Clinical Observational Studies Research Articles

Positive Results Using Variable Fixation in Medial Opening Wedge High Tibial Osteotomies in Patients with Unilateral Knee Osteoarthritis: An Observational Clinical Investigation

Background: Medial opening wedge high tibial osteotomy (HTO) treats medial knee osteoarthritis by realigning the knee joint, though it still carries quite a high risk of complications. A new Variable Fixation Locking Screw technology, designed to gradually reduce construct stiffness and promote bone healing, aims to address these issues. This observational study evaluates the safety and effectiveness of this innovative approach in improving clinical outcomes. Methods: Data were prospectively collected on a cohort of the first ten consecutive patients (over 18 years of age) who underwent corrective medial opening wedge high tibial osteotomy using Variable Fixation Locking Screws (VFLSs). The procedure followed the standard surgical technique, with osteotomies stabilized using a Tomofix plate and a combination of standard locking screws and VFLSs. This study aimed to evaluate outcomes such as fracture healing, patient safety, and procedural success at 6 and 12 weeks and at 6 months. Results: No complications, side effects, or need for implant removal were observed. By six months, 70% of patients showed radiographic and clinical healing, and 100% of patients achieved full functional recovery without any issues like length discrepancy, instability, pain, or joint stiffness. Conclusions: This first clinical observation study indicates that Variable Fixation Locking Screws are safe and effective for medial opening wedge high tibial osteotomies, showing promising results in reducing the risk of delayed closure or non-closure of the wedge. Further studies with a larger patient population are needed to confirm their effectiveness.

Kahook Dual Blade Goniotomy versus iStent Implantation Combined with Phacoemulsification: A Systematic Review and Meta-analysis.

In this meta-analysis, Kahook dual blade goniotomy achieved higher rates of surgical success compared to iStent/iStent inject implantation combined with phacoemulsification. KDB goniotomy demonstrated better IOP reduction at month 6 compared to the Stent group. To compare the outcomes of phacoemulsification combined with either Kahook Dual Blade (KDB) goniotomy (phaco-KDB) or trabecular microbypass stent (iStent and iStent inject) implantation (phaco-Stent). A literature search was performed on PubMed, Embase, Web of Science, and Cochrane Library from inception to April 2024. Randomized clinical trials and observational studies that compared KDB goniotomy to the first or second generation iStent combined with phacoemulsification were included. The main outcomes measures were surgical success, mean change in intraocular pressure (IOP) and medication number, and complication rates. Mean differences (MD) and pooled odds ratios (OR) were used to analyze continuous and binary outcomes, respectively. Fourteen studies were included with a total of 1959 eyes (958 phaco-KDB, and 1000 phaco-Stent including 753 phaco-iStent and 207 phaco-iStent inject). The combined findings showed significantly higher rates of surgical success in the phaco-KDB group versus the phaco-Stent group (OR: 0.68; 95% CI:0.50 to 0.92; P=0.01; I2=40%), and greater IOP reduction in the phaco-KDB group versus the phaco-Stent group at month 6 (MD: 1.13mmHg; 95% CI: 0.43 to 1.83; P=0.002; I2=51%). By month 12, both groups demonstrated similar IOP reduction. Subgroup analysis at month 12 showed greater IOP reduction in the phaco-KDB group versus the phaco-iStent group (MD: 1.69mmHg; 95% CI:0.44 to 2.95; P=0.008; I2=74%). However, compared to the phaco-iStent inject group, there was no significant difference in IOP reduction (MD: -0.72mmHg; 95% CI: -3.69 to 2.24; P=0.63; I2=64%). Medication reduction and the incidence of adverse events were comparable between groups. KDB goniotomy may offer better surgical success compared to Stent implantation, when used in combination with phacoemulsification. KDB goniotomy demonstrated better IOP reduction at month 12 compared to iStent. However, iStent inject showed similar IOP reduction to KDB.

Influence of The Anabolic Steroid Usage on The Physical Health: A Review

Introduction: Anabolic steroids are synthetic derivatives of testosterone commonly used to enhance athletic performance and physical appearance. Despite their popularity, their non-medical use is associated with significant health risks. This review aims to synthesize current knowledge on the impact of anabolic steroid use on physical health, emphasizing cardiovascular, hepatic, endocrine, and musculoskeletal systems, as well as broader systemic effects. Materials and Methods: A systematic literature review was conducted using peer-reviewed articles from databases such as PubMed, Scopus, and Google Scholar published between 2000 and 2023. Studies were selected based on relevance, with particular focus on human clinical trials, observational studies, and meta-analyses. Keywords included "anabolic steroids," "health effects," "cardiovascular risk," and "endocrine disruption." Results: Anabolic steroid use is linked to increased cardiovascular risks, liver dysfunction, endocrine disturbances, and musculoskeletal injuries. Key effects include hypertension, hepatotoxicity, testosterone suppression, infertility, and tendon injuries. Psychological impacts such as aggression and mood changes were also observed. Conclusions: Anabolic steroid use poses significant risks to multiple organ systems and overall health. Despite widespread awareness of these dangers, misuse persists, often driven by societal pressures and misinformation. Healthcare providers should prioritize prevention through education, early intervention, and support for individuals at risk. Future research should focus on long-term effects and effective strategies for harm reduction.

Performance of atraumatic restorative treatment in primary care: A study in the elderly with home-based dental care.

To assess the performance of atraumatic restorative treatment (ART) in primary care among an elderly population in need of home-based dental care. It is an observational clinical study, more specifically a descriptive cohort study. The status of these restorations was evaluated1 year after placement. The analysis of ART's clinical performance was conducted through the direct clinical evaluation method, following criteria previously defined in earlier studies. Data were tabulated into sets of descriptive categories, allowing classification into a frequency distribution according to the evaluation score. Success and failure results underwent statistical evaluation using the chi-square test, with a significance level set at 5%. Elderly individuals (n = 35) participated in the study, where 103 restorations were performed in the home environment. The majority of participants were women (68.6%) with an average age of 72.3 years, and 54.3% faced difficulties in motor mobility. All received dental care exclusively at home, and 45.7% used dentures. There was a statistically significant difference (p = 0.0156) between the percentage of failures and successful cases (73.8%) without the need for ART replacement. The majority of ART interventions were on occlusal surfaces (44.9%), showing the highest percentage of restorations in good condition (84.8%), followed by mesio-occlusal (81.3%), while disto-occlusal cavities exhibited the highest failure rate (38.4%). The ART demonstrates satisfactory survival rates in elderly patients after 1 year. This restoration can be a viable alternative for the treatment of older adults, especially in situations that require domiciliary dental care.

The role of p16 gene and P16INK4a protein in hematologic malignancies and therapeutic implications: A systematic review.

Hematological malignancies encompass a diverse group of cancers affecting the blood, bone marrow and lymph nodes. The p16 gene, encoding the P16INK4A protein, plays a pivotal role in cell cycle regulation and tumor suppression. Understanding the involvement of p16 in the development and progression of hematological malignancies is crucial for advancing therapeutic strategies. This systematic review aims to elucidate the multifaceted roles of the p16 gene and P16INK4A protein in hematological malignancies, focusing on their impact on disease pathogenesis, prognostic significance and therapeutic implications. A comprehensive search was conducted across electronic databases, including PubMed, Scopus and Google Scholar, using predefined search terms related to p16, P16INK4A, hematological malignancies, and therapy. Studies published up to 2023 were included, encompassing clinical trials, observational studies, meta-analyses, and preclinical research. The review synthesizes evidence highlighting the dysregulation of the p16 pathway in various hematological cancers. Alterations in p16 expression levels, genetic mutations and epigenetic modifications contribute to disease initiation and progression. Moreover, the prognostic significance of p16 status in predicting therapeutic outcomes and patient survival is explored. The p16 gene and P16INK4A protein emerge as promising biomarkers and therapeutic targets in hematological malignancies. Integrating knowledge of p16 dysregulation into clinical practice holds the potential to optimize treatment strategies, enhance patient outcomes and pave the way for personalized medicine approaches in the management of these challenging diseases.

Therapeutic Drug Monitoring of Nirmatrelvir/Ritonavir (Paxlovid) in Patients Treated for COVID-19: Results from a Prospective Multicenter Observational Study

Background: Paxlovid is a combination of the antiviral agents nirmatrelvir and ritonavir indicated for the oral treatment of high-risk, symptomatic patients with coronavirus disease 2019 (COVID-19). As real-world data on the plasma concentrations of nirmatrelvir/ritonavir (Paxlovid) are limited, the aim of this study was to investigate nirmatrelvir/ritonavir plasma trough levels in a clinical setting using therapeutic drug monitoring. Methods: A prospective, noninterventional, multicenter, observational clinical study was conducted in which the plasma trough levels of nirmatrelvir/ritonavir were simultaneously determined by using liquid chromatography tandem mass spectrometry in patients with symptomatic COVID-19. The blood samples were collected on days 1, 3, and 5 after the first full-dose day (day 0), and patient data such as sex, height, weight, renal function, liver enzymes, and concomitant (co-) medications were obtained to describe the plasma levels with respect to potential influencing factors. Results: A total of 46 blood samples from 21 patients were analyzed. The geometric mean Cmin was 4997 ng/mL for nirmatrelvir and 529.4 ng/mL for ritonavir. The plasma concentrations covered a wide range, the highest being observed in patients with advanced age and renally excreted comedications. Patients older than 65 years had a significantly higher risk of achieving excessive plasma trough concentrations above 8840 ng/mL for nirmatrelvir and 1440 ng/mL for ritonavir compared with younger patients (odds ratio 11.2, 95% confidence interval 1.04–120.4). Conclusions: The plasma trough concentrations of nirmatrelvir and ritonavir in patients treated for symptomatic COVID-19 were higher than the reference values of 2210 ng/mL for nirmatrelvir and 360 ng/mL for ritonavir stated in the product characteristics. Advanced age and renally eliminated comedication were identified as possible influencing factors that warrant further investigation.

Telemedicine for Managing Type 1 Diabetes in Children and Adolescents Before and After the COVID-19 Pandemic.

The COVID-19 pandemic has catalyzed the rapid expansion of telemedicine for managing chronic conditions such as type 1 diabetes (T1D) in children and adolescents. This narrative review aims to explore the role of telemedicine in pediatric T1D management by comparing its use before and after the pandemic. We conducted a comprehensive literature review covering studies published between 2000 and 2024, focusing on telemedicine applications in pediatric T1D care. The review includes clinical trials, systematic reviews, and observational studies examining telemedicine's impact on glycemic control, patient satisfaction, and healthcare delivery. Results reveal that telemedicine has enhanced access to care, improved glycated hemoglobin (HbA1c) levels, and reduced diabetic ketoacidosis and hypoglycemic events. Patients and caregivers expressed high satisfaction, especially when using continuous glucose monitoring and insulin pump technologies integrated with telemedicine platforms. However, challenges such as digital literacy gaps, variability in healthcare provider training, and logistical issues like reimbursement policies persist. The pandemic highlighted the potential of telemedicine to supplement traditional in-person care, showing promise in enhancing patient outcomes and reducing healthcare burdens. Further research is needed to optimize telemedicine models for T1D, addressing barriers to implementation and exploring its long-term cost-effectiveness. This review underscores telemedicine's evolving role as a complementary approach in managing pediatric T1D, advocating for the development of standardized care protocols to fully integrate digital health solutions into routine clinical practice.

Impact of DPP-4 Inhibitors in Patients with Diabetes Mellitus and Heart Failure: An In-Depth Review

The increasing prevalence of both type 2 diabetes mellitus and heart failure has underscored the urgent need for optimized therapeutic strategies that address the complex interplay between these conditions. Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a popular class of glucose-lowering agents due to their favorable glycemic effects, safety profile, and potential cardiovascular benefits. However, the impact of DPP-4 inhibitors on heart failure outcomes in patients with diabetes remains contentious, with conflicting evidence from clinical trials and observational studies. This review critically examines current evidence on the use of DPP-4 inhibitors in patients with coexisting diabetes and heart failure, focusing on pharmacodynamics, safety, and efficacy outcomes. We explore the physiological mechanisms by which DPP-4 inhibitors may influence heart failure risk, including modulation of inflammation, oxidative stress, and myocardial fibrosis. Clinical trials such as SAVOR-TIMI 53, EXAMINE, and TECOS are evaluated to provide a comprehensive analysis of DPP-4 inhibitors’ effects on hospitalization for heart failure, mortality, and cardiovascular events in diabetic patients. While some trials suggest an increased risk of HF hospitalizations with specific DPP-4 inhibitors (e.g., saxagliptin), others report neutral effects, raising questions about the class effects versus individual drug characteristics within this group. Additionally, we address discrepancies in outcomes related to patient demographics, HF phenotype, and comorbid conditions that may influence DPP-4 inhibitors’ risk–benefit profile. Comparative insights into alternative glucose-lowering therapies such as SGLT2 inhibitors and GLP-1 receptor agonists are also provided, highlighting potential implications for treatment selection in this high-risk population. In summary, this review synthesizes available evidence on DPP-4 inhibitors’ impact in diabetic patients with heart failure, aiming to guide clinicians in making informed therapeutic decisions. While DPP-4 inhibitors remain a viable option in diabetes management, caution is warranted in patients with advanced heart failure, and future research is essential to refine patient-specific guidelines.

Diabetes specialist nurse support, training and 'virtual' advice reduces district nurse visits and improves outcomes for people with diabetes requiring visits for insulin administration.

We evaluated the effectiveness of a community diabetes specialist nurse (cDSN) working with district nurses (DNs) to optimise insulin therapy on DN workload and patient outcomes. This was an observational clinical improvement study of outcomes pre- and post-introduction of an intervention within a community diabetes service in an areas of England. Patients were followed up for 6 months. The intervention was a cDSN providing advice and support to DNs in safe diabetes management, with a particular focus on insulin use. in total, 148 of 224 patients were reviewed; 130 (87.8 %) were available for follow up 6 months after their first review. Comparing pre- to post-intervention outcomes, number of patients with a hypoglycaemic event reduced from 21/129 to 1/128 (X2 = 19.71, p < 0.001) as did the number with a hyperglycaemic event; 53/129 to 23/128 (X2 = 16.48, p < 0.001). Number of DN visits and use of acute hospital services also improved significantly. Estimated cost savings through reduced DN visits, insulin usage, and hospital service use totalled £1.9 million. Significant financial savings and reduced patient harms were identified following our intervention in this cohort. Roll-out to other sites in England is a next step.

Carpal Tunnel Syndrome as a Potential Indicator of Cardiac Amyloidosis: A Systematic Review and Meta-Analysis.

Carpal tunnel syndrome (CTS) and cardiac amyloidosis (CA) are seemingly disparate medical conditions but may be linked. CTS can be a sign of early CA, and CA can be a hidden cause of heart failure. Therefore, in this systematic review and meta-analysis, we aim to investigate the expected correlation between the occurrence of CTS and CA. A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Scopus, and Cochrane Library, to get relevant studies previously published before June 2023. No language restrictions were applied. Randomized clinical trials and observational studies have been included to investigate the proportion of patients reporting CA among patients with an established diagnosis of CA, and also the incidence of patients who have CTS among patients with CA has been investigated with a pooled estimation of the expected time from the diagnosis of CTS till the development of CA.Studies that did not report data on CTS or CA or lacked sufficient details were excluded. Meta-analysis of data for each outcome was performed using R version R.4.3.2 software (RFoundation for Statistical Computing, Vienna, Austria) using the Meta package. Heterogeneity across studies was assessed using the I² statistic. A meta-analysis of 15 studies, including 1416 patients, evaluated the relationship between CTSand CA. Among these, 495 patients with CTS were assessed for the presence of CA, and 915 patients with CA were evaluated for the presence of CTS. The pooled meta-analysis of eight studies, which included 915 patients with CA, revealed that 38% (95% CI: 35%-41%) had a history of CTS. Conversely, the proportion of patients with CTS who developed CA was 13% (95% CI: 4%-35%). The pooled mean time from CTS to the development of CA, based on 639 patients across four studies, was 6.02 years (95% CI: 3.76-8.36).Significant heterogeneity was noted for some outcomes (e.g., proportion of CA in patients with CTS: I²=93%), likely influenced by variations in study populations, age distributions, and diagnostic criteria. Our review of the literature suggests that there may be a link between CTS and CA. However, more research is needed to confirm this link and to understand how the two conditions are related. It is important to consider the possibility of CA in patients with CTS, as screening, early detection, and timely treatment can improve outcomes by slowing disease progression and reducing complications.

Prognostic Factors in 26 Cats Undergoing Surgery for Extra-Hepatic Biliary Obstruction

Surgical management of feline extra-hepatic biliary obstruction (EHBO) has poor survival rates with few prognostic factors reported in the literature. The etiology and clinical findings of feline EHBO and their influence on short-(2 weeks–6 months) and long-term (&gt;6 months) survival and prognosis were examined in an observational clinical retrospective study of 26 client-owned cats undergoing surgery for biliary obstruction at one institution between 2012 and 2020. The etiology of EHBO was determined in 21/26 cats, which included inflammatory causes (14/21), neoplastic causes (6/21), and a duodenal foreign body (1/21). Pre-operative hyperbilirubinemia and post-extubation hypotension (mean arterial pressure &lt; 60 mmHg) were statistically associated with reduced short- and long-term survival. Short-term survival was documented in 17/26 cats, and long-term survival in 13/26 cats. Median survival time (MST) was 86 days (range, 0–1497). An MST of 17 days (range, 2–520) in cats with malignancies was found compared to an MST of 1165 days (range, 61–2268) in EHBO resulting from inflammatory complexes. Pre-operative hyperbilirubinemia and immediate post-operative hypotension may represent prognostic factors for cats undergoing surgery for EHBO. Cats with inflammatory causes of EHBO carry a more favorable prognosis than neoplastic causes. Further studies are required to evaluate the validity of the observed associations.

Causal relationship between hypothyroidism and peripheral neuropathy: a Mendelian randomization study of European ancestry.

Metabolic disorders are significant risk factors for peripheral neuropathy (PN) diseases. However, current clinical observational studies cannot fully determine the causal relationships between hypothyroidism (HT) and PN diseases. We performed univariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with hypothyroidism and two diseases clinically presented as HT (autoimmune thyroid disease and benign neoplasm of the pituitary gland and craniopharyngeal duct) as instrumental variables. We selected eight peripheral neuropathy diseases (diabetic neuropathy, nerve root/plexus disorder, carpal tunnel syndrome, polyneuropathies, sciatica with lumbago, trigeminal neuralgia, postherpetic neuralgia, small fiber neuropathy) as outcomes. Genetic data were sourced from authoritative genome-wide association study (GWAS) datasets. We primarily used the inverse variance-weighted (IVW) method and conducted a comprehensive sensitivity analysis to ensure robustness. The IVW results indicated that HT was significantly associated with an increased risk of diabetic peripheral neuropathy (OR = 1.22, p = 6.49E-05). HT was also significantly linked to nerve root/plexus disorder (OR = 1.04, p = 6.43E-06) and carpal tunnel syndrome (OR = 1.04, p = 0.004), but appeared to be a potential protective factor for polyneuropathies (OR = 0.93, p = 0.0009). Additionally, autoimmune thyroid disease (AITD) was identified as a potential risk factor for carpal tunnel syndrome (OR = 13.79, p = 0.006) and a protective factor for polyneuropathies (OR = 0.0011; p = 4.44E-5). This study provides genetic evidence supporting potential causal links between hypothyroidism and various peripheral neuropathy diseases.

Lifestyle and the Gut-Brain Axis Insights into Mental Health and Microbiome Interactions

Introduction: The intricate relationship between lifestyle factors and gut health has become a focus of recent research, emphasizing the significant role of the gut-brain axis (GBA) in regulating both physical and emotional well- being. Unhealthy lifestyle choices, including a diet high in ultra-processed foods, irregular sleep patterns, physical inactivity, and substance abuse, have been closely associated with gut dysbiosis, leading to gastrointestinal (GI) symptoms and mood disturbances such as anxiety and depression. The gut microbiota, through the production of neurotransmitters like serotonin and dopamine, as well as short-chain fatty acids (SCFAs), influences mood and mental health via the GBA. Maintaining a healthy lifestyle, characterized by balanced nutrition, regular physical activity, and good sleep quality, is critical in fostering a diverse and stable gut microbiome, which in turn supports emotional stability.  Aim: This review aims to examine the existing literature on the impact of lifestyle factors, such as diet, physical activity, sleep, smoking, alcohol consumption, and stress management, on gut health and emotional well-being. The goal is to highlight the importance of gut microbiota in mental health and the potential therapeutic strategies to enhance gut health for improved emotional outcomes.  Methodology: A comprehensive search of peer-reviewed journal articles was conducted using databases such as PubMed, Google Scholar, and Web of Science. Keywords like "lifestyle," "gut health," "emotional well-being," "dietary habits," "physical activity," "sleep patterns," and "gut-brain axis" were used to identify relevant studies. Inclusion criteria focused on human clinical trials and observational studies published within the last 16 years. Studies involving animal subjects, non-peer- reviewed articles, and outdated research were excluded.  Results: The literature shows that diets high in fiber and low in processed foods support a healthier gut microbiome, while high consumption of ultra-processed foods disrupts gut bacteria, leading to GI symptoms and mood disorders. Regular physical activity was found to enhance gut microbiota diversity, contributing to better emotional well-being. Conversely, poor sleep quality and chronic stress were linked to gut dysbiosis, which exacerbated mood disturbances. Smoking and excessive alcohol consumption further damaged gut health, contributing to mood dysregulation. Probiotic and prebiotic interventions, particularly synbiotics, were found to restore gut balance and improve both GI and mental health outcomes.  Conclusion: This review underscores the pivotal role of lifestyle choices in shaping gut health and emotional well-being. A balanced diet, regular exercise, sufficient sleep, and stress management are essential for maintaining a healthy gut microbiome, which, in turn, supports emotional stability. Therapeutic strategies involving prebiotics, probiotics, and synbiotics offer promising avenues for improving both gut health and mood. Addressing lifestyle factors and promoting gut health can potentially serve as an effective approach for enhancing overall well-being and preventing mood disorders.

Update on Cannabidiol in Drug-Resistant Epilepsy.

Cannabidiol (CBD) has arisen as a promising therapeutic option for children with drug-resistant epilepsy (DRE). CBD has received regulatory nod from different regulatory authorities in the United States, Europe, and India for children with DRE particularly, Dravet syndrome (DS), Lennox Gastaut syndrome (LGS), and Tuberous sclerosis complex (TSC). Recent clinical trials and observational studies highlight the potential of CBD to lower seizure frequency and provide better quality of life in children affected by these disorders. The safety profile is generally favorable with minor common adverse events such as somnolence, diarrhea, and gastrointestinal issues. Furthermore, the expense associated with CBD remains a notable concern, especially in low- and middle-income countries such as India, where access to this promising treatment may be constrained. This draws attention to the cost-effective perspective of CBD. This review aims to explore the pharmacological properties of CBD, its mechanisms of action, and the clinical evidence supporting its use in various pediatric epilepsies, including LGS, DS, and TSC. Additionally, this review sheds light on the current regulatory landscape in India where CBD use is still in its nascent stages, and discusses the challenges and opportunities for integrating CBD into clinical practice.

Medication adherence, sensory attributes, and adverse effects of intranasal corticosteroids in allergic rhinitis patients: A systematic review and meta-analysis.

Intranasal corticosteroid (INCS) remains the primary treatment for allergic rhinitis (AR). Understanding adherence, safety concerns and sensory preferences is crucial for optimal care. This review aims to determine medication adherence, sensory attributes and adverse effects of INCS in AR patients. A systematic search of PubMed, Web of Science, Scopus, and Cochrane database was conducted for English articles published from 2004 to 2023. Eligibility includes clinical trials and observational studies with adult patients (18 years old or older) receiving INCS for AR (both intermittent and persistent). Thirty-one studies with 10,582 patients, comprising 10 cross-sectional studies and 21 randomized controlled trials (RCT) were included. Adherence rates ranged from 28% to 87%, with an average of 55.8%. Forgetfulness was the primary reason for non-adherence (63.1-77.8%), followed by adverse events (26.4-61.5%) and fear of adverse events (3.8-31.5%). Scent (38%), taste (28.5%), or aftertaste (24.3%) were the main differentiators for sensory attribute, with varying levels of intensity and preferences for each INCS. Common adverse events encompass epistaxis, nasal dryness/irritation, headache and nasopharyngitis. A meta-analysis of eight RCT detected no significant difference in adverse events between the INCS and control groups (risk ratio 1.05; 95% confidence interval, 0.88-1.24; p = 0.61). The findings of this review indicate that medication adherence to INCS is not optimal, with non-adherence mostly attributed to forgetfulness, preferences for sensory attributes, and unpleasant effects associated with INCS. The underlying factors should be addressed as part of a multimodal strategy to improve adherence.

Impact of post RFA treatment on neosquamous epithelium microstructure

Radiofrequency ablation (RFA) is effective treatment for Barrett’s esophagus (BE). Product of successful RFA is neosquamous epithelium (NSE), which resembles native squamous epithelium and has lower risk for neoplastic transformation. Dilated intercellular spaces (IS) are common microscopic feature of reflux induced injury of esophagus. The aim of this study was to analyze the ultrastructure of NSE by transmission electron microscopy (TEM), depending on the post RFA treatment modalities and to asses impact of these findings on BE recurrence. Prospective observational clinical study based on TEM analysis of biopsy of specimens obtained from patients in whom CE of BE was achieved minimum 6 months after the last RFA session. In each patient biopsies were taken from NSE and proximal esophagus. Two groups of patients were defined according to the post RFA treatment: proton pump inhibitors (PPI’s) or laparoscopic Nissen fundoplication (LNF). Comparative analysis of IS length was made between two groups. Endoscopic surveillance with biopsies was conducted for 5 years. Overall 22 patients with CE of BE after RFA underwent complete study protocol, out of whom in 10 LNF was performed, while 12 were treated with PPI’s. The mean values of IS length in the proximal esophagus and NSE in LNF group were 0.378 ± 0.116 µm and 0.878 ± 0.354, while in PPI’s group 0.724 ± 0.325 µm and 1.228 ± 0.226 µm, respectively. Mean lenghts of IS were statistically significantly higher in PPI’s group both in NSE (p = 0.032) and proximal esophagus (p = 0.009). There were 5 BE recurrences after 5 years surveillance, 4 in PPI group and 1 in LNF group, without statistical significance (p = 0.084). Dilated IS are commonly presented in NSE of patients with CE of BE with RFA who are treated with PPI’s. LNF provides may offer better reflux protection of NSE than PPI’s and may reduce the rates of recurrence after successful RFA treatment.

Selinexor combined with bortezomib, lenalidomide, and dexamethasone for the treatment of newly diagnosed multiple myeloma with extramedullary disease

Objective: We aimed to explore the efficacy and safety of Selinexor combined bortezomib, lenalidomide, and dexamethasone (XVRd) protocol in newly diagnosed multiple myeloma with extramedullary disease. Methods: This is a single-arm, open, observational clinical study. For induction/consolidation(21-day cycles), patients received 8 cycles of XVRd protocol. In maintenance (28-day cycles), patients received XR (Selinexor + Lenalidomide) at least 2 years until disease progression, death or withdrawal. The primary endpoints were overall response rates and minimal residual disease negative rates. Results: The median age of the 10 patients was 62 (range 55–81) years. R-ISS stage 3 was present in 2 (20%) patients. 3 patients had high risk cytogenetic and 1 patient with plasma cell leukocyte. According to IMWG criteria, the ORR of 10 patients with NDMM was 100%, including 2 stringent complete response (sCR), 2 complete remission (CR), 4 very good partial response (VGPR) and 2 partial response (PR). Median progression-free survival and overall survival were not achieved. The most common grade 3–4 treatment-emergent adverse events (occurring in 10% of patients) were thrombocytopenia. The most common non-hematological adverse events were grade 1 or 2, including nausea (30%), fatigue (40%), and anorexia (20%). Overall, the severe toxicities were manageable. Conclusion: The XVRd regimen had good efficacy and safety in newly diagnosed multiple myeloma with extramedullary disease.

Uncemented Total Knee Arthroplasty: An Analysis of Biomechanical, Clinical, and Technological Aspects

Introduction: Total knee arthroplasty (TKA) is widely used for treating advanced osteoarthritis and other degenerative conditions, providing pain relief and improved joint function. Traditionally, cemented TKA is preferred for its reliable initial fixation, especially in elderly patients with compromised bone quality. However, with increasing life expectancy and physical demands, uncemented TKA has emerged as a promising alternative, offering benefits in bone preservation and greater implant durability. This study reviews the biomechanical, clinical, and technological aspects of uncemented TKA compared to cemented TKA. Objective: To critically evaluate the effectiveness of uncemented TKA, identifying factors that influence long-term outcomes and comparing its benefits and limitations to cemented TKA. Methods: A review was conducted based on articles published over the last 20 years, including clinical studies, systematic reviews, experimental trials, and observational studies. The search was carried out in the PubMed, Scopus, and Web of Science databases, using specific terms and Boolean operators. Studies were selected according to predefined inclusion and exclusion criteria, and data were extracted and analyzed to compare the outcomes between TKA techniques. Results: Uncemented TKA showed advantages in preserving bone density and reducing reoperation rates in young and active patients due to osteointegration facilitated by materials such as trabecular titanium and hydroxyapatite coatings. However, challenges persist, particularly in patients with osteoporosis, where fixation may be less effective. On the other hand, cemented TKA offers superior initial stability in older patients. Conclusion: Uncemented TKA provides significant benefits, especially for younger patients, but the choice between cemented and uncemented TKA should be personalized, considering factors such as age, bone quality, and physical activity level. Ongoing advances in materials and technologies may further improve uncemented TKA outcomes, but additional studies are needed to strengthen the evidence.

GAMETERAPIA NA FISIOTERAPIA: UM RECURSO PARA REDUZIR O RISCO DE QUEDAS EM IDOSOS DA COMUNIDADE - REVISÃO DE LITERATURA.

The aging population worldwide has led to an increased prevalence of falls among older adults, resulting in fractures, loss of mobility, and increased dependency. This systematic review analyzed the effectiveness of gamification and virtual reality in preventing falls and improving balance in older adults, promoting active aging. Studies published between 2019 and 2024 were analyzed in the Google Scholar, PubMed (Medline), and Lilacs (BVS) databases, considering clinical trials and observational studies with individuals over 65 years of age. The results indicate that the inclusion of gamification with conventional physiotherapy can be effective in improving balance, muscle strength, and cognitive function in older adults, reducing the risk of falls and promoting independence. Due to its playful and motivating nature, it facilitates adherence, just as virtual reality offers an immersive experience that reduces the fear of falling. It is concluded that these interventions require more research to personalize the games and adapt the technologies to the specific needs of the elderly population. Furthermore, it is essential to investigate the long-term effects of gamification and its integration into public health programs.

Definitions of clinical study outcome measures for cardiovascular diseases: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

Standardized definitions for outcome measures in randomized clinical trials and observational studies are essential for robust and valid evaluation of medical products, interventions, care, and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology aimed to create international data standards for cardiovascular clinical study outcome measures. The EuroHeart methods for data standard development were used. From a Global Cardiovascular Outcomes Consortium of 82 experts, five Working Groups were formed to identify and define key outcome measures for: cardiovascular disease (generic outcomes), acute coronary syndrome and percutaneous coronary intervention (ACS/PCI), atrial fibrillation (AF), heart failure (HF) and transcatheter aortic valve implantation (TAVI). A systematic review of the literature informed a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition and categorized the variable as mandatory (Level 1) or optional (Level 2) based on its clinical importance and feasibility. Across the five domains, 24 Level 1 (generic: 5, ACS/PCI: 8, AF: 2; HF: 5, TAVI: 4) and 48 Level 2 (generic: 18, ACS-PCI: 7, AF: 6, HF: 2, TAVI: 15) outcome measures were defined. Internationally derived and endorsed definitions for outcome measures for a range of common cardiovascular diseases and interventions are presented. These may be used for data alignment to enable high-quality observational and randomized clinical research, audit, and quality improvement for patient benefit.