Small Study Research Articles

Nasal and pharyngeal mucosal immunity to poliovirus in children following routine immunization with inactivated polio vaccine (IPV) in the United States of America.

Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.

Hemodynamic parameters and diabetes mellitus in community-dwelling middle-aged adults and elders: a community-based study

Hemodynamic parameters have been correlated with stroke, hypertension, and arterial stenosis. While only a few small studies have examined the link between hemodynamics and diabetes mellitus (DM). This case-control study enrolled 417 DM patients and 3475 non-DM controls from a community-based cohort. Peak systolic velocity (PSV), end-diastolic velocity (EDV), blood flow velocity (MFV), pulsatility index (PI), and the resistance index (RI) of the common carotid arteries were measured by color Doppler ultrasonography. Generalized linear regression analyses showed that as compared to the non-DM controls, the age-sex-adjusted means of PSV, EDV, and MFV were − 3.28 cm/sec, − 1.94 cm/sec, and − 2.38 cm/sec, respectively, lower and the age-sex-adjusted means of RI and PI were 0.013 and 0.0061, respectively, higher for the DM cases (all p-values < 0.0005). As compared to the lowest quartiles, the multivariable-adjusted ORs of DM for the highest quartiles of PSV, EDV, MFV, RI, and PI were 0.59 (95% confidence interval [CI] 0.41–0.83), 0.45 (95% CI 0.31–0.66), 0.53 (95% CI 0.37–0.77), 1.61 (95% CI 1.15–2.25), and 1.58 (95% CI 1.12–2.23), respectively. More importantly, the additions of EDV significantly improved the predictabilities of the regression models on DM. As compared to the model contained conventional CVD risk factors alone, the area under the receiver operating curve (AUROC) increased by 1.00% (95% CI 0.29–1.73%; p = 0.0059) and 0.80% (95% CI 0.15–1.46%; p = 0.017) for models that added EDV in continuous and quartile scales, respectively. Additionally, the additions of PSV and MFV also significantly improved the predictabilities of the regression models (all 0.01 < p-value < 0.05). This study reveals a significant correlation between DM and altered hemodynamic parameters. Understanding this relationship could help identify individuals at higher risk of DM and facilitate targeted preventive strategies to reduce cardiovascular complications in DM patients.

Lower dose radiotherapy did not alter cardiac function and was not pro-arrhythmic: results of the small prospective HALO trial

Abstract Background Stereotactic arrhythmia radiotherapy (STAR) is a highly promising bail-out treatment for patients with therapy-refractory ventricular tachycardia (VT). Despite precise, noninvasive targeting of the pro-arrhythmic area, surrounding healthy cardiac tissue inadvertently receives low-dose radiation. There is a historical notion that collateral cardiac damage from radiation of extra-cardiac structures can cause heart failure and arrhythmias. In the HALO trial, where non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) received relatively low-dose radiotherapy to the heart, detailed cardiac safety after radiotherapy was therefore evaluated. Objective The aim of this study was to prospectively evaluate cardiac function after collateral radiotherapy on the heart in patients with NSCLC treated with SABR. Methods The HALO trial was a prospective observational trial evaluating cardiac adverse effects in patients treated with SABR for early stage NSCLC. Patients with a tumour within 3cm of the pericardium were eligible to participate. The mean radiotherapy dose per segment was calculated by semi-automated angulation and segmentation using an in-house developed tool. The heart was segmented according to the AHA 17-segment model. Patients underwent cardiac magnetic resonance imaging (CMR) pre-treatment, 3 and 12 months after treatment. CMR strain-analysis was conducted by two independent observers using cvi42 software. Longitudinal, radial and circumferential strain were measured both globally and segmentally and evaluated for dose-dependent effects. Results Ten patients were included in this study. Two patients dropped out before first follow-up and were not included in this analysis. Median age was 66 years (range 58-81) and four were male (50%). Median distance between the tumour and pericardium was 0.46cm (range 0.00-2.80). Patients were treated with 8 fractions of 7.0-7.5 Gy (n=6), 5 fractions of 11.0 Gy (n=1) or 3 fractions of 18.0 Gy (n=1). Median global cardiac radiotherapy dose was 6.7 Gy (range 0.1-17.9). Pre-treatment, median left ventricular ejection fraction as measured on CMR was 65% (range 40-75), global longitudinal strain was -15% (-20 - -9), global circumferential strain was -17% (-26 - -9) and global radial strain was 28% (11-60). These did not significantly change comparing 3 months and 12 months after treatment with pre-treatment. As can be appreciated from Table 1, there were no dose-dependent effects on segmental longitudinal, radial and circumferential strain both 3 months or 12 months after SABR. There were no ventricular arrhythmias observed during follow-up. Conclusion In this small study, collateral radiotherapy in patients with NSCLC treated with SABR did not significantly alter cardiac function as measured on CMR, and no relevant pro-arrhythmic effects were observed during short term follow-up. Extending the research into a larger dataset is warranted.

Pulsed field ablation for atrial fibrillation: efficacy, safety and lesion durability in patients with recurrences

Abstract Background Initial findings from feasibility studies regarding pulsed field ablation (PFA) for atrial fibrillation (AF) indicated substantial efficacy and safety of the procedure, including high rates of lesion durability upon systematic remapping. However, data regarding PFA for AF in real-life settings remains scarce. Objective This pooled analysis was conducted to provide insights into PFA’s practical performance and safety profile in real-life settings, as well as information regarding lesion durability in patients with arrhythmia recurrences. Methods MEDLINE/EMBASE databases were searched up to August 31, 2023 for studies including patients undergoing catheter ablation for AF using PFA. Independent searches were performed by 2 investigators (K.B. and K.V.). Feasibility studies, first-in-human studies, small studies with population overlap, and those with a follow-up duration shorter than one year were excluded from the analysis. Authors were contacted for missing information or to confirm the absence of population overlap. Two investigators (K.B. and K.V.) independently extracted data from studies meeting inclusion criteria. Any discrepancies were resolved by a third experienced reviewer. Results We assessed for relevance a total of 952 references. Five studies met the inclusion criteria (comprising of 1 randomized trial, 2 single arm prospective trials, and 2 post-market registries), with a combined cohort of 2,359 patients who underwent PFA for AF. The pooled rate of acute PVI was 99.6% (95%CI 99.2-99.8, I2:7%). The pooled one-year rates of freedom from atrial arrhythmia for individuals with paroxysmal or persistent AF were 79.5% (95%CI 75.7-83.1, I2:70%) and 67.5% (95%CI 60.9-73.7, I2:60%), respectively. Among patients who underwent repeat catheter ablation for AF recurrences (n=197), the pooled rate of durable PVI per patient was 48.9% (95%CI 30.4-67.7, I2:71%), while durable PVI per vein was 74.1% (95%CI 65.1-82.2, I2: 75%). Incidence of overall complications and serious procedure-related complications were 1.8% (95% CI: 0.2-4.8, I2: 92%) and 0.9% (95% CI: 0.3-1.7, I2:59%), respectively. The most prevalent complication types were access site complications (48.6%), pericardial effusions/tamponades (24.8%) and stroke/transient ischemic attack (9.5%). No esophageal damage or PV stenosis were reported . There was one case of persistent phrenic nerve palsy and two cases of reversible coronary spasm (during ablation along the posterior mitral isthmus, and during PVI, both resolving with intracoronary nitroglycerin). Conclusion This pooled analysis confirms that catheter ablation of atrial fibrillation using pulsed field ablation is associated with high rates of atrial arrhythmia-free survival at one year while maintaining low rates of procedure-related complications. Durable pulmonary vein isolation is observed in approximately half of the patients undergoing a repeat procedure for atrial fibrillation recurrence.

Sinus nodal denervation by targeting the superior paraseptal ganglionated plexus: randomized comparison of right-atrial and bi-atrial cardioneuroablation guided by ablation index

Abstract Background Radiofrequency (RF) catheter ablation of superior paraseptal ganglionic plexus (SPSGP) that significantly suppresses the vagal modulation of the sinus node is used for the treatment of functional bradyarrhythmias. A reasonable effect can be achieved by targeting this plexus from the endocardial aspect of both the right and left atria. Purpose The study aimed to compare the acute efficacy of unifocal right-atrial (RA) and comparably extensive bi-atrial (BA) ablation of SPSGP for sinus nodal denervation as assessed by intraprocedural extracardiac vagus nerve stimulation (ECVS). Methods A population of 22 patients (age: 43±9 years, 55% males) undergoing cardioneuroablation (CAN) for functional bradyarrhythmias were randomized 1:1 to two ablation strategies that included: [1] single RF lesion at the very posterior site of the junction between right atrium and superior vena cava with ablation index (AI) = 800 (RA group) and [2] the same but twice smaller RF lesion (AI = 400) complemented with strictly contralateral left-atrial lesion (AI = 400) at the anterior vestibulum of right superior pulmonary vein (BA group). The effect of ablation was investigated by the post-ablation change in sinus rate and the attenuation of the response of the sinus node to ECVS (frequency: 50 Hz, pulse width: 0.05 ms, output: 1 V/kg [&amp;lt;70V], duration: 5 s) via the right internal jugular vein. Results Per-protocol ablation resulted in sinus acceleration by 9±15 bpm vs. 15±16 bpm (P=0.40) in RA vs. BA groups, respectively. Inducible sinus arrests were shortened by 4.7±4.2 s vs. 6.2±1.5 s (P=0.27) and reached the post-ablation level of 3.0±3.7 s vs. 1.0±0.3 s (P=0.08) in RA vs. BA groups, respectively. The results are also displayed in the Figure as medians, interquartile range (boxes) and total range (whiskers). Complete sinus nodal denervation was achieved in 8/11=73% vs. 11/11=100% patients (Fisher exact test P=0.21) in RA vs. BA groups, respectively. Practically 100% denervation efficacy in the BA group contrasted with 3 patients in the RA group in whom ablation had virtually no effect on ECVS-based indices (duration of post-ablation sinus arrests: 11.2, 8.7, and 5.2 s). Acute effects did not change substantially during the waiting period of 20±5 min. Conclusions In this small study with acute procedural endpoints, unifocal RA ablation of SPSGP appeared numerically less effective for sinus nodal denervation than comparably extensive BA ablation although the difference was formally non-significant. The ECVS-based outcome measure was valuable in detecting the differences between study groups. Change in sinus rate was not a reliable marker of sinus nodal denervation.

P.142 The use of intraoperative magnetic resonance imaging for endoscopic transnasal transsphenoid surgery in children

Background: Sellar and suprasellar pediatric lesions are uncommon. Endoscopic transnasal transphenoidal surgery (ETTS) is the preferred treatment, but early post-op MRI is hindered by sphenoidal packing. This study aims to assess iMRI safety and efficacy in pediatric ETTS cases. Methods: We performed a retrospective review from Jan 01, 2015 to Dec 31, 2022, evaluating use of iMRI. We determined if the goals of the surgery (biopsy, cyst decompression, subtotal resection, gross total resection) were met, and iMRI’s influence on surgery outcomes. We examined patient age, surgery duration, length of stay, histopathology results, surgical complications, post-op MRIs within 1 month, and tumor progression/recurrence. Results: Over eight years, 20 pediatric ETTS procedures, 14 with iMRI, were conducted. Achieving goals in 13 cases, iMRI prompted extra surgery once. Two adenomas progressed, requiring a second surgery, and craniopharyngioma cases had complications, needing further interventions. Hospital stays varied (1-9 days), with a mean surgery duration of 6 hours and 47 minutes. The study underscores iMRI’s potential impact, stressing the necessity for more research in pediatric transsphenoidal surgeries. Conclusions: While intraoperative MRI in pediatric transsphenoidal surgeries may aid goal verification, this small study doesn’t conclusively demonstrate improved outcomes. Complication rates align with non-IMRI procedures, highlighting the need for further research.

Clinical and long term safety outcomes of conduction system pacing compared to biventricular pacing : a large retrospective cohort study

Abstract Background Biventricular pacing (BVP) is the gold standard for cardiac resynchronization therapy (CRT). Recently, studies have shown promising results for conduction system pacing (CSP) as an alternative to BVP. However, the small study samples and paucity of data concerning long term safety of these devices prevent CSP from being used as first line therapy. Purpose This study examines clinical outcomes and long term safety of CSP compared to BVP. Methods We conducted a retrospective cohort study from patients receiving CSP or BVP. All patients implanted with either CSP (N = 282) or BVP (N = 216) from 2018 to 2023 were included. Patients had to complete at least 3 months of follow-up and CSP patients had to pace at least 20% of time at first visit. The outcomes were defined as at least one heart failure hospitalization and the complication rates for both arms. Results Median [IQR] follow-up time was 1.64 years [0.73 – 2.80]. Heart failure admissions were numerically lower for CSP group but when adjusted to confounders the adjusted odds ratio was 0.75 in the CSP group compared to BVP ([95% CI, 0.43-1.31]; P = 0.32). Long term complication rates (infection, lead dysfunction, diaphragmatic stimulation requiring system revision, etc.) were lower in the CSP group (4 [1.4%] vs 10 [4.7%]; odds ratio, 0.21 [95% CI, 0.06-0.69]; P = 0.01). Short term complication rates (lead displacement, infection, pneumothorax, etc.) were however similar for both arms (16 [5.7%] vs 11 [5.1%]; odds ratio, 1.53 [95% CI, 0.64-3.65]; P = 0.33). In two patients, septal lead extraction after over a year was possible without any sequelae. The change in the QRS duration went from 150 ms to 149 ms for group (p=NS) and from 153ms to 144ms for comparable CSP group (P = 0,01). Left ventricular ejection fraction (LVEF) increased from 28% to 40% in the BVP group and from 32% to 40% in the CSP group with pre intervention LVEF less than 50% (P &amp;lt; 0.0001 for both groups). Procedure duration was significantly shorter for CSP (82.3 minutes [32] vs 93.1[39.1]; P = .0002). Conclusion CSP approach achieves similar clinical results as BVP, with significantly less complications, shorter implant times, shorter QRS durations and comparable LVEF improvement. All these favorable results are obtained using less leads and simpler devices.

Generalization of a Deep Learning Model for Continuous Glucose Monitoring-Based Hypoglycemia Prediction: Algorithm Development and Validation Study.

Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.

#2990 Prevalence and risk factors of altered control of BP during the night in a large hemodialysis population investigated by 48 hours ABPM

Abstract Background and Aims Altered BP control during the night (non-dipping, reverse dipping and nocturnal hypertension) is recognized as a powerful risk factor for death and CV events in the hemodialysis (HD) population. However, these alterations have been described in relatively small studies and the epidemiology and risk factors for subtypes non-dipping and nocturnal hypertension are still poorly characterized in the current literature. We investigated the problem in a large Registry (The EURECAm Registry) that is the sole that adopted state of the art 48 h ABPM recording in the HD population. Method We included in this analysis 534 HD patients, enrolled in 7 centers, led by members of the EURECA-m working group, in 3 European countries. 48 h ABPM was measured by using well validated instruments (AAMI/ESH/ISO). As recommended by the European Society of Hypertension guidelines, recordings were made at 15-minute intervals during the day and 30 minutes during the night. Hypertension was defined as 48 h blood pressure (BP) &amp;gt;130/80, nocturnal hypertension as a nighttime BP &amp;gt;120/70 mmHg, non-dipping as a night/day systolic BP fall &amp;lt;10% and reverse dipping as a night/day ratio &amp;gt;1. Results Among 534 HD patients, 317 were hypertensive and. 217 normotensive. As many as 274 patients were non-dippers (51%), 32% were reverse dippers, and 381 (71%) had nocturnal hypertension. Of note, forty-one per cent of non-dippers, 37% of reverse dippers and 19% of patients with nocturnal hypertension were normotensives. As expected, the majority of reverse dippers (87%) had frank nocturnal hypertension. In a combined analysis of non-dippers and reverse dippers, as compared to dippers, these patients more frequently exhibited atrial fibrillation and had lower Heart Rate both pre-dialysis (72± 11 vs 77±13 bpm, P = 0.004) and post-dialysis (74± 13 vs 78±14 bpm, P = 0.03) and lower serum albumin (3.9±0.4 vs 4.0±0.3 g/dL, P = 0.02) but did not differ for age and gender. Conclusion In a large cohort of HD patients investigated by the state-of-the-art technique, 48 h ABPM alterations in the nocturnal BP profile were almost universal, and nocturnal hypertension was the more prevalent alteration, followed by non-dipping and reverse dipping. These alterations were independent of age and gender. Long-term, granular follow-up analyses are warranted to identify the prognostic value of these alterations.

#1636 Treatment of Tolvaptan related polyuria with bendroflumethiazide for ADPKD: Does it really work?

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease worldwide and accounts for 10% of patients on renal replacement therapy. Currently, the arginine vasopressin (AVP) V2 receptor antagonist Tolvaptan is the only available treatment for ADPKD which slows cyst formation and thus the progression of kidney disease by inducing AVP resistance. However, its aquaretic side effects can be debilitating and is the most common reason for medication discontinuation. Thiazides such as bendroflumethiazide are natriuresis-promoting diuretics through their action on the sodium-chloride channel in the distal convoluted tubule that are widely used to treat polyuria in inherited AVP deficiency or resistance. However, there is limited information about their effect in patients treated with Tolvaptan. The aim of this observational study is to review the impact on patients’ quality of life by using a low dose bendroflumethiazide with Tolvaptan in patients with ADPKD who are suffering from Tolvaptan induced aquaretic side effects. Method Details of all patients with ADPKD who are on Tolvaptan with or without bendroflumethiazide who are currently attending the polycystic kidney disease (PKD) clinic at Royal Free London NHS Foundation Trust were obtained, and their medications reviewed. Patients who have previously been or were currently on bendroflumethiazide to enable them to continue Tolvaptan therapy were identified. Information about the impact of bendroflumethiazide on their quality of life and their aquaretic side effects were obtained via phone call. If they discontinued bendroflumethiazide, the reason for this was explored. In addition, eGFR, sodium, potassium, and calcium at the time of bendroflumethiazide initiation as well as at three, six, nine and twelve months post bendroflumethiazide initiation were obtained. Results Out of 136 patients receiving Tolvaptan for treatment of ADPKD at our centre, eight (5.8%) were prescribed bendroflumethiazide for treatment of their aquaretic side effects from Tolvaptan. Two of these eight patients (25%) stopped bendroflumethiazide due to adverse reactions. The remaining six patients (75%) remained on the medication, and all reported significant subjective improvement in their symptoms of polyuria, nocturia and in their overall quality of life. Two of the six patients (33.3%) that remained on bendroflumethiazide had also subsequently increased their Tolvaptan dose. No electrolyte disturbances were noted after initiation of bendroflumethiazide. Conclusion Using bendroflumethiazide appears to improve the quality of life through reduction of polyuria and nocturia in patients suffering from Tolvaptan-induced aquaretic side effects with some patients subsequently able to increase their Tolvaptan dose by taking bendroflumethiazide which might result in augmented therapeutic benefit of Tolvaptan. Further placebo-controlled randomised studies with longitudinal will be needed to determine the true benefit-disbenefit balance of thiazide therapy in patients taking tolvaptan, especially to determine whether there is a negative effect on efficacy of tolvaptan on the underlying ADPKD. However, based on our small observational study, the number of patients needed to determine whether bendroflumethiazide improves the tolerability and medication adherence in patients who are debilitated by the aquaretic side effects of Tolvaptan would be small.

#2028 Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: a systematic review and meta-analysis

Abstract Background and Aims Hyperphosphatemia is a common and clinically significant complication in severe chronic kidney disease (CKD), associated with higher cardiovascular adverse events and higher mortality rates. High serum phosphate is also associated with a heightened risk of cardiovascular issues such as hypertension, left ventricular hypertrophy, atherosclerosis, and vascular calcifications. Phosphate binders are commonly used in patients receiving renal replacement therapy (RRT), aiming to reduce and maintain serum phosphorus. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving RRT. Method Data sources included MEDLINE(PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with the search cut-off in October 2023. We examined RCTs that comparing sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving RRT. Data extraction followed the PICOS protocol and bias risk was assessed using the Rob-2 tool. We performed a meta-analysis combining the data from RCTs, using R-studio. The primary endpoint of this study is the change in the serum phosphorus levels from baseline to end of treatment. Secondary outcomes included changes in serum intact parathormone (i-PTH) levels from baseline to end of treatment as well as the adverse events ratio during the study period. Given the prevalence of gastrointestinal side effects for both drugs, which often leads to drug discontinuation or patient non-adherence, a separate analysis focused on gastrointestinal-related adverse events. Results Inclusion criteria were met by 5 RCTs. No statistically significant difference was found in serum phosphorus reduction between the two groups {MD: −0.07 mmol/l,95% CI-random effects: −0.15 to 0.02}. Similarly, serum i-PTH reduction showed no statistically significant difference between the two drugs {MD = −1.53 mg/dl, 95% CI = (−4.45, 1.4), p = 0.26, random effects model}. Adverse events were comparable between the groups (OR: 1.11, 95% CI: 0.65-1.88, random effects model). However, further analysis of gastrointestinal adverse evets indicated a 60% increase with sevelamer carbonate {OR: 1.60, 95% CI 1.31-1.97, common(fixed) effect model}. Funnel plot examination for both continuous and dichotomous outcomes revealed a high chance for small study effect and publication bias. Conclusion This meta-analysis found that sucroferric oxyhydroxide and sevelamer carbonate are equally effective in controlling serum phosphorus and i-PTH levels. Sucroferric oxyhydroxide, however, demonstrated a more favorable profile regarding gastrointestinal adverse events. Our findings suggest sucroferric oxyhydroxide as a valuable alternative for RRT patients who have difficulty tolerating sevelamer carbonate.

The relationship between dietary total flavonoids and thyroid function in U.S.adults, NHANES 2007-2010.

Although small studies have shown that flavonoids can affect thyroid disease, few epidemiological studies have explored the relationship between dietary total flavonoids (TFs) intake and serum thyroid function. The aim of this research was to evaluate the relationship between TFs and serum thyroid function. Our study included 4,949 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariable linear regression, subgroup analyses, and interaction terms were used to explore the relationships between TFs and thyroid function. And we also used restricted cubic splines (RCS) to investigate possible nonlinear relationships. After adjusting for covariates, we found that log10-transformated dietary total flavonoids intake (LgTFs) was negatively associated with total thyroxine (TT4) (β = -0.153, 95% CI = -0.222 to -0.084, P<0.001). Subgroup analyses revealed a stronger and statistically supported association in subjects with high annual family income (β = -0.367, P<0.001, P for interaction = 0.026) and subjects with high poverty to income ratio (PIR) (β = -0.622, P<0.001, P for interaction = 0.042). And we found a U-shaped curve association between LgTFs and free triiodothyronine (FT3) (inflection point for LgTFs: 2.063). The results of our study demonstrated that a higher intake of total flavonoids in the diet was negatively associated with a lower TT4. Furthermore, the associations were more pronounced in high annual family income and high PIR adults. And we found a U-shaped relationship between LgTFs and FT3. These findings provided guidance for future thyroid dysfunction diet guidelines.

Experiment and simulation study on the functional fatigue of shape memory alloy beam actuators

The functional fatigue behavior of shape memory alloy (SMA) beam actuators is gaining importance as their utilization in engineering applications becomes more widespread. However, research on the functional fatigue behavior of SMA beam actuators under bending conditions is not as extensive as that on SMA wires. In this paper, an experimental study and theoretical analysis of the functional fatigue behavior of SMA beam actuators were conducted. A measuring method for bending deflection and an automatic thermal cyclic test bench was designed. A series of functional fatigue tests were conducted on SMA beam actuators under different bias load conditions and the functional fatigue patterns were obtained. The material damage factor is defined and calculated through specimen tests. By incorporating the damage factor to modify the existing constitutive model, a model considering functional fatigue and tension-compression asymmetry is obtained. Finite element analysis (FEA) is performed based on this modified model to simulate the actuating performance of SMA beam actuators and to compute the deflection at different numbers of cycles. Additionally, a small parameter study on the actuator shape is conducted using FEA. By comparing the FEA results with functional fatigue experimental data, the effectiveness of the modified model is validated, demonstrating its capability to describe functional fatigue and predict actuator lifespan.

Usefulness of Fluorescence imaging with indocyanine green for evaluation of bowel perfusion in the urgency setting: a systematic review and meta-analysis.

Fluorescence imaging with indocyanine (ICG) has been extensively utilized to assess bowel perfusion in oncologic surgery. In the emergency setting there are many situations in which bowel perfusion assessment is required. Large prospective studies or RCTs evaluating feasibility, safety and utility of ICG in the emergency setting are lacking. The primary aim is to assess the usefulness of ICG for evaluation of bowel perfusion in the emergency setting. The manuscript was drafted following the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). A systematic literature search was carried out through Pubmed, Scopus, and the ISI Web of Science. Assessment of included study using the methodological index for non-randomized studies (MINORS) was calculated. The meta-analysis was carried out in line with recommendations from the Cochrane Collaboration and Meta-analysis of Observational Studies in Epidemiology guidelines, and the Mantel-Haenszel random effects model was used to calculate effect sizes. 10,093 papers were identified. 84 were reviewed in full-text, and 78 were excluded: 64 were case reports; 10 were reviews without original data; 2 were letters to the editor; and 2 contained unextractable data. Finally, six studies22-27 were available for quality assessment and quantitative synthesis. The probability of reoperation using ICG fluorescence angiography resulted similar to the traditional assessment of bowel perfusion with a RD was -0.04 (95% CI:-0.147 to 0.060). The results were statistically significant P=0.029, although the heterogeneity was not negligible with a 59.9% of the I2 index. No small study effect or publication bias were found. This first metanalysis on the use of IGC fluorescence for ischemic bowel disease showed that this methodology is a safe and feasible tool in the assessment of bowel perfusion in the emergency setting. This topic should be further investigated in high quality studies.

Outcome of Transjugular Intrahepatic Portosystemic Shunt in Patients with Cirrhosis and Refractory Hepatic Hydrothorax: A Systematic Review and Meta-analysis

Abstract Background Around 5% of patients with cirrhosis of the liver develop hepatic hydrothorax (HH). For patients with refractory HH (RHH), transjugular intrahepatic portosystemic shunt (TIPS) has been investigated in small studies. Hence, the present meta-analysis aimed to summarize the current data on the outcome of TIPS in patients with RHH. Methods From inception through June 2023, MEDLINE, Embase, and Scopus were searched for studies analyzing the outcome of TIPS in RHH. Clinical response, adverse events (AEs), mortality, and shunt dysfunction were the primary outcomes assessed. The event rates with their 95% confidence interval were calculated using a random-effects model. Results A total of 12 studies (n = 466) were included in the final analysis. The pooled complete and partial response rates were 47.2% (35.8–58.5%) and 25.5% (16.7–34.3%), respectively. The pooled incidences of serious AEs and post-TIPS liver failure after TIPS in RHH were 5.6% (2.1–9.0%) and 7.6% (3.1–12.1%), respectively. The pooled incidences of overall hepatic encephalopathy (HE) and severe HE nonresponsive to standard treatment after TIPS in RHH were 33.2% (20.0–46.4%) and 3.6% (0.4–6.8%), respectively. The pooled 1-month and 1-year mortality rates were 14.0% (8.3–19.6%) and 42.0% (33.5–50.4%), respectively. The pooled incidence of shunt dysfunction after TIPS in RHH was 24.2% (16.3–32.2%). Conclusion RHH has a modest response to TIPS in patients with cirrhosis, with only half having a complete response. Further studies are required to ascertain whether early TIPS can improve the outcome of patients with cirrhosis and HH.

Digital literacy scale: Validity and reliability study with the rasch model

AbstractThe study aimed to develop a Likert-type measurement tool (Digital Literacy Scale, DLS) to determine the digital literacy levels of secondary school students. The validity and reliability of the developed measurement tool were verified using the Rasch model. The Rasch Model can estimate missing data and allow for small study groups (Rasch, Rasch, Probabilistic models for some intelligence and attainment tests, Danish Institute for Educational Research, 1960). Additionally, this model can verify the expected pattern of the measurement tool by calibrating it across participants and items. The content validity of DLS was ensured by expert opinion, and the construct validity was ensured by using the Rach model. In the content validity study, a 25-item pool was created for the draft DLS, and 5 items were removed from the draft DLS at this stage. Construct validity studies were carried out with the remaining 20 items using the classical test theory and item response theory (Rasch model). Exploratory Factor Analysis (EFA) and first-level Confirmatory Factor Analysis (CFA) were used within the scope of classical test theory. Then some Rasch assumptions such as dimensionlessness, local independence, monotonicity, and bias were tested for DLS. In the validity and reliability analysis of DLS, no items were eliminated, and the quantitative theoretical results were statistically confirmed. The analysis results showed that the minimum statistical values required for a good measurement tool were met. Accordingly, 20 valid and reliable compatible items that can be used to determine the digital literacy status of secondary school students were produced.

Risk of stroke in women using levonorgestrel-releasing intra-uterine device (IUD) for contraception.

Background: The commonly used combined hormonal contraceptives with progestins and ethinylestradiol are associated with an increased risk of ischemic stroke (IS). Progestin-only preparations, including levonorgestrel-releasing intra-uterine devices (LG-IUD), are not associated with an increased risk, and in smaller studies, the risk is even reduced. The risk of intracerebral hemorrhage (ICH) has never been investigated. We studied the risk of IS and ICH in women using LG-IUDs compared to women not using hormonal contraceptives. Methods: In this Danish historical cohort study (2004-2021) we followed non-pregnant women (18-49 years) registering incident IS and ICH in relation to use of LG-IUD/non-use of hormonal contraceptives utilizing Danish high-quality registries with nation-wide coverage. Poisson regression models adjusting for age, ethnicity, education, calendar-year, and medication use for risk factors were applied. Results: A total of 1,681,611 non-pregnant women contributed 11,971,745 person-years (py) of observation. Mean age at inclusion was 30.0 years; mean length of follow-up was 7.1 years; 2916 women (24.4 per 100,000 py) had IS; 367 (3.1 per 100,000 py) had ICH. Of these 364,784 were users of LG-IUD contributing 1,720,311 py to the investigation; mean age at start of usage was 34.6 years. Non-users of hormonal contraceptives contributed 10,251,434 py; mean age at inclusion was 30.0 years. Incidence rate of IS/ICH among LG-IUD users was 19.2/3.0 and among non-users it was 25.2/3.1 per 100,000 py. After adjustment incidence rate ratio for IS was 0.78 (CI: 0.70; 0.88), and for ICH it was 0.94 (CI: 0.69; 1.28). Conclusions:Use of LG-IUD was associated with a 22% lower incidence rate of IS without raising incidence rate of ICH. The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent IS.

Rationale for the Potential Use of Recombinant Activated Factor VII in Severe Post-Partum Hemorrhage.

Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH.

Is There an Alternative Oral Anticoagulation to Vitamin-K-Antagonists for Patients with Mechanical Aortic Valve Replacement? - A Literature Review.

Current guidelines exclusively recommend vitamin-K-antagonists (VKA) as anticoagulation for patients after mechanical aortic valve replacement due to the increased postoperative risk of valve thrombosis and thrombo-embolism. Strict and regular assessments are mandatory during VKA therapy to ensure a potent anticoagulatory effect within the desired range. From the patients' perspective, VKA are associated with relevant interactions and side effects reducing the quality of life and contributing to a high number of patients not achieving the optimal therapeutic target. Direct oral anticoagulants (DOAC) have replaced VKA therapy in the past for several indications, e.g., atrial fibrillation. However, it is still unclear if DOACs could replace VKA therapy in patients after mechanical aortic valve replacement. While the PROACT-Xa study did not show a sufficient anticoagulatory effect of apixaban plus aspirin compared to VKA therapy in patients after mechanical aortic valve replacement, the direct thrombin inhibitor dabigatran and the oral factor Xa inhibitors apixaban and rivaroxaban showed promising results in comparable patient cohorts in smaller studies and case reports. Factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients after mechanical aortic valve replacement. Therefore, factor Xa inhibitors or factor XI inhibitors could provide a potent alternative to VKA for patients after a mechanical aortic valve replacement.

The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature

ImportanceResearch is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis (MS).ObservationsGenerally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer’s disease, followed by Parkinson’s disease, and then little in MS. The data for MS is encouraging despite this.Conclusions and relevanceWhile the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.