Efficacy of Semi-Rigid Ureteroscopy and Holmium:YAG Laser Lithotripsy in the Treatment of Ureteric Calculi, a Retrospective Study

Background: Urolithiasis is a common worldwide health problem. Many endosurgical treatments became available for urinary calculi.Objectives: To find out the success clearance and complication rates of ureteric stone treatment using semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy as a day case procedure.Methods: In the period from April 2011 to October 2013, a total of 64 patients who were treated by laser lithotripsy were reviewed retrospectively using Fedail Hospital data. Diagnosis was radiologically confirmed. Semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy was conducted as a day case surgery. Operative details, clearance of stone fragments, failure and complications were analysed. Cases were followed clinically and radiologically after one week and one month.Results: The studied cases were 47 males and 17 females with average age of 47.3 years and ASA I in 52(81.3%). Those who had left ureteric stones were 28(43.8%) patients, only one patient had bilateral stones and 60(93.8%) patients had single stones. The largest stone diameter was 1.9cm. 68.8% had distal ureteric stones, 14.1% had mid third stones, and 17.2% had upper third stones. Most cases 96.9% were operated under spinal anaesthesia with mean operation time 61.2 minutes. Seven patients needed VUJ balloon dilatation to get access to the ureter.20 watt Holmium:YAG laser fibres were used for stone disintegration. 92.2% of cases had uncomplicated clearance, 3.1% minor complications and 4.7% failure of the procedure.100% clearance was confirmed during follow up. Conclusion: Semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy is a safe treatment for ureteric calculi and can be conducted as a day case with high success rate and very low morbidity.Key words: ureteric stone, Semi-rigid ureteroscopy, Holmium:YAG laser lithotripsy

Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

Funding Information: The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research grant number (DSR2020-04-421 )Peer reviewedPostprin

Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease

Peer reviewedPostprin

Synthesis of a New Chelating Iminophosphorane Derivative (Phosphazene) for U(VI) Recovery

A new synthetic chelating N–hydroxy–N–trioctyl iminophosphorane (HTIP) was prepared through the reaction of trioctylphosphine oxide (TOPO) with N–hydroxylamine hydrochloride in the presence of a Lewis acid (AlCl3 ). Specifications for the HTIP chelating ligand were successfully determined using many analytical techniques,13C–NMR,1H–NMR, FTIR, EDX, and GC–MS analyses, which assured a reasonable synthesis of the HTIP ligand. The ability of HTIP to retain U(VI) ions was investigated. The optimum experimental factors, pH value, experimental time, initial U(VI) ion concentration, HTIP dosage, ambient temperature, and eluents, were attained with solvent extraction techniques. The utmost retention capacity of HTIP/CHCl3 was 247.5 mg/g; it was achieved at pH = 3.0, 25◦C, with 30 min of shaking and 0.99 × 10−3 mol/L. From the stoichiometric calculations, approximately 1.5 hydrogen atoms are released during the extraction at pH 3.0, and 4.0 moles of HTIP ligand were responsible for chelation of one mole of uranyl ions. According to kinetic studies, the pseudo–first order model accurately predicted the kinetics of U(VI) extraction by HTIP ligand with a retention power of 245.47 mg/g. The thermodynamic parameters ∆S◦, ∆H◦, and ∆G◦ were also calculated; the extraction process was predicted as an exothermic, spontaneous, and advantageous extraction at low temperatures. As the temperature increased, the value of ∆G◦ increased. The elution of uranium ions from the loaded HTIP/CHCl3 was achieved using 2.0 mol of H2SO4 with a 99.0% efficiency rate. Finally, the extended variables were used to obtain a uranium concentrate (Na2U2O7, Y.C) with a uranium grade of 69.93% and purity of 93.24%. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Princess Nourah Bint Abdulrahman University, PNU: PNURSP2022R13The authors express their gratitude for the support from Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R13), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Design, Synthesis and Biological Evaluation of Novel Benzo[4,5]thiazolo[2,3-c][1,2,4]triazole Derivatives as Potential Anticancer Agents

In the present study, we have designed and synthesized a novel series of benzothiazolotriazole derivatives as potential anticancer agents. The anticancer activity of the newly synthesized compounds was evaluated against three cancerous cell lines; A549 (human lung adenocarcinoma), MCF-7 (human breast carcinoma) and Hep3B (human hepatocellular carcinoma) using MTT assay. Among this series, compounds 15 and 16 showed the most promising anticancer activity with IC50 values between 11.1 to 21.5 μM. Kinase profiling was performed for the most potent compounds 15 and 16 and it revealed weak inhibitory activity against 10 various kinases, where the highest inhibition was against CDK2/Cyclin A1 by compound 15. Furthermore, caspase-3/7 assay also indicated that the same compound 15 has the ability to induce apoptosis through the activation of effector caspase-3/7 family. Therefore, it could be deduced that the S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole is a promising novel anticancer scaffold with antiproliferative and apoptosis-inducing activities deserves to be taken up as a lead for further structural optimization

Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile