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.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

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.

Renal Histopathological Changes in Coronavirus Disease 2019 Patients: A Systematic Review and Meta-analysis of Individual Patient Data.

The major targets of coronavirus disease 2019 (COVID-19) are the respiratory and immune systems. However, a significant proportion of hospitalized patients had kidney dysfunction. The histopathological surveys have principally focused on respiratory, hematopoietic, and immune systems, whereas histopathologic data of kidney injury are lacking. Our study aimed to summarize the renal histopathological findings in COVID-19 from the published case report and case series. We conducted a systematic searching of databases such as MEDLINE, EMBASE, and Cochrane Library for published reports of COVID-19 patients with renal histopathological changes from autopsy studies and from "for cause" indication biopsies. Included in our study are case reports and case series with extractable quantitative data on patient demographics such as age, sex, ethnicity, as well as data on renal function tests, their comorbidities, and biopsy to study the histopathological changes. Data were analyzed with Microsoft Excel. To evaluate the methodological quality, we chose the framework for appraisal, synthesis, and application of evidence suggested by Murad et al. Systematic searches of literature found 31 studies that fulfilled the eligibility criteria. These studies included a total of 139 cases, where individual case details including clinical and histopathological findings were available. The median age of the cases was 62 years with a male:female ratio of 2.5:1. Associated comorbidities were noted in 78.4% of cases. The majority of the cases had renal dysfunction with proteinuria which was documented in more than two-thirds of the cases. The histopathological findings observed the frequent tubular involvement manifested by acute tubular injury. Regarding glomerular pathology, collapsing glomerulopathy emerged as a distinct lesion in these patients and was noted among 46.8% of cases with glomerular lesions. A small subset of cases (4.3%) had thrombotic microangiopathy. Collapsing glomerulopathy emerged as a hallmark of glomerular changes among COVID-19 patients. Tubular damage is common and is linked to multiple factors including ischemia, sepsis among others. In the form of thrombotic microangiopathy seen in a subset of patients, vascular damage hints toward the hyper-coagulable state associated with the infection. The demonstration of viral particles in renal tissue remains debatable and requires further study.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Endocannabinoid System: A Multi-Facet Therapeutic Target.

Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions. Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson's disease, Huntington's disease, Alzheimer's disease and Tourette's syndrome could possibly be treated by drugs modulating endocannabinoid system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008. Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.