Search Results (687)

Melanoma has important burden in older populations due to high incidence and aggressive biology. The emergence of immunotherapy with immune checkpoint inhibitors and targeted therapy (BRAF/MEK inhibitors) significantly improved melanoma prognosis. Currently, the body of knowledge on the efficacy and tolerability of these treatments in geriatric patients is primarily based on the results outside of clinical trials since the majority of clinical studies do not include older patients. We present a comprehensive narrative review of published data regarding efficacy and safety of therapeutic modalities using immune checkpoint inhibitors in patients age 65–75 years and >75 years: the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor (ipilimumab), the anti-programmed death-ligand 1 (PD-1) inhibitors (nivolumab and pembrolizumab), and the lymphocyte activation gene-3 (LAG-3) inhibitor (relatlimab). We carefully address difficulties in multi-disciplinary clinical decision-making in care of older melanoma patients. Although many older patients may not be offered immunotherapy, the available evidence indicates that immunotherapy is equally beneficial in the older patients and does not have higher incidence of adverse events in this group of patients compared to younger population. Full article

Background/Objectives: To assess the incidence and factors associated with urethral stricture following monopolar transurethral resection of the prostate (mTURP) and open simple prostatectomy (OSP) over a 21-year period. Methods: We conducted a retrospective cohort study of adult male patients insured by Clalit Health Services in Israel, who underwent either mTURP or OSP at multiple centers. Key baseline characteristics, including age, body mass index (BMI), socioeconomic status, Charlson comorbidity index score, and the incidence of urethral stricture, were collected. Postoperative urethral strictures were identified using the ICD-10 code N35.9 (urethral stricture, unspecified). Results: Between January 2000 and December 2021, 54,872 patients underwent simple prostatectomy across 29 hospitals, with 43,525 (79%) undergoing mTURP and 11,347 (21%) undergoing OSP. The median age of patients undergoing mTURP was 73.6 years, while those undergoing OSP had a median age of 72.1 years (p < 0.0001). The incidence of urethral strictures was 1.15% (500) following mTURP and 0.538% (61) following OSP, with an incidence rate ratio (IRR) of 2.139 (p < 0.0001). On multivariable analysis, factors associated with the development of urethral stricture included the type of procedure (HR = 2.349, 95% CI: 2.081–2.653, p < 0.0001), older age at surgery (HR = 1.012, 95% CI: 1.007–1.018, p < 0.0001), higher Charlson Index score (HR = 1.128, 95% CI: 1.109–1.148, p < 0.0001), and lower BMI (HR = 0.990, 95% CI: 0.982–0.999, p = 0.027). Conclusions: Our study highlights a higher incidence of urethral stricture following mTURP compared to OSP. Additionally, older age and a higher Charlson comorbidity index were associated with increased risk of stricture development postsurgery. Full article

Eye-tracking studies in virtual reality (VR) deliver insights into behavioral function. The gold standard of evaluating gaze behavior is based on manual scoring, which is labor-intensive. Previously proposed automated eye-tracking algorithms for VR head mount display (HMD) were not validated against manual scoring, or tested in dynamic areas of interest (AOIs). Our study validates the accuracy of an automated scoring algorithm, which determines temporal fixation behavior on static and dynamic AOIs in VR, against subjective human annotation. The interclass-correlation coefficient (ICC) was calculated for the time of first fixation (TOFF) and total fixation duration (TFD), in ten participants, each presented with 36 static and dynamic AOIs. High ICC values (≥0.982; p < 0.0001) were obtained when comparing the algorithm-generated TOFF and TFD to the raters’ annotations. In sum, our algorithm is accurate in determining temporal parameters related to gaze behavior when using HMD-based VR. Thus, the significant time required for human scoring among numerous raters can be rendered obsolete with a reliable automated scoring system. The algorithm proposed here was designed to sub-serve a separate study that uses TOFF and TFD to differentiate apathy from depression in those suffering from Alzheimer’s dementia. Full article

The implementation and practice of palliative medicine have numerous boundaries in low- and middle-income countries (LMICs), stemming from various cultural, legal, and religious concerns. Additionally, professional education in palliative care medicine in these countries is severely lacking, especially when compared with developed countries. Background/Objectives: To enhance and demystify palliative medicine practice to health care providers in LMICs. Methods: We developed a novel and comprehensive course in palliative care medicine and end-of-life (EOL) care, specifically within the context of management of patients with traumatic brain injury (TBI). We performed both immediate pre-course and post-course analysis of course participant comprehension and feedback, as well as a one-year post-course analysis and small group discussion. Results: The comprehension of the course material was strong, as participants scored an average of 13.9 points better on the post-test compared to the pre-test (49.6% vs. 35.7%, p < 0.001). Participants in the one-year follow-up session reported long-term applicability of the course material in their respective practice settings, with all participants reporting that they utilize the course material often. Small group discussion responses indicated a strong level of comprehension of the course material. Conclusions: Providing education in palliative medicine to health care professionals in LMICs is feasible, and likely to be both well-received and strongly influential to local medical practice. Local cultural and religious practices may be less of a barrier to the provision of palliative medicine than previously considered. Practicing palliative medicine, particularly at EOL, may strengthen patient–provider relationships, improve job satisfaction among health care providers, and improve the perception of medical care provided in LMIC medical settings. Full article

Background: Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive, ab interno conjunctival-sparing glaucoma surgery aimed at the trabecular meshwork and the inner wall of Schlemm’s canal. The goal of this study is to report on the success of GATT in a large group of patients with a wide variety of open- and closed-angle glaucomas with or without cataract extraction and to report on risk factors for failure. Methods: A retrospective chart review of consecutive patients with primary or secondary open- or closed-angle glaucoma who underwent GATT, with or without concomitant phacoemulsification. Demographics, baseline clinical characteristics, and postoperative outcomes were collected from patients’ medical records. Primary outcomes were success rates (IOP of 18 mmHg or lower and one of the following: IOP reduction > 30% from baseline on the same or fewer medications or an IOP ≤ baseline with fewer medications as compared to baseline) and complication rates. Intraocular pressure (IOP) and the number of glaucoma medications were secondary outcome measures. Results: GATT was performed on 126 eyes of 121 patients. Mean follow-up was 583 ± 266 days. Cumulative success at 1Y was 0.88 for GATT combined with cataract extraction, 0.96 for GATT alone, 0.88 for primary open-angle glaucoma (POAG), 0.89 for secondary open-angle glaucoma (SOAG), and 0.76 for primary angle-closure glaucoma (PACG). IOP decreased from a mean of 20.65 mmHg to 14.1 mmHg, and medication decreased from a mean of 3.47 to 1.4 at the last follow-up. Forty-four eyes (34%) were classified as failures. Factors associated with an increased risk of failure were worse preoperative corrected visual acuity (OR = 2.46, p = 0.024) and a postoperative IOP spike (OR = 2.62, p = 0.028). Twelve eyes (9.5%) required further surgery for IOP control. Risk factors for requiring further surgery for IOP control were preoperative maximal IOP (OR = 1.066, p = 0.047) and a postoperative IOP spike (OR = 4.531, p = 0.036). Conclusions: GATT achieved good surgical success with good IOP and medication reduction across a wide range of glaucomas, in combination with lens extraction or as a standalone procedure. GATT should be considered early in the treatment paradigm of medically uncontrolled glaucoma. Full article

Background/Objectives: Up to 75% of patients with major depressive disorder (MDD) exhibit persistent anhedonia symptoms related to abnormalities in the positive valence system. Cumulative evidence points to brain dysfunction in the reward system (RS), including in the ventral striatum, in patients with MDD with anhedonia. This study aims to evaluate the safety and efficacy of a novel neurofeedback (NF) device (termed Prism) which incorporates the EEG–FRI-Pattern biomarker of the reward system (RS-EFP) for use in self-neuromodulation training (RS-EFP-NF) for alleviating depression in patients with MDD with anhedonia. Methods: A total of 49 adults (age range: M = 39.9 ± 11.03) with a DSM-5 diagnosis of MDD with anhedonia (per a SHAPS-C score ≥ 25) were screened for the administration of ten sessions of RS-EFP-NF twice a week on nonconsecutive days. Depression and anhedonia severity was assessed, respectively, by HDRS-17 and SHAPS-C at baseline, midway, and treatment end. Results: A total of 34 patients (77%) completed the protocol and were included in the analyses. No device-related adverse events were serious or required treatment. Depression symptoms were reduced at end of treatment as indicated by the HDRS-17, with a reduction of eight points on average (95% CI: −10.5 to −5.41, p < 0.0001), a clinical improvement rate of 78.47%, and a remission rate of 32.25%. Anhedonia, as indicated by the SHAPS-C score, was diminished, showing an average reduction of 6.3 points (95% CI: −8.51 to −4.14, p < 0.0001). Conclusions: Self-neuromodulation using RS-EFP-NF is a promising and safe treatment for MDD with anhedonia. The intervention demonstrates substantial clinical effects on both depression and anhedonia symptoms, with high patient acceptability and retention. Prism may address a critical mechanism-driven treatment gap for anhedonia that often persists despite conventional therapies. Larger controlled implementation, efficacy, and dosing studies are warranted. Full article

