Adjunctive Therapy Research Articles

Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

BackgroundSafinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. MethodsThis multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. ResultsIn total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. ConclusionSafinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. Study registrationUniversity Hospital Medical Information Network in Japan; study ID: UMIN000044341.

Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m2, p = 0.04), body fat (SMD -0.50%, p = 0.02), fat mass (SMD -0.63 kg, p = 0.04), hip circumference (MD -3.14 cm, p = 0.02), and fat-free mass (SMD 1.03 kg, p < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, p = 0.008), natural killer cells (SMD 0.42%, p = 0.04), reductions in triglycerides (MD -81.90 mg/dL, p < 0.01), total cholesterol (SMD -0.95 mmol/L, p < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, p = 0.03), and leptin (SMD -0.63 ng/mL, p = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, p = 0.03), sleep (SMD -1.17, p < 0.001), and quality of life (SMD 2.94, p = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.

The use of mouthwash containing trimetaphosphate as an adjunct therapy to fluoridated toothpaste reduces enamel demineralization

IntroductionThe decline in dental caries has been attributed to the widespread use of fluoride (F). Two forms of presentation are fluoridated toothpaste (FT) and mouthwash (MW), widely used by the population. Materials and methodsThis study aimed to evaluate in vitro the effects of combining FT and MW, whether supplemented with sodium trimetaphosphate (TMP) or not, on dental enamel demineralization. Bovine enamel blocks (n = 60) were selected based on initial surface hardness (SHi) and divided into 5 experimental groups (n = 12 each): I) Placebo Toothpaste (without F/TMP); II) 1100 ppm F Toothpaste (FT); III) 1100F associated with a MW at 100 ppm F (FT + MW 100F); IV) 1100F associated with a MW at 225 ppm F (FT + MW 250F); and V) 1100F associated with a MW at 100 ppm F supplemented with 0.4% TMP (FT + MW 100F-TMP). The blocks were treated twice a day, undergoing 5 pH cycles over 7 days. Thus, the percentage change in surface hardness (%SH), integrated subsurface hardness loss (ΔKHN), and the concentration of F, phosphorus (P), and calcium (Ca) in the enamel were determined. The data were submitted to ANOVA and Student-Newman-Keuls test (p < 0.001). ResultsThe 1100F group was statistically inferior to the groups associated with MW for %SH, ΔKHN, and the concentration of P and Ca in the enamel (p < 0.001). Blocks treated with FT + MW 225F and FT + MW 100F-TMP showed significantly lower %SH compared to the other groups (p < 0.001). The FT + MW 100F - TMP group exhibited the lowest depth mineral loss (ΔKHN), and higher concentration de P in enamel (p < 0.001). ConclusionThe adjunct use of MW with FT produces a greater protective effect in inhibiting enamel demineralization, and the supplementation of TMP to the MW with 100F provides a superior effect compared to MW with 225F. Clinical significanceThis combination of treatments could be regarded as one of several alternative fluoride supplements for subjects at elevated risk of caries.

Biological effects of corticosteroids on pneumococcal pneumonia in Mice—translational significance

BackgroundStreptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples.MethodsWe carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice.ResultsIn mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples.ConclusionsIn combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer's Disease.

Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer's disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.

Does adjunctive clindamycin have a role in Staphylococcus aureus bacteremia? A protocol for the adjunctive treatment domain of the S. aureus Network Adaptive Platform (SNAP) randomized controlled trial.

The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and is recommended in many guidelines, but there is limited evidence underpinning this. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leucocidins (e.g., Panton-Valentine Leucocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multi-center adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either five days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard of care antibiotics. Most participants with SAB (within 72hr of index blood culture and not contraindicated) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and PVL-positive isolate.

Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis.

Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. Open Science Framework: https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Efficacy and Safety of Bromocriptine-QR as an Adjunctive Therapy on Glycemic Control in Subjects with Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Efficacy and Safety of Bromocriptine-QR as an Adjunctive Therapy on Glycemic Control in Subjects with Uncontrolled Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Effect of physical rehabilitation using oromotor stimulation, manual airway clearance technique, positioning, tactile and kinaesthetic stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonatal respiratory distress syndrome (NRDS)- a protocol for randomized controlled trial

Background Neonatal Respiratory Distress Syndrome (NRDS) remains a significant challenge in neonatal care, often leading to respiratory compromise and neuromuscular dysfunction. While advances in medical management have improved outcomes, adjunctive therapies such as physical rehabilitation offer potential benefits yet require further investigation. This protocol outlines a randomized controlled trial aiming to evaluate the effect of Physical Rehabilitation using Oro Motor Stimulation, Manual Airway Clearance Technique, Positioning, Tactile, and Kinesthetic Stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonates with NRDS. Methods The trial will include 38 neonates diagnosed with NRDS, randomly allocated into two groups: the intervention group receiving the PROMPT protocol alongside standard care, and the control group receiving standard care alone. The PROMPT protocol comprises a comprehensive approach targeting oromotor stimulation, manual airway clearance technique, optimal positioning, and tactile/kinesthetic stimulation. Outcome measures Primary outcomes will focus on respiratory parameters such as oxygenation index, ventilatory support requirements, and neuromuscular function assessed through muscle tone and reflexes. Secondary outcomes will encompass length of hospital stay, incidence of complications, and neurodevelopmental outcomes at follow-up. Results Data analysis will employ appropriate statistical methods to compare outcomes between the intervention and control groups, with adjustments for potential confounders. Ethical approval has been obtained, and informed consent will be obtained from parents or legal guardians before enrolment. Conclusion This trial protocol aims to provide valuable insights into the efficacy and safety of the PROMPT protocol as a rehabilitative intervention for NRDS. The findings may inform future clinical practice and contribute to optimizing care strategies for neonates with NRDS, ultimately improving their short- and long-term outcomes. Registration CTRI/2024/03/064911

Decision-making on peri-implant mucositis management and treatment approaches.

Peri-implant mucositis is characterised by inflammation of soft tissues surrounding a dental implant without associated bone loss beyond initial remodelling. Early detection and timely intervention are critical to prevent its progression to peri-implantitis. This paper focuses on various treatment options for treating peri-implant mucositis. The cornerstone of professional treatment lies in the mechanical disruption and removal of microbial biofilms around the implant. This can be achieved through careful use of manual or powered instruments, such as ultrasonic scalers or air polishing devices. However, there is a need for further research to determine the most effective single approach for treating peri-implant mucositis. Current evidence does not support the combination of mechanical debridement with locally administered antibiotics. Contrarily, evidence strongly supports the removal, cleaning, and modifications of prostheses to improve both self-performance and professional cleanability. The use of adjunctive therapies like photodynamic therapy and diode laser, in conjunction with mechanical instrumentation, is not currently recommended due to the limited strength of available evidence. Preventive measures emphasise the importance of comprehensive oral hygiene care, encompassing professional guidance and at-home practices, to manage biofilms effectively. This encompasses oral hygiene instruction, regular debridement, and maintenance care. Supporting peri-implant therapy is also vital for ongoing implant monitoring, preventing the recurrence of mucositis, and halting its progression to peri-implantitis. This multifaceted approach is key to effectively managing and treating peri-implant mucositis.

Gardasil® as adjunctive therapy for respiratory papillomatosis at Red Cross Children’s Hospital, Cape Town

Background: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is an incurable condition caused by human papilloma virus (HPV) types 6 and 11, often requiring repeated surgeries and in severe cases, tracheostomy. This imposes a significant socioeconomic burden on patients and families. Gardasil®, a proven prophylactic HPV vaccine, is emerging as a potential adjuvant therapy. We studied its response on JoRRP patients at our center.Methods: We conducted a retrospective review at Red Cross War Memorial Children’s Hospital from January 2015 to June 2022 on histologically confirmed JoRRP cases. Age at diagnosis, baseline and post-dosing Derkay-Coltrera (DC) scores (disease severity measure), inter-surgical intervals and tracheostomy, were collected.Results: Twenty-five of 30 confirmed cases were included. Average age at diagnosis was 60 months (about 5 years old), with HPV Type 6 in 40% and Type 11 in 48% of patients. All patients received at least one Gardasil® dose, 84% received a second dose and 64% a third dose. Total population DC score decreased from an average of 17 (range: 4-34) pre-first dose to 8 (range: 0-16) after three doses, indicating a 50% reduction. Surgical intervals modestly increased. More significant improvements were seen in patients with aggressive forms of the disease.Conclusion: This is the first study in Southern Africa highlighting Gardasil® as adjuvant therapy. Despite our limited sample size, new cases observed a linear reduction in DC scores and tracheostomy rates.Contribution: This suggests that Gardasil® as adjuvant therapy has the potential to reduce disease severity and extend surgical intervals.

#624 The impact of hemoadsorption in patients with borderline chronic kidney disease undergoing coronary artery bypass grafting

Abstract Background and Aims With an annual incidence of up to 30%, cardiac surgery–associated acute kidney injury (CSA-AKI) may be one of the most underappreciated yet frequent complications and renal protective adjustments are crucial. We evaluated the impact of hemoadsorption as adjunctive therapy on clinical outcome in Kidney Disease Improving Global Outcomes (KDIGO) G2/A2) patients undergoing coronary artery bypass grafting (CABG). Method During a three-year period, 40 patients undergoing CABG with borderline chronic kidney disease (KDIGO-G2/A2) were treated with adjunctive hemoadsorption therapy and were compared by propensity score-matched 40 patients (KDIGO G2/A2) (Control). Primary endpoints were the need for renal replacement therapy (RRT)/dialysis and/or worsening of KDIGO stage in the perioperative period. Secondary endpoints were the change in inflammatory biomarkers, vasopressor requirement and ICU/hospital stay. In the study group, a 300 mL hemoadsorber (Cytosorbents Inc, NJ) was used for the entire duration of cardiopulmonary bypass (CPB). All patients were prepared via enhanced recovery after surgery (ERAS) protocol and surgical procedures were performed under moderate hypothermia with pulsatile flow and ultrafiltration. Patients with septic shock, limited life expectancy and refused to give consent were excluded. Results After institutional ethics committee approval was obtained, written informed consent was received from each patient. No significant difference was noted between groups in demographic, operative data and preoperative baseline laboratory. At the end of CPB; s-Creatinine (mg/dL) (1.85 ± 0.6 vs 2.751 ± 0.6; p = 0.035), NT-proBNP (pg/L) (130 ± 30 vs 180 ± 40; p = 0.04), IL-6 (pg/mL) (8.2 ± 4 vs 22.2 ± 4; p = 0.012) and myoglobulin (pg/L) (210 ± 75 vs 310 ± 80; p = 0.04) levels were significantly lower in the study group versus control. Clinical outcome is summarized in Figure. Conclusion This pioneering study demonstrated the additional protective effects of hemoadsorption in patients with borderline chronic kidney disease (KDIGO-G2/A2) undergoing CABG. Elimination of inflammatory parameters might be a complementary mechanism resulting in lesser worsening of kidney function/need of RRT and ICU stay. These findings require validation in large, multicenter trials.

#510 Evaluating tolvaptan as a protective agent for cardiac insufficiency in peritoneal dialysis patients

Abstract Introduction Peritoneal dialysis serves as a highly effective renal replacement therapy, offering prolonged preservation of residual renal function, improved blood pressure regulation, and enhanced quality of life. While diuretics are generally considered safe and beneficial in this context, their efficacy may be limited in certain cases. Background and Aims The rationale behind investigating the potential benefits of tolvaptan in peritoneal dialysis stems from existing studies in Asia, where the use of tolvaptan has been approved in this population. These studies, conducted on patients undergoing peritoneal dialysis, indicate notable improvements in urine output and key heart failure indicators such as Left Ventricular Mass Index (LVMI) and Brain Natriuretic Peptide (BNP). Materials &amp; Methods Recognizing the significance of these findings, a recent meta-analysis was conducted to comprehensively assess the collective data. The meta-analysis encompassed data from five pertinent studies involving a total of 70 peritoneal dialysis patients, with an average age of 66.1 ± 15 years. Participants received tolvaptan in doses of up to 15 mg, and the mean follow-up period was 8.2 ± 3.9 months. Results Results from the meta-analysis revealed a significant increase in urine volume in two out of four instances (Mean Difference [MD]= +554.5 cc [379,730], I²=61.5). While most studies did not indicate substantial changes in body weight or renal kt/V, a notable reduction in Left Ventricular Mass Index was evident in two studies (MD= -43.28 [-84.9,-1.6], I²=80.6%). Additionally, a substantial reduction in BNP was reported in one study, with no documented adverse events across the studies. Conclusion As an adjunct therapy, tolvaptan exhibits potential benefits in volume control, potentially contributing to improved cardiac function in peritoneal dialysis patients. The findings of this study align with existing research, highlighting the positive impact of tolvaptan on heart failure markers. Nevertheless, further high-quality studies are imperative to consolidate and validate these observed benefits in the peritoneal dialysis population.

#2188 Challenges in lipid control in the advanced chronic kidney disease clinic: findings from a cross-sectional study

Abstract Background and Aims Chronic kidney disease (CKD) is associated with lipid metabolism disruptions and heightens cardiovascular (CV) risk. International guidelines categorize CKD patients into high CV risk (LDL target &amp;lt; 70 mg/dL and a reduction &amp;gt;50% from baseline) for CKD G3b A1, CKD G3a A2, and CKD G2 A3; and very high CV risk (LDL target &amp;lt; 55 mg/dL and a reduction &amp;gt;50% from baseline) for CKD G4 and G5, CKD G3b A2-3, and those with type 2 diabetes and G3a A2-3, G3b regardless of UACR, or UACR &amp;gt; 300 mg/g regardless of eGFR. This cross-sectional study aims to evaluate the challenges of achieving LDL targets in advanced CKD patients, focusing on statin use. Method A cross-sectional study enrolled 312 patients with advanced CKD. Collected data included demographics, renal function stage, albuminuria/proteinuria, diabetes, and cardiovascular history. Documented statin use specified type and potency. Statistical analysis employed descriptive measures. Results Of the 312 patients, 207 were males, with a mean age of 69.18 ± 10.26 years, mean eGFR of 27.54 ± 12.22, and LDL of 86.64 ± 32.9. The majority had a history of diabetes (158) and previous cardiovascular disease (100). 69.6% used statins, with atorvastatin being the most common (165), followed by simvastatin (26), pravastatin (11), rosuvastatin (10), and pitavastatin (5). Statin potency varied, with high potency in 49.4%, moderate in 49.2%, and low in 1.4%. Only 19.6% of patients achieved adequate lipid control per guidelines. Conclusion This study underscores the high prevalence of dyslipidemia and the challenges in achieving LDL targets in advanced CKD patients. Despite the presence of cardiovascular risk factors, including a history of cardiovascular events, the majority did not attain adequate lipid control, highlighting the imperative to address therapeutic inertia to prevent LDL detrimental consequences. Specific strategies are warranted, focusing on mitigating statins’ underutilization and low potency. Additionally, consideration of adjunct therapies such as ezetimibe and bempedoic acid is crucial. Exploring novel agents like iPCSK9 or inclisiran emerges as promising avenues for safer and more effective alternatives in this population at high cardiovascular risk.

#2014 Exercise safety and efficacy as a rehabilitation therapy for patients on hemodiafiltration: a 6-month controlled study

Abstract Background and Aims Individuals with chronic kidney disease (CKD) stage 5D face challenges due to the accumulation of uremic toxins. Hemodiafiltration (HDF) stands out for its efficacy in removing solutes of various molecular weights, offering mortality benefits. Although exercise rehabilitation is established as a beneficial adjunct therapy for patients on maintenance hemodialysis, its impact on maintenance HDF programs remains understudied. The primary aim was to evaluate the safety and efficacy of exercise as rehabilitation in patients undergoing HDF. The secondary aim was to compare the outcomes between intra- and inter-HDF exercise sessions. Method This study enrolled CKD 5D patients at Fenix Nephrology Group from 2021 to 2023. The assessment occurred at the initiation of the exercise program and after six months of exercise rehabilitation. Physical tests included the step-test, handgrip, and one-repetition maximum (1RM), and the Kidney Disease Quality of Life Short Form (KDQOL-SF), a patient-reported outcome measure. The urea reduction ratio (URR) reflected HDF adequacy. Patients engaged in twice-weekly aerobic exercises achieving 70% of maximum heart rate and resistance exercises (60% 1RM). Results Data from 234 patients were obtained, and 81 were not on the exercise program. From the remaining 153 patients, we excluded 64. Twelve patients were excluded because underwent kidney transplantation during their participation, 41 had incomplete data, and 11 patients carried out less than 80% of the scheduled exercise sessions. We included in our final analysis data from 89 patients (55 ± 15 years; 58.4% male). The mean dialysis vintage was 9 ± 7 years, including high-flux hemodialysis and HDF. Specifically, for HDF, the mean dialysis vintage was 5 ± 4 years. Mean exercise session adherence was 94 ± 4%, and the mean number of sessions was 39 ± 4. Concerning the performance outcomes, we observed significant improvements in the step-test (80 ± 22 to 93 ± 25 steps; p &amp;lt; 0.001) and handgrip measurement (28 ± 7 to 30 ± 7 kgf; p &amp;lt; 0.001), alongside an approximate 4% increase in lean body mass (13 ± 2 to 14 ± 2 kg; p &amp;lt; 0.001) during the 6 months. The KDQOL-SF improved in physical functioning (64 ± 22 to 72 ± 23; p &amp;lt; 0.001), general health (55 ± 23 to 61 ± 2; p = 0.01), social function (73 ± 26 to 80 ± 21; p = 0.004), physical (43 ± 9 to 47 ± 8; p &amp;lt; 0.001) and mental composite scores (46 ± 10 to 48 ± 9; p = 0.04), along with a reduction in fatigue (57 ± 17 to 60 ± 17; p = 0.03). A similar favorable trend was observed for the URR (68 ± 10% vs. 71 ± 8%; p &amp;lt; 0.05). We also analyzed the exercise rehabilitation program in two different groups. Thirty-five patients carried out intradialytic exercise (i.e., during the dialysis session). In this group, the mean dialysis vintage was 10 ± 7 years and specifically 5 ± 3 years on HDF. The other group included 54 patients performing interdialytic exercise (i.e., pre- or post-session). In this group, the mean dialysis vintage was 8 ± 6 years and specifically 4 ± 2 years on HDF. We did not observe complications during the exercise program, and no sessions were interrupted due to adverse events. Demographic and anthropometric data (age, sex, weight, and body mass index) were comparable between the groups. Furthermore, exercise performance was equivalent in both groups. Conclusion Our findings suggest that a supervised exercise program for maintenance dialysis patients performing HDF is safe and efficacious, yielding substantial improvements in patient-reported and performance outcomes. Notably, the positive effects of exercise persisted whether conducted during intradialytic or interdialytic periods.

#2196 Impact of intradialytic exercise on blood pressure and quality of life in hemodialysis patients: a randomized controlled trial

Abstract Background and Aims Hemodialysis is essential for end-stage renal disease (ESRD) patients, but they often face complications affecting their quality of life and cardiovascular health. Exercise has emerged as a potential adjunct therapy for improving outcomes in hemodialysis patients. This study aimed to examine the effects of exercise during dialysis on laboratory parameters, intradialytic blood pressure events, and quality of life in hemodialysis patients. Method An Egyptian dialysis center conducted a 6-month randomized controlled trial involving 80 hemodialysis patients. Patients were randomized into two groups: an intervention group (40 patients), which engaged in 30-minute exercise)in the form of 15 minutes for cycler and 15 minutes for hand grip (three times per week during dialysis sessions, and a control group (40 patients), which did not exercise. Laboratory investigations were performed before and after the intervention, measuring hemoglobin, serum sodium, potassium, calcium, phosphorus, and intact parathyroid hormone (iPTH). Intradialytic blood pressure events were recorded, and quality of life (QOL) was assessed using the Arabic version of the kidney disease and Quality of Life-Short Form 36 (KDQOL-SF™) Questionnaire. Results The intervention group exhibited a statistically significant reduction in inter-dialytic hypertension episodes compared to the control group (partial η² = .142, Cohen's f = .407). Additionally, the intervention group showed a significant increase in the physical composite score (partial η² = .178, Cohen's f = .465) accompanied by a significant decrease in the mental composite score (partial η² = .232, Cohen's f = .550) Moreover, The intervention group demonstrated a significant reduction in serum calcium levels post-intervention compared to the control group (partial η² = .069, Cohen's f = .272), with a positive correlation between the change in calcium level and the change in the physical composite score. Conclusion These findings indicate that exercise during haemodialysis may contribute to better blood pressure control and improved physical functioning. Incorporating exercise into the dialysis routine may serve as an effective approach to optimize the health and well-being of haemodialysis patients. Further research should focus on long-term effects and optimal exercise protocols to maximize these benefits.

Combination SGLT2 Inhibitor and Glucagon Receptor Antagonist Therapy in Type 1 Diabetes: A Randomized Clinical Trial.

To examine the effects of insulin-adjunctive therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and a glucagon receptor antagonist (GRA) on glycemia, insulin use, and ketogenesis during insulinopenia in type 1 diabetes. In a randomized, double-blind, placebo-controlled, crossover trial we assessed the effects of adjunctive SGLT2 inhibitor therapy (dapagliflozin 10 mg daily) alone and in combination with the GRA volagidemab (70 mg weekly) in 12 adults with type 1 diabetes. Continuous glucose monitoring, insulin dosing, and insulin withdrawal tests (IWT) for measurement of glucose and ketogenesis during insulinopenia were completed during insulin-only (Baseline), SGLT2 inhibitor, and combination (SGLT2 inhibitor + GRA) therapy periods. Average glucose and percent time with glucose in range (70-180 mg/dL) improved with combination therapy versus Baseline and SGLT2 inhibitor (131 vs. 150 and 138 mg/dL [P < 0.001 and P = 0.01] and 86% vs. 70% and 78% [P < 0.001 and P = 0.03], respectively) without increased hypoglycemia. Total daily insulin use decreased with combination therapy versus Baseline and SGLT2 inhibitor (0.41 vs. 0.56 and 0.52 units/kg/day [P < 0.001 and P = 0.002]). Peak β-hydroxybutyrate levels during IWT were lower with combination therapy than with SGLT2 inhibitor (2.0 vs. 2.4 mmol/L; P = 0.048) and similar to levels reached during the Baseline testing period (2.1 mmol/L). Participants reported enhanced treatment acceptability and satisfaction with combination therapy. Glucagon antagonism enhances the therapeutic effects of SGLT2 inhibition in type 1 diabetes. Combination therapy improves glycemic control, reduces insulin dosing, and suggests a strategy to unlock the benefits of SGLT2 inhibitors while mitigating the risk of diabetic ketoacidosis.

A Comparative Clinical Evaluation of Subgingivally Delivered 0.5% Azithromycin Gel and 1% Chlorhexidine Gel as an Adjunct to Scaling and Root Planing in the Treatment of Chronic Periodontitis

ABSTRACT Background: Chronic periodontitis is a prevalent inflammatory condition affecting the supporting structures of teeth. Adjunctive therapies to scaling and root planing (SRP) play a crucial role in enhancing treatment outcomes. This study aimed to compare the clinical effectiveness of subgingivally delivered 0.5% azithromycin gel and 1% chlorhexidine gel as adjuncts to SRP in the management of chronic periodontitis. Materials and Methods: A comparative clinical evaluation was conducted involving 60 participants diagnosed with chronic periodontitis. They were randomly assigned to two groups: Group A received subgingival application of 0.5% azithromycin gel after SRP, whereas Group B received 1% chlorhexidine gel in a similar manner. Clinical parameters including probing pocket depth (PPD), clinical attachment level (CAL), and gingival index (GI) were recorded at baseline and 3-month follow-up. Results: Both groups demonstrated significant improvements in clinical parameters after treatment. However, Group A exhibited a greater reduction in PPD (mean decrease of 2.5 mm) compared with Group B (mean decrease of 1.8 mm). Similarly, Group A showed a higher gain in CAL (mean gain of 2.3 mm) compared with Group B (mean gain of 1.5 mm). In addition, a significant reduction in GI was observed in both groups, with Group A showing slightly better outcomes. Conclusion: Subgingivally delivered 0.5% azithromycin gel demonstrated superior clinical efficacy as an adjunct to SRP in the treatment of chronic periodontitis compared with 1% chlorhexidine gel. The findings suggest that azithromycin gel may serve as a promising therapeutic option in managing periodontal disease.

Catheter ablation as an adjunctive therapy to ICD implantation in Brugada syndrome.

Brugada Syndrome (BrS) is a life-threatening cardiac arrhythmia disorder associated with an increased risk ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Current management primarily relies on implantable cardioverter-defibrillators (ICDs), but patients may experience ICD shocks. Catheter ablation (CA) has emerged as a potential intervention to target the arrhythmogenic substrate. This systematic review aims to evaluate the safety and efficacy of catheter ablation in BrS patients. Studies with BrS patients undergoing catheter ablation for VAs were included. 14 studies that involved a total population of 709 BrS patients, with catheter ablation performed in 528 of them, were included. Catheter ablation resulted in non-inducibility of VAs in 91% (95% CI: 83-99, I2=76%) and resolution of Type 1 ECG Brugada pattern in 88% (95% CI: 81-96.2, I2=91%) of the patients. After a mean follow-up of 30.7 months, 87% (95% CI: 80-94, I2=82%) of patients remained free from VAs. The incidence of VAs during follow-up was significantly lower in the ablation cohort in comparison to the group receiving only ICD therapy (OR=0.03, 95% CI: 0.01-0.12, I2=0%). Catheter ablation shows potential as a therapeutic approach to reduce VAs and improve outcomes in BrS patients. While further research with long follow-up period is required to confirm these findings, it represents a valuable tool as an add-on intervention to ICD implantation in BrS patients with high burden of VAs.Protocol registration: CRD42024506439.

Effects of jujube (Ziziphus jujuba mill.) fruit extracts on oxidative stress: A systematic review and meta‐analysis of rodent studies

AbstractThis study aimed to evaluate the effects of jujube (Ziziphus jujuba Mill.) fruit extracts on oxidative stress levels in rodent models. Animal studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Periodical Service Platform. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk‐of‐bias tool was used to evaluate the risk of bias in the included studies. A meta‐analysis was performed based on the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) by using Stata 17.0 software. Nineteen studies were included in the meta‐analysis. Jujube fruit extracts significantly decreased the level of malonaldehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px). Meanwhile, there was no significant improvement in the catalase (CAT) levels. In addition, there was considerable heterogeneity in the results of the meta‐analysis. The results of the subgroup analysis indicated that the animal model, type of extracts, and source of target parameters may have contributed to the heterogeneity. Jujube fruit extracts are healthy and effective antioxidant dietary supplements that may be an effective adjunctive therapy for diseases in which oxidative stress is a major pathological factor. However, the overall methodological quality of the included studies was low, and additional research is warranted.