National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions:a systematic review and meta-analysis

Background Globally,populations afflicted by armed conflict are known to have high rates of mental health disorders.Aims This meta-analysis aims to estimate the prevalence of post-traumatic stress disorder(PTSD)and depressive symptoms among civilians residing in armed conflictaffected regions.Methods This meta-analysis was conducted in accordance with the Preferred Reporting Items forSystematic Reviews and Meta-Analyses.A literature search employing MEDLINE(R),Embase Classic+Embase,APA PsyclNFO,Ovid Healthstar,Journal@Ovid Full Text,Cochrane,PTSDpubs and CINAHL was conducted from inception until 19 March 2024 to identify relevant studies.Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies,and a Comprehensive Meta-Analysiswas usedto conduct the statistical analysis.Results The search yielded 38595 articles,of which 57 were considered eligible for inclusion.The included studies comprised data from 64596 participants.We estimated a prevalence of 23.70%(95%CI 19.50%to28.40%)forPTSD symptomsand 25.60%(95%Cl 20.70%to 31.10%)for depressive features among war-afflicted civilians.The subgroup analysis based on time since the war and the country's economic status revealed the highest prevalence for both PTSD and depressive symptoms was present during the years of war and in low/middle-incomecountries.Conclusions The results of this study provide conclusive evidence of the detrimental impacts of armed conflict on mental health outcomes.Hence,it is crucial to emphasise the significance of both physical and mental health in the aftermath of war and take appropriate humanistic measures to overcome challenges in the management of psychiatric illnesses.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome:A systematic review and meta-analysis

BACKGROUND In severe cases of coronary artery disease,percutaneous coronary intervention provide promising results.The stent used could be a drug-eluting stent(DES)or a titanium-nitride-oxide coated stent(TiNOS).AIM To compare the 5-year effectiveness and safety of the two stent types.METHODS The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines,and PubMed/MEDLINE,Scopus,and Cochrane Central were searched from inception till August 2023.Primary outcomes were major adverse cardiac events(MACE),cardiac death,myocardial infarction(MI),cardiac death or MI,and ischemia-driven total lesion revascularization(ID-TLR).RESULTS Four randomized controlled trials(RCT),which analyzed a sum total of 3045 patients with acute coronary syndrome(ACS)after a median follow-up time of 5 years were included.Though statistically insignificant,an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs.In addition,MI,cardiac death and MI,and definite stent thrombosis(DST)were significantly decreased in the TiNOS arm.Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI(NSTEMI)as a statistically significant covariate in the outcome of MACE.CONCLUSION TiNOS was found to be superior to DES in terms of MI,cardiac death or MI,and DST outcomes,however,the effect of the two stent types on ID-TLR and MACE was not significant.A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

Impact of non-alcoholic fatty liver disease on coronavirus disease 2019: A systematic review

BACKGROUND Many studies have revealed a link between non-alcoholic fatty liver disease(NA-FLD)and coronavirus disease 2019(COVID-19),making understanding the relationship between these two conditions an absolute requirement.AIM To provide a qualitative synthesis on the currently present data evaluating COVID-19 and NAFLD.METHODS This systematic review was conducted in accordance with the guidelines pro-vided by preferred reporting items for systematic reviews and meta-analyses and the questionnaire utilized the population,intervention,comparison,and outcome framework.The search strategy was run on three separate databases,PubMed/MEDLINE,Scopus,and Cochrane Central,which were systematically searched from inception until March 2024 to select all relevant studies.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched to identify grey literature.RESULTS After retrieval of 11 studies,a total of 39282 patients data were pooled.Mortality was found in 11.5%and 9.4%of people in NAFLD and non-NAFLD groups.In all,23.2%of NAFLD patients and 22%of non-NAFLD admissions diagnosed with COVID-19 were admitted to the intensive care unit,with days of stay varying.Ventilatory support ranged from 5%to 40.5%in the NAFLD cohort and from 3.1%to 20%in the non-NAFLD cohort.The incidence of acute liver injury showed significance.Clinical improvement on days 7 and 14 between the two classifications was significant.Hospitalization stay ranged from 9.6 days to 18.8 days and 7.3 days to 16.4 days in the aforementioned cohorts respectively,with 73.3%and 76.3%of patients being discharged.Readmission rates varied.CONCLUSION Clinical outcomes except mortality consistently showed a worsening trend in patients with NAFLD and concomitant COVID-19.Further research in conducting prospective longitudinal studies is essential for a more powerful conclusion.

