Preferred Therapy Research Articles

Combination Inhaled Corticosteroid and Short-acting Beta2 Agonist (ICS-SABA) Use for Older Adults With Asthma

The first combination inhaled corticosteroid and short-acting beta2 agonist (ICS-SABA) was approved by the Food and Drug Administration (FDA) in 2023 for as-needed treatment or prevention of bronchoconstriction and to reduce the risk of asthma exacerbations in patients 18 years of age and older. The recently approved product contains an ICS-albuterol combination. The 2024 Global Initiative for Asthma (GINA) guidelines recommend as-needed ICS-formoterol as the preferred asthma reliever therapy; however, a GINA alternative recommendation is the use of ICS whenever an as-needed (SABA) is used. There is no difference in as-needed asthma treatment recommended by the GINA guidelines in older adults, and there has been minimal study in older adults. Because of limited guidance on the use of the ICS-SABA reliever inhaler in older adults, the purpose of this review is to evaluate the DENALI and MANDALA studies and the potential role of ICS-SABA in older adults. The mean ages in both studies were 50 years. The MANDALA primary outcome result was a statistically significant lower risk of severe exacerbations in the ICS-SABA reliever group compared with the as-needed albuterol (ALB) group at 24 weeks. In the MANDALA older adults subgroup analysis, there was not a statistically significant difference in the ICS-SABA reliever group compared with the as-needed ALB-alone group but the results favored ICS-SABA. The DENALI primary outcome results were a greater change from baseline in forced expiratory volume in the first second (FEV1) area under the curve averaged over 12 weeks with albuterol/budesonide (ALB-BUD) 180/160 ug compared with budesonide alone and placebo and a greater change from baseline in trough FEV1 with ALB-BUD 180/160 ug and 180/80 ug than ALB-alone and placebo. Because of minimal adverse effects in both trials and the benefits in preventing asthma exacerbations reported in the MANDALA trial, it is important to assess and recommend that older adults with asthma receive inhaled corticosteroid with their reliever asthma inhaler.

Data Insights on the Risks of Local Heat and Massage in Gouty Arthritis Treatment.

Gouty arthritis is a common inflammatory condition caused by the deposition of uric acid crystals in the joints, leading to intense pain, swelling, and functional impairment. Thermal therapies, including hot and cold fomentation, are often used as adjunctive treatments for managing inflammation and pain in various musculoskeletal conditions. However, the efficacy of these therapies in acute gout remains underexplored. This study aims to compare the effects of hot fomentation versus cold fomentation in patients experiencing acute gout flares, assessing pain reduction, swelling, joint mobility, and overall patient satisfaction. A randomized controlled trial was conducted with 2,400 patients diagnosed with acute gouty arthritis, divided into two equal groups: Group A received hot fomentation (38°C-42°C) and Group B received cold fomentation (5°C-10°C). Both interventions were applied twice daily for 20 min over 5 days, alongside standard gout care. Pain intensity was measured using the visual analog scale (VAS), while joint circumference, range of motion, and patient satisfaction were recorded at baseline, day 3, and day 5. Statistical analyses compared outcomes between the two groups. Cold fomentation significantly reduced pain intensity (VAS score reduction of 68% by day 5) compared to hot fomentation (26% reduction, P < 0.001). Joint swelling decreased by 25% in the cold group versus 5% in the hot group, with cold therapy also leading to greater improvements in joint mobility (average increase of 15° vs. 5°, P < 0.01). Notably, 35% of patients in the hot fomentation group experienced flare-ups, compared to only 2% in the cold fomentation group (P < 0.001). Patient satisfaction was also higher in the cold group, with 85% of participants reporting satisfaction versus 30% in the hot group. This study demonstrates that cold fomentation is significantly more effective than hot fomentation in managing acute gouty arthritis. Cold therapy provided superior pain relief, reduced swelling, improved joint mobility, and minimized the risk of symptom exacerbation. In contrast, hot fomentation often worsened symptoms, making it unsuitable for acute gout management. These findings suggest that cold fomentation should be the preferred thermal therapy for gout flare-ups, while heat applications should be avoided.

Trans-Catheter Device Closure of Atrial Septal Defect in Symptomatic Children Up to 10 Kg of Body Weight: A Multicentric Retrospective Observational Cohort Study to Assess Feasibility, Safety and Midterm Results After Closure

Background: Atrial septal defect (ASD) is the second most prevalent congenital heart diseases (CHD) encompassing 8-10% of all CHDs beyond neonatal period. Although relatively benign, if left untreated can amount to several adverse outcomes. Trans-catheter Device closure of ASD is a preferred therapy for a hemodynamically significant shunt. Despite multitude of septal occluders being available these days, paucity of literature concerning appropriateness of device sizing, and various adaptations of techniques for device deployment in large ASDs with deficient rims and their outcomes in children up to 10 kg weight nevertheless still exists. Aims and Methods: A retrospective multi-centric observational study, was conducted in a cohort of children who underwent ASD device closure weighing up to 10 kg conducted over a period of 4 years, to assess its safety and feasibility. Results: Of the included 85 patients, 63% were females and 37% were males with mean age at intervention being 32 months. The mean weight and height were 9.17 Kg and 88 cm respectively. Mean of maximum ASD dimension was 14.92mm. Hemodynamic assessment with invasive PA pressures recordings suggested normal PA pressure in 82%, while 18% had pulmonary arterial hypertension. Mean Qp/Qs and PVR was 2.58 and 1.8 Wood units respectively. Average device: weight ratio was 1.9. Arrhythmias occurred in 6 children, five had Adenosine sensitive SVTs and one had persisting CHB necessitating surgical device retrieval and Permanent pacemaker implantation. No mortality occurred in this study. Conclusion: Trans-catheter closure of ASD is indeed safe and effective procedure if performed in children weighing up to 10 Kg, in a hemodynamically significant shunt, adopting modified techniques, even in presence of flimsy or deficient rims with device weight ratio up to 3:1

Lysozyme/Tracheal Antimicrobial Peptide‐Based Tissue‐Specific Expression Antimicrobial Plasmids Show Broad‐Spectrum Antibacterial Activities in the Treatment of Mastitis in Mice

AbstractThe use of antibiotics is the preferred therapy for bacterial diseases. However, overusing antibiotics has led to the development of antibiotic resistance in bacteria, which is now a major public health concern. Therefore, in this study, the performance of lysozyme (LYZ)/tracheal antimicrobial peptide (TAP)–based tissue‐specific expression antimicrobial plasmids (TSEAP) have been evaluated in the treatment of mastitis in mice. The results show that LYZ/ and TAP‐based TSEAP could effectively reduce the clinical symptoms caused by Staphylococcus sciuri, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa–induced mastitis. In addition, the studies of behavioral tests, parameters of weight growth, blood biochemistry, and organ coefficients comprehensively indicate that the transfection of LYZ/TAP‐based TSEAP is safe in mice. Taken together, LYZ/TAP‐based TSEAP have broad‐spectrum antibacterial activity and may provide new insight for the non‐antibiotic treatment of bacterial diseases.

The role of macrolides in severe community-acquired pneumonia and the potential impact of macrolide-resistant Mycoplamsa pneumoniae.

Define the utility of adjunctive macrolide therapy in patients with more severe forms of community-acquired pneumonia (CAP). Guidelines recommend adjunctive macrolide therapy as an option for patients with CAP, admitted to the hospital. A large data set collected both retrospectively and prospectively, including several recent randomized controlled trials (RCTs) have shown that adjunctive macrolide therapy can reduce mortality and improve outcomes in patients with severe CAP, more effectively than other alternative therapies. This effect appears to be most evident in those with severe illness and appears to be independent of direct antimicrobial effects and may be a result of the immunomodulatory properties of macrolides. A recent RCT, the ACCESS study, showed a clinical benefit of macrolides in severe CAP patients, but this may have been the result of a reversal of infection-related immunoparalysis. Macrolides appear to be valuable for patients with more severe CAP, but their therapeutic value is being challenged by the recent emergence of macrolide-resistant Mycoplasma pneumoniae; however, the optimal therapy for this pathogen still needs to be defined. New evidence has further advanced the role of macrolides as preferred adjunctive therapy for patients with severe CAP.

Optimizing growth in pediatric renal transplant recipients: An update.

Growth retardation is a significant complication observed in pediatric renal transplant recipients, originating from a multifactorial etiology. Factors contributing to growth impairment encompass pre-transplant conditions such as primary kidney disease, malnutrition, quality of care, growth deficits at the time of transplantation, dialysis adequacy, and the use of recombinant human growth hormone. Additionally, elements related to the renal transplant itself, such as living donors, corticosteroid usage, and graft functioning, further compound the challenge. Although renal transplantation is the preferred renal replacement therapy, its impact on achieving final height and normal growth in children remains uncertain. The consequences of growth delay extend beyond the physiological realm, negatively influencing the quality of life and social conditions of pediatric renal transplant recipients, and ultimately affecting their educational and employment outcomes. Despite advancements in graft survival rates, growth retardation remains a formidable clinical concern among children undergoing renal transplantation. Major risk factors for delayed final adult height include young age at transplantation, pre-existing short stature, and the use of specific immunosuppressive drugs, particularly steroids. Effective management of growth retardation necessitates early intervention, commencing even before transplantation. Strategies involving the administration of recombinant growth hormone both pre- and post-transplant, along with protocols aimed at minimizing steroid usage, are important for achieving catch-up growth. This review provides a comprehensive outline of the multifaceted nature of growth retardation in pediatric renal transplant recipients, emphasizing the importance of early and targeted interventions to mitigate its impact on the long-term well-being of these children from birth to adolescence.

An open label, single arm, pilot study to evaluate the safety, tolerability, and efficacy of daily fluconazole 150 mg in subjects suffering from Tinea cruris and Tinea corporis

Background Dermatophytes are the most common superficial fungal infections worldwide and are treated with prescribed regimens of terbinafine and itraconazole, or with weekly doses of fluconazole. Dermatologists are increasingly encountering treatment failures, and experts suggest that standard treatment regimens are not applicable anymore. We planned an open-label study to evaluate the results of fluconazole 150 mg daily for 8 weeks in patients with tinea cruris and tinea corporis. Methods Patients were enrolled from the La’Mer Clinic, Mumbai, India. We included adult subjects with uncomplicated dermatophytosis confirmed by microscopic examination of skin scrapings. Pregnancy, poor renal function, and recent exposure to anti-fungal therapy were exclusion criteria. Patients were reviewed on days 14, 28 and 56. The treating doctor scored the severity of erythema, scaling, and pruritus on a four-point scale: absent, mild, moderate, and severe. Of 107 subjects screened, 100 were finally included in the study. Eleven were lost to follow up and one subject withdrew consent. Results The site of disease was body alone in 29, groin alone in 7, and both body and groin in 64 cases. At 5 weeks, 98%, 100%, and 97% of patients had no scaling, erythema, and pruritus, respectively. Skin scrapings showed 100% mycological cure. In one patient the alanine transaminase level rose from 54.9 to 100.2 U/L, and qualified as a grade 1 adverse event not requiring intervention. No other significant adverse events were noted. Conclusions Our results suggest that fluconazole 150 mg daily for eight weeks effectively treats dermatophytosis. This regimen is safe and well-tolerated even in patients with co-morbidities. Fluconazole is about eight times less expensive than itraconazole or terbinafine and may be the preferred therapy. Registration The trial was registered with Clinical Trials Registry, India (Registration number CTRI/2020/06/026110) on 24 June 2020. FDC Company, India, provided financial support for the study.

Current Practice Patterns in the Management of Bell's Palsy Among Physiotherapists of Sargodha, Pakistan

Objectives: We intend to find out current practice patterns in managing Bell’s palsy among the physiotherapists of Sargodha, Pakistan. Methods: A cross-sectional study was conducted from May to August 2022. Data were obtained from 50 physiotherapists working in various clinical settings of Sargodha with more than 2 years of clinical experience. They were selected using convenient sampling. A self-designed questionnaire was used to gather all necessary information regarding the physical therapy practice patterns of Bell’s palsy. The obtained data were analyzed by using SPSS software, version 20. Results: Proprioceptive neuromuscular facilitation (PNF) was the preferred (42%) neurodevelopmental technique used in current practice patterns to manage Bell’s palsy. The most used therapeutic exercises by the physiotherapists were facial expression coordination exercises (66%). Also, 44% of physiotherapists used electrical muscle stimulation as the preferred electrotherapeutic modality in their current practice. Soft tissue release (54%) was the most preferred manual therapy technique in Bell’s palsy patients. The combination of electrical muscle stimulation, facial exercises, and biofeedback was the most used (54%) among physiotherapists. Discussion: Current practice for Bell’s palsy treatment includes PNF techniques, facial expression coordination exercises, soft tissue release, and electrical muscle stimulation by most physiotherapists in Sargodha. The most preferred combination was facial exercises, electrical stimulation, and biofeedback.

AGITG MONARCC: A Randomized Phase 2 Study of Panitumumab Monotherapy and Panitumumab Plus 5-Fluorouracil as First-Line Therapy for Older Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer. A Study by the Australasian Gastro-Intestinal Trials Group (AGITG).

Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens. Prospective, noncomparative, randomized (1:1) phase 2 study of pan alone (Arm A) or pan plus FU (Arm B). Previously untreated mCRC were ≥70 years; RAS/BRAF wild type. 6-month progression-free survival (PFS). Secondary endpoints included: overall survival (OS), response rate (RR), feasibility of geriatric assessments and overall treatment utility (OTU)-a composite measure based on radiological response, clinical progress, toxicity and patient-reported treatment worth. Planned sample size was 40 patients per arm. 36 patients (Arm A n = 19, Arm B n = 17) were randomized between June 2018 and June 2021. Median age was 79 and 80 years respectively. 6-month PFS 63% (95% CI 38%-80%) arm A 82% (95%CI 55%-94%) Arm B. Median OS 21 months Arm A (95%CI 13-31) 28 (95%CI 14-39) months Arm B. RR 47% and 65% Arms A and B respectively. Baseline comprehensive geriatric assessments were completed in >80% of patients. At week 16, OTU was categorized as good in 92% (Arm A) and 90% (Arm B). No unexpected adverse events were seen. Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.

The in vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant Klebsiella pneumoniae.

This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). The broth microdilution assay assessed the in vitro susceptibility of CRKP to OMC. The checkerboard assay was performed to evaluate the activity of OMC combined with polymyxin B (PB), amikacin (AN), or meropenem (MEM) against KPC-producing (class A) CRKP strains, and OMC combined with PB, aztreonam (ATM), MEM, or AN against class B and class A plus class B CRKP strains. Synergistic effects of OMC and PB were further evaluated by time-kill assays in the KPC-producing CRKP strains. Broth microdilution assays revealed a notable variation in susceptibility between KPC-producing and class B CRKP strains, with MIC50/90 of 32/32 mg/L and 0.5/8 mg/L, respectively. Although KPC-producing CRKP strains were resistant to OMC, a synergistic effect was observed in 37.5% of KPC-producing CRKP strains when OMC was combined with PB. In the nine KPC-producing CRKP strains, time-kill assays found that cell densities of six strains (66.7%) decreased by 3.61 ± 0.23 log10 CFU/mL compared to the initial inoculum after 2hours of PB exposure. The cell densities further decreased by an average of 2.38 ± 0.23 log10 CFU/mL when the six strains were exposed to OMC plus PB, confirming their potent synergism. OMC monotherapy is ineffective against KPC-producing CRKP strains, but OMC plus PB has a potent synergistic effect on them, suggesting that OMC plus PB is the preferred combination therapy against KPC-producing CRKP in vitro.

Real-world practitioner perceptions of CARTITUDE-4 results for patients with previously treated multiple myeloma.

Initially approved for the fifth-line or later therapeutic setting, the chimeric antigen receptor (CAR) T-cell regimen ciltacabtagene autoleucel (cilta-cel) was recently approved for second-line (2L) treatment in relapsed/refractory multiple myeloma (RRMM). Oncology practitioners use clinical trials to inform treatment, but real-world impressions and impact on practice are lacking. We aimed to determine whether presenting CARTITUDE-4 clinical trial data would impact real-world preferences/perceptions around CAR T-cell therapy. Recruiting from the Cardinal Health Oncology Provider Extended Network (OPEN), we surveyed hematologists/oncologists to investigate fourth-line (4L) preferences in a hypothetical patient with triple-class-refractory MM. We posed the same questions and answers before and after the trial presentation and compared pre-/post-preferences toward cilta-cel and sequencing relative to bispecific antibodies (BsAbs). Using the same methodology as described above, we also performed a secondary analysis comparing pre-/post-perceptions on the use of CAR T-cell therapy in earlier lines for patients with triple-class-refractory MM. Among 50 respondents, decision-making factors before the trial presentation included CAR T-cell center availability (58%), comorbidities (52%), and center locations (34%). Additionally, 48% of 46 respondents chose 4L cilta-cel. Among 47, 40% wanted more real-world/long-term CAR T-cell therapy outcomes in any line, 38% wanted more 2L data, and 34% favored 2L/third-line (3L) use. After the presentation, the preference for cilta-cel doubled from 48% to 88% (p<0.001) among 50 respondents and rose from 34% to 55% (p=0.001) for earlier-line CAR T-cell therapy among 49. Moreover, 55% of 49 respondents preferred CAR T-cell therapy prior to BsAbs. We have shown that making oncology practitioners aware of trials precipitated decision-making factors and led to notable, significant shifts in future intended practice patterns. Being aware of trial data enables practitioners to make more informed decisions, tailor therapies to individual patients, and ultimately improve outcomes.

Abstract 4136563: In-Hospital Outcomes of Percutaneous Versus Surgical Mitral Valve Repair in Patients With COPD

Background: Percutaneous mitral valve repair has been increasingly utilized for the treatment of mitral valve disease in the recent years, although surgical mitral valve repair and/or replacement remains the preferred therapy, especially for primary mitral regurgitation. Chronic obstructive pulmonary disease (COPD) is a common comorbidity that can adversely affect outcomes of cardiac procedures. While COPD is an independent predictor of adverse outcomes after surgical mitral valve repair, its effects on percutaneous mitral valve repair is not well-defined. Methods: Using National Inpatient Sample data from 2011 to 2019, we conducted a retrospective study of adult patients with COPD who underwent surgical or percutaneous mitral valve repair, using ICD-9 and ICD-10 codes. We excluded patients with surgical mitral valve replacement. Patient baseline characteristics and in-hospital outcomes were compared and adjusted for covariates to investigate outcomes using a logistic regression model. Statistical significance was determined with a p-value of &lt;0.001. Results: A total of 18,050 patients with COPD were included. Of these, 10,308 (57.1%) underwent surgical mitral valve repair and 7,742 (42.9%) underwent percutaneous mitral valve repair. The percutaneous cohort had a higher prevalence of heart failure, previous myocardial infarction, pulmonary hypertension, chronic kidney disease, and diabetes, while the surgical cohort had a higher prevalence of obesity and atrial tachyarrhythmias. Percutaneous repair was associated with lower rates of mortality, intraoperative complications, postoperative shock, acute coronary syndrome, and transfusions. Upon logistic regression, percutaneous repair was associated with lower rates of mortality (OR 0.28; 99% CI [0.19-0.40]), acute kidney injury (OR 0.38; 99% CI [0.33-0.44]), pneumothorax (OR 0.14; 99% CI [0.09-0.22]), vascular complications (OR 0.40; 99% CI [0.26-0.62]), and infection (OR 0.54; 99% CI [0.39-0.73]; p&lt;0.001 for all groups). Conclusions: In patients with COPD, percutaneous mitral valve repair is associated with lower mortality and procedural complications compared to surgical repair. The presence of COPD should be taken into consideration when deciding treatment strategy for patients with mitral valve disease.

First-choice hormonal therapies for children with infantile epileptic spasms syndrome in South Asia: A network meta-analysis of randomized controlled trials.

Considering the peculiar challenges with infantile epileptic spasms syndrome (IESS) in South Asia and a wide variation in the usage of hormonal therapies, we compared the efficacy and safety of various hormonal therapies for children with IESS in South Asia. We searched PubMed, Embase, Scopus, and Web of Science databases from the inception until April 2024. We included only randomized clinical trials (RCTs) evaluating the efficacy and safety of hormonal therapies for IESS in the South Asian region. Complete cessation of epileptic spasms (ES), electro-clinical response, and time taken to be spasm-free at 2 or 6 weeks of therapy were efficacy outcomes, while the occurrence of adverse events was the safety outcome. Effect estimates were reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) and Cochrane risk of bias 2.0 (ROB 2.0) used for quality assessment of each study. The surface under the cumulative ranking curve (SUCRA) was used to rank the different therapies and reported as a p-score ranging from 0 to 1. Of 747 citations, nine RCTs comprising 566 children with IESS were included. After 2-week treatment, dexamethasone (OR: 6.72; 95% CI: 1.47, 30.72), adrenocorticotropic hormone therapy (ACTH) high dose (HD) (OR: 5.30; 95% CI: 1.05, 26.91), and prednisolone HD (OR: 2.41; 95% CI:1.07, 5.46) had shown significantly greater efficacy for cessation of EScompared with ACTH low dose (LD). Similarly, for electroclinical response, dexamethasone (OR: 9.63; 95% CI: 1.99, 46.70) and prednisolone HD (OR: 3.46; 95% CI: 1.38, 8.68) had greater efficacy compared with ACTH LD. Safety outcomes revealed that hypertension was significantly less common with ACTH LD and prednisolone HD as compared with ACTH HD. This study provides quality evidence on preferred first-choice hormonal therapy for managing IESS in South Asia. ACTH HD, dexamethasone, and prednisolone HD are the most effective hormonal therapy options with dose-dependent therapeutic efficacy. PLAIN LANGUAGE SUMMARY: This study provides insights into the selection of first-line hormonal therapies among the various treatments for managing infantile epileptic spasms syndrome (IESS) in South Asia. The study findings suggested that the effectiveness of these therapies is dose-dependent, with high doses of ACTH, dexamethasone, and prednisolone being the most effective for achieving cessation of epileptic spasms.

Is radiotherapy still the optimal initial choice for patients with early-stage low-grade follicular lymphoma in the modern era? A population-based study.

Despite radiotherapy (RT) is recognized as preferred initial therapy for early-stage low-grade follicular lymphoma (FL) by many international practice guidelines, the medical oncologist has improperly underutilized RT, and diverse management strategies, including systemic therapy (ST), combined modality (CM) and watch and wait (WW), are still used. Except survival outcomes, previous studies concerned little about the treatment-related toxicity, which is also important factor in choosing initial management strategy, especially second primary malignancies (SPMs). The aim of this study was to compare the overall survival (OS) and the SPMs risk between different management strategies, which can provide guidance for the choice of optimal initial management strategy. Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Finally, A total 10,900 patients were identified, in which 930 cases developed SPMs. The use of radiotherapy (RT) has remained consistently low, with a utilization rate of around 20%, while most patients have received watchful waiting (WW) and systemic therapy (ST). In the rituximab era, multivariate analysis indicated that RT exhibited significantly superior OS and did not increase SPMs risk in comparison with ST and WW. At the same time, although there were no significant differences in OS between CM and RT, RT had significantly lower SPMs risk in comparison with CM. The use of RT improved the OS and did not increase the SPMs risk in comparison with other management strategies. Considering the low application rate of RT, oncologists should emphasize and increase the use of RT as an initial management strategy in patients with early-stage low-grade FL.

Single-Center Experience With Endovascular Therapy in Acute Occlusion of ICAS: Preferred Stent Thrombectomy Versus Preferred Angioplasty.

The preferred endovascular therapy (EVT) for large-vessel occlusion in intracranial atherosclerosis (ICAS) is unknown. We compared the efficacy of preferred stent thrombectomy and preferred angioplasty in patients with acute large-vessel occlusion in ICAS. Data from consecutive EVT patients (May 2020 to September 2023) with acute middle cerebral artery occlusion in ICAS were retrospectively analyzed. Preferred angioplasty was performed if there was a preoperative "microcatheter first-pass effect;" otherwise, preferred stent thrombectomy was performed. Analyses were grouped according to the two EVT treatments. Clinical data of all patients, including the time from puncture to recanalization, rate of successful reperfusion, early neurological improvement, intracranial hemorrhage, and modified Rankin Scale score at 90 days, were recorded and analyzed. Six-two patients were enrolled in this study (mean age was 60.66±13.21y, 22.6% female). The preferred angioplasty group had a higher first-pass recanalization rate than the preferred stent thrombectomy group (61.3% vs. 21.9%, P <0.001) and a higher proportion of patients who were functionally independent (defined as a modified Rankin Scale score of 0 to 3) at 90 days [odds ratio,3.681; 95% confidence interval (CI):1.009 to 13.428; P =0.048]. There was no significant difference between the groups in the time from puncture to recanalization, the frequency of successful reperfusion, and early neurological improvement, or intracranial hemorrhage ( P >0.05). This study suggests that for acute middle cerebral artery occlusion in ICAS, preferred angioplasty may be a safe and effective procedure.

Lower incidence of hepatocellular carcinoma with tenofovir alafenamide in chronic hepatitis B: Evidence from a large-scale cohort

Background & AimsThe newer tenofovir alafenamide (TAF) lacks extensive research regarding its impact on hepatocellular carcinoma (HCC). This study aims to evaluate and compare the effects of TAF, tenofovir disoproxil fumarate (TDF), and entecavir (ETV) on HCC incidence using nationwide claim data. MethodsA total of 75,816 treatment-naïve chronic hepatitis B patients were included and divided into TAF (n=25,680), TDF (n=26,954), and ETV (n=23,182) groups after exclusions. Propensity score matching (1:1:1) resulted in 17,537 patients per group, and HCC incidence rates were compared. ResultsBefore matching, the incidence of HCC was significantly lower in the TAF group compared to the TDF and ETV groups (11.47 vs. 15.04 and 14.24 per 1,000 person-years). The incidence rate ratio for TDF was 1.31 (1.19-1.44) and for ETV was 1.24 (1.12-1.37). Before matching, the TAF group had a significantly lower HCC compared to TDF and ETV in both cirrhotic and non-cirrhotic patients. After matching, the TAF group had a lower HCC incidence compared to TDF (12.38 vs. 15.39, incidence rate ratio 1.24, p<0.001) but not ETV (incidence rate ratio 1.08, p=0.219). In cirrhotic patients, TAF had lower HCC incidence than TDF and ETV (30.25 vs. 39.56 and 38.51). In non-cirrhotic patients, TAF had lower HCC incidence than TDF (incidence rate ratio 1.19, p=0.030) but not ETV (incidence rate ratio 0.85, p=0.066). Cox regression analysis showed TAF had a significantly lower HCC incidence compared to TDF (hazard ratio 1.335, p<0.001) and ETV (hazard ratio 1.162, p=0.011), after adjusting for age, gender, and cirrhosis status. ConclusionsThe TAF group consistently demonstrated a lower incidence of HCC compared to the TDF and ETV groups, especially in patients with cirrhosis. IMPACT and IMPLICATIONSThe scientific justification for this work lies in its potential to fill the knowledge gap regarding the comparative efficacy of Tenofovir Alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF), and Entecavir (ETV) in reducing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B patients. The study's findings are particularly crucial for healthcare providers and policymakers, as they highlight the significantly lower incidence of HCC associated with TAF, especially in patients with cirrhosis. These results suggest that TAF could be a preferable antiviral therapy option to mitigate HCC risk, thus influencing clinical decision-making and healthcare guidelines. Practically, these findings can guide physicians in prescribing more effective treatments, assist researchers in designing further studies to explore the mechanisms behind TAF's effectiveness, and inform policymakers in crafting healthcare policies that optimize patient outcomes while considering potential limitations such as the observational nature of the study and residual confounding factors.

Reintegration Into the Workforce After Kidney Transplantation Based on Urbanization Status in Switzerland

IntroductionSwitzerland's urban areas concentrate most of its population and employment opportunities. While kidney transplantation (KT) is the preferred therapy for eligible candidates, individuals in rural areas face challenges accessing specialized medical services due to longer travel distances. Limited understanding exists regarding patients' perspectives on returning to work after KT and whether this correlates with their urbanization status, potentially influencing outcomes. MethodsRetrospective, nationwide (Swiss Transplant Cohort Study) study, from May 2008 to 2020, including 1926 patients aged 18-60 years who underwent KT. We investigated the self-reported work reintegration at 1-, 3- and 5-years after the KT, the recipient and allograft survival and the allograft function at 12 months, contingent on urbanization status (urban, suburban, rural). ResultsThe return rate of sufficiently filled-in questionnaires was 81% (1053 participants). Urban recipients were younger, had longer dialysis time before KT, less living donor KT (LDT). At baseline, the level of education was lower, as well as the workforce, defined as work capacity > 50% (37% urban, 39% suburban, 47% rural). Regression analysis revealed significantly higher Odds Ratio (OR) for employment 1-year post-KT among patients residing in rural and suburban areas (OR 1.31 [CI: 1.04-1.65] and 1.52 [CI: 1.16-1.98], respectively) compared to patients from urban regions. Stratified according to urbanization environment, recipient and allograft survival were comparable across groups. ConclusionsPatient and graft outcomes were favorable, with improved work reintegration observed at the 1-year mark post-KT for recipients from rural backgrounds compared to those from suburban and urban areas.

Bacillus Calmette-Guérin (BCG) Refractory Non-Muscle-Invasive Bladder Cancer (NMIBC): Current Guidance and Experience from Clinical Practice.

BCG is the standard of care for non-muscle invasive high-risk bladder cancer. Notwithstanding the high rate of cure, cancer may recur. A non-muscle invasive high-risk recurrence may be defined as BCG refractory or naïve. BCG refractory patients have been further divided into BCG unresponsive and BCG exposed. A recurrent high-risk bladder cancer within 1 year after BCG induction plus maintenance or two courses of BCG induction defines an unresponsive disease. Any recurrence after 24 months since induction and maintenance should be considered as BCG naïve. The remaining cases are BCG exposed. The standard of care for BCG exposed and naïve patients is another cycle of BCG in the first place, while radical cystectomy should be discussed as alternative with the patient. The preferred therapy for BCG unresponsive patients is radical cystectomy according to AUA or EAU guidelines. However, systemic immunotherapy with pembrolizumab or gene therapy with intravesical nadofaragene firadenovec may be administered for patients unfit or unwilling to undergo radical cystectomy with outcomes superior to intravesical docetaxel, gemcitabine or valrubicin. Our narrative review tries to elucidate BCG refractory definition and treatment specifically regarding alternative therapies to radical cystectomy yet approved or under investigation. The last years have been exciting regarding new developments in this field after a long period of stagnation. Unfortunately, data available on some alternative therapies are mainly limited mainly to Phase I or II studies with a lack of robust evidence, but a clear trend in future treatments has just been drawn.

Perspectives on Treatment Decisions, Preferences, and Adherence and Long-Term Management in Asthma and COPD: A Qualitative Analysis of Patient, Caregiver, and Healthcare Provider Insights.

Asthma and chronic obstructive pulmonary disease (COPD) are associated with substantial morbidity and mortality. This analysis assessed patient, caregiver, and healthcare provider (HCP) opinions regarding asthma and COPD diagnosis and treatment, including inhaler device preferences. Insights were from: (1) face-to-face/telephone patient/HCP communications with GSK Global Medical Teams; (2) social media listening; (3) a self-completed online patient/caregiver survey. Data were anonymized and informed consent was provided. Qualitative outputs were extracted, analyzed inductively, and coded per key themes, such as treatment preferences (including perceptions of single inhaler triple therapy [SITT] versus multiple inhaler triple therapy [MITT]) and long-term treatment goals. Data could be assigned to ≥1 theme. Overall, 2966 patient and HCP insights (patients, 1150; HCPs, 1816), 988 social media posts, and 44 survey responses (patients, 33; caregivers, 11) were included. Within this analysis, some patients delayed seeking medical advice due to lack of disease understanding and used alternative information sources to better understand treatment options (eg, social media). Patients preferred SITT over MITT in terms of convenience, ease of use, and perceived efficacy; some believed that MITT provided greater coverage due to frequent dosing. HCPs recognized the tendency of patient preferences to drive treatment decisions, and highlighted a reluctance to change therapy among some patients, particularly those well controlled in current therapy. Patients preferred therapies with a shorter onset of action. Patients tended to measure treatment success by symptom improvement and quality of life, whereas HCPs measured treatment success through clinical tests. HCPs reported a lack of patient awareness of the mortality risk associated with COPD. There is discordance between patient and HCP perceptions of treatment success and goals in asthma and COPD. Improved patient education and HCP-patient communication are needed to facilitate meaningful shared decision-making, optimize care plans, and provide early treatment options.

Preliminary study on the potential impact of probiotic combination therapy on Helicobacter pylori infection in children using 16S gene sequencing and untargeted metabolomics approach.

The purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics. Twenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics. There was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis. Probiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.