Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.

Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m2), Cyclophosphamide (600 mg/m2) with or without Taxane (75-175 mg/m2) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.

Efficacy, Safety, and Cost-Effectiveness of Healthium Theruptor Versus 3M Tegaderm Versus Plain Gauze Dressing for Wound Dressings Used in Abdominal and Joint Surgeries: A Prospective, Multicentric, Randomized Study.

Background In the realm of surgical and postoperative care, the application of wound dressings is a standard practice to facilitate healing, minimize infection risks, and offer a protective barrier against pathogens for optimal recovery. For instance, Theruptor is an active advanced wound care product with patented microbicidal technology. In the present study, we conducted a randomized clinical trial to compare the clinical efficacy and safety of Healthium Theruptor, 3M Tegaderm, and plain gauze dressings in patients undergoing abdominal and joint surgeries. Methodology This was a multicenter, prospective, three-arm, randomized, double-blind study conducted between April and November 2022 at three different sites in India, viz., All India Institute of Medical Sciences, Jodhpur; Mahatma Gandhi Medical College and Research Institute, Puducherry; and SRM Institute of Science and Technology, Chennai. A total of 210 patients were randomized to receive either of the following three interventions: Theruptor, Tegaderm, and plain gauze dressing (n = 70 each) based on computer-generated randomization sequences using sequentially numbered, opaque, sealed envelopes. Demographic data and surgery details were obtained and recorded at baseline. Parameters such as rate of wound healing, incidence of surgical site infections (SSIs), adverse events, product performance, and pain score were assessed and compared during the weekly follow-up visits until 28 days. In addition, wound assessments using the Stony Brook Scar evaluation scale, Cardiff Wound Impact Questionnaire, and Modified Hollander Wound Evaluation Scale were conducted to provide additional insights on the efficacy of the dressings (days 3, 7, 14, and 28). Lastly, the cost of wound management was assessed at the end of the study. The statistical analysis of the data was performed using a one-way analysis of variance followed by a Bonferroni post-hoc test on GraphPad software. Results All three dressings were equally effective in healing the wound and reducing the incidence of SSIs. The median healing time was estimated to be seven days. Further, no significant difference was observed in wound dehiscence, wound pain, clinical wound parameters, cosmetic assessment, and quality of life among the three groups (p > 0.05) during the follow-up visits. However, the product performance of Theruptor and Tegaderm was significantly better than plain gauze dressing in terms of ease of application (82.87% and 84.13% vs. 71.7%), ease of removal (83.09% and 83.67% vs. 70.79%), comfort to wear (82.59% and 84.47% vs. 72.83%), exudate management (84.35% and 85.7% vs. 77.23%), mean wear time in hours (65.57 and 65.92 vs. 49 hours), and mobility of the patient (p < 0.05). Further, the total cost of wound management with Theruptor dressing was significantly lower than with Tegaderm dressing (₹1117.2 ± 269.86 vs. ₹1474 ± 455.63; p < 0.0001). Conclusions Although all three dressings were equally safe and clinically efficacious, Theruptor was more cost-effective with better product performance. Thus, Theruptor may be a considerate option in the postoperative wound management of abdominal and joint surgeries.

Euglycemic diabetic ketoacidosis associated with SGLT2 inhibitors: A systematic review and quantitative analysis.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) rarely cause euglycemic diabetic ketoacidosis (euDKA) in diabetic patients. The aim was to identify demographic, clinical, and predisposing factors for euDKA from published case reports. Methods: A systematic review of published case reports of euDKA in patients receiving SGLT2 inhibitors and meta-analysis of clinical trials to quantify the risk ratio (RR) of DKA in patients receiving SGLT2 inhibitors. PubMed and EMBASE databases were searched for the case reports of and clinical trials from January 2010 to August 2020. Studies published in English language were included and other languages were excluded. Data related to patients' demography, clinical presentation, drug and dose of SGLT2 inhibitors, and concomitant medication were extracted. Incidence of diabetic ketoacidosis (DKA) extracted from clinical trials. Data related to demographic, clinical, and other parameters presented as ratios and proportions and incidence of DKA in RR using Review Manager 5.3. Results: Forty-seven of 160 reports with an aggregate of 77 patients were included in the analysis. The majority of the patients were females (67.53%), with T2DM and with gastrointestinal symptoms (58%). Surgery was the most common precipitating factor (n/N = 15/77). Canagliflozin (n/N = 34/77) was the commonest SGLT2 inhibitor reported along with metformin as the concomitant medication (63.6%). The pooled RR of DKA was 3.70 (95%CI 2.58, 5.29) and I2 = 0%. Conclusion: euDKA is commonly seen in middle-aged female, T2DM patients taking SGLT2 inhibitors along with metformin. The risk of DKA in patients receiving SGLT2 inhibitors increases by 3.7 times than the other medication.

Clinical characteristic, red blood cell indices, iron profile and prognosis of heart failure in females.

Background: Heart failure is a leading killer worldwide, with concurrent anaemia and iron deficiency portending sepulchral prognosis. Anaemia is rampant, with 53% prevalence in Indian females, but iron deficiency can be present even without anaemia. Therefore, this study was planned to determine the clinical profile, red blood cell indices, and effects of iron deficiency, on the course and prognosis of heart failure in Indian females. Materials and methods: This was a hospital-based observational study, conducted at a tertiary care teaching institute in India. Data from 147 females enrolled in the study between September 2017 to March 2020 was collected out of all patients enrolled in ongoing heart failure registry at the institute. Clinical characteristics at presentation, iron profile, red blood cell indices, treatment and mortality data was collected. Results: Mean age of the subjects (n = 147) was 53.31 ± 17.1 years with 55% non-rheumatic and 45% with rheumatic heart disease. The patients with rheumatic heart disease were younger, with a higher prevalence of atrial fibrillation. Non-rheumatic patients had a higher prevalence of CV risk factors like diabetes, hypertension, renal failure, more patients in NYHA IV, and 83% patients had LVEF ≤40%. Anaemia was present in 49%, however iron deficiency was present in 89% (absolute iron deficiency in 80% and functional iron deficiency in 9%) with no significant difference between rheumatic and non-rheumatic group. Red blood cell indices showed no significant difference across the spectrum of iron deficiency and anaemia, except lower mean corpuscular volume in patients with both iron deficiency and anaemia. The mean survival time was 840 days, with no significant difference between groups. There was significantly higher mortality in patients with iron deficiency (log rank 0.045). Conclusion: Iron deficiency-with or without anaemia-is very high in Indian females, worsening survival in heart failure. Proper diagnosis with iron supplementation will improve the prognosis.

Efficacy of procalcitonin and pentraxin-3 as early biomarkers for differential diagnosis of pleural effusions.

OBJECTIVES: Pleural effusion, defined as an abnormal accumulation of fluid in pleural space, can be of two types: transudative and exudative. The primary aim of the study was to assess the predictive accuracy of procalcitonin (PCT) and pentraxin-3 (PTX-3) in comparison to other biochemical markers such as C-reactive protein (CRP), and adenosine deaminase (ADA) in the differential diagnosis of pleural effusions. METHODS: A cross-sectional analytical study was conducted on patients with pleural effusion. Multiple comparisons and receiver-operating characteristics (ROC) analyses were made to evaluate the diagnostic significance of biochemical markers. RESULTS: Sixty-six patients with exudative pleural effusion classified as malignant, tuberculous, and parapneumonic effusions (malignant pleural effusion [MPE], tuberculous [TPE], and parapneumonic [PPE]) were included. Significant differences in pleural fluid levels in both PCT (p-value: 0.001) and PTX-3(p-value: 0.001), as well as serum levels of PCT (p-value: 0.001), were observed between the three groups. ROC analysis showed both PTX-3 and PCT having favorable discrimination ability with high sensitivity (≥90%) and specificity to predict PPE from TPE and MPE. CONCLUSIONS: Evaluation of serum and pleural fluid PCT and levels of PTX-3 in the pleural fluid may be used as an early biomarker to differentiate the etiology of pleural effusion.

Is it time to reconsider prophylactic antimicrobial use for hematopoietic stem cell transplantation? a narrative review of antimicrobials in stem cell transplantation.

INTRODUCTION: Hematopoietic Stem Cell Transplantation (HSCT) is a life-saving procedure for multiple types of hematological cancer, autoimmune diseases, and genetic-linked metabolic diseases in humans. Recipients of HSCT transplant are at high risk of microbial infections that significantly correlate with the presence of graft-versus-host disease (GVHD) and the degree of immunosuppression. Infection in HSCT patients is a leading cause of life-threatening complications and mortality. AREAS COVERED: This review covers issues pertinent to infection in the HSCT patient, including bacterial and viral infection; strategies to reduce GVHD; infection patterns; resistance and treatment options; adverse drug reactions to antimicrobials, problems of antimicrobial resistance; perturbation of the microbiome; the role of prebiotics, probiotics, and antimicrobial peptides. We highlight potential strategies to minimize the use of antimicrobials. EXPERT OPINION: Measures to control infection and its transmission remain significant HSCT management policy and planning issues. Transplant centers need to consider carefully prophylactic use of antimicrobials for neutropenic patients. The judicious use of appropriate antimicrobials remains a crucial part of the treatment protocol. However, antimicrobials' adverse effects cause microbiome diversity and dysbiosis and have been shown to increase morbidity and mortality.

Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications.

Objectives: Remdesivir has shown promise in the management of patients with COVID-19 although recent studies have shown concerns with its effectiveness in practice. Despite this there is a need to document potential adverse drug events (ADEs) to guide future decisions as limited ADE data available before the COVID-19 pandemic. Methods: Interrogation of WHO VigiBase® from 2015 to 2020 coupled with published studies of ADEs in COVID-19 patients. The main outcome measures are the extent of ADEs broken down by factors including age, seriousness, region and organ. Results: A total 1086 ADEs were reported from the 439 individual case reports up to July 19, 2020, in the VigiBase®, reduced to 1004 once duplicates were excluded. Almost all ADEs concerned COVID-19 patients (92.5%), with an appreciable number from the Americas (67.7%). The majority of ADEs were from males > 45 years and were serious (82.5%). An increase in hepatic enzymes (32.1%), renal injury (14.4%), rise in creatinine levels (11.2%), and respiratory failure (6.4%) were the most frequently reported ADEs. Conclusions: Deterioration of liver and kidney function are frequently observed ADEs with remdesivir; consequently, patients should be monitored for these ADEs. The findings are in line with ADEs included in regulatory authority documents.

The Double Burden of the COVID-19 Pandemic and Polypharmacy on Geriatric Population - Public Health Implications.

COVID-19 pandemic is inducing acute respiratory distress syndrome, multi-organ failure, and eventual death. Respiratory failure is the leading cause of mortality in the elderly population with pre-existing medical conditions. This group is particularly vulnerable to infections due to a declined immune system, comorbidities, geriatric syndrome, and potentially inappropriate polypharmacy. These conditions make the elderly population more susceptible to the harmful effects of medications and the deleterious consequences of infections, including MERS-CoV, SARS-CoV, and SARS-CoV-2. Chronic diseases among elderlies, including respiratory diseases, hypertension, diabetes, and coronary heart diseases, present a significant challenge for healthcare professionals. To comply with the clinical guidelines, the practitioner may prescribe a complex medication regimen that adds up to the burden of pre-existing treatment, potentially inducing adverse drug reactions and leading to harmful side-effects. Consequently, the geriatric population is at increased risk of falls, frailty, and dependence that enhances their susceptibility to morbidity and mortality due to SARS-CoV-2 respiratory syndrome, particularly interstitial pneumonia. The major challenge resides in the detection of infection that may present as atypical manifestations in this age group. Healthy aging can be possible with adequate preventive measures and appropriate medication regimen and follow-up. Adherence to the guidelines and recommendations of WHO, CDC, and other national/regional/international agencies can reduce the risks of SARS-CoV-2 infection. Better training programs are needed to enhance the skill of health care professionals and patient's caregivers. This review explains the public health implications associated with polypharmacy on the geriatric population with pre-existing co-morbidities during the COVID-19 pandemic.

