Observation Period Research Articles

Proton radiotherapy for rectal cancer

AIM: to assess the effectiveness of proton radiotherapy as part of a combined approach to the treatment of rectal malignancies and to assess acute radiation toxicity, which directly affects patients’ quality of life.PATIENTS AND METHODS: between 2020 and 2023, a study included 74 patients with rectal cancer. The mean age of the patients was 65 ± 9.9 years, 44 (60%) males. Stage I occurred in 8 (10.8%) patients, stage II — in 14 (18.9%) patients, stage III — in 52 (70.3%) patients. At the first stage, all patients completed proton radiation therapy in the classical fractionation mode.RESULTS: of the adverse events, 49 (66%) patients had grade 1–2 radiation reactions in the form of proctitis and cystitis. There were no local radiation reactions of grade 3 or higher. Systemic complications of grade 3 were noted in 2 (2%) patients in the form of hematological toxicity — anemia (1%), afebrile neutropenia (2%). Of the 62 operated patients, 12 (19.3%) people showed complete therapeutic pathomorphosis. With a median follow-up of 23 months (13;35), 1 (1.35%) patient showed continued tumor growth 28 months after completed radiotherapy, 2 (2.7%) patients had local recurrence 3 and 18 months after treatment. Distant metastases to the lungs, liver, or bones were detected in 9 (12.2%) patients, median — 12 months (6;23). Mortality during the entire observation period was 9 (12.2%) patients. Sixty-two (83.8%) patients showed no signs of relapse or progression of the disease, of which 9 (14.5%) patients did not receive any treatment after chemoradiotherapy and are in the process of active follow-up.CONCLUSION: proton radiation therapy in patients with rectal cancer in two-year overall survival (90.5%) and progression-free survival (88.9%) are comparable with the literature data of recent studies, but are superior in overall survival pathological response (19.3%).

Intercontinental Comparison of Immunohistochemical Subtypes Among Individuals With Breast Cancer in South-East Asia and South America: A Scoping Systematic Review and Meta-Analysis of Observational Studies.

Breast cancer (BC) remains a significant global concern, particularly among developing countries in South-East Asia (SEA) and South America (SA). The socioeconomic burdens of oncologic care in those countries were often originated from limited accessibility on attainable therapeutic options and reliability on identifying essential information of cancer cells, i.e., immunohistochemical (IHC) subtyping to determine suitable approaches. The triple-negative breast cancer (TNBC) is among the most aggressive category in breast malignancy, therefore, requiring more specific molecular pathway blocking to exhaust the cells. However, large-scale epidemiological investigation on its rate among BC remains unavailable to date. This study aimed to describe the prevalence of TNBC in the SEA and SA continents since it may guide the future direction of oncologic research and trials. This review focuses on observational studies from the SEA and SA continents from the last decade. Each study represents its country or cities, period of observation, population size, and the TNBC-BC rate as the main outcomes. Therefore, we may also limit the reporting bias originated from same-patient data on the specific occasions. The analysis will be derived to SEA-SA comparison, plus SEA/SA-specific session as processed in Comprehensive Meta-Analysis (CMA) version 3.0. The statistical analysis will be performed in random effects model (REM) within 95% confidence interval (CI). From 46 studies included in the final analysis with a total enlisted population of 34,346 unique individuals with BC, the TNBC rate was higher in the SEA compared to the SA region (19.3% vs. 15.7%; P < 0.05 in 95% CI), with the highest prevalence observed in Vietnam (22.4%) and Peru (17.8%), if it was restricted on countries with two or more studies. Interestingly, both Laos and Argentina possessed significant differences compared to other countries within their respective continents, with the highest and lowest TNBC rates (P < 0.05). The IHC characteristics in SEA differ from those in the SA continent as mainly represented by TNBC prevalence, possibly shaping the course of future trials in the respective region based on IHC expressivity status.

An integrated cost based approach for warehouse performance evaluation: A new multiphase model

Warehouses represent key links in domestic and international commodity flows. The increasing shortage of workers and increasing costs on the one hand, and the increasing number and stricter demands of users on the other hand lead warehouse managers to realize their operations as efficiently as possible. A proposed model has an objective of enabling companies to monitor warehouse performance in an authoritative, reliable, and simple way and define appropriate corrective measures accordingly. The proposed empirical research consists of three stages, where in the first stage a combination of Principal Component Analysis-Data Envelopment Analysis methods was applied in order to determine efficient warehouses based on 90 decision making units. In the second phase, a completely new method called Interval Fuzzy Rough Pivot Pair-wise Relative Criteria Importance Assessment method used for determining criteria weights was developed and applied, which is one of the most important novelties of this study. In the last phase, the Interval Fuzzy Rough Measurement of Alternatives and Ranking according to the Compromise Solution method was applied to rank the alternatives. Twelve criteria were observed to evaluate 21 alternatives. Based on the results, it was concluded that salary stood out as the most important criterion, while amortization stood out as the least significant criterion. On the other hand, alternatives A9 and A10 stood out as the best-ranked alternatives while A1, A2, and A3 stood out as the least efficient ones. The paper provides clear scientific contributions that are reflected in the reduction of the gap that was observed after reviewing the literature where there is a lack of papers dealing with this task. Also, the combination of methods applied in the paper has not been used so far, so it can be said that this paper represents an excellent basis for further research. The model has practical contributions as it allows decision-makers to make quality decisions regarding the operation of their warehouses in different time periods or observation periods, as well as it represents a decision support tool that can be used for better warehouse management.

Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort

BackgroundBecause exacerbation of severe asthma decreases patients’ quality of life, this study aimed to identify predictive factors for asthma exacerbation. MethodsJapanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). ResultsA total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51–72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49–436)/μL, 28 (IQR, 15–43) ppb, 172 (IQR, 56–473) IU/mL, and 80.0 (IQR, 61.1–96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. ConclusionsExacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

Short- and long-term performance of risk calculation tools for mortality in patients with acute coronary syndrome

BackgroundThe mortality rate of acute coronary syndrome (ACS) remains high. Therefore, patients with ACS should undergo early risk stratification, for which various risk calculation tools are available. However, it remains uncertain whether the predictive performance varies over time between risk calculation tools for different target periods. This study aimed to compare the predictive performance of risk calculation tools in estimating short- and long-term mortality risks in patients with ACS, while considering different observation periods using time-dependent receiver operating characteristic (ROC) analysis.MethodsThis study included 404 consecutive patients with ACS who underwent coronary angiography at our hospital from March 2017 to January 2021. The ACTION and GRACE scores for short-term risk stratification purposes and CRUSADE scores for long-term risk stratification purposes were calculated for all participants. The participants were followed up for 36 months to assess mortality. Using time-dependent ROC analysis, we evaluated the area under the curve (AUC) of the ACTION, CRUSADE, and GRACE scores at 1, 6, 12, 24, and 36 months.ResultsSixty-six patients died during the observation periods. The AUCs at 1, 6, 12, 24, and 36 months of the ACTION score were 0.942, 0.925, 0.889, 0.856, and 0.832; those of the CRUSADE score were 0.881, 0.883, 0.862, 0.876, and 0.862; and those of the GRACE score 0.949, 0.928, 0.888, 0.875, and 0.860, respectively.ConclusionsThe ACTION and GRACE scores were excellent risk stratification tools for mortality in the short term. The prognostic performance of each risk score was almost similar in the long term, but the CRUSADE score might be a superior risk stratification tool in the longer term than 3 years.

Prognostic impact of plasma volume status during hospital admission in patients with acute decompensated heart failure.

Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9±12.9years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134days). The primary endpoint of this study was all-cause mortality. The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P=0.016, P=0.005 and P<0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR)=1.06 (1.00-1.12), P=0.048] was an independent poor prognostic factor for ADHF. This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.

Leaching and cytotoxicity of bismuth oxide in ProRoot MTA - A laboratory investigation.

The present study examined the leaching and cytotoxicity of bismuth from ProRoot MTA and aimed to identify whether bismuth leaching was affected by the cement base and the immersion regime used. The leaching profile of bismuth was examined from ProRoot MTA and compared with hydroxyapatite containing 20% bismuth oxide as well as hydroxyapatite and tricalcium silicate to investigate whether bismuth release changed depending on the cement base. Bismuth leaching was determined after 30 and 180 days of ageing immersed in Dulbecco's modified Eagle's medium (DMEM) using mass spectroscopy (ICP-MS). The media were either unchanged or regularly replenished. The pH, surface microstructure and phase changes of aged materials were assessed. Wistar rat femoral bone marrow stromal cells (BMSCs) and cutaneous fibroblasts were isolated, cultured and seeded for cell counting (trypan blue live/dead) after exposure to non-aged, 30- and 180-days-aged samples in regularly replenished DMEM. Aged DMEM in contact with materials was also used to culture BMSCs to investigate the effect of material leachates on the cells. Gene expression analysis was also carried out after direct exposure of cells to non-aged materials. Differences between groups were statistically tested at a significance level of 5%. All materials exhibited alterations after immersion in DMEM and this increased with longer exposure times. The bismuth leached from ProRoot MTA as detected by ICP-MS. Aged ProRoot MTA samples exhibited a black discolouration and surface calcium carbonate deposition. ProRoot MTA influenced cell counts after direct exposure and its 180-days leachates reduced BMSC viability. After direct BMSC contact with non-aged ProRoot MTA an upregulation of metallothionein (MT1 and MT2A) expression and down-regulation of collagen-1a (Col-1a) and bone sialoprotein (BSP) expression was identified. Bismuth leaching was observed throughout 180-days observation period from all materials containing bismuth oxide. This negatively influenced cell viability and gene expression associated with bismuth exposure. This is the first study to report that metallothionein gene expression was influenced by exposure to ProRoot MTA.

Heterogeneity in the definition of major adverse kidney events: a scoping review.

Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions.

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Portal hypertension and its prognostic implications in patients with Wilson's disease.

Wilson's disease may progress to cirrhosis and clinically significant portal hypertension (CSPH). We aimed to assess the prevalence and prognostic impact of CSPH-related features on hepatic decompensation and transplant-free survival in patients with Wilson's disease. About 137 patients with Wilson's disease (Leipzig score ≥4), followed for a median observation period of 9.0 (3.9-17.7) years at the Vienna General Hospital, were included in this retrospective study. Overall, 49 (35.8%) developed features of CSPH: 14 (10.2%) varices, 40 (29.2%) splenomegaly, 20 (14.6%) ascites, 18 (13.1%) hepatic encephalopathy and 3 (2.2%) experienced acute variceal bleeding. Overall, 8 (5.8%) patients died, including three deaths caused by CSPH-related complications. Within 10 years, compensated patients with features of CSPH developed more decompensation events (8.3% vs. 1.5% in patients without CSPH, p = 0.3) and had worse transplant-free-survival (91.7% vs. 98.6%), which further declined in patients with hepatic decompensation (26.7%, log-rank: p < 0.0001). Patients with liver stiffness <15 kPa and normal platelets (≥150 G/L) were less likely to decompensate within 10 years (2.6% vs. 8.4%, p = 0.002) and had a better 10-year transplant-free-survival (97.7% vs. 83.9%, p = 0.006). Patients with Wilson's disease developing features of CSPH are at an increased risk for hepatic decompensation and liver-related mortality, warranting for regular screening and timely initiation of effective CSPH-directed treatments.

A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection.

Antibody-mediated rejection is a leading cause of kidney-transplant failure. The targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells may be a therapeutic option. In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with antibody-mediated rejection that had occurred at least 180 days after transplantation to receive nine infusions of the CD38 monoclonal antibody felzartamab (at a dose of 16 mg per kilogram of body weight) or placebo for 6 months, followed by a 6-month observation period. The primary outcome was the safety and side-effect profile of felzartamab. Key secondary outcomes were renal-biopsy results at 24 and 52 weeks, donor-specific antibody levels, peripheral NK-cell counts, and donor-derived cell-free DNA levels. A total of 22 patients underwent randomization (11 to receive felzartamab and 11 to receive placebo). The median time from transplantation until trial inclusion was 9 years. Mild or moderate infusion reactions occurred in 8 patients in the felzartamab group. Serious adverse events occurred in 1 patient in the felzartamab group and in 4 patients in the placebo group; graft loss occurred in 1 patient in the placebo group. After week 24, resolution of morphologic antibody-mediated rejection was more frequent with felzartamab (in 9 of 11 patients [82%]) than with placebo (in 2 of 10 patients [20%]), for a difference of 62 percentage points (95% confidence interval [CI], 19 to 100) and a risk ratio of 0.23 (95% confidence interval [CI], 0.06 to 0.83). The median microvascular inflammation score was lower in the felzartamab group than in the placebo group (0 vs. 2.5), for a mean difference of -1.95 (95% CI, -2.97 to -0.92). Also lower was a molecular score reflecting the probability of antibody-mediated rejection (0.17 vs. 0.77) and the level of donor-derived cell-free DNA (0.31% vs. 0.82%). At week 52, the recurrence of antibody-mediated rejection was reported in 3 of 9 patients who had a response to felzartamab, with an increase in molecular activity and biomarker levels toward baseline levels. Felzartamab had acceptable safety and side-effect profiles in patients with antibody-mediated rejection. (Funded by MorphoSys and Human Immunology Biosciences; ClinicalTrials.gov number, NCT05021484; and EUDRACT number, 2021-000545-40.).

Adherence to remote monitoring recommendations in current clinical practice: data from a remote monitoring database

Abstract Background The recently published Expert Consensus Statement on the Practical Management of Remote Device Clinic offers evidence-based recommendations for managing patients with cardiovascular implantable electronic devices (CIEDs). Purpose We examined data from a remote monitoring (RM) database to evaluate adherence to RM recommendations in current clinical practice. Methods According to RM guidelines, patients should be enrolled within 2 weeks of implantation for earlier detection of actionable events, and in any case, within 3 months, as it is associated with improved survival. Continuous connectivity should be maintained. In patients with continuous connectivity, alert-based RM may replace structured intermittent device follow-up. We analyzed data from 4427 CIED patients followed on the LATITUDE (Boston Scientific) remote network at 20 Italian centers. Patients were enrolled between 2010 and 2023, with a median RM duration of 37 months (25th-75th percentile: 21-60). Results The number of patients enrolled at the centers significantly increased during the observation period (Figure). In the overall RM population, we identified a group of patients (56%) enrolled after implantation (within 6 months) and a group of patients enrolled late during their follow-up. In the first group, RM receiver activation occurred within 2 weeks in 62% and within 3 months in 90% of patients. The second group consisted mainly of patients not yet in RM at the time of COVID-19 outbreak and included to allow RM of all patients at the centers. Overall, 96% of enrolled patients performed remote data transmissions during the observation period. As of the July 2023 data extraction, 1405 (33%) patients were not monitored, with no significant differences among CIED types (CRT-D: 37%; ICD: 32%; S-ICD: 32; Pacemaker: 30%). Most not-monitored patients (30%) had not transmitted data for over a year, likely due to patient death, CIED extraction, or other irreversible causes. For the remaining 3%, the recent loss of connection (occurring within a timeframe shorter than the scheduled transmission interval) should have prompted interventions to restore connection. Scheduled device transmissions occurred at least once every 3 months in 94% of patients. Considering individual device programming, the 2836 patients with consistent connectivity performed 25,281 scheduled transmissions in one year. Conclusions In current clinical practice, RM adoption is continually increasing, with generally observed adherence to post-implantation patient enrollment recommendations. However, a significant proportion of patients may activate RM earlier. Centers must implement solutions to ensure transmission continuity in a substantial percentage of patients. Nevertheless, the workload generated by this activity could be effectively balanced by adopting an alert-based RM strategy and reducing unnecessary scheduled transmissions.Enrolled patients trend

Polygenic risk score for Atrial Fibrillation as a predictor for the incidence of Sick Sinus Syndrome: A comprehensive analysis from the UK biobank

Abstract Background Sick sinus syndrome (SSS) and atrial fibrillation (AF) often coexist, demonstrating a bidirectional relationship. The polygenic risk score (PRS) represents the cumulative risk of disease onset based on variations at multiple genetic loci and is known as a predictor for disease incidence. However, the PRS for SSS remains under-investigated. This study aims to evaluate whether the PRS for AF can predict the incidence of SSS in the general population. Methods The UK biobank, comprising of about 500,000 participants aged 40 to 70, was established across 22 centres in the UK between 2006 and 2010. After excluding missing values, prior AF history, and valvular heart disease, a total of 101,654 participants without AF (median age, 56.0 [interquartile range (IQR), 49.0–63.0] years; 44,851 [44.1%] male) were analyzed. Participants were divided into quartiles according to a validated PRS for AF. Throughout the observation period, the incidence of SSS event was documented. Results During a follow-up period of 11.7 (IQR 11.0-12.5) years, a total of 157 cases of Sick sinus syndrome were identified. In the new-onset SSS group, age, PRS for AF, BMI, and waist measurements were significantly higher. Additionally, there was a statistically significant increase in the proportions of male sex, hypertension, previous MI, hypothyroidism, dyslipidemia, and ESRD/CKD. The Kaplan-Meier analysis demonstrated an association between the highest quartile and an increased incidence of SSS compared to the other quartiles. (Log-rank P &amp;lt; 0.001) The Cox regression model revealed that a PRS for AF was associated with an increased risk of incidence of sick sinus syndrome (aHR 1.29, 95% CI 1.10-1.51, p-value 0.002). Notably, the discriminative power of our model was substantial, yielding a C-index of 0.746. Conclusion In our study, the PRS for AF effectively predicted the incidence of SSS. In the absence of a dedicated PRS for SSS, the AF PRS may offer insights into developing one for SSS.

Long-term recurrence-free survival following second-generation cryoballoon ablation for persistent atrial fibrillation: role of the autonomic nervous system

Abstract Background The cardiac autonomic nervous system (ANS) plays a pivotal role in the regulation of atrial fibrillation (AF). Cryoballon (CB)-guided pulmonary vein isolation (PVI) is an established treatment for AF. Purpose In our present study we evaluated the impact of vagal reactions (VRs), as a surrogate parameter for ANS modulation, on the long-term outcome of CB-ablation in patients with persistent AF (PERS AF). Methods Data from consecutive PERS AF patients undergoing primary CB-guided PVI for symptomatic drug refractory AF between 2013-2023 were analysed. VRs were defined as bradycardia &amp;lt; 40 beats/min, asystole or higher-degree atrioventricular block. Long-term follow-up data were assessed. AF-recurrence was defined as AF lasting &amp;gt; 30 seconds beyond a 3-month blanking period. Results A total of 250 consecutive patients (mean age 63.9±10.0 years, 30% female) were included. VRs were recorded in 61 patients (24%, mean age 64.2±13.0 years, 30% female). The mean follow-up duration amounted to 84±14 months. Within this observation period 101 patients (40%) developed AF-recurrence. Re-ablation procedures were performed in 61 patients (60%). Patients with PVI-associated VRs presented with a significantly higher estimated AF-free survival rate (log-rank p-value &amp;lt; 0.001) (Figure 1) and a significantly longer median AF-free survival time (75 months, interquartile range (IR) 63-92 months) compared to those without (69 months, IR 13-79 months) (p=0.002). Beyond that Kaplan-Meier plot analyses revealed significant gender differences (Figure 1). Multivariate cox regression analyses confirmed VRs (Confidence interval (CI) 0.294-0.838, Hazard Ratio (HR) 0.497, p=0.009) and male gender (CI 0.352-0.781, HR, 524, p=0.001) as independent predictors (IPs) for AF-free-survival. Conclusion CB-ablation procedure associated VRs and male gender seem to be associated with a favorable long-term outcome in PERS AF. Further studies are warranted to verify our observations.Kaplan Meier plot on long-term AF-free s

Device programming and SMART pass algorithm activation in subcutaneous implantable defibrillator patients: data from a remote monitoring database

Abstract Background In subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients, a previous study demonstrated very low rates of delivered shocks and inappropriate shocks on programming a conditional zone between 200 and 250 bpm and a shock zone for arrhythmias &amp;gt;250 bpm. The extent to which this programming approach is adopted in clinical practice has been little studied, as the activation status of the SMART Pass filter, that was implemented to reduce inappropriate shocks and enhanced over time. Purpose We assessed device programming during follow-up and the rate of detected arrhythmias in a cohort of consecutive S-ICD recipients. Methods We analyzed data from 670 S-ICD patients followed on the remote network at 17 Italian centers for a median of 31 months (25th-75th percentile: 16-51). The enhanced SMART Pass version was available for all patients after October 2022. It makes the deactivation monitor less sensitive to premature ventricular contractions or other transient amplitude changes while maintaining arrhythmia sensitivity and specificity, and it was expected to reduce unintentional deactivation rate. Results At the last remote data transmission, the median programmed conditional zone cut-off was set to 210 bpm (25th-75th percentile: 200-220), the shock zone cut-off was 250 bpm (25th-75th percentile: 240-250), and the SMART Pass was enabled in 586 (87%) patients. During follow-up, 194 automatic deactivation events (0.10/patient-year) were reported in 118 (18%) patients. The SMART Pass-disabled time was 13% of the total observation period. Shocks were delivered in 129 (19%) patients (rate: 0.13/patient-year), and untreated arrhythmias were recorded in 136 (20%) patients (rate: 0.14/patient-year). The rate of shocks was lower when SMART Pass was enabled – 0.12/patient-year (95% CI: 0.10-0.14) versus 0.20 (95%CI: 0.15-0.26) (p=0.002), as it was the rate of untreated arrhythmias – 0.12/patient-year (95% CI: 0.11-0.14) versus 0.23 (95%CI: 0.18-0.30) (p=0.001). The enhanced SMART Pass version was associated with a lower rate of deactivations – 0.04/patient-year (95%CI: 0.02-0.05) versus 0.14 (95% CI: 0.12-0.16) (p&amp;lt;0.001), and with a reduction in treated and untreated arrhythmias (Incidence rate ratios: 0.40 (95%CI: 0.28-0.53) and 0.40 (95%CI: 0.30-0.55), respectively (p&amp;lt;0.001)). Conclusions In current clinical practice, S-ICD implantation centers often program high cut-off rates for arrhythmia detection. Most patients have SMART Pass consistently enabled during follow-up. This is associated with significantly lower rates of detected and treated arrhythmias. The enhanced SMART Pass version seems associated with lower deactivation rate, and with further decrease in treated and untreated detected arrhythmias.

Rapid high-latitude cooling in the southeastern Pacific sector driven by North Atlantic warming during 1979–2013 in CESM1

During the 1979–2013 satellite observation period, the sea surface temperature (SST) has cooled substantially in the high-latitude Southern Ocean, with the most pronounced cooling tendency centered in the southeastern Pacific domain. Previous hypotheses have commonly ascribed the recent Southern Ocean cooling to either the tropical eastern Pacific cooling or North Atlantic and tropical Indian Ocean SST warming. However, the mechanisms underpinning significant cooling in the southeastern Pacific sector remain debatable. By diagnosing three pacemaker experiments with a state-of-the-art global climate model in which SSTs in the North Atlantic, tropical central-eastern Pacific, and tropical Indian Ocean-western Pacific are individually nudged to mimic the observed trajectory, we show that the North Atlantic dominates in the cold SST response of the southeastern Pacific sector during 1979–2013. Anomalous North Atlantic warming initiates a quasi-stationary Rossby wave response to a south-to-north cross-equatorial Hadley circulation strengthening, leading to an enhanced Amundsen Sea Low. As a result, due primarily to the increased low-level marine cloud cover, the net surface shortwave radiation reduction triggers rapid SST cooling in the southeastern Pacific domain. The southeastern Pacific cold SST anomalies are further maintained via the shortwave radiation-low-cloud-SST positive feedback on decadal timescales. Our results suggest that the shortwave radiation-low-cloud SST feedback is fundamental to the observed long-term cooling of the high-latitude Southern Ocean, with profound climate consequences worldwide.

#2373 Malignant tumors of the urinary bladder and Balkan endemic nephropathy – a 45 year study

Abstract Background and Aims Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium. Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium. Method Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium. Results During the observed period, there were a total of 1447 cases of MTUB - 1109 (76.64%) male patients and 338 (33.36%) female patients. The average annual incidence rate (AAIR) of MTUB in endemic settlements for the observed period (1978-2024) is 15.64; in hypoendemic areas is 13.89, and in non-endemic areas is 14.62. The AAIR of MTUB in endemic settlements is 1.13 times higher than the rate in hypoendemic areas and 1.07 times higher compared to non-endemic settlements. It is noteworthy that in the first period of observation, the AAIR of MTUB in endemic areas is 2.24 times higher than the rate in hypoendemic areas and 4.09 times higher than the rate in non-endemic areas. However, in the second and third periods of the study, it is significantly lower compared to the rates in hypoendemic and non-endemic areas. The linear trend of MTUB for the observed period in endemic settlements is negative without statistical significance (y = −0.012x + 701; r2 = 0.048), while in non-endemic areas, it is positive and statistically significant (y = 1.340x + 0.172; r2 = 0.647). Conclusion The higher frequency of MTUB in the Jablanica district over the 45-year study of the region with BEN is limited to the first part of the research and may indicate a common nephropathogenic and carcinogenic etiological factor, confirming a positive correlation between BEN and malignant urothelial tumors. At the same time, in the last 25 years of the observed period, there has been a drastic decline in the frequency of both BEN and MTUB, as well as malignant tumors of the upper urothelium.

#492 Ten-year experience treating osteoporosis with bisphosphonate in hemodialysis patients

Abstract Background and Aims The treatment of osteoporosis in patients undergoing hemodialysis (HD) has not been established, as there is insufficient evidence regarding the treatment of osteoporosis. The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 guidelines suggest that determining the bone marrow density (BMD) of HD patients is useful. In 2011, we began treating HD patients' osteoporosis with alendronate. Herein, we describe the effects of the treatment based on our 10-year experience. Method This was a single-center prospective observational study of 85 HD patients (age 67.8 ± 11.0 yrs; 47 females, 38 males) treated for osteoporosis with alendronate at our hospital during the 10 years 2011–2021. The average observational period was 3.9 ± 2.9 years. The patients' BMD values including those at the lumbar spine, femoral neck, and total hip were determined by dual-energy X-ray absorptiometry. The patients whose first T-score was ≤ −2.5 were treated with alendronate. We evaluated the patients' yearly BMD measurements and their yearly values of bone metabolism markers, i.e., parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Results We compared the data before and after the start of alendronate treatment by dividing the patients into a responder group (the patients whose T-score had improved at 1 year after treatment started; n=44) and a non-responder group (the patients whose T-score had not improved; n=32). The mean observational period of the responder group was significantly longer than that of the non-responder group (p&amp;lt;0.01). In a multiple regression analysis, a longer observational period was significantly associated with the improvement of T-scores (p=0.02). Only the mean T-score of the lumbar spine gradually improved during the study period; those of the femoral neck and total hip did not. Conclusion A long-term use of alendronate for the treatment of osteoporosis may be effective in hemodialysis patients, especially for the lumbar spine. Decisions regarding the effect of alendronate treatment for osteoporosis patients undergoing HD should not be made within only a year after the treatment initiation; rather, a longer observation period is necessary.

#237 Carbapenemase producing Enterobacteriaceae rectal colonization in dialysis patients: a large monocentric retrospective analysis

Abstract Background and Aims Carbapenemase-producing Enterobacteriaceae (CPE) represent a growing global public health concern due to their increasing prevalence and resistance to carbapenems. Dialysis patients are particularly vulnerable to infections that represent the second cause of death in dialysis’ cohorts. Considering the immunosuppression, dialysis patients constitute a highly immunocompromised population and represent a unique setting similar to intensive care, hematology, or transplant recipients. Several studies have already been conducted in these populations, demonstrating the high infectious risk, increased mortality and morbidity burdened by CPE. Our study aims to analyze a large dialysis population and assess if there is an increased risk of mortality, sepsis, and/or hospitalizations within this cohort. Considering the frequency of evaluations for these patients, we have also decided to evaluate the treatments to which these patients are subjected, their antibiotic exposure, the number of hospitalizations and specific infections, while seeking predisposing or protective factors within this specific patient group. Method Our work is a retrospective, single-center cohort study that analyzes patients on HD and PD who were followed by the Nephrology and Dialysis Department of the Ravenna Hospital from 01/01/2015 to 31/12/2021 (674 patients). We analyzed demographic data (Date of birth, gender, blood type), comorbidities (Diabetes, hypertension), dialysis data (type of dialysis technique, dialytic age), blood tests (hemoglobin, white blood cells, platelets, albumin, ALT, lipase, C-reactive protein), serology and markers (HBV, HCV, HIV, EBV, CMV, Quantiferon, Helicobacter pylori colonization, SARS-COV2), therapies (antihypertensives, proton pump inhibitors, calcium-based phosphorus binders, non-calcium-based phosphorus binders, potassium binders, iron therapy, erythropoietin-stimulating agents), antibiotics (cephalosporins, penicillins, fluoroquinolones, macrolides, aminoglycosides, carbapenems, tetracyclines, vancomycin, linezolid, cefepime/avibactam), hospitalizations, colonization or lack thereof by CPE bacteria, infections (urinary tract infections and pneumonias) or sepsis and responsible microorganisms, survival. We exclude patients who had stomas or those who received chemotherapy or immunotherapy for a period longer than 3 months. Results Overall we considered for our analysis 528 patients and 51 presented CPE positive rectal swab during the period of observation. In our population CPE colonized patients present a higher risk to develop pneumonias (HR 2.048, p = 0.003). 178 patients presented 497 episodes of sepsis, 451 episodes in the non CPE colonized and 46 episodes in the CPE colonized (HR 2.057, p-value 0.001). Considering CPE-induced sepsis, a substantial difference was observed between the two groups. The colonized patient group had 7 (15.2%) cases of CPE sepsis, while the non-colonized group did not have any (0%). The result shows statistical significance, although the limited number of infections does not allow for definitive conclusions on this matter. Concerning the re-hospitalization rate we evidenced a significative difference between the two groups, displaying an involvement of CPE colonization (HR1.367, p-value = 0.038). Conclusion Our study highlighted that a colonization by CPE lead to a greater number of episodes of all bacterial sepsis, of CPE sepsis, of pneumonias and of re-hospitalizations. Colonization by CPE conferm an increased risk of CPE sepsis, and therefore, future research should focus on determining whether it is worthwhile to treat hyperpyrexia in colonized CPE dialysis patients as if it were CPE-related sepsis. This is a significant question that can guide our clinical practice.

#2499 Multicenter observational study on the impact of continuous monitoring of vascular access on the survival and quality of life of patients on dialysis

Abstract Background and Aims AVE is a multicenter observational study aimed at evaluating the improvements in dialysis efficiency, AVF longevity and mortality that can be achieved by implementing both monitoring by a multidisciplinary team. The universal goal of AV monitoring is to identify early events such as stenosis and intervene before thrombosis, thus maximizing the longevity of access and minimizing morbidity. Method This study takes advantage of the opportunity to use data from 19 hemodialysis centers and approximately 1000 patients and to correlate and examine variables that are commonly reported with each treatment, trends in AV use, trends in patient characteristics, and the practice associated with VA. The data were collected by nurses in a specific section of the management database at each treatment for 5 years. Results Trends at the beginning and at the end of the study were evaluated, and Kaplan Maier curves were performed regarding the survival of the VA and the survival of the patients. The average age of 1000 patients enrolled was 73.5 years. Native AVF was used by 79%, AVG by 2% and CVC by 19%. With increasing age, the use of CVC goes from 6% (15-39 years) to 50.5% in patients over 85 years old. The most frequent complications were: Thrombosis 16.5%, Infections 5.5%. VA-related hospitalization days are 28.7% of total days. The average dialysis goals achieved were: QB 290 ml/Min; purified blood 69.7 L; KT/V:1.35. The AVE study, the survival curves evaluated in aggregate were not different between men and women during the observation period (year 2018: p = 0.327; year 2019: p = 0.174; year 2020: p = 0.343). This finding was also confirmed when the survival data were analyzed according to gender and chronological age. No difference was observed between genders while the significant difference (p = 0.000) between chronological age levels was confirmed as shown in the Figure Conclusion By interpreting data collection for specific performance measures using accurate reports, healthcare professionals can highlight AV performance/inefficiencies and provide correct information to clinical staff to support them in their daily clinical practice and decision making.