehydration solution (ORS), zinc, other drugs and feeding practices. Four hundred children under-five years of age having acute diarrhoea were included in the study by systematic random sampling. A structured, pretested, interviewer-administered questionnaire was used to collect data from mothers of children having diarrhoeal diseases. ORS was offered by 360(90.00%) of the mothers. Out of which 279(77.50%) used it by their own knowledge. One hundred and ninety-one (53.06%) mothers prepared it correctly, while 169(46.94%) prepared it incorrectly. Of 169, 129(35.83%) mothers used less amount of water, while 40(11.11%) mothers used much amount of water to prepare ORS. Of 360 mothers, 89(24.72%) mixed part of the content of ORS sachet at a time. Of 360 mothers, only 55(15.28%) offered correct amount of ORS after each purging. Zinc was offered in 142(35.50%) children. Of 400, only 13(3.25%) mothers used recommended home-based fluid, while 70(17.50%) mothers offered increased amount of fluid to their child. Drugs other than zinc and ORS were used in 247(61.75%) children. Among drugs, other than zinc and ORS, antibiotics was used in 109(44.13%) cases, whereas antiprotozoal in 97(39.27%) cases. Amount of liquid given was more than usual in 70(17.50%) children, same as usual in 57(14.25%) children and less than usual in 273(68.25%) children. Amount of food given was same as usual in 59(14.75%) children, while less than usual in 341(85.25%) children. Control of diarrhoeal diseases programme is successful in introducing ORS at mass level. Great emphasis is needed to educate mothers about preparation and quantity of ORS to be given to children with diarrhoeal diseases.

Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.

BACKGROUND: Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion. METHODS: Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD. RESULTS: From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative. CONCLUSIONS: The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD.

Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.

BACKGROUND: The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON. METHODS: A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis. RESULTS: Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21%; hazard ratio (HR) 0.48, 95% CI 0.26-0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43-1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone. CONCLUSIONS: HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.

Evaluation of the outcome of replacement hemiarthroplasty by uncemented bipolar prosthesis in displaced fracture neck femur.

Despite continued discussion regarding the treatment of displaced femoral neck fractures, controversies continue regarding their optimal treatment, including the choice of implant and fixation method. Hemiarthroplasty is one of the option which eliminate concerns about fixation failure, nonunion, and avascular necrosis and has become the choice of surgery among the aged >60. This prospective interventional study was carried out on 28 cases at the Department of Orthopaedic Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), from July 2009 to April 2012 to evaluate cementless, bipolar prosthesis among the active elderly patients. All subjects were evaluated with regard to postoperative clinical, functional and activity outcome (Modified Harris Hip Scoring and Hip Outcome Scoring), intra and post operative complications. One case was dropped from follow up and 22(81.48%) patients were considered to have satisfactory outcome after statistical analysis by chi-square test on at least 12 months follow up records. Although prosthetic stem valgus and periprosthetic fracture developed in 02 cases and 01 patient had sunken prosthesis, uncemented bipolar hemiarthroplasty can give significantly good functional outcomes with minimal complications for displaced intracapsular femoral neck fracture in active elderly patients.