Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
BACKGROUND Pediatric candiduria is a frequently overlooked manifestation of healthcareassociated fungal infections.Candida species are increasingly being identified in the urine of neonates and infants,with non-albica...BACKGROUND Pediatric candiduria is a frequently overlooked manifestation of healthcareassociated fungal infections.Candida species are increasingly being identified in the urine of neonates and infants,with non-albicans Candida(NAC)species being more prevalent than Candida albicans.AIM To determine the rate of Candida species isolation among pediatric patients with suspected urinary tract infections(UTI)at a tertiary care hospital.METHODS A total of 436 children with a clinical suspicion of UTI were enrolled in this laboratory-based descriptive observational study.The samples were then subjected to urine mounting and subcultured on Sabouraud dextrose agar.Candida isolates were identified based on the color of the colonies on CHROM agar,Dalmau plate culture,and germ tube formation.The results were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry,followed by Antifungal susceptibility testing using Vitek®2 AST-YS07 cards.RESULTS A total of 79 Candida isolates(18.12%)were identified.Of these,39(49.37%)were neonates,with a male-to-female ratio of 3.39:1.The intensive care unit(ICU)recorded 52 patients(65.82%).Of the 79 patients,57(72.15%)received broadspectrum antibiotics for more than 7 days.Our study revealed a higher prevalence of NAC species,with Candida tropicalis accounting for 34 cases(43.04%).Amphotericin B showed the highest susceptibility,with 68 isolates(86.08%)being susceptible to this Antifungal agent.CONCLUSION Pediatric patients with Candiduria present atypical and vague symptoms.This may be the initial symptom of disseminated Candidiasis in the presence of predisposing factors.Isolation of these pathogens,along with their Antifungal susceptibility patterns,aids in a better prognosis.展开更多
BACKGROUND Acute colonic pseudo-obstruction(ACPO)is defined as colonic obstruction without a mechanical or extrinsic inflammatory factor.Colonic decompression is advised for patients with ACPO after the failure of con...BACKGROUND Acute colonic pseudo-obstruction(ACPO)is defined as colonic obstruction without a mechanical or extrinsic inflammatory factor.Colonic decompression is advised for patients with ACPO after the failure of conservative and medical management.AIM To systematically review and analyze the efficacy and safety of colonoscopic decompression in ACPO.METHODS A search was conducted in MEDLINE,EMBASE,and Scopus from inception to August 2024.Studies reporting the clinical success,perforation,recurrence,and need for surgery after colonoscopic decompression in ACPO were included.A random-effects inverse-variance model was used to calculate the pooled proportion.RESULTS Sixteen studies were included in the final analysis.The pooled rates of success after the first session of colonoscopic decompression and overall success were 78.8%(95%CI:72.0-85.6)and 91.5%(95%CI:87.0-96.0),respectively.The first session of colonoscopic decompression had a significantly higher success than the first dose of neostigmine with OR 3.85(95%CI:2.00-7.42).The pooled incidence of perforation was 0.9%(95%CI:0.0-2.0),while recurrence was observed in 17.1%(95%CI:12.9-21.3)of the patients after clinical success.The pooled rates of surgery in all cases undergoing colonoscopic decompression and those who had a successful procedure were 10.5%(95%CI:5.0-15.9)and 3.7%(95%CI:0.3-7.1),respectively.Subgroup analysis,excluding the low-quality studies,did not significantly change the event rates.CONCLUSION Colonoscopic decompression for ACPO is associated with a clinical success rate of>90%with a perforation rate of<1%,demonstrating high efficacy and safety.展开更多
Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant pote...Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant potential for promoting technologic progress in this field.Herein,we present Cu-ZSM-5 zeolite as a highly effective catalyst for alkane aromatization,achieving outstanding aromatics selectivity.In-situ Fourier transform infrared spectra of adsorbed nitric oxide,high-angle annular dark field scanning transmission electron microscopy,X-ray absorption spectroscopy,and electron paramagnetic resonance analyses reveal that the Cu^(2+)species act as the primary active centers for aromatics formation.During aromatization of alkanes,the reduction of Cu^(2+)to Cu^(+)species correlates with diminished aromatics selectivity.Notably,introducing CO_(2)into the reaction feed not only enhances aromatics selectivity by maintaining Cu^(2+)species in their active oxidation state under reducing conditions,but also improves catalytic stability by eliminating coke.Furthermore,CO_(2)is converted into CO and aromatic products during the reaction,offering a novel way for CO_(2)utilization through the coupling reaction of alkane and CO_(2).展开更多
Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study i...Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study investigates the nutritional quality of A.japonicus from different geographical regions and identifies genetic markers associated with these traits through a genome-wide association study(GWAS).We observed significant regional variations in the nutritional content of A.japonicus.Samples collected from Nanhuangcheng Island displayed the highest levels of saponins,whereas those from Laizhou exhibited the highest concentrations of glycosaminoglycans.Lingshan Island samples were the richest in amino acids,while samples from Rizhao contained the highest levels of polyunsaturated fatty acids.Through GWAS,265 candidate genes and related single nucleotide polymorphisms(SNPs)were identified as being significantly associated with essential nutritional traits,including genes like ubiquitin domain-containing protein 1(UBTD1),inactive pancreatic lipase-related protein 1,protein arginine N-methyltransferase 5(PRMT5)and GDP-fucose protein O-fucosyltransferase 1(POFUT1).This study advanced our knowledge of the genetic mechanisms underlying the nutritional quality of A.japonicus.The genetic markers identified herein o ffer crucial insights for breeding initiatives aimed at optimizing the nutritional profile of sea cucumbers.展开更多
The gastrointestinal(GI)tract is essential for digestion,absorption,excretion,and protection,supported by a diverse microbial ecosystem.Traditional in-vitro models often fall short in capturing the physiological compl...The gastrointestinal(GI)tract is essential for digestion,absorption,excretion,and protection,supported by a diverse microbial ecosystem.Traditional in-vitro models often fall short in capturing the physiological complexity of the GI tract,limiting their translational applications.A comprehensive approach is needed to bridge the gap between simple cell cultures and more complex systems used in translational research.This review explores the limitations of conventional twodimensional cell cultures and emphasizes the emerging use of three-dimensional and microfluidic systems that better replicate the GI tract’s structure and functions.It highlights the importance of incorporating patient-derived cells and engineered microenvironments to enhance model relevance and support personalized medicine.The review also discusses advanced fabrication techniques such as micro-extrusion and laser-assisted bioprinting,which enable the creation of sophisticated tissue models capable of simulating critical GI processes,including molecular transport,peristalsis,and liver coupling.Advancing the complexity of in-vitro systems will help replicate the GI tract’s interactions and physiological phenomena,thus improving the translational potential of GI research.This review provides valuable insights into the advancements and challenges in GI modeling,serving as a comprehensive guide for developing models that bridge the gap between basic cell cultures and clinically relevant systems.展开更多
Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while add...Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.展开更多
AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which prov...AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which provide estimates of relative risk （RR） and 95%CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke （ETS）： The spouse; household; workplace; childhood; travel; social and other; and total. A wide range of study details were entered into a database, and the RRs for each study, including descriptions of the comparisons made, were entered into a linked database. RRs were derived where necessary. Results were entered, where available, for all lung cancer, and for squamous cell cancer and adenocarcinoma. “Most adjusted” results were entered based on results available, adjusted for the greatest number of potential confounding variables. “Least adjusted” results were also entered, with a preference for results adjusted at least for age for prospective studies. A pre-planned series of fxed-effects and random-effects meta-analyses were conducted. Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex, and results for childhood exposure given by source of ETS exposure. For spousal exposure, more extensive analyses provide results by various aspects of study design and defnition of the RR. For smoking by the husband （or nearest equivalent）, additional analyses were carried out both for overall risk, and for risk per 10 cigarettes per day smoked by the husband. These adjusted for uncontrolled confounding by four factors （fruit, vegetable and dietary fat consumption, and education）, and corrected for misclassification of smoking status of the wife. For the confounding adjustment, estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure, and on the correlations between the factors. The bias due to misclassifcation was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere, and that those who deny smoking have the same risk as those who admit it. This approach, justifed in previous work, balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS： One hundred and two studies were identifed for inclusion, published in 1981 onwards, 45 in Asia, 31 in North America, 21 in Europe, and fve elsewhere. Eighty-fve were of case-control design and 17 were prospective. Significant （P 〈 0.05） associations were noted, with random-effects of （RR = 1.22, 95%CI： 1.14-1.31, n = 93） for smoking by the husband （RR = 1.14, 95%CI： 1.01-1.29, n = 45） for smoking by the wife （RR = 1.22, 95%CI： 1.15-1.30, n = 47） for workplace exposure （RR = 1.15, 95%CI： 1.02-1.29, n = 41） for childhood exposure, and （RR = 1.31, 95%CI： 1.19-1.45, n = 48） for total exposure. No signifcant association was seen for ETS exposure in travel （RR = 1.34, 95%CI： 0.94-1.93, n = 8） or in social situations （RR = 1.01, 95%CI： 0.82-1.24, n = 15）. A signifcant negative association （RR = 0.78, 95%CI： 0.64-0.94, n = 8） was seen for ETS exposure in childhood, specifically from the parents. Significant associations were also seen for spousal smoking for both squamous cell carcinoma （RR = 1.44, 95%CI： 1.15-1.80, n = 24） and adenocarcinoma （RR = 1.33,95%CI： 1.17-1.51, n = 30）. Results generally showed marked heterogeneity between studies. For smoking by either the husband or wife, where 119 RR estimates gave an overall estimate of （RR = 1.21, 95%CI： 1.14-1.29）, the heterogeneity was highly significant （P 〈 0.001）, with evidence that the largest RRs were seen in studies published in 1981-89, in small studies （1-49 cases）, and for estimates unadjusted by age. For smoking by the husband, the additional analyses showed that adjustment for the four factors reduced the overall （RR = 1.22, 95%CI： 1.14-1.31） based on 93 estimates to （RR = 1.14, 95%CI： 1.06-1.22）, implying bias due to uncontrolled confounding of 7%. Further correction for misclassification reduced the estimate to a marginally non-signifcant （RR = 1.08, 95%CI： 0.999-1.16）. In the fully adjusted and corrected analyses, there was evidence of an increase in Asia （RR = 1.18, 95%CI： 1.07-1.30, n = 44）, but not in other regions （RR = 0.96, 95%CI： 0.86-1.07, n = 49）. Studies published in the 1980’s, studies providing dose-response data, and studies only providing results unadjusted for age showed elevated RRs, but later published studies, studies not providing dose-response data, and studies adjusting for age did not. The pattern of results for RRs per 10 cigs/d was similar, with no signifcant association in the adjusted and corrected results （RR = 1.03, 95%CI： 0.994-1.07）.CONCLUSION： Most, if not all, of the ETS/lung cancer association can be explained by confounding adjustment and misclassifcation correction. Any causal relationship is not convincingly demonstrated.展开更多
BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating excl...BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating exclusive cigar smoking to risk of the major smoking-related diseases.METHODS Literature searches detected studies carried out in the United States which estimated the risk of lung cancer,chronic obstructive pulmonary disease(COPD),heart disease,stroke or overall circulatory disease in exclusive cigar smokers as compared to those who had never smoked any tobacco product.Papers were identified from reviews and detailed searches on MEDLINE.For each study,data were extracted onto a study database and a linked relative risk database.Relative risks and 95%CIs were extracted,or estimated,relating to current,former or ever exclusive cigar smokers,and meta-analysed using standard methods.Sensitivity analyses were conducted including or excluding results from studies that did not quite fit the full selection criteria(for example,a paper presenting combined results from five studies,where 86%of the population were in the United States).RESULTS The literature searches identified 17 relevant publications for lung cancer,four for COPD and 12 for heart disease,stroke and circulatory disease.These related to 11 studies for lung cancer,to four studies for COPD and to eight studies for heart disease,stroke or overall circulatory disease.As some studies provided results for more than one disease,the total number of studies considered was 13,with results from four of these used in sensitivity analyses.There was evidence of significant heterogeneity in some of the meta-analyses so the random-effects estimates are summarized below.As the results from the sensitivity analyses were generally very similar to those from the main analyses,and involved more data,only the sensitivity results are summarized below.For lung cancer,relative risks(95%CI)for current,former and ever smokers were respectively,2.98(2.08 to 4.26),1.61(1.23 to 2.09),and 2.22(1.79 to 2.74)based on 6,4 and 10 individual study estimates.For COPD,the corresponding estimates were 1.44(1.16 to 1.77),0.47(0.02 to 9.88),and 0.86(0.48 to 1.54)based on 4,2 and 2 estimates.For ischaemic heart disease(IHD)the estimates were 1.11(1.04 to 1.19),1.26(1.03 to 1.53)and 1.15(1.08 to 1.23)based on 6,3 and 4 estimates,while for stroke they were 1.02(0.92 to 1.13),1.08(0.85 to 1.38),and 1.11(0.95 to 1.31)based on 5,3 and 4 estimates.For overall circulatory disease they were 1.10(1.05 to 1.16),1.11(0.84 to 1.46),and 1.15(1.06 to 1.26)based on 3,3 and 4 estimates.CONCLUSION Exclusive cigar smoking is associated with an increased risk of lung cancer,and less so with COPD and IHD.The increases are lower than for cigarettes.展开更多
The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruc...The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.展开更多
AIM: To investigate the role of preoperative biliary drainage (PBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pa...AIM: To investigate the role of preoperative biliary drainage (PBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at SMS medical college, Jaipur, India. Demographic variables, details of preoperative stenting, operative procedure and post operative complications were noted. RESULTS: Preoperative biliary drainage was performed in 21 patients (43.5%). The incidence of septic complications was significantly higher in patients with biliary stent placement (P < 0.05, 0 vs 4). This group of patients also had a significantly higher minor biliary leak rate. Mortality and hospital stay in each group was comparable. CONCLUSION: Within this study population the use of PBD by endoscopic stenting was associated with a high incidence of infective complications. These findings do not support the routine use of biliary stenting in patients prior to pancreatico-duodenectomy.展开更多
AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out usin...AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pub Med until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out.RESULTS: Fourteen studies reported the prevalence of extramural venous invasion(EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26(0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395(0.29, 0.51)].CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future.展开更多
Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alt...Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.展开更多
There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-sma...There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.展开更多
In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribu...In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribution strategies,i.e.,＇Center of Strength-Center of Mass（CV-CM） coinciding＇ and ＇Balanced Center of Strength-Center of Resistance（CVCR）＇ are adopted.Design charts for the seismic demand of classical uni-directionally and bi-directionally asymmetric systems are developed in a simple unified format.A conceptual framework is also outlined to conveniently apply the design charts.Illustrations are included to explain the use of the current recommendations in practical design.The study also highlights the relative performance of ＇CV-CM coinciding＇ and ＇Balanced CV-CR＇ criteria.展开更多
AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis. METHODS: We prospectively assessed the pancreatic involvement in patients with acute...AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis. METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain. RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment. The etiology of pancreatitis was hepatitis E virus in 4, hepatitis A virus in 2, and hepatitis B virus in 1 patient. One patient had biliary sludge along with HEV infection. The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule. CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.展开更多
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
文摘BACKGROUND Pediatric candiduria is a frequently overlooked manifestation of healthcareassociated fungal infections.Candida species are increasingly being identified in the urine of neonates and infants,with non-albicans Candida(NAC)species being more prevalent than Candida albicans.AIM To determine the rate of Candida species isolation among pediatric patients with suspected urinary tract infections(UTI)at a tertiary care hospital.METHODS A total of 436 children with a clinical suspicion of UTI were enrolled in this laboratory-based descriptive observational study.The samples were then subjected to urine mounting and subcultured on Sabouraud dextrose agar.Candida isolates were identified based on the color of the colonies on CHROM agar,Dalmau plate culture,and germ tube formation.The results were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry,followed by Antifungal susceptibility testing using Vitek®2 AST-YS07 cards.RESULTS A total of 79 Candida isolates(18.12%)were identified.Of these,39(49.37%)were neonates,with a male-to-female ratio of 3.39:1.The intensive care unit(ICU)recorded 52 patients(65.82%).Of the 79 patients,57(72.15%)received broadspectrum antibiotics for more than 7 days.Our study revealed a higher prevalence of NAC species,with Candida tropicalis accounting for 34 cases(43.04%).Amphotericin B showed the highest susceptibility,with 68 isolates(86.08%)being susceptible to this Antifungal agent.CONCLUSION Pediatric patients with Candiduria present atypical and vague symptoms.This may be the initial symptom of disseminated Candidiasis in the presence of predisposing factors.Isolation of these pathogens,along with their Antifungal susceptibility patterns,aids in a better prognosis.