Risk factors and outcomes of peptic ulcer bleed in a Pakistani population:A single-center observational study

BACKGROUND Peptic ulcer disease(PUD)remains a significant healthcare burden,contributing to morbidity and mortality worldwide.Despite advancements in therapies,its prevalence persists,particularly in regions with widespread nonsteroidal antiinflammatory drugs(NSAIDs)use and Helicobacter pylori infection.AIM To comprehensively analyse the risk factors and outcomes of PUD-related upper gastrointestinal(GI)bleeding in Pakistani population.METHODS This retrospective cohort study included 142 patients with peptic ulcer bleeding who underwent upper GI endoscopy from January to December 2022.Data on demographics,symptoms,length of stay,mortality,re-bleed,and Forrest classification was collected.RESULTS The mean age of patients was 53 years,and the majority was men(68.3%).Hematemesis(82.4%)and epigastric pain(75.4%)were the most common presenting symptoms.Most patients(73.2%)were discharged within five days.The mortality rates at one week and one month were 10.6%and 14.8%,respectively.Re-bleed within 24 h and seven days occurred in 14.1%and 18.3%of patients,respectively.Most ulcers were Forrest class(FC)Ⅲ(72.5%).Antiplatelet use was associated with higher mortality at 7 and 30 d,while alternative medications were linked to higher 24-hour re-bleed rates.NSAID use was associated with more FCⅢulcers.Re-bleed at 24 h and 7 d was strongly associated with one-week or one-month mortality.CONCLUSION Antiplatelet use and rebleeding increase the risk of early mortality in PUD-related upper GI bleeding,while alternative medicines are associated with early rebleeding.

Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and metaanalysis

BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.

Dosage and utilization of dexamethasone in the management of COVID-19: A critical review

BACKGROUND The severe respiratory manifestations observed in severe coronavirus disease 2019(COVID-19)cases are often associated with an excessive inflammatory response.Dexamethasone,a synthetic glucocorticoid,exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells.This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases.Early on in the pandemic,the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support.However,the optimal dosage of corticosteroids remains debatable.Several studies that compare different doses of dexamethasone in COVID-19 exist,but the results are conflicting.AIM To review the latest evidence regarding dosage,safety,and efficacy of dexamethasone in severe COVID-19.METHODS We followed preferred reporting items for systematic reviews and meta-analysis guidelines.A detailed literature search was conducted across PubMed,Google Scholar,and Medline to include publications up to March 2024.Our keywords included“COVID-19”“SARS-CoV-2”“dexamethasone”“corticosteroid”“steroid”and“glucocorticoid”-along with their combinations.We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies.A meta-analysis was conducted using a random-effects model,assessing pooled odds ratios and mean differences,with heterogeneity gauged by the I2 statistic and theχ^(2) tests.RESULTS No statistical differences were found in 28-day all-cause mortality[pooled odds ratio(OR)=1.109,95%CI:0.918-1.340],60-day all-cause mortality(OR=0.873,95%CI:0.744-1.024;I2=47.29%),mean length of hospital stay(mean difference=-0.08 days,95%CI:-0.001 to 0.161)and adverse events(OR=0.877,95%CI:0.707-1.087).CONCLUSION Differing doses of corticosteroids have no clinical implications on mortality,mean length of hospital stay,and adverse events in COVID-19 patients.Additional research is required in patients requiring invasive or noninvasive ventilation.

Future of mental health in the metaverse

The metaverse and non-fungible tokens(NFTs)were some of the hottest tech terms in 2021,according to a Google Trends search.Our review aims to describe the metaverse and NFTs in the context of their potential application in the treatment of mental health disorders.Advancements in technology have been changing human lives at an ever-increasing pace.Metaverse,also known as the threedimensional(3D)internet,is the convergence of virtual reality(VR)and physical reality in a digital space.It could potentially change the internet as we know it,with NFTs as the key building blocks in the new expansive virtual ecosystem.This immersive 3D virtual world boasts the features of the real world with the added ability to change the surrounding environment according to individual needs and requirements.VR,augmented reality(AR)and mixed reality(MR)have been employed as tools in the treatment of various mental health disorders for the past decade.Studies have reported positive results on their effectiveness in the diagnosis and treatment of mental health disorders.VR/AR/MR have been hailed as a solution to the acute shortage of mental health professionals and the lack of access to mental healthcare.But,on the flip side,young adults tend to spend a significant amount of time playing 3D immersive games and using social media,which can lead to insecurity,anxiety,depression,and behavioural addiction.Additionally,endless scrolling through social media platforms negatively affects individuals'attention span as well as aggravating the symptoms of adolescents with attention deficit hyperactivity disorder.We aimed to explore the ramifications of expanding applications of the metaverse on mental health.So far,no other review has explored the future of mental health in the context of the metaverse.

