Unveiling diagnostic prowess: a comparative study of exercise treadmill test and CT coronary in coronary artery disease detection in Pakistan (2021-2023).

Coronary Artery Disease (CAD) is a global health concern, with diagnostic modalities and risk factors that exhibit regional variations. This study, conducted at the Islamabad Diagnostic Center, Pakistan, aimed to provide a comprehensive assessment of CAD prevalence, severity, and associated risk factors, while also evaluating the diagnostic accuracy of Computed Tomography Coronary Test (CTT) and Exercise Treadmill Test (ETT) in a cohort of 2909 patients. Among the patients assessed via CT Coronary scans, CAD was universally observed, presenting with varying degrees of severity. Our findings indicated that 24.5% of patients had mild CAD, 28.6% exhibited mild to moderate CAD, 16.3% were diagnosed with moderate CAD, 18.4% demonstrated moderate to severe CAD, and 20.4% displayed severe CAD. This spectrum underscores the diverse nature of CAD within the study population. In addition to CTT, we conducted a detailed evaluation of ETT results in 49 patients. These results revealed that 55.1% of patients tested positive for ischemia during the exercise test, emphasizing the prevalence of cardiac stress and underlying CAD. Conversely, 32.7% of patients exhibited negative ETT results, indicating favorable cardiac tolerance during physical activity. A subset of patients yielded non-diagnostic or inconclusive results, necessitating further clinical assessment. Disease history analysis showed a dichotomy within the cohort, with 20.4% having a known medical history and 79.6% possessing an unknown disease history, highlighting the importance of comprehensive medical records in clinical practice. Hypertension, a critical cardiovascular risk factor, was identified in 87.8% of patients, underscoring its significance. Smoking history displayed notable variation, with 69.4% categorized as smokers, 14.3% as ex-smokers, and 10.2% as non-smokers. Lipid profile analysis indicated that 69.4% of patients had abnormal lipid levels. To assess the diagnostic accuracy of CTT and ETT, we calculated Positive Predictive Values (PPV) and Negative Predictive Values (NPV). CTT exhibited a PPV of approximately 5.99% and an NPV of approximately 4.40%, whereas ETT displayed a higher PPV of around 26.44% and a substantially higher NPV of about 49.24%. This study offers valuable insights into CAD prevalence, severity, and associated risk factors in a Pakistani cohort, emphasizing the importance of holistic risk assessment and tailored interventions in clinical practice. Our findings also highlight the diagnostic utility of ETT in CAD assessment.

SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.

Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.

Hepatitis C virus associated ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 19-9, iPTH biomarkers, computed tomography and HCV burden of disease during pre COVID-19 era (2018-2019) and post COVID-19 era (2020-2022) in Pakistan.

The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.

Hepatitis C virus induces oxidative stress and DNA damage by regulating DNAPKCs, ATM, ATR and PARP mediated signaling and guards cell from cancerous condition by upregulating RB, P53 and downregulating VEGF.

Hepatitis C virus is responsible for liver damage and various metabolic disorders. HCV infections promote oxidative stress and cause damage to macromolecules. The aim of our study was to design a preliminary study with establishment of HCV genotype 3a infectivity assay in order to determine DNA damage in Huh-7 cell line at 72 hours post inoculation. Quantitative expression levels of COX-2 and GSR (oxidants and antioxidants), DNAPKCs, ATM, ATR and PARP (DNA damage and repair genes), RB and P53 (tumor suppressor genes) and VEGF (angiogenesis marker) were observed via real time PCR. Our findings revealed 1.533 fold upregulated expression of COX-2. The expression level of GSR was increased by1.27 fold and VEGF expression decreased by 0.367 fold. Thus, preventing cells to enter cancerous phase.

LRIG1 expression during homeostasis and skin wound healing in mice.

Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 belong to the family of proteins known to be expressed in skin. Ablation of LRIG1 in mice results in epidermal hyperplasia and its aberrant expression levels have been reported in pathological conditions such as psoriasis, thus evident of an indispensible role of LRIG1 in maintaining epidermal homeostasis. In order to gain insight into the homeostatic expression of LRIG1 and in various stages of cutaneous wound healing, LRIG1 expression was immunohistochemically analyzed in full thickness skin wounds in mice. The full thickness skin wounds were established on the dorsal back of Balb/c mice (n=6). LRIG1 expression at various post wounding days (1, 2, 3, 6 and 14) was determined through Immunohistochemical analysis (IHC) of the murine skin sections. The injury caused a sharp decline in LRIG1 expression in the basal epidermal cells and appendages surrounding the wound which correlates with the re-epithelialization phase of healing. LRIG1 expression remained down regulated during most of the wound healing stages. LRIG1+ cells were found to re-populate the neo-epidermis on day 14, suggesting an important homeostatic role of LRIG1 in skin.