A randomized, placebo controlled, double blinded, parallel group clinical study to evaluate the efficacy and safety of AEV01 along with standard care for elderly patients with mild COVID-19.

BACKGROUND: While several drugs are in the pipeline for treatment of various grades of COVID-19 disease, none of them have shown promise until now. Medicinal plants are crucial in developing and developed countries for their primary and basic health needs owing to better tolerability, superior compatibility with human body and having lesser side effects. OBJECTIVE: To test adjuvant effect of AEV01, a patented herbal extract of kutki (Picrorhiza kurroa), in mild COVID19 in elderly patients at risk of complications and aging immunity. METHODS: A prospective, phase 3, randomized, multicentric, placebo controlled double blinded parallel group interventional trial was conducted in elderly patients aged above 50 years diagnosed as COVID-19 with mild symptoms. 70 patients were randomized into two groups to receive AEV01 capsule (100 mg) and placebo respectively thrice daily for 30 days along with standard care of treatment as per national (WHO/ICMR) guidelines in both the groups. Clinical improvement timelines and corresponding scores using 8-point ordinal scale and NEWS were assessed for efficacy and safety of AEV01 in COVID-19 patients. RESULTS: AEV01 group showed a significant improvement (p = 0.0001) in the normalization of the SpO2 rate and relief from cough. There was also significant difference in time to recovery, with patients in the AEV01 drug treated group recovering in 4.5 days as compared to Placebo in 9.1 days. ESR, LDH, serum ferritin, Neutrophil-Lymphocyte ratio (NLR), TNF- alpha, IL-6 and CD4 cell counts, which are considered as prognostic markers in COVID-19 infected patients, showed a significant improvement in patients treated with AEV01. The AEV01 drug treated group showed significant clinical improvement in the 8-point ordinal scale severity rating and National Early Warning Score (NEW) Score from day 3 onwards which continued up to end of study. CONCLUSION: AEV01 has shown a significant improvement in clinical and laboratory parameters. There was also reduction in the progression of the COVID-19 disease in unvaccinated elderly patients from mild to moderate when treated at an earlier stage.

Identification of Probucol as a candidate for combination therapy with Metformin for Type 2 diabetes.

Type 2 Diabetes (T2D) is often managed with metformin as the drug of choice. While it is effective overall, many patients progress to exhibit complications. Strategic drug combinations to tackle this problem would be useful. We constructed a genome-wide protein-protein interaction network capturing a global perspective of perturbations in diabetes by integrating T2D subjects' transcriptomic data. We computed a 'frequently perturbed subnetwork' in T2D that captures common perturbations across tissue types and mapped the possible effects of Metformin onto it. We then identified a set of remaining T2D perturbations and potential drug targets among them, related to oxidative stress and hypercholesterolemia. We then identified Probucol as the potential co-drug for adjunct therapy with Metformin and evaluated the efficacy of the combination in a rat model of diabetes. We find Metformin-Probucol at 5:0.5 mg/kg effective in restoring near-normal serum glucose, lipid, and cholesterol levels.

Evaluation of Cord Blood - Haematological Scoring System as an Early Predictive Screening Method for the Detection of Early Onset Neonatal Sepsis.

BACKGROUND: Sepsis is one of the major causes of neonatal morbidity and mortality. Early recognition and diagnosis of neonatal sepsis are difficult because of the variable and non-specific clinical presentation of this condition. Hence, there is a need for early predictive screening method for neonatal sepsis. OBJECTIVES: To evaluate the role of Cord blood Haematological Scoring System as an early predictive screening method for detection of early onset neonatal sepsis and also to identify the neonates who are at risk of developing neonatal sepsis using cord blood. SETTINGS AND DESIGN: The present prospective cross-sectional study was conducted by taking 153 cord blood samples of full term newborns immediately after delivery in the hospital. Pre-term, still birth and emergency deliveries were excluded from the study. MATERIALS AND METHODS: The cord blood was collected and analysed for various Haematological parameters like Total leucocyte count, Absolute Neutrophil count, Immature to mature Neutrophil ratio, immature to mature ratio, Neutrophil morphology, nucleated erythrocytes, platelet count, micro erythrocyte sedimentation rate. Blood cultures were performed as gold standard for diagnosing neonatal sepsis. STATISTICAL ANALYSIS: Chi-square test, Risk ratio, risks in exposed and risk in unexposed were performed. RESULTS: Of 153 newborns for analysis, 59 (38.56%) developed sepsis. The haematological scoring system found that an abnormal immature to total neutrophil ratio, Neutropenia, micro erythrocyte sedimentation rate followed by an abnormal immature to mature neutrophil ratio were the most sensitive indicators in identifying infants with sepsis. The study also found that higher the score, the greater the certainty of sepsis being present. CONCLUSION: The haematological scoring system using cord blood can be considered as an early predictive screening method for detection of early onset neonatal sepsis. Identifying the risk of developing sepsis early can prevent morbidity and mortality of the neonates.

Primary papillary carcinoma of the thyroid arising in a branchial cyst: case report and review of the literature.

We report a case of papillary carcinoma of the thyroid that arose in a branchial cyst. The patient, a 45-year-old woman, presented with a left lateral neck mass of 3 months' duration. The cyst was removed intact. Because we could not rule out the possibility that a small primary malignancy was present within the gland, we performed a total thyroidectomy; however, no occult primary tumor of the thyroid was found. The patient was placed on thyroid hormone replacement therapy, and she was well at 2 years of follow-up. We briefly review the literature regarding the possible embryologic origin of such a phenomenon and the role of fine-needle aspiration cytology in differentiating a branchial cyst from a metastatic lymph node. To the best of our knowledge, this is only the 11th reported case of a thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst, and the second such report from India.

Rapid detection of malaria parasite by toluidine blue method: a new staining method.

BACKGROUND: Malaria is a commonest mosquito-borne infectious disease worldwide. Early identification and management of malaria prevents complications and mortality. Identification of the malaria mainly relies on detection of the parasite on blood smears. The present study was conducted to compare Toluidine blue method with Leishman method for detection of malaria parasite and also to study the efficacy and advantages of using Toluidine blue method. MATERIALS AND METHODS: In 540 consecutive patients with clinical suspicion of malaria, peripheral smears were prepared. Smears were processed for both conventional Leishman method and Toluidine blue method simultaneously. The significance of Toluidine blue method over Leishman method was analyzed using Chi-square (χ(2)) test. RESULTS: Out of 540 smears, 28.3% (153/540) were positive for malaria parasite on conventional Leishman method, while the smear positivity was more by Toluidine blue method to 33.3% (180/540) [P value < 0.01]. The remaining 66.67% (360/540) were negative by both Toluidine blue method and conventional Leishman method. CONCLUSION: The Toluidine blue method is simple, rapid, inexpensive, and easily available. The implementation of Toluidine blue method clearly improves microscopic detection of malaria parasite and can be a useful contribution to routine hematology even at rural health sectors.

Bilateral congenital cystic adenomatoid malformation, stocker type III with associated findings and review of literature.

Congenital cystic adenomatoid malformation (CCAM) of the lung, Stocker's type III is a rare anomaly characterized by replacement of normal pulmonary tissue with cysts of variable size and distribution. We report here a 16-week stillborn fetus with Stocker's type III bilateral CCAM involving the entire lungs. The additional associated malformations included collapsed nasal bridge, low set ears, malformed ears, absence of neck folds, absence of nipples and areolas, tracheal stenosis, fetal hydrops and small heart. The pathogenesis, radiological findings, pathological findings and prognosis of CCAM are discussed along with review of literature.

Clinicopathological study of itchy folliculitis in HIV-infected patients.

BACKGROUND: Itchy folliculitis are pruritic, folliculo-papular lesions seen in human immunodeficiency virus (HIV)-infected patients. Previous studies have shown that it was impossible to clinically differentiate between eosinophilic folliculitis (EF) and infective folliculitis (IF). Also, attempts to suppress the intense itch of EF were ineffective. AIMS: The present study is aimed at correlating clinical, histopathological and immunological features of itchy folliculitis in HIV patients along with their treatment. METHODS: The present prospective study lasted for 36 months (September, 2005 to August, 2008) after informed consent, data on skin disorders, HIV status and CD4 count were obtained by physical examination, histopathological examination and laboratory methods. RESULTS: Of 51 HIV-positive patients with itchy folliculitis, the predominant lesion was EF in 23 (45.1%) followed by bacterial folliculitis in 21 (41.2%), Pityrosporum folliculitis in five (9.8%) and Demodex folliculitis in two (3.9%) patients. The diagnosis was based on characteristic histopathological features and was also associated with microbiology confirmation wherever required. EF was associated with a lower mean CD4 count (180.58 +/- 48.07 cells/mm3, P-value < 0.05), higher mean CD8 count (1675.42 +/- 407.62 cells/mm3) and CD8/CD4 ratio of 9.27:1. There was significant reduction in lesions following specific treatment for the specific lesion identified. CONCLUSION: Clinically, it is impossible to differentiate itchy folliculitis and therefore it requires histopathological confirmation. Appropriate antimicrobial treatment for IF can be rapidly beneficial. The highly active antiretroviral therapy along with Isotretinoin therapy has shown marked reduction in the lesions of EF. Familiarity with these lesions may help in improving the quality of lives of the patients.

Histopathological study of pruritic papular eruptions in HIV-infected patients in relationship with CD4, CD8 counts.

BACKGROUND: Pruritic papular eruptions (PPE) are common cutaneous manifestations in HIV-infected patients. Their frequencies, patterns and associated factors vary from region to region. There is no clear consensus on the etiology of PPE, the exact spectrum of the condition, the pathologic findings, or treatment. The present study is aimed at documenting the histopathological patterns of PPE, and their relation with CD4, CD8 counts in HIV-infected patients. MATERIALS AND METHODS: The present study lasted for 12 months (September 2005 to August 2006). After informed consent, data on skin disorders, HIV status, CD4 and CD8 counts were obtained by physical examination and laboratory methods. RESULTS: Of the 36 HIV-infected patients with clinical diagnosis of PPE, the most common histopathological patterns were prurigo simplex and eosinophilic folliculitis. The mean CD4 count of PPE was 186.49 cells/mm3 with mean CD8 count of 619.60 cells/ mm3, and the CD4:CD8 ratio was 0.32. Patients with prurigo simplex had significantly lower mean CD4 counts (50.36 +/- 30.67 cells/cmm 3 , P < 0.001) while in eosinophilic folliculitis, the mean CD8 counts were higher (1239.77 +/- 402.30 cells/cmm3). CONCLUSION: We conclude that histopathology helps in specifying the pattern of PPE and also indicates underlying immunosuppression and can be a marker of advanced HIV infection. Thus, correlation between the histopathology and immunology findings helps to know the disease process.

Improved microscopical detection of acid-fast bacilli by the modified bleach method in lymphnode aspirates.

OBJECTIVES: To improve the smear microscopy for detection of acid-fast bacilli (AFB) in fine needle aspiration cytology (FNAC) of lymph node using the bleach method and also to compare this with cytological diagnosis and the conventional Ziehl-Neelsen (ZN) method. STUDY DESIGN: In 99 consecutive patients with clinical suspicion of tuberculosis (TB) presenting with lymphadenopathy, FNACs were performed. Smears from the aspirates were processed for routine cytology and the conventional ZN method. The remaining material in the needle hub and/or the syringe was used for the bleach method. The significance of the bleach method over the conventional ZN method and cytology was analyzed using the chi2 test. RESULTS: Of 99 aspirates, 93 were studied and the remaining six were excluded from the study due to diagnosis of malignancy in 4.04% (4/6) and inadequate aspiration in 2.02% (2/6). Among the 93 aspirates, 33.33% (31/93) were positive for AFB on conventional ZN method, 41.94% (39/93) were indicative of TB on cytology and the smear positivity increased to 63.44% (59/93) on bleach method. CONCLUSION: The bleach method is simple, inexpensive and potent disinfectant, also limiting the risk of laboratory-acquired infections. The implementation of the bleach method clearly improves microscopic detection and can be a useful contribution to routine cytology.

Comparison of the modified fluorescent method and conventional Ziehl-Neelsen method in the detection of acidfast bacilli in lymphnode aspirates.

OBJECTIVES: The objectives were to correlate the modified fluorescent method with the conventional Ziehl-Neelsen (ZN) method for the detection of acid-fast bacilli (AFB) and, also to study the efficacy and advantages of using the auramine-rhodamine stain on lymph node aspirates under fluorescent microscopy. METHODS: In 108 consecutive patients with a clinical suspicion of tuberculosis (TB) presenting with lymphadenopathy, fine needle aspirations were performed. Smears from the aspirates were processed for routine cytology, the conventional ZN method, and the modified fluorescent method. The significance of the modified fluorescent method over the conventional ZN method was analyzed using the chi-square test. RESULTS: Out of 108 aspirates, 102 were studied and remaining 6 were excluded from the study due to diagnosis of malignancy in 4.04% (4/6) and inadequate aspiration in 2.02% (2/6). Among the 102 aspirates, 44.11% (45/102) were positive for AFB on the conventional ZN method, 58.9% (60/102) were indicative of TB on cytology, while the smear positive increased to 81.37% (83/102) on the modified fluorescent method. CONCLUSIONS: Fluorescent microscopy has the advantage of speed and ease of screening, and reduces observer fatigue. The modified fluorescent method was found to be more advantageous than routine cytology and conventional ZN method, particularly in paucibacillary cases. The bacillary positivity rates were higher in the modified fluorescent method than in the ZN method. Hence, the modified fluorescent method can be an adjuvant when used with routine cytology for the identification of AFB.

Total antioxidant capacity--a novel early bio-chemical marker of oxidative stress in HIV infected individuals.

BACKGROUND: Oxidative stress induced by the production of reactive oxygen species may play a critical role in the stimulation of HIV replication and the development of immunodeficiency. This study was conducted as there are limited and inconclusive studies on the significance of a novel early marker of oxidative stress which can reflect the total antioxidant capacity in HIV patients, METHODS: Total antioxidant capacity (TAC) and lipid peroxidation were evaluated in 50 HIV-1 seropositive patients (including HIV-1 symptomatics and asymptomatics). Controls included 50 age and sex matched and apparently healthy HIV-1 seronegative subjects. Serum malondialdehyde (MDA), Total antioxidant capacity [TAC] (by ferric reducing antioxidant power assay), vitamin E, vitamin C and superoxide dismutase (SOD) enzyme activity were estimated among controls and cases. Statistical comparisons and correlations at 5% level of significance were determined. RESULTS AND DISCUSSION: The mean MDA concentrations were significantly elevated in both HIV-1 asymptomatic (CD4+ count > 500 cells/microliter) and HIV-1 symptomatic (CD4+ count <500 cells/microliter) groups (Mean +/- S.D values were 2.2 +/- 0.7 nmol/ml and 2.8 +/- 0.8 nmol/ml respectively) when compared with the control group (mean +/- S.D value was 0.9 +/- 0.2 nmol/ml) (p < 0.01). The mean TAC of HIV-1 asymptomatic and HIV-1 symptomatic (Mean +/- S.D values were 754.6 +/- 135.6 micromol/L and 676.6 +/- 154.1 micromol/L respectively) patients were significantly reduced compared with the control group (Mean +/- S.D value was 1018.7 +/- 125.6 micromol/L) (p < 0.01). Also, there were significantly decreased levels of vitamin E, vitamin C and SOD among HIV-1 seropositive patients(controls > asymptomatic > symptomatic) compared to controls (p < 0.01). TAC showed significant negative correlation with MDA among HIV-1 infected patients (p < 0.01). CONCLUSION: Our results clearly show that severe oxidative stress occurs in the HIV-1 seropositive patients in comparison with controls, and increases significantly with the progression of disease, i.e. HIV-1 symptomatics > asymptomatics > controls. TAC can be used as a novel early bio-chemical marker of oxidative stress in HIV-1 infected patients which may result in reduced tissue damage by free radicals and help to monitor and optimize antioxidant therapy in such patients.

Clinicopathologic profile of significant cervical lymphadenopathy in children aged 1-12 years.

OBJECTIVE: To emphasize the role of fine needle aspiration cytology (FNAC) in etiologic workup in significant cervical lymphadenopathy in children. STUDY DESIGN: A total of 336 consecutive children, aged 1 month to 12 years, with significant cervical lymphadenopathy were subjected to FNAC. Children on empirical/specific therapy for lymphadenopathy for >2 months and children with lymphadenopathy other than cervical region were excluded from this study. RESULTS: Of 324 cases, the cytomorphologic features observed were reactive lymphadenitis in 58.02% of cases, granulomatous lymphadenitis in 30.55%, suppurative lymphadenitis in 7.10% and malignancies in 5.62%. The remaining 3. 57% of cases were excluded because of inadequate aspiration. The most common cause diagnosed was tuberculosis in 29.01% of cases followed by chronic tonsillopharyngitis in 28.39%, suppurative lymphadenitis in 7.10%, human immune deficiency infection in 5.55% and malignancies in CONCLUSION: FNAC is an important diagnostic modality for the etiologic workup in significant cervical lymphadenopathy in children. It is almost as sensitive and specific as excision lymph node biopsy when an adequate aspirate is examined by expert eyes.

Isolated frontal sinusitis due to Pseudallescheria boydii.

We report a case of recurrent sino-nasal fungal infection due to Pseudallescheria boydii (P. boydii) in a 33-year-old diabetic woman. It is very essential to identify P. boydii, as Miconazole is the only antifungal drug of choice. However, histological examination of the specimen for clinching clues such as intercalary conidia and chlamydoconidia plays an important role in identifying P. boydii, when fungal culture fails to yield the growth. On follow-up, the woman responded for the treatment with Miconazole and is free of symptoms, with no recurrence after 6 months.

Co-infection of molluscum contagiosum virus and cryptococcosis in the same skin lesion in a HIV-infected patient.

A young human immunodeficiency virus-infected man was admitted in unconsciousness state. Few papular skin lesions resembling molluscum contagiosum (MC) were present on the face. He was found to have cryptococcal meningitis using India ink preparation of cerebrospinal fluid. Histopathological examination of skin lesion revealed the presence of capsulated yeast forms of Cryptococcus within the lesion of MC. The co-existence of MC and cryptococcosis in the same cutaneous lesion is rare, and it could be because of immunosuppression (low CD4 count).

Primary mucinous adenocarcinoma in an ileostomy with adjacent skin invasion: a late complication of surgery for ulcerative colitis.

INTRODUCTION: Adenocarcinoma of the ileostomy after colectomy performed for non-neoplastic condition are relatively uncommon. Mucinous adenocarcinoma at an ileostomy site represents a late complication of total colectomy performed for ulcerative colitis. CASE REPORT: We here report a case of mucinous adenocarcinoma of the mucocutaneous junction at the ileostomy site with adjacent skin invasion occurring 35 years after total colectomy for ulcerative colitis. Wide excision with refashioning of the ileostomy was performed.