Project description:IntroductionHuman dirofilariasis is a disease historically linked to the Mediterranean area. For the last few decades, however, Dirofilaria nematodes have been spreading, both in terms of prevalence and the geographical expansion in non-endemic areas. Currently, cases of human dirofilariasis are recorded in more than 40 countries worldwide. Croatia is considered an endemic area of the Adriatic basin.MethodsIn a nationwide investigation, new and previously published cases of human dirofilariasis in Croatia were analyzed.ResultsSince 1996, 30 cases of human dirofilariosis were reported in Croatia. A total of 14 (46,67%) cases were from the coastal and 16 (53,33%) from continental regions of the country. Based on anatomical location, 13 (43,33%) cases were subcutaneous, 12 (40%) were ocular and five (16,67%) occurred in the reproductive organs. In all 30 cases, Dirofilaria repens was identified as the causative agent.ConclusionsAn increase in air temperature as climate change, changes in mosquito fauna, high prevalence of D. repens in dogs and limited use of chemoprophylaxis are possible risk factors for Dirofilaria infection in the Croatian population. Since reporting to epidemiological services is not mandatory in this country, the real number of human dirofilariasis cases is probably significantly higher than published. This emphasizes the need for mandatory reporting of human cases and surveillance of Dirofilaria infection in dogs and mosquitoes in Croatia, following the "One Health" concept.
Project description:Peripartum cardiomyopathy is a disease that occurs during or after pregnancy and leads to a significant decline in cardiac function in previously healthy women. Peripartum cardiomyopathy has a varying prevalence among women depending on the part of the world where they live, but it is associated with a significant mortality and morbidity in this population. Therefore, timely diagnosis, treatment, and monitoring of this disease from its onset are of utmost importance. Although many risk factors are associated with the occurrence of peripartum cardiomyopathy, such as conditions of life, age of the woman, nutrient deficiencies, or multiple pregnancies, the exact cause of its onset remains unknown. Advances in research on the genetic associations with cardiomyopathies have provided a wealth of data indicating a possible association with peripartum cardiomyopathy, but due to numerous mutations and data inconsistencies, the exact connection remains unclear. Significant insights into the pathophysiological mechanisms underlying peripartum cardiomyopathy have been provided by the theory of an abnormal 16-kDa prolactin, which may be generated in an oxidative stress environment and lead to vascular and consequently myocardial damage. Recent studies supporting this disease mechanism also include research on the efficacy of bromocriptine (a prolactin synthesis inhibitor) in restoring cardiac function in affected patients. Despite significant progress in the research of this disease, there are still insufficient data on the safety of use of certain drugs treating heart failure during pregnancy and breastfeeding. Considering the metabolic changes that occur in different stages of pregnancy and the postpartum period, determining the correct dosing regimen of medications is of utmost importance not only for better treatment and survival of mothers but also for reducing the risk of toxic effects on the fetus.
Project description:BackgroundGlobal healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends.Material and methodsThe authors reviewed the ACS-NSQIP database (2008-2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model.ResultsDuring the review period, median age increased by 3 years, and median BMI by 0.9 kg/m2. The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m2. Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade.ConclusionGeneral population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care.
Project description:Implantable neurostimulation devices provide a direct therapeutic link to the nervous system and can be considered brain-computer interfaces (BCI). Under this definition, BCI are not simply science fiction, they are part of existing neurosurgical practice. Clinical BCI are standard of care for historically difficult to treat neurological disorders. These systems target the central and peripheral nervous system and include Vagus Nerve Stimulation, Responsive Neurostimulation, and Deep Brain Stimulation. Recent advances in clinical BCI have focused on creating "closed-loop" systems. These systems rely on biomarker feedback and promise individualized therapy with optimal stimulation delivery and minimal side effects. Success of clinical BCI has paralleled research efforts to create BCI that restore upper extremity motor and sensory function to patients. Efforts to develop closed loop motor/sensory BCI is linked to the successes of today's clinical BCI.
Project description:Pertussis is a highly communicable acute respiratory infection caused by Bordetella pertussis. Immunity is not lifelong after natural infection or vaccination. Pertussis outbreaks occur cyclically worldwide and effective vaccination strategies are needed to control disease. Whole-cell pertussis (wP) vaccines became available in the 1940s but have been replaced in many countries with acellular pertussis (aP) vaccines. This review summarizes disease epidemiology before and after the introduction of wP and aP vaccines, discusses the rationale and clinical implications for antigen inclusion in aP vaccines, and provides an overview of novel vaccine strategies aimed at better combating pertussis in the future.
Project description:Artificial intelligence-powered medical technologies are rapidly evolving into applicable solutions for clinical practice. Deep learning algorithms can deal with increasing amounts of data provided by wearables, smartphones, and other mobile monitoring sensors in different areas of medicine. Currently, only very specific settings in clinical practice benefit from the application of artificial intelligence, such as the detection of atrial fibrillation, epilepsy seizures, and hypoglycemia, or the diagnosis of disease based on histopathological examination or medical imaging. The implementation of augmented medicine is long-awaited by patients because it allows for a greater autonomy and a more personalized treatment, however, it is met with resistance from physicians which were not prepared for such an evolution of clinical practice. This phenomenon also creates the need to validate these modern tools with traditional clinical trials, debate the educational upgrade of the medical curriculum in light of digital medicine as well as ethical consideration of the ongoing connected monitoring. The aim of this paper is to discuss recent scientific literature and provide a perspective on the benefits, future opportunities and risks of established artificial intelligence applications in clinical practice on physicians, healthcare institutions, medical education, and bioethics.
Project description:Abatacept is the only T cell co-stimulation modulator approved thus far for the treatment of moderate-to-severe rheumatoid arthritis (RA) and is licensed for use in patients with an inadequate response to methotrexate (MTX) and/or anti-tumor necrosis factor (anti-TNF) therapy. The upstream mechanism of action of abatacept leads to downstream effects in a variety of cell types associated with the production of autoantibodies and pro-inflammatory cytokines implicated in RA. Accumulating data also suggest effects on other cells involved in the pathogenesis of RA, including regulatory T cells and osteoclasts. Clinical trials have demonstrated that abatacept is an effective and well-tolerated treatment in RA. More recently, evidence from the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial showed that complete drug-free remission following treatment with abatacept may be a possibility in some patients with early RA, indicating that the disease course could be altered by early intervention. Equivalent efficacy and onset of action of abatacept and anti-TNF therapy have also been demonstrated in patients with an inadequate response to MTX in the Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background methotrexate (AMPLE) trial. Together, these findings support the use of abatacept in early and established RA.
Project description:Survival for patients with unresectable advanced or recurrent gastric cancer (GC) remains poor and the historical lack of evidence-based therapeutic options after second-line therapy is reflected in current clinical guidelines for this condition. Despite uncertainty about optimal therapeutic strategies, further treatment is appropriate for some patients after failure of second line and may prolong survival. This approach has been reported in clinical trials and is becoming more common in real-world clinical settings. Several prognostic factors may increase the likelihood that a patient will be eligible for treatment in the third-line setting, including geographic location, status at diagnosis and response to treatment. There has been little progress over the last decade until the results from two large phase III randomized controlled trials completed in the last year: the ATTRACTION-2 trial with the programmed cell death-1 (PD-1) inhibitor, nivolumab, in an Asian population; and the TAGS trial with the oral chemotherapy trifluridine/tipiracil in a global population. Both ATTRACTION-2 and TAGS reported positive results in third-line treatment in advanced GC in specific patient groups. A further recently reported study, KEYNOTE-059, which was a single-arm phase II trial of the PD-1 inhibitor pembrolizumab in a mainly non-Asian population, has provided evidence supporting the use of this immunotherapy in patients with advanced GC. As further third-line options become available, more GC patients are expected to benefit from an individualized evidence-based approach to later-line therapy, with a common goal of extending survival and improving outcomes for their refractory disease.
Project description:Genetically-encoded fluorescent sensors have been actively developed over the last few decades and used in live imaging and drug screening. Real-time monitoring of drug action in a specific cellular compartment, organ, or tissue type; the ability to screen at the single-cell resolution; and the elimination of false-positive results caused by low drug bioavailability that is not detected by in vitro testing methods are a few of the obvious benefits of using genetically-encoded fluorescent sensors in drug screening. In combination with high-throughput screening (HTS), some genetically-encoded fluorescent sensors may provide high reproducibility and robustness to assays. We provide a brief overview of successful, perspective, and hopeful attempts at using genetically encoded fluorescent sensors in HTS of modulators of ion channels, Ca2+ homeostasis, GPCR activity, and for screening cytotoxic, anticancer, and anti-parasitic compounds. We discuss the advantages of sensors in whole organism drug screening models and the perspectives of the combination of human disease modeling by CRISPR techniques with genetically encoded fluorescent sensors for drug screening.
Project description:Training the Trainers of Tomorrow Today (T4) is a new way to deliver "Training for Trainers". Responding to local dissatisfaction with existing arrangements, T4 builds on 3 essential requirements for a future shape of training: 1. Clinical Leadership and a Collaborative Approach 2. Cross-Specialty Design and Participation 3. Local Delivery and Governance Networks Design principles also included: 3 levels of training to reflect differing needs of clinical supervisors, educational supervisors and medical education leader, mapping to GMC requirements and the London Deanery's Professional Development Framework; alignment of service, educational theory and research; recognition of challenges in delivering and ensuring attendance in busy acute and mental health settings, and the development of a faculty network. The delivery plan took into account census of professional development uptake and GMC Trainee Surveys. Strong engagement and uptake from the 11 Trusts in NW London has been achieved, with powerful penetration into all specialties. Attendance has exceeded expectations. Against an initial 12 month target of 350 attendances, 693 were achieved in the first 8 months. Evaluation of content demonstrates modules are pitched appropriately to attendees needs, with positive feedback from trainers new to the role. Delivery style has attracted high ratings of satisfaction: 87% attendees rating delivery as "good\excellent". External evaluation of impact demonstrated improved training experiences through changes in supervision, the learning environment and understanding of learning styles. We have addressed sustainability of the programme by advertising and recruiting Local Faculty Development Trainers. Volunteer consultants and higher trainees are trained to deliver the programme on a cascade model, supported by the Specialty Tutors, individual coaching and educational bursaries. The Trainers are local champions for excellence in training, provide a communication between the programme and local providers, are a repository of expertise in their service, and trouble shoot local barriers to engagement.