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ABSTRACT: The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte (CAR‐T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI‐related myocarditis with cardiogenic shock to more common complications including less severe ICI‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR‐T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

Abstract Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice.

Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with HF.This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF.The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors.SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.

Advances in cancer therapeutics have led to dramatic improvements in survival, now inclusive of nearly 20 million patients and rising. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Advances in cardiovascular imaging have solidified the critical role for robust methods for detecting, monitoring, and prognosticating cardiac risk among patients with cancer. However, decentralized evaluations have led to a lack of consensus on the optimal uses of imaging in contemporary cancer treatment (eg, immunotherapy, targeted, or biological therapy) settings. Similarly, available isolated preclinical and clinical studies have provided incomplete insights into the effectiveness of multiple modalities for cardiovascular imaging in cancer care. The aims of this scientific statement are to define the current state of evidence for cardiovascular imaging in the cancer treatment and survivorship settings and to propose novel methodological approaches to inform the optimal application of cardiovascular imaging in future clinical trials and registries. We also propose an evidence-based integrated approach to the use of cardiovascular imaging in routine clinical settings. This scientific statement summarizes and clarifies available evidence while providing guidance on the optimal uses of multimodality cardiovascular imaging in the era of emerging anticancer therapies.

Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry.We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative.A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment.We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

BACKGROUND: Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. METHODS: The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Womens Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. RESULTS: Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p

AimsHaematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant haematologic conditions. Patients undergoing HSCT are at an increased risk of developing atrial fibrillation (AF). We hypothesized that a diagnosis of AF would be associated with poor outcomes in patients undergoing HSCT.Methods and resultsThe National Inpatient Sample (2016-19) was queried with ICD-10 codes to identify patients aged >50 years undergoing HSCT. Clinical outcomes were compared between patients with and without AF. A multivariable regression model adjusting for demographics and comorbidities was used to calculate the adjusted odds ratio (aOR) and regression coefficients with corresponding 95% confidence intervals and P-values. A total of 50 570 weighted hospitalizations for HSCT were identified, out of which 5820 (11.5%) had AF. Atrial fibrillation was found to be independently associated with higher inpatient mortality (aOR 2.75; 1.9-3.98; P < 0.001), cardiac arrest (aOR 2.86; 1.55-5.26; P = 0.001), acute kidney injury (aOR 1.89; 1.6-2.23; P < 0.001), acute heart failure exacerbation (aOR 5.01; 3.54-7.1; P < 0.001), cardiogenic shock (aOR 7.73; 3.17-18.8; P < 0.001), and acute respiratory failure (aOR 3.24; 2.56-4.1; P < 0.001) as well as higher mean length of stay (LOS) (+2.67; 1.79-3.55; P < 0.001) and cost of care (+67 529; 36 630-98 427; P < 0.001).ConclusionAmong patients undergoing HSCT, AF was independently associated with poor in-hospital outcomes, higher LOS, and cost of care.

BackgroundReducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes.MethodsWe estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest.FindingsFrom an estimated 13·7 million (95% UI 10·9-17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7-10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2-18·1) of all global deaths and 56·2% (52·1-60·1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54·9% (52·9-56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4-71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths.InterpretationThe 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development.FundingBill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

Background: Evidence regarding the effect of long-term exposure to particulate matter (PM) 2.5 and comorbid cancer and cardiovascular disease (CVD) mortality is limited. Objectives: In this study, the author report the association between long-term exposure to PM 2.5 and CVD mortality, cancer mortality and comorbid cancer and CVD mortality in the U.S. population. Methods: The Centers for Disease Control and Prevention (CDC) WONDER (Wide-Ranging Online Data for Epidemiologic Research) multiple-cause-of-death database was used to obtain U.S. county-level mortality and population estimates from 2016 to 2020. Data on average daily density of PM 2.5 were abstracted from the 2018 CDC’s National Environmental Public Health Tracking system. Counties were divided into quartiles with Q1 representing counties with least average daily density and Q4 representing counties with maximum average daily density of PM 2.5. Age-adjusted mortality rates were abstracted for each quartile, for the overall population and subgroups of population. Results: The age-adjusted mortality rates for CVD, cancer, and comorbid cancer and CVD mortality were 505.3 (range: 505.0-505.7), 210.7 (range: 210.5-210.9), and 62.0 (range: 61.8-62.1) per 100,000 person-years, respectively. CVD mortality had the highest percentage excess mortality in Q4 compared with Q1, followed by comorbid cancer and CVD. Cancer had the least percentage excess mortality. A disproportionate effect of PM 2.5 exposure was noted on vulnerable and minority groups, based on Social Vulnerability Index and race stratification, respectively. Conclusions: Higher levels of long-term PM 2.5 exposure reported increased CVD mortality, cancer mortality and comorbid cancer and CVD disease mortality, with a pronounced detrimental effect in vulnerable and minority population.

Background Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1‐point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. Methods and Results Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010–2019) and followed up at a large, hybrid academic‐community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0–11). Adjusted Fine–Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2‐year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1‐point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06–1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12–1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08–1.19]). When considering AL as a time‐varying exposure, the peak associated MACE risk occurred with a 1‐point AL rise between 6 and 12 months post‐ breast cancer, lung cancer, and colorectal cancer diagnosis. Conclusions AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

BackgroundThe occupational burnout epidemic is a growing issue, and in the United States, up to 60% of medical students, residents, physicians, and registered nurses experience symptoms. Wearable technologies may provide an opportunity to predict the onset of burnout and other forms of distress using physiological markers. ObjectiveThis study aims to identify physiological biomarkers of burnout, and establish what gaps are currently present in the use of wearable technologies for burnout prediction among health care professionals (HCPs). MethodsA comprehensive search of several databases was performed on June 7, 2022. No date limits were set for the search. The databases were Ovid: MEDLINE(R), Embase, Healthstar, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection via Clarivate Analytics, Scopus via Elsevier, EBSCOhost: Academic Search Premier, CINAHL with Full Text, and Business Source Premier. Studies observing anxiety, burnout, stress, and depression using a wearable device worn by an HCP were included, with HCP defined as medical students, residents, physicians, and nurses. Bias was assessed using the Newcastle Ottawa Quality Assessment Form for Cohort Studies. ResultsThe initial search yielded 505 papers, from which 10 (1.95%) studies were included in this review. The majority (n=9) used wrist-worn biosensors and described observational cohort studies (n=8), with a low risk of bias. While no physiological measures were reliably associated with burnout or anxiety, step count and time in bed were associated with depressive symptoms, and heart rate and heart rate variability were associated with acute stress. Studies were limited with long-term observations (eg, ≥12 months) and large sample sizes, with limited integration of wearable data with system-level information (eg, acuity) to predict burnout. Reporting standards were also insufficient, particularly in device adherence and sampling frequency used for physiological measurements. ConclusionsWith wearables offering promise for digital health assessments of human functioning, it is possible to see wearables as a frontier for predicting burnout. Future digital health studies exploring the utility of wearable technologies for burnout prediction should address the limitations of data standardization and strategies to improve adherence and inclusivity in study participation.

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

Racial and social disparities exist in outcomes related to cancer and cardiovascular disease (CVD).The aim of this cross-sectional study was to study the impact of social vulnerability on mortality attributed to comorbid cancer and CVD.The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (2015-2019) was used to obtain county-level mortality data attributed to cancer, CVD, and comorbid cancer and CVD. County-level social vulnerability index (SVI) data (2014-2018) were obtained from the CDC's Agency for Toxic Substances and Disease Registry. SVI percentiles were generated for each county and aggregated to form SVI quartiles. Age-adjusted mortality rates (AAMRs) were estimated and compared across SVI quartiles to assess the impact of social vulnerability on mortality related to cancer, CVD, and comorbid cancer and CVD.The AAMR for comorbid cancer and CVD was 47.75 (95% CI: 47.66-47.85) per 100,000 person-years, with higher mortality in counties with greater social vulnerability. AAMRs for cancer and CVD were also significantly greater in counties with the highest SVIs. However, the proportional increase in mortality between the highest and lowest SVI counties was greater for comorbid cancer and CVD than for either cancer or CVD alone. Adults

Calibration of low-cost humidity sensors such as the HTS221TR is critical for accurate measurements, especially in smart devices. This study compares two calibration methods: machine learning (PyTorchNeural Network regression model) and optimization algorithm with Engineering Equation Solver. The critical role of temperature in humidity measurement emphasizes that it must be included for a valid calibration. The machine learning approach significantly reduced the average deviation of humidity, reaching ±2,5% compared to the original ±13,4%. Additionally, it aligned mean values along the identity line. However, the performance of the model varied across the different humidity ranges. Applying the model to real-world scenarios showed that the model underestimates humidity, likely due to the sensor's inherent tendency to overestimate humidity, especially at higher temperatures. Despite these challenges, both calibration methods offer simple and effective approaches for correcting low-cost sensor measurements, with machine learning enabling faster processing. This study not only improves the accuracy of the HTS221TR sensor, but also paves the way for more accurate and affordable humidity measurement technologies in general.

Due to the growing importance of new generations in upcoming market trends, attitudes, and behaviors of the young generation (Millennials and Z generation) towards the use of the sharing economy (SE) concept in Croatia were explored. The literature that connects SE and sustainability, and the Millennials and Z generation, with economic, social, technological, and environmental SE factors, was examined. A survey on a sample of 181 respondents was also conducted. The results present the attitudes of the young generation on SE factors, which SE concepts they use, and which they intend to use. Good command of new technologies, ratings and comments on the Internet are important. SE brings benefit to individuals and the economy and helps in preserving the environment. The biggest disadvantages of SE are pricing and socialization, while the advantage is accessibility. Those who use it least often have a significantly lower perception of the safety. The Z generation values influencer recommendations in SE usage more than Millennials. Also, younger participants, those who are more of a Z generation, had a lower perception that sharing helps in waste reduction. Booking.com and Uber are most often used, and apps for food delivery and skill sharing have the greatest perspective. This paper provides information about the attitudes, behaviors, and motivation of young people for using certain categories of SE, for both policymakers and managers of companies involved in SE businesses.

We report a surgically challenging case, in the context of a diagnosis of juvenile glaucoma refractory to drug therapy, multi-operated, known patient with congenital ichthyosis, part of Dorfman–Chanarin Syndrome (DCS), with a single functional eye. She is a young patient (54) and housewife in an urban environment known to have DCS and BE (both eyes), strong myopia, and congenital nystagmus. She initially underwent cataract surgery in 2015 and again in 2017. As of 2015, she was known to have juvenile glaucoma under maximal therapy. The important increases in pressure started in 2020 when the dermatological condition worsened (exacerbation of skin changes in the context of ichthyosis), the patient is in menopause, and presbyopia has set in. The glaucoma could no longer be controlled with medication and required serial surgery in both eyes (initially in the right eye in 2020 and in the left eye in 2023). The right eye showed a favorable evolution until 2024, when a second trabeculectomy became necessary, with a favorable evolution. Conclusions: To our knowledge, such a case has not been documented in the medical literature. Frequent monitoring of intraocular pressures and prompt treatment are required. It is a rare association, a very complicated case of managing a patient with refractory glaucoma and multiple associated ophthalmic and systemic pathologies. We are also dealing with a single functional eye, difficult to manage due to a thin sclera that has caused intraoperative difficulties, and the association of congenital nystagmus and strabismus.

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs—miR-199a, miR-20a, and miR-30c—in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.

The impact of the long-term historical contamination of the Mrežnica River with textile industry wastewaters on metal/metalloid bioaccumulation in the muscles of the young northern pike (Esox lucius) (0+ to 3+) was evaluated, as well as the association of bioaccumulated metal/metalloid concentrations in the muscle with fish physiology. Increased levels of several elements (As, Bi, Cs, Co, Cu, Zn), bioaccumulated in fish muscle, were occasionally found in front of the former factory, but the obtained metal/metalloid concentrations in muscle were in general either comparable or even lower than in the fish from moderately contaminated freshwaters. Calculated target hazard quotients indicated that the current risk for humans, arising from consumption of the northern pike meat originating from a historically contaminated section of the Mrežnica River, was negligible. The influence of biological factors, especially seasonal physiological changes, on metal/metalloid bioaccumulation was confirmed, indicating the importance of the involvement of these parameters in the freshwater pollution assessment, but also in the estimation of the human health hazard. The increased bioaccumulation of several metals/metalloids in fish muscle at a historically contaminated site pointed to the need for continuous supervision of fish health and biodiversity in freshwaters impacted by currently suspended long-term contamination sources.

Background: Glaucoma is a leading cause of irreversible blindness worldwide and is particularly challenging to treat in its refractory forms. The Ahmed valve offers a potential solution for these difficult cases. This research aims to assess the initial clinical experience with Ahmed valve implantation in Romania, evaluating its effectiveness, associated complications, and overall patient outcomes over a five-year period. Methods: We conducted a prospective study on 50 patients who underwent Ahmed valve implantation due to various types of glaucoma. Patients were monitored at several intervals, up to five years post-surgery. Intraocular pressure and visual acuity were the primary measures of success. Results: On average, patients maintained the intraocular pressure within the targeted range, with the mean intraocular pressure being 17 mmHg 5 years post-surgery. Success, defined as maintaining target intraocular pressure without additional surgery, was achieved in 82% at 1 year, 68% at 3 years, and 60% after 5 years postoperative. Conclusion: Ahmed valve implantation is a viable treatment option for refractory glaucoma, demonstrating significant intraocular pressure reduction and manageable complication rates over a five-year follow-up period. Future research should focus on long-term outcomes and optimization of surgical techniques to further reduce complication rates and improve patient quality of life.