Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn's disease in real world-data: a retrospective study.

BACKGROUND: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. METHODS: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. RESULTS: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44). CONCLUSION: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

Gender Difference of Blood Pressure Control Rate and Clinical Prognosis in Patients With Resistant Hypertension: Real-World Observation Study.

BACKGROUND: There are several differences in the clinical course of hypertension due to the biological and social differences between men and women. Resistant hypertension is an advanced disease state, and significant gender difference could be expected, but much has not been revealed yet. The purpose of this study was to compare gender differences on the current status of blood pressure (BP) control and clinical prognosis in patients with resistant hypertension. METHODS: This is a multicenter, retrospective cohort study using common data model databases of 3 tertiary hospitals in Korea. Total 4,926 patients with resistant hypertension were selected from January 2017 to December 2018. Occurrence of dialysis, heart failure (HF) hospitalization, myocardial infarction, stroke, dementia or all-cause mortality was followed up for 3 years. RESULTS: Male patients with resistant hypertension were younger but had a higher cardiovascular risk than female patients. Prevalence of left ventricular hypertrophy and proteinuria was higher in men than in women. On-treatment diastolic BP was lower in women than in men and target BP achievement rate was higher in women than in men. During 3 years, the incidence of dialysis and myocardial infarction was higher in men, and the incidence of stroke and dementia was higher in women. After adjustment, male sex was an independent risk factor for HF hospitalization, myocardial infarction, and all-cause death. CONCLUSION: In resistant hypertension, men were younger than women, but end-organ damage was more common and the risk of cardiovascular event was higher. More intensive cardiovascular prevention strategies may be required in male patients with resistant hypertension.

Traditional health services utilization in rural Indonesia: does socioeconomic status matter?

INTRODUCTION: The presence of traditional health services (THS) is expected by governments to fill the lack of modern health facilities available in rural areas. Also, the proportion of poor people in rural areas has been increasing more rapidly than it has in urban areas. The present study analyzed the socioeconomic status and THS utilization in rural Indonesia. METHODS: This cross-sectional study analyzed data from the 2018 Indonesian Basic Health Survey. The study analyzed 357 556 adults (age ≥15 years), examining age, gender, marital status, education, and occupation as control factors, in addition to socioeconomic status (SES; with five divisions from 'lowest' to 'highest') and THS utilization. Binary logistic regression was used to evaluate the data. RESULTS: The results show that those with lower SES were 1.111 times more likely to utilize THS than those with the lowest SES (adjusted odds ratio (AOR) 1.111; 95% confidence interval (CI) 1.085-1.137). Those with middle SES were 1.113 times more likely than those with the lowest SES to utilize THS (AOR 1.113; 95%CI 1.086-1.140). Meanwhile, those with a higher SES are 1.166 times more likely than those with the lowest SES to use THS in rural Indonesia (AOR 1.166; 95%CI 1.139-1.194). Those with the highest SES were 1.166 times more likely than those with the lowest SES to use THS in rural Indonesia (AOR 1.166; 95%CI 1.134-1.200). CONCLUSION: The study concluded that SES status relates to THS utilization in rural Indonesia. All SES levels are more likely than those with the lowest SES to utilize the THS in rural Indonesia. The results indicate that although all SES levels can receive it, the lowest SES group rarely accesses THS.

CLINICAL EFFICACY OF TREATMENT OF WOMEN WITH CHRONIC RECURRENT UROGENITAL CHLAMYDIA INFECTION.

OBJECTIVE: Aim: To to increase the efficacy of the treatment of women diagnosed with complicated urogenital chlamydia infection based on the study of the immune status, clinical and pathogenetic features of the course, development and implementation of pathogenetically substantiated therapy methods. PATIENTS AND METHODS: Materials and methods: Laboratory diagnostics of chlamydia infection was conducted with the use of direct immunofluorescence, enzyme immunoassay and cytological method. The dynamics of clinical symptoms was studied in the patients of Group I (64 women) who received Wobenzym in combination with Doxycycline and Group II (64 women) who were treated with conventional therapy (CT). RESULTS: Results: Clinical effectiveness of the treatment of women in Groups I and II was analyzed. The treatment according to our developed method was well tolerated by all the patients. No manifestations of the disease exacerbation which could be associated with the inclusion of these drugs in the comprehensive treatment were noted. The insignificant effectiveness of our treatment in the examined patients with complicated urogenital chlamydia infection in Groups I and II was distributed as follows: only 1 (1.56%) woman (Group I) had an insignificant improvement in clinical manifestations after the treatment according to our method. An insignificant improvement in the clinical manifestations after the treatment with conventional therapy (Group II) was observed in 4 women constituting 6.25%. Unfortunately, a small percentage of women in Groups I and II with no changes in clinical symptoms after the treatment was observed. In particular, the absence of treatment effectiveness was noted in 3 (4.69%) women after the application of our method and in 6 women (9.38%) who were treated by the conventional therapy. Therefore, these women were prescribed an additional course of treatment. CONCLUSION: Conclusions: The dynamics of clinical symptoms was found to be significantly more pronounced and fast in the patients of Group I compared to the patients in Group II who were treated with conventional therapy.

Efficacy of Robot-Assisted Gait Therapy Compared to Conventional Therapy or Treadmill Training in Children with Cerebral Palsy: A Systematic Review with Meta-Analysis.

BACKGROUND: Motor, gait and balance disorders reduce functional capabilities for activities of daily living in children with cerebral palsy (CP). Robot-assisted gait therapy (RAGT) is being used to complement conventional therapy (CT) or treadmill therapy (TT) in CP rehabilitation. The aim of this systematic review is to assess the effect of RAGT on gait, balance and functional independence in CP children, in comparison to CT or TT. METHODS: We have conducted a systematic review with meta-analysis. A search in PubMed Medline, Web of Science, Scopus, CINAHL, PEDro and SciELO has been conducted for articles published until October 2022. Controlled clinical trials (CCT), in which RAGT was compared to TT or CT and assessed gait speed, step and stride length, width step, walking distance, cadence, standing ability, walking, running and jumping ability, gross motor function and functional independence in children with CP, have been included. Methodological quality was assessed with the PEDro scale and the pooled effect was calculated with Cohen's Standardized Mean Difference (SMD) and its 95% Confidence Interval (95% CI). RESULTS: A total of 15 CCTs have been included, providing data from 413 participants, with an averaged methodological quality of 5.73 ± 1.1 points in PEDro. The main findings of this review are that RAGT shows better results than CT in the post-intervention assessment for gait speed (SMD 0.56; 95% CI 0.03 to 1.1), walking distance (SMD 2; 95% CI 0.36 to 3.65) and walking, running and jumping ability (SMD 0.63; 95% CI 0.12 to 1.14). CONCLUSIONS: This study shows that the effect of RAGT is superior to CT on gait speed, walking distance and walking, running and jumping ability in post-intervention, although no differences were found between RAGT and TT or CT for the remaining variables.

Effects of task oriented rehabilitation of upper extremity after stroke: A systematic review.

OBJECTIVE: To explore the current scientific evidence on the effects of task-oriented rehabilitation programme of upper extremity post-stroke. METHODS: The systematic review comprised studies from 2012 to August 2020 which were both Hand-searched and explored on Cochrane, PubMed, PEDro and MEDLINE databases with authentic search techniques using population-intervention-control-outcomes format and Boolean operator. Randomised controlled trials on the use of task-oriented training for the improvement of upper extremity functional outcomes in subjects with stroke were shortlisted and reviewed. The risk bias tool was used to evaluate the biasness in the studies and the PEDro scale was used to evaluate the methodological quality of the studies. RESULTS: Of the 28 articles assessed, 16(%) were included for detailed review. All studies varied significantly with PEDro scores between 6 and 10. There were 12(75%) high-quality studies and 4(25%) fell in fair category. All the studies showed significant results in the improvement of upper extremity after stroke through task-oriented training rehabilitation (p<0.05). CONCLUSIONS: Evidence supports the beneficial effects of task-oriented rehabilitation for the improvement of upper extremity functions post-stroke.

Burden of illness in patients with chronic hypoparathyroidism not adequately controlled with conventional therapy: a Belgium and the Netherlands survey.

PURPOSE: To determine the burden of illness in patients with not adequately controlled chronic hypoparathyroidism receiving conventional therapy in Belgium and the Netherlands. METHODS: Data were generated from a cross-sectional, two-part online survey where endocrinologists from both countries and nephrologists from Belgium were invited by phone to participate. Part 1 included collecting data on general management of patients with hypoparathyroidism. In Part 2, physicians were requested to provide data on one or two current cases of patients with chronic hypoparathyroidism not adequately controlled on conventional therapy. Data collected included aetiology of hypoparathyroidism, clinical manifestations, comorbidities, results of laboratory and other investigations used for diagnosis and screening for complications, therapy received, and physician's perception of impaired quality of life (QoL). RESULTS: Thirty-six endocrinologists and 29 nephrologists from Belgium and 28 endocrinologists from the Netherlands participated in the survey. Data included clinical symptoms, biochemical parameters, and QoL for 97 current patients with not adequately controlled chronic hypoparathyroidism on conventional therapy. Median duration of not adequately controlled hypoparathyroidism was 2.2 years, range 0.17-20.0. Most patients had neuromuscular (85%) and/or neurological (67%) symptoms, 71% had abnormal biochemical parameters, 10% were overweight, and physicians perceived that 71% had impaired QoL. Most frequently reported comorbidities included hypertension (25%), renal comorbidity (20%), diabetes mellitus (12%), and dyslipidaemia (11%). CONCLUSION: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy experience a substantial burden of illness, mainly due to persistence of symptoms and presence of multiple comorbidities.

Unravelling Toxoplasma treatment: conventional drugs toward nanomedicine.

Toxoplasma gondii is a worldwide protozoan parasite that infects almost all warm-blooded animals. Although human toxoplasmosis is mostly latent, pregnant women and immunocompromised patients need effective treatment. There are drugs of choice for treatment of toxoplasmosis; however, due to their side effects and/or their disease stage-specificity, prescription of them is limited. During recent years, nanomedicine has been employed to overcome limitations of conventional drugs. Here, we provided a state-of-the-art review of experimental toxoplasmosis treatment using nanotechnology.

Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH).

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized. We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions. Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated. The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization. Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles. Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

Sialic Acid-Siglec Axis as Molecular Checkpoints Targeting of Immune System: Smart Players in Pathology and Conventional Therapy.

The sialic acid-based molecular mimicry in pathogens and malignant cells is a regulatory mechanism that leads to cross-reactivity with host antigens resulting in suppression and tolerance in the immune system. The interplay between sialoglycans and immunoregulatory Siglec receptors promotes foreign antigens hiding and immunosurveillance impairment. Therefore, molecular targeting of immune checkpoints, including sialic acid-Siglec axis, is a promising new field of inflammatory disorders and cancer therapy. However, the conventional drugs used in regular management can interfere with glycome machinery and exert a divergent effect on immune controlling systems. Here, we focus on the known effects of standard therapies on the sialoglycan-Siglec checkpoint and their importance in diagnosis, prediction, and clinical outcomes.

Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients.

Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients' medical records from 2006-2017. Eleven of the 26 patients accepted relatives' derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30×108 per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.

Renal denervation for the treatment of cardiovascular high risk-hypertension or beyond?

Hypertension imposes a major burden of morbidity and mortality and is associated with sympathetic nervous system overactivity. Renal sympathetic denervation has been shown to reduce office blood pressure, ambulatory blood pressure, and sympathetic activity in patients with resistant hypertension. Therefore, the procedure has attracted a lot of attention. Beyond blood pressure, renal denervation has been shown to improve glucose tolerance, microalbuminuria, and arrhythmias in several experimental models and, in admittedly, often uncontrolled clinical studies. It has been demonstrated to reduce myocardial hypertrophy in a blood pressure-independent and blood pressure-dependent way. The first studies on heart failure with preserved and reduced ejection fraction are ongoing. Renal sympathetic denervation holds promise for future indications in hypertension and related comorbidities and consequences, such as metabolic disease, renal failure, and heart failure. Published data in a placebo-control blinded study, however, are needed. The aim of this review is to provide a critical and comprehensive overview of heretofore generated data on renal denervation in experimental models, in human hypertension, and on early developments in new indications, which should indicate the way to powered and performed, controlled clinical studies appropriately.

Clinical features and survival of 338 multiple myeloma patients treated with hematopoietic stem cell transplantation or conventional chemotherapy.

Therapeutic approaches against multiple myeloma (MM) have largely changed during the past decade. Hematopoietic stem cell transplantation (HSCT) and licensing of immunomodulators and proteasome inhibitors have resulted in better response and increased overall survival rates compared to previous conventional therapies. To assess the impact that these new strategies have had on outcome of patients with symptomatic MM in Spain, we conducted an epidemiological retrospective analysis of 338 newly diagnosed patients with stage II-III MM who started first-line treatment over a 2-yr period (2003-2005) by collecting data from their medical records. Most patients had been diagnosed with secretory MM (94.4%), 41.7% stage II and 58.3% stage III. The presence of bone lesions (72.2%), as well as anemia (79.8%) and elevated beta2-microglobulin levels (62.3%), was a common finding; in contrast, hypercalcemia and elevated serum creatinine were less frequent (25% each). First-line treatment had consisted of either conventional chemotherapy (62%) or induction treatment plus autologous HSCT (38%), as per standard clinical practice. HSCT not only resulted in greater objective response rates (93% vs. 50%), but also contributed to a significant increase in 3-yr survival (85% vs. 49.7%; 95% CI, range 77-91 vs. 41-58; P < 0.001). Overall, 55% of patients presented treatment-related adverse events, mainly hematological. Toxicity rates were higher among patients treated with alkylating-based regimens and in those undergoing transplantation. In conclusion, data analysis shows an adequate balance between increased response rates and safety that supports the use of up-front high-dose HSCT therapy in younger patients. Most importantly, this study provides further confirmation that the introduction of HSCT has significantly prolonged survival of patients with MM.

Treatment of recalcitrant bullous pemphigoid (BP) with a novel protocol: A retrospective study with a 6-year follow-up.

BACKGROUND: Bullous pemphigoid is an autoimmune blistering skin disease that predominantly affects the elderly. Conventional therapy using high-dose systemic corticosteroids and immunosuppressive agents can be ineffective in some patients and produce adverse events and relapses. Hence, alternate therapies are required. OBJECTIVE: The clinical outcomes of patients with extensive, recalcitrant bullous pemphigoid treated with a combination therapy of rituximab (RTX) and intravenous immunoglobulin were evaluated. METHODS: In this retrospective study, 12 patients (mean age of 68.25 years) unresponsive to previous conventional immunosuppressive therapy, intravenous immunoglobulin, and/or RTX were treated with this combination therapy. RESULTS: Complete clinical resolution occurred in a mean of 4.6 months and previous systemic therapy was discontinued in 6.2 months. Two patients had a recurrence posttherapy and responded to additional RTX infusions. The remaining 10 patients had no recurrences. Patients were followed up for a mean of 73.8 months after discontinuation of all systemic therapy. All have remained in remission without adverse events for 6 years. LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSION: The combination of RTX and intravenous immunoglobulin produced a sustained clinical remission without adverse events, infections, and hospitalizations. This specific combination protocol offers a promising therapy for patients with recalcitrant bullous pemphigoid.

Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial.

AIM: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities. METHODS: Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n = 115) to maintain HbA1c levels at <6.5% for 2 years. RESULTS: Participants receiving triple therapy experienced a significantly greater reduction in HbA1c level than those receiving conventional therapy (5.95 vs. 6.50%; p < 0.001). Despite lower HbA1c values, participants receiving triple therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with participants receiving conventional therapy. Participants receiving triple therapy experienced a mean weight loss of 1.2 kg versus a mean weight gain of 4.1 kg (p < 0.01) in those receiving conventional therapy. CONCLUSION: The results of this exploratory study show that combination therapy with metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more effective and results in fewer hypoglycaemic events than sequential add-on therapy with metformin, sulfonylurea and then basal insulin.

Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. METHODS AND RESULTS: A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (-10.1/-10.2/-11.7 mm Hg, P<0.001), diastolic BP (-4.8/-4.9/-7.4 mm Hg, P<0.001), maximum SBP (-11.7/-10.0/-6.1 mm Hg, P<0.001) and minimum SBP (-6.0/-9.4/-13.1 mm Hg, P<0.001) at 3, 6, and 12 months, respectively. There was no effect on ambulatory BP monitoring in pseudoresistant patients, whereas office BP was reduced to a similar extent. RDN was equally effective in reducing BP in different subgroups of patients. Office SBP at baseline was the only independent correlate of BP response. CONCLUSIONS: RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.

Investigating the therapeutic promise of Drug-Repurposed-Loaded Nanocarriers: A pioneering strategy in advancing colorectal cancer treatment.

Globally, colorectal cancer is a major health problem that ranks in third place in terms of occurrences and second in terms of mortality worldwide. New cases increase annually, with the absence of effective therapies, especially for metastatic colorectal cancer, emphasizing the need for novel therapeutic approaches. Although conventional treatments are commonly used in oncotherapy, their success rate is low, which leads to the exploration of novel technologies. Recent efforts have focused on developing safe and efficient cancer nanocarriers. With their nanoscale properties, nanocarriers have the potential to utilize internal metabolic modifications amid cancer cells and healthy cells. Drug repurposing is an emerging strategy in cancer management as it is a faster, cheaper, and safer method than conventional drug development. However, most repurposed drugs are characterized by low-key pharmacokinetic characteristics, such as poor aqueous solubility, permeability, retention, and bioavailability. Nanoparticle formulations and delivery have expanded over the past few decades, creating opportunities for drug repurposing and promises as an advanced cancer modality. This review provides a concise and updated overview of colorectal cancer treatment regimens and their therapeutic limitations. Furthermore, the chemotherapeutic effect of various FDA-approved medications, including statins, non-steroidal anti-inflammatory drugs, antidiabetic and anthelmintic agents, and their significance in colorectal cancer management. Along with the role of various nanocarrier systems in achieving the desired therapeutic outcomes of employing these redefined drugs.

Comprehensive insights on treatment modalities with conventional and herbal drugs for the treatment of duodenal ulcers.

Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal tract mucosa. Peptic ulcer disease is the term for this illness (PUD). About 80% of peptic ulcers are duodenal ulcers, with stomach ulcers accounting for the remaining 20%. Duodenal ulcers are linked to the two primary results about Helicobacter pylori infection and COX inhibitor users. Additional causes might include drinking, smoking, stress, and coffee consumption. The indications and symptoms of a duodenal ulcer depend on the patient's age and the lesion's location. For duodenal ulcers, proton pump inhibitors (PPIs) are the usual course of treatment. This comprehensive study included an in-depth literature search in the literature and methods section using electronic databases such as PubMed, ScienceDirect, and Google Scholar. The search method included publications published from the inception of the relevant database to the present. Inclusion criteria included studies investigating different treatment options for duodenal ulcer disease, including traditional pharmacotherapy and naturopathic treatments. Data mining includes information on treatment techniques, treatment outcomes, and possible synergies between conventional and herbal treatments. In addition, this review critically examines the available information on the effectiveness, safety, and possible side effects of different treatments. The inclusion of conventional and herbal treatments is intended to provide a comprehensive overview of the many treatment options available for duodenal ulcer disease. A more comprehensive and personalized treatment plan can be achieved by incorporating dietary changes, lifestyle modifications, and, if necessary, herbal therapies to complement other treatments normally.

Evaluating Catheter Ablation Versus Conventional Management for Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy: A Five-Year Retrospective Cohort Study.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a challenging genetic disorder marked by ventricular arrhythmias and sudden cardiac death, particularly in athletes and young adults. Despite its clinical significance, the relative effectiveness and safety of catheter ablation versus conventional management in ARVC are not fully delineated. Objective This study evaluates the efficacy and safety of catheter ablation compared to conventional management in reducing ventricular arrhythmias and improving patient outcomes over five years in ARVC patients. Methods In a retrospective cohort design at Lady Reading Hospital, Peshawar, we analyzed 120 ARVC patients from January 2018 to December 2023. Patients were divided into two groups: those undergoing catheter ablation and those receiving conventional management. Primary outcomes assessed were recurrence of ventricular arrhythmias, procedural complications, hospitalization duration, and mortality rates. Logistic regression was adjusted for demographics and clinical variables. Results Catheter ablation significantly lowered the recurrence of ventricular arrhythmias (20% vs. 55%, p<0.01) and reduced hospital stay duration (4 ± 2 days vs. 7 ± 3 days, p<0.05). A trend toward reduced five-year mortality was observed in the catheter ablation group (5% vs. 15%, p=0.07). Age, New York Heart Association class, and exercise capacity emerged as significant predictors of outcomes. Conclusions Catheter ablation outperforms conventional management in reducing the recurrence of ventricular arrhythmias and hospitalization in ARVC patients, with a promising trend toward enhanced survival. These findings advocate for personalized management strategies in ARVC, highlighting the necessity for further research to establish the long-term benefits of catheter ablation.