Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center.

Aim and background: Sepsis is a major global health affecting millions worldwide, hence understanding its contributing factors becomes paramount. This cross-sectional study at a tertiary care center explores the relationship between iron profile, vitamin D levels, and outcomes in sepsis and septic shock patients. The primary objective was to explore the prevalence of iron profile and vitamin D parameters during early intensive care unit (ICU) admission and their association with 28-day mortality. Materials and methods: Spanning 18 months, the study enrolled adult patients meeting sepsis or septic shock criteria at the ICU. Data collection included demographic information, clinical characteristics, and blood samples for iron profile and vitamin D levels at admission. Disease severity was assessed using sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores, and treatment was administered as per surviving sepsis-3 guidelines. Results: The research involved 142 participants, uncovering prevalent organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Noteworthy connections to mortality were identified for factors including vasopressor support, ICU stay duration, SOFA score, and APACHE-II score. Interestingly, age, gender, and vitamin D levels showed no significant associations. However, the study did reveal a significant association between iron, ferritin, and transferrin saturation levels with increased 28-day mortality. Conclusion: Our study concluded that low Iron, elevated ferritin, and decreased transferrin saturation levels maintained associations with the outcome of interest. While no such relationship was established with vitamin D levels. These results suggest potential implications for patient management and prognosis, warranting further exploration in future research. How to cite this article: Bairwa M, Jatteppanavar B, Kant R, Singh M, Choudhury A. Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center. Indian J Crit Care Med 2024;28(6):569-574.

Prevalence and impact of endocrine disorders in advanced metastatic cancer patients undergoing cancer-directed therapy: A prospective observational study.

BACKGROUND: Noncommunicable diseases (NCDs) contribute significantly to global morbidity and mortality, with cancer being one of the leading causes. In this prospective observational study, we aimed to investigate the prevalence and impact of endocrine disorders, specifically diabetes and thyroid dysfunction, in patients with advanced metastatic cancer undergoing cancer-directed therapy. METHODS: Over 15 months, we recruited 100 histologically proven advanced metastatic cancer patients from the Department of Medical Oncology Haematology, All India Institute of Medical Sciences, Rishikesh, and conducted institutional-based prospective observational study. All participants over 18 years of age, treatment-naive, and potential candidates for systemic chemotherapy with an expected clinical survival of at least 6 months were included in the study. Patients with prior therapy, secondary neoplasms, and those unable to complete 3 months of palliative chemotherapy were excluded. Patients were assessed for diabetes and thyroid function at presentation, after 3 and 6 months of cancer-directed standard therapy. These data were analyzed, processed, and presented as results. RESULTS: The mean age of participants was 50.45 years, with a near-equal distribution of males and females. At baseline, 10% of the study population had preexisting endocrine disorders (2% hypothyroidism, 8% diabetes). By the end of 6 months, the prevalence increased to 18%, with females being more affected. Notably, the prevalence of new-onset endocrine disorders during cancer-directed therapy was only 3% for diabetes and 4% for thyroid dysfunction. CONCLUSION: Analysis of sociodemographic and cancer-related characteristics showed no significant association with changes in diabetic and thyroid status at 3 and 6 months. However, substance use, particularly smoking, was associated with an increased risk of diabetes development (p < .05). Cancer type and treatment regimen did not show statistically significant correlations with endocrine dysfunction. IMPLICATIONS: Our study highlights the importance of considering endocrine disorders in advanced metastatic cancer patients undergoing therapy. The prevalence of diabetes and thyroid dysfunction increased during cancer-directed therapy, particularly in females. Careful monitoring and timely intervention are essential to improve the quality of life for these patients. Further research is warranted to explore the long-term effects of cancer-directed therapy on endocrine health and develop tailored management strategies for this vulnerable population.

Impact of oil massage on newborn behavioural responses in rural India.

The initial weeks of a newborn's life are marked by rapid physiological and behavioural adjustments as the infant adapts to the external environment. This critical period necessitates attentive care, prompting exploration into traditional practices such as oil massage, which holds cultural significance and is believed to enhance neonatal well-being. Despite its prevalence, empirical evidence supporting the efficacy of oil massage remains limited. This study, conducted in a rural setting, aims to bridge traditional practices with evidence-based care, exploring the impact of oil massage on newborn behavioural responses. A quasi-experimental design involving 60 newborns (30 in each group) assessed behavioural responses through a pre and post-test approach. Results indicate a significant improvement in selected behavioural responses among newborns receiving oil massage, emphasizing its potential integration into routine care. The control group showed a pre-test mean of 14.83 (SD = 2.41) and a post-test mean of 16.23, while the experimental group exhibited a pre-test mean of 15.83 (SD = 1.80) and a post-test mean of 26.07. T-test values of 5.194 for the control group and 26.137 for the experimental group were indicative of statistically significant changes. The study contributes insights into neonatal care practices, urging further exploration of contextual intricacies and demographic influences on newborn behaviour.

Anterolateral and Medial Locking Compression Plates for the Management of Distal Tibial Fractures: A Comparative Prospective Study.

INTRODUCTION: Open/close reduction (OR/CR) and internal fixation (IF) of displaced fractures of distal tibia with either a medial or anterolateral plate is a commonly performed procedure. Anterolateral plating avoids an incision along the medial subcutaneous border of tibia and has been shown to have reduced risk of wound complications. The aim of our study was to determine the functional outcome of these fractures treated with anterolateral and medial distal tibial locking compression plates. METHODS: This was a prospective study that included 60 patients with distal tibial fractures (close or grade I open injury) divided into two groups with 30 patients in each where one group was treated with OR/CR and IF using an anterolateral distal tibial locking plate (Group A) and the other using a medial distal tibial locking plate (Group B). The duration of surgery and intraoperative blood loss and time to union were recorded for all the patients. Functional evaluation was done at one year in terms of pain, function and alignment using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and complications, if any, were noted. RESULTS: Both the groups were comparable in terms of age, gender, time of presentation, AO classification and presence of wound. The mean duration of surgery as well as the intraoperative blood loss were more in the anterolateral plate group than in the medial plate group, but the difference was statistically insignificant. Ten patients (33%) with medial plates had symptomatic hardware and 7 (23.3%) underwent removal while only 3 (10%) patients in the anterolateral plate group had similar complaints and none had to undergo removal. Two patients with anterolateral plate and one with medial plate had malunion. The mean time to fracture union as well as the rate of infection was less and the functional outcome at one year was better in the group treated with anterolateral plates as compared to the one with medial plates, but the difference again was not statistically significant for all the parameters. CONCLUSION: With reduced risk of soft tissue complications and by obviating the need for implant removal, anterolateral plates can prove to be a better alternative to the medial plates especially in elderly patients in the management of these fractures.

An atypical manifestation of pheochromocytoma crisis: Acute delirium.

Pheochromocytoma is a rare neuroendocrine tumor presenting with a classical triad of symptoms. In 10% of the cases, the presentation can be atypical, and the diagnosis is often missed for several years. Most common neurological manifestations are haemorrhage, seizures, etc., but pheochromocytoma crisis presenting as delirium has been infrequently reported. We present a case of a middle-aged female who presented with hypertensive emergency and an acute confusional state. Other causes of delirium were ruled out in the patient and a timely diagnosis of pheochromocytoma was made with CT abdomen showed a large right suprarenal mass which was confirmed on 123I-MIBG scan and supported by elevated plasma metanephrines. She responded to alpha and beta blockers following which her blood pressure spikes were controlled, and subsequently, her sensorium improved significantly. Patient underwent surgical resection of the tumor and was followed up after 2 weeks with her blood pressure controlled without any medications. Conclusion: A high degree of clinical suspicion is essential in such rare presentations of pheochromocytoma. Early diagnosis, adequate preoperative preoperative stabilization followed by a definitive surgical excision offers a complete cure to such patients.

Preventive hepatology: An ounce of prevention or pounds of cure to curb liver diseases.

Liver diseases are now the leading cause of both morbidity and mortality profile globally with rising trends due to unhealthy lifestyle. Most of the liver diseases are preventable. Scientific evidences have well supported and documented that almost 90 percent of all major liver diseases are either the manifestations of asymptomatic hepatitis virus infections or poor lifestyle choices leading to accumulation of fat in liver that could be detected even before they present themselves as chronic liver diseases. Understanding liver diseases as a preventable disease and practising necessary preventive measures will help in lowering the risks of various types of liver diseases as well as liver cancer.

A review article on the dosimetry in intraluminal HDR brachytherapy of lung carcinoma.

Lung cancer is one of the most common cancers in the world. Intraluminal brachytherapy (BT) is one of the most adopted treatment modalities for lung malignancies with Ir-192 source in radiotherapy. In intraluminal BT, treatment delivery is required to be very accurate and precise with respect to the plan created in the treatment planning system (TPS). The BT dosimetry is necessary for better treatment outcomes. Therefore in this review article, some relevant studies were identified and analyzed for dosimetric outcomes in intraluminal BT in lung malignancies. The dosimetry in BT for plan verification is not presently in practice, which needs to be performed to check the variation between the planned and measured doses. The necessary dosimetric work done by the various researchers in intraluminal BT such as the Monte Carlo CYLTRAN code was used to calculate and measure the dose rate in any medium. Anthropomorphic phantom was used to measure doses at some distance from the source with Thermo luminescence dosimeters (TLDs). The dosimetric influence of air passage in the bronchus was evaluated with the GEANT4 Monte Carlo method. A pinpoint chamber was used to measure and quantify the impact of inhomogeneity in wax phantom for the Ir-192 source. The Gafchromic films and Monte Carlo methods were used to find the phantom and heterogeneities, which were found to underestimate the dose for the lungs and overestimated for the bones in TPS. The exact tool to quantify the variation in planned and delivered doses should be cost-effective and easy to use possibly with tissue equivalent phantoms and Gafchromic films in lung malignancies treatment.

Angle of concavity in planning target volume can be adopted as selection criteria for intensity-modulated radiation therapy or three-dimensional conformal radiotherapy technique in brain tumors.

Introduction: With innovation of medical imaging, radiotherapy attempts to conform the high dose region to the planning target volume (PTV). The present work aimed to assess the angle of concavity in PTV can be adopted as selection criteria for intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT) technique in Brain tumors. Materials and Methods: Thirty previously irradiated patients with brain tumors were replanned with both 3DCRT and IMRT technique. Angle of concavity (dip) in the PTV near the organs at risk was measured in the contoured structure set images of each patient. These cases were divided into three groups where angles were 0°, >120° and <120°. Dose of 60 Gy/30# was fixed. Results: In Group 1, the IMRT plan had better TV95% as compared to 3DCRT respectively with significant P value (P = 0.002). Mean of conformity index (CI) and Homogeneity Index (HI) were comparable. For Group 2 (angle >120°), the IMRT plan had better TV95% as compared to 3DCRT respectively with a significant P value (P = 0.021). HI and CI were not significant. For Group 3 (<120°), IMRT plan had better TV95% as compared to 3DCRT respectively with a significant P value (P = 0.001). HI and CI were better in IMRT arm with significant P value. Conclusion: The results from this study showed that the angle of concavity can be considered as an additional objective tool for selection criteria whether tumor can be treated with IMRT or 3DCRT. Tumors where angle of concavity was <120°, HI and CI provided more uniformity and conformity of dose distribution inside PTV with significant P values.

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

A Rare Case of Disseminated Histoplasmosis With Hemophagocytic Syndrome in a Patient With Diabetes Mellitus: A Case Report.

We report a case of Histoplasma-associated hemophagocytic syndrome in a diabetes mellitus patient. The patient presented with a fever, cough, and an ulcer on the tongue. The biopsy confirmed the diagnosis of histoplasmosis from the tongue ulcer. Other investigations revealed normal clusters of differentiation 4 (CD4) count and increased hemoglobin A1c (HbA1c) and lactate dehydrogenase (LDH) levels. The patient was diagnosed with hemophagocytic syndrome secondary to Histoplasma after fulfilling the hemophagocytic lymphohistiocytosis (HLH)-2004 criteria required for diagnosis, including fever (with peak temperatures of >38.5° C), splenomegaly, cytopenia affecting two cell lineages in peripheral blood, hypertriglyceridemia (fasting triglycerides >265 mg/dL), and hemophagocytosis in the bone marrow biopsy. The patient was started on injection amphotericin B with remarkable improvement.

Adherent-invasive Escherichia coli associated with granulomatous colitis and extraintestinal dissemination in a Sphynx cat.

This case report describes a case of granulomatous colitis (GC) associated with adherent-invasive Escherichia coli (AIEC) with extension to cecum and ileum and dissemination to multiple lymph nodes, the spleen, and brain in a 10-year-old, male Sphynx cat. The cat had an episode of diarrhea 4 months prior to consultation due to sudden blindness. Signs rapidly progressed to ataxia, seizures, and death. Gross and histologic findings were consistent with granulomatous inflammation in all affected organs. In situ hybridization confirmed the presence of intracellular E. coli within enterocytes and infiltrating macrophages, and whole genome sequencing identified virulence traits commonly linked to AIEC strain. This is the first characterization of GC in a cat associated to AIEC resembling the metastatic form of Crohn's disease in humans and GC of dogs. Extraintestinal involvement might provide evidence of the ability of AIEC to promote granulomatous inflammation beyond the gut.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Hypercalcemic Crisis: A Rare Presentation of Ewing's Sarcoma.

Ewing's sarcoma (ES) is a rare malignancy of adolescence that usually presents with clinically apparent disease involving long bones, brought to attention by trauma and/or fractures. Hypercalcemia of malignancy is a well-known phenomenon; however, hypercalcemia is exceptionally rare in ES. This case report discusses a 20-year-old lady who experienced chronic bone pains in her hip and lower limbs, ultimately leading to a hypercalcemic crisis. We emphasize the importance of considering ES as a potential cause of hypercalcemia, highlighting the mechanism, diagnostic and therapeutic challenges, the associated poor prognosis, and the necessity for a multidisciplinary approach to managing the condition.

Effect of non-pharmacological interventions on adults with cardiovascular risk in a rural community.

Background: Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide, with three-fourth of deaths occurring in low- and middle-income countries (LMICs) like India. Currently, three out of the top five causes of morbidity and mortality in the country are NCDs. Objective: This study evaluated the impact of non-pharmacological interventions as a comprehensive approach toward adults with cardiovascular risk in Indian rural communities. Material and Methods: It was a quasi-experimental study conducted in Rishikesh, a holy city of Uttarakhand known as the world's yoga capital at the foothills of Himalaya. Out of 87 villages, four villages were randomly selected. Eighty-eight participants were enrolled (22 from each village and household). It was a multi-stage random sampling. All the participants with cardiovascular risk and age >30 years were recruited. Pregnant, severely ill, and unwilling to consent were excluded. Non-pharmacological intervention as a comprehensive approach, including yoga, meditation, mental health counseling, dietary counseling, tobacco, and alcohol cessation counseling has been provided to cardiovascular risk participants. Results: Data of 76 participants were analyzed as the per-protocol analysis method. The drop-out rate was 13.63%. Male and female participants were 52 (68.4%) and 24 (31.6%) in number. Mean age of the participants was 55.28 ± 13.64 years. Diastolic blood pressure or DBP (P = 0.017*), systolic blood pressure or SBP (P = 0.008**), waist circumference (WC) (P = 0.000**), waist-to-hip ratio (P = 0.000**) and waist-to-height ratio (P = 0.000**) significantly improved in the post intervention group. Conclusion: Non-pharmacological interventions as a comprehensive approach can significantly reduce modifiable risk factors for cardio-metabolic disease.

Case Report: Groove pancreatitis-a lesser-known entity.

Groove pancreatitis is an uncommon disease affecting the pancreatic groove region within the dorsal-cranial aspect of the head of the pancreas, duodenum, and common bile duct. The diagnosis is challenging as pancreatic adenocarcinoma also presents similarly. The patient can present with diffuse pain abdomen, weight loss, nausea, and vomiting. The diagnosis is quite challenging, as it is difficult to differentiate it from other diagnoses on radiological imaging. Medical management is the pillar of therapy, and surgical management is indicated in recurrent and intractable symptomatic cases. Here, we present a case diagnosed as groove pancreatitis and managed conservatively.

Cytochrome C as a potential clinical marker for diagnosis and treatment of glioma.

Gliomas are the most prevalent kind of malignant and severe brain cancer. Apoptosis regulating mechanisms are disturbed in malignant gliomas, as they are in added forms of malignancy. Understanding apoptosis and other associated processes are thought to be critical for understanding the origins of malignant tumors and designing anti-cancerous drugs for the treatment. The purpose of this study was to evaluate the variation in the expression level of several apoptotic proteins that are responsible for apoptosis in low to high-grade glioma. This suggests a significant change in the expression of five apoptotic proteins: Clusterin, HSP27, Catalase, Cytochrome C, and SMAC. Cytochrome C, one of the five substantially altered proteins, is a crucial component of the apoptotic cascade. The complex enzyme Cytochrome C is involved in metabolic pathways such as respiration and cell death. The results demonstrated that Cytochrome C expression levels are lower in glioma tissues than in normal tissues. What's more intriguing is that the expression level decreases with an increase in glioma grades. As a result, the discovery shows that Cytochrome C may be a target for glioma prognostic biomarkers.

Detection of differential expression of miRNAs in computerized tomography-guided lung biopsy.

Aims: Nonsmall-cell lung carcinoma comprises 85% of lung malignancies and is usually associated with a poor prognosis due to diagnosis at advanced stages. Molecular diagnosis of computerized tomography (CT)-guided biopsy has the potential to identify subtypes of lung carcinoma like adenocarcinoma (AC) and squamous cell carcinoma (SCC) along with its molecular stratification. This approach will help predict the genetic signature of lung cancer in individual patients. Subjects and Methods: Histopathologically proved a CT-guided biopsy sample of lung cancer cases was used to screen for the expression of microRNA (miRNA) earlier quantitated in blood plasma. Primers against hsa-miR2114, hsa-miR2115, hsa-miR2116, hsa-miR2117, hsa-miR449c, and hsa-miR548q with control RNU6 were used to screen 30 AC, 30 SCC, 5 nonspecific granulomatous inflammation, and 8 control samples. Reverse transcription polymerase chain reaction (RT-PCR) data revealed expression of hsa-miR2114 and hsa-miR548q in AC as well as SCC. Results: RT-PCR data revealed that the expression of hsa-miR2116 and hsa-miR449c was found upregulated in AC while hsa-miR2117 was expressed in SCC cases. Bioinformatic analysis revealed that genes, where these miRNAs are located, were also upregulated while targets of these miRNAs were downregulated. Conclusions: miRNAs expression pattern in the CT-guided biopsy samples can be used as a potential tool to differentially diagnose lung cancer subtypes. The expression pattern of miRNAs matches very well in blood plasma and tissue samples, albeit levels were very low in the earlier case than later. This approach can also be used for screening mutations and other molecular markers in a personalized manner for the management of lung cancer patients.

Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach.

Detection of metabolic disturbances in lung cancer (LC) has the potential to aid early diagnosis/prognosis and hence improve disease management strategies through reliable grading, staging, and determination of neoadjuvant status in LC. However, a majority of previous metabolomics studies compare the normalized spectral features which not only provide ambiguous information but further limit the clinical translation of this information. Various such issues can be resolved by performing the concentration profiling of various metabolites with respect to formate as an internal reference using commercial software Chenomx. Continuing our efforts in this direction, the serum metabolic profiles were measured on 39 LC patients and 42 normal controls (NCs, comparable in age/sex) using high-field 800 MHz NMR spectroscopy and compared using multivariate statistical analysis tools to identify metabolic disturbances and metabolites of diagnostic potential. Partial least-squares discriminant analysis (PLS-DA) model revealed a distinct separation between LC and NC groups and resulted in excellent discriminatory ability with the area under the receiver-operating characteristic (AUROC) = 0.97 [95% CI = 0.89-1.00]. The metabolic features contributing to the differentiation of LC from NC samples were identified first using variable importance in projection (VIP) score analysis and then checked for their statistical significance (with p-value < 0.05) and diagnostic potential using the ROC curve analysis. The analysis revealed relevant metabolic disturbances associated with LC. Among various circulatory metabolites, six metabolites, including histidine, glutamine, glycine, threonine, alanine, and valine, were found to be of apposite diagnostic potential for clinical implications. These metabolic alterations indicated altered glucose metabolism, aberrant fatty acid synthesis, and augmented utilization of various amino acids including active glutaminolysis in LC.