Drug repurposing for COVID-19 using computational screening: Is Fostamatinib/R406 a potential candidate?

With the gradual increase in the COVID-19 mortality rate, there is an urgent need for an effective drug/vaccine. Several drugs like Remdesivir, Azithromycin, Favirapir, Ritonavir, Darunavir, etc., are put under evaluation in more than 300 clinical trials to treat COVID-19. On the other hand, several vaccines like Pfizer-BioNTech, Moderna, Johnson & Johnson's Janssen, Sputnik V, Covishield, Covaxin, etc., also evolved from the research study. While few of them already gets approved, others show encouraging results and are still under assessment. In parallel, there are also significant developments in new drug development. But, since the approval of new molecules takes substantial time, drug repurposing studies have also gained considerable momentum. The primary agent of the disease progression of COVID-19 is SARS-CoV2/nCoV, which is believed to have ~89% genetic resemblance with SARS-CoV, a coronavirus responsible for the massive outbreak in 2003. With this hypothesis, Human-SARS-CoV protein interactions are used to develop an in-silico Human-nCoV network by identifying potential COVID-19 human spreader proteins by applying the SIS model and fuzzy thresholding by a possible COVID-19 FDA drugs target-based validation. At first, the complete list of FDA drugs is identified for the level-1 and level-2 spreader proteins in this network, followed by applying a drug consensus scoring strategy. The same consensus strategy is involved in the second analysis but on a curated overlapping set of key genes/proteins identified from COVID-19 symptoms. Validation using subsequent docking study has also been performed on COVID-19 potential drugs with the available major COVID-19 crystal structures whose PDB IDs are: 6LU7, 6M2Q, 6W9C, 6M0J, 6M71 and 6VXX. Our computational study and docking results suggest that Fostamatinib (R406 as its active promoiety) may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19.

Study of Complete Haemogram and Iron Profile From Cord Blood of Newborn with Respect to Primigravida, Multigravida and Apgar Score.

Study of different parameters of cord blood usually reflects neonatal health status. One of the widely used system for assessing neonatal health is APGAR score. It is assed at 1 and 5 min from baby's birth. Immediate medical care may improve 5 min score of neonate who showed poor score at 1 min. The main objective of this study is to establish whether any correlation exists between complete hemogram and iron profile with APGAR score and gravid of mother. Cord blood was collected from 96 new born, delivered vaginally, mothers having no chronic medical disease. Different parameters of complete hemogram were assessed along with iron profile and statistical analysis was done by Graph pad Instat3 soft ware. Statistically significant correlation exists between APGAR score (5 min) and MCV (p = 0.005), MCHC (p = 0.016), nRBC (p = 0.002), platelet count (p = 0.001), RDW (p = 0.001). Statistically weak correlation exists between TLC (p = 0.08). Comparing complete blood count with gravid of mother by unpaired t test significant correlation was obtained for HCT (p = 0.035) and RDW (p = 0.03). Apgar score and complete hemogram from cord blood are both non-invasive procedure which help us to asses fetal wellbeing as well as requirement of immediate management. Further more studies are essential to establish the relationship.

Disseminated Cryptococcosis in an Immunocompetent Child.

A case of disseminated cryptococcus infection in an immunocompetent host is described. The present case attests to the importance of using a cautious approach for the diagnosis of granulomatous lymphadenitis. The patient was initially misdiagnosed and treated as disseminated tuberculosis. Later the patient developed visual loss and skin lesions. Periodic Acid Schiff stained sections of lymph node biopsy and cerebrospinal fluid culture established the diagnosis.

Comparative Study of Imprint Cytology and Histopathology of Soft Tissue Tumors.

BACKGROUND: The components of soft tissue are fibroblasts, collagen, vascular structures, fatty tissue, skeletal muscles, smooth muscles, and neural tissue. The real incidence of soft tissue tumors (STTs) is difficult to estimate because most of them are benign (Benign: Malignant-100:1). AIMS: The aim of the present study was undertaken to note the patterns of presentation of patients with STTs and to evaluate the findings of imprint cytology (IC) and histopathological examination (HPE) of STTs. MATERIALS AND METHODS: The present study was undertaken for 1 year. A total of 41 patients with clinically and radiologically diagnosed STTs were included in the study. Following surgery, imprint smear was taken for each tumor, before delivering the tissue to 10% formalin. HPE was subsequently performed. RESULTS: The age of the patients ranged from 4 months to 80 years with a mean of 35.6 ± 17.5 years. The ratio of males to females was 1.05:1. HPE revealed that 21 (51.2%) tumors were benign and 20 (48.8%) malignant. Imprint smears revealed 16 (39%) tumors to be benign and 20 (48.8%) malignant. IC was inconclusive in 5 (12.2%) cases. The sensitivity of IC was found to be 89.5% and specificity 82.35%. The positive predictive value of IC was 85%. The accuracy of IC for diagnosis of both benign and malignant tumors was found to be 75%. CONCLUSION: IC of STTs is a rapid and simple method of intraoperative diagnosis, and it can serve as a viable alternative to frozen section biopsy, particularly in rural settings.

A clinicopathological study of mediastinal masses operated in a tertiary care hospital in Eastern India in 3 years with special reference to thymoma.

INTRODUCTION: The mediastinum is the central portion of the thoracic cavity, limited by pleural cavities laterally, thoracic inlet superiorly, and the diaphragm inferiorly. Housing numerous organs, it is a veritable Pandora's box, within which various lesions may develop. This study was conducted to assess the epidemiologic profile, clinicoradiological features, cytological, and histopathological findings in patients presenting with mediastinal masses in a tertiary care hospital over a period of 3 years. MATERIALS AND METHODS: This is a retrospective study of cases presenting with mediastinal masses attending the Cardiothoracic Surgery Department of Medical College, Kolkata between May 2011 and April 2014. Detailed history, physical, and radiological findings were noted. Fine needle aspiration cytology (FNAC) was performed when feasible. Following surgery, histopathological, and immunohistochemical (IHC) examinations of the specimens were undertaken. RESULTS: Of the 22 cases included in our study, ten were anterior, seven middle, and five posterior mediastinal masses. Fifteen cases were male and seven were female. Thymic pathology was detected in seven cases, lymphoma in five, extragonadal germ cell tumor (GCT) in three, schwannoma and pericardial cyst in two cases each and neurofibroma, ganglioneuroma, and retrosternal thyroid in one case each. The age group of the patients for each diagnostic category was found to be of significance. FNAC was done in 15 cases. IHC was required for classification of lymphoma cases (CD45, CD15, CD30, CD20, CD3, Tdt, CD34, and Ki-67). CONCLUSION: This study reflects the incidence of different mediastinal masses in West Bengal with their clinicopathologic correlation.

Carcinosarcoma of ovary with its various immunohistochemical expression: Report of a rare case.

Ovarian carcinosarcoma is an extremely rare tumor with an incidence of <2%. A report of such a rare case in a 40-year-old multiparous woman is being presented here. The patient complained of abdominal pain and distension. Abdominal computed tomography revealed a variegated mass in the right adnexal region. The CA-125 level was 1635 U/ml. The patient underwent laparotomy and the tumor was removed. Microscopic examination of the tumor showed presence of both carcinomatous and sarcomatous elements. Immunohistochemical analysis revealed that the carcinomatous component was positive for cytokeratin and estrogen receptor and negative for progesterone receptor. The sarcomatous component was positive for vimentin. Ki-67 was positive in 60% cells. A final diagnosis of ovarian carcinosarcoma was rendered. This case is significant owing to extreme rarity of the tumor. Records of similar cases must be maintained for future reference with regard to impact of treatment protocol followed on prognosis.

Collecting duct carcinoma: a rare malignancy.

A 45-years old man complained of hematuria, and subsequent examination and ultrasonography revealed a mass in the left kidney. Nephrectomy was performed and macroscopically an ill-defined pale-cream, irregular mass was identified which occupied predominantly the renal medulla. Histopathologic examination showed slit like tubular ducts lined by atypical cuboidal to polygonal cells and a marked desmoplastic stromal reaction. The diagnosis of collecting duct carcinoma was made. Patient is now doing well after 11 months of follow up.

Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma.

CONTEXT: The diagnosis of papillary thyroid carcinoma (PTC) is based on nuclear features. These features may be present in focal areas in benign thyroid diseases and follicular adenoma (FA), leading to diagnostic difficulty. AIMS: To evaluate the expression and pattern of the distribution of cytokeratin 19 (CK19) in PTC and compare its reactivity with other neoplastic and non-neoplastic conditions to assess its potential as a useful marker for PTC. MATERIALS AND METHODS: Twenty two cases of papillary carcinoma (usual type, follicular and diffuse sclerosing variant), eight follicular adenomas, eight multinodular goiters (MNG) were collected for a period of two years and six months. Sections were taken from thyroidectomy specimens fixed in 10% buffered neutral formalin. Hematoxylin and eosin staining and immunohistochemical staining for CK19 were done using standard protocol. Results were semiquantitatively scored as follows: 1+ (<5% positively stained cells), 2+ (5-25%), 3+ (25-75%) and 4+ (>75%), and then analyzed. STATISTICAL ANALYSIS AND RESULTS: All 22 (100%) papillary carcinomas showed diffuse and strong (3+ and 4+) CK19 expression. Six out of eight (75%) FAs and four out of eight (50%) MNG were positive for CK19, but it was of weaker intensity (1+ and 2+) and focal in distribution. CONCLUSION: Focal CK19 staining may be found in benign disease, but diffuse and strong positivity is characteristic of PTC, which can be used in the diagnosis of PTC in lesions of equivocal morphological appearances.

A clinicopathological study of mediastinal masses operated in a tertiary care hospital in Eastern India in 3 years with special reference to thymoma.

Introduction: The mediastinum is the central portion of the thoracic cavity, limited by pleural cavities laterally, thoracic inlet superiorly, and the diaphragm inferiorly. Housing numerous organs, it is a veritable Pandora’s box, within which various lesions may develop. This study was conducted to assess the epidemiologic profile, clinicoradiological features, cytological, and histopathological findings in patients presenting with mediastinal masses in a tertiary care hospital over a period of 3 years. Materials and Methods: This is a retrospective study of cases presenting with mediastinal masses attending the Cardiothoracic Surgery Department of Medical College, Kolkata between May 2011 and April 2014. Detailed history, physical, and radiological findings were noted. Fine needle aspiration cytology (FNAC) was performed when feasible. Following surgery, histopathological, and immunohistochemical (IHC) examinations of the specimens were undertaken. Results: Of the 22 cases included in our study, ten were anterior, seven middle, and five posterior mediastinal masses. Fifteen cases were male and seven were female. Thymic pathology was detected in seven cases, lymphoma in five, extragonadal germ cell tumor (GCT) in three, schwannoma and pericardial cyst in two cases each and neurofibroma, ganglioneuroma, and retrosternal thyroid in one case each. The age group of the patients for each diagnostic category was found to be of significance. FNAC was done in 15 cases. IHC was required for classification of lymphoma cases (CD45, CD15, CD30, CD20, CD3, Tdt, CD34, and Ki‑67). Conclusion: This study reflects the incidence of different mediastinal masses in West Bengal with their clinicopathologic correlation.