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Objective: We sought to evaluate the association between constipation severity, productivity losses and healthcare utilization in a national sample of Italian patients with chronic non-organic constipation (CC)., Methods: We enrolled 878 outpatients with CC. Clinical and demographic data were collected by physicians during clinical examinations. Patients completed a self-administered questionnaire (Patient Assessment of Constipation-Symptoms, PAC-SYM; Work Productivity and Activity Impairment; healthcare utilization, and Symptoms Checklist 90 Revised - Somatization Scale, SCL-90 R)., Results: Mean PAC-SYM score was 1.62 ± 0.69. Mean weekly sick time due to constipation was 2.7 ± 8.6 h and productivity losses due to presenteeism was 19.7% ± 22.3%. Adjusted productivity losses in patients with severe CC (PAC-SYM score 2.3-4.0) compared to patients with mild symptoms (PAC-SYM score 0.0-1.0) was Italian Purchase Power Parity US$ 6160. Constipation severity (PAC-SYM quintiles) was associated with higher healthcare utilization (RRPAC-SYM 4/01.84; p-value for linear trend <0.01). After adjustment for somatization scores, the association of constipation severity with productivity losses and healthcare utilization rates was attenuated yet statistically significant., Conclusions: We observed a graded increase in productivity losses and healthcare utilization with increasing constipation severity. Further studies should evaluate whether significant savings might be achieved with regimens aimed at reducing the constipation severity.

Pain originating from the female reproductive organs is a substantial clinical problem to treat. Experimental models may be a tool for the study of visceral pain mechanisms and hence provide information to aid in formulating new treatment strategies. The aim was to develop and evaluate the performance and safety of a model for nociceptive stimulation of the uterine cervix by balloon dilatation using impedance planimetry. Three consecutive (repeated) dilatations at 1 ml/min, an isovolumetric and a fast dilatation at 2 ml/min were performed. Pilot studies were conducted in vitro on hysterectomy specimens, followed by application of the model in 14 healthy females. Subjects indicated the quality of perception and pain during dilatations by verbal reports and the McGill Pain Questionnaire (MPQ), and the intensity by a continuous electronic visual analog scale. The pain location was marked on an anatomical map. The balloon cross-sectional area (CSA) was measured simultaneously. The experimental procedure was atraumatic. Pain was evoked in all subjects, with referral to the hypogastric and low back regions. The word descriptors on the MPQ and the areas of referred sensations were similar to that seen clinically in abortion, labor and menstrual pain. The pain intensity correlated with balloon CSA (r=0.9, P<0.001). No significant differences were found for the balloon volumes (4.2, 3.8 and 3.9 ml) or CSA (163, 122 and 123 mm(2)) to pain threshold (PT) for repeated dilatations, suggesting the reliability of the model. There was significant correlation between the balloon volume and CSA to reach the PT for single and repeated cervical dilatations. During isovolumetric distension, greater overall pain intensity was demonstrated for the prolonged as compared to the shorter duration cervical stimulation. In conclusion, this is the first human experimental pain model for dilatation of the uterine cervix, providing a safe, controlled, quantifiable stimulus that evoked reliable pain scores. The model thus provides a new possibility to study gynecological pain and may lead to better characterization and treatment of female visceral pain syndromes.

Objectives: The current knowledge about the role of comorbidities in systemic sclerosis (SSc) is limited. Therefore, the aim of this study was to evaluate the prevalence of comorbidities and their impact on disease activity and prognosis in the Systemic sclerosis PRogression INvestiGation (SPRING) registry., Methods: SSc patients from the SPRING registry, fulfilling the ACR/EULAR 2013 classification criteria, with complete data on baseline comorbidities were enrolled. The Charlson comorbidity index (CCI) was used to quantify the overall comorbidity burden. The disease activity was calculated using the revised EUSTAR activity index (AI). The impact of SSc features on CCI, the effect of CCI on SSc disease activity and mortality were tested with multivariable regression models., Results: Among 1910 SSc patients enrolled, 67.3 % had at least one comorbidity at baseline. The most frequent comorbidities were systemic arterial hypertension (23.7 %), osteoporosis (12.9 %) and dyslipidemia (11 %). The mean value of CCI score was 2.0 ± 1.8. When patients were grouped according to increasing levels of CCI, a clear separation in the distribution of SSc-related clinical features could be observed. Among over 900 patients with available follow-up, no association between baseline CCI and changes in disease activity was observed. Conversely, the risk of death over time was independently predicted by both CCI and AI., Conclusions: Comorbidities and disease activity independently impact on the prognosis of SSc patients. This suggests that the management of comorbidities, together with the reduction of disease activity, is fundamental to improve patient survival., Competing Interests: Declaration of competing interest Orlandi M, Bellando-Randone S, Ferri C, Foti R, Codullo V, De Angelis R, Cuomo G, Campochiaro C, Luca Magnani, Cacciapaglia F, Ariani A, Giuggioli D, and Guiducci S have no conflict of interest to declare. Matucci-Cerinic M received fees from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche. Bruni C received consulting fees and/or honoraria from Eli-Lilly, Boehringer Ingelheim, Research grants from Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis foundation for biomedical research. Congress supports from Boehringer-Ingelheim. Educational grants from AbbVie and Wellcome Trust., (Copyright © 2024. Published by Elsevier B.V.)

Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.