Effect of disease activity on the clinical outcome of SARS CoV-2 in patients with underlying rheumatic diseases; data from global rheumatology alliance.

Objectives: To determine the effect of disease activity on clinical outcomes of coronavirus disease-2019 in patients with rheumatic diseases. METHODS: The prospective, cohort study was conducted from January 1st to June 30th, 2021, at Rheumatology department, Fauji Foundation Hospital, Rawalpindi. It comprised patients of rheumatic disorders who were affected by coronavirus disease-2019. The patients were categorised according to rheumatic disease activity into remission group I, low disease activity group II, moderate group III and high-activity group IV. Coronavirus disease-2019 outcomes compared included recovered vs death, hospitalisation yes vs no, mechanical ventilation yes vs no. The association of disease activity status with coronavirus disease-2019 outcomes was explored. Data was analysed using SPSS 23. RESULTS: Of the 100 patients, 78(78%) were females and 22(22%) were males. The overall mean age was 45.60±13.7 years. There were 23(23%) patients in group I, 42(42%) patients in group II, 21(21%) patients in group III and 14(14%) patients in group IV. Overall,17(17%) patients died and 83(83%) patients survived. In group III, 7(33.3%) patients died, followed by 6(42.9%) in group IV (p<0.05). In total, 7(7%) patients needed mechanical ventilation, with 3(21.4%) being in group IV (p<0.05). Hospitalisation was needed in 33(33%) cases, and intergroup comparison was non-significant (p>0.05). CONCLUSIONS: Patients with severe rheumatic autoimmune disease affected by coronavirus disease-2019 were more likely to die and require invasive ventilation.

Posterior reversible encephalopathy syndrome: A rare complication of rituximab therapy in rheumatoid arthritis.

Rituximab, a murine-human chimeric monoclonal antibody targeting CD20-positive B lymphocytes, has established itself as an effective and relatively safe biologic therapy for patients with refractory rheumatoid arthritis. Most common side effects associated with its use include infusion related reactions and cytopenia. Rare adverse effects such as progressive multifocal leukoencephalopathy and posterior reversible encephalopathy syndrome (PRES) have also been reported. Diagnosis of PRES following rituximab treatment requires a high index of suspicion correlated with clinical and radiological features in individuals at risk. Early diagnosis and prompt treatment is associated with a favorable prognosis. We present a case of a young man who developed PRES following rituximab administration on account of active rheumatoid arthritis. Timely diagnosis and prompt treatment ensured his uneventful recovery without residual neurological deficit.

Child-Pugh Score, MELD Score and Glasgow Blatchford Score to Predict the In-Hospital Outcome of Portal Hypertensive Patients Presenting with Upper Gastrointestinal Bleeding: An Experience from Tertiary Healthcare System.

The two most familiar scores used for prognostication of liver cirrhosis are the Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP), while the Glasgow-Blatchford (GB) score is used for sorting non-variceal upper gastrointestinal hemorrhage into high- or low-risk categories. This study evaluates the validity of the CTP, MELD, and GB scoring systems in prognosticating the in-hospital outcome of bleeding portal hypertensive patients. In this study, the ROC curve and Younden index determine the efficacy of three scoring systems. The results indicate that CTP was the most efficient score as the predictor of outcome (AUC = 0.9, cut-off value > 7); followed by MELD (AUC = 0.8, cut-off value > 18) and then the GB score (AUC = 0.64, cut-off value > 14) (p < 0.05). In pair-wise comparison, the difference between CTP and MELD was insignificant (p > 0.05). Patients with a CTP score of >7 had notably higher in-hospital mortality (19.8% vs. 0.9%, p < 0.0001). Similarly, mortality with a MELD score > 18 was significant (14.8% vs. 5.9% (p < 0.0001). The GB score was not a good indicator of the outcome. Platelets, albumin, CTP, and MELD scores were the independent contributors to mortality. Thus, as liver cirrhosis prognosticators, CTP and MELD scores can also both be used as predictive scores of the in-hospital outcomes of bleeding patients due to portal hypertension. Compared to the GB score, CTP and MELD scores are fairly efficient predictors in these patients.

Outcome Of Short And Long Duration Steroid Therapy In Childhood Nephrotic Syndrome In Terms Of Frequency Of Relapse Rate.

BACKGROUND: Nephrotic syndrome is a clinical syndrome defined by massive proteinuria (greater than 40 mg/m2/hour) responsible for hypoalbuminemia (less than 30 g/L) resulting in oedema and hyperlipidaemia. Objective of the study was to compare the frequency of relapse rate with short and long duration steroid therapy in Nephrotic syndrome. It was a Quasiexperimental control group design, conducted at the Department of Paediatric Nephrology, The Children's Hospital and Institute of Child Health, Lahore. Duration of study: One year. METHODS: The data of 150 patients with steroid sensitive nephrotic syndrome was included with clinical presentation and diagnostic investigations. The children were randomly divided into long and short duration steroid treatment groups. Outcome was determined in terms of relapse rate after achieving remission with both treatment strategies. Independent sample t test was applied to compare the outcome in both groups with p≤0.05 considered as significant. Data was stratified for all the effect modifiers like age and gender and poststratification chi square test was applied to see the effect on the outcome, taking p≤0.05 as significant. RESULTS: The relapse rate of the disease was 0.8±0.72 per year in short-duration group and 1.28±0.61 per year in subjects receiving long-duration steroids, and difference between the two groups was found to be statistically significant (p<0.001). The relapse rate was less in the short duration therapy group as compared to the long duration therapy 62.7% (n=47) patients in group A had one or more relapses of the disease within one year of follow up in contrast to 94.7% (n=71) children in group B (p<0.001). CONCLUSIONS: Patients receiving short duration steroid therapy showed a lower relapse rate as compared to those who were administered long term steroids.

Corona Virus Disease-19 Vaccine-associated Autoimmune Disorders.

Coronavirus disease is a highly infectious viral disease caused by severe acute respiratory syndrome virus (SARS nCoV2). It was declared a pandemic within a few months of identification of its index case. The spread of COVID-19 across the globe was rampant, overwhelming healthcare systems and crippling global economies. Since the world was caught off guard by the pandemic, vaccine programs had to be rolled out in emergency to curb its spread. Ten vaccines have been granted Emergency Use Authorization thus far. Much of the side effects we know today are post-marketing adverse effects. Most of them are mild like myalgia and injection-site reactions, but a few of them such as post-vaccination autoimmune diseases have alerted the medical community. These include vaccine-induced thrombotic thrombocytopenia, autoimmune hepatitis, myocarditis, and Graves' disease. We attempt to summarize the diverse autoimmune phenomena reported after COVID-19 vaccination, with an aim to sensitize the medical community so that they can be better equipped in management when confronted with these diseases. This review by no means refutes the potential benefit of COVID-19 vaccination which has consolidated its place in preventing infections and substantially reducing severity and mortality.

Synthesis and Evaluation of Bis-Schiff Bases of Carbohydrazide as Antioxidant and Cytotoxic Agents.

INTRODUCTION: Antioxidants are known to prevent oxidative stress-induced damage to the biomolecules and thus, delay the onset of cancers and many age-related diseases. Therefore, the development of novel and potent antioxidants is justified. METHODS: During this study, we synthesized symmetrical Bis-Schiff bases of carbohydrazide 1-27, and evaluated their in vitro antioxidative activity and cytotoxic activity. RESULTS: Among synthesized compounds, six compounds 20 (IC50 = 12.89 ± 0.02 µM), 16 (IC50 = 14.32 ± 0.43 µM), 17 (IC50 = 18.52 ± 0.83 µM), 19 (IC50 = 22.84 ± 0.62 µM), 24 (IC50 = 35.1 ± 0.82 µM) and 15 (IC50 = 40.03 ± 1.06 µM) showed an excellent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, better than the standard butylatedhydroxyanisole (BHA) (IC50 = 44.6 ± 0.6 µM). Likewise, two compounds 16 (IC50 = 4.3 ± 1.3 µM) and 20 (IC50 = 6.6 ± 1.6 µM) showed oxidative burst scavenging activity better than the standard drug ibuprofen (IC50 = 11.2 ± 1.9 µM). Some synthesized compounds showed good to moderate toxicity against prostate cancer (PC-3) cell lines. CONCLUSION: This study has identified potent antioxidants and good cytotoxic agents with the potential to further investigate.

Internet addiction and sleep quality among medical students during the COVID-19 pandemic: A multinational cross-sectional survey.

