Targeting immune-onco-metabolism for precision cancer therapy.

Immune cells play a key role in host defence against infection and cancer. Unlike infection, cancer is a multidimensional disease where cancer cells require continuous activation of certain pathways to sustain their growth and survival. The tumour milieu plays an important role in defining the metabolic reprogramming to support this growth and evasion from the immune system. Cancer and stromal cells modulate each other's metabolism during cancer progression or regression. The mechanism related to change in the metabolism and its role in the crosstalk between tumour and immune cells is still an area of immense importance. Current treatment modalities can be immensely complemented and benefited by targeting the immuno-oncology metabolism, that can improve patient prognosis. This emerging aspect of immune-oncology metabolism is reviewed here, discussing therapeutic possibilities within various metabolic pathways and their effect on immune and cancer cell metabolism.

Association of COVID-19 Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Cycle Threshold Value With Surrogate Markers of Disease Severity.

Introduction The cycle threshold (Ct) value in real-time reverse transcription-polymerase chain reaction (RT-PCR) serves as a criterion to diagnose coronavirus disease 2019 (COVID-19) and is inversely proportional to viral load. Levels of inflammatory markers such as aspartate aminotransferase (AST), ferritin, D-dimer, high sensitivity C-reactive protein (hs-CRP), and lactate dehydrogenase (LDH) are used as quantitative measures of COVID-19 severity. We examined the association between these markers and Ct values. Methodology This retrospective data analysis included 400 patients with positive RT-PCR results for COVID-19 who were admitted to a tertiary care hospital. Clinical and biochemical data were accessed from the hospital information management system. Associations of clinical parameters and markers of disease severity (e.g., polymorph, AST, hs-CRP, D-dimer, LDH, and ferritin levels) with Ct values were assessed. Observations LDH, ferritin, D-dimer, and hs-CRP were found to be significantly higher in moderate and severe groups than in the mild COVID-19 group. AST, ferritin, and hs-CRP levels were also significantly higher in severe COVID-19 subjects, compared to moderate COVID-19 subjects. Ct values for the E (envelop) gene and ORF (open reading frame) 1b gene were found to be significantly higher in those with severe COVID-19. Polymorph counts in subjects with Ct values of 25 or higher were significantly increased, compared to those with Ct values under 30. LDH, D-dimer, and hs-CRP levels in subjects with Ct values over 30 were significantly lower than for those with Ct values under 30. Ferritin was the best independent predictor of non-survival in study subjects, with an area under the curve (AUC) of 85.5% (95% confidence interval = 73.2-95.9). The Ct value for the E gene had an AUC of 75.1%, and the ORF1b gene had an AUC of 64.5%. However, no significant correlation was detected between any parameter and Ct value. Conclusion Polymorph, LDH, ferritin, D-dimer, and hs-CRP levels were significantly elevated in subjects with low E gene Ct values. Also, these subjects were at risk of severe disease and fatality. Ct values for the E gene thus could serve as an early indicator for patients at risk of severe disease and death.

Evaluating Ischemia-Modified Albumin as an Early Biomarker for Hypertensive Disorders During Pregnancy: A Case-Control Study.

Background Ischemia-modified albumin (IMA) is looked upon as a newer marker of myocardial ischemia. There is a paucity of literature however with regard to studies correlating levels of IMA in patients with hypertensive disorders of pregnancy. The present study therefore aimed at estimating the levels of IMA in patients with gestational hypertension and assessing its utility in predicting hypertensive disorders of pregnancy. Methods The present study was a hospital-based case-control study conducted in the Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Nagpur. IMA was estimated in 30 controls (Group I) and 20 cases of gestational hypertension (Group II) using a spectrophotometric assay detecting free unbound Cobalt left behind. The clinical data and lab results were presented as mean ± SD. Student's t-test was applied and Pearson's correlation coefficient was calculated. A value of p < 0.05 was taken as statistically significant. The ROC (Receiver Operator Characteristic) curve was used to establish the cut-off of serum IMA levels in pregnancy-induced hypertension (PIH). Results There was no significant difference in age and period of gestation (POG) at the time of sample collection between the groups. There was a significant difference in the systolic and diastolic blood pressures (BPs) of both groups. The mean level of serum IMA was significantly higher in cases of gestational hypertension (0.88 ± 0.14 absorbance units {ABSU}) as compared to controls (0.69 ± 0.08 ABSU) (p<0.001). On correlation analysis, the systolic and diastolic BPs were found to be highly positively correlated with serum IMA levels (p<0.001). ROC curve analysis suggested that at a cut-off of 0.73 ABSU, IMA has 85% sensitivity and 80% specificity for predicting gestational hypertension. Conclusion Statistically significant results of serum IMA levels obtained in gestational hypertension which falls on the lesser severe spectrum of the disease imply that serum IMA can be used for early diagnosis of gestational hypertension and impending Pre-eclampsia (PE) and Eclampsia.

Implication of COVID-19 in patients of HIV with hepatitis C.

HIV with coexisting Hepatitis C infection has been a global health problem. HIV with Hepatitis C prevalence is significantly higher in people living with HIV. These patients being immunocompromised are at higher risk of contracting COVID-19 infection. Super added COVID-19 infection may prove to be fatal in these patients. We decided to review literature for assessing the clinical manifestations and management of these patients contracting COVID-19 infection and explore the public health measures in practice in the current scenario. Practices of safety norms against COVID-19 shall prevent associated health morbidity and mortality. Moreover, management of these patients needs to be judiciously done by Physicians as COVID-19 infection may worsen their condition. The Public Health Specialist are playing a crucial role in management of COVID-19 pandemic especially by strategy planning for surveillance, health education and preparedness for any future wave of COVID-19 infection.