Acceptance,availability and feasibility of RTS,S/AS01 malaria vaccine:A review of literature

Malaria remains the most serious infectious disease and is one of the leading causes of death among children in malaria endemic areas.The development of malaria vaccines has been underway since 1960s.Significant progress in the development of vaccine has been made in the last decade.On 6 October 2021,World Health Organization recommended widespread use of the RTS,S/AS01 malaria vaccine.The level of acceptance of RTS,S/AS01 malaria vaccine is relatively low in middle-income countries.This might be because of lack of information regarding vaccine implementation in such countries.The proper and efficient execution of the malaria vaccination program necessitates careful consideration of each community's socio-cultural setting.The most prominent RTS,S/AS01 vaccine trial was conducted from 2009 to 2011 in which eleven sites in seven African countries participated.Results of the trial,published in 2015,provided a promising advance in the development of a malaria vaccine for African children.As of 2019,large-scale pilot studies of the vaccine have been conducted in Ghana,Kenya,and Malawi,involving several hundreds of thousands of infants.The RTS,S/AS01 vaccine shows modest efficacy against malaria and has a feasible mode of administration.Although there is increased risk of meningitis,cerebral malaria,pneumonia,anemia,febrile convulsions and gastroenteritis,the vaccine still has a feasible mode of administration and high cost effectiveness and can be easily implemented in resource-limited settings.

Attitudes and understanding of complementary and alternative medicine in cancer care:An exploratory study of patients’perspectives in Karachi,Pakistan

Objective:To evaluate the prevalence and types of complementary and alternative medicine(CAM)modalities among patients with cancer in Karachi,Pakistan.Methods:This descriptive cross-sectional study was conducted from March 2021 to December 2021.Five hundred patients with cancer were invited to participate in the study.Electronic databases,namely,Google scholar,Publons,EMBASE,PubMed,Chinese National Knowledge Infrastructure Database,and ResearchGate was used for questionnaire designed.The self-administered survey included questions on demographic characteristics,education level,socio-economic conditions and information about CAM therapies,prevalence,effectiveness,and common CAM modalities.Statistical analysis was conducted using SPSS software version 22.Results:Out of the 500 invited patients,433(86.6%)successfully completed and returned the questionnaires.In contrast to patients who were with younger,highly educated,professionally active,higher income,and had advanced cancer,time since diagnosis,type of treatment,cancer types and family history are significantly associated with CAM use.The results showed that 59.8%of the participants were acquainted with complementary and/or alternative medicine and considered safe owing to its natural ingredients.The prevalence of CAM usage among cancer patients was 40.9%and the most widely used CAM modality was herbal medicine(27.7%)and dietary supplements(28.8%).Patients used CAM as a complementary therapy to improve the morphological parameter(28.2%),strengthen the immune system(6.8%),and to decrease the side effects of conventional treatment(18.1%).Most of the respondents get the information regarding CAM therapy from the electronic media(43.2%)and the family members(48%)rather than healthcare personnel.Conclusions:Participants used CAM modalities along with the conventional health care practices.Further multicentre studies should be conducted to provide information regarding the usage of CAM therapies and their eventual benefits in patients with cancer.