文摘BACKGROUND Acute colonic pseudo-obstruction(ACPO)is defined as colonic obstruction without a mechanical or extrinsic inflammatory factor.Colonic decompression is advised for patients with ACPO after the failure of conservative and medical management.AIM To systematically review and analyze the efficacy and safety of colonoscopic decompression in ACPO.METHODS A search was conducted in MEDLINE,EMBASE,and Scopus from inception to August 2024.Studies reporting the clinical success,perforation,recurrence,and need for surgery after colonoscopic decompression in ACPO were included.A random-effects inverse-variance model was used to calculate the pooled proportion.RESULTS Sixteen studies were included in the final analysis.The pooled rates of success after the first session of colonoscopic decompression and overall success were 78.8%(95%CI:72.0-85.6)and 91.5%(95%CI:87.0-96.0),respectively.The first session of colonoscopic decompression had a significantly higher success than the first dose of neostigmine with OR 3.85(95%CI:2.00-7.42).The pooled incidence of perforation was 0.9%(95%CI:0.0-2.0),while recurrence was observed in 17.1%(95%CI:12.9-21.3)of the patients after clinical success.The pooled rates of surgery in all cases undergoing colonoscopic decompression and those who had a successful procedure were 10.5%(95%CI:5.0-15.9)and 3.7%(95%CI:0.3-7.1),respectively.Subgroup analysis,excluding the low-quality studies,did not significantly change the event rates.CONCLUSION Colonoscopic decompression for ACPO is associated with a clinical success rate of>90%with a perforation rate of<1%,demonstrating high efficacy and safety.
基金supported by the National Natural Science Foundation of China(Grant Nos.22288101,22472016)the National Key Research and Development Program of the Ministry of Science and Technology(No.2022YFE0116000)+1 种基金the Chinese Academy of Sciences Strategy Leading Technology Project(No.XDA29000000)the Youth Innovation Promotion Association CAS(No.2021182)。
文摘Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant potential for promoting technologic progress in this field.Herein,we present Cu-ZSM-5 zeolite as a highly effective catalyst for alkane aromatization,achieving outstanding aromatics selectivity.In-situ Fourier transform infrared spectra of adsorbed nitric oxide,high-angle annular dark field scanning transmission electron microscopy,X-ray absorption spectroscopy,and electron paramagnetic resonance analyses reveal that the Cu^(2+)species act as the primary active centers for aromatics formation.During aromatization of alkanes,the reduction of Cu^(2+)to Cu^(+)species correlates with diminished aromatics selectivity.Notably,introducing CO_(2)into the reaction feed not only enhances aromatics selectivity by maintaining Cu^(2+)species in their active oxidation state under reducing conditions,but also improves catalytic stability by eliminating coke.Furthermore,CO_(2)is converted into CO and aromatic products during the reaction,offering a novel way for CO_(2)utilization through the coupling reaction of alkane and CO_(2).
基金Supported by the Key Research and Development Program of Shandong(Nos.2021LZGC029,2023LZGC019)the National Natural Science Foundation of China(No.42076093)+1 种基金the Special Funds for the Central Government to Guide Local Science and Technology Development(No.YDZX2023043)the Taishan Scholars Program(No.tsqn202306279)。
文摘Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study investigates the nutritional quality of A.japonicus from different geographical regions and identifies genetic markers associated with these traits through a genome-wide association study(GWAS).We observed significant regional variations in the nutritional content of A.japonicus.Samples collected from Nanhuangcheng Island displayed the highest levels of saponins,whereas those from Laizhou exhibited the highest concentrations of glycosaminoglycans.Lingshan Island samples were the richest in amino acids,while samples from Rizhao contained the highest levels of polyunsaturated fatty acids.Through GWAS,265 candidate genes and related single nucleotide polymorphisms(SNPs)were identified as being significantly associated with essential nutritional traits,including genes like ubiquitin domain-containing protein 1(UBTD1),inactive pancreatic lipase-related protein 1,protein arginine N-methyltransferase 5(PRMT5)and GDP-fucose protein O-fucosyltransferase 1(POFUT1).This study advanced our knowledge of the genetic mechanisms underlying the nutritional quality of A.japonicus.The genetic markers identified herein o ffer crucial insights for breeding initiatives aimed at optimizing the nutritional profile of sea cucumbers.
基金Supported by Javna Agencija za Raziskovalno in Inovacijsko Dejavnost RS,No.P3-0036,No.I0-0029,No.J3-50098,and No.N1-0305University medical center Maribor,No.IRP-2021/02-05Swiss National Science Foundation(SNF)Postdoctoral Fellowship,No.P500PM217647/1.
文摘The gastrointestinal(GI)tract is essential for digestion,absorption,excretion,and protection,supported by a diverse microbial ecosystem.Traditional in-vitro models often fall short in capturing the physiological complexity of the GI tract,limiting their translational applications.A comprehensive approach is needed to bridge the gap between simple cell cultures and more complex systems used in translational research.This review explores the limitations of conventional twodimensional cell cultures and emphasizes the emerging use of three-dimensional and microfluidic systems that better replicate the GI tract’s structure and functions.It highlights the importance of incorporating patient-derived cells and engineered microenvironments to enhance model relevance and support personalized medicine.The review also discusses advanced fabrication techniques such as micro-extrusion and laser-assisted bioprinting,which enable the creation of sophisticated tissue models capable of simulating critical GI processes,including molecular transport,peristalsis,and liver coupling.Advancing the complexity of in-vitro systems will help replicate the GI tract’s interactions and physiological phenomena,thus improving the translational potential of GI research.This review provides valuable insights into the advancements and challenges in GI modeling,serving as a comprehensive guide for developing models that bridge the gap between basic cell cultures and clinically relevant systems.
文摘Background:Gastric Cancer(GC)is the 5th most prevalent and 4th most deadly neoplasm globally.Immunotherapy has emerged as a promising treatment approach in GC,potentially improving positive clinical outcomes while addressing the limitations of conventional therapies.GC immunotherapy modalities consist of adoptive cell therapy(ACT),cancer vaccines,and immune checkpoint inhibitors(ICI).Objectives:This systematic review aims to provide an overview of the advances in immune-based therapeutic approaches in GC,highlighting the potential of this therapy as a strategy for GC treatment.Methods:Key studies investigating several immunotherapeutic agents and combination therapies were searched in PUBMED and included in this study.Specific cancer outcomes related to disease progression or survival were analyzed.Results:After screening 236 studies,the results revealed that immunotherapy,particularly the ICI pembrolizumab,demonstrated promising efficacy in the treatment of GC,as several studies reported improved OS,PFS,and objective response rate with the use of pembrolizumab alone or in combination with other treatment modalities.Conclusion:Safety analysis showed that immunotherapy was mostly well-tolerated,with manageable adverse events and relatively good safety profiles.Nonetheless,further research is required to understand the mechanisms of tumor resistance better and identify predictive biomarkers that can direct treatment optimization.
文摘AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which provide estimates of relative risk （RR） and 95%CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke （ETS）： The spouse; household; workplace; childhood; travel; social and other; and total. A wide range of study details were entered into a database, and the RRs for each study, including descriptions of the comparisons made, were entered into a linked database. RRs were derived where necessary. Results were entered, where available, for all lung cancer, and for squamous cell cancer and adenocarcinoma. “Most adjusted” results were entered based on results available, adjusted for the greatest number of potential confounding variables. “Least adjusted” results were also entered, with a preference for results adjusted at least for age for prospective studies. A pre-planned series of fxed-effects and random-effects meta-analyses were conducted. Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex, and results for childhood exposure given by source of ETS exposure. For spousal exposure, more extensive analyses provide results by various aspects of study design and defnition of the RR. For smoking by the husband （or nearest equivalent）, additional analyses were carried out both for overall risk, and for risk per 10 cigarettes per day smoked by the husband. These adjusted for uncontrolled confounding by four factors （fruit, vegetable and dietary fat consumption, and education）, and corrected for misclassification of smoking status of the wife. For the confounding adjustment, estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure, and on the correlations between the factors. The bias due to misclassifcation was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere, and that those who deny smoking have the same risk as those who admit it. This approach, justifed in previous work, balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS： One hundred and two studies were identifed for inclusion, published in 1981 onwards, 45 in Asia, 31 in North America, 21 in Europe, and fve elsewhere. Eighty-fve were of case-control design and 17 were prospective. Significant （P 〈 0.05） associations were noted, with random-effects of （RR = 1.22, 95%CI： 1.14-1.31, n = 93） for smoking by the husband （RR = 1.14, 95%CI： 1.01-1.29, n = 45） for smoking by the wife （RR = 1.22, 95%CI： 1.15-1.30, n = 47） for workplace exposure （RR = 1.15, 95%CI： 1.02-1.29, n = 41） for childhood exposure, and （RR = 1.31, 95%CI： 1.19-1.45, n = 48） for total exposure. No signifcant association was seen for ETS exposure in travel （RR = 1.34, 95%CI： 0.94-1.93, n = 8） or in social situations （RR = 1.01, 95%CI： 0.82-1.24, n = 15）. A signifcant negative association （RR = 0.78, 95%CI： 0.64-0.94, n = 8） was seen for ETS exposure in childhood, specifically from the parents. Significant associations were also seen for spousal smoking for both squamous cell carcinoma （RR = 1.44, 95%CI： 1.15-1.80, n = 24） and adenocarcinoma （RR = 1.33,95%CI： 1.17-1.51, n = 30）. Results generally showed marked heterogeneity between studies. For smoking by either the husband or wife, where 119 RR estimates gave an overall estimate of （RR = 1.21, 95%CI： 1.14-1.29）, the heterogeneity was highly significant （P 〈 0.001）, with evidence that the largest RRs were seen in studies published in 1981-89, in small studies （1-49 cases）, and for estimates unadjusted by age. For smoking by the husband, the additional analyses showed that adjustment for the four factors reduced the overall （RR = 1.22, 95%CI： 1.14-1.31） based on 93 estimates to （RR = 1.14, 95%CI： 1.06-1.22）, implying bias due to uncontrolled confounding of 7%. Further correction for misclassification reduced the estimate to a marginally non-signifcant （RR = 1.08, 95%CI： 0.999-1.16）. In the fully adjusted and corrected analyses, there was evidence of an increase in Asia （RR = 1.18, 95%CI： 1.07-1.30, n = 44）, but not in other regions （RR = 0.96, 95%CI： 0.86-1.07, n = 49）. Studies published in the 1980’s, studies providing dose-response data, and studies only providing results unadjusted for age showed elevated RRs, but later published studies, studies not providing dose-response data, and studies adjusting for age did not. The pattern of results for RRs per 10 cigs/d was similar, with no signifcant association in the adjusted and corrected results （RR = 1.03, 95%CI： 0.994-1.07）.CONCLUSION： Most, if not all, of the ETS/lung cancer association can be explained by confounding adjustment and misclassifcation correction. Any causal relationship is not convincingly demonstrated.
基金Supported by the JT International SA,Assignment Schedule,No.14.
