Human sinusoidal subendothelial cells regulate homing and invasion of circulating metastatic prostate cancer cells to bone marrow

: Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenvironment (HME) generating humanized bone/BM ossicles. To create a mouse model of hematogenous metastasis of human prostate cancer (PC) cells to human bone/BM, we injected PC cells in the blood circulatory system of Severe Combined Immunodeficiency (SCID)/beige mice bearing heterotopic ossicles. Results indicate that PC cells could efficiently home to mice-implanted extraskeletal BM ossicles, but were not able to colonize mice skeletal segments. In humanized bone/BM ossicles, early foci of PC cells occupied a perisinusoidal position, in close contact with perivascular stromal cells. These findings demonstrate the importance of the SSC compartment in recreating a suitable environment to metastatic PC cells. Our data support the hypothesis that BM SSCs committed to a pericyte fate can specify for homing niches of PC cells, suggesting an involvement of specific interactions with subendothelial stromal cells in extravasation of circulating metastatic PC cells to BM

Secondary post-oncologic vulvar reconstruction – a simplified algorithm

IntroductionSurgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature.MethodsIn this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making.ResultsSixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm2 ± 163 cm2. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flaps still available after previous surgery.DiscussionA systematic approach to secondary vulvar reconstruction can provide good surgical results with a low rate of complications. The geometry of the defect and the use of both traditional and perforator flaps should guide the choice of the reconstructive technique

Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α1-adrenergic receptors

Aim: As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of β3-adrenoceptors which also seem to mediate endothelium-dependent vasodilation in disparate human vascular beds. We characterized, therefore, the vasomotor function of mirabegron in human adipose tissue arteries and the underlying mechanisms. Methods: Small arteries (116-734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions. Results: Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-K+ (both P > 0.05). Notably, mirabegron markedly blunted the contractile effect of the α1-adrenergic receptor agonist phenylephrine (P < 0.001) either in presence or absence of the vascular endothelium. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective β3-adrenoceptor blocker L-748,337 (P < 0.05); lack of involvement of β3-adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry. Conclusions: Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α1-adrenoceptors

Bariatric and metabolic surgery during COVID-19 outbreak phase 2 in Italy: why, when and how to restart

In Italy elective bariatric and metabolic surgery was cancelled on February 21,2020 at the beginning of the so-called phase 1 of the SARS-CoV-2 outbreak. Gradually it was restarted on May 4,2020 at the beginning of the so-called phase 2, when epidemiological data showed containment of the infection. Before the outbreak in eight high-volume bariatric centers 840 patients were surgically treated developing a Covid-19 infection, during phase 1, in only 5 cases (0.6%) without mortality. The post-operative complication rate was similar when compared to the 836 subjects submitted to bariatric surgery the year before. Since the high prevalence of infection in subjects with BMI. 30, it was argued that early intervention on obesity during phase 2 could help to minimize the effects of the disease in the event of a possible reversion to a SARS-CoV-2 outbreak phase 1. At the same time a prospective observational study from July 1 till the WHO declaration of the end of the pandemic has started in the eight high volume centers to monitor the post-operative outcome and its effect on SARS-CoV2 infection. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved

Clinical Study Integrated Approaches for the Management of Staple Line Leaks following Sleeve Gastrectomy

Introduction. Aim of the study was trying to draw a final flow chart for the management of gastric leaks after laparoscopic sleeve gastrectomy, based on the review of our cases over 10 years' experience. Material and Methods. We retrospectively reviewed all patients who underwent LSG as a primary operation at the Bariatric Unit of Tor Vergata University Hospital in Rome from 2007 to 2015. Results. Patients included in the study were 418. There were 6 staple line leaks (1.44%). All patients with diagnosis of a leak were initially discharged home in good clinical conditions and then returned to A&E because of the complication. The mean interval between surgery and readmission for leak was 13,4 days (range 6-34 days, SD ± 11.85). We recorded one death (16.67%) due to sepsis. The remaining five cases were successfully treated with a mean healing time of the gastric leak of 55,5 days (range 26-83 days; SD ± 25.44). Conclusion. Choosing the proper treatment depends on clinical stability and on the presence or not of collected abscess. Our treatment protocol showed being associated with low complication rate and minor discomfort to the patients, reducing the need for more invasive procedures

Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up

Doppler and Spectral Ultrasound of Sacroiliac Joints in Pediatric Patients with Suspected Juvenile Spondyloarthritis

Background: Power Doppler ultrasound (PDUS) with spectral wave analysis (SWA) has been compared with magnetic resonance imaging (MRI) in documenting active sacroiliitis in early spondyloarthritis (SpