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Dexmedetomidine, a selective α2-adrenergic agonist, is favoured in intensive care for its minimal respiratory depression. This study evaluated the reporting frequency of rhabdomyolysis with dexmedetomidine compared to midazolam and propofol using the European pharmacovigilance database Eudravigilance. We conducted an observational, retrospective analysis of Individual Case Safety Reports (ICSRs) from 1 January 2013, to 31 December 2023. Primary and secondary outcomes included the reporting frequencies of rhabdomyolysis and its indicative signs and symptoms, respectively. We retrieved 19,268 ICSRs, of which 364 reported rhabdomyolysis associated with dexmedetomidine (3.8%), midazolam (10.2%), propofol (76.9%), or combinations thereof (9.1%). Dexmedetomidine showed a significantly lower reporting frequency of rhabdomyolysis compared to propofol (ROR, 0.32; 95% CI, 0.19–0.55) but no significant difference compared to midazolam. Subgroup analyses revealed higher frequencies in males, especially with propofol. Despite limitations such as underreporting, our findings suggest dexmedetomidine poses a lower rhabdomyolysis risk than propofol, supporting its safe use for sedation in high-risk patients. It is important to note that due to the retrospective design of this study our findings are indicative of correlations rather than causation. Continuous monitoring and further studies are recommended to validate these results. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen−) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen−. Sixteen Gen+/Phen− (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH−) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (−19.8 ± 0.4 vs. −22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen− subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment. [ABSTRACT FROM AUTHOR]

Malignant pleural effusion (MPE) from patients with advanced non-small-cell lung cancer (NSCLC) has been proven valuable for molecular analysis; however, simultaneous detection of driver fusions in MPE is still challenging. In this study, we investigated the Idylla™ GeneFusion Panel, a stand-alone test in tissue samples, in the evaluation of ALK, ROS1, RET and MET ex14 skipping mutations in MPE and compared its performance with routine reference methods (Real-time-based and Next-generation Sequencing—NGS). The inclusion criteria for sample selection were as follows: advanced NSCLC harboring ALK, ROS1, RET fusions or MET exon-skipping alterations and the availability of MPE collected at diagnosis or disease progression. Molecular alterations have been investigated on tissue by fluorescence in situ hybridization (FISH) or Real-time PCR or NGS. For molecular profiling with the Idylla™ GeneFusion, 200 µL of MPE supernatants combined with 50 µL of RNA Later solution were loaded into the Idylla™ cartridge without cfRNA extraction. The Idylla™ GeneFusion Assay performed on MPEs was able to confirm molecular profile, previously diagnosed with conventional methods, in all cases. Our data confirm that MPE are suitable material for investigating fusion alterations. The Idylla™ GeneFusion, although indicated for investigation of tissue samples, offers the possibility of performing a molecular characterization of supernatants without undertaking the entire cfRNA extraction procedure providing a rapid and reliable strategy for the detection of actionable genetic alterations. [ABSTRACT FROM AUTHOR]

Motivated by applications to gas filtration problems, we study the regularity of weak solutions to the strongly degenerate parabolic PDE u t - div ⁡ ( (| D ⁢ u | - ν) + p - 1 ⁢ D ⁢ u | D ⁢ u | ) = f in ⁢ Ω T = Ω × (0 , T) , where Ω is a bounded domain in ℝ n for n ≥ 2 , p ≥ 2 , ν is a positive constant and (⋅) + stands for the positive part. Assuming that the datum f belongs to a suitable Lebesgue–Sobolev parabolic space, we establish the Sobolev spatial regularity of a nonlinear function of the spatial gradient of the weak solutions, which in turn implies the existence of the weak time derivative u t . The main novelty here is that the structure function of the above equation satisfies standard growth and ellipticity conditions only outside a ball with radius ν centered at the origin. We would like to point out that the first result obtained here can be considered, on the one hand, as the parabolic counterpart of an elliptic result established in [L. Brasco, G. Carlier and F. Santambrogio, Congested traffic dynamics, weak flows and very degenerate elliptic equations [corrected version of mr2584740], J. Math. Pures Appl. (9) 93 2010, 6, 652–671], and on the other hand as the extension to a strongly degenerate context of some known results for less degenerate parabolic equations. [ABSTRACT FROM AUTHOR]

In this paper we study the C1 regularity of the weak solutions to the widely degenerate parabolic system ∂tu - div ((| Du| - 1)+p-1Du-|Du|) = 0 in ΩT, where p > 1, ΩT = Ω x (0, T) is a parabolic cylinder with a bounded domain Ω ⊂ Rn, T> 0. For the weak solutions u: ΩT → RN with N ≥ 1 we prove that K (Du) is continuous in ΩT, for any continuous function K : ΩT → RNn → RNn vanishing on the set {ξ ∈ RNn : |ξ ≤| 1}. [ABSTRACT FROM AUTHOR]

Purpose: Despite the evidence of higher effectiveness of psychological interventions for insomnia compared to pharmacological ones, drug prescriptions for insomnia remain frequent. This study has assessed patterns of prescriptions of BZDs for insomnia before and after the delivery of a training in psychological interventions to professionals working in the services of a Department of Mental Health in northern Italy. Methods: The intervention consisted in two training sessions about psychological interventions for insomnia delivered to professionals of the participating services. The prevalence of users with a prescription of BZDs for insomnia in an index period after the delivery of the training was compared to the prevalence in an index period before the training. Results: Among 727 people assessed for BZDs prescription at pre-intervention, 306 (42.1%, 95% CI 0.39–0.46) had a prescription, and 344 (49.2%, 95% CI 0.45–0.53) had a prescription among 699 people assessed at post-intervention, corresponding to a significant odds ratio of 1.33 to be prescribed with BZDs in the second index period compared to the first one. Psychological interventions were offered to a small group of patients. Conclusion: Prescribing attitudes of BZDs for insomnia were not modified after the training and delivery of a psychological intervention in a mental healthcare outpatient setting. Prescribing habits should be addressed more directly in training, and professionals should be more aware of risks of BZDs assumption. The failure in changing drug prescriptions in this study should prompt more real-world studies of the application of evidence-based strategies, particularly in outpatient mental health settings. [ABSTRACT FROM AUTHOR]

Background. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder stemming from mutations in the TNFRSF1A gene affecting the tumor necrosis factor receptor (TNFR)-1. These mutations lead to dysregulated inflammatory responses, primarily mediated by augmented interleukin (IL)-1β release. Case Presentation. We present the case of a 29-year-old woman with a history of recurrent febrile episodes, abdominal pain, and joint manifestations, eventually diagnosed with TRAPS following genetic testing revealing a heterozygous R92Q mutation in TNFRSF1A. Further genetic examinations unveiled additional clinically significant mutations, complicating the clinical picture. Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. Discussion. Gastrointestinal involvement in TRAPS is common but can present diagnostic challenges. Following colon resection, histological examination revealed amyloid deposition, underscoring the importance of a comprehensive evaluation of these patients. Isolated colic amyloidosis has significant diagnostic and prognostic implications, warranting cautious monitoring and tailored management strategies. Treatment of TRAPS typically involves anti-inflammatory agents such as IL-1 inhibitors, with our patient experiencing clinical improvement on anakinra and canakinumab. Conclusion. This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications. [ABSTRACT FROM AUTHOR]