GENERAL TREATMENT PROTOCOL OF POISONING AND TWENTY FOUR TREATMENT MODALITIES BY ACHARYA CHARAK - A REVIEW

Ayurveda has its own way of approach towards the management of Visha (Poison), Agadtantra is a special branch of Ashtang Ayurveda having its own importance in Visha Chikitsa. A general principle of treatment of poisoning is explained in Ayurvedic Samhitas (Treatises) like Charaka, Sushruta and Vagbhata. Acharya Charak has explained Twenty four modalities in the treatment of poisoning irrespective of animate or inanimate poisoning. Other scholars have stated specific treatment in the poisoning cases but still 24 modalities retains its importance. Toxicology also explains general treatment protocol for management of poisoning. The Protocol consists of vital establishment, removal of poison, use of antidote, general and psychiatric care of patient. But due to complexity of poisoning cases; General Treatment protocol becomes the guideline for the further management. When we compare both Ayurveda and modern medicine with respect to this aspect, we find that all these principles which are suggested by modern medicine are already described in Ayurvedic Samhitas before thousands of years. Chaturvimshati Upakrama (24 modalities) are like the treatment principle which directs the actual treatment regime in individual cases. General treatment protocol of poisoning is the modern replica of Acharya Charak’s Chaturvimshati Upakarama. A comparison of twenty four modalities with the general treatment protocol of poisoning is attempted in this review article

The safety, tolerability and efficacy of LP-10 in subjects with refractory moderate to severe hemorrhagic cystitis: Phase 2a multicenter dose escalation clinical trial.

e24064 Background: Hemorrhagic Cystitis (HC), a rare but highly morbid disease for which there are currently no FDA approved treatments, can occur in cancer survivors including patients with prostate cancer, cervical/uterine cancer and colon cancer. Lipella Pharmaceuticals received orphan disease designation for HC, and recently completed a phase 2a clinical trial of LP-10 (intravesical tacrolimus) for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study (clinicaltrials.gov: NCT01393223). The study recruited subjects with moderate to severe refractory HC. These subjects were treated with up to two courses of LP-10 intravesical bladder instillations (liposomal formulation of tacrolimus at 2 mg, 4 mg and 8 mg). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n = 9), bladder cancer (n = 2) and lymphoma (n = 2). Mean duration of HC was 4 years and ranged from 1-14 years. No subject discontinued treatment or were lost to follow-up. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. 12 AEs were reported in 6 subjects. Pharmacokinetic analysis demonstrated short duration of low systemic uptake of tacrolimus. A dose response was noted with higher efficacy at both the 4mg and 8 mg dose groups. After LP-10 treatment, the number of cystoscopic bleeding sites and bladder ulcerations decreased and patients’ urinary symptoms improved. Conclusions: This first phase 2a study demonstrated safety and a signal of efficacy at intravesical tacrolimus (LP-10) doses of 4 mg and 8 mg for the treatment for HC, a rare and serious disease. Clinical trial information: NCT01393223 . [Table: see text

Differences in failure-free survival after salvage radiotherapy guided by conventional imaging versus 18F-fluciclovine PET/CT in postprostatectomy patients : a post hoc substratification analysis of the EMPIRE-1 trial

Please read abstract in the article.The National Institutes of Health and Blue Earth Diagnostics.http://jnm.snmjournals.orghj2023Nuclear Medicin

AUDITORY ACUITY IN DIABETES MELLITUS TYPE II: A CASE–CONTROL STUDY

Objectives: The objective of the study was to analyze the status of auditory acuity in patients with Type II diabetes mellitus (DM) as compared to healthy individuals of comparable age groups using pure tone audiometry. Methods: This was a case–control study in which 80 known cases of DM were enrolled as cases (Group D) and a similar number of age-matched healthy individuals were included as the control group (Group N). Demographic details such as age and gender were compared. A detailed history was taken and a general and systemic examination was done. Pure tone audiometry (250Hz, 500Hz, 1000Hz, 2000Hz, 4000Hz, 6000Hz, and 8000 Hertz frequencies) was done in all the patients, and air conduction and bone conduction of both the ears were determined. SSPE 21 software was used for statistical analysis. p<0.05 was considered to be statistically significant. Results: Both groups were found to be comparable in terms of gender and age distribution with no statistically significant difference (p<0.05). Mean fasting and postprandial blood sugar levels as well as HbA1c were found to be higher in Group D as compared to Group N and the difference was highly significant (p<0.0001). In Group D (Diabetic patients), mild, moderate, and severe sensorineural hearing loss (SNHL) at speech frequency was seen in 31 (38.75%) whereas moderate and severe SNHL was seen in 22 (27.50%) and 18 (22.50%) patients. In Group N (Non-diabetic), 5 (6.25%) patients had mild SNHL and moderate and severe hearing loss was not seen in any of the patients. The mean hearing threshold (Both Ears) for bone as well as air conduction was found to be more in Group D as compared to Group N at all frequencies and the difference was statistically significant (p<0.05). Conclusion: Individuals with Type II DM are found to have an increased incidence of subclinical hearing loss. This subtle hearing loss may go undetected for a considerable period of time and hence regular audiometric evaluation is required for early diagnosis of subclinical hearing loss in patients of DM

RISK FACTORS, CLINICAL PROFILE, AND MANAGEMENT OF PATIENTS PRESENTING WITH EPISTAXIS: A CROSS-SECTIONAL STUDY

Objective: To analyze risk factors, clinical profile, and management strategies for patients presenting with epistaxis. Methods: This was a cross-sectional study that was undertaken in the department of otorhinolaryngology at a tertiary care medical college. 60 adult patients presenting with epistaxis were included in this study. Demographic details, such as age and gender, were noted. Patients were evaluated for the presence of risk factors such as hypertension, bleeding disorder, or clotting defects. The clinical presentation of patients was also studied. Patients were managed as per standard protocol. Statistical analysis was done using SSPS 21.0 software, and p<0.05 was taken as statistically significant. Results: There were 44 males (73.33%) and 16 females (26.67%) with a M: F ratio of 1:0.36. The mean age of male and female patients was found to be 63.48±16.18 and 58.46±13.24, respectively. Assault or road traffic accidents, which were seen in 15 (25.00%) patients. The other common causes included hypertension (18.33%), nose picking (15%), and medication (such as antiplatelet or anticoagulant drugs)-induced (10%). Out of 60 patients, the majority (60.00%) were stable hemodynamically. 11 (18.33%) patients were found to have elevated blood pressure in addition to epistaxis. 5 (11.67%) patients were in hypotension, and hence fluid resuscitation was required. In 2 (3.33%) patients, the airway needed to be secured because of a compromised airway. The majority of the patients (75.00%) responded well to conservative measures. Posterior nasal packing (in addition to anterior nasal packing), cauterization, closed reduction of facial fractures, surgery for nasal mass, and functional endoscopic sinus surgery in remaining patients. Conclusion: Facial trauma, hypertension, and nose picking were the most common cases of epistaxis. Majority of the patients were hemodynamically stable and could be treated conservatively with measures such as medical management and anterior nasal packing

Effects of tumor size and location on survival in upper tract urothelial carcinoma after nephroureterectomy

Introduction: Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with few prognostic determinants. We sought to evaluate the impact of tumor size and location on patient survival following nephroureterectomy for UTUC. Materials and Methods: Data on 8284 patients treated with radical nephroureterectomy for UTUC in the United States between 1998 and 2011 were analyzed from the National Cancer Data Base. Univariable survivorship curves were generated based on pT stage, pN stage, grade, tumor size, and tumor site (renal pelvis vs. ureter). A Cox proportional hazards model was used to evaluate the effect of age, comorbidity, T stage, lymph node involvement, tumor site, and tumor size on survival. Results: The median follow-up time was 46 months. A majority of the patients were male (55.4%) with a tumor size of ≥3.5 cm (52.0%) and pT stage <T2 (47.8%). The overall 5 years survival overall survival (OS) for the entire cohort was 51.6%. When stratified by tumor size <3.5 cm or ≥3.5 cm the 5-year OS was 45.9% and 58.5%, respectively. On multivariable analysis controlling for age, Charlson comorbidity index, grade, and tumor stage, tumor size ≥3.5 cm was independently predictive of worse OS (odds ratio: 1.13 [95% confidence interval: 1.02–1.26], P = 0.023). Conclusions: Using the largest series of patients with UTUC undergoing nephroureterectomy, we demonstrated a worse survival in patients with larger tumor sizes (≥3.5 cm) but no difference in survival based on tumor location while controlling for other pathologic characteristics. Incorporation of tumor size into perioperative risk modeling may help with patient stratification and provide further prognostic information for patient counseling

Challenges and opportunities in the management of non-urothelial bladder cancers

Urothelial carcinoma accounts for approximately 90% of all bladder cancer diagnoses. Localized, muscle-invasive disease is often managed with a multidisciplinary approach including either neoadjuvant chemotherapy (NAC) followed by radical cystectomy or concurrent chemoradiation, whereas multiple immunotherapies and novel antibody drug conjugates have recently joined platinum-based chemotherapy as standard of care therapy for metastatic disease. However, the clinical trials leading to these standards often require majority if not complete urothelial histology for eligibility. As many as one quarter of patients diagnosed with bladder cancer will have either divergent differentiation of their urothelial carcinoma or an alternate epithelial tumor such as squamous cell carcinoma, adenocarcinoma, or small cell carcinoma; even more rare are non-epithelial tumors such as sarcoma. The rarity of these diseases and their general exclusion from treatment within prospective clinical trials has created a challenging situation where treatment plans are often derived from case series or extrapolated from other disease types and outcomes are poor compared to pure urothelial carcinoma. In this review, we summarize the existing data on the diagnosis and treatment of epithelial, non-urothelial bladder cancers including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma in their localized and advances stages. We will also review the current clinical trial landscape investigating novel approaches to these diseases

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures

Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health&rsquo;s personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and &gt;95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health