Advancements in medical treatment for pancreatic neuroendocrine tumors:A beacon of hope

This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.

Cardiovascular complications following medical termination of pregnancy: An updated review

BACKGROUND Around 1 million cases of medical termination of pregnancy(MTP)take place yearly in the United States of America with around 2 percent of this population developing complications.The cardiovascular(CVD)complications occurring post MTP or after stillbirth is not very well described.AIM To help the reader better understand,prepare,and manage these complications by reviewing various cardiac comorbidities seen after MTP.METHODS We performed a literature search in PubMed,Medline,RCA,and google scholar,using the search terms“abortions”or“medical/legal termination of pregnancy”and“cardiac complications”or“cardiovascular complications”.RESULTS The most common complications described in the literature following MTP were infective endocarditis(IE)(n=16),takotsubo cardiomyopathy(TTC)(n=7),arrhythmias(n=5),and sudden coronary artery dissection(SCAD)(n=4).The most common valve involved in IE was the tricuspid valve in 69%(n=10).The most observed causative organism was group B Streptococcus in 81%(n=12).The most common type of TTC was apical type in 57%(n=4).Out of five patients de veloping arrhythmia,bradycardia was the most common and was seen in 60%(3/5)of the patients.All four cases of SCAD-P type presented as acute coronary syndrome 10-14 d post termination of pregnancy with predominant involvement of the right coronary artery.Mortality was only reported following IE in 6.25%.Clinical recovery was reported consistently after optimal medical management following all these complications.CONCLUSION In conclusion,the occurrence of CVD complications following pregnancy termination is infrequently documented in the existing literature.In this review,the most common CVD complication following MTP was noted to be IE and TTC.

Can we predict the incidence of high-grade Clavien-Dindo complications in patients with forgotten encrusted stents undergoing endourologic management?

Objective:Ureteral stents are customarily inserted to facilitate urinary drainage,but they come with their own glitches of being forgotten and/or encrusted leading to serious consequences.The present study aimed to report the complications in patients with forgotten and encrusted stents according to the Clavien-Dindo system specific to urological procedures and identify the factors leading to high-grade(Clavien-Dindo Grade 4A or above)complications.Methods:The hospital records of patients with forgotten encrusted double-J stents over a period of 8 years were reviewed.The parameters recorded included patient demographics,indwelling time,need for percutaneous nephrostomy,hemodialysis,urine culture,blood culture,total blood counts,serum creatinine,radiologic findings,management techniques,number of surgical interventions,modified Clavien-Dindo complications,follow-up,and mortality,if any.Results:Forty patients were included in the study.The median age was 52(range 6-85)years.Of the total,25(62.5%)patients had a“significant”stent load;31(77.5%)had renal failure or acute kidney injury on presentation;19(47.5%)patients had sepsis at presentation.Among the patients presented with sepsis,11(57.9%)patients demonstrated a positive urine culture;and 7/11(63.6%)patients exhibited pan-resistant organisms.Twelve out of 40(30.0%)patients in our series developed high-grade Clavien-Dindo complications.On univariate analysis,sepsis at presentation(p=0.007),stent load(p=0.031),diabetes(p=0.023),positive urine culture(p=0.007),and stent indwelling time of more than 1 year(p=0.031)were found to be significant.On multivariate logistic regression analysis,sepsis at presentation(p=0.017)and positive urine culture(p=0.016)were significant predictors for high-grade complications.Conclusion:It is prudent to identify specific risk factors,namely sepsis at presentation and positive urine culture to triage and optimize these patients before surgical management.

Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

Machine learning insights on intensive care unit-acquired weakness

Intensive care unit-acquired weakness(ICU-AW)significantly hampers patient recovery and increases morbidity.With the absence of established preventive strategies,this study utilizes advanced machine learning methodologies to unearth key predictors of ICU-AW.Employing a sophisticated multilayer perceptron neural network,the research methodically assesses the predictive power for ICU-AW,pinpointing the length of ICU stay and duration of mechanical ventilation as pivotal risk factors.The findings advocate for minimizing these elements as a preventive approach,offering a novel perspective on combating ICU-AW.This research illuminates critical risk factors and lays the groundwork for future explorations into effective prevention and intervention strategies.

