Characterization of digital annular pulleys and their entheses: an ultrasonographic study with anatomical and histological correlations

Objectives: Digital annular pulleys (DAP) are important anatomical structures for finger function. The anatomy, histology, and imaging assessment of DAP, particularly at the level of their entheses is still not clearly defined. The advent of high-frequency ultrasound (US) transducers opened new perspectives in evaluating sub-millimeter scale structures, such as pulleys, paving the way for their global assessment. The study aimed at characterizing DAP from an anatomical, histological, and US perspective, focusing on the detection and complete description of pulley entheses. Methods: US assessment and gross anatomy dissection were conducted on 20 cadaveric hands to study DAP thickness and structure including enthesis identification. The results of the US and anatomical measurements were correlated. DAP entheses identified by US were characterized via histological analysis. DAP in 20 healthy controls (HC) were detected and measured by US. The A1, A2, and A4 DAP entheses were assessed using a new dynamic maneuver to better evaluate those structures. Results: 1200 DAP (400 cadaveric, 800 HC) were analyzed. The cadaveric study demonstrated strong correlation between anatomical and US measurement of DAP (r = 0.96). At histological level, DAP entheses at the volar plate, sesamoid bones, or phalangeal ridges contained fibrous and fibrocartilaginous tissue. The US assessment of A1, A2, and A4 DAP in HC allowed the identification of 718/720 (99.73%) entheses. Conclusion: US is an effective tool to detect and study DAP. DAP entheses reveal both fibrous and fibrocartilaginous characteristics. A newly described maneuver to optimize DAP enthesis visualization enhances their detection by US

Effects of sex hormones on bronchial reactivity during the menstrual cycle

Background: Many asthmatic women complain of symptom exacerbations in particular periods, i.e. during pregnancy and menstrual cycles (perimenstrual asthma: PMA)". The goal of this study was to study the effect of the luteal and follicular phases of the menstrual cycle on bronchial reactivity (BR) in a group of asthmatic women. Methods: For this purpose, 36 pre-menopausal women were enrolled and underwent testing for resting pulmonary function, measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured plasma hormone levels and levels of cyclic adenosine monophosphate (cAMP; a mediator of bronchial smooth muscle contraction) and testosterone in induced sputum samples. Results: Our study showed that about 30% of the asthmatic women had decreased PC20FEV1.0 in the follicular phase of menstrual cycle with a significant correlation between PC20FEV1.0 and serum testosterone levels. Moreover, marked increases in sputum testosterone levels (mean = 2.6-fold increase) together with significant increases in sputum cAMP concentrations (mean = 3.6-fold increases) were observed during the luteal phase of asthmatic patients, suggesting that testosterone contributes to the pathophysiology of PMA. We excluded the possibility that testosterone directly inhibits phosphodiesterase (PDE) activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity. Conclusions: In conclusion, our data show that PC20FEV1.0 was decreased in the follicular phase of the menstrual cycle in about 30% of women and was associated with lower cAMP levels in sputum samples, which may contribute to bronchoconstriction. Our results also suggest a link between PMA and testosterone levels. However, whether these findings are of clinical significance in terms of the management of asthma or asthma worsening during the menstrual cycle needs further investigation

Which Patients with Chronic Periprosthetic Joint Infection Are Less Suitable to Successful Two Stage Exchange Arthroplasty Surgery? A Retrospective Clinical Trial

Which Patients with Chronic Periprosthetic Joint Infection Are Less Suitable to Successful Two Stage Exchange Arthroplasty Surgery? A Retrospective Clinical Tria

DEDALO: PHASE II STUDY OF DARATUMUMAB PLUS POMALIDOMIDE AND DEXAMETHASONE (DPD) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND 17P DELETION

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High-resolution marine data and transient simulations support orbital forcing of ENSO amplitude since the mid-Holocene

Lack of constraint on spatial and long-term temporal variability of the El Niño southern Oscillation (ENSO) and its sensitivity to external forcing limit our ability to evaluate climate models and ENSO future projections. Current knowledge of Holocene ENSO variability derived from paleoclimate reconstructions does not separate the role of insolation forcing from internal climate variability. Using an updated synthesis of coral and bivalve monthly resolved records, we build composite records of seasonality and interannual variability in four regions of the tropical Pacific: Eastern Pacific (EP), Central Pacific (CP), Western Pacific (WP) and South West Pacific (SWP). An analysis of the uncertainties due to the sampling of chaotic multidecadal to centennial variability by short records allows for an objective comparison with transient simulations (mid-Holocene to present) performed using four different Earth System models. Sea surface temperature and pseudo-δ18O are used in model-data comparisons to assess the potential influence of hydroclimate change on records. We confirm the significance of the Holocene ENSO minimum (HEM) 3-6ka compared to low frequency unforced modulation of ENSO, with a reduction of ENSO variance of ∼50 % in EP and ∼80 % in CP. The approach suggests that the increasing trend of ENSO since 6ka can be attributed to insolation, while models underestimate ENSO sensitivity to orbital forcing by a factor of 4.7 compared to data, even when accounting for the large multidecadal variability. Precession-induced change in seasonal temperature range is positively linked to ENSO variance in EP and to a lesser extent in other regions, in both models and observations. Our regional approach yields insights into the past spatial expression of ENSO across the tropical Pacific. In the SWP, today under the influence of the South Pacific Convergence Zone (SPCZ), interannual variability was increased by ∼200 % during the HEM, indicating that SPCZ variability is independent from ENSO on millennial time scales

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer

Background: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. Methods: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). Discussion: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. Trial registration: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered

Assessing Disease Activity in Psoriatic Arthritis: A Literature Review

Psoriatic arthritis (PsA) is a multifaceted disease, with a high impact on patients’ psychological and physical well-being. There is increasing recognition that assessment of both clinical aspects of disease and patient identified concerns, such as fatigue, work disability, and treatment satisfaction need to be addressed. Only then can we fully understand disease burden and make well-informed treatment decisions aimed at improving patients’ lives. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as questionnaires capturing the patient’s perspective in psoriatic disease. Despite these advances, there remains disagreement amongst clinicians as to which instruments should be used. As a consequence, they are yet to receive widespread implementation in routine clinical practice. This review aims to summarize currently available clinical and patient-derived assessment tools, which will provide clinicians with a practical and informative resource

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns