Utility of Serum Procalcitonin and Its Clearance in Predicting Outcomes in COVID-19 Patients.

Introduction Identification of coronavirus disease 2019 (COVID-19) patients at risk of worse clinical outcomes is crucial to improving patient care. Various biochemical markers have been used to predict outcomes in such patients. We aimed to evaluate the role of serum PCT (procalcitonin) and the utility of PCT clearance (PCTc) in predicting the outcome of patients with COVID-19 illness. Methods We prospectively included 39 patients with severe or critical COVID-19 illness with an age equal to more than 18 years. In addition to routine baseline investigations, serum PCT was measured at admission (PCT1) and day 5 of hospitalization (PCT2). PCTc was calculated using the formula [Formula: see text]. Results We observed that serum PCT at admission was significantly higher in non-survivors (median: 1.9 ng/ml IQR: 0.51-4.23) compared to survivors (median 0.35 (IQR: 0.1-1.2), p 0.002). On serial serum-PCT estimation, non-survivors had persistently elevated serum-PCT (median PCT1:1.9 ng/ml (IQR: 0.51-4.23) to median PCT2: 1.9ng/ml (IQR: 0.83-2.72), p 0.51) than survivors (median PCT1:0.35ng/ml (IQR: 0.1-1.19) to median PCT2: 0.15ng/ml (IQR: 0.05-0.29), p 0.01). However, no difference in serum PCTc was observed between the two groups (median: 35.3% (IQR: 12.5-84.9) in survivors vs. 71.7% (33.3-91.7) in non-survivors, p = 0.165). Conclusion Serum PCT is a potential biochemical marker that could predict outcomes in COVID-19 patients. Measurement of serial serum PCT and estimation of PCT clearance may serve as better predictors than a single value; however, well-designed studies are required to identify the definite role of serum PCT in COVID-19 patients of varying severity.

Addition of Mask to High-flow Nasal Oxygen: A Strategy to Improve Oxygenation in Hypoxemic Respiratory Failure Secondary to COVID-19.

PURPOSE: High-flow nasal cannula (HFNO) reduces the need for invasive mechanical ventilation in COVID-19 patients with hypoxemic-respiratory failure. During HFNO entrainment of room air dilutes the delivered fractional inspiratory oxygen (FiO2), thereby preventing improvement in oxygenation. The placement of a mask over HFNO to improve oxygenation has provided conflicting results. We aimed to determine and compare the effect of placing various mask types over HFNO on oxygen saturation (SPO2). MATERIALS AND METHODS: In this prospective physiological study 40 patients with COVID-19-associated hypoxemic respiratory failure on HFNO with O2 concentration <92% were included. The effect of placing different masks over HFNO on oxygenation, respiratory rate, heart rate, blood pressure, patient comfort, and partial pressure of carbon dioxide level (pCO2) was recorded after a prespecified time interval. RESULTS: We observed a significantly higher mean SPO2 and lower mean respiratory rate on using various study masks over HFNO compared to HFNO alone. On comparing various mask types, the use of N95 masks and nonrebreather (NRB) masks with O2 showed a significant increase in O2 concentration and reduction in respiratory rate compared to surgical mask (SM) and NRB without O2. The proportion of patients who achieved SPO2 of >92% was higher with the use of N95 masks (47.5%) or NRB with O2 (45%) over HFNO compared to SM (35%) and NRB without O2 (35%). No significant change was observed in heart rate, blood pressure, and CO2 level with the use of any mask over HFNO. CONCLUSION: This study demonstrates improvement in oxygenation and reduction in respiratory rate with the use of various masks over HFNO in patients of COVID-19-related hypoxemic-respiratory-failure. Significantly greater benefit was achieved with the use of N95 or NRB with O2 compared to SM or NRB without O2.

Clinicopathological Features and Status of Programmed Death Ligand-1 (PD-L1) Expression in Lung Cancer: A Single Centre Study From North India.

Introduction Programmed death ligand-1 (PD-L1) is an immunological checkpoint that supports the inhibition of the anti-tumor immune system. A higher level of PD-L1 expression was also discovered on the cell surfaces of several cancer cells, including non-small cell lung carcinoma (NSCLC). Identifying individuals who would benefit from PD-1/PD-L1 antibody immunotherapy is crucial in the era of precision medicine. The study's objective was to assess the distribution and degree of PD-L1 ligand expression in various forms of lung cancer and examine its link to clinicopathological variables. Methods This prospective, observational, cross-sectional study was done in a tertiary care hospital in North India over 2 years from 2019 to 2021. A total of 100 patients diagnosed with lung cancer through either endobronchial or image-guided biopsies were enrolled. The biopsy specimens of lung cancer patients have been subjected to immunohistochemistry (IHC) staining. PD-L1 expression was positive when at least 1% of tumor cells were stained. In our study, we used the rabbit monoclonal Anti-PD-L1 antibody (CAL10) (ab237726) (Abcam Plc, UK).  Results  Of the 100 patients, Squamous cell carcinoma (SQCC) was the predominant histological pattern. The mean age of the study group was 57.26 ± 10.53 years. High PDL-1 positivity (>50% ) is seen in a total of 10 patients, while low PD-L1 positivity (1-50%) is seen in 24 patients. Of all patients with high PD-L1 positivity (n=10), 80% had stage IV at the time of diagnosis. However, on similar lines, 71 % of patients with low PD-L1 positivity presented with stage IV at the time of diagnosis. (p value=0.09). Among 10 patients with epidermal growth factor receptor (EGFR) positive status, high PD-L1 positivity is seen in 20%. Among 3 patients with anaplastic lymphoma kinase (ALK) positive status, only one patient showed high PD-L1 positivity, whereas negative PDL-1 was seen in 2 patients, which was not statistically significant. Conclusion  The management of lung cancer is driven by precision medicine, including PDL-1 expression, which correlates with immune checkpoint inhibitor response. In our cohort, PD-L1 expression appears to be mostly linked to the squamous cell subtype of lung cancer, with elevated tumor stage and mediastinal lymphadenopathy in Kashmiri people. Other oncogenic driver mutations are not connected to PD-L1 expression. The function of PD-L1 expression in lung tumors requires more study.

Prevalence of obstructive sleep apnea in patients with chronic kidney disease: a hospital-based study.

BACKGROUND: Chronic kidney disease (CKD) is has been rising over the past few years, and obstructive sleep apnea (OSA) is a prevalent comorbidity in this population. AIM: To determine the prevalence of OSA in patients with chronic kidney disease stages I-V and end-stage renal disease (ESRD). METHODS: Patients with CKD of varying grades and ESRD routinely visiting outpatient nephrology clinic or admitted in department of nephrology were included in the study. Stages I-III were categorized as early stages of CKD and stages IV-V and ESRD as late stages of CKD. Patients were categorized into a high risk group based on STOP-BANG and Berlin questionnaires. Patients who were high risk were subjected to in-hospital overnight level III polysomnography. Student's independent t-test and analysis of variance (ANOVA) were employed for the comparison of continuous variables. Chi-square test and Fisher's exact test, as appropriate, were used for the comparison of categorical variables. RESULTS: Of 111 patients, 46 (41%) were found to have OSA. Of these patients, 15 (33%) had mild OSA (AHI 5-14/h), 13 (28%) had moderate OSA (15-29/h), and 18 (39%) had severe OSA (AHI ≥ 30/h). Overall, 31% of patients in the early stage of CKD and 45% in the late stage were found to have OSA. CONCLUSION: This study demonstrated a high prevalence of OSA in patients with CKD when compared to the general population affecting both genders equally. The risk of OSA was higher in the advanced stages of CKD compared to the early stages, and dialysis had no effect on prevalence. Since OSA increases the cardiovascular morbidity in CKD the leading cause of death in these patients, early diagnosis and treatment of OSA may have promise to affect the mortality.

Prevalence and predictors of pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The prevalence of pulmonary embolism (PE) in patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) varies over a wide range. Early detection and treatment of PE in AECOPD is a key to improve patient outcome. The purpose of the study was to investigate the prevalence and predictors of PE in patients of AECOPD in a high burden region of North India. MATERIALS AND METHODS: This prospective study included patients of AECOPD with no obvious cause of exacerbation on initial evaluation. Apart from routine workup, the participants underwent assessment of D-dimer, compression ultrasound and venous Doppler ultrasound of the lower limbs and pelvic veins, and a multidetector computed tomography pulmonary angiography. RESULTS: A total of 100 patients of AECOPD with unknown etiology were included. PE as a possible cause of AE-COPD was observed in 14% of patients. Among the participants with PE, 63% (n = 9) had a concomitant presence of lower extremity deep venous thrombosis. Hemoptysis and chest pain were significantly higher in patients of AECOPD with PE ([35.7% vs. 7%, P = 0.002] and [92.9% vs. 38.4%, P = 0.001]). Likelihood of PE was significantly higher in patients who presented with tachycardia, tachypnea, respiratory alkalosis (PaCO2 <45 mmHg and pH >7.45), and hypotension. No difference was observed between the two groups in terms of in-hospital mortality, age, sex distribution, and risk factors for embolism except for the previous history of venous thromboembolism (35.7% vs. 12.8% P = 0.03). CONCLUSION: PE was probably responsible for AECOPD in 14% of patients with no obvious cause on initial assessment. Patients who present with chest pain, hemoptysis, tachypnea, tachycardia, and respiratory alkalosis should be particularly screened for PE.

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

BACKGROUND: Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. METHODS: 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. RESULTS: Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). CONCLUSION: The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

Glycation induced conformational alterations in caprine brain cystatin (CBC) leads to aggregation via passage through a partially folded state.

Glycation induced advanced glycation end products (AGEs) of proteins formed as a result of Maillard reaction is currently at the heart of a number of pathological conditions. The formation of chemically stable AGEs can permanently alter protein structure and function; hence can serve as an implication in long term complications. Cystatins with high amyloidogenic inclination are implicated in various diseases including cancer and neurodegenerative conditions. The aggregates of cystatin purified from caprine brain have been studied on addition of glucose and ribose using UV absorption, fluorescence emission, circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). In the present study AGEs have been monitored and characterized. CBC was incubated for varying time intervals up to 41days in the presence of 17 and 100mM each of glucose and ribose. Ribose at both the concentrations was found to be more potent glycating agent as compared to glucose at these concentrations which is evident from UV and fluorescence spectroscopic studies. Altered intrinsic and high ANS fluorescence for 100mM and 17mM sugar concentrations respectively, suggested the existence of molten globule state of CBC. Glycated CBC as AGEs and aggregates were observed on day 27 and 41 respectively. Formation of AGEs was confirmed by employing AGEs specific fluorescence studies. CBC aggregates confirmed the presence of ß-sheet structure as shown by far-UV CD, dye binding assay and transmission electron microscopy (TEM). Current study is of immense importance as cystatin is a potential candidate of amyloidogenic tendency and a potent endogenous regulator of thiol proteases; hence serves to be an attractive model to study amyloidogenesis of brain cysteine protease inhibitor.