Evolving paradigm of thrombolysis in pulmonary embolism:Comprehensive review of clinical manifestations,indications,recent advances and guideline

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability symptoms.This prevents the progression of right heart failure and impending hemodynamic collapse.Diagnosing PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition.Traditionally,systemic thrombolysis has been utilized to lyse the emboli in PE.However,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk groups.Additional newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with aspiration.Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be difficult.To help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many institutions.Hence to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports

BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2)inhibitors can induce eu-DKA in diabetic patients.Notably,coronavirus disease 2019(COVID-19)-infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets.This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis.Additionally,we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors,providing indispensable insights for healthcare professionals managing this specific patient population.AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.METHODS We conducted an exhaustive search across prominent electronic databases,including PubMed,SCOPUS,Web of Science,and Google Scholar.This search encompassed the period from December 2019 to May 2022,incorporating published studies and pre-prints.The search terms employed encompassed“SGLT2 inhibitors”,“euglycemic DKA”,“COVID-19”,and related variations.By incorporating these diverse sources,our objective was to ensure a thorough exploration of the existing literature on this subject,thereby augmenting the validity and robustness of our findings.RESULTS Our search yielded a total of seven case reports and one case series,collectively comprising a cohort of twelve patients.These reports detailed instances of eu-DKA in individuals with COVID-19.Crucially,all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication.Upon admission,all oral medications were promptly discontinued,and the patients were initiated on intravenous insulin therapy to effectively manage the DKA.Encouragingly,eleven patients demonstrated a favorable outcome,while regrettably,one patient succumbed to the condition.Subsequently,SGLT2 were discontinued for all patients upon their discharge from the hospital.These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2,underscoring the critical importance of prompt intervention and vigilant medication adjustments.CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA,as well as encountering adverse outcomes in the context of COVID-19,despite maintaining satisfactory glycemic control.The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous.Consequently,this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.

Effect of fibrinolytic therapy on ST-elevation myocardial infarction clinical outcomes during the COVID-19 pandemic:A systematic review and meta-analysis

BACKGROUND ST-elevation myocardial infarction(STEMI)is the result of transmural ischemia of the myocardium and is associated with a high mortality rate.Primary percutaneous coronary intervention(PPCI)is the recommended first-line treatment strategy for patients with STEMI.The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019(COVID-19)pandemic,leading to a projected steep rise in mortality.These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion.It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints.AIM To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes.METHODS PubMed,Google Scholar,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic.Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality.Data were meta-analyzed using the random effects model to derive odds ratios(OR)and 95%confidence intervals.Quality assessment was carried out using the Newcastle-Ottawa scale.RESULTS Fourteen studies including 50136 STEMI patients(n=15142 in the pandemic arm;n=34994 in the pre-pandemic arm)were included.The mean age was 61 years;79%were male,27%had type 2 diabetes,and 47%were smokers.Compared with the pre-pandemic period,there was a significantly increased overall incidence of fibrinolysis during the pandemic period[OR:1.80(1.18 to 2.75);I2=78%;P=0.00;GRADE:Very low].The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting.The countries with a low-and middle-income status reported a higher incidence of fibrinolysis[OR:5.16(2.18 to 12.22);I2=81%;P=0.00;GRADE:Very low]and an increased risk of all-cause mortality in STEMI patients[OR:1.16(1.03 to 1.30);I2=0%;P=0.01;GRADE:Very low].Meta-regression analysis showed a positive correlation of hyperlipidemia(P=0.001)and hypertension(P<0.001)with all-cause mortality.CONCLUSION There is an increased incidence of fibrinolysis during the pandemic period,but it has no effect on the risk of all-cause mortality.The low-and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Challenges in integrating traditional Chinese medicine and gut microbiota research for insomnia treatment

The gut microbiome is an extensive variety of bacteria with a range of metabolic capabilities that can be pathogenic,beneficial,or opportunistic.Changes in the gut microbiota's composition can affect the link between gut integrity and host health as well as cause disruptions to numerous neurological systems.The second most prevalent mental health problem,insomnia has a negative social and economic impact.Currently,it is becoming increasingly obvious how crucial it is to preserve the delicate balance of gut microbiota to treat illness-related symptoms like insomnia.Although traditional Chinese medicine has proposed an effective strategy against insomnia through gut microbiota alteration in animal models,studies in human models are limited.This decreases the predictive value of the studies in terms of human outcomes.This editorial places an emphasis on cultural sensitivity rather than scientific reasoning that promotes the use of traditional Chinese medicine(TCM).We aim to emphasize the concern that promoting TCM could divert resources from conventional medical research,leading to suboptimal care.

Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is a liver condition marked by excessive fat buildup in the absence of heavy alcohol use.It is primarily linked with metabolic issues like insulin resistance,obesity,and abnormal lipid levels,and is often observed with other conditions such as type 2 diabetes and cardiovascular disease.However,whether the subtypes of MAFLD based on the metabolic disorder differentially impact liver fibrosis is not well explicated,especially in the Asian population.AIM To compare the severity of liver fibrosis among different MAFLD subtypes.METHODS A total of 322 adult patients of either gender with fatty liver on ultrasound were enrolled between January to December 2021.MAFLD was defined as per the Asian Pacific Association for the Study of the Liver guidelines.Fibrosis-4 index(Fib-4)and nonalcoholic fatty liver disease fibrosis score(NFS)were employed to evaluate liver fibrosis.RESULTS The mean age was 44.84±11 years.Seventy-two percent of the patients were female.Two hundred and seventy-three patients were classified as having MAFLD,of which 110(40.3%)carried a single,129(47.3%)had two,and 34(12.5%)had all three metabolic conditions.The cumulative number of metabolic conditions was related to elevated body mass index,triglyceride(TG)levels,and glycated hemoglobin,lower high-density lipoprotein(HDL)levels,higher liver inflammation(by aspartate aminotransferase andγ-glutamyl transferase),and higher likelihood of fibrosis(by NFS and Fib-4 scores)(P<0.05 for all).The proportion of advanced fibrosis also increased with an increase in the number of metabolic conditions(4.1%,25.5%,35.6%,and 44.1%by NFS and 6.1%,10.9%,17%,and 26.5%by Fib-4 for no MAFLD and MAFLD with 1,2,and 3 conditions,respectively).Among MAFLD patients,those with diabetes alone were the eldest and had the highest mean value of NFS score and Fib-4 score(P<0.05),while MAFLD patients diagnosed with lean metabolic dysfunction exhibited the highest levels of TG and alanine aminotransferase but the lowest HDL levels(P<0.05).CONCLUSION The study suggests that the severity of liver fibrosis in MAFLD patients is influenced by the number and type of metabolic conditions present.Early identification and management of MAFLD,particularly in patients with multiple metabolic conditions,are crucial to prevent liver-related complications.

Infectious diseases in the aftermath of monsoon flooding in Pakistan

Pakistan is ranked 9th in terms of flood-affected countries worldwide.In the summer of 2010,the northern province of Khyber-Pakhtunkhwa received more than 312 mm of rain in a 56 hour period.This resulted in over 1 600 deaths across the region.In addition,over 14 million people were directly affected by this record-breaking deluge.Flood affected regions serve as ideal breeding grounds for pathogens,leading to the spread of diseases.The poor standards of hygiene in camps set up for individuals displaced by the floods also contribute to this.It is essential that those involved in relief efforts are aware of the epidemiology of diseases that have historically seen a sudden upsurge after natural disasters.Keeping this in mind,we conducted a simple review of literature.An extensive literature search was conducted using the PubMed data base and online search engines.Articles published in the last 20 years were considered along with some historical articles where a background was required.Seven major diseases were identified to increase substantially in the aftermath of natural disasters.They were then classified into acute and sub-acute settings.Diarrhea,skin&eye infections and leptospirosis were identified in the acute setting while malaria,leishmaniasis,respiratory infections and hepatitis were identified in the sub-acute setting.

New Method for Optimization and Simultaneous Determination of Sparfloxacin and Non Steroidal Anti-Inflammatory Drugs: Its <i>In-Vitro</i>Application

A simple reversed phase HPLC method was developed and validated for the simultaneous determination of sparfloxacin (SPFX), diclofenac sodium, meloxicam, ibuprofen, flurbiprofen, naproxen and mefenemic acid in a relatively short time with high linearity in bulk material, pharmaceutical formulations and human serum. Purospher STAR C18 (250 × 4.6 mm, 5 μm) column was utilized with mobile phase, methanol and water (90:10, v/v pH 2.70 adjusted by phosphoric acid), was delivered at a flow rate of 1.5 mL.min–1. Eluent was monitored using UV detector at 240 nm. The proposed method is specific, accurate (98.42% - 102.75%), precise (intra-day and inter-day variation 0.011% - 1.85%) and linear (R2 > 0.999) with in the desired range 0.15 - 40 μg.mL–1 and the detection and quantification limit was 1.19E+08 – 0.150 μg.mL–1 and 3.62E+08 – 0.4574 μg.mL–1 respectively for SPFX and NSAIDs. The analysis of variance (ANOVA) and student’s t-test were applied to verify the results. The anticipated method is applicable to routine analysis of SPFX and NSAIDs in pharmaceutical formulations as well as in human serum samples. It has also applied on interaction of SPFX with NSAIDs.

Determination of correlation of Adjusted Blood Requirement Index with outcome in patients presenting with acute variceal bleeding

AIM： To determine the correlation of Adjusted Blood Requirement Index （ABRI） with the 7th day outcome in patients presenting with acute variceal bleeding.METHODS： All patients presenting with acute variceal hemorrhage （AVH） were included. Patients with previous band ligation, sclerotherapy, gastrointestinal or hepatic malignancies were excluded. Patients were managed as per standard protocol for AVH with terlipressin and band ligation. ABRI scores were calculated using the formula outcome of alive or expired up to the 7th day after treatment. The correlation between ABRI and mortality was estimated and a receiver operative characteristic （ROC） curve was plotted.RESULTS： A total of 113 patients （76 male; 37 female） were included. On assessment, 18 were in Child＇s Pugh Class A, 82 in Class B and 13 were in Class C. The median number of blood units transfused ± inter-quartile range was 3.0 ± 2.0. The median ± inter-quartile range for ABRI was 1.3 ± 1.1. The ROC curve of ABRI for expiry showed a significantly large area of 0.848 （P 〈 0.0001; 95% CI： 0.75-0.95）. A significant correlation of log transformation of ABRI with an outcome of mortality was present （P 〈 0.0001）.

Combination of mesenchymal stem cells and three-dimensional collagen scaffold preserves ventricular remodeling in rat myocardial infarction model

BACKGROUND Cardiovascular diseases are the major cause of mortality worldwide.Regeneration of the damaged myocardium remains a challenge due to mechanical constraints and limited healing ability of the adult heart tissue.Cardiac tissue engineering using biomaterial scaffolds combined with stem cells and bioactive molecules could be a highly promising approach for cardiac repair.Use of biomaterials can provide suitable microenvironment to the cells and can solve cell engraftment problems associated with cell transplantation alone.Mesenchymal stem cells(MSCs)are potential candidates in cardiac tissue engineering because of their multilineage differentiation potential and ease of isolation.Use of DNA methyl transferase inhibitor,such as zebularine,in combination with three-dimensional(3D)scaffold can promote efficient MSC differentiation into cardiac lineage,as epigenetic modifications play a fundamental role in determining cell fate and lineage specific gene expression.AIM To investigate the role of collagen scaffold and zebularine in the differentiation of rat bone marrow(BM)-MSCs and their subsequent in vivo effects.METHODS MSCs were isolated from rat BM and characterized morphologically,immunophenotypically and by multilineage differentiation potential.MSCs were seeded in collagen scaffold and treated with 3μmol/L zebularine in three different ways.Cytotoxicity analysis was done and cardiac differentiation was analyzed at the gene and protein levels.Treated and untreated MSC-seeded scaffolds were transplanted in the rat myocardial infarction(MI)model and cardiac function was assessed by echocardiography.Cell tracking was performed by DiI dye labeling,while regeneration and neovascularization were evaluated by histological and immunohistochemical analysis,respectively.RESULTS MSCs were successfully isolated and seeded in collagen scaffold.Cytotoxicity analysis revealed that zebularine was not cytotoxic in any of the treatment groups.Cardiac differentiation analysis showed more pronounced results in the type 3 treatment group which was subsequently chosen for the transplantation in the in vivo MI model.Significant improvement in cardiac function was observed in the zebularine treated MSC-seeded scaffold group as compared to the MI control.Histological analysis also showed reduction in fibrotic scar,improvement in left ventricular wall thickness and preservation of ventricular remodeling in the zebularine treated MSC-seeded scaffold group.Immunohistochemical analysis revealed significant expression of cardiac proteins in DiI labeled transplanted cells and a significant increase in the number of blood vessels in the zebularine treated MSC-seeded collagen scaffold transplanted group.CONCLUSION Combination of 3D collagen scaffold and zebularine treatment enhances cardiac differentiation potential of MSCs,improves cell engraftment at the infarcted region,reduces infarct size and improves cardiac function.