Clinical Investigation Research Articles

Integration of Clinical Trial Development in Hematology-Oncology Fellowship Training.

Several barriers to physicians becoming clinical investigators exist, including inexperience, lack of available mentors, and inconsistent instructive approaches with varying degrees of participation during training. These barriers cause fewer hematology-oncology fellows to pursue academic careers. A consensus is needed on structuring education in clinical investigation paired with active participation in development of a clinical trial guided by a mentor with the goal of increasing fellow interest in clinical research and pursuit of careers in academic medicine. The clinical trial development (CTD) program was initiated at Washington University School of Medicine in St. Louis in 2002 as a hands-on learning experience for hematology and oncology fellows in the design, implementation, and publication of clinical trials. Each fellow was required to identify a mentor and propose at least 1 prospective investigator-initiated clinical trial. At the time of data abstraction in July 2023, 118 fellows had participated in the CTD program and initiated protocols in a variety of areas according to their interests. Fellows were included in data abstraction if their fellowship began in 2002 through 2021; the program is ongoing, and the most recent class will graduate in 2024. Disease types were evenly distributed between solid tumor oncology (60 [51%]) or classic and malignant hematology (58 [49%]). Ninety-three fellows (79%) obtained institutional review board approval, and 60 (65%) published their results. Among graduating fellows, 67 (66%) secured an academic faculty appointment. Fellows with institutional review board-approved projects had significantly higher odds of obtaining an academic faculty appointment (odds ratio, 4.96; 95% confidence interval, 1.54, 15.98; P = .007).Next StepsNext steps will be to further evaluate the effect of the mentorship network on early career productivity of trainees that graduate and the feasibility of extending the program to another institution.

Rhabdomyolysis – A Rare Presentation of COVID-19

Abstract COVID-19 pandemic presented a great global health-care challenge. The spectrum of illness comprises pulmonary and extrapulmonary manifestations including hepatic, renal, and neurological complications. Our patient is a young male who presented with fever, severe myalgia, and respiratory distress. After a thorough clinical examination and laboratory investigations, the diagnosis of COVID-19 pneumonia and associated rhabdomyolysis was made. He developed acute renal failure for which intravenous hydration was given. He also required renal replacement therapy. He was successfully treated and discharged with complete remission of symptoms. We did a literature search for similar cases and have discussed the potential mechanisms implied for these complications.

A Rare Case of Cardiac Amyloidosis Secondary to Multiple Myeloma in A Young Male Presenting with Shortness of Breath

Introduction: Multiple myeloma (MM) is a haematological malignancy associated with various systemic manifestations, including AL amyloidosis.AL amyloidosis is a systemic condition arising from abnormal protein misfolding and deposition, leading to organ dysfunction. Cardiorenal involvement is characteristic. Cardiac amyloidosis causes significant morbidity and mortality, particularly in MM patients. Case Report: A 40-year-old previously well male presented with exertional dyspnoea, lower limb swelling, and frothy urine. Clinical examination and investigations were consistent with an MM complicated by AL amyloidosis affecting the heart and kidneys. The diagnosis of amyloidosis was confirmed through renal biopsies revealing Congo red positivity, along with cardiac imaging showing typical amyloidosis findings. The presence of bone marrow plasma cells 72% confirmed myeloma. Conclusion: This case highlights the challenges in managing MM-associated AL amyloidosis with cardiac and renal involvement. It underscores the importance of comprehensive diagnostic approaches, multidisciplinary collaboration, and tailored treatment strategies. Despite the poor prognosis, diligent management can lead to favourable outcomes and improved quality of life for affected individuals.

The role of immunotherapy in urological cancers.

Immunotherapy is defined as a therapeutic approach that targets or manipulates the immune system. A deeper understanding of the cellular and molecular composition of the tumour environment, as well as the mechanisms controlling the immune system, has made possible the development and clinical investigation of many innovative cancer therapies. Historically, immunotherapy has played an essential role in treating urologic malignancies, while in the modern era, the development of immune checkpoint inhibitors (ICIs) has been critical to urology. Urothelial carcinoma is a common type of cancer in the genitourinary system, and treatment strategies in this area are constantly evolving. Intravesical and systemic immunotherapeutic agents have begun to be used increasingly frequently in treating urothelial carcinoma. These agents increase the anti-tumour response by affecting the body's defence mechanisms. Immunotherapeutic agents used in urothelial carcinoma include various options such as BCG, interferon, anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 (atezolizumab, avelumab, durvalumab). Renal cell carcinoma (RCC) has been known for many years as a tumour with unique sensitivity to immunotherapies. The recent emergence of ICIs that block PD-1/PD-L1 (pembrolizumab, nivolumab, atezolizumab) or CTLA4 (ipilimumab) signalling pathways has reestablished systemic immunotherapy as central to the treatment of advanced RCC. In light of randomized clinical trials conducted with increasing interest in the application of immunotherapies in the adjuvant setting, combination therapies (nivolumab/ipilimumab, nivolumab/cabozantinib, pembrolizumab/ axitinib, pembrolizumab/lenvantinib) have become the standard first-line treatment of metastatic RCC. Prostate cancer is in the immunologically "cold" tumour category; on the contrary, in recent years, immunotherapeutic agents have come to the fore as an essential area in the treatment of this disease. Especially in the treatment of castration-resistant prostate cancer, immunotherapeutic agents constitute an alternative treatment method besides androgen deprivation therapy and chemotherapy. Ipilimumab, nivolumab, pembrolizumab, atezolizumab, and Sipuleucel T (Vaccine-based) are promising alternative treatment options. Considering ongoing randomized clinical trials, immunotherapeutic agents promise to transform the uro-oncology field significantly. In this review, we aimed to summarize the role of immunotherapy in urothelial, renal and prostate cancer in the light of randomized clinical trials.

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders

Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders Abstract: As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.

Navigating the landscape of theranostics in nuclear medicine: current practice and future prospects.

Theranostics refers to the combination of diagnostic biomarkers with therapeutic agents that share a specific target expressed by diseased cells and tissues. Nuclear medicine is an exciting component explored for itsapplicability in theranostic concepts in clinical and research investigations. Nuclear theranostics is based on the employment of radioactive compounds delivering ionizing radiation to diagnose and manage certain diseases employing binding with specifically expressed targets. In the realm of personalized medicine, nuclear theranostics stands as a beacon of potential, potentially revolutionizing disease management. Studies exploring the theranostic profile of radioactive compounds have been presented in this review along with a detailed explanation of radioactive compounds and their theranostic applicability in several diseases. It furnishes insights into their applicability across diverse diseases, elucidating the intricate interplay between these compounds and disease pathologies. Light is shed on the important milestones of nuclear theranostics beginning with radioiodine therapy in thyroid carcinomas, MIBG labelled with iodine in neuroblastoma, and several others. Our perspectives have been put forth regarding the most important theranostic agents along with emerging trends and prospects.

30years of prophylactic thyroidectomy for hereditary medullary thyroid cancer : Amilestone in translational medicine

Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, atumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on apositive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to alesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: ashining example for the success of translational transnational medical research for the benefit of patients.

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

Development of an Emulgel for the Effective Treatment of Atopic Dermatitis: Biocompatibility and Clinical Investigation.

Atopic dermatitis (AD) is a common dermatological disease affecting both children and adults. No drug-free emulgel has been developed and studied in vitro and in vivo for the treatment of AD. The aim of this study was to develop and assess the efficacy of a topical emulgel containing hyaluronic acid, glycerol, Calendula officinalis, Aloe vera, polyphenols and EGF for the concomitant treatment in patients with AD aged over 14. Objective skin barrier function parameters were included, such as transepidermal water loss (TEWL), skin temperature, pH, stratum corneum hydration, skin elasticity and erythema. The subjective opinion of the patients was determined including acceptability, absorption, comfort of use and tolerability, as well as the degree of improvement in patients' quality of life. We observed an improvement in the subjective parameters studied and statistically significant differences in the objective parameters. Specifically, we found an improvement in TEWL (p = 0.006), erythema (p = 0.008) and hydration (p < 0.001), parameters indicating an improvement in the epidermal barrier. One hundred per cent of patients were satisfied with the product. Therefore, these results suggest that the product may contribute to the treatment of AD.

Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis.

Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects.

Evaluating effectiveness and safety of combined percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy in acute cholecystitis patients: Meta-analysis.

Acute cholecystitis (AC) is a common disease in general surgery. Laparoscopic cholecystectomy (LC) is widely recognized as the "gold standard" surgical procedure for treating AC. For low-risk patients without complications, LC is the recommended treatment plan, but there is still controversy regarding the treatment strategy for moderate AC patients, which relies more on the surgeon's experience and the medical platform of the visiting unit. Percutaneous transhepatic gallbladder puncture drainage (PTGBD) can effectively alleviate gallbladder inflammation, reduce gallbladder wall edema and adhesion around the gallbladder, and create a "time window" for elective surgery. To compare the clinical efficacy and safety of LC or PTGBD combined with LC for treating AC patients, providing a theoretical basis for choosing reasonable surgical methods for AC patients. In this study, we conducted a clinical investigation regarding the combined use of PTGBD tubes for the treatment of gastric cancer patients with AC. We performed searches in the following databases: PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database. The search encompassed literature published from the inception of these databases to the present. Subsequently, relevant data were extracted, and a meta-analysis was conducted using RevMan 5.3 software. A comprehensive analysis was conducted, encompassing 24 studies involving a total of 2564 patients. These patients were categorized into two groups: 1371 in the LC group and 1193 in the PTGBD + LC group. The outcomes of the meta-analysis revealed noteworthy disparities between the PTGBD + LC group and the LC group in multiple dimensions: (1) Operative time: Mean difference (MD) = 17.51, 95%CI: 9.53-25.49, P < 0.01; (2) Conversion to open surgery rate: Odds ratio (OR) = 2.95, 95%CI: 1.90-4.58, P < 0.01; (3) Intraoperative bleeding loss: MD = 32.27, 95%CI: 23.03-41.50, P < 0.01; (4) Postoperative hospital stay: MD = 1.44, 95%CI: 0.14-2.73, P = 0.03; (5) Overall postoperative complication rate: OR = 1.88, 95%CI: 1.45-2.43, P < 0.01; (6) Bile duct injury: OR = 2.17, 95%CI: 1.30-3.64, P = 0.003; (7) Intra-abdominal hemorrhage: OR = 2.45, 95%CI: 1.06-5.64, P = 0.004; and (8) Wound infection: OR = 0. These findings consistently favored the PTGBD + LC group over the LC group. There were no significant differences in the total duration of hospitalization [MD = -1.85, 95%CI: -4.86-1.16, P = 0.23] or bile leakage [OR = 1.33, 95%CI: 0.81-2.18, P = 0.26] between the two groups. The combination of PTGBD tubes with LC for AC treatment demonstrated superior clinical efficacy and enhanced safety, suggesting its broader application value in clinical practice.

Gossypetin targets the liver-brain axis to alleviate pre-existing liver fibrosis and hippocampal neuroinflammation in mice.

Liver fibrosis occurs in response to chronic damage and inflammation to the liver. Leaving untreated, it can lead to decreased liver function and can eventually progress to cirrhosis, a more advanced and irreversible state of liver damage. Clinical investigations showed that chronic liver disease associated with neurological symptoms including anxiety, depression, and cognitive decline. However, few therapeutic options are available for treating liver and related brain pathologies simultaneously. In this study, we aim to find therapeutic candidates that target the liver-brain axis. Gossypetin, a flavonoid from sedum, shows promising capability in treating liver and brain pathologies in CCl4-induced mouse model. Short term of gossypetin administration is sufficient to ameliorate impaired liver function and pre-existing liver fibrosis, suppress MKK3/6-p38 MAPK and p53 activation, and abolish the activation of hepatic stellate cells and Kupffer cells. Although we observe no neuronal loss in the brain of mice with liver fibrosis, we do observe astrogliosis and microglial activation in certain brain regions, especially the hippocampus. Brief gossypetin administration also shows potential in alleviating neuroinflammation in these regions. These results suggest that gossypetin can target the liver-brain axis and be a promising candidate for treating chronic liver fibrosis patients with neurological symptoms.

Hidden in plain sight: delayed ADHD diagnosis among girls and women - a commentary on Skoglund etal. (2023).

Skoglund etal. (Journal of Child Psychology and Psychiatry, 2023) finds women with ADHD experience a nearly 4-year delay in receiving an ADHD diagnosis compared to men, despite also having high rates of prior contact with the mental health care system. In this commentary, I discuss the findings of Skoglund etal. and how they shed light on possible explanations for this diagnostic delay among women, and the need to consider women-specific issues, like times of hormonal change, in ADHD diagnosis and treatment.

Hyperthermia for Targeting Cancer and Cancer Stem Cells: Insights from Novel Cellular and Clinical Approaches.

The Cellular Heat Shock Response and in particular heat shock protein activation are vital stress reactions observed in both healthy and cancer cells. Hyperthermia (HT) has been proposed for several years as an advancing non-invasive cancer therapy. It selectively targets cancer cells through mechanisms influenced by temperature and temperature variations. This article delves into the impact of HT on cancer cells, especially cancer stem cells (CSCs), essential contributors to cancer recurrence and metastasis. HT has shown promise in eliminating CSCs, sensitizing them to conventional treatments and modulating the tumor microenvironment. The exploration extends to mesenchymal stem cells (MSCs), which exhibit both pro-tumorigenic and anti-tumorigenic effects. HT's potential in recruiting therapeutic MSCs for targeted delivery of antitumoral agents is also discussed. Furthermore, the article introduces Brain Thermodynamics-guided Hyperthermia (BTGH) technology, a breakthrough in temperature control and modulation of heat transfer under different conditions. This non-invasive method leverages the brain-eyelid thermal tunnel (BTT) to monitor and regulate internal brain temperature. BTGH technology, with its precision and noninvasive continuous monitoring capabilities, is under clinical investigation for applications in neurological disorders and cancer. The innovative three-phase approach involves whole-body HT, targeted brain HT, and organ-specific HT. In conclusion, the exploration of localized or whole-body HT offers promising avenues for cancer, psychiatric and neurological diseases. The ongoing clinical investigations and potential applications underscore the significance of understanding and harnessing heat's responses to enhance human health.

Ameliorative properties of quercetin in the treatment of traumatic brain injury: a mechanistic review based on underlying mechanisms.

Traumatic brain injury (TBI) is a leading cause of disability worldwide, with an estimated annual incidence of 27-69million. TBI is a severe condition that can lead to high mortality rates and long-term cognitive, behavioral, and physical impairments in young adults. It is a significant public health concern due to the lack of effective treatments available. Quercetin, a natural flavonoid found in various fruits and vegetables, has demonstrated therapeutic potential with anti-inflammatory, antioxidant, and neuroprotective properties. Recently, some evidence has accentuated the ameliorating effects of quercetin on TBI. This review discusses quercetin's ability to reduce TBI-related damage by regulating many cellular and molecular pathways. Quercetin in vitro and in vivo studies exhibit promise in reducing inflammation, oxidative stress, apoptosis, and enhancing cognitive function post-TBI. Further clinical investigation into quercetin's therapeutic potential as a readily available adjuvant in the treatment of TBI is warranted in light of these findings. This review adds to our knowledge of quercetin's potential in treating TBI by clarifying its mechanisms of action.

Therapeutic Approaches of Nutraceuticals in Neurological Disorders: A Review

A big problem in healthcare around the world is neurological illnesses. There is a huge healthcare and financial burden on society worldwide due to the dramatically increased risk of chronic sickness and diseases linked with posed lifestyle changes. Fine treatment for sick illnesses with few known adverse effects is the goal of research. A number of functional food studies have been launched in the last few decades in an effort to identify meals with enhanced therapeutic activity and reduced adverse effects. As a result, research into nutraceutical therapy for illness prevention and various extraction procedures for disorders has been underway. Progressive memory loss characterises Alzheimer's disease (AD), a neurodegenerative disorder. The pharmaceutical options available today are expensive, come with unwanted side effects, and are in short supply. Scientists and researchers have noticed that nutraceuticals have a big impact. The anti-Alzheimer's efficacy of nutraceuticals was examined in a number of clinical and preclinical investigations. The study of new therapeutic targets, such as the pathophysiological mechanisms and unique cascades, has resulted from the growing understanding of the AD pathogenesis. Therefore, the most effective and well-known nutraceuticals will be showcased in the present development, together with brief mechanisms involving antioxidants, autophagy control, anti-inflammatory, mitochondrial homeostasis, and more. Nutraceuticals have real-world impacts, and getting your hands on phytochemicals and other vital bioactive ingredients from therapeutically active foods is a top priority. Because of this, the term "functional foods" has been muddied and replaced with similar ones such as "pharmafoods," "medifoods," "vita foods," or "medicinal foods." Nutraceuticals are in high demand to counteract neurological interventions, and there is an urgent need to stick to healthy options. Nutraceuticals may play a preventative role in neurological therapies due to the demonstrated correlation between dietary patterns and lifestyle factors and neurodegeneration. Examining high-quality clinical trials is the focus of the present study, which touches on several important neurological topics. In light of nutraceuticals' promise as multi-targeted therapy for Alzheimer's disease, it is critical to assess them as promising lead molecules for the development of new drugs. Prospective studies should, according to the authors' understanding, take into account blood-brain barrier permeability alteration, bioavailability, and features of randomised clinical trials.

ECG screening and Sudden Cardiac Death prevention in endurance athletes

Abstract Introduction Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport activity. Identifying non-invasive and repeatable risk markers during annual athletes screening remains a crucial goal for the scientific community for the prevention of cardiovascular disease. The ECG, exercise test and spirometry are part of the annual screening program in the sport population over 40 years of age. The Heart Rate Variability (HRV) has been shown to be an independent predictor of mortality in populations with CV disease, but its relationship with SCD has been little explored in those at low risk, including athletes. This study aims to use a 5 minute ECG screening in a specific population of athletes practicing endurance sports and evaluate its clinical repercussions. Aims The primary aim of the study is to assess whether morphological and spectral ECG analysis in endurance athletes by the 5-minute 'mini Holter ECG' can add information to the annual screening for the prevention of CV diseases and SCD. Materials The study population were selected from Endurance Marathon athletes. A control group was also collected for comparison. The 5 minutes ECG was recorded at rest with the Kardia Mobile 6L™ device that use three electrodes, which allows 6 leads recording. HRV indices were obtained using the Kubios software. A morphological analysis was performed and the HRV parameters were analyzed in the time and frequency domains. Results A total of 554 subjects (220 athletes-334 controls, 325 male-229 women) were analyzed. A higher incidence of sinus arrhythmias, LAFB, 1stdegree AVB, J point/ST-segment abnormalities in athletes compared to controls was observed. Athletes had a significantly shorter QTc than the control group (394.87±30.55 ms vs. 407.01±29.09 ms), suggestive of greater protection from malignant ventricular arrhythmias. The HRV PNS (-0.73±1.25 vs -0.21±1.45) and SNS (1.71±1.91 vs 0.58 ± 1.43) indices were also higher and lower in the athlete group than in the control group, suggestive for higher vagal tone. Given the absence of a normality range of standard HRV parameters in the athlete population, values in the normal range of the 5th to 95th percentile were extrapolated in the whole population for the main HRV parameters. The project, therefore, is to evaluate patients with HRV values higher or lower than 5-95 percentile to identify those deserving further clinical investigations and closer follow-up for suspected increased risk of CV disease and SCD. Conclusions The 5-minute cardiac Holter, combining a more accurate analysis in terms of morphology and arrhythmias than the 12-lead ECG, allows a greater number of static and dynamic alterations to be detected; moreover, the analysis of HRV could provide even more information, such that it could be considered as a complementary tool during the examination and FUP of athletes. Further long-term prospective studies are needed to correlate alterations in HRV and clinical events.

ECG screening and prevention of sudden cardiac death in endurance athletes over 40

Abstract Introduction CV diseases increase with age. There are many athletes aged &amp;gt;40 years who practise in certain endurance sports (marathon, ultramarathon and cycling), that involve very high intensity physical exertion and prolonged efforts. This population, like others athletes, undergo to annual examination with a medical history, spirometry, urine test and exercise test. CVdisease and sudden cardiac death (SCD) are the main cause of mortality in athletes during sport and this specific population group are at increased CV risk due to their multiple comorbidities, so this kind of screening remains controversial. Aims The primary aim of the study is to evaluate whether a 5-minute 'mini Holter ECG', associated with the conventional examination, can have an additional role for early screening and prevention of CV diseases in older endurance sport population. Materials The population were selected as part of the larger 'Heart And Run' project, an ECG collection of endurance athletes of the main sports clubs in Rome - Italy. A control group of healty individiuals was collected for comparison. The ECG traces were recorded at rest for 5 minutes with the Kardia Mobile device 6L™. HRV indices were analysed using the software Kubios. The study group were compared for an ECG morphological analysis and HRV parameters in the time and frequency domain. Results A total of 353 subjects (182 athletes, 171 controls) were analysed. The athlets show a significantly higher incidence of sinus arrhythmias, LAFB, 1°degree AVB, Jpoint elevation and STsegment abnormalities. We found also a significantly shorter QTc in athlets compared to controls (395.95 ± 29.51 ms vs. 411.6 ± 29.01 ms), suggestive of greater protection from malignant ventricular arrhythmias. In line with the ECG findings, the HRV PNS (-0.25 ± 1.25 vs -1.05 ± 1.45) and SNS (0.69 ± 1.44 vs 2.38 ± 1.89) indices were respectively higher and lower in the athletes group than in the controls group. Differences between the two groups were also found in the time and frequency HRV domain analysis (SDNN, RMSSD, NN50 and pNN50). Due to the absence of normality range, we considered values lower of the 5th or higher of the 95th percentile range, for the main HRV parameters, as abnormals. We identified 29/182 virtually abnormal HRV individuals. Those patients could be at increased CV risk, worthy of further investigation. In total, out-of-range HRV values or morphological abnormalities were detected in 54 athletes (29%), a population that will need further attention through follow-up and additional examinations. Conclusions Despite competitive endurance sports are associated with increased vagal tone, which is virtually protective against CV diseases, even in athletes over 40, the addition of the 5-minute cardiac 'mini Holter' could increase the sensitivity in detection of CV disease, in a specific high-risk group of athletes, suggesting additional clinical and instrumental investigations in such patients.

Low serum irisin levels predicted newly atrial fibrillation in patients with any phenotypes of chronic heart failure

Abstract Background Atrial fibrillation (AF) continues to be a major health problem among patients with known cardiovascular disease including heart failure (HF). AF is not only powerful risk factor for newly HF, but also it contributes to untoward clinical course of the condition. Although, natriuretic peptides are well-validated biomarkers to predict poor clinical outcomes of HF, their accuracy for AF in patients with different phenotypes of HF is not optimal. Recent studies showed that adipocytokines including irisin affect the risk of AF occurrence. We hypothesized that serum irisin can have additional discriminative potency for AF among HF in patients. Methods The study group comprised 541 consecutive patients with chronic HF aged 41 to 76 years recruited for the study from October 2020 to December 2022. We included 153 patients with any phenotypes of HF who were hospitalized due to paroxysmal or persistent AF and a control group of 388 age- and sex-matched individuals admitted to hospitals due to exacerbation of HF. All patients included in the study were examined by conventional general clinical and physical investigations, B-mode echocardiography and Doppler. The plasma levels N-terminal-natriuretic pro-peptide (NT-proBNP), high sensitivity (hs) C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), hs-troponin T, adropin, apelin, leptin, adiponectin, and irisin were measured using ELISA. Results Compared with patients from control groups, patients with AF had greater left atrial volume index (LAVI), higher serum levels of NT-proBNP, hs-CRP, TNF-alpha, and lower left ventricular ejection fraction (LVEF), irisin and apelin levels. There were no significant difference between groups in left ventricular mass index, the serum levels of hs-troponin T, adropin, leptin, and adiponectin. Multivariate linear regression adjusted to LVEF and LAVI revealed that irisin and NT-proBNP were the predictors for AF. We found that the well-balanced cut-off point for serum concentration of irisin (AF versus non-AF) were 10.5 ng/mL (area under curve [AUC] = 0.96, sensitivity = 81.0%, specificity = 88.0%; P = 0.0001). Cutoff point of NT-proBNP that distinguished patients with AF and without AF was 750 pmol/L (AUC = 0.96; sensitivity = 72.7%, specificity 76.5%, р = 0.0001). Multivariate Cox regression model yielded that the serum levels of irisin &amp;lt; 10.5 ng/mL (odds ratio [OR] = 1.40; P = 0.001) and NT-proBNP &amp;gt; 750 pmol/mL (OR = 1.22; P = 0.012), LAVI &amp;gt; 34 mL/m2 (OR = 1.06; P = 0.010) remained to be strong predictors for newly AF. Add-on of irisin &amp;lt; 10.5 ng/mL to the predictive model constructed from NT-proBNP (&amp;gt; 750 pg/mL) significantly improved discriminatory potency of the whole model for HF. Conclusion We found that decreased serum levels of irisin significantly predicted newly AF in patients with any phenotypes of HF.

Transfemoral leadless pacemaker implantation after tricuspid valve surgery and intervention

Abstract Background and Purpose Pacemaker (PM) implantation after surgical or transcatheter tricuspid valve (TV) repair or replacement may be challenging. Transcatheter leadless pacemaker (LPM) implantation has become a routine procedure and is frequently adopted in patients without the need for an atrial lead, in cases with cardiac implantable device infection or in patients with marked comorbidities. The use of LPM in patients with previous TV repair or replacement has only been described in singular cases in literature. We present our single center experience of LPM implantation after TV repair. Methods Patients with a history of TV repair or replacement who underwent LPM in our institution between 01/2020 and 11/2023 were retrospectively analyzed. All patients underwent routine clinical follow-up investigations including LPM interrogation and transthoracic echocardiography to assess for TV status. For LPM implantation right anterior oblique (RAO) and left anterior oblique (LAO) caudal fluoroscopy projections were utilized to enable LPM device passage across the TV. Results The study population consisted of 10 patients (9 females, mean age 74.0±10.0 years). Two patients had a history of surgical TV annuloplasty repair and two patients a history of surgical valve replacement, four patients of transcatheter TV repair (one through the mitral clip), one patient of transcatheter valve-in-ring bio prosthesis implantation prosthesis after previous surgical ring deployment and one patient transcatheter TV replacement (Figure1). All patients suffered from permanent atrial fibrillation previous to implantation procedures. Three patients were on chronic hemodialysis therapy before LPM implantation. LPM systems were successfully implanted in all cases with a mean procedure time of 43.5±26.5 minutes and a mean fluoroscopy time of 5.9±5.5 minutes and a radiation dose of 1148,7±1424,9 cGy·cm2. For fluoroscopically guided TV crossing a mean LAO angle of 43.6±14.1° (range 22 to 53°) and caudal angle of 8.5±6.9° (range 0 to 20°) was utilized (Figure 2). The LPM device was positioned in the first positioning attempt in a right ventricular high septal localization in 8 cases. Mean pacing threshold was 0.36±0.07 V at 0.25 ms, with a mean sensing amplitude of 10.5±2.9 mV and a mean of 853±324 Ohms pacing impedance. No periprocedural complications occurred. Mean duration of follow-up was 8.1±9.2 months. There were no newly developed TV regurgitations noted. Pacing thresholds (0.37±0.1 V/0.25 ms), sensing amplitude (11.8±4.5 mV) as well as pacing impedances (865±365 Ohms) remained stable until the last follow-up investigation. Conclusion LPM implantation was feasible in patients with a history of TV repair or replacement. LPM implantation was safe and effective in various modalities of TV repair. LPM may be an alternative to conventional pacemaker implantations as well as surgical lead placement in selected patients.Figure 1.Figure 2.