Navigating the kidney organoid: insights into assessment and enhancement of nephron function.

Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care.NEW & NOTEWORTHY Kidney organoids are three-dimensional structures derived from stem cells, mimicking the major components of mammalian kidneys. Although they show great promise, their functional capacity has become a critical question. This review explores the advancements and challenges in evaluating and enhancing kidney organoid function, including the use of organ-on-chip technologies, multiomics data, and in vivo transplantation. Integrating these approaches to further enhance their physiological relevance will continue to advance disease modeling and regenerative medicine applications.

Cost of screening, out-of-pocket expenditure & quality of life for diabetes & hypertension in India.

Background & objectives: The Government of India has initiated a population based screening (PBS) for noncommunicable diseases (NCDs). A health technology assessment agency in India commissioned a study to assess the cost-effectiveness of screening diabetes and hypertension. The present study was undertaken to estimate the cost of PBS for Type II diabetes and hypertension. Second, out-of-pocket expenditure (OOPE) for outpatient care and health-related quality of life (HRQoL) among diabetes and hypertension patients were estimated. Methods: Economic cost of PBS of diabetes and hypertension was assessed using micro-costing methodology from a health system perspective in two States. A total of 165 outpatients with diabetes, 300 with hypertension and 497 with both were recruited to collect data on OOPE and HRQoL. Results: On coverage of 50 per cent, the PBS of diabetes and hypertension incurred a cost of ₹ 45.2 per person screened. The mean OOPE on outpatient consultation for a patient with diabetes, hypertension and both diabetes and hypertension was ₹ 4381 (95% confidence interval [CI]: 3786-4976), ₹ 1427 (95% CI: 1278-1576) and ₹ 3932 (95% CI: 3614-4250), respectively. Catastrophic health expenditure was incurred by 20, 1.3 and 14.8 per cent of patients with diabetes, hypertension and both diabetes and hypertension, respectively. The mean HRQoL score of patients with diabetes, hypertension and both was 0.76 (95% CI: 0.72-0.8), 0.89 (95% CI: 0.87-0.91) and 0.68 (95% CI: 0.66-0.7), respectively. Interpretations & conclusions: The findings of our study are useful for assessing cost-effectiveness of screening strategies for diabetes and hypertension.

Antibody-conjugated pH-sensitive liposomes for HER-2 positive breast cancer: development, characterization, in vitro and in vivo assessment.

The object of the current study was to develop and evaluate trastuzumab-conjugated Paclitaxel (PTX) and Elacridar (ELA)-loaded PEGylated pH-sensitive liposomes (TPPLs) for site-specific delivery of an anticancer drug. In this study, paclitaxel is used as an anticancer drug which promotes microtubules polymerization and arrest cell cycle progression at mitosis and subsequently leading to cell death. The single use of PTX causes multiple drug resistance (MDR) and results failure of the therapy. Hence, the combination of PTX and P-glycoprotein inhibitor (ELA) are used to achieve maximum therapeutic effects of PTX. Moreover, monoclonal antibody (trastuzumab) is used as ligand for the targeting the drug bearing carriers to BC. Thus, trastuzumab anchored pH-sensitive liposomes bearing PTX and ELA were developed using thin film hydration method and Box-Behnken Design (BBD) for optimizing various formulation variables. The optimized liposomes undergo characterization such as vesicle size, PDI, and zeta potential, which were observed to be 122 ± 2.14 nm, 0.224, and -15.5 mV for PEGylated pH-sensitive liposomes (PEG-Ls) and 134 ± 1.88 nm, 0.238, and -13.98 mV for TPPLs, respectively. The results of the in vitro drug release study of both formulations (PEG-Ls and TPPLs) showed enhanced percentage drug release at an acidic pH 5 as compared to drug release at a physiological pH 7.4. Further, the in vitro cytotoxicity studies were performed in the SK-BR-3 and MDA-MB-231 cell lines. The cellular uptake study of FITC-loaded TPPLs in SK-BR-3 cells showed greater uptake than FITC-loaded PEG-Ls, while in MDA-MB-231 cells there was no significant difference in cell uptake between FITC-loaded TPPLs and FITC-loaded PEG-Ls. Hence, it can be concluded that the HER-2 overexpressing cancer cell line (SK-BR-3) was showed better cytotoxicity and cell uptake of TPPLs than the cells that expressed low levels of HER2 (MDA-MB-231). The in vivo tumor regression study, TPPLs showed significantly more tumor burden reduction i.e. up ∼74% as compared to other liposomes after 28 days. Furthermore, the in vivo studies of TPPLs showed a minimal toxicity profile, minimal hemolysis, higher tumor tissue distribution, and superior antitumor efficacy as compared to other formulations. These studies confirmed that TPPLs are a safe and efficacious treatment for breast cancer.

Glacial lake outburst flood risk assessment using remote sensing and hydrodynamic modeling: a case study of Satluj basin, Western Himalayas, India.

Glacier-associated hazards are becoming a common and serious challenge to the high mountainous regions of the world. Glacial lake outburst floods (GLOFs) are one of the most serious unanticipated glacier hazards, with the potential to release a huge amount of water and debris in a short span of time, resulting in the loss of lives, property, and severe damage to downstream valleys. The present study used multi-temporal Landsat and Google earth imageries to analyze the spatio-temporal dynamism of the selected glacial lake (moraine-dammed) in the Satluj basin of Western Himalayas. Furthermore, GLOF susceptibility of the lake was assessed using a multi-criteria decision-based method. The results show that the lake area has increased from 0.11 to 0.26 km2 over the past 28 years from 1990 to 2018. The susceptibility index value for the lake was calculated as 0.75, which indicates that the lake is highly susceptible to the GLOF. The depth and volume of the lake were estimated to be 16 m and 57 × 105 m3, respectively, using an empirical formula. HEC-RAS, HECGeo-RAS, and Arc-GIS software were utilized in this study to perform unsteady flow analysis and to determine the GLOF impact on the downstream area. The worst-case GLOF scenario (breach width of 75 m) was revealed during an overtopping failure of the moraine dam, resulted in a peak discharge of 4060 m3/s and releasing a total water volume of 57 × 105 m3. The breach hydrograph has been routed to calculate the spatial and temporal distribution of peak flood, inundation depth, velocity, water surface elevation, and flood peak arrival time along the river channel. The analysis further reveals that the routed flood waves reach the nearest settlement, i.e., Rajpur town, situated at a distance of 102 km in the downstream valley of the lake at 6 h after the beginning of the lake breach event with a peak discharge/flood of 1757 m3/s and maximum flow velocity of 1.5 m/s. With the ongoing climate warming and glacier retreat, moraine-dammed lakes are becoming more hazardous and thus increasing the total threat. Therefore, it is mandatory to monitor and assess such lakes at regular intervals of time to lessen the disastrous impacts of GLOFs on the livelihood and infrastructure in the downstream valleys. The findings of this study will aid in the creation of risk management plans, preparatory tactics, and risk reduction techniques for GLOF hazards in the region.

Cost-effectiveness of population-based screening for diabetes and hypertension in India: an economic modelling study.

BACKGROUND: India faces a high burden of diabetes and hypertension. Currently, there is a dearth of economic evidence about screening programmes, affected age groups, and frequency of screening for these diseases in Indian settings. We assessed the cost effectiveness of population-based screening for diabetes and hypertension compared with current practice in India for different scenarios, according to type of screening test, population age group, and pattern of health-care use. METHODS: We used a hybrid decision model (decision tree and Markov model) to estimate the lifetime costs and consequences from a societal perspective. A meta-analysis was done to assess the effectiveness of population-based screening. Primary data were collected from two Indian states (Haryana and Tamil Nadu) to assess the cost of screening. The data from the National Health System Cost Database and the Costing of Health Services in India study were used to determine the health system cost of diagnostic tests and cost of treating diabetes or hypertension and their complications. A total of 962 patients were recruited to assess out-of-pocket expenditure and quality of life. Parameter uncertainty was evaluated using univariate and multivariable probabilistic sensitivity analyses. Finally, we estimated the incremental cost per quality-adjusted life-year (QALY) gained with alternative scenarios of scaling up primary health care through a health and wellness centre programme for the treatment of diabetes and hypertension. FINDINGS: The incremental cost per QALY gained across various strategies for population-based screening for diabetes and hypertension ranged from US$0·02 million to $0·03 million. At the current pattern of health services use, none of the screening strategies of annual screening, screening every 3 years, and screening every 5 years was cost-effective at a threshold of 1-time per capita gross domestic product in India. In the scenario in which health and wellness centres provided primary care to 20% of patients who were newly diagnosed with uncomplicated diabetes or hypertension, screening the group aged between 30 and 65 years every 5 years or 3 years for either diabetes, hypertension, or a comorbid state (both diabetes and hypertension) became cost-effective. If the share of treatment for patients with newly diagnosed uncomplicated diabetes or hypertension at health and wellness centres increases to 70%, from the existing 4% at subcentres and primary health centres, annual population-based screening becomes a cost saving strategy. INTERPRETATION: Population-based screening for diabetes and hypertension in India could potentially reduce time to diagnosis and treatment and be cost-effective if it is linked to comprehensive primary health care through health and wellness centres for provision of treatment to patients who screen positive. FUNDING: Department of Health Research, Government of India.

