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Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. However, there is a lack of comprehensive data from low- and middle-income countries (LMICs) regarding factors influencing COPD outcomes, particularly in regions where biomass exposure is prevalent. Objective: The Factors Affecting Survival in Severe and Very Severe COPD Patients Admitted to Tertiary Centers of India (FAST) study aims to address this gap by evaluating factors impacting survival and exacerbation rates among COPD patients in LMICs like India, with a specific focus on biomass exposure, clinical phenotypes, and nutritional status in patients admitted to the Intensive Care Unit (ICU). Methods: The FAST study is an observational cohort study conducted in university teaching hospitals across India. The study aims to enroll 1000 COPD patients admitted to the ICU meeting specific inclusion criteria, with follow-up assessments conducted every 6 months over a 2-year period. Data collection includes demographic information, clinical manifestations, laboratory investigations, pulmonary function tests, medications, nutritional status, mental health, and health-related quality of life. Adjudication of exacerbations and mortality will also be undertaken. The FAST study seeks to provide crucial insights into COPD outcomes in LMICs, informing more precise management strategies and mitigating the burden of COPD in these settings. By evaluating factors such as biomass exposure, clinical phenotypes, and nutritional status, the study aims to address key knowledge gaps in COPD research. How to cite this article: Arunachala S, Devapal S, Swamy DSN, Greeshma MV, Ul Hussain I, Siddaiah JB, et al. Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study. Indian J Crit Care Med 2024;28(6):552-560.
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AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.
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Proteína BRCA1 , Neoplasias Ovarianas , Humanos , Feminino , Proteína BRCA1/genética , Terapia Neoadjuvante , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA MensageiroRESUMO
Background: Laboratories across the world are successfully using quality indicators (QIs) to monitor their performance. We aimed to analyze the effectiveness of using the peer group comparison and statistical tools such as sigma metrics for periodic evaluation of QIs and identify potential errors in the preanalytical, analytical, and postanalytical phases. Methods: We evaluated the monthly QIs for 1 year. A total of 11 QIs were evaluated across the three phases of the total testing process, using percentage variance, and sigma metric analysis. Results: Our study observed that based on sigma metric analysis, the performance was good for all the QIs except for the number of samples with the inappropriate specimen hemolyzed samples, clotted samples, and turnaround time (Sigma value < 3). The percentage variance of QIs in all the phases was plotted in a Pareto chart, which helped us in identifying turnaround time and internal quality control performance are the key areas that contribute to almost 80% of the errors among all the QIs. Conclusion: Laboratory performance evaluation using QIs and sigma metric analysis helped us in identifying and prioritizing the corrective actions in the key areas of the total testing process.
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Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases.
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Tumor do Seio Endodérmico/complicações , Hemoperitônio/etiologia , Úraco/diagnóstico por imagem , Neoplasias da Bexiga Urinária/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Terapia Combinada , Consanguinidade , Emergências , Tumor do Seio Endodérmico/química , Tumor do Seio Endodérmico/diagnóstico por imagem , Tumor do Seio Endodérmico/terapia , Etoposídeo/administração & dosagem , Humanos , Lactente , Laparotomia , Masculino , Ruptura Espontânea , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/terapiaRESUMO
OBJECTIVES: Retrospective analysis of the utility of serial measurements of serum acetylcholinesterase (AChE) in predicting the duration of stay in the intensive care unit (ICU), duration of mechanical ventilation (MV) and outcome of the patient from MV in organophosphate (OP) compound poisoning patients. MATERIALS AND METHODS: The medical records of patients who presented to tertiary care hospital with symptomatic insecticidal poisoning from January 2009 to December 2010 were utilized for the study purpose. Forty four patients with history of poisoning were admitted during this period. Out of these 37 patients with history of OP poisoning, without any underlying diseases and whose serial AChE activity levels were available were included in the study. Data regarding clinical manifestation at presentation, AChE activity results and its interpretation, details of patient management and data on outcomes of patients were noted. RESULTS: Serum acetycholinesterase levels below 1,250IU/L, 1,789IU/L and 2,764IU/L on day three, day four and five respectively indicates longer duration of stay in the ICU. Patients with serum AChE levels below 975IU/L, 876IU/L, 1,245IU/L, 1,395IU/L and 1,875IU/L on day one, two, three, four and five respectively take a longer time to be out of mechanical ventilation. Levels below 870IU/L, 1,110IU/L, 1,020IU/L and 885IU/L on day two, three, four and five respectively indicate poor prognosis of the patient and mortality. CONCLUSION: We conclude that the serial measurements of serum acetylcholinesterase levels can be useful in predicting the length of ICU stay, duration of mechanical ventilation and the prognosis of the patient with OP poisoning.
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Background & Objective: Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma. Methods: The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute. Results: A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively. Conclusion: Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to diagnosis of the process.
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Introduction Diabetes risk-screening tools are validated and implemented across various countries. There is a need for improvement in these risk scores with suitable modifications so as to make them more sensitive, specific, and suitable to the local population. Objectives The aim of this study was to evaluate and compare the diagnostic accuracy and clinical utility of the Indian diabetes risk score (IDRS), the American diabetic association (ADA) risk score, and the Finnish Diabetes Risk Score in healthy subjects of South Indian origin in predicting the risk of diabetes and to correlate these risk scores with the blood glucose and hemoglobin A1c (HbA1c) levels in the study population. Materials and Methods A total of 160 subjects attending the master health checkup/outpatient department of a tertiary care hospital were included in the study. Each subject was asked to fill a questionnaire. Details obtained using the questionnaire were assessed as per the three diabetic risk scores. Fasting blood sugar/random blood sugar and HbA1c were estimated. Statistical Analysis Used Data analysis was done using SPSS 22/23. Pearson correlation was used to compare continuous variables, with p < 0.05 considered statistically significant. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and Mitchell's clinical utility indices were calculated for each risk tool. Results We found the prevalence of diabetes to be 11.9%. ADA risk score was the only risk score that showed a statistically significant difference ( p -value = 0.05) between the low- and high-risk subjects. Conclusions ADA or IDRS risk scores can be used for screening diabetes in the South Indian population. We suggest that inclusion of the history of gestational diabetes and hypertension in the IDRS risk score might improve its sensitivity as a screening tool in our local population.
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BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.
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Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisolona/uso terapêutico , Recidiva , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Owing to the aggressive nature of high-grade gliomas (HGGs), its early diagnosis holds the key to a favorable prognosis. Currently, tissue biopsy is the gold standard to verify HGG's initial diagnosis and can be challenging due to its invasive nature. In this study, our objective was a noninvasive panel for timely detection of HGG and its progression using cell-free circulating tumor DNA (cfTDNA). MATERIALS AND METHODS: Twenty-seven patients with HGG were tested with a 50-gene tumor panel. cfTDNA isolated from serum was checked for single-nucleotide variations (SNVs) or copy number alterations using targeted next-generation sequencing, with further validation of results by checking respective formalin-fixed paraffin-embedded tumor tissues for the same genetic alterations. RESULTS: About 88.8% of the patients were detected with HGG-associated cfTDNA. Around 25% patients were detected with one, 25% patients had three, 25% patients had four, and 12.5% patients each had five and six genetic alterations. About 12 of 50 genes were detected in the serum samples. The SNVs detected included TP53 in 87.5% of patients; PIK3CA and EGFR in 50% of patients; PTEN in 37.5%; KIT and VHL in each 25% of patients; and RB1, NF2, MET, ATRX, CDK2A, and CTNNB1 each in 8.3%-16.6%. On combining EGFR, KIT, PTEN, PIK3CA, TP53, and VHL genes (Govardhan Diagnostic Genetic Module for high-grade glioma), at least one of the genetic alterations was found in 100% of patients. CONCLUSION: These findings illustrate that cfTDNA is easily demonstrable and can be used as a surrogate to tissue biopsy in brain tumor.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Glioma/diagnóstico , Adulto , Neoplasias Encefálicas/genética , Ácidos Nucleicos Livres/análise , DNA Tumoral Circulante/análise , Feminino , Seguimentos , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estudos Prospectivos , Adulto JovemRESUMO
Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.
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Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Neoplasias Primárias Múltiplas/terapia , Neoplasias Retais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Quimiorradioterapia Adjuvante/métodos , Fluoruracila/uso terapêutico , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Nefrectomia , Compostos Organoplatínicos/uso terapêutico , Protectomia , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
CONTEXT: Although the incidence rate of colorectal cancer (CRC) in all Indian cancer registries is very close to the lowest rate in the world, westernization has shown an increasing trend in the recent years. Recurrence is reported in CRC because the slowly proliferating stem cells escape the chemotherapeutic regimen. AIM: To detect the presence of CD133 and CD44 in human CRC specimens and to correlate the level of marker expression with tumor staging. MATERIALS AND METHODS: We included 26 colorectal carcinoma patients between 20 and 70 years of age. Histological and immunohistochemical analysis of CD133 and CD44 was done in sections of 5 µm prepared from paraffin-embedded blocks with most representative areas. STATISTICAL ANALYSIS: All analyses were performed using Microsoft Excel 2010 and SPSS version 22. RESULTS: CD133 expression was seen exclusively on the cell membrane at the glandular luminal surface with dot-like cytoplasmic staining. In the normal mucosa, CD44 expression was seen in the superficial region of the cell, whereas in most of the carcinomas, the staining was localized in the basolateral region of the cell. Both CD133 and CD44 showed significant correlation with tumor stage. CONCLUSIONS: In the present study, CD133 and CD44 show significant correlation with tumor staging. Cancer stem cell markers have shown similar pattern of expression in the patients of Indian origin. Using combination of markers for staging is preferred as it increases the sensitivity and specificity.
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Antígeno AC133/análise , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Receptores de Hialuronatos/análise , Células-Tronco Neoplásicas/patologia , Antígeno AC133/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Colo/patologia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reto/patologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
Primary follicular lymphoma (PFL) of gastrointestinal tract (GIT) is rare and account for 1%-3% of non-Hodgkin lymphoma. Within the small intestine, the PFL is more common in jejunum than in the ileum. Due to low prevalence of the disease, the clinical manifestations are not well known, and diagnosis is usually delayed leading to complications. We herein report a case of PFL of GIT who presented with intestinal obstruction and unique gross morphology. Diagnosis was made by morphology and supported by immunohistochemistry.
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Trato Gastrointestinal/patologia , Intestino Delgado/patologia , Linfoma Folicular/diagnóstico , Adulto , Biópsia , Feminino , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/citologia , Trato Gastrointestinal/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Obstrução Intestinal/etiologia , Intestino Delgado/diagnóstico por imagem , Linfoma Folicular/patologia , Tomografia Computadorizada por Raios XRESUMO
Cryptorchidism is the most common predisposing factor in the development of testicular germ cell tumors. Seminoma is the most common malignancy developing in a cryptorchid testis, usually has lymphatic but rarely hematogenous metastasis. The Urinary Bladder is an extremely rare site of metastasis of seminoma metastasis. A 29-year-old male patient presented to us with a history of infertility and an intra-abdominal mass. He was investigated and treated and was found to have an intra-abdominal seminoma with synchronous urinary bladder metastasis. He was treated with appropriate chemotherapy and continues to be in good health.
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Sarcomatoid carcinomas are biphasic tumours, which occur at any site in the human body. It rarely affects the penis, with only 38 cases being reported in literature. It may be considered as a variant of squamous cell carcinoma or a dedifferentiated tumour. We report a 60-year old gentleman who presented with a swelling in the glans penis. He underwent a partial penectomy. Histopathology revealed sarcomatoid carcinoma of the penis, which was confirmed by immunohistochemistry. The rarity of this clinical entity makes its diagnosis difficult.
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CONTEXT: During pregnancy, an adequate intake of vitamins and minerals is recommended, to prevent the occurrence of adverse effects in the mother and the foetus. AIM: In our study, we aimed to study the levels of the micronutrients like iron, zinc and copper in the third trimester of pregnancy and to assess the neonatal outcome in them. MATERIAL AND METHODS: Fifty pregnant women who were aged 20-30 years, who had completed 24 weeks of gestation, who were on regular antenatal checkups, were included. The collected venous blood samples were used for the estimation of haemoglobin, serum ferritin, zinc and copper. They were followed up till their deliveries and the neonatal outcomes were noted. The gestational ages, weight of the babies, the lengths of the babies and their head circumferences and any complications which had occurred during and after the deliveries, were noted in the proforma. RESULTS: The serum ferritin levels did not significantly correlate with the other study parameters. The zinc levels decreased with an increase in the parity (p<0.05). The copper levels decreased with an increase in the BMI (p<0.05). With an increase in haemoglobin, there was an increase in the levels of zinc and ferritin (p<0.05). With an increase in the parity, there was a decrease in the neonatal birth weight. CONCLUSION: Our study clearly brought out a correlation between the microminerals such as iron, zinc and copper during late pregnancies. An improvement in the iron status brings out a positive effect on the ferritin and zinc levels, thus indicating better outcomes of the pregnancies.
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Macrophages are key players of the immune system and express a variety of surface receptors. CD163 is one such receptor which belongs to the scavenger receptor cysteine-rich super family (SRCR-SF) class B. It has four isoforms which differ in the structure of their cytoplasmic domains and putative phosphorylation sites. Expression of CD163 is tightly regulated with a general tendency of anti-inflammatory signals to induce its synthesis, while pro-inflammatory signals downregulate its expression. Previously the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes. However, it also plays a crucial role in the control of inflammatory processes by induction of anti-inflammatory pathways. Soluble CD163, which is generated via ectodomain shedding, serves as a potential diagnostic tool in a variety of disease states, such as inflammation, atherosclerosis, transplant rejection and carcinoma. Recently, CD163 has been identified as a promising target for cell directed therapy. In this review we aim to summarize the current knowledge of CD163.
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Antígenos CD/fisiologia , Antígenos de Diferenciação Mielomonocítica/fisiologia , Receptores de Superfície Celular/fisiologia , Antígenos CD/química , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/química , Antígenos de Diferenciação Mielomonocítica/genética , Regulação da Expressão Gênica , Humanos , Fosforilação , Conformação Proteica , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genéticaRESUMO
CONTEXT: Body mass index (BMI), serum albumin, and C-reactive protein (CRP) appear to be major determinants of hospitalization. AIM: To determine the predictive ability of BMI, Sequential Organ Failure Assessment (SOFA score), serum albumin, and CRP to assess the duration and outcome of mechanical ventilation (MV). MATERIALS AND METHODS: Thirty patients aged >18 years who required mechanical ventilation (MV) were enrolled for the study. They were divided into two groups; patients who improved (Group 1), patients who expired (Group 2). Group 1 was further divided into two groups: patients on MV for <5 days (Group A), and patients on MV for >5days (Group B). BMI and SOFA score were calculated, and serum albumin and CRP were estimated. RESULTS AND DISCUSSION: Out of the 30 patients, 18 patients successfully improved after MV (Group 1) and 12 patients expired (Group 2). Among the 18 patients in group 1, ten patients improved within 5 days (Group A) and 8 patients after 5 days (Group B). SOFA score and CRP were significantly increased (P value 0.0003 and 0.0001, respectively) in group 2 when compared to group 1. CRP >24.2 mg/L or SOFA score >7 at the start of MV increases the probability of mortality by factor 13.08 or 3.92, respectively The above parameters did not show any statistical difference when group A was compared to group B. CONCLUSION: Simple, economic and easily accessible markers like CRP and assessment tools of critically ill patients with SOFA score are important determinants of possible outcomes of a patient from MV.