Fluid-dependent single-frequency bioelectrical impedance fat mass estimates compared to digital imaging and dual X-ray absorptiometry

The need for a practical method for routine determination of body fat has progressed from body mass index (BMI) to bioelectrical impedance analysis (BIA) and smartphone two-dimensional imaging. We determined agreement in fat mass (FM) estimated with 50 kHz BIA and smartphone single lateral standing digital image (SLSDI) compared to dual X-ray absorptiometry (DXA) in 188 healthy adults (69 females and 119 males). BIA underestimated (p 25 kg/m2, 54 male rugby players, compared to 40 male non-rugby players, had greater (p < 0.001) BMI and FFM but less (p < 0.001) FM and ECW/ICW. BIA underestimated (p < 0.001) FM in the non-rugby men, but SLSDI and DXA FM estimates were not different in both groups. This finding is consistent with the expansion of ECW in individuals with excess body fat due to increased adipose tissue mass and its water content. Unlike SLSDI, 50 kHz BIA predictions of FM are affected by an increased ECW/ICW associated with greater adipose tissue. These findings demonstrate the validity, practicality, and convenience of smartphone SLSDI to estimate FM, seemingly not influenced by variable hydration states, for healthcare providers in clinical and field settings.Peer ReviewedPostprint (published version

Long‑term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real‑world Setting: An Interim Analysis Through 48 Weeks of Observation

Background Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate- severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. Methods This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. Results One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physicianreported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. Conclusion This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change

Activity of sotorasib against brain metastases from NSCLC harboring KRAS p.G12C mutation: a case report

In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib. Our report suggests that sotorasib may be active against untreated or progressive brain metastases, supporting further evaluation of sotorasib in this setting

Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death

We present here the differential analysis of metabolite-metabolite association networks constructed from an array of 24 serum metabolites identified and quantified via nuclear magnetic resonance spectroscopy in a cohort of 825 patients of which 123 died within 2 years from acute myocardial infarction (AMI). We investigated differences in metabolite connectivity of patients who survived, at 2 years, the AMI event, and we characterized metabolite-metabolite association networks specific to high and low risks of death according to four different risk parameters, namely, acute coronary syndrome classification, Killip, Global Registry of Acute Coronary Events risk score, and metabolomics NOESY RF risk score. We show significant differences in the connectivity patterns of several low-molecular-weight molecules, implying variations in the regulation of several metabolic pathways regarding branched-chain amino acids, alanine, creatinine, mannose, ketone bodies, and energetic metabolism. Our results demonstrate that the characterization of metabolite-metabolite association networks is a promising and powerful tool to investigate AMI patients according to their outcomes at a molecular level.</p

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p &lt; 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed &gt; 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

The immunopathogenesis of HS is partially understood and exhibits features of an autoinflammatory disease; it is associated with the potential involvement of B cells and the contribution of Th1 or Th17 cell subsets. Recently, the pathogenic role of both innate immunity and IL-1 family cytokines in HS has been deeply investigated. Several agents targeting the IL-1 family pathway at different levels are currently available and under investigation for the treatment of HS. HS is still characterized by unmet clinical needs and represents an expanding field in the current scientific research. The aim of this narrative review is to describe the pathological dysregulation of IL-1 family members in HS and to provide an update on therapeutic strategies targeting IL-1 family cytokine signaling. Further clinical and preclinical data may likely lead to the enrichment of the therapeutic armamentarium of HS with IL-1 family cytokine antagonists

Head Injury Assessment in Italian rugby union: a two-seasons prospective analysis

Background: In Italy, to the best of our knowledge, there is no literature relating to injury and concussion epidemiology in rugby union. Therefore, the primary aim of this study is to describe the incidence of sport-related concussion in Italian rugby union and the associated management of Head Injury Assessment (HIA). Methods: This is an observational prospective study, analysing the Italian elite rugby championship (Top 12 and Coppa Italia) for two seasons (2018/2019 and 2019/2020). Twelve male teams of the Italian elite rugby championship were included. The diagnosis of traumatic brain injury was provided by a team doctor with HIA, while no match day doctor or video analysis was available. A concussion expert of Italian Rugby Federation reviewed all the HIAs. The outcome of interest were: incidence, playing situation and mechanism responsible for traumatic brain injury. Results: In the study period, 47 HIAs were performed during matches (45.3/1000 player-match-hours) and 7 concussions were diagnosed by team doctors (6.75/1000 player-match-hours). After the concussion expert HIAs' review, the thirty-three percent of 16 diagnoses were made later, during follow-up, or based on clinical suspicion. Most symptoms complained about by players were neck pain and headache, in 14.6% and 13.4% of HIA, respectively. Concussions were predominately the result of tackling (46.5%) for the tackler (90.9%). Conclusions: The incidence of concussion in Italian Rugby appears to be low compared to that of rugby outside Italy, which is likely due to the learning curve of HIA and the absence of video analysis and match day doctors during competitions. The implementation of educational projects may be fundamental to promoting HIA process

“Tailored” antiplatelet bridging therapy with cangrelor: moving toward personalized medicine

In the setting of patients with indication to receive dual antiplatelet therapy undergoing surgery or invasive procedures, the risk of perioperative cardiac ischemic events, particularly stent thrombosis, is high, because surgery has a prothrombotic effect and antiplatelet therapy is withdrawn in order to avoid bleeding complications. Cangrelor, an intravenous P2Y12 receptor antagonist, has been tested in a randomized trial as a “bridge” to cardiac surgery from discontinuation of oral P2Y12 receptor antagonists. Thus, a consensus document extended its off-label use in this setting and before non-cardiac surgery. Currently, despite the implementation of a standardized bridging protocol with cangrelor, a residual risk of adverse outcome mainly due to bleeding events, still persist during the perioperative phase. Accordingly, a personalized management driven by platelet reactivity serial measurements and careful assessment of ischemic and bleeding risks has potential to optimize outcomes and costs as compared to a standardized bridging protocol, based on average pharmacodynamic data of oral P2Y12 inhibitors. While specific indications for bridging have been extensively addressed in the aforementioned consensus statement, the aim of the present document is the proposal of a “tailored” clinical decision-making algorithm inspired to the principle of personalized medicine dealing with complex clinical scenarios