Assessment and Efficacy of Low-Dose CT Screening and Primary Care Providers Perspective on Lung Cancer Screening: An Institutional Review.

Lung cancer is the most common cause of death in both men and women. The United States Preventive Services Task Force (USPSTF) recommends annual lung screening with low-dose computed tomography (LDCT) chest for individuals aged 55-80 who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. We reviewed the electronic medical records of patients visiting our outpatient clinic over a period of one year. We included all eligible individuals according to USPSTF guidelines for LDCT to identify screening rates at our institution. All primary care physicians, including residents and attendings, were given a prepared questionnaire to understand their beliefs and concerns with the implementation of this program. A total of 13,500 patients visited the outpatient clinic and 1178 were eligible for LDCT. Forty-five percent (45%) of patients received LDCT screening, which was higher than the national average of 2%-5%. A total of 50 primary care providers were included in the survey. The majority of the providers were aware of the USPSTF guidelines and believed that patients with multiple comorbidities and insurance issues were barriers in initiating LDCT screening. Lung cancer screening is an important component in cancer preventive strategies. Widespread awareness among the primary care providers and the public is extremely necessary for improving the use of LDCT.

Fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis, assessment of disease activity and therapeutic response in relapsing polychondritis.

OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) PET/CT in the assessment of disease activity, extent of the disease and response to therapy in relapsing polychondritis. METHODS: Twenty-five patients (9 men, 16 women) with a mean age of 38.2 years (s.d. 13.7; range 18-62), diagnosed to have relapsing polychondritis according to Damiani and Levine's modification of McAdam's criteria, who underwent PET/CT examination were included. Ten patients underwent a second PET/CT examination after therapy or during follow-up. Clinical symptoms and auxiliary examination findings were recorded. PET/CT findings were reviewed and correlated with the clinical symptoms. RESULTS: The major symptoms were aural pain (n = 21), nasal pain (n = 10), stridor (n = 5), cough (n = 9), fever (n = 8) and laryngeal tenderness (n = 8). The initial PET/CT was positive in 23/25 patients. PET/CT revealed involvement of auricular (n = 14), nasal (n = 8), laryngeal (n = 7), tracheobronchial (n = 6) and Eustachian (n = 3) cartilages with a mean maximum standardized uptake value (SUVmax) of 4.1 (s.d. 2.5; range 1.7-12.7). Fair correlation of aural/nasal pain/stridor with FDG avidity of cartilage involvement on PET/CT was noted. The key finding was detection of asymptomatic large airway involvement in seven patients (28%). Re-examination PET in 10 patients revealed complete therapeutic response (n = 5), partial response (n = 1), stable disease (n = 1), progressive disease (n = 1) and disease recurrence (n = 2). CONCLUSION: FDG PET/CT is a useful tool for the assessment of the disease activity and extent. It identified activity in clinically inaccessible sites that are of clinical significance. It is also useful in assessing treatment response and finding relapse.

Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation.

Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imaging allows for longitudinal, noninvasive assessments and can provide key information about infectious processes deep within the body.