Unlocking new potential of clinical diagnosis with artificial intelligence:Finding new patterns of clinical and lab data

Recent advancements in science and technology,coupled with the proliferation of data,have also urged laboratory medicine to integrate with the era of artificial intelligence(AI)and machine learning(ML).In the current practices of evidencebased medicine,the laboratory tests analysing disease patterns through the association rule mining(ARM)have emerged as a modern tool for the risk assessment and the disease stratification,with the potential to reduce cardiovascular disease(CVD)mortality.CVDs are the well recognised leading global cause of mortality with the higher fatality rates in the Indian population due to associated factors like hypertension,diabetes,and lifestyle choices.AI-driven algorithms have offered deep insights in this field while addressing various challenges such as healthcare systems grappling with the physician shortages.Personalized medicine,well driven by the big data necessitates the integration of ML techniques and high-quality electronic health records to direct the meaningful outcome.These technological advancements enhance the computational analyses for both research and clinical practice.ARM plays a pivotal role by uncovering meaningful relationships within databases,aiding in patient survival prediction and risk factor identification.AI potential in laboratory medicine is vast and it must be cautiously integrated while considering potential ethical,legal,and privacy concerns.Thus,an AI ethics framework is essential to guide its responsible use.Aligning AI algorithms with existing lab practices,promoting education among healthcare professionals,and fostering careful integration into clinical settings are imperative for harnessing the benefits of this transformative technology.

Debate on direct-anterior vs posterior approach for hip hemiarthroplasty:The authors’insights

We read and discussed the study entitled“Complication rates after direct anterior vs posterior approach for Hip Hemiarthroplasty in elderly individuals with femoral neck fractures”with great interest.The authors have done justice to the topic of comparison of anterior and posterior surgical approaches for bipolar hemiarthroplasty which has been an everlasting debate in the existing literature.However,there are certain aspects of this study that need clarification from the authors.

Digital psychiatry in low-and-middle-income countries:New developments and the way forward

Low-and middle-income countries(LMICs)bear the greater share of the global mental health burden but are ill-equipped to deal with it because of severe resource constraints leading to a large treatment gap.The remote provision of mental health services by digital means can effectively augment conventional services in LMICs to reduce the treatment gap.Digital psychiatry in LMICs has always lagged behind high-income countries,but there have been encouraging developments in the last decade.There is increasing research on the efficacy of digital psychiatric interventions.However,the evidence is not adequate to conclude that digital psychiatric interventions are invariably effective in LMICs.A striking development has been the rise in mobile and smartphone ownership in LMICs,which has driven the increasing use of mobile technologies to deliver mental health services.An innovative use of mobile technologies has been to optimize task-shifting,which involves delivering mental healthcare services in community settings using non-specialist health professionals.Emerging evidence from LMICs shows that it is possible to use digital tools to train non-specialist workers effectively and ensure that the psychosocial interventions they deliver are efficacious.Despite these promising developments,many barriers such as service costs,underdeveloped infrastructure,lack of trained professionals,and significant disparities in access to digital services impede the progress of digital psychiatry in LMICs.To overcome these barriers,digital psychiatric services in LMICs should address contextual factors influencing the delivery of digital services,ensure collaboration between different stakeholders,and focus on reducing the digital divide.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Fatal cases in pediatric patients after post-exposure prophylaxis for rabies:A report of two cases

Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.

Understanding the molecular crossroads in acute liver failure:A pathway to new therapies

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Endoscopic ultrasound-guided pancreatic fluid collection drainage: Where are we?

Pancreatic fluid collections(PFCs)result from injury to the pancreas from acute or chronic pancreatitis,surgery,or trauma.Management of these collections has evolved over the last 2 decades.The choice of interventions includes percu-taneous,endoscopic,minimally invasive surgery,or a combined approach.Endoscopic drainage is the drainage of PFCs by creating an artificial communi-cation between the collection and gastrointestinal lumen that is maintained by placing a stent across the fistulous tract.In this editorial,we endeavored to update the current status of endoscopic ultrasound-guided drainage of PFCs.

Diabetes is affecting everyone everywhere

The article titled“Accessibility and Utilization of Healthcare Services Among Diabetic Patients:Is Diabetes a Poor Man’s Ailment?”gave insights into a pandemic systemic disease known as diabetes mellitus.This modern-era pandemic affects everyone,regardless of their financial background.As a result,diabetes is not a systemic disease which just involves people of low socioeconomic status.

Angioinvasive mucormycosis in burn intensive care units:A case report and review of literature

BACKGROUND Mucormycosis is a rare,rapidly progressive and often fatal fungal infection.The rarity of the condition lends itself to unfamiliarity,delayed treatment,and poor outcomes.Diagnosis of fungal infections early enough to enable appropriate treatment occurs in less than half of affected patients.CASE SUMMARY An 11-year-old girl with a history of 15%total body surface area scald burns involving both lower limbs progressed to develop angioinvasive mucormycosis.This further led to a thrombosis of the right external iliac artery and vein and rapidly progressive necrosis of surrounding soft tissues.She also had dextrocardia and patent foramen ovale.A right hip disarticulation and serial aggressive debridements were performed but she went on to develop systemic sepsis with multisystem involvement and succumbed to the infection.Pathology revealed mucor species with extensive vascular invasion.CONCLUSION This case highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are signs of fulminant wound infection.

Unveiling significant risk factors for intensive care unit-acquired weakness:Advancing preventive care

In this editorial,we discuss an article titled,“Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning,”published in a recent issue of the World Journal of Clinical Cases.Intensive care unit-acquired weakness(ICU-AW)is a debilitating condition that affects critically ill patients,with significant implications for patient outcomes and their quality of life.This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors.Data from a cohort of 1063 adult intensive care unit(ICU)patients were analyzed,with a particular emphasis on variables such as duration of ICU stay,duration of mechanical ventilation,doses of sedatives and vasopressors,and underlying comorbidities.A multilayer perceptron neural network model was developed,which exhibited a remarkable impressive prediction accuracy of 86.2%on the training set and 85.5%on the test set.The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

Discovering hidden patterns:Association rules for cardiovascular diseases in type 2 diabetes mellitus

BACKGROUND It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus(T2DM)and coronary artery disease(CAD),and studies are able to correlate their relationships with available biological and clinical evidence.The aim of the current study was to apply association rule mining(ARM)to discover whether there are consistent patterns of clinical features relevant to these diseases.ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care.AIM To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery.METHODS This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi,involving a total of 300 consented subjects categorized into three groups:CAD with diabetes,CAD without diabetes,and healthy controls,with 100 subjects in each group.The participants were enrolled from the Cardiology IPD&OPD for the sample collection.The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value.RESULTS The clinical dataset comprised 35 attributes from enrolled subjects.The analysis produced rules with a maximum branching factor of 4 and a rule length of 5,necessitating a 1%probability increase for enhancement.Prominent patterns emerged,highlighting strong links between health indicators and diabetes likelihood,particularly elevated HbA1C and random blood sugar levels.The ARM technique identified individuals with a random blood sugar level>175 and HbA1C>6.6 are likely in the“CAD-with-diabetes”group,offering valuable insights into health indicators and influencing factors on disease outcomes.CONCLUSION The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes.Implying artificial intelligence techniques with medical data,we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug development.However,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted therapies.Furthermore,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection

BACKGROUND Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection(ESD);however,the preoperative evaluation of tumor size is often different from histological assessment.Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD.METHODS This was a retrospective study conducted at a single institution.A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected.We first assessed the difference in size with an absolute per-centage of the scaling discrepancy.Subsequently,we compared the clinicopatho-logical characteristics of the correct scaling group(>-33%and<33%)with that of the incorrect scaling group(<-33%or>33%),which was further subdivided into the underscaling group(-33%or less of the discrepancy)and overscaling group(33%or more of the discrepancy),respectively.As secondary outcome measures,parameters on size estimation were compared between the underscaling and correct scaling groups,as well as between the overscaling and correct scaling groups.Finally,multivariate analysis was performed in terms of the following relevant parameters on size estimation:Pathological size,location,and possible influential factors(P<0.1)in the univariate analysis.RESULTS The mean of absolute percentage in the scaling discordance was 21%,and 91 lesions were considered to be incorrectly estimated in size.The incorrect scaling was significantly remarkable in larger lesions(40 mm vs 28 mm;P<0.001)and less experience(P<0.001),and these two factors were influential on the underscaling(75 lesions;P<0.001).Conversely,compared with the correct scaling group,16 lesions in the overscaling group were significantly small(20 mm vs 28 mm;P<0.001),and the small lesion size was influential on the overscaling(P=0.002).CONCLUSION Lesions indicated for colorectal ESD tended to be underestimated in large tumors,but overestimated in small ones.This discrepancy appears worth understanding for optimal procedural preparation.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.