文摘BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating exclusive cigar smoking to risk of the major smoking-related diseases.METHODS Literature searches detected studies carried out in the United States which estimated the risk of lung cancer,chronic obstructive pulmonary disease(COPD),heart disease,stroke or overall circulatory disease in exclusive cigar smokers as compared to those who had never smoked any tobacco product.Papers were identified from reviews and detailed searches on MEDLINE.For each study,data were extracted onto a study database and a linked relative risk database.Relative risks and 95%CIs were extracted,or estimated,relating to current,former or ever exclusive cigar smokers,and meta-analysed using standard methods.Sensitivity analyses were conducted including or excluding results from studies that did not quite fit the full selection criteria(for example,a paper presenting combined results from five studies,where 86%of the population were in the United States).RESULTS The literature searches identified 17 relevant publications for lung cancer,four for COPD and 12 for heart disease,stroke and circulatory disease.These related to 11 studies for lung cancer,to four studies for COPD and to eight studies for heart disease,stroke or overall circulatory disease.As some studies provided results for more than one disease,the total number of studies considered was 13,with results from four of these used in sensitivity analyses.There was evidence of significant heterogeneity in some of the meta-analyses so the random-effects estimates are summarized below.As the results from the sensitivity analyses were generally very similar to those from the main analyses,and involved more data,only the sensitivity results are summarized below.For lung cancer,relative risks(95%CI)for current,former and ever smokers were respectively,2.98(2.08 to 4.26),1.61(1.23 to 2.09),and 2.22(1.79 to 2.74)based on 6,4 and 10 individual study estimates.For COPD,the corresponding estimates were 1.44(1.16 to 1.77),0.47(0.02 to 9.88),and 0.86(0.48 to 1.54)based on 4,2 and 2 estimates.For ischaemic heart disease(IHD)the estimates were 1.11(1.04 to 1.19),1.26(1.03 to 1.53)and 1.15(1.08 to 1.23)based on 6,3 and 4 estimates,while for stroke they were 1.02(0.92 to 1.13),1.08(0.85 to 1.38),and 1.11(0.95 to 1.31)based on 5,3 and 4 estimates.For overall circulatory disease they were 1.10(1.05 to 1.16),1.11(0.84 to 1.46),and 1.15(1.06 to 1.26)based on 3,3 and 4 estimates.CONCLUSION Exclusive cigar smoking is associated with an increased risk of lung cancer,and less so with COPD and IHD.The increases are lower than for cigarettes.
文摘The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.
文摘AIM: To investigate the role of preoperative biliary drainage (PBD) in the outcome of classical pancreaticodu odenectomy. METHODS: A 10-year retrospective data analysis was performed on patients (n = 48) undergoing pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at SMS medical college, Jaipur, India. Demographic variables, details of preoperative stenting, operative procedure and post operative complications were noted. RESULTS: Preoperative biliary drainage was performed in 21 patients (43.5%). The incidence of septic complications was significantly higher in patients with biliary stent placement (P < 0.05, 0 vs 4). This group of patients also had a significantly higher minor biliary leak rate. Mortality and hospital stay in each group was comparable. CONCLUSION: Within this study population the use of PBD by endoscopic stenting was associated with a high incidence of infective complications. These findings do not support the routine use of biliary stenting in patients prior to pancreatico-duodenectomy.
文摘AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer.METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pub Med until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out.RESULTS: Fourteen studies reported the prevalence of extramural venous invasion(EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26(0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395(0.29, 0.51)].CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future.
文摘Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.
文摘There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.
文摘In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribution strategies,i.e.,＇Center of Strength-Center of Mass（CV-CM） coinciding＇ and ＇Balanced Center of Strength-Center of Resistance（CVCR）＇ are adopted.Design charts for the seismic demand of classical uni-directionally and bi-directionally asymmetric systems are developed in a simple unified format.A conceptual framework is also outlined to conveniently apply the design charts.Illustrations are included to explain the use of the current recommendations in practical design.The study also highlights the relative performance of ＇CV-CM coinciding＇ and ＇Balanced CV-CR＇ criteria.
文摘AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis. METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain. RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment. The etiology of pancreatitis was hepatitis E virus in 4, hepatitis A virus in 2, and hepatitis B virus in 1 patient. One patient had biliary sludge along with HEV infection. The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule. CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.
