在有经历非肝的外科的肝疾病的病人的 Perioperative 风险因素

The patients with liver disease present for various surgical interventions. Surgery may lead to complications in a significant proportion of these patients. These complications may result in considerable morbidity and mortality. Preoperative assessment can predict survival to some extent in patients with liver disease undergoing surgical procedures. A review of literature suggests nature and the type of surgery in these patients determines the peri-operative morbidity and mortality. Optimization of premorbid factors may help to reduce perioperative mortality and morbidity. The purpose of this review is to discuss the effect of liver disease on perioperative outcome; to understand various risk scoring systems and their prognostic significance; to delineate different preoperative variables implicated in postoperative complications and morbidity; to establish the effect of nature and type of surgery on postoperative outcome in patients with liver disease and to discuss optimal anaesthesia strategy in patients with liver disease.

Future of liver transplantation: Non-human primates for patient-specific organs from induced pluripotent stem cells

Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.

Prospects for 3D bioprinting of organoids

Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies.However,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these impediments.In this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids.We also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue organization.To fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.

Antitubercular therapy in patients with cirrhosis:Challenges and options

Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.

Association of obesity with hypertension and type 2 diabetes mellitus in India:A meta-analysis of observational studies

AIM To perform a meta-analysis of the association of obesity with hypertension and type 2 diabetes mellitus(T2DM) in India among adults. METHODS To conduct meta-analysis, we performed comprehensive, electronic literature search in the PubM ed, CINAHL Plus, and Google Scholar. We restricted the analysis to studies with documentation of some measure of obesity namely; body mass index, waist-hip ratio, waist circumference and diagnosis of hypertension or diagnosis of T2DM. By obtaining summary estimates of all included studies, the meta-analysis was performed using both RevM an version 5 and "metan" command STATA version 11. Heterogeneity was measured by I^2 statistic. Funnel plot analysis has been done to assess the study publication bias.RESULTS Of the 956 studies screened, 18 met the eligibility criteria. The pooled odds ratio between obesity and hypertension was 3.82(95%CI: 3.39 to 4.25). The heterogeneity around this estimate(I^2 statistic) was 0%, indicating low variability. The pooled odds ratio from the included studies showed a statistically significant association between obesity and T2DM(OR = 1.14, 95%CI: 1.04 to 1.24) with a high degree of variability.CONCLUSION Despite methodological differences, obesity showed significant, potentially plausible association with hypertension and T2DM in studies conducted in India. Being a modifiable risk factor, our study informs setting policy priority and intervention efforts to prevent debilitating complications.

Assessing resource vulnerability quadrants under changing precipitation trends in Uttarakhand,Central Himalayan region

The Central Himalayan region is vulnerable to the adverse effects of climate change and characterized by regional climatic conditions.The livelihood of the mountain communities across the Himalaya is at risk owing to the consequences of variable precipitation patterns.There exists limited empirical research on precipitation variability due to inadequate hydro-meteorological stations at highaltitude regions.The study uses a novel methodology which integrates precipitation variability with resource sensitivity over the three verticals of Central Himalaya:Himadri,Himachal and Shivaliks and across four major river basins:Yamuna,Upper Ganga,Ghaghar and Ramganga.The magnitude of the significant precipitation trends was estimated through time series analysis at a 95%confidence interval.To assess the sensitivity of natural resources(forest,water and land)and human resources,fourteen mountain-specific indicators were identified which captured resource index using data standardization and principal component analysis.Sen’s slope and Resource index were plotted in a 2D Cartesian coordinate to draw precipitation-resource quadrants with their effective coverage area:High Precipitation and Scarce Resources(35.92%);Low Precipitation and Abundant Resources(30.10%);Low Precipitation and Scarce Resources(22.33%)and High Precipitation and Abundant Resources(11.65%).This helped in developing quadrant-specific adaptation strategies under regional variability of precipitation.The methodology and the research findings will certainly assist water experts,resource managers and policy makers to strengthen adaptive capacity and improve the resilience of vulnerable communities across Himalaya.

Soil pH as a Phenotype Determinant in Humans: Proposing a Scientific Hypothesis

Plant growth, habitat of various microorganisms, sustenance conditions for the fauna and flora, are determined by the quality of soil. However, alteration in the properties of soil leads to various deficiencies/diseases in plants and thereby affects dependent fauna. The alkalinity and acidity of the soil refer to the change in pH value of the soil. In the North East India, most of the soils lack calcium (Ca) and are acidic. Therefore, majority of the fauna and flora have lower availability of Ca due to leaching, caused by the heavy rainfall. The present study hypothesizes that the life originating from areas deficient in Ca, impacts their bone concentration and facial formation. This makes them phenotypically distinct from their counterparts residing in the other regions which have alkaline soils or have the optimum pH value of soil. Strongly acidic soils, might have led to the formation of the major Mongolian Race in humans.

Challenges faced for undertaking a stem cell based clinical trial in spinal cord injury in emerging countries

Repair and regeneration after spinal cord injury(SCI)is an unmet need and research into finding new avenues to achieve this are ongoing worldwide.Stem cells with their immense potential to proliferate and differentiate have been identified as prime candidates for spinal cord regeneration.Pre-clinical data on their efficacy has been very encouraging,especially in case of adult stem cells.Although clinical translation of these findings has not been so successful,due to the ease of obtaining autologous adult bone marrow stem cells and their perceived therapeutic potential,these cells have been offered as a“therapy”in many countries without any scientific evidence generated though a valid clinical trial.In this review,we attempt to highlight the need for conducting clinical trials and the challenges faced in case of emerging countries.The current scenario of regulations governing the use of stem cells in emerging countries is also discussed.

印度儿童的皮肤结核:筛查受累的内脏器官的重要性

Aims and objectives. Resurgence of skin tuberculosis especially with drug-resistant strains has been well documented in recent years, but this problem has not received much attention in the paediatric age group. Hence, we carried out the present study to analyse the clinical and therapeutic aspects of cutaneous tuberculosis in children. Materials and methods. A detailed clinical examination, investigations, such as haemogram, serology for HIV, Mantoux test, chest X-ray, cytology, culture and histopathologywere carried out in all children. They were treated with antitubercular therapy (WHO regimen), and the clinical response was followed up. Results. Of 142 patients with cutaneous tuberculosis, 68 were children (40 females, 28 males). These children were aged from 9 months to 14 years. The duration of the disease varied from 1 month to 6 years. Family history of tuberculosis was present in 28 (41.2%) of the patients. Scrofulodermawas themost commonpresentation encountered in 30 (44.1%) patients with preferential involvement of the cervical (56.2%) and inguinal (20%) regions. Fifteen (22.1%) patients had lupus vulgaris, of which the keratotic type was the most common (46.7%), 16 had lichen scrofulosorum, three had tuberculosis verrucosa cutis, and four had more than one type of tuberculosis. Involvement of the lung in 14 (20.6%), bone in seven (10.2%), and both in four (5.9%) was found. Histopathology corroborated the clinical diagnosis in 54 (80.6%), culture was positive in six (8.8%). Fifty (73.5%)-patients completed the treatment with an excellent response, no multi-drug resistant cases were seen. Conclusions. Cutaneous tuberculosis in children continues to be an important cause of morbidity, there is a high likelihood of internal involvement, especially in patients with scrofuloderma. A search is required for more sensitive, economic diagnostic tools. Response to treatment at 4 weeks often helps in substantiating the diagnosis of tuberculosis in doubtful cases.

Electron-Proton Pairing at High Temperatures, Solar Flares, and the FIP Effect

We analyze the line data from solar flares to present evidence for the emission spectrum of the recently discussed electron-proton pairs at high temperatures. We also point out that since the pairing phenomenon provides an additional source for these lines—the conventional source being the highly ionized high-Z atoms already existing in the solar atmosphere, we have a plausible explanation of the FIP effect.

CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis

Background and Aims:Cirrhosis patients exhibit cyto-penia,and,at times refractory neutropenia to granulocyte colony-stimulating factor(G-CSF),which acts through the CSF3-receptor(CSF3R),and changes in CSF3R can affect the response.We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients.Methods:Cirrhotic patients(n=127)and controls(n=26)with clini-cally indicated bone marrow(BM)examination were stud-ied.BM assessment was done by qRT-PCR and immunohis-tochemistry(IHC)for CSF3R.Circulating G-CSF,CSF3R,and carcinoembryonic antigen cell adhesion molecule-1(CEACAM1)were measured.BM hematopoietic precursor cells and their alterations were examined by flow cytom-etry.The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia.Results:The mean age was 48.6±13.4 years,and 80.3%were men.Circulatory CSF3R reduction was noted with the advance-ment of cirrhosis,and confirmed by qRT-PCR and IHC in BM.CSF3R decline was related to decreased hematopoietic stem cells(HSCs)and downregulation of CSF3R in the re-maining HSCs.Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation.Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up.Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia.Conclu-sions:Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circula-tion,making patients prone to infection and inadequate response to exogenous G-CSF.

EUS-guided Gall Bladder Drainage in Severe Liver Disease: A Single-center Experience in Critically Ill Cirrhotics

Background and Aims:Acute calculous cholecystitis with impending gall bladder perforation in severe liver diseases including decompensated cirrhosis and acute-on-chronic liver failure(ACLF)is difficult to manage,due to the procedures such as cholecystectomy and percutaneous cholecystostomy being associated with high risk and complications in these patients.Methods:Four cases of severe liver disease with acute calculous cholecystitis who presented to the Institute of Liver and Biliary Sciences(New Delhi,India)for further management were included in the study if they underwent endoscopic ultrasound-guided gall bladder drainage(EUS-GBD).The patients were followed up for a minimum of 3 months and outcomes were recorded.Results:Four cases of severe liver disease(three ACLF and one decompensated cirrhosis),with model for end-stage liver disease scores of 24,26,23 and 25 respectively,presented with acute calculous cholecystitis(Tokyo grade III)and systemic sepsis(high total leukocyte counts).Their international normalized ratios were 2.3,2.6,2.2 and 2.9 respectively,and two were in shock,requiring inotropes at presentation.Ultrasonography of the abdomen confirmed hugely distended gall bladder with stone impacted at the neck and moderate ascites.All these cases underwent EUS-GBD by linear echo endoscope,and had the gastric wall punctured in the antrum using a 19G access needle followed by dilatation of the tract using controlled radial expansion balloon and Sohendra dilator.In three cases,the plastic stents were placed.In the fourth case,a Nagi stent was placed.All the patients recovered and were discharged within a week.Conclusions:EUS-GBD is challenging in severe liver disease but represents a life-saving procedure,and hence can be attempted in such critically ill patients with utmost care and precaution.

肝移植术后并发症的影像学诊断全景

肝脏是第二常见的移植器官,仅次于肾脏,显然,肝脏疾病是全球范围内一种常见且严重的疾病。随着外科学、肿瘤学及影像学技术的发展,原位肝移植已经成为许多终末期肝病患者的一线治疗方案。超声和多普勒彩超是评估肝移植术后液体积聚和血管并发症最经济、性价比最高的影像学方法。CT可用以进一步证实超声检查结果,并可用于肺部并发症的诊断。磁共振成像可用于发现肝管并发症、胆漏及神经系统并发症。本文论述了对于肝移植术后各种可能的并发症,如何进行影像学技术的选择。

A Novel Numerical Method of O(h^(4))for Three-Dimensional Non-Linear Triharmonic Equations

In this article,we present two new novel finite difference approximations of order two and four,respectively,for the three dimensional non-linear triharmonic partial differential equations on a compact stencil where the values of u,δ^(2)u/δn^(2)andδ^(4)u/δn^(4)are prescribed on the boundary.We introduce new ideas to handle the boundary conditions and there is no need to discretize the derivative boundary conditions.We require only 7-and 19-grid points on the compact cell for the second and fourth order approximation,respectively.The Laplacian and the biharmonic of the solution are obtained as by-product of the methods.We require only system of three equations to obtain the solution.Numerical results are provided to illustrate the usefulness of the proposed methods.