Platelet count and Superoxide Dismutase as a marker for severity of Plasmodium infection.

Background: Malaria continues to be an important public health problem in developing and underdeveloped countries with high morbidity and mortality. It continues to be one of the major public health problems in India. Plasmodium vivax is the major parasite type causing malaria and Plasmodium falciparum is the major cause of serious and complicated disease. Haematological abnormality which is most commonly seen in malaria is thrombocytopenia followed by anaemia. Identification of predictors of disease severity is critical to improve patient care. This study was undertaken to evaluate the severity of thrombocytopenia and erythrocyte SOD level in infections by plasmodium vivax, falciparum and mixed infection.Methods: A hospital based cross sectional study done on confirmed cases of malaria in a tertiary care hospital in costal Karnataka. All patients tested positive for malaria (either by rapid diagnostic test or peripheral smear) were included and patients presenting with fever who were but treated empirically for malaria were excluded in the study. The type of malarial infection was diagnosed with QBC and thin peripheral smear method; platelet count was done by automated cell counter and estimation of superoxide dismutase (SOD) by nitro blue tetrazolium chloride reduction method.Results: A total of forty infected malaria patients were evaluated. The age range of the infective patients were between 15 to 70 years. Males were more commonly affected than females in the ratio of 5.6:1. The most common type of malaria infection was from P. vivax and mixed infection (40% each) followed by P. falciparum (20%). Majority (50%) of the patient had severe infection followed by mild infection (35%) and moderate infection. The mean platelet count was 1,14,250/cu mm in P.falciparum, 85,000/cu mm in P.vivax infection and 60,625/cu mm in mixed infection. The mean platelet count was least (56,181/cu mm) in severe infective patients than in moderate (91,666/cu mm) and mild (1,21,500/cu mm) infections. The SOD levels was reduced more in P. vivax (26.43U/mg Hb) and mixed infection (20.96U/mg Hb) than P.falciparum (32.74U/mg Hb). SOD levels were proportionally low in severe infection (14.94U/mg Hb), when compared to moderate (20.35 U/mg Hb) and mild infection (32.19 U/mg Hb).Conclusions: Anaemia and thrombocytopenia are the most frequent haematological complications associated malaria. Thrombocytopenia is associated with increase in parasite density and severity of the infection, its more common in P.vivax and mixed infection than P.falciparum infection. The SOD level substantially reduces depending on the severity of malaria. Thrombocytopenia and reduced SOD level is a powerful predictor of disease severity. These parameters could be useful in the clinical approach of patients with malaria for prompt timely initiation of anti-malarial therapy and reduce the mortality

Exaggerated placental site reaction: case report of a rare benign trophoblastic lesion

Exaggerated placental site is a rare benign non-neoplastic trophoblastic lesion in which the intermediate trophoblastic cells extensively infiltrate into the endometrium and the underlying myometrium. The importance of this lesion lies in that the cells of this lesion display an identical morphological and immunophenotypic profile to the intermediate trophoblastic cells found placental site trophoblastic tumour, which are closely related neoplastic lesions Also differentials for this lesion are placental site nodule, choriocarcinoma and epithelioid trophoblastic tumour all of which have varied lines of treatment and interventions. We present a rare case of an exaggerated placental site reaction in a lady, who was in her first trimester of pregnancy and presented with signs of a septic abortion

A Tale of 5Ms: Massive Uterine Leiomyoma Mimicking Ovarian Malignancy along with Multiple Fibroids Displaying Multiple Degenerations

Background: Leiomyomas are by far the commonest uterine neoplasms in the female reproductive age group. Giant leiomyomas are quite scarce and when longstanding tend to undergo various degenerations owing to decreased blood supply which on imaging may simulate malignancy owing to compromised blood supply and may simulate malignancy on imaging.Case Presentation: We present a case of a 48-year-old post-menopausal multiparous woman complaining of intermittent lower abdominal pain for a month. Suspected as an ovarian tumor clinically and on ultrasound, this was seconded by raised serum CA125 levels. Histopathological examination gave a definitive diagnosis of a giant uterine leiomyoma along with multiple fibroids exhibiting multiple degenerations.Conclusion: Degenerated leiomyomas can masquerade malignancy and hence should be one of the first differentials in women of reproductive age group presenting with complex abdominopelvic masses

Post salpingectomy intraluminal endometriosis in a premenopausal lady - an incidental finding often paid less attention to

Endometriosis of the fallopian tube is often incidentally picked up in hysterectomy specimens that are sent for histopathological examination for other obvious pathological conditions. Post-salpingectomy endometriosis is one such entity that is known to occur in the tip of the proximal stump of the fallopian tube years after tubal ligation. As mere visualization of the endometriotic lesions is inadequate for an accurate diagnosis, histopathologic analysis of the biopsy samples becomes mandatory for confirmation. We report a case of post salpingectomy endometriosis which was incidentally discovered in a peri menopausal lady who was operated for multiple fibroids of the uterus. This case not only highlights an entity which is challenging to visualize radiologically and suspect clinically, but is also underrecognized, as very little attention is given to the fallopian tube during routine grossing.

Scleroderma: a case report

Scleroderma is systemic multi organ autoimmune disorder characterized by hardening of skin. Also known as systemic sclerosis. Estimated annual incidences of approximately 19 cases per million persons. The limited skin disease has a 10-year survival rate of 71%, whereas those with diffuse skin disease have a 10-year survival rate of just 21%. Risk is higher in women than men and peak in individuals aged 30-50 years. It has no definitive treatment. It may be limited or diffuse depending upon manifestations of symptoms or signs affecting internal organs especially lungs, heart, or kidney. We report a case of scleroderma with pulmonary hypertension and interstitial lung disease in our hospital who presented with tightening of skin, joint pain, dysphagia, and breathlessness. On examination skin appeared dark, shiny, and tight, with loss of hair, paraesthesia and digital ulceration. Patient also has history of Raynaud's phenomenon. On investigation, Scl-70 and ANA (antinuclear antibodies) by enzyme immunoassay came positive. HRCT thorax was suggestive of interstitial fibrosis and PFT revealed moderate restriction. On 2D echocardiography, mild pulmonary hypertension was present while barium swallow showed motility disorder involving oesophagus. On view of extensive systemic involvement like skin, respiratory system, gastrointestinal system and heart, we would like to present this rare disorder

Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Blood donation amidst the COVID pandemic: knowledge, attitude and practice of non-medical professionals

Background The COVID-19 pandemic has affected blood transfusion services globally. A drastic reduction in blood donation has been observed with potential donors hindered by apprehension and confusion. This study was conducted to assess knowledge, attitude and practice related to blood donation among non-medical working professionals, with an emphasis on donation following COVID-19 infection and vaccination