Most premature adult deaths and chronic diseases, with their associated costs, are directly related to unhealthy behaviors, particularly poor nutrition. The 2022 White House Conference on Hunger, Nutrition, and Health emphasized the importance of nutrition equity and security as a key to preventing chronic diseases. What and how we eat also have important environmental impacts, with 26% of anthropogenic greenhouse gas emissions attributed to the total food supply chain, primarily ultra-processed food (UPF) production. A new paradigm is needed to better educate patients and the public to adopt healthier eating behaviors. Culinary education, emphasizing skills such as shopping, food storage, and meal preparation is a burgeoning field, aimed at reducing UPF consumption and improving nutrition while addressing cultural and socioeconomic factors. The term Culinary Medicine (CM) is becoming popular in describing these interventions; however, a consensus on its definition has not yet been reached. There are no consensual curricular outlines and/or competencies, and the potential for addressing food security and equity has not yet been fully developed. We believe that consensual competencies will formalize CM and ensure appropriate outcomes followed by improved assessments of learners, thus promoting CM research and further implementation of this novel nutrition education approach. Full article

Cutaneous fungal infections predominantly caused by dermatophytes are a global concern. These infections vary widely by region, age, and body site, with recent shifts in the pathogen distribution. This study examines the distribution and trends of superficial fungal infections in a large tertiary care center in Israel from 2019 to 2022. A retrospective analysis of 2244 patients with suspected fungal infections was performed, utilizing PCR and fungal cultures for diagnosis. Confirmed fungal infections were present in 53.0% of cases. In adults, infections predominantly affected the nails and feet, while in children, the scalp and nails were the most involved sites. Trichophyton rubrum was the most common pathogen overall, but T. tonsurans was the leading cause of scalp, face, and neck infections, as well as tinea corporis in children. T. tonsurans incidence significantly increased in adults and became the most frequent agent of upper-body tinea corporis by 2022. These findings highlight a shift in pathogen distribution, with T. tonsurans emerging as the leading cause of upper-body skin infections, underscoring the need for targeted prevention strategies and further investigation of its transmission routes. Full article

Background: Working memory (WM) impairment is a potential consequence of motor aphasia resulting from left-hemisphere ischemic stroke. While verbal WM has been studied extensively in this disorder, research regarding non-verbal modalities remains limited, particularly visuospatial WM, tactile WM, and the relationship between them. Additionally, language impairments limit the ability to assess WM in aphasia patients, highlighting the necessity of non-verbal diagnostic tools in clinical practice. The current study’s objectives were to compare tactile and visuospatial WM in patients with post-stroke motor aphasia and to validate the one-hand version of the Tactual Span task as a clinical measure of WM. Methods: A total of 29 participants—14 with post-stroke motor aphasia and 15 healthy controls—completed a battery of cognitive tests, including the Raven’s Colored Progressive Matrices Test, the Visuospatial Span, the Tactual Span, and a visual 1-Back task. Results: There was significantly lower performance across all WM tasks in the aphasia group compared to the controls. Additionally, the Tactual Span successfully discriminated between patients and controls, showing sensitivity estimates of 92.9% and a specificity of 66.7%, with a cut-off score of 4.5 (AUC = 0.91), for the forward stage. The backward stage revealed a sensitivity of 71.4% and a specificity of 73.3%, with a cut-off score of 3.5 (AUC = 0.83). Conclusions: The findings may suggest that non-verbal WM impairment in post-stroke aphasia affects both visuospatial and tactile modalities similarly. Furthermore, the Tactual Span appears to be sensitive to left-hemisphere stroke damage, suggesting its potential utility as a clinical tool for WM assessment in patients with motor aphasia. Full article

It is now known that diet or food is one of the environmental factors that can induce or contribute to autoimmunity. In a healthy person with a normal functioning immune system, food substances encounter no resistance and are allowed passage through the immune barriers without triggering immune reactivity. However, clinicians are becoming increasingly aware that modern food-processing methods can increase or decrease the immune reactivity of foods, including allergic reactions. Immune reactions to undigested food antigens could result in the production of IgE antibodies, which are involved in immediate immune reactivity, and in IgG and IgA antibodies, which are involved in delayed immune reactivity. Currently, measurements of these antibodies are generally only performed against antigens derived from raw foods. However, testing for food reactivity based only on raw food consumption is inaccurate because people eat both raw and cooked foods. Even home-cooked foods undergo different kinds of preparation or processing. Food processing can change the structure of raw food materials into secondary, tertiary, and quaternary structures that can have different reactive properties. This can affect the body’s normal oral tolerance of food, causing the immune system to mistakenly identify food as a harmful foreign substance and react to it immunologically, leading to food immune reactivity. This abnormal reaction to food molecules can lead to the production of antibodies against not just target food antigens but also the body’s own tissues, which can have significant implications in autoimmunity induction due to cross-reactivity and the other mechanisms discussed here. We hope that this present review will stimulate further research on the role of modified food antigens in the induction of autoimmunity based on some or all of the key points discussed in this review. Full article

Background: Neutrophils are key innate immune cells in peripheral blood. In recent years, sub-populations of neutrophils have been identified. In addition to the normal-density neutrophils (NDNs) in both healthy subjects and patients, low-density neutrophils (LDNs) were described in chronic inflammation and cancer. In lung transplants (LTx), neutrophils play crucial roles in reperfusion injury, acute rejection, and chronic lung allograft dysfunction. Our pilot study examines neutrophil subsets and function in LTx recipients during the first post-transplant year. Methods: We collected blood from 11 LTx recipients at various intervals. LDNs and normal-density neutrophils (NDNs) were isolated. The production of reactive oxygen species (ROS) by NDNs was measured after PMA activation using a Luminol-HRP assay. Neutrophil phenotypic markers were analyzed with flow cytometry. Results: The LDN-to-NDN ratio increased at 3 and 6 months post-transplant. Expression levels of CD62-L (aging marker), PDL-1 (immune checkpoint), CD15 (maturation), and CXCR4 (homeostasis regulator) showed modulation. Interestingly, ROS production by NDNs was mildly elevated at baseline, reduced at 6 months, and returned to baseline levels by 9 months post-transplant. Conclusions: Neutrophils exhibit dynamic changes in the first post-LTx year. Investigating neutrophil plasticity could reveal clinically relevant biomarkers and facilitate the development of diagnostic and therapeutic tools in LTx. Full article

Background: Respiratory Syncytial Virus (RSV) is a significant cause of morbidity and mortality among lung transplant (LTx) recipients. Therapeutic options are limited, emphasizing the importance of prevention. The Arexvy^® vaccine (RSVPreF3) showed promising efficacy among immunocompetent adults; however, data on its immunogenicity in solid organ transplant recipients remain unclear. Methods: A single-center retrospective cohort study, including all LTx recipients who were vaccinated with Arexvy in February 2024. Baseline and follow-up serum samples (1, 3, and 6 months post-vaccination) were analyzed for antibody responses using a commercial RSV ELISA kit and micro-neutralization assays against historical reference RSV A/B ATCC strains and seasonal RSV strains. Adverse events were documented. Results: A total of 28 recipients received the vaccine. Twenty-one (75%) were male, and the median age was 62 years (interquartile range [IQR], 53–67). The median time from transplant was 486 days (IQR, 243–966). Vaccination elicited strong immunogenic responses, demonstrating a twofold increase in ELISA-determined antibody levels at one month post-vaccination, which were sustained for six months. At one month, 67% of recipients had antibody levels exceeding the cutoff threshold. Micro-neutralization assays showed a significant increase in neutralizing antibodies against all tested variants (RSV A/B ATCC and seasonal RSV A/B), with titers remaining at least twofold higher than pre-vaccination levels. No serious adverse events were observed. Conclusions: Our findings demonstrate a sustained antibody response to the Arexvy^® vaccine in a cohort of LTx recipients, with antibody titers sustained over six months. Further research is needed to assess the long-term durability of the immune response and the potential immunogenicity of this vaccine in LTx populations. Full article

Objectives: Corneal refractive surgery aims to correct refractive errors. Proper corneal alignment is crucial. Eye-tracking technologies, specifically designed to address cyclotorsion using iris registration, help reduce the effects of cyclotorsion during surgery. The timing of iris registration can influence the efficacy of these technologies. This study compared cyclotorsion measurements before and after flap elevation/epithelium removal in FemtoLASIK and alcohol-assisted (aa) PRK. Methods: This retrospective cohort study was conducted at Einaim Medical Centers, Israel, and included patients who underwent refractive surgery using the VISX Star S4 IR excimer laser. Cyclotorsion measurements were obtained pre- and post-flap elevation or removal using the Wavescan™ and VISX Star S4 iris registration systems. Patients’ data were collected and analyzed retrospectively. Results: Overall, 152 eyes of 86 patients were included. In the FemtoLASIK group, 73 eyes from 45 patients were analyzed. For pre-flap lift, 34.2% had incyclotorsion and 65.8% had excyclotorsion, with a mean cyclotorsion of 2.3 ± 1.5 degrees. For post-flap lift, the mean cyclotorsion was 2.8 ± 1.9 degrees, showing a significant difference (p = 0.01). In the aa-PRK group, 79 eyes from 41 patients were analyzed. For pre-flap removal, 45.6% had incyclotorsion and 53.2% had excyclotorsion, with a mean cyclotorsion of 2.6 ± 1.8 degrees. For post-flap removal, the mean cyclotorsion was 2.5 ± 2.1 degrees, with no significant difference (p = 0.47) and a mean change of 1.6 ± 1.2 degrees. A total of 15.2% of eyes in the aa-PRK group and 13.6% in the LASIK group exhibited more than 3 degrees of cyclotorsional difference before and after flap lift or epithelial removal. Conclusions: Cyclotorsion occurs after flap lift/removal. To minimize residual astigmatism, iris registration should be performed post-flap elevation. Full article

Objective: We aimed to study the association of patient’s body mass index (BMI) with postoperative complications in patients surgically treated for endometrial intraepithelial neoplasia, with and without sentinel lymph node biopsy. Methods: A cohort study using the prospective National Surgical Quality Improvement Program database. Women with endometrial intraepithelial neoplasia on postoperative pathology who underwent minimally invasive hysterectomy from January 2012 to December 2020 were included. The cohort was dichotomized based on the performance of sentinel lymph node biopsy. We analyzed postoperative complications based on the World Health Organization (WHO) categories of BMI. Results: A total of 4428 patients met the inclusion criteria. Of those, 584 (13.2%) had sentinel lymph node biopsy. Overall, 76.5% of patients (n = 3389) were obese (BMI > 30.0), with 1840 (41.6%) patients of BMI ≥ 40.0. The rate of any complications was 6.0% (n = 264), major complications 2.3% (n = 101), and minor complications 4.2% (n = 187). When comparing the rate of any complications between patients who had sentinel lymph node biopsy vs. those without a sentinel lymph node biopsy procedure, stratified by BMI category, there was no association between sentinel lymph node biopsy performance and any complications in any of the BMI categories. In a multivariable binary regression analysis, BMI and the performance of sentinel lymph node biopsy were not independently associated with any complication [adjusted odds ratio (aORs) 1.001, 95% confidence interval (CI) (0.98–1.01), and aORs 1.1, 95% CI (0.82–1.65), respectively]. In an analysis of the cohort of patients who underwent sentinel lymph node biopsy, there was no association between the rates of any major or minor complications with BMI categories or obesity. ROC analyses for the association between BMI and occurrence of any major or minor complications had a low performance. Conclusions: In minimally invasive surgery for endometrial intraepithelial neoplasia, there is no association between body mass index and increased risk for postoperative complications when performing hysterectomy with sentinel lymph node biopsy versus hysterectomy alone. Full article

Objectives: We aimed to investigate the association between acute kidney injury (AKI) and the risk for long-term (up to 10 years) all-cause mortality among elderly compared with younger patients following an acute myocardial infarction (AMI). Methods: This study was a retrospective analysis of the Soroka Acute Myocardial Infarction registry and covered the years 2002 to 2017. It included patients diagnosed with an AMI who had a baseline estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m² and serum creatinine measurements available during hospitalization. The patients were stratified by age: elderly (aged 65 years or older at admission) and younger. In each stratum, two groups were defined based on the presence of an AKI. The survival approach (Kaplan–Meier survival curves, log-rank test and Cox regressions) was utilized to estimate and compare the probability of long-term (up to 10 years) all-cause mortality in each group. Results: Among the 10,511 eligible patients, which consisted of 6132 younger patients (58.3%) and 4379 elderly (41.7%), an AKI occurred in 15.2% of cases, where the elderly patients experienced a higher incidence than the younger patients (20.9% vs. 11.2%, p < 0.001). The presence of an AKI significantly increased the risk of death in both age groups, with the association being stronger among the younger patients (AdjHR = 1.634, 95% CI: 1.363–1.959, p < 0.001) than among the elderly (AdjHR = 1.278, 95% CI: 1.154–1.415, p < 0.001, p-for-interaction = 0.020). Conclusions: An AKI following an AMI was associated with a high risk for long-term all-cause mortality in both age groups, with a stronger association among younger patients. Full article