COMPARISON OF XANTHINE OXIDASE INHIBITORS IN GOUTY PATIENTS WITH HYPERURICEMIA

Objective: Febuxostat is more effective/superior to Allopurinol in reducing the serum uric acid (SUA) level in the treatment of hyperuricemic withgout.Methods: This randomized control study included 200 hyperuricemic patients with gout, at Multi-center study including Outdoor Departments ofMedicine from four different hospitals of Lahore, Pakistan. Patients age range 18-50 years diagnosis with hyperuricemia and gout, SUA >8 mg/dlwere included while severe renal impairment and alanine aminotransferase and aspartate aminotransferase patients were excluded from the study.Results: About 200 patients treated with hyperuricemic with gout were randomly divided into four groups (50%) patients were in each groupreceived different treatment. Out of 200 patients, 118 (59%) were male and 82 (41%) were female with mean age 42.37±9.47 years. Among theFebuxostat group, patients' success rate of lowering SUA level was found to be 32 (64%) as compared to Allopurinol 16 (32%). Drug compliance wassimilar among treatment groups, i.e. Allopurinol and Febuxostat while the trend toward drug compliance in Allopurinol + Vitamin C and Febuxostat +Vitamin C groups showed similar in number.Conclusion: Febuxostat is safe and effective to Allopurinol for the treatment of hyperuricemia with gout as the Febuxostat has a significant associationwith lowering SUA concentration <6 mg/dl. It is concluded that although Febuxostat is safe and effect alone in gouty patients, but it has somehow alittle effect with Vitamin C especially in patients who are feeble.Keywords: Febuxostat, Allopurinol, Serum uric acid.Â

Optimal 3D UAV BS Placement by Considering Autonomous Coverage Hole Detection, Wireless Backhaul and User Demand

The rising number of technological advanced devices making network coverage planning very challenging tasks for network operators. The transmission quality between the transmitter and the end users has to be optimum for the best performance out of any device. Besides, the presence of coverage hole is also an ongoing issue for operators which cannot be ignored throughout the whole operational stage. Any coverage hole in network operators' coverage region will hamper the communication applications and degrade the reputation of the operator's services. Presently, there are techniques to detect coverage holes such as drive test or minimization of drive test. However, these approaches have many limitations. The extreme costs, outdated information about the radio environment and high time consumption do not allow to meet the requirement competently. To overcome these problems, we take advantage of Unmanned aerial vehicle (UAV) and Q-learning to autonomously detect coverage hole in a given area and then deploy UAV based base station (UAV-BS) by considering wireless back-haul with the core network and users demand. This machine learning mechanism will help the UAV to eliminate human-in-the-loop (HiTL) model. Later, we formulate an optimisation problem for 3D UAV-BS placement at various angular positions to maximise the number of users associated with the UAV-BS. In summary, we have illustrated a cost-effective as well as time saving approach of detecting coverage hole and providing on-demand coverage in this article

Papillary thyroid cancer associated with syndrome of inappropriate antidiuresis: a case report

<p>Abstract</p> <p>Introduction</p> <p>The syndrome of inappropriate antidiuresis is the most common cause of euvolemic hypo-osmolality. This syndrome is associated with a wide variety of diseases. However, its most frequent causes are related to malignancies, especially lung cancer. In this case report, we describe an unknown association of the syndrome of inappropriate antidiuresis with papillary thyroid cancer.</p> <p>Case presentation</p> <p>We present the case of a 71-year-old Caucasian, German woman with marked hyponatremia and neurological symptoms. After a detailed clinical investigation, the common causes of syndrome of inappropriate antidiuresis and other malignancies were ruled out. A thyroid nodule was detected by ultrasound and magnetic resonance imaging. Although fine needle aspiration cytology showed negative results, our patient underwent surgery. Papillary thyroid cancer was later diagnosed. After total thyroidectomy, a complete remission of the clinical symptoms occurred and our patient subsequently had iodine-131 radioactive therapy. Hyponatremia was no longer observed during the follow-up investigations.</p> <p>Conclusion</p> <p>This is the first reported case of paraneoplastic syndrome of inappropriate antidiuresis caused by papillary thyroid carcinoma. Since its symptoms occurred before the development of local symptoms, total thyroidectomy may provide a timely and efficient treatment for the underlying malignancy.</p

Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group

BackgroundTo determine shortâ and longâ term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET).MethodsThe data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multiâ institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.ResultsA total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000â 2004: 9.3% vs 2013â 2016: 54.8%; Pâ <â 0.01). In the matched cohort (nâ =â 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200â mL, Pâ <â 0.001), lower incidence of Clavienâ Dindoâ â ¥â III complications (12.1% vs 24.8%, Pâ =â 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, Pâ =â 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5â year cumulative recurrence, 10.1% vs 31.1%, Pâ <â 0.001), yet equivalent overall survival (OS) rate (5â year OS, 92.1% vs 90.9%, Pâ =â 0.550) compared with patients who underwent OPD.ConclusionPatients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar longâ term OS.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150595/1/jso25481_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150595/2/jso25481.pd

Evaluation of adjunctive HPV testing by Hybrid Capture II(® )in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy

BACKGROUND: As a proportion of high grade cervical intraepithelial neoplasia (CIN2/3) are associated with equivocal cervical smears, which show borderline or mild dyskaryosis, follow up with repeat smears, colposcopy and biopsy is required. Since infection with oncogenic Human Papilloma Virus (HR HPV) has been found to be associated with the development of cervical cancer, HRHPV testing appears to be an alternative. OBJECTIVE: The present study assesses if HRHPV testing can predict CIN2/3 in women referred for mild dyskaryosis and borderline cytological changes in an health authority with a referral policy to colposcopy after one single mild dyskaryotic Pap smear. STUDY DESIGN: The HPV DNA Hybrid Capture II (Digene/Abbott, Maidenhead) was evaluated on 110 consenting women with mild dyskaryosis and 23 women with persistent borderline changes, who were referred for colposcopy between May and November 2001. A cost comparison between two referral policies was performed. RESULTS: CIN2/3 was diagnosed histologically in 30 of 133 women (22%) with minor cytological abnormalities. As the Receiver Operator Characteristics plot suggested a cut-off of 3 pg/ml the HRHPV HCII was evaluated at 3 RLU (relative light units) and at the manufacturer's recommendation of 1 RLU. At both cut-offs sensitivity and negative predictive value were high at 97%. Specificity was low at 37% at a cut-off of 1 pg/ml and 46% at a cut-off of 3 RLU. To remain cost neutral in comparison to immediate colposcopy the costs for one HR HPV HC II must not exceed £34.37 per test at a cut off of 3 pg/ml. CONCLUSION: The negative likelihood ratio (NLR) was of good diagnostic value with 0.089 at 1 RLU and 0.072 at 3 RLU, which reduces the post-test probability for CIN2/3 to 2% in this population. Women with minor cytological disorders can be excluded from colposcopy on a negative HR HPV result. Specificity can be improved by restricting HR HPV testing to women with persistent borderline cytological changes or to women over 30 years

Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting

Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶ 100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226), an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio

The Caenorhabditis elegans Elongator Complex Regulates Neuronal α-tubulin Acetylation

Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore, a genetic screen was employed in the nematode Caenorhabditis elegans that identified the Elongator complex as a possible regulator of α-tubulin acetylation. Detailed characterization of mutant animals revealed that the acetyltransferase activity of the Elongator is indeed required for correct acetylation of microtubules and for neuronal development. Moreover, the velocity of vesicles on microtubules was affected by mutations in Elongator. Elongator mutants also displayed defects in neurotransmitter levels. Furthermore, acetylation of α-tubulin was shown to act as a novel signal for the fine-tuning of microtubules dynamics by modulating α-tubulin turnover, which in turn affected neuronal shape. Given that mutations in the acetyltransferase subunit of the Elongator (Elp3) and in a scaffold subunit (Elp1) have previously been linked to human neurodegenerative diseases, namely Amyotrophic Lateral Sclerosis and Familial Dysautonomia respectively highlights the importance of this work and offers new insights to understand their etiology

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes

ICAR: endoscopic skull‐base surgery

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