Monoclonal Antibodies: A Review.

BACKGROUND: Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb was the first FDA approved therapeutic MAb for the prevention of kidney transplant rejection. Since its approval in 1986, there has been a decline in further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of lowgrade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, the rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically. As of March 2017, FDA has approved approximately 60 therapeutic MAbs which are currently under evaluation in various phases of clinical trials. OBJECTIVE: MAbs are approved for the treatment of diseases belonging to various systems like cardiovascular, respiratory, hematology, kidney, immunology and oncology. MAbs are approved for the treatment of orphan diseases or indications such as paroxysmal nocturnal hemoglobinuria as well as cancers and multiple sclerosis where hundreds of patients are treated and even diseases such as breast cancer, asthma and rheumatoid arthritis where millions are being treated. This review focuses briefly on types, molecular targets, mechanism of actions and therapeutic indications of FDA approved MAb products that are currently available in the market. CONCLUSION: With the advent of fully human MAbs, the efficacy and safety have improved in the treatment of various cardiovascular, cancer, respiratory, hematology, autoimmune diseases and infections. The introduction of biosimilars will increase the affordability and utilization of MAbs in the treatment of various diseases.

Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV. METHODS: We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs). RESULTS: Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47-1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39-2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings. CONCLUSIONS: Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.

Drug advertisements published in Indian Medical Journals: Are they ethical?

CONTEXT: It is observed in studies done for western medical journals that insufficient information related to drug is usually provided in the drug advertisements published in them. AIMS: As data for advertisements published in Indian Medical Journals were lacking, this study was designed with the aim of evaluating drug advertisements published in Indian Medical Journals for adequacy of information on drug and references given to support the claim made in the advertisements. SETTINGS AND DESIGN: Cross-sectional survey. METHODS AND MATERIALS: All medical journals related to clinical practice subscribed by the Central Library of Government Medical College, Surat, (Indian Journal of Pediatrics [IJP], Indian Pediatrics [IP], Journal of the Association of Physicians of India [JAPI], Journal of Indian Medical Association [JIMA], Indian Journal of Critical Care Medicine [IJCCM], Indian Journal of Medical and Pediatric Oncology [IJMPO], Indian Journal of Gastroenterology [IJG], Indian Journal of Ophthalmology [IJO], and Journal of Obstetrics and Gynecology of India [JOGI] were evaluated for adequacy of reporting of various parameters in drug advertisements published in these journals on the basis of "World Heath Organization (WHO)" criteria. References mentioned to support claims were also evaluated. STATISTICAL ANALYSIS USED: Descriptive statistics was used to describe data as frequencies, percentages, and 95% confidence interval around the percentage. RESULTS: Generic name was mentioned in 90% advertisements. Indications were mentioned in 84% advertisements. Dose, precautions, and contraindications were mentioned in 24%, 17%, and 16% advertisements, respectively. Adverse effects and postal address of pharmaceutical company was mentioned in 19% and 74% advertisements, respectively. Price was mentioned in only 5% advertisements. Only 28% claims were supported by references. Most common references were Journal articles (75%). CONCLUSION: Drug advertisements published in Indian Medical Journals are poor in reporting various parameters according to WHO criteria.