Untangling the water-food-energy-environment nexus for global change adaptation in a complex Himalayan water resource system.

Holistic water management approaches are essential under future climate and socio-economic changes, especially while trying to achieve inter-disciplinary societal goals such as the Sustainable Development Goals (SDGs) of clean water, hunger eradication, clean energy and life on land. Assessing water resources within a water-food-energy-environment nexus approach enables the relationships between water-related sectors to be untangled while incorporating impacts of societal changes. We use a systems modelling approach to explore global change impacts on the nexus in the mid-21st century in a complex western Himalayan water resource system in India, considering a range of climate change and alternative socio-economic development scenarios. Results show that future socio-economic changes will have a much stronger impact on the nexus compared to climate change. Hydropower generation and environmental protection represent the major opportunities and limitations for adaptation in the studied system and should, thereby, be the focus for actions and systemic transformations in pursue of the SDGs. The emergence of scenario-specific synergies and trade-offs between nexus component indicators demonstrates the benefits that water resource systems models can make to designing better responses to the complex nexus challenges associated with future global change.

Modeling the cost and benefit of proteome regulation in a growing bacterial cell.

Escherichia coli cells differentially regulate the production of metabolic and ribosomal proteins in order to stay close to an optimal growth rate in different environments, and exhibit the bacterial growth laws as a consequence. We present a simple mathematical model of a growing-dividing cell in which an internal dynamical mechanism regulates the allocation of proteomic resources between different protein sectors. The model allows an endogenous determination of the growth rate of the cell as a function of cellular and environmental parameters, and reproduces the bacterial growth laws. We use the model and its variants to study the balance between the cost and benefit of regulation. A cost is incurred because cellular resources are diverted to produce the regulatory apparatus. We show that there is a window of environments or a 'niche' in which the unregulated cell has a higher fitness than the regulated cell. Outside this niche there is a large space of constant and time varying environments in which regulation is an advantage. A knowledge of the 'niche boundaries' allows one to gain an intuitive understanding of the class of environments in which regulation is an advantage for the organism and which would therefore favour the evolution of regulation. The model allows us to determine the 'niche boundaries' as a function of cellular parameters such as the size of the burden of the regulatory apparatus. This class of models may be useful in elucidating various tradeoffs in cells and in making in-silico predictions relevant for synthetic biology.

To reduce routine computed tomographic angiography for thoracic aortic injury assessment in level II blunt trauma patients using three mediastinal signs on the initial chest radiograph: a preliminary report.

PURPOSE: CTA is routinely ordered on level II blunt thoraco-abdominally injured patients for assessment of injury to the thoracic aorta. The vast majority of such assessments are negative. The question being asked is, Does the accurate interpretation of the three mediastinal signs permit reliable determination of which patients need CTA for aortic assessment? The purpose of this investigation was to evaluate the role of three specifically selected mediastinal anatomic signs on the initial supine chest radiograph (CXR) of adult level II blunt thoraco-abdominally injured patients for the presence or absence of a mediastinal hematoma. The presence of a mediastinal hematoma is typically used as an indicator for computed tomographic angiography (CTA). The three mediastinal signs are the right para-tracheal stripe (RPTS), left para-spinal line (LPSL), and the left apical extra-pleural area (LAPA). MATERIALS AND METHODS: The patient triage designation (level II trauma) was made by the attending physician at the time of admission. The initial CXR image and the CTA report of the 197 adult blunt level II thoraco-abdominally injured patients obtained on the day of admission were compared. The CXR of each of the 197 patients was independently assessed by each of four observers specifically for the status of the three mediastinal signs. Each observer was blinded to the CTA report until after the status of the three mediastinal sign evaluation had been determined. Two or three of the mediastinal signs being positive were required to determine that the CXR was positive for a mediastinal hematoma. RESULTS: Two or three of the selected mediastinal signs were normal in 192 (97.5%) patients. None of these patients had either a mediastinal hematoma or a major aortic injury on CTA. In each of the remaining five (2.5%) patients, two or three of the mediastinal signs were abnormal. Each of these patients had a mediastinal hematoma and a major thoracic aortic injury on CTA. CONCLUSIONS: This preliminary study suggests that the accurate interpretation of the three specifically selected mediastinal signs on the initial supine CXR of adult level II blunt thoraco-abdominally injured patients could reduce the need for routine CTA for thoracic aortic injury assessment, and requires verification by an additional study.

