C-Reactive Protein-to-Albumin Ratio as a Prognostic Inflammatory Marker in COVID-19

Objectives As a result of developed generalized inflammation, the main prognostic factor determining morbidity and mortality in coronavirus disease 2019 (COVID-19) patients is acute respiratory distress syndrome. The purpose of our study was to define (1) the laboratory tests that will contribute to the diagnosis and follow-up of COVID-19 patients, (2) the differences between the laboratory-confirmed (LC), unconfirmed (LUC), and control (C) groups, and (3) the variation between groups of acute-phase reactants and biomarkers that can be used as an indicator of disease severity and inflammation. Materials and Methods A total of 102 patients undergoing treatment with COVID-19 interim guidelines were evaluated. Reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive in 56 (LC), classified as mild or severe, and negative in 46 (LUC) patients. In addition, 30 healthy subjects (C) with negative RT-PCR tests were also evaluated.All statistical analyses were performed with the SPSS 22.0 program and the p-values for significant findings were less than 0.05. Parametric/nonparametric distribution was determined by performing the Kolmogorov–Smirnov test for all groups. Student's t-test was used for variables with parametric distribution and the Mann–Whitney U-test for variables with the nonparametric distribution. A cut-off level for biomarkers was determined using the ROC (receiver operator characteristic) curve. Results In the LC group, platelet, platecrit, mean platelet volume, platelet diameter width, white blood cell, lymphocyte, eosinophil, neutrophil, immature granulocyte, immature lymphocyte, immature monocyte, large immune cell, and atypical lymphocyte counts among the complete blood count parameters of mature and immature cell counts showed a significant difference according to the C and LUC groups. C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio (CAR) indices were significantly elevated in LC patients and were significantly higher in patients classified as severe compared to mild. When CAR optimal cutoff was determined as 0.475, area under the curve was 0.934, sensitivity was 90.91%, specificity was 86.21%, positive predictive value was 92.59%, and negative predictive value was 83.33%. The diagnostic accuracy for CAR was 89.29%. Conclusion The CAR index with the highest diagnostic value and the highest predictability could be the most useful biomarker in the diagnosis and evaluation of disease severity in COVID-19 patients.

An Update on Secondary Bacterial and Fungal Infections and Their Antimicrobial Resistance Pattern (AMR) in COVID-19 Confirmed Patients at a Tertiary Care Hospital

Introduction Since coronavirus disease 2019 (COVID-19) has limited treatment options, concern has been raised over secondary infections and antimicrobial resistance (AMR) patterns. It has been observed that patients who were infected with COVID-19 were predisposed to develop secondary infections. The purpose of the study is to ascertain the prevalence of the bacterial and fungal coinfections in COVID-19 patients, and also to assess the AMR patterns in the obtained isolates. Methods We have studied 200 clinical samples obtained from 122 COVID-19 positive patients. Pathogens were identified using Vitek 2 system. The demographic and clinical patterns were also observed. Results A total of 122 patients developed secondary infections. Patients aged more than 40 years were majorly affected (p-value < 0.0001). Respiratory samples (n = 96) were predominant. Klebsiella pneumoniae (n = 68) was the most common pathogen isolated followed by Acinetobacter baumannii (n = 54) and an overall 6% rise in the Carbapenem resistance was observed in the isolates. Conclusion To contain the secondary infections in COVID-19 patients, it is imperative to adhere to antimicrobial stewardship program and timely revise the empirical antibiotic policy.

Attenuation of Oxidative Stress, Interleukin-6, High-Sensitivity C-Reactive Protein, Plasminogen Activator Inhibitor-1, and Fibrinogen with Oral Vitamin D Supplementation for Six Months in Patients with Type 2 Diabetes Mellitus having Vitamin D Deficiency

Objectives Type 2 diabetes mellitus (T2DM) associated with oxidative stress and inflammation causes endothelial dysfunction, which promotes cardiovascular risk. Vitamin D with its pleiotropic effect is said to protect against cardiovascular risk. However, with vitamin D deficiency being more prevalent in T2DM, the cardiovascular risk may get compounded. Materials and Methods An interventional study was conducted on 100 patients with T2DM having vitamin D deficiency (vitamin D < 20 ng/mL), who were given oral supplementation of 2,000 IU/day of vitamin D for a period of 6 months. Serum vitamin D, biomarkers of oxidative stress, malondialdehyde (MDA), oxidized LDL (OxLDL), ferric reducing ability of plasma (FRAP), biomarkers of inflammation, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen were measured at baseline and at the end of the third and sixth month of vitamin D supplementation. Statistical Analysis Repeated measures analysis of variance (ANOVA) was applied for comparison between baseline and third- and sixth-month data after vitamin D supplementation. Linear regression by generalized estimating equations (GEE), which grouped repeated measures for each subject and accounted for correlations that may occur from multiple observations within subjects, was applied. Results Serum vitamin D levels reached normal levels with a significant decrease in OxLDL, hsCRP, IL-6, PAI-1, and fibrinogen levels, with a significant increase in FRAP (p = 0.001) levels at the end of 6 months of vitamin D supplementation. These changes were observed even after correction with glycemic control (HbA1c). However, a significant decrease in MDA was observed only at the end of the sixth month of vitamin D supplementation. Vitamin D levels showed a significant negative association with Ox-LDL, Hs-CRP, IL-6, PAI-1, and fibrinogen, even after adjusting for BMI and statin use (p = 0.001). Conclusion Supplementation of vitamin D for a period of 6 months in patients with T2DM having vitamin D deficiency is beneficial in the attenuation of oxidative stress and inflammation.

Variation in Laboratory Utilization and Correlation with Hospital Bed Utilization: Experience of a Trauma-Care Hospital during the COVID-19 Pandemic

Objectives The present study was planned with the following objectives: (i) to calculate the difference in frequency of laboratory test ordered and use of consumables between the prepandemic and pandemic phases, (ii) to determine and compare the monthly average number of tests ordered per patient between the prepandemic and pandemic phases, and (iii) to correlate the monthly test ordering frequency with the monthly bed occupancy rate in both phases. Materials and Methods Records of laboratory tests ordered and use of consumables were collected for the prepandemic phase (1.8.2019 to 31.3.2020) and the pandemic phase (1.4.2020 to 31.10.2020). The absolute and relative differences were calculated. Monthly average number of tests ordered per patient and bed occupancy rate between prepandemic and pandemic phases was determined, compared, and correlated. Statistical Analysis The absolute and the relative differences between the two periods were calculated. The continuous variables were analyzed between groups using Mann–Whitney U test. Spearman correlation was used to correlate the monthly test ordering frequency with the monthly bed occupancy rate in both phases. Results A total of 946,421 tests were ordered, of which 370,270 (39%) tests were ordered during the pandemic period. There was a decrease in the number of the overall laboratory tests ordered (12%), and in the use of blood collection tubes (34%), and an increase in the consumption of sanitizers (18%), disinfectants (3%), masks (1633%), and gloves (7011%) during the pandemic period. Also, the monthly average number of tests ordered per patients significantly reduced (p-value < 0.001). Test ordering frequency had strong positive correlation with bed occupancy rate during pandemic (Spearman co-efficient = 0.73, p-value = 0.03). Conclusions An overall decline in laboratory utilization during pandemic period was observed. Understanding and correlating the trends with hospital bed utilization can maximize the productivity of the laboratory and help in better preparedness for the challenges imposed during similar exigencies.

Lymphoepithelioma-Like Carcinoma of Urinary Bladder with Diagnostic Dilemma: Case Report of A Rare Variant of Urothelial Carcinoma

Lymphoepithelioma-like carcinoma of the urinary bladder is a rare variant of urothelial carcinoma that was first described by Zukerberg in 1991 and confirmed as a type of urothelial carcinoma by the WHO classification of the urinary system tumors. A 63-year-old man presented with the chief complaint of gross hematuria for 2 months. Sections from transurethral resection of the bladder revealed urothelial carcinoma. A radical cystoprostatectomy was performed and a final histopathological examination revealed high-grade muscle-invasive urothelial carcinoma, lymphoepithelial variant. The patient has been receiving adjuvant chemotherapy with no recurrence reported to date. This is the third case reported in India to date to the best of our knowledge. Owing to its rare presentation, no definite treatment guidelines have been established for this entity. Various studies from the English literature suggest a conservative approach.

Occurrence of Dengue Virus Infection with Multiple Serotypes at Central Karnataka, India

Objective To find the incidence of concurrent infection of dengue and correlate the difference in clinical features, laboratory diagnoses, and outcomes between dengue and dengue-like illnesses. Methodology A total of 2,256 patients with suspected dengue fever during the period of July 2014 to June 2020 as per the WHO case definition for dengue fever were enrolled in the study. All patients admitted with a suspected dengue fever were studied in detail in terms of demographic features, clinical features, and laboratory profiles. Two blood samples were collected from each patient with a history of fever for 5 to 7 days. Investigation consisted of CBC, Widal test, malarial card test, Weil Felix test, Scrub typhus test, chikungunya, dengue parameters such as dengue NS1, IgM, and IgG, and real-time PCR for dengue serotypes were performed for each sample. Results A total of 1,412 males (62.6%) and 844 females (37.4%) of age 2 to 44 years were hospitalized. Out of 2,256 clinically suspected dengue cases, 1,306 cases were positive and 950 were negative by RT-PCR test. Fever was the most common clinical features among the RT-PCR-positive cases, followed by retroorbital pain (85.9%), flushing in 77.5%, and rashes in 84.8% of patients. ARDS was seen in 9.7% and splenomegaly in 27.5% patients. A platelet count of less than 100,000 was observed in 1,838 (81.5%) patients, and a platelet count of less than 20,000 was observed in 147 (6.5%) patients.Of 2,256 samples, 1,306 (57.9%) tested positive for dengue viral RNA by RT-PCR. Also, 798 cases were infected with a single DENV serotype, and 608 had a concurrent infection. Of the 798 single DENV serotype infection cases, 392 (54.2%) were typed as DENV-2 and 218 (29.2%) as DENV-3. Coinfection with serotypes DENV-2 and DENV-3 was found to account for 67.8% of all concurrent infections. Conclusion The study showed that dengue fever with concurrent infection with multiple serotypes is on the rise, and an occurrence of recombination may lead to the emergence of more virulent strains showing varied clinical presentations.

Evaluation of Tear Film Urea Level as a Diagnostic Marker of Dry Eye Disease: A Pilot Study

Introduction Urea secreted in the sweat is important for skin moisture. Similarly, ocular surface moisture is maintained by the conjunctiva. Based on this, the level of urea in tear film can be used as a potential diagnostic test for dry eye disease (DED). One of the standard tests for DED is Schirmer's test (ST). The aim of this study was to compare tear film urea to values of ST. Methods Fifty patients symptomatic for DED having ST ≤ 10 mm/5 min were enrolled in the study. Fifty age- and sex-matched asymptomatic subjects with ST > 10 mm/5 min were taken as controls. All patients were subjected to an estimation of tear film urea, collected using micropipettes, and analyzed by an Erba Chem 5 semi-autoanalyzer. Based on the ST reading as per the Dry Eye Workshop 2007 (DEWS) classification, dry eye was classified as dry eye (≤ 10 mm/5 min), severe dry eye (≤ 5 mm/5 min), and very severe dry eye (≤ 2 mm/5 min). Tear film urea values were compared with ST values that were considered standard. Statistical analysis was done using Medcalc version 19.7. A p-value ≤ 0.05 was considered significant. Results The mean tear film urea levels in cases were (26.78 ± 5.70 mg/dL) significantly lower compared with controls (41.72 ± 6.86 mg/dL). The area under the receiver characteristic operator curve (AUC) for tear film urea in diagnosing DED was 0.936 (p < 0.0001) with a cutoff of ≤ 37.2 mg/dL, yielding a sensitivity of 96% and a specificity of 76%. For diagnosing severe DED, the AUC for tear film urea was 0.824 (p < 0.0001) with a cutoff value of ≤ 23.4 mg/dL, yielding a sensitivity of 60.8% and a specificity of 92.59%. For diagnosis of very severe DED, the AUC for tear film urea was 0.972 (p < 0.0001) with a cutoff value of ≤ 19.8 mg/dL, yielding a sensitivity of 100% and a specificity of 93.62%. On comparing ST values to tear film urea, the regression coefficient was 0.85 (p < 0.0001), suggesting a linear relationship between ST and tear film urea. Conclusion The study demonstrates that tear film urea can be a potential diagnostic marker for DED. The study also indicates that tear film urea level is linearly related to Schirmer's test values and provides an approximate diagnostic cutoff level for the design of future large-scale studies.

Acquaintance and Awareness of Budding Physicians toward Antimicrobials' Use: Need of the Hour

Background Development of new antibiotics has been slow in the past decades, despite the urgent need. Final-year undergraduate students, interns, and postgraduate students are future prescribers of antimicrobials. It is important they have proper knowledge and attitude toward antibiotic prescription, so that antibiotic resistance could be dealt wisely. Aims The aim of this study was to assess the knowledge and attitude of undergraduate, interns, and postgraduate medical students regarding antimicrobials, antibiotics resistance, and associated factors. Methodology A total of 150 final-year medical students, interns, and resident doctors were included, 50 in each group. Participants were contacted individually and were asked to fill a prevalidated questionnaire. Information was collected on three broad categories: basic information about antimicrobials, knowledge regarding treatment of common infections, and belief and attitude toward antimicrobials. Percentages were calculated for the categorical data and chi-squared test was used for univariate analysis of the categorical data, where p-value less than 0.05 was considered to be significant. Results Precisely, 80.67% were able to answer which type of infections need antibiotics; 19.33% responded that both viral and bacterial infections need antibiotics; 44.67% preferred using broad-spectrum antibiotics for definitive treatment; 28.66% answered macrolides as most commonly used for upper respiratory tract infection; 56% considered fluoroquinolones are most commonly used for urinary tract infection with p-value less than 0.05 between the groups; 43.33% were unaware of the infection control program; while 72.66% were unaware about the antibiotic policy in their institute. Conclusion The majority had sufficient basic knowledge about antibiotics, yet there were areas for concern. Study findings may help to formulate new learning objectives for medical students to inculcate proper knowledge and attitude toward antibiotic prescription.

Immunoexpression of PD-L1 and PD-1 and Its Clinicopathological Correlation in Urothelial Carcinomas

Introduction Urothelial carcinomas are the most common types of bladder tumors that have recently shown a changing trend in treatment protocols with the introduction and approval of immune checkpoint inhibitors. The most important immune checkpoint lies with the PD-1–PD-L1 axis. Although multiple drugs have been approved, there is uncertainty about patient selection criteria and diagnostic assays. Recent studies related to the laboratory-developed tests have opened up the horizon of PD-1 and PD-L1 immunohistochemistry even at resource-constrained laboratories. We propose to study these immunohistochemistry markers in our laboratory using newer clones. Materials and Methods We selected 116 consecutive cases of transurethral bladder tumor resection from our laboratory archive and applied PD-1 and PD-L1 immunohistochemistry. The study was approved by the institution's ethics committee. Results We found high expression of PD-1 and PD-L1 in urothelial carcinoma even with different cut-offs of PD-L1. Muscle invasion, lamina invasion, and grade of carcinoma had a statistically significant effect on the expression; however, age and sex did not affect the expression. Conclusion Based on our current study, we can conclude that the clones used in our study show high expression in urothelial carcinoma and can aid in patient selection and treatment protocol, irrespective of age and sex.