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Impaired immune response to COVID-19 (coronavirus disease 2019) vaccination has been reported in patients with inborn errors of immunity (IEI). Repetitive vaccinations are recommended for this vulnerable group. Due to the high diversity within IEI patients, additional safety and immunogenicity data are needed to better understand these aspects especially in less common immunodeficiency syndromes. In this prospective open-label clinical trial, we assessed the humoral immune response and the T‑cell response in patients with IEI or severe MBL (mannose-binding lectin) deficiency (IEI/MBLdef) after three vaccinations. A total of 16 patients and 16 matched healthy controls (HC) with suboptimal humoral response defined by anti-SARS-CoV‑2 RBD (severe acute respiratory syndrome coronavirus type 2 receptor binding domain) antibodies below 1500 BAU/ml (binding antibody units per ml) after the second COVID-19 vaccination were enrolled in this study and qualified for a third mRNA vaccine dose. After 4 weeks following vaccination, 100% of HC and 75% of IEI/MBLdef patients exhibited anti-SARS-CoV‑2 RBD antibodies > 1500 BAU/ml, although the difference was not statistically significant (75% vs. 100%; p = 0.109). Although post-vaccination IEI/MBLdef patients demonstrated significantly increased anti-SARS-CoV‑2 RBD antibodies and neutralizing antibodies compared to baseline, these responses were significantly lower in IEI/MBLdef patients compared to HCs. Notably, the third vaccination augmented the cellular immune response to both wild-type and omicron peptide stimulation. No serious adverse events were reported within the 4‑week follow-up period and, importantly, vaccination had little to no effect on the long-term disease activity and fatigue. This trial strongly supports the recommendation of repeated COVID-19 vaccinations for patients suffering from immunodeficiencies, especially when they exhibit an initially limited response to the vaccine., (© 2024. The Author(s).)

The relation between Body Mass Index (BMI) and adverse outcomes after endovascular therapy (EVT) for patients with lower extremity artery disease (LEAD) remains incompletely understood. From April 2010 to March 2020, 199 consecutive patients who underwent EVT for LEAD were retrospectively analyzed. The patients were divided into three groups based on BMI; underweight < 18.5 kg/m 2 , normal weight ≥ 18.5 and < 25.0 kg/m 2 , and overweight ≥ 25.0 kg/m 2 . The endpoint of this study was a composite of all-cause mortality, major amputation, and major bleeding. Patients who were underweight often exhibited anemia (53.3 vs. 22.3 vs. 15.4%, respectively; p = 0.001) and severe chronic kidney disease (50.0 vs. 30.8 vs. 20.5%, respectively; p = 0.03). Furthermore, these patients had higher incidences of Trans-Atlantic Inter-Society Consensus class C or D lesions (40.0 vs. 20.0 vs. 10.3%, respectively; p = 0.01). During the median follow-up duration of 3.6 years (interquartile range: 1.2 to 6.7 years), there were 73 incidents of the composite endpoint. When the overweight group was assigned as the reference group, the adjusted hazard ratios for the composite endpoint for the underweight and normal weight patients were 3.67 (95% confidence interval [CI] 1.39-10.83, p = 0.008) and 2.35 (95% CI 1.06-6.23, p = 0.03), respectively. Kaplan-Meier curve demonstrated that the freedom from the composite endpoint for underweight, normal weight, and overweight patients was 41.6%, 60.0%, 83.8%, respectively (p < 0.001). These results suggest that there was an inverse association between BMI and adverse outcomes composed of mortality, limb amputation, and bleeding in patients with LEAD undergoing EVT., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Purpose: To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications., Methods: Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia., Results: We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population., Conclusion: This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field., (© 2024. The Author(s).)

This paper offers a comprehensive review of the gestational surrogacy process in the US, as well as internationally, focusing on the legal and ethical challenges that gestational carriers, intended parents, fertility providers, and OB/GYNs may face. The objective of this review article is to serve as an overview and provide information on legal, cultural, and ethical aspects of the decisions to pursue gestational surrogacy both for intended parents and gestational carriers in the US and globally. By understanding the surrogacy landscape and the obstacles, the surrogacy agencies and other involved parties can improve the surrogacy process to better serve all parties involved., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This nationwide multidisciplinary survey found dissatisfaction among physicians with current osteoporotic vertebral compression fracture care, revealing significant disparities in diagnosis, treatment, and follow-up practices. Issues include poor communication and differing guidelines. Improving interdisciplinary collaboration and standardized care strategies is essential for better patient outcomes., Purpose: This survey aims to assess current preferred care practices for symptomatic osteoporotic vertebral compression fractures (OVCF) in the Netherlands, focusing on guideline adherence, identifying knowledge gaps, and clarifying consensus and collaboration across medical disciplines in OVCF treatment., Methods: This cross-sectional study was conducted via Qualtrics (Provo, UT) using a self-administered online survey distributed to 238 general practitioners and physicians in orthopedics, traumatology, internal medicine, rheumatology, and geriatrics working at 51 hospitals in the Netherlands. The survey, conducted in Dutch, included 36 multiple-choice and two open questions and was accessible via an anonymous email link or QR code. General practitioners received additional questions specific to their role. Data was anonymized, stored securely, and analyzed using descriptive statistics in Microsoft Excel and SPSS (Version 24). Open-ended responses were coded and categorized. The survey was conducted prior to the publication of the updated Federation of Medical Specialists guidelines in 2024., Results: Physicians across various disciplines uniformly expressed dissatisfaction with current OVCF care. The survey highlighted significant disparities in diagnosis, treatment, and follow-up practices. A lack of communication between primary and secondary care providers and differing guidelines further complicate OVCF management. These issues point to considerable variation in clinical practice and gaps in interdisciplinary collaboration., Conclusion: Addressing the identified issues requires fostering interdisciplinary collaboration and creating cohesive care strategies. Ensuring access to diagnostic resources in both primary and secondary care and establishing coordinated care models promises more structured and standardized treatment. These steps are crucial for enhancing patient outcomes in OVCF management., (© 2024. The Author(s).)

Several recent studies have investigated the validity of precautionary practices for lymphedema risk reduction after breast cancer treatment, such as avoidance of blood pressure measurements, skin puncture, blood draws, and use of prophylactic compression during air travel. Other studies have elucidated risk factors for breast cancer-related lymphedema, such as axillary lymph node dissection and skin infection (cellulitis). Combining the current evidence base with the consensus opinion of lymphatic experts assembled at the American Cancer Society/Lymphology Association of North America Summit in October 2023, updated evidence-based risk reduction recommendations are presented for those with or at risk of breast cancer-related lymphedema. Recommendation topics include prospective surveillance, patient education, individual risk factors, exercise, blood pressure, skin care and hygiene, skin puncture and blood draws, surgical procedures, prophylactic compression, air travel, and hot climate and sauna. These recommendations will help inform education and medical choices for individuals treated for breast cancer who are at risk of or diagnosed with breast cancer-related lymphedema. More high-quality evidence is required to allow the development of risk reduction recommendations for other cancer types such as gynecological, melanoma, and head and neck. It is recommended that clinicians and organizations serving people at risk of or with lymphedema align risk reduction guidelines with the evidence-based recommendations provided within this consensus document and companion manuscripts from the American Cancer Society/Lymphology Association of North America Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Misinformation and vaccination hesitancy contribute to disparities in vaccination rates, particularly in under-resourced communities. This study aims to investigate perceptions and factors influencing vaccination decisions at free clinics serving diverse, under-resourced communities., Methods: Surveys were conducted across eight free clinics in the Greater Sacramento area, targeting uninsured or underinsured individuals. Information on demographics, sources of vaccine information, access to vaccines, vaccine perceptions, and vaccination decisions as pertaining to influenza and COVID-19 were collected on Qualtrics software. Chi-square and t-tests were used to analyze associations between demographics and vaccination rates., Results: Among 109 participants (24-82 years old), vaccination rates were found to be higher than the county average, with notable demographic variations. Contrary to initial hypotheses, men had higher vaccination rates than women, and recent immigrants exhibited higher vaccination rates than more long-term U.S. residents. A higher number of participants regarded the COVID-19 vaccine as effective than as safe, while the reverse was true for the influenza vaccine. Healthcare providers were the most trusted and influential sources for vaccine information, followed by government agencies, and then family and friends. Answers to hypothetical vaccine scenarios elicited assessments on risks and benefits., Conclusion: The study provides insight into the dynamics of vaccine hesitancy and factors that play into the decision-making process in under-resourced communities, underscoring the role of trust in healthcare providers. These findings are vital for tailoring community outreach strategies to create trust, address barriers, and enhance vaccine uptake within free community clinics., (© 2024. The Author(s).)

Cell surface cortical actin is a regulatory target for viral infection. We aimed to investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on host cell cortical stiffness, an indicator of cortical actin structure. The receptor-binding domain (RBD) of SARS-CoV-2 Spike (S) protein induced a reduction in cortical stiffness in ACE2-expressing cells. The interaction of RBD with ACE2 caused the inactivation of Ezrin/Radixin/Moesin (ERM) proteins. We further investigated the effects of the RBD of SARS-CoV-2 Omicron variants, BA.1 and BA.5. These RBDs influenced cortical stiffness depending on their affinity for ACE2. Our study provides the first evidence that the interaction of the SARS-CoV-2 S protein with ACE2 induces mechanobiological signals and attenuates the cortical actin., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Nanoflowers, an innovative class of nanoparticles with a distinctive flower-like structure, have garnered significant interest for their straightforward synthesis, remarkable stability, and heightened efficiency. Nanoflowers demonstrate versatile applications, serving as highly sensitive biosensors for rapidly and accurately detecting conditions such as diabetes, Parkinson's, Alzheimer's, and foodborne infections. Nanoflowers, with their intricate structure, show significant potential for targeted drug delivery and site-specific action, while also exhibiting versatility in applications such as enzyme purification, water purification from dyes and heavy metals, and gas sensing through materials like nickel oxide. This review also addresses the structural characteristics, surface modification, and operational mechanisms of nanoflowers. The nanoflowers play a crucial role in preventing premature drug leakage from nanocarriers. Additionally, the nanoflowers contribute to averting systemic toxicity and suboptimal therapy efficiency caused by hypoxia in the tumor microenvironment during chemotherapy and photodynamic therapy. This review entails the role of nanoflowers in cancer diagnosis and treatment. In the imminent future, the nanoflowers system is poised to revolutionize as a smart material, leveraging its exceptional surface-to-volume ratio to significantly augment adsorption efficiency across its intricate petals. This review delves into the merits and drawbacks of nanoflowers, exploring synthesis techniques, types, and their evolving applications in cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The response of carbohydrate antigen (CA) 19-9 to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) may contribute to outcomes. This study aimed to investigate the effect of changes in NAT regimens based on CA19-9 level., Methods: This single-center retrospective study included patients with resectable/borderline resectable (R/BR)-PDAC undergoing NAT from 2008 to 2022. A CA19-9 level lower than 150 IU/mL after NAT was the criterion for resection. If the level did not decrease, the chemotherapy regimen was changed to satisfy the criterion. The patient cohort was divided into group A (satisfied criterion without changing chemotherapy), group B (did not receive chemotherapy change, could not satisfy the criterion), group C (received chemotherapy change, satisfied the criterion), and group D (received chemotherapy change, could not satisfy the criterion)., Results: The study cohort included 283 patients. After first-line chemotherapy, 112 (39.6%) patients did not satisfy the criterion (groups B [n = 64], C [n = 32], and D [n = 16]). Of the 283 patients, 48 (17%) received a chemotherapy change (groups C and D). The patients in groups C and D showed significantly better overall survival (OS, 35.9 months) than the group B patients (25.7 months) (P = 0.035). The OS of the group C patients (63.8 months) was similar to the OS of the group A patients (n = 171: 56.3 months; P = 0.430). Multivariate analysis of the patients in groups B, C, and D identified chemotherapy change as an independent prognostic factor for OS and progression-free survival., Conclusion: Changing the chemotherapy targeting the CA19-9 level can improve the outcome of R/BR-PDAC patients with poor biologic response to first-line NAT., (© 2024. Society of Surgical Oncology.)

Empathy, defined as the ability to understand and share another person's feelings, is crucial in the healthcare setting, particularly for patients with cancer who face significant psychosocial challenges. We aimed to develop a novel tool, the Empathy, Life with Cancer, and Psychosocial Skills (ELPIS) Scale that prioritizes emotional and cognitive components in order to determine the reflection of the negative stigmatization of cancer in societies on individuals, excluding the behavioral and ethical dimensions of empathy. The study was conducted using a quantitative research design with a sample of first- and second-year medical students in Türkiye. An initial pool of 48 items was developed based on an extensive review of the literature and existing empathy scales. Following expert review and pilot testing, the scale was refined to 24 items. Exploratory factor analysis and confirmatory factor analysis were conducted to establish the scale's factor structure and validate its reliability and validity. The exploratory factor analysis revealed a three-factor structure comprising "emotional empathy," "sympathetic responses," and "realistic approaches," with a total of 20 items after refinement. Confirmatory factor analysis confirmed the model fit, with the scale demonstrating high internal consistency across all three dimensions. The scale's reliability was further supported by high Cronbach's alpha values. The results suggest that the ELPIS Scale is a reliable and valid instrument for measuring emotional empathy toward cancer patients. It offers a nuanced approach by separately assessing emotional, sympathetic, and realistic components of empathy, making it a valuable tool for both educational and clinical applications. Future research should explore the scale's application in diverse populations and settings, as well as its utility in tracking empathy development over time. In conclusion, the ELPIS Scale, which focuses on the emotional and cognitive components of empathy, a multifaceted construct, fills a critical gap in the measurement of empathy in the context of cancer care and provides a comprehensive tool that can improve both patient care and the education of healthcare providers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

It remains unknown whether frailty status confers an increased risk of readmission in patients with rheumatoid arthritis (RA). From the 2018 Nationwide Readmissions Database (NRD), we identified adult patients (age ≥ 18 years) admitted with a diagnosis of RA between January to June 2018. Utilizing validated Hospital Frailty Score, patients' frailty risk score was calculated at the time of index admission and categorized into frail (score ≥ 5) and non-frail (score < 5) groups. Our primary outcomes of interest were (1) 180- day readmission rate (2) inpatient mortality; secondary outcomes included prolonged length of stay, LOS (LOS ≥ 7 days), and costs of hospitalization. Multivariable Cox proportional hazard analysis was performed to evaluate the independent effect of frailty adjusting for confounding variables. 133,187 patients met inclusion criteria, with mean age 67.7 years, of whom 64,131 (48.1%) patients were categorized as frail. The rate of readmission was significantly higher in the frail (56.60%) compared to the non-frail group (30.61%). At index hospitalization, frail patients also had significantly higher inpatient mortality compared to non-frail patients (3.36% vs 0.39%, p < 0.005), longer LOS (26.24% vs 7.82%, p < 0.005). On multivariate analysis frailty was independently associated with a 9% increased risk of readmission (adjusted hazard ratio, 1.09; 95% confidence interval, 1.08 - 1.11). People with RA who are frail have higher rates of readmission than those who are not frail. These findings are crucial in identifying at-risk patients with RA and in discharge planning after hospitalization. Key Points • People with RA who are frail have higher rates of readmission than those who are not frail. • Frail RA patients are also at higher risk of hospitalization-related adverse outcomes, including inpatient mortality and longer hospital stay. • Sepsis is the most common cause for readmission identified in frail patients with RA. • These findings suggest that frailty may be a useful metric in identifying patients with RA at an increased risk of adverse health outcomes., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Fibromyalgia (FM) in systemic lupus erythematosus (SLE) patients contributes to increased fatigue, anxiety, depression, and mental exhaustion. This study's objective is to systematically review the literature and to determine the frequency of FM in patients with SLE and its associated factors. A literature review was conducted to assess the prevalence of FM in SLE patients and to identify FM-associated factors. This involved searching the PubMed and Cochrane Library databases from 1959 to 2023. Cohorts, case-control, and population-based studies were included, while those not focusing on FM rates in SLE patients were excluded. Data on FM-associated factors and FM frequency in control or connective tissue disease (CTD) groups were obtained if available. Secondary analyses compared FM frequencies in SLE and other groups (healthy controls or CTD groups). Fifty-six studies met the eligibility criteria. Out of the 56 studies, nine included comparative data between SLE patients and healthy controls, while six presented data comparing the frequency of FM in patients with SLE and other CTDs. The combined cohorts included 58,052 SLE patients. Among 5063 SLE patients, FM was detected. The overall random-effects pooled prevalence of FM was 15.8% (95% CI, 13.4-18.5) with high heterogeneity (I 2 , 97.9%). Our analysis revealed a significantly higher risk of FM in patients with SLE compared to controls (OR, 3.7; 95% CI, 2.74-5.0). There was a higher risk of FM in SLE patients compared to other rheumatic diseases, but the difference was not significant. Our study showed that the prevalence of FM is higher in patients with SLE compared to the general population. FM in SLE may act as a confounding factor when assessing disease activity and treatment response. Research results indicate that concurrent FM is a frequent comorbidity in SLE, emphasizing the importance of recognizing its occurrence in SLE patients., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: To determine the spectrum, clinical features and outcomes in systemic lupus erythematosus (SLE) patients with acute abdominal pain (AAP)., Method: Medical records of SLE patients in a lupus cohort from January 1987 to June 2023 were reviewed. Patients with AAP requiring hospitalization were identified and categorized into 3 groups: lupus mesenteric vasculitis (LMV), non-LMV, and surgical AAP. Each AAP episode represented one patient., Results: Of 1,538 patients in the cohort, 62 (4.03%) had 93 episodes of AAP. After exclusion, 31 patients had 39 LMV episodes, and 30 had 40 non-LMV episodes (19 due to surgical AAP). Seventy-six of the 79 AAP episodes (96.20%) were in females, with a mean ± SD age and median (IQR) disease duration of 36.76 ± 13.60 years and 6 (2, 9) years, respectively. Patients in the LMV group had more fever, nausea and vomiting, and diarrhea than those in the non-LMV group. They also had more small bowel involvement, bowel wall thickening, target water enhancement signs, mesenteric vessels engorgement and mesenteric fat cloudiness, and higher SLE disease activity. These differences were more pronounced when compared to the surgical AAP group. Treatment with corticosteroids and immunosuppressive drugs gave favorable outcomes in the LMV group. Two of 40 (5.00%) non-LMV AAP patients died, of which 1 (5.26%) was in the surgical AAP group., Conclusion: LMV was common among SLE patients admitted for AAP. LMV usually presented with fever, gastrointestinal dysmotility symptoms, diffused abdominal pain, together with evidence of active disease. Localized abdominal pain with peritoneal signs favored surgical AAP. Key Points • Lupus mesenteric vasculitis is common among SLE patients presenting with acute abdominal pain. Its presence often associates with gastrointestinal symptoms together with other clinical manifestations of SLE • The signs in abdominal computed tomography findings are not specific and could be observed in other causes of abdominal pain in SLE. Interpretation of these signs should be cautionary and accompanied by history taking and physical abdominal findings • Treatment of lupus mesenteric vasculitis with corticosteroids alone, or in combination with immunosuppressive drugs, usually results in good outcomes., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction: Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital., Methods: It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed., Results: 80 patients, aged of 49.7 ± 16.6 years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO 2  = 52.5 ± 17.4 mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%)., Conclusion: HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation., Trial Registration: An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice., (© 2024. The Author(s).)

Objectives: Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines., Methods: An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data., Results: A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87 h [95%CI - 1.23 h to - 0.51 h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11 ml [95%CI - 5.93 ml to 1.72 ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03 days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome., Conclusions: POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Background: Risk factors for pancreatic ductal adenocarcinoma (PDAC) include tobacco/alcohol abuse, genetic predisposition, insulin resistance, and pancreatic cysts. Despite these well-established risk factors and the screening of high-risk individuals, some people still develop PDAC. This study aims to explore a potential risk factor for PDAC by investigating the association between fungal toxins (FT) and environmental toxins (ET) and the disease. We predicted that individuals with PDAC would have higher levels of these toxins compared to healthy controls. The rationale behind this hypothesis is that exposure to FT and ET might contribute to the development of PDAC by elevating cancer risk., Methods: A pilot retrospective cohort study was conducted at Moffitt Cancer Center from 2022 to 2023. This study compared FT and ET levels, demographic data, and PDAC features between subjects with PDAC and healthy controls., Results: Forty subjects were enrolled in the study, comprising 20 with pancreatic ductal adenocarcinoma (PDAC) and 20 healthy controls. Baseline demographics were similar between the two groups. Among the PDAC subjects, the most common tumor location was the head of the pancreas (55%); 30% had locally advanced disease, 45% were borderline resectable, and 10% had metastatic disease. Compared to the controls, subjects with PDAC had significantly higher levels of fungal toxins (FTs) including ochratoxin, gliotoxin, and citrinin (p < 0.05). Additionally, PDAC patients had significantly elevated levels of environmental toxins (ETs) such as methyl tert-butyl ether (MTBE), xylene, styrene, acrylonitrile, perchlorate, diphenyl phosphate, bromopropane, organophosphates, acrolein, tiglylglycine, and diethylphosphate (p < 0.05)., Conclusion: Our study demonstrates that subjects with PDAC, without other risk factors, have higher FT and ET levels than controls. Further studies are needed to evaluate whether ET and FT exposure can be clinically utilized as a risk factor for PDAC development., (© 2024. The Author(s).)

Ultrasound (US) evaluation of the spleen is mandatory in the assessment of patients with chronic liver disease, and splenomegaly can be a sign of systemic diseases. However, due to the lack of distinctive ultrasound findings in specific splenic pathologies, clinical diagnosis can be very challenging. Splenomegaly, defined by increased splenic dimensions, can indicate underlying systemic conditions and is a common manifestation of portal hypertension (PH). Ultrasound and Doppler techniques help assessing splenic involvement in PH. Splenic stiffness measurement, using elastography, offers additional diagnostic accuracy, especially when liver stiffness measurements are inconclusive. CEUS enhances the diagnostic capability for focal splenic lesions, differentiating between benign and malignant lesions by their distinct enhancement patterns, and plays also a critical role in the context of splenic traumatic pathology. Overall, CEUS significantly improves the characterization of splenic pathology, reducing the need for invasive procedures and ensuring appropriate patient management. This review article describes the normal US findings of the spleen and examines the role of multiparametric US in the evaluation of the most common splenic pathologies encountered in the daily clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Continuous kidney replacement therapy (CKRT) is the predominant form of acute kidney support used for hemodynamically unstable adult ICU patients with severe AKI (KDIGO stage 3). The success of CKRT depends on the achieved doses. Practice patterns worldwide are highly variable. A contemporary understanding of treatment adequacy is essential. The KDIGO AKI clinical guidelines recommend delivering effluent volumes of 20-25 ml/kg/hour for CKRT in the ICU setting, with the caveat that higher prescribed doses (25-30 ml(kg/h) may be necessary to achieve adequate delivered CKRT doses. The reference landmark trials provide definitive evidence that increases of delivered CKRT doses beyond the recommended dose are not beneficial for unselected ICU patients with severe AKI. However, the minimum delivered CKRT intensity at which underdosing becomes harmful remains unknown. The answer to this question has clinical relevance (dosing of critically ill patients with obesity or Covid-19 disease, minimizing adverse effects of CKRT) and a relevant impact on the costs of CKRT. The delivered dose of CKRT for Japanese ICU patients with severe AKI has been generally smaller (median 15 ml/h/kg) than the recommended delivered KDIGO dose. The most recently published retrospective cohort study by Okamoto et al. demonstrated that low delivered CKRT doses were associated with a higher mortality among critically ill patients with severe AKI. These data challenge the nation-wide accepted hypothesis that a lower limit of delivered CKRT (< 20 ml/ kg/h) may adequately control uremia/volume overload. Thus, there is an unmet clinical need for prospective randomized trials defining the minimal effective dose of CKRT. Given the dynamic nature of the precipitating critical illness and the natural course of most episodes of AKI, CKRT dose targets are likely to vary. Doses should be tailored to the needs of the individual patient within the limits of the KDIGO guideline recommendations. The Japanese experience with low-dose CKRT is not practice changing., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Multitarget stool DNA (MT-sDNA) tests (here, Cologuard®) are currently used in average-risk patients as a primary method of screening for colorectal cancer. However, MT-sDNA testing has also been used in patients who previously underwent colonoscopy who wish to avoid repeat colonoscopy. Here, in a large primary care practice setting, our aim was to evaluate the diagnostic performance of MT-sDNA testing in patients with a previously normal colonoscopy., Methods: This retrospective cohort study included 5827 patients from 35 different primary locations in South Carolina. Patients aged 45 and above with a previously documented normal, high-quality colonoscopy prior to the MT-sDNA test date were included. High-risk patients and those with a previous negative MT-sDNA result were excluded., Results: Of 5827 ordered MT-sDNA tests, 248 patients had a prior normal colonoscopy. The average time from initial colonoscopy to MT-sDNA testing was 7.3 years. Of the 63 patients who had a positive MT-sDNA test, 41 patients (65%) completed follow-up colonoscopy and 40 patients had complete colonoscopy data. Of these 40 patients, 12 patients (30%) had advanced adenomas and none had colorectal cancer. Compared to patients without a previous colonoscopy, patients with prior colonoscopies had fewer adenomas of all types (1.6 vs 2.4) and fewer advanced adenomas (1.4 vs 2.0)., Conclusion: Patients with a previously negative colonoscopy and subsequent positive MT-sDNA test were found to have a high rate of advanced adenomas on follow-up colonoscopy (30%). Thus, in patients with a previously negative colonoscopy, MT-sDNA testing may be a reasonable alternative screening option., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Differentiation of the cause of left ventricular hypertrophy (LVH) is challenging in cases with co-existing hypertension. CMR offers assessment of diffuse myocardial abnormalities via T1 mapping with extracellular volume fraction (ECV) and macroscopic fibrosis via late gadolinium enhancement imaging (LGE). The goal of the study was to understand if CMR parameters can differentiate hypertensive cardiomyopathy (HC) from cardiac amyloidosis (CA) in patients with hypertension and heart failure, using endomyocardial biopsy (EMB) as the gold standard., Methods: We retrospectively analyzed patients with hypertension, LVH, and heart failure undergoing EMB due to uncertain diagnosis. CMR parameters including cine, LGE characteristics, T1 mapping, and ECV were analyzed., Results: A total of 34 patients were included (mean age 66.5 ± 10.7 years, 79.4% male). The final EMB-based diagnosis was HC (10, 29%), light chain (AL) CA (7, 21%), and transthyretin (ATTR) CA (17, 50%). There was a significant difference in subendocardial LGE (p = 0.03) and number of AHA segments with subendocardial LGE (p = 0.005). The subendocardial LGE pattern was most common in AL-CA (85.7%) and African American with HC (80%). ECV elevation (≥ 29%) was present in all patients with CA (AL-CA: 57.6 ± 5.2%, ATTR-CA: 59.1 ± 15.3%) and HC (37.3 ± 4.5%)., Conclusions: Extensive subendocardial LGE pattern is not pathognomonic for CA but might also be present in African American patients with longstanding or poorly controlled HTN. The ECV elevation in HC with HF might be more significant than previously reported with an overlap of ECV values in HC and CA, particularly in younger African American patients., (© 2024. The Author(s).)

Purpose: Sepsis is a leading cause of morbidity and mortality globally. The lack of specific prognostic markers necessitates tools for early risk identification in patients with suspected infections in emergency department (ED). This study evaluates the prognostic accuracy of various Early Warning Scores (EWS)-MEWS, NEWS, NEWS-2, and qSOFA-for in-hospital mortality, 30-day mortality, and ICU admission, considering the site of infection., Methods: A retrospective analysis was conducted using data from the Acutelines cohort, which included data collected from patients admitted to the University Medical Centre Groningen ED between September 2020 and July 2023. Patients were included if they had an ICD-10 code for infection. EWS were calculated using clinical data within 8 h post-admission. Predictive performance was assessed using AUC-ROC, calibration by the Hosmer-Lemeshow test and calibration curves, and operative characteristics like sensitivity and specificity., Results: A total of 1661 patients were analyzed, with infections distributed as follows: lower respiratory tract (32.9%), urinary tract (30.7%), abdominal (12.5%), skin and soft tissue (9.5%), and others (8.2%). The overall in-hospital mortality was 6.7%, and ICU admission was 7.1%. The highest AUC-ROC for in-hospital mortality prediction was observed with NEWS and NEWS-2 in abdominal infections (0.86), while the lowest was for qSOFA in skin and soft tissue infections (0.57). Predictive performance varied by infection site., Conclusions: The study highlights the variability in EWS performance based on infection site, emphasizing the need to consider the source of infection in EWS development for sepsis prognosis. Tailored or hybrid models may enhance predictive accuracy, balancing simplicity and specificity., (© 2024. The Author(s).)

Fibromuscular dysplasia is a rare, idiopathic, systemic, non-inflammatory, and non-atherosclerotic vascular disease that primarily affects young women. It often presents as renal artery stenosis. Fibromuscular dysplasia can induce tissue damage in the post-stenotic kidney. Treatment options include antihypertensive therapy, surgical revascularization, and transluminal angioplasty with stent implantation. However, kidney autotransplantation is an alternative when these treatments are not feasible. This study presents a case report of a 22-year-old woman with fibromuscular dysplasia, highlighting the long-term success of kidney autotransplantation and reviewing the related literature. A multidisciplinary approach was employed in the treatment of this patient presenting with intermittent headaches, hypertension, and acute kidney disease, and who was diagnosed with fibromuscular dysplasia. She underwent left aorta-renal bypass and right autotransplantation. Following the procedure, her serum creatinine level decreased from 2.74 to 1.1 mg/dL, with an eight-year follow-up confirming the favorable outcome. Renal artery stenosis is a significant contributor to secondary hypertension, with fibromuscular dysplasia being a rare cause. While medical and interventional treatments are usually effective, complex cases may necessitate alternative approaches. Kidney autotransplantation, albeit uncommon, is an effective option for patients who are unresponsive to conventional therapies. This case demonstrates the successful management of fibromuscular dysplasia-associated renovascular hypertension via kidney autotransplantation, resulting in controlled blood pressure and preserved kidney function. In conclusion, kidney autotransplantation represents a valuable therapeutic option for severe renal artery stenosis caused by fibromuscular dysplasia, particularly when percutaneous procedures are impractical., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD)., Methods: This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy., Results: A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed to hormone replacement therapy showed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality., Conclusions: This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objectives: To develop and evaluate a multi-task deep-learning (DL) model for automated segment-level coronary artery calcium (CAC) scoring on non-contrast computed tomography (CT) for precise localization and quantification of calcifications in the coronary artery tree., Methods: This study included 1514 patients (mean age, 60.0 ± 10.2 years; 56.0% female) with stable chest pain from 26 centers participating in the multicenter DISCHARGE trial (NCT02400229). The patients were randomly assigned to a training/validation set (1059) and a test set (455). We developed a multi-task neural network for performing the segmentation of calcifications on the segment level as the main task and the segmentation of coronary artery segment regions with weak annotations as an auxiliary task. Model performance was evaluated using (micro-average) sensitivity, specificity, F1-score, and weighted Cohen's κ for segment-level agreement based on the Agatston score and performing interobserver variability analysis., Results: In the test set of 455 patients with 1797 calcifications, the model assigned 73.2% (1316/1797) to the correct coronary artery segment. The model achieved a micro-average sensitivity of 0.732 (95% CI: 0.710-0.754), a micro-average specificity of 0.978 (95% CI: 0.976-0.980), and a micro-average F1-score of 0.717 (95% CI: 0.695-0.739). The segment-level agreement was good with a weighted Cohen's κ of 0.808 (95% CI: 0.790-0.824), which was only slightly lower than the agreement between the first and second observer (0.809 (95% CI: 0.798-0.845))., Conclusion: Automated segment-level CAC scoring using a multi-task neural network approach showed good agreement on the segment level, indicating that DL has the potential for automated coronary artery calcification classification., Critical Relevance Statement: Multi-task deep learning can perform automated coronary calcium scoring on the segment level with good agreement and may contribute to the development of new and improved calcium scoring methods., Key Points: Segment-level coronary artery calcium scoring is a tedious and error-prone task. The proposed multi-task model achieved good agreement with a human observer on the segment level. Deep learning can contribute to the automation of segment-level coronary artery calcium scoring., (© 2024. The Author(s).)

Gastrointestinal involvement (GI) is a frequent and troublesome complication of systemic sclerosis (SSc), whose etiology is poorly understood, though it is hypothesized that autoimmunity and progressive vasculopathy may play a role. Vasculopathy is considered one of the main pathogenetic pathways responsible for many of the clinical manifestations of SSc, and, therefore, studying the principal splanchnic vessels (i.e., superior mesenteric artery-SMA and inferior mesenteric artery-IMA) with Doppler Ultrasound (DUS) may provide further insights into measuring the progression of vasculopathy, evaluating its possible association with SSc GI symptoms, and determining whether it plays a role in the development or severity of SSc GI disease. A cohort of SSc patients consecutively recruited underwent DUS examination, and associations with GI (UCLA-GIT 2.0 questionnaire) and extraintestinal SSc characteristics were evaluated. Semiquantitative DUS parameters (resistive index-RI and pulsatility index-PI), were applied for splanchnic vessel assessment in SSc patients and healthy subjects (HS). Moreover, a review and meta-analysis of the literature to understand which the values of the main semiquantitative DUS parameters (RI and PI) are both in SSc patients and HS has been conducted. Seventy-eight patients completed DUS examinations and clinical assessments. 30 (39%) were classified as diffuse cutaneous SSc (dcSSC), 35 (45%) as limited cutaneous SSc (lcSSc) and 13 (17%) as sine scleroderma. A significant difference was found both for SMA RI (p for trend = 0.032) and SMA PI (p for trend = 0.004) between patients with sine scleroderma, lcSSc and dcSSc, with lower values observed in the sine scleroderma and lcSSc groups. IMA RI and PI were significantly correlated with GI symptoms such as fecal incontinence (ῥ - 0.33, p = 0.008 and ῥ - 0.30, p = 0.021, respectively). By multivariate analysis, significant associations were confirmed between SMA RI and SMA PI and mRSS (β 0.248, p = 0.030 and β 2.995, p = 0.004, respectively) and with bosentan (β 0.400, p = 0.003 and β 3.508, p = 0.001, respectively), but not with anticentromere antibody (ACA). No significant differences were found between the weighted median values of SMA RI and SMA PI of SSc patients compared to those of HS that were derived from the meta-analysis of the literature (p = 0.72 and p = 0.64, respectively). This cross-sectional study confirms that the splanchnic vasculature of SSc patients can noninvasively been studied with DUS. Vascular splanchnic involvement correlates with the presence and/or severity of specific clinical features in SSc, including GI. Larger and prospective studies are needed to confirm these preliminary observations and to examine the role of DUS in SSc-risk stratification and GI progression and to obtain definitive data regarding both HS and SSc patients splanchnic DUS parameters., (© 2024. The Author(s).)

Introduction: The optimal prednisolone dose for managing acute calcium pyrophosphate (CPP) crystal arthritis remains unclear. We compared the efficacy and safety of 10- and 30-mg daily doses of prednisolone for acute CPP crystal arthritis., Method: This randomized, controlled, open-label trial included patients with acute CPP crystal arthritis and symptoms that had begun less than 72 h earlier. Patients without CPP crystals, those with septic arthritis, and those with uncontrolled infections were excluded. Participants received either 10 or 30 mg of prednisolone daily for 7 days. The primary outcome was time until complete resolution of symptoms; secondary outcomes included time until clinical resolution, recurrence rates, laboratory profiles, and adverse events, adjusted for confounders., Results: Seventy-nine patients participated. Baseline characteristics were comparable, except that the 30-mg recipients had more initial inpatient visits (p = 0.03). The median time until complete resolution was 7 days in both groups (p = 0.73). The 30-mg recipients exhibited faster clinical resolution (1 vs. 3 days; p = 0.03), but adjusted analyses revealed no significant differences in time until complete resolution (6.2 vs. 6.5 days; p = 0.68) or clinical resolution (2.4 vs. 2 days; p = 0.27). The overall recurrence rate was 14.3%; the 30-mg recipients experienced slightly more recurrences (p = 0.08). The other secondary outcomes did not differ significantly., Conclusions: The 10- and 30-mg daily doses of prednisolone were equally effective in treating acute symptoms of CPP crystal arthritis, with no significant differences in resolution time, recurrence rates, or safety outcomes., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Older patients with heart failure are particularly vulnerable due to a wide range of associated comorbidities, disability, and frailty. This population often receives multiple prescriptions, increasing the risk of adverse drug reactions, non-adherence, and drug interactions. Deprescribing, which involves reducing the number of medications to the lowest clinically reasonable limit, has the potential to decrease the risk of drug interactions and enhance patients' quality of life. Moreover, simplifying medication regimens may improve adherence to essential heart failure therapies. This scientific review aims to comprehensively examine deprescribing strategies in older patients with heart failure. It explores the rationale, challenges, benefits, and potential approaches to optimizing medication regimens in this vulnerable population. Furthermore, the review suggests a practical, step-by-step approach for performing deprescribing in older patients with heart failure., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

A 52-year-old male comes to the internal medicine clinic for a follow-up for the management of hypertension. He was initially diagnosed with hypertension 5 years ago. His other past medical history includes obesity and hyperlipidemia. His current medications currently include losartan 100 mg daily, hydrochlorothiazide 25 mg, and amlodipine 10 mg. His physical exam is significant for an elevated in-office blood pressure of 160/105 mmHg, BMI 38, and neck circumference > 40 cm. He also reports snoring at night and having significant daytime sleepiness despite getting over 8 hours of sleep each night. This patient meets the most recent diagnostic criteria per the American Heart Association for resistant hypertension. Resistant hypertension is an increasingly prevalent phenotype encountered in both primary care and subspecialty clinics. Multiple comorbidities, including obesity, sleep apnea, chronic kidney disease, heart failure, and diabetes mellitus, are associated with resistant hypertension. Our understanding of the potential etiologies for this condition continues to evolve rapidly. We used a narrative review to explore four research areas in the pathophysiology of resistant hypertension (the sympathetic nervous system, aldosterone excess, endothelial dysfunction, and inflammation) and explore the novel therapies currently in development., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: The anti-COVID vaccination campaign has led to a significant increase in the demand for allergology consultations in patients considered at risk of reaction to anti-COVID-19 vaccines. This study aims to describe the experience of the vaccination campaign held in Piedmont (Italy) which developed a new service of Allergy Call Center (ACC) thus providing for the screening and management of allergy high-risk patients during pandemic., Study Design: A retrospective analysis was performed on all patients considered at high risk for the development of allergic reactions who were referred by the Immunology and Allergy Unit of Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022 and also on ACC consultations., Methods: During the COVID-19 pandemic, Piedmont Region instituted the ACC, active from May 10th, 2021 to December 31st 2022, to allow vaccinating doctors to require a telephonic consultation for patients who were considered at high risk for the development of allergic reactions. If further diagnostic evaluations were required, the ACC scheduled a visit with a Consultant of the Unit to better assess the clinical situation of the patient. Furthermore, patients referred by General Practitioners, Occupational Doctors and other consultants were also evaluated by the Unit when required., Results: During the operational period the ACC received a total of 15,865 calls and referred only 336 patients to the unit (27.4% of the total referrals), while General Practitioners referred 499 patients (40.8%), Occupational Doctors referred 61 patients (4.9%), and other consultants referred 326 patients (26.6%)., Conclusions: Evaluation and management of a large volume of requests seemed to be facilitated by a proactive framework for screening patients at high risk for allergic reactions as the ones referred by our ACC. This approach led to a prominent decrease in allergological visits to our tertiary care Centre, reducing the waiting times and providing additional support for both patients and healthcare providers, thus allowing the vaccinations to be more easily handled., (© 2024. The Author(s).)

Background: Peripheral artery disease (PAD) is a global health concern associated with arterial narrowing or blockage, leading to significant morbidity and mortality. The aim of this study is to assess the disease burden and trends in mortality utilizing nationwide administrative health data., Methods: This retrospective study utilized data from the Unified National Electronic Healthcare System (UNEHS) from 2014 to 2021. Patients meeting PAD criteria were included, with demographic and clinical data analyzed. Cox regression and Competing Risk Analysis assessed mortality risks., Results: Between 2014 and 2021, 19,507 individuals were hospitalized due to PAD, with 8,332 (43%) being women and 11,175 (57%) men. The incidence of PAD increased markedly over the observation period, rising from 79 individuals per million population (PMP) in 2014 to 309 PMP in 2021. Concurrent heart failure (HF), acute myocardial infarction (AMI), diabetes, and essential hypertension were prevalent in 50%, 27%, 27%, and 26% of the PAD patients, respectively. Competing Risk Analysis showed a subdistribution hazard ratio (SHR) of 6.53 [95% CI: 4.65-9.19] for individuals over 80 years. Heart failure was associated with lower all-cause HR [0.80, 95% CI: 0.76-0.86, p < 0.001] but higher SHR [1.30, 95% CI: 1.18-1.44, p < 0.001]. Comorbidities such as heart failure, stroke, and acute myocardial infarction significantly increased mortality risks, while essential hypertension was associated with lower risk of death., Conclusion: The significant rise in the incidence rate of PAD underscores the growing burden of the disease, highlighting the urgent need for targeted preventive and management strategies in Kazakhstan., (© 2024. The Author(s).)

Purpose: The human AlkB homolog (ALKBH) dioxygenase superfamily plays a crucial role in gene regulation and is implicated in cancer progression. Under hypoxic conditions, hypoxia-inducible factors (HIFs) dynamically regulate methylation by controlling various dioxygenases, thereby modulating gene expression. However, the role of hypoxia-responsive AlkB dioxygenase remains unclear., Methods: The molecular events were examined using real-time PCR and Western blot analysis. Tumor cell aggressiveness was evaluated through migration, invasion, MTT, trypan blue exclusion, and colony formation assays. In vivo metastatic models and xenograft experiments were conducted to evaluate tumor progression., Results: Here, we examined the expression of the ALKBH superfamily under hypoxic conditions and found that ALKBH4 expression was negatively regulated by hypoxia. Knockdown of ALKBH4 enhanced the epithelial-mesenchymal transition (EMT), cell migration, invasion, and growth in vitro. The silencing of ALKBH4 enhanced metastatic ability and tumor growth in vivo. Conversely, overexpression of ALLKBH4 reversed these observations. Furthermore, overexpression of ALKBH4 significantly reversed hypoxia/HIF-1α-induced EMT, cell migration, invasion, tumor metastasis, and tumorigenicity. Notably, high expression of ALKBH4 was associated with better outcomes in head and neck cancer and breast cancer patients. Enrichment analysis also revealed that ALKBH4 was negatively enriched in hypoxia-related pathways. Clinically, a negative correlation between ALKBH4 and HIF-1α protein expression has been observed in tissues from both head and neck cancers and breast cancers., Conclusion: These findings collectively suggest that ALKBH4 acts as a tumor suppressor and holds therapeutic potential for hypoxic tumors., (© 2024. The Author(s).)

Background: The aim of this study was to elucidate the critical role of autophagy-related gene aggregation in gastric cancer tumor microenvironment cells and to investigate their major roles in cellular functions. In particular, the expression of these genes in tumor-associated fibroblast subtypes was scrutinized in an attempt to explain their cell-subpopulation-specific roles in cell-cell communication and regulation of cellular functions., Methods: In this study, single-cell RNA sequencing data were first analyzed in multiple steps, including data preprocessing, cell clustering, and cell classification. Cell subpopulations and gene expression patterns were identified and analyzed using unsupervised non-negative matrix factorization (NMF) techniques. The dynamic expression of autophagy-related gene aggregates in various cell types was deciphered by pseudotime trajectory analysis (PTA). Intercellular communication analysis was performed using the CellChat R software package, revealing the intricate communication patterns and exchange of key signaling molecules between cell subpopulations, and SCENIC analysis was used to identify gene regulatory networks and reveal the mechanisms behind cellular heterogeneity., Result: Cell subpopulations associated with pan-apoptosis were identified by NMF decomposition and SCENIC analysis. Cell-cell communication analysis revealed intricate communication patterns and exchange of key signaling molecules between cell subpopulations. Dynamic expression of autophagy-related genes aggregated in the pseudotemporal trajectory of STAD was observed by PTA. In the fibroblast subtype, different ligand-receptor interactions and their key roles in immunomodulation were observed., Conclusion: By deeply analyzing and comparing gene expression patterns within cellular subpopulations and intercellular communication, this study provides new insights into the role of pan-apoptosis-related genes in regulating immune responses and cellular functions in gastric cancer. These findings pave the way for further exploration of the role of these genes in tumorigenesis and immune regulation, as well as laying the foundation for potential therapeutic strategies., (© 2024. The Author(s).)

Purpose: This paper outlines the consensus of the Italian Association for Neuroendocrine Tumors(Itanet), the Italian Association of Nuclear Medicine (AIMN), the Italian Society of Endocrinology (SIE), and the Italian Association of Medical Oncology (AIOM) on treating neuroendocrine neoplasms (NENs)with radioligand therapy (RLT)., Methods: A list of 10 questions regarding using RLT ingastroenteropancreatic neuroendocrine tumors (GEP-NETs) was addressed after a careful review of theavailable literature. compiling information from the MEDLINE database, augmented with expert opinionsand recommendations, aligns with the latest scientific research and the author's extensive knowledge.The recommendations are evaluated using the GRADE system, showcasing the level of evidence andthe strength of the recommendations., Results and Conclusions: Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines., (© 2024. The Author(s).)

Purpose: We aimed to evaluate an approach with resting echocardiography (TTE) and stress myocardial perfusion scintigraphy (MPS) compared to standard MPS in patients with stable angina and normal left ventricle (LV). We hypothesized that normal LV on TTE may allow for the elimination of rest MPS without compromising accuracy and offering an efficient diagnostic pathway with reduced radiation exposure., Methods: In a prospective, non-randomized study TTE was performed prior to MPS in patients (pts) referred for assessment of coronary artery disease (CAD). In pts with normal LV assessment was performed using the hybrid and the standard approach. TTE and MPS were interpreted by two TTE readers (ER1-2) and two MPS readers (NR1-2). ECHO-MPS was compared with standard MPS for diagnostic accuracy., Results: 103 patients, mean age 61 ± 12 year, (63 M, 40 W) were recruited. Standard MPS were normal in 75 patients and abnormal in 28 patients, with the hybrid approach 79 studies were reported as normal and 24 studies as abnormal. Kappa values were 0.580, (p < 0.001) for large, 0.394, (p < 0.001) for medium, and 0.298 (p = 0.002) for small defects. With standard MPS as a reference, sensitivity for detection of perfusion defects by ECHO-MPS was 75% (95% CI 0.67-0.83) [NR2] and 78% (95% CI 0.70-0.86)[NR1]. Specificity was 95% (95% CI 0.90-0.99) [NR2] and 95% (CI 95%CI 0.90-0.99) [NR1]., Conclusions: ECHO-MPS protocol provides similar diagnostic accuracy as standard stress-rest MPS. In patients with normal systolic LV function in TTE, performing only stress MPS provides similar information as standard rest and stress MPS., (© 2024. The Author(s).)

Background and Aim: Although appendicular skeletal muscle mass (ASM) has been linked to the severity of hepatic steatosis, investigations of its correlation among younger age groups are lacking. We aimed to elucidate the role of ASM in determining the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in younger patients., Methods: Retrospective data were collected from patients younger than 35 years who visited the Armed Forces Goyang Hospital between June 2022 and February 2024. Steatosis presence was determined by a controlled attenuation parameter score ≥ 250 dB/m, and significant fibrosis was identified with liver stiffness measurement > 8.0 kPa. ASM was measured using multifrequency bioelectrical impedance analysis (InBody 620)., Results: Of 910 participants, 630 were diagnosed with MASLD. Patients with MASLD had lower ASM/fat mass (ASM/F) (1.02 vs. 1.91; p < 0.001), ASM/body mass index (BMI) (0.91 vs. 1.04/m 2 ; p < 0.001), and ASM/body weight (ASM/W) (29.5% vs. 33.8%; p < 0.001) than non-MASLD patients. Additionally, ASM/F, ASM/BMI, and ASM/W significantly decreased with worsening steatosis severity and were notably lower in patients with significant fibrosis. Among 107 patients with MASLD who underwent two examinations with a median interval of 6.0 months, those with increased ASM/F showed a higher proportion of steatosis regression and a lower proportion of steatosis worsening than those with decreased ASM/F (steatosis regression, 43.1% vs. 22.9%; worsening, 11.1% vs. 28.6%; p = 0.031). All three ASM indices were significant factors in steatosis regression during the study period., Conclusions: ASM is associated with the severity of steatosis and significant fibrosis in MASLD in young adults < 35 years., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: The optimal diameter for endoscopic dilatation of anastomotic strictures after esophagectomy has not been elucidated. This study aimed to determine the optimal target diameter for endoscopic dilatation for anastomotic stricture after esophagectomy., Methods: The medical records of patients who underwent endoscopic dilatation for anastomotic stricture after esophagectomy between January 2009 and June 2024 at Pusan National University Yangsan Hospital were reviewed. The stricture recurrence rate, dilatation-free period, and complications according to the dilatation diameter were collected and included in the analysis., Results: We analyzed 149 endoscopic dilatations (diameters from 10 to 18 mm) in 43 patients. The median follow-up period was 47 months (range, 5-157). The stricture recurrence rate was 72.5%, and the median dilatation-free period was 60 days. The stricture recurrence rate was the lowest (41.7%, p = 0.022), and the overall dilatation-free period was the longest (median 490 days, p = 0.171) in dilations up to 16.5 mm. The stricture recurrence rate was higher in dilations up to 18 mm than in those up to 16.5 mm (54.5% vs. 41.7%, p = 0.331). Moreover, the bleeding rate was higher in patients with dilations up to 18 mm (18.2% vs. 4.2%, p = 0.205)., Conclusion: In patients with anastomotic strictures after esophagectomy, dilation up to 16.5 mm showed a lower stricture recurrence rate, longer dilation-free period, and less postprocedural bleeding than those of dilation up to 18 mm., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction/objectives: The aim of this study was to develop and validate the Raynaud Specific Quality of Life Questionnaire (RQLQ) for assessing health-related quality (HRQOL) of life in patients with Raynaud's disease (RD)., Method: The questionnaire was developed and validated in three stages. Initially, semi-structured interviews with 28 RD patients identified domains of everyday life affected by RD, leading to the creation of the initial RQLQ. In the first quantitative stage, 101 patients completed the RQLQ, and exploratory factor analysis assessed dimensionality and factor structure. After removing poorly performing items, the final RQLQ was tested with 102 patients. This stage also evaluated convergent, divergent, and discriminant validity, as well as internal reliability., Results: From the interviews, 135 items were generated, with factor analysis refining the measure to 29 items across five subscales, showing good internal consistency. The RQLQ demonstrated significant correlations with self-rated quality of life and physical and mental health outcomes, confirming convergent and divergent validity. It also showed discriminant validity for different levels of disease activity., Conclusions: The RQLQ is the first specific HRQOL measure for RD patients, proving to be a psychometrically sound, reliable, and valid tool for clinical research and practice. Key Points • The Raynaud Specific Quality of Life Questionnaire (RQLQ) is an important scale that evaluates the quality of life of patients with Raynaud's disease. • The questionnaire showed good validity and reliability a capturing disease-specific quality of life. • This tool may aid in clinical research and practice., (© 2024. The Author(s).)

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57-0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis., Methods: In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007-2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge., Results: In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1-5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5-53). The median extent of LGE was 7% (IQR, 4-10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29-17.49; p < 0.001). Patients with the transmural extension of LGE had a shorter event-free time on Kaplan-Meier analysis (log-rank p < 0.001)., Conclusions: MACE occurred in 14% of patients with infarct-like myocarditis during follow-up. A transmural extension of non-ischemic LGE was associated with a worse long-term prognosis., Critical Relevance Statement: CMR-based assessment of transmural extension of non-ischemic LGE holds the potential to serve as an easily assessable marker for risk stratification in patients with infarct-like myocarditis., Key Points: The prognostic value of CMR was studied in patients with infarct-like myocarditis. The extent of LGE and transmural extension were linked to adverse cardiac events. Transmural non-ischemic LGE can serve as an easily assessable prognostic marker., (© 2024. The Author(s).)

Toxoplasmosis is one of the most common parasites affecting humans in diverse populations caused by T. gondii. This study aims to systematically review and analyze the prevalence of T. gondii infection among various population categories in Saudi Arabia. Our search was done in five databases: PubMed, Scopus, Cochrane Library, Embase, and Web of Science to find the relevant studies from inception to November 2023. The pooled prevalence of toxoplasmosis among the total population living in Saudi Arabia was estimated using a random-effect meta-analysis approach, and Comprehensive Meta-Analysis software was utilized for this analysis. Our study included 30 case-control and retrospective studies published from 1994 to 2023 involving 20,699 patients from different regions in the Kingdom of Saudi Arabia. Various cities were included, such as Al-Ahsa, Najran, Riyadh, Arar, Mecca, al Khobar, Mushait, Tabuk, jazan, Hail City, Almadinah Almunawwarah, AL-Ahsa, and Abha; 27 reported outcomes related to IgG seroprevalence, revealing an overall toxoplasmosis prevalence of 27.5% in Saudi Arabia. Fifteen studies that measured IgM seroprevalence found an overall toxoplasmosis prevalence of 2.2%. Specifically for pregnant women, IgG seroprevalence was 28%. Among different age categories, the highest toxoplasmosis prevalence was observed in the group aged 31-45 years, reaching 32.5%, while the lowest prevalence was in the 10-20 years category at 19.3%. Regarding gravidity, the grand multi-gravida group exhibited the highest prevalence at 32.9%, with an upper limit of 47.8%. Furthermore, individuals who consumed freshwater demonstrated a higher incidence than those drinking bottled water, with respective prevalence rates of 33.5% and 29.4%. In conclusion, the prevalence of toxoplasmosis in Saudi Arabia is lower than the global average, with significant variations across different age groups, water sources, and dietary habits. Targeted educational programs and public health interventions are essential to raise awareness and reduce the risk of T. gondii infection. Future research should focus on improving study quality and exploring the broader implications of toxoplasmosis on public health in Saudi Arabia., (© 2024. The Author(s).)

Administering zoledronic acid (ZA) to older hip fracture patients during the hospital stay has faced safety concerns. However, in this study of 161 patients, no ZA-related side effects or readmissions were observed, demonstrating that ZA administration during hospitalization is safe and effective for secondary fracture prevention., Purpose: According to the 2022 Dutch 'Osteoporosis and fracture prevention' guideline, zoledronic acid (ZA) is the preferred osteoporosis treatment for hip fracture patients. Less than 25% of hip fracture patients visit the outpatient fracture liaison service, therefore inpatient administration of ZA during the hip fracture hospitalization is now recommended in patients > 75 years. In the OLVG Hospital, inpatient administration of ZA during hospitalization for hip fracture in older patients has been standard of care since 2020., Methods: This single center retrospective observational follow-up study included hip fracture patients > 75 years admitted to the orthogeriatric ward of the OLVG Hospital, and treated with 5 mg of ZA intravenously on the day of hospital discharge between June 2020 and December 2022. Life expectancy estimated < 12 months, creatinine clearance < 35 ml/min, hypocalcemia, and high risk of osteonecrosis of the jaw were contra-indications. During three months of follow-up (FU) adverse events, emergency room visits, hospital readmissions, and death were recorded., Results: In 161 consecutive hospitalized hip fracture patients (mean age 86 ± 6 years, 65% female, 18% nursing home) ZA was administered and no adverse events were recorded. During 3 months of FU, 8 patients (5%) visited the emergency room, 19 patients (12%) were re-admitted to the hospital, 3 with a new fracture (2 contralateral hip, 1 radius), and 17 patients (11%) died of reasons unrelated to ZA., Conclusion: This study shows that inpatient administration of zoledronic acid during hip fracture hospitalization is safe and feasible to prevent future fragility fractures in older hip fracture patients., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)