Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p≤0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results

Adequacy of phosphodiesterase inhibitor in prevention and treatment of LPS induced organ failure in BALB/c mice

Background: Even though with immense improvement and extensive understanding of pathophysiology of sepsis induced organ failure and affected population, it continues to put hundreds of people worldwide to eternal sleep due to lack of targeted therapy. Newer treatment modalities is the dire need of time. The present study was aimed to ascertain the adequacy of phosphodiesterases inhibitor - pentoxifylline (75mg/kg i.p) in endotoxin/LPS induced hepatotoxicity in BALB/c mice.Methods: The number of animals in each group was six. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E. coli intraperitoneally. To ascertain the Preventive role, pentoxifylline was administered forehand LPS injection whereas therapeutic potential adjuged via post LPS delivering. The extent of liver damage was evaluated through serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Results set forth that serum ALT, AST levels and histological alteration abated considerably (p ≤0.05) both in animals subjected to pentoxifylline pre and post-treatment.Conclusions: Pentoxifylline set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure

Comparison of hepatoprotective effect of aqueous and ethanolic extracts of Berberis lycium Royale (Sumbloo) in isoniazid induced hepatotoxicity in male mice model

Background: The objective of the study was to compare the hepatoprotective effect of aqueous and ethanolic extracts of stem bark of Berberis lycium Royle in isoniazid (INH) induced hepatotoxicity in mice model.Methods: This randomized controlled in-vivo study conducted in male mice model from 10th April 2014 till 10th May 2014 at National Institute of Health, Islamabad. Group (C) was given normal diet and water. Group (D) was given isoniazid (50 mg/kg BW) to produce hepatotoxicity. Group (LA) and (HA) were given isoniazid (INH) plus low and high dose of aqueous extract of stem bark of Berberis lycium Royle respectively. Group (L.E) and (H.E) were given INH plus low and high dose of ethanolic extract of stem bark of Berberis lycium Royle respectively.Results: Hepatotoxicity produced by INH was shown by raised serum liver function tests (LFT’s), marked hepatocytic ballooning, significant steatosis and inflammation. Mice receiving simultaneous treatment of INH, low and high dose of aqueous extract of Berberis lycium Royle showed decrease serum LFT’s and their liver sections showed improved histological picture but more significant reduction in hepatotoxic effects were observed in animals receiving low and high doses of ethanolic extract.Conclusions: Hepatotoxicity of INH can be more fully reversed by simultaneous use of INH with ethanolic extract as it has better hepatoprotective potential in dose dependent manner as compare to aqueous extract of stem bark of Berberis lycium Royle

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: Multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P \u3c 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (β coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p≤0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results

Evaluation of visual outcomes with toric intraocular lens implantation using digital marker during cataract surgery

Objective: To assess the visual improvement and mean residual astigmatism in patients who underwent cataract surgery with toric intraocular lens. Method: The retrospective, observational study was conducted at the Department of Ophthalmology, Aga Khan University Hospital, Karachi, and comprised data from January 1, 2018, to December 31, 2020, related to adult patients who had regular astigmatism of at least 0.75D and underwent cataract surgery with toric intraocular lens implantation using a digital marker. The patients were followed up on post-operative days 1, 7, 30, 90 and 180. Along with age, the degree of astigmatism was noted. The visual acuity was calculated pre- and post-operatively. The mean residual astigmatism was then noted for all patients post-operatively. Data was analysed using SPSS 22. Results: The sample comprised 240 eyes of 177 patients; 99(55.9%) males and 78(44.1%) females. The mean age of the sample was 62.5±10.6 years. The mean unaided visual acuity improved post-operatively from 0.57±0.38 to 0.07±0.22 at 90 days. At the 30-day follow-up, mean residual astigmatism had reduced from 1.52±0.84 to 0.01±0.09 (p<0.001). The mean intraocular lens rotation from the intended axis was 0.73°±0.92° on day 30. Conclusion: Toric intraocular lens implantation using a digital marker could effectively reduce the post-operative cylinder, and improve the unaided visual acuity following cataract surgery. Key Words: Intraocular lens implantation, Cataract, Toric IOL, Accuracy of toric IOL

Sex differences in altmetric attention scores and traditional impact metrics of top-cited general surgery literature: Cracks in the ceiling?

Background: Sex disparities have previously been identified in surgical academia. This study examines sex differences in the top-cited contemporary general surgery articles and compares Altimetric Attention Score (AAS) and other impact metrics between male and female corresponding authors (CAs).Methods: We conducted a bibliometric analysis of the 100 most cited articles published between 2019 and 2021 in each of the top 10 general surgery journals based on the 2021 Journal Impact Factor. Impact metrics included AAS, citation count, and H-index of the CA. We used multivariable regression analyses to investigate whether the sex of the CA or first author (FA) was independently associated with AAS and citation count.Results: Among 1000 articles, 23.1% had female CAs and 27.4% female FAs. Female CA articles had higher AAS (13.0 [2.0-63.0] vs. 8.0 [1.0-28.5]; p \u3c 0.001) and lower H-indices (24.0 [11.0-45.0] vs. 31.0 [17.0-50.0]; p = 0.015). Although median citation count did not differ by CA sex, articles with Level 1 evidence and a female CA were cited more often (35.5 [24.0-85.0] vs. 25.0 [16.0 vs. 46.0]; p \u3c 0.05). In multivariable regression, female CA articles had higher AAS (OR: 1.002 [95% CI: 1.001-1.004]) and lower H-index (OR: 0.987 [95% CI: 0.977-0.997]).Conclusion: Despite having similar citation counts, articles authored by female CAs exhibit higher AAS scores compared to those authored by their male counterparts. While it is heartening that research authored by female surgeons achieves significant visibility, it remains to be understood how this translates into academic impact and scholarly recognition