BACKGROUND: The emergence of the COVID-19 pandemic has affected the lives of many people, including medical students. The present study explored internet addiction and changes in sleep patterns among medical students during the pandemic and assessed the relationship between them. METHODS: A cross-sectional study was carried out in seven countries, the Dominican Republic, Egypt, Guyana, India, Mexico, Pakistan, and Sudan, using a convenience sampling technique, an online survey comprising demographic details, information regarding COVID-19, the Pittsburgh Sleep Quality Index (PSQI), and the Internet Addiction Test (IAT). RESULTS: In total, 2749 participants completed the questionnaire. Of the total, 67.6% scored above 30 in the IAT, suggesting the presence of an Internet addiction, and 73.5% scored equal and above 5 in the PSQI, suggesting poor sleep quality. Internet addiction was found to be significant predictors of poor sleep quality, causing 13.2% of the variance in poor sleep quality. Participants who reported COVID-19 related symptoms had disturbed sleep and higher internet addiction levels when compared with those who did not. Participants who reported a diagnosis of COVID-19 reported poor sleep quality. Those living with a COVID-19 diagnosed patient reported higher internet addiction and worse sleep quality compared with those who did not have any COVID-19 patients in their surroundings. CONCLUSION: The results of this study suggest that internet addiction and poor sleep quality are two issues that require addressing amongst medical students. Medical training institutions should do their best to minimize their negative impact, particularly during the current COVID-19 pandemic.

Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception.

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied. Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer. Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother's age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi. Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.

Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages.

BACKGROUND: Miscarriage is a common complication of early pregnancy, mostly occurring in the first trimester. However, the etiological factors and prognostic and diagnostic biomarkers are not well known. Neurokinin-1 receptor (NK-1R) is a receptor of tachykinin peptide substance P (SP) and has a role in various pathological conditions, cancers, but its association with miscarriages and significance as a clinicopathological parameter are not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception (POC). The role of NK-1R is not known in miscarriages. MATERIALS AND METHODS: NK-1R expression was assessed in POC and normal placental tissues by immunohistochemistry. Three- to four-micrometer-thin sections of formalin-fixed paraffin-embedded tissues were used for this purpose. Tissues were processed and then immunohistochemically stained with NK-1R antibody. Brain tissue was used as control for antibody. Protein expression was evaluated using the nuclear labeling index (%). Tissues were counterstained with 3,3'-diaminobenzidine (DAB), and microscopy was performed at 10×, 20×, and 40× magnifications. RESULTS: Ten human POC tissues and 10 normal placental tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of both groups. NK-1R expression showed no notable differences among different cases of miscarriages as well as normal deliveries at full term regardless of the mother's age and gestational age at which the event occurred. Statistically, no difference was found in both groups, which is in agreement with our hypothesis and previous findings. CONCLUSION: The expression of NK-1R was similar in all the cases, and it was intense. It shows that dysregulation of NK-1R along with its ligand SP might be involved in miscarriages and also involved in normal delivery. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK-1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time the expression and localization of NK-1R in POC. We suggest NK-1R antagonist in addition to the immunoglobulins and human chorionic gonadotropin to diagnose and treat spontaneous miscarriages.

Coronary Sinus Ablation Is a Key Player Substrate in Recurrence of Persistent Atrial Fibrillation.

Atrial fibrillation (AF) is the most frequent atrial arrhythmia. During the last few decades, owing to numerous advancements in the field of electrophysiology, we reached satisfactory outcomes for paroxysmal AF with the help of ablation procedures. But the most challenging type is still persistent AF. The recurrence rate of AF in patients with persistent AF is very high, which shows the inadequacy of pulmonary vein isolation (PVI). Over the last few decades, we have been trying to gain insight into AF mechanisms, and have come to the conclusion that there must be some triggers and substrates other than pulmonary veins. According to many studies, PVI alone is not enough to deal with persistent AF. The purpose of our review is to summarize updates and to clarify the role of coronary sinus (CS) in AF induction and propagation. This review will provide updated knowledge on developmental, histological, and macroscopic anatomical aspects of CS with its role as arrhythmogenic substrate. This review will also inform readers about application of CS in other electrophysiological procedures.

Role of neurotransmitter Substance P in progression of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most frequent type of head and neck cancers. OBJECTIVES: In the present study, we evaluated the expression and distribution of Substance P (SP) in different grades of OSCC and role of SP in its proliferation and progression. SUBJECTS AND METHODS: Forty OSCC biopsies were immunohistochemically analyzed by using SP antibody, including 29 male and 11 female cases. 35% were well differentiated, 35% moderately differentiated and 30% poorly differentiated OSCC. The majority of patients were in the age range of 41-80 years. 62% of the cases were positive for SP. SP positivity was expressed in the cytoplasm of the tumor cells. Most of the positive cases were from the tongue region. RESULTS: 93% of moderately differentiated, 92% of poorly differentiated and 8% of well-differentiated carcinomas were SP-positive, but SP expression intensity was highest in poorly differentiated cases (+3). More positive patients were males (68.96% of all male patients) with moderately and poorly differentiated OSCC. Among all positive cases, 48% were poorly differentiated, 48% moderately differentiated and 4% well differentiated. CONCLUSION: Strong expression of SP in poorly and moderately differentiated cases suggests a role of SP in the progression and development of tumor. Expression of SP in the current study increased as the proliferation of cells increased. Prevalence of oral cancer in males may be due to the fact that they smoke and use pan, chewing gum, beetle nut etc. in this region. SP antagonists can help in the reduction and inhibition of oral cancer. SP has a diagnostic value with sensitivity of 92.5% and specificity of 93.7%. The positive predictive value is 96.2% and the negative predictive value 88.2%.

Iridoid glycoside from the leaves of Clerodendrum volubile beauv. shows potent antioxidant activity against oxidative stress in rat brain and hepatic tissues.

AIM: This study aims at reporting the isolation, structure elucidation, and antioxidant potentials of ajugoside from C. volubile leaves in sodium nitroprusside (SNP)-induced oxidative stressed rat brain and hepatic tissues. MATERIALS AND METHOD: An iridoid monoterpene, ajugoside was isolated from the n-butanol fraction of C. volubile and evaluated for its antioxidant protective potential on brain and liver tissues of male Wister rats in an ex vivo model. Two molar concentrations (6.4 × 10(-4) M and 1.28 × 10(-3) M) of the metabolite and SNP were incubated with the tissues homogenate at 37°C for 2 hr prior to the test and assayed for catalase, superoxide dismutase (SOD) activities, and lipid peroxidation. α tocopherol (6.4 × 10(-4) M) was used as standard. RESULTS: Both molar concentrations exhibited high catalase activity in the tissues. However, 6.4 × 10(-4) M ajugoside exhibited a very high SOD activity (liver: 96.45 and brain: 96.30%) and inhibition of lipid peroxidation (liver: 88.11 and brain: 93.27%) compared to the standard. 1.28 × 10(-3) M ajugoside also exhibited good activities but lower than that of the standard and 6.4 × 10(-4) M ajugoside. DISCUSSION AND CONCLUSION: Ajugoside showed potent antioxidant activities as evidenced by the synergistic high activities of SOD and catalase as well as inhibition of lipid peroxidation in the studied tissues.

Effect of Grewia asiatica fruit on glycemic index and phagocytosis tested in healthy human subjects.

The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production.

Modified method of AgNOR staining for tissue and interpretation in histopathology.

This study was conducted in the department of Pathology King Edward Medical University, from June to December 2002 to introduce the new method of AgNOR staining and its interpretation to increase its reliability. A total of 60 brain specimens were stained with modified AgNOR technique. The diagnosis of malignancy was made on H & E staining. AgNOR counts, variation in size and dispersion of AgNOR dots in cells were graded and compared in malignant and non-malignant lesions. Modified method of AgNOR staining and interpretation was an easy, reliable and reproducible alternative to traditional AgNOR techniques for evaluating proliferation activity of cells in malignant and benign brain lesions. mAgNOR counts of different grades of astrocytoma (2.97+/-0.96, 3.97+/-0.43, 6.01+/-2.74 and 8.01+/-3.56) were significantly (P<0.01) greater when compared with counts of normal brain (0.40+/-0.01), and reactive gliosis (0.60+/-0.01). AgNOR size and dispersion were of higher grade in a significantly greater proportion of malignancy when compared with benign conditions (P<0.05). The AgNOR dots were brighter and more clear with modified staining when compared with previous studies. We conclude that modified AgNOR staining technique is simple, quick and reliable to evaluate cell proliferation by detecting AgNORs size and dispersion. In future, AgNOR size and dispersion should be considered rather than the count only. We recommend the use of morphometry for AgNOR size in future. We also recommend the use of modified AgNOR staining for obtaining sound and confidant results in routine paraffin sections.