Multi-radial LBP Features as a Tool for Rapid Glomerular Detection and Assessment in Whole Slide Histopathology Images.

We demonstrate a simple and effective automated method for the localization of glomeruli in large (~1 gigapixel) histopathological whole-slide images (WSIs) of thin renal tissue sections and biopsies, using an adaptation of the well-known local binary patterns (LBP) image feature vector to train a support vector machine (SVM) model. Our method offers high precision (>90%) and reasonable recall (>70%) for glomeruli from WSIs, is readily adaptable to glomeruli from multiple species, including mouse, rat, and human, and is robust to diverse slide staining methods. Using 5 Intel(R) Core(TM) i7-4790 CPUs with 40 GB RAM, our method typically requires ~15 sec for training and ~2 min to extract glomeruli reproducibly from a WSI. Deploying a deep convolutional neural network trained for glomerular recognition in tandem with the SVM suffices to reduce false positives to below 3%. We also apply our LBP-based descriptor to successfully detect pathologic changes in a mouse model of diabetic nephropathy. We envision potential clinical and laboratory applications for this approach in the study and diagnosis of glomerular disease, and as a means of greatly accelerating the construction of feature sets to fuel deep learning studies into tissue structure and pathology.

Systemic Nonurological Symptoms in Patients with Overactive Bladder.

PURPOSE: We compare the systemic (nonurological) symptoms between patients with overactive bladder and subjects without overactive bladder. We also compare the urinary symptoms, quality of life and psychosocial measures between the 2 subgroups of patients with overactive bladder with a high vs low systemic symptom burden. MATERIALS AND METHODS: Patients diagnosed with overactive bladder (51) and age matched individuals without overactive bladder (30) were administered the polysymptomatic, polysyndromic questionnaire to assess the numbers and distribution of systemic symptoms across multiple organ systems. Validated instruments were administered to evaluate urinary symptoms (ICIQ-UI, ICIQ-OAB, OAB-q, USS), quality of life (UDI-6, IIQ-7, OAB-q) and psychosocial difficulties (depression, anxiety, stress, sexual trauma, sleep, fatigue). Patients with overactive bladder were divided into 2 subgroups (with and without widespread systemic symptoms) and their responses were compared. RESULTS: Patients with overactive bladder reported significantly more systemic (nonurological) symptoms compared to controls (mean ± SD 17.5 ± 12.3 vs 6.4 ± 7.9 symptoms, p <0.001). Differences were observed across multiple organ systems (neurologic, cardiopulmonary, gastrointestinal, sexual, musculoskeletal and gynecologic, p <0.05). About a third of patients with overactive bladder (31.4%) reported widespread systemic symptoms across multiple organ systems (mean 32.0 symptoms). The presence of widespread systemic symptoms among patients with overactive bladder was correlated with worse incontinence/overactive bladder symptoms (ICIQ-UI, OAB-q), poorer quality of life (UDI-6, IIQ-7, OAB-q) and more psychosocial difficulties (depression, anxiety, fatigue and higher stress, p <0.05). CONCLUSIONS: The increased presence of nonurological symptoms in overactive bladder suggests an underlying systemic etiology and pathogenetic mechanisms that may contribute to overactive bladder. This study highlights the importance of understanding systemic factors in urological conditions otherwise thought to be organ specific.

Groundwater quality assessment at Pali, Rajasthan (India).

Chemical analysis of groundwater samples collected from Pali, Rajasthan (India) showed the direct impact of textile effluents on its quality. Textile printing and dyeing units discharge large volume of effluent per day through lined and unlined channels directed towards the Bandi River. It was observed that the groundwater upstream at Pali has dissolved oxygen (4.06-4.26 mg/L), low salinity (2020-3350 microS/cm), sodium (400-600 mg/L), chloride (545-496 mg/L) and sulphate (88-300 mg/L). It was found that groundwater downstream at Pali is oxygen deficient with dissolved oxygen (0 mg/L), extremely saline (7050-28000 microS/cm), alkaline (330-1430 mg CaCO3/L), rich in sodium (1300-7130 mg/L), chloride (61-818 mg/L) and sulphate (466-4006 mg/L) exhibiting high chemical oxygen demand (153-1788 mg/L). Most of the wells had greenish tinge in water and high salinity. Most of the polluted water had sodium adsorption ratio value above 20 which in combination with high salinity is responsible for reduced crop yield, and low soil permeability has been observed in the affected area.

A World Wide Web-based antimicrobial stewardship program improves efficiency, communication, and user satisfaction and reduces cost in a tertiary care pediatric medical center.

BACKGROUND: Antimicrobial stewardship programs aim to reduce inappropriate hospital antimicrobial use. At the Johns Hopkins Children's Medical and Surgical Center (Baltimore, MD), we implemented a World Wide Web-based antimicrobial restriction program to address problems with the existing restriction program. METHODS: A user survey identified opportunities for improvement of an existing antimicrobial restriction program and resulted in subsequent design, implementation, and evaluation of a World Wide Web-based antimicrobial restriction program at a 175-bed, tertiary care pediatric teaching hospital. The program provided automated clinical decision support, facilitated approval, and enhanced real-time communication among prescribers, pharmacists, and pediatric infectious diseases fellows. Approval status, duration, and rationale; missing request notifications; and expiring approvals were stored in a database that is accessible via a secure Intranet site. Before and after implementation of the program, user satisfaction, reports of missed and/or delayed doses, antimicrobial dispensing times, and cost were evaluated. RESULTS: After implementation of the program, there was a $370,069 reduction in projected annual cost associated with restricted antimicrobial use and an 11.6% reduction in the number of dispensed doses. User satisfaction increased from 22% to 68% and from 13% to 69% among prescribers and pharmacists, respectively. There were 21% and 32% reductions in the number of prescriber reports of missed and delayed doses, respectively, and there was a 37% reduction in the number of pharmacist reports of delayed approvals; measured dispensing times were unchanged (P = .24). In addition, 40% fewer restricted antimicrobial-related phone calls were noted by the pharmacy. CONCLUSION: The World Wide Web-based antimicrobial approval program led to improved communication, more-efficient antimicrobial administration, increased user satisfaction, and significant cost savings. Integrated tools, such as this World Wide Web-based antimicrobial approval program, will effectively enhance antimicrobial stewardship programs.

Outcome of adult acute lymphoblastic leukemia with BFM protocol in a resource-constrained setting.

Cure rates for adult acute lymphoblastic leukemia (ALL) in developing countries are significantly lower because of problems unique to these countries. We assessed some of the problems in adult ALL patients (>12 years of age) in a tertiary care hospital of northwest India with modified BFM regimen. The diagnosis of ALL was made according to FAB criteria. The protocol consisted of Phase I & II induction, consolidation, reinduction and maintenance phases. CNS prophylaxis was administered with 24 Gy radiation and intrathecal methotrexate. One hundred and eighteen patients (72.9% males), aged 12-68 years (median 23 years) were treated from January 1997 till December 2003. Follow-up of patients was done till December 2005. Complete remission (CR) was achieved in 85.6% patients after induction therapy and 40% patient relapsed. Most patients (23.7%) relapsed during the maintenance phase or after completion of chemotherapy. At least 15% of patients (15/101) after successful induction abandoned the treatment because of financial constraints, prolonged travel time to treatment facility and switching over to alternative medicines. Fatal infectious complications occurred in 19.5% of patients. The 3-year and 5-year event free survival rates were 29.8% and 21.6% respectively. In conclusion, modified BFM regimen resulted in high induction rates but relatively poor 5-year event free survival. Infections related death and post induction abandonment of treatment were the main reasons for poor overall results.

Early indicators of prognosis in fulminant hepatic failure: an assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital criteria.

While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 +/- 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age >or=50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time >or=35 seconds, and creatinine >or=1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of >or=33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c-statistic [95% confidence interval]: CPI 0.802 [0.726-0.878], MELD 0.717 [0.636-0.789], and KCH criteria 0.676 (0.588-0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis.