Recent publications
- Alexandros Kalkanis
- Dimitrios Papadopoulos
- Sophia E Schiza
- [...]
- Pawel Sliwinski
Study objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA).
Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP. The non-respiratory arousal ratio (NRAR) was defined as the ratio of non-respiratory to total arousals at baseline PSG. A linear mixed model tested the effect of NRAR tertiles on residual sleepiness. Baseline variables that differed significantly between groups were included as covariates.
Results: 800 patients with OSA (69.6 % male, mean age 57.1 ± 12.0 years, mean NRAR 0.22 ± 0.20) were evaluated during three follow up visits at a mean of 197.4, 499.3, and 731.6 days after PAP initiation. The interaction between time and NRAR tertile was statistically significant (F = 4.55, p = 0.001). The lowest NRAR tertile was associated with lower residual sleepiness over time compared to the highest NRAR tertile. The associations were independent of sex, comorbidities, body mass index, blood pressure, baseline apnea-hypopnea index, and baseline ESS score.
Conclusions: NRAR at baseline PSG predicts residual sleepiness in PAP-treated OSA patients. The findings offer new insights into OSA phenotyping and have important implications for patient care.
Aims
Exercise stress test (EST) represents the gold standard for diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). We aimed to determine the relevance of exercise induced VT for the occurrence of LAE at follow-up.
Methods and results
In RYR2-related CPVT patients who underwent a baseline EST, we assessed the incidence and severity of ventricular arrhythmias (VA). Data were analysed using logistic regression models and Cox proportional hazards models. The primary outcome was the occurrence of life-threatening arrhythmic event (LAE; composite of sudden cardiac death, aborted cardiac arrest, or hemodynamically non-tolerated VT) at follow-up. In 102 RYR2-related CPVT patients (65 females; median age 16 years, IQR: 11–36 years), exercise-induced VT (bidirectional in 64% of cases) was elicited in 56% patients. VT could not be induced in pre-school children. Lower basal heart rate, early onset VA (within the first step of EST) and heart rate at the first minute of recovery were associated with exercise-induced VT. Cox analyses showed that early onset VA (HR 6.0, 95% CI: 1.3–27.9, P = 0.022) and exercise-induced VT (HR 6.6, 95% CI: 1.5–29.1, P = 0.012) at baseline EST were significantly associated with the occurrence of LAE at follow-up, and remained associated even after correction for symptoms.
Conclusion
Early onset VA and exercise-induced VT at baseline EST was associated with LAE at follow-up, allowing to identify a sub-set of patients at higher risk already at diagnosis.
Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a global public health challenge, complicating treatment strategies and requiring advanced therapeutic approaches. The persistence of MDR-TB has led to a demand for regimens that are more effective in improving treatment outcomes and controlling transmission. This systematic review and meta-analysis sought to examine the efficacy of linezolid (LZD) and bedaquiline (BDQ) in MDR-TB treatment regimens, evaluating their roles in enhancing therapeutic success and informing optimized management of MDR-TB. Methods: A comprehensive search was conducted across MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials assessing the efficacy of LZD and BDQ in MDR-TB patients up to September 14, 2024. We analyzed treatment outcomes, reporting favorable outcomes (cured and treatment completed) and unfavorable outcomes (death, treatment failure, and loss to follow-up) with a 95% confidence interval. Results: Our analysis included 11 trials, with a total of 1,999 participants. The findings indicate that BDQ+LZD-containing regimens yield significantly higher favorable treatment outcomes (84.5%; 95% CI, 79.8%-88.2%) and lower unfavorable outcomes (15.4%; 95% CI, 11.6%-20.2%). In contrast, regimens lacking either LZD or BDQ show lower efficacy, with favorable outcomes at 66.8% (95% CI, 59.5%-73.4%) and unfavorable outcomes at 33.0% (95% CI, 25.6%-41.4%). Conclusions: MDR-TB treatment regimens including BDQ and LZD lead to significantly better patient outcomes. The combined bactericidal and protein synthesis-inhibiting effects of BDQ and LZD create a powerful therapeutic synergy. Adding pretomanid further enhances this effectiveness, highlighting its value in complex cases. Future research should focus on optimizing these regimens for safety and efficacy and explore adjunctive therapies to improve MDR-TB outcomes even further.
Introduction
As the COVID‐19 pandemic transitions, understanding the intricate dynamics of the disease becomes paramount. This systematic review explores the role of antiphospholipid antibodies in COVID‐19, focusing on their potential clinical implications.
Methods
This systematic review, following PRISMA guidelines, assesses studies exploring the link between antiphospholipid antibodies and COVID‐19. PubMed/Medline, Embase, and Scopus were searched for relevant studies published up to December 22, 2024. Inclusion criteria comprised studies involving patients diagnosed with COVID‐19 and reporting on the presence of antiphospholipid antibodies. The risk of bias in individual studies was evaluated using the Joanna Briggs Institute appraisal tool.
Results
Our Study includes 59 records involving a total of 28,489 COVID‐19 patients. Antiphospholipid antibodies were tested in 14,498 COVID‐19 patients. It was observed that 50.84% of patients tested positive for antiphospholipid antibodies. Various types of antiphospholipid antibodies, including Anticardiolipin, Anti beta2 glycoproteins, and Lupus anticoagulant antibody, displayed prevalence rates in the patients with thrombosis. The overall frequency of antiphospholipid antibodies in thrombosis patients was 38.55%.
Conclusion
The presence of antiphospholipid antibodies in a significant proportion of COVID‐19 patients underscores the need for a detailed investigation into their role in thrombotic events. Our study highlights potential avenues for targeted interventions. However, the evolving nature of COVID‐19 necessitates continued research efforts to clarify clinical implications and optimize management strategies in this complex landscape of thrombosis and immunology. The review reveals some limitations, such as variability in study designs and demographics and inherent differences in methodologies among included studies. Future studies should address these limitations with standardized methodologies for more conclusive findings.
Purpose
Planar cardiac scintigraphy with [ ¹²³ I]I-mIBG is widely used to image myocardial sympathetic activity. In multicentre studies, different γ-cameras can cause variability in quantitative parameters. This study aimed to harmonise multicentre [ ¹²³ I]I-mIBG data using a custom-designed phantom and to assess its feasibility and acceptability.
Methods
A ‘tube and bottle’ phantom was designed to standardise the heart-to-mediastinum (H/M) ratio across 15 centres. Each centre prepared three versions of the phantom (A, B, and C) with varying pertechnetate ([ 99m Tc]Tc-O4-) activities, acquired static images using their own γ-camera, and uploaded DICOM data to a shared platform. In the phantom, the tube and bottle represent the heart and mediastinum, respectively, with the tube-to-bottle (T/B) ratio simulating the H/M ratio. The reference centre analysed the images and calculated the T/B ratios, applying linear regression for data harmonisation. A survey was conducted to assess the phantom’s usability.
Results
The harmonised T/B ratios for versions A and B were 20.46 ± 0.78 and 6.19 ± 0.39, respectively. The average slope and intercept of the regression line across the participating centres resulted in 1.07 ± 0.38 and − 0.82 ± 4.95. Survey feedback indicated high feasibility and acceptability, with all centres recommending the phantom for multicentre harmonisation.
Conclusions
The custom-made phantom effectively harmonised experimental data across different centres, supporting its use in multicentre studies to improve data consistency.
Background
Coronavirus disease 19 (COVID-19) patients might develop sequelae after apparent resolution of the infection. Autonomic dysfunction and baroreflex failure have been frequently reported. However, the long-term effect of COVID-19 on cardiorespiratory and cardiovascular neural controls has not been investigated with directional approaches able to open the closed-loop relationship between physiological variables.
Methods
A model-based causal spectral approach, namely causal squared coherence (CK²), was applied to the beat-to-beat variability series of heart period (HP) and systolic arterial pressure (SAP), and to the respiratory signal (RESP) acquired at rest in supine position and during active standing (STAND) in COVID-19 survivors 9 months after their hospital discharge. Patients were categorized according to their need of ventilatory support during hospitalization as individuals that had no need of continuous positive airway pressure (noCPAP, n = 27), need of continuous positive airway pressure in sub-intensive care unit (CPAP, n = 14) and need of invasive mechanical ventilation in intensive care unit (IMV, n = 8).
Results
The expected decrease of the strength of the HP-RESP dynamic interactions as well as the expected increase of the dependence of HP on SAP along baroreflex during STAND was not observed and this result held regardless of the severity of the disease, namely in noCPAP, CPAP and IMV cohorts. Regardless of the experimental condition, spectral causality markers did not vary across groups either.
Conclusions
CK² markers, in association with an orthostatic challenge, were able to characterize the impairment of cardiorespiratory control and baroreflex in COVID-19 patients long after acute infection resolution and could be exploited to monitor the evolution of the COVID-19 patients after hospital discharge.
Background
Thyroid nodules classified cytologically as low-risk indeterminate lesions (TIR3A) on fine-needle aspiration biopsy (FNAB) present a clinical challenge due to their uncertain malignancy risk. This single-center study aimed to evaluate the natural history of TIR3A nodules.
Materials and methods
FNABs performed between July 2017 and December 2019 were retrospectively retrieved and patients with TIR3A nodules were evaluated at baseline and throughout a follow-up based on ultrasound (US) parameters and clinical data.
Results
The final study group encompassed 371 patients with an initial TIR3A cytological result. Among them 102 were addressed to surgery after the first endocrinological evaluation, and 269 were addressed to conservative follow-up. Repeat FNAB was performed in 120 out of 269 and 13 further patients underwent surgery following FNAB repetition. The malignancy rate among TIR3A nodules was 16.5%, with most interventions being performed for reasons unrelated to the TIR3A result. Repeat FNAB provided a more definitive diagnosis in 40% of cases, with a 5% increase in malignancy risk. The remaining patients were monitored with clinical and US follow-up. Among all patients with TIR3A cytology managed conservatively (149 without FNAB repetition and 66 with at least one FNAB repetition), no significant changes in nodule size and/or US pattern were observed during a median follow-up of 3.3 years.
Conclusions
These findings suggest that active surveillance is a safe option for managing TIR3A nodules, particularly when no additional risk factors are present. The study highlights the role of repeat FNAB in reducing unnecessary surgeries and underscores the generally indolent nature of TIR3A nodules.
INTRODUCTION
Long-term prognosis of non-celiac enteropathies (NCEs) is poorly understood. We aimed to evaluate long-term outcomes and develop a prognostic score for NCEs.
METHODS
NCEs patients from an international multicenter cohort (4 Italian centers,1 UK, 1 French,1 Norwegian,1 USA,1 Indian) followed-up over 30 years were enrolled. Complications and mortality were analysed with Kaplan-Meier curves, standardized mortality ratios (SMR) and multivariate Cox regression. A clinical score to identify patients at risk of poor outcomes was developed.
RESULTS
261 patients were enrolled (144F, mean age at diagnosis 49±18 years, median follow-up 70 months, IQR 24-109). The most common etiologies were idiopathic villous atrophy (39%), drug-related (17%), common variable immune-deficiency (15%), infectious (10%) and autoimmune enteropathy (9%). 5-year and 10-year complication-free survival were 89% and 77%, respectively, while 5-year and 10-year overall survival were 88% and 74%, respectively. Causes of death included sepsis/major infections (22%), lymphoproliferative disorders (22%), solid-organ malignancies (12%), cardiovascular/metabolic disease (10%), and was unknown in 33%. Mortality was increased in NCEs compared with the general population (SMR 3.17, 95%CI 2.24-4.34). Older age at diagnosis (p<0.001), anemia (HR 2.53,95%CI 1.33-4.80,p<0.01), lack of clinical (HR 3.21,95%CI 1.68-6.18,p<0.01) and histological response (HR 2.14,95%CI 1.08-4.23,p=0.04) were independent predictors of mortality at Cox regression. A 5-point score was developed to identify high-risk patients: very low risk (0pts), low risk (1-2pts), intermediate risk (3pts) and high risk (4-5pts), with 10-year survival rates of 100%, 87%, 62% and 16%, respectively.
CONCLUSIONS
Mortality in NCEs is increased due to complications and lack of response to current therapies. We developed a clinical score to personalise follow-up. Targeted treatments are needed to improve outcomes.
Background
Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study.
Methods
Data from 18,694 subjects were analyzed from Uric acid Right foR heArt Healt (URRAH) database. The study evaluated the association between TG/HDL-C ratio and SUA/GFR ratio, as well as their impact on the development of outcomes during the follow-up study period. The primary endpoint was CV mortality.
Results
After a mean follow-up of 124 ± 64 months, 2,665 (14.2%) CV deaths occurred. The incidence of fatal and non-fatal CV events increased in parallel with the increase of TG/HDL-C quintiles. TG/HDL-C ratio showed a positive association with increasing of SUA/GFR ratio, even in non-diabetic patients. Multivariate analysis showed that the TG/HDL-C ratio increases the mortality risk even after adjustment for potential confounding factors. Finally, IR and GFR-adjusted hyperuricemia showed an additive effect on CV mortality.
Conclusions
Both IR and SUA/GFR ratio independently predict CV mortality, regardless of age, gender, BMI, diabetes, hypertension and statin use. The joint effect of the TG/HDL-C ratio and the elevated SUA/GFR ratio was greater than the presence of each single risk factor on CV mortality. This highlights the importance of monitoring these markers to better assess cardiovascular risk.
Objective: The prevalence of Thyroid-Cancer (TC) has increased worldwide and an association with metabolic and cardio-vascular disorders has been reported. Moreover, an increasing percentage of patients are currently diagnosed incidentally through non-thyroid related imaging for other clinical conditions. Our aim was to assess the prevalence of Thyroid-Related (TD) versus Incidental (ID) pre-surgery reasons leading to TC diagnosis and to compare the two groups in terms of clinical characteristics, size and severity of TC at presentation and rate of non-thyroid cancers and cardiovascular/metabolic comorbidities.
Design: we performed a retrospective cohort study in three high-volume hospital-based centers for thyroid diseases (Pavia, Latina and Messina) in Italy.
Patients: Consecutive patients with TC
Measurements: data on pre-surgery reasons leading to TC diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities and non-thyroid cancer.
Results: among the 327 enrolled subjects the diagnosis of TC was prompted by thyroid-related reasons in 262 (80.1%, TD group) and incidental in 65 (19.9%, ID group). The ID group patients were more frequently males, significantly older and with a higher BMI than the TD group ones, they had a higher rate of non-thyroidal cancers and cardiovascular/metabolic comorbidities. No significant differences could be observed in terms of TC histotype, cancer size, extra-thyroidal extension, lymph-node metastases, AJCC Staging or ATA Risk stratification.
Conclusions: biological features of TC are similar in the TD and ID groups, but patients in the two groups display significant differences regarding their clinical features.
Background
Polypharmacy (i.e., treatment with ≥ 5 drugs) is common in patients with atrial fibrillation (AF) and has been associated with suboptimal management and worse outcomes. Little is known about how prescribed drug patterns affect management and prognosis in patients with AF.
Methods
Based on data from the prospective global GLORIA-AF Registry Phase III (recruiting patients with AF and CHA2DS2-VASc score ≥ 1), we performed a latent class analysis to identify treatment patterns based on 14 drug classes including cardiovascular (CV) and non-CV drugs. We analysed associations with oral anticoagulant (OAC) use and risk of a composite primary outcome (all-cause death and major adverse cardiovascular events (MACE)) and secondary outcomes.
Results
Among 21,245 patients (mean age 70.2 ± 10.3 years, 44.9% females), we identified 6 patterns: i) Low Medicated pattern (18.3%); ii) Hypertension pattern (21.1%); iii) Heart Failure pattern (20.0%); iv) CV Prevention pattern (21.0%); v) Mixed Morbidity pattern (4.5%); and vi) High Medicated pattern (15.0%). All groups had higher odds of OAC use vs the Low Medicated pattern, with highest prevalences in the Heart Failure pattern (OR [95%CI]: 2.17 [1.90–2.48]) and the High Medicated pattern (OR [95%CI]: 2.08 [1.77–2.44]). Over 3-year follow-up, Heart Failure, Mixed Morbidity and High Medicated patterns were associated with higher risk of the primary composite outcome (aHR [95%CI]: 1.32 [1.14–1.53]; 1.45 [1.17–1.80] and 1.35 [1.14–1.60], respectively). Similar results were observed for all-cause mortality.
Conclusions
In patients with AF, different treatment patterns can be identified. Each pattern was associated with unique OAC use and long-term clinical outcomes.
Background
The reported prevalence of coeliac disease (CD) in rheumatoid arthritis (RA) is variable.
Objective
To evaluate the prevalence and incidence of CD in RA and controls.
Design
Case-control study on administrative data.
Methods
The RECord linkage On Rheumatic Disease database (administrative data, 2004–2013) was used to retrieve patients with RA and age and sex-matched controls. Prevalence and incidence of CD were calculated and stratified according to age, gender, and calendar year.
Results
The cohort included 346,956 subjects (mean age 59.9 (14.5), 70.7% females), of which 70,061 RA and 276,895 controls. Median follow-up was 9 years (IQR 9–9). The prevalence of CD was higher in RA (171/70,061 = 0.24% (0.2–0.3%) vs 398/276895 = 0.14% (0.1–0.2%), p < 0.001). The prevalence of CD among females with RA was increased compared to controls (0.3% vs 0.08%, p < 0.001), but was not increased in males with RA. The incidence was higher in RA and remained stable throughout the observation period.
Conclusion
The prevalence and incidence of CD were increased in RA, particularly in females.
Introduction: Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies, calling for enhanced research. Pancreatic ductal adenocarcinoma (PDAC) represents 70–80% of all cases and is known for its resistance to conventional therapies. Carbon-ion radiotherapy (CIRT) has emerged as a promising approach due to its ability to deliver highly localized doses and unique radiobiological properties compared to X-rays. In vitro radiobiology has relied on two-dimensional (2D) cell culture models so far; however, these are not sufficient to replicate the complexity of the in vivo tumor architecture. Three-dimensional (3D) models become a paradigm shift, surpassing the constraints of traditional models by accurately re-creating morphological, histological, and genetic characteristics as well as the interaction of tumour cells with the microenvironment. Materials and Methods: This study investigates the survival of pancreatic cancer cells in both 2D and spheroids, a 3D model, following photon, proton, and carbon-ion irradiation by means of clonogenic, MTT, spheroid growth, and vitality assays. Results: Our results demonstrate that carbon ions are more efficient in reducing cancer cell survival compared to photons and protons. In 2D cultures, carbon-ion irradiation reduced cell survival to approximately 15%, compared to 45% with photons and 30% with protons. In the 3D culture model, spheroid growth was similarly inhibited by carbon-ion irradiation; however, the overall survival rates were higher across all irradiation modalities compared to the 2D cultures. Carbon ions consistently showed the highest efficacy in reducing cell viability in both models. Conclusions: Our research highlights the pivotal role of 3D models in unraveling the complexities of pancreatic cancer radiobiology, offering new avenues for designing more effective and precise treatment protocols.
Background
Left Ventricular Assist Device (LVAD) implantation is an important treatment option for patients with advanced CHF. Referral to an early, intensive cardiac rehabilitation (CR) program in these patients seems still underused. This observational descriptive study aimed to evaluate the feasibility and efficacy of an early intensive CR program in LVAD recipients, also comparing results with a matched group of advanced HFrEF patients.
Methods
The study involved patients with LVAD implantation due to HFrEF who were admitted to our intensive post‐acute CR program from several surgery wards from 2009 to 2023. They underwent a twice‐a‐day individualized exercise program and physiotherapeutic treatment, according to clinical stability and functional assessment. The study exclusively focused on the in‐hospital rehabilitation period and documented cardiac and non‐cardiac complications, including the Hemocompatibility‐Related Adverse Events (HRAEs). The Barthel index (BI) was used to assess functional recovery from admission to discharge. Results in a subgroup of 210 LVAD patients matched on a 1:1 basis with an HFrEF population were also analyzed.
Results
One patient died during the inward rehabilitation period (respiratory failure). The majority (70.0%) of patients improved their disability (BI 67 ± 24 to 84 ± 23, p < 0.001). HRAEs occurred in 25 patients (9.1%). Compared to the HFrEF group, LVAD patients showed similar improvement in disability ( p = 0.54).
Conclusions
The study suggests that an early intensive post‐acute CR program can significantly improve functional capacity and disability in LVAD patients, similar to HFrEF patients admitted to the same program. Our data support scientific recommendations suggesting participation of LVAD to a CR.
Introduction
Cognitive symptoms are common in Parkinson's Disease (PD), and digital interventions like telerehabilitation other an accessible way to manage these symptoms. This study aimed to assess the effectiveness of a Home-Based Computerized Cognitive Training (HB-CCT) program in individuals with PD using a pilot randomized cross-over design.
Methods
Twenty-five participants (mean age 69.32 ± 7.21 years, mean MDS-UPDRS III 33.76 ± 14.25) with PD and mild cognitive impairment were enrolled. They underwent neuropsychological assessments at three time points (5-week intervals): Baseline, after the HB-CCTi, and after Standard Care. The HB-CCT consisted of the Neurotablet® platform that was used to target cognitive domains such as Attention, Memory, Perception, Executive Functioning and Language. All participants completed both the Neurotablet intervention and Standard Care blocks in a randomized order. After a Shapiro-Wilk test, non-parametric repeated measures analyses of variance (Friedman's test) and post-hoc comparisons corrected with the Benjamini-Hochberg approach were performed to compare the effects on primary and secondary cognitive outcomes over experimental intervention and Standard Care.
Results
The results from the Friedman analysis revealed significant improvements in Word List Immediate Recall, Digit Span Forward and Complex Figure Recall (all p < 0.001) following the HB-CCT, compared to the Baseline. Additionally, Naming performance showed significant improvement after the HB-CCT (p = 0.02). Significant differences were also observed when comparing the HB-CCT with Standard Care, with improved performance in TMT-A (p = 0.02), Phonemic Fluency (p < 0.01), and Digit Span Forward (p < 0.01).
Discussion
These findings suggest that HB-CCT via Neurotablet can effectively enhance specific cognitive abilities in PD, supporting the role of digital, home-based interventions as feasible strategies to mitigate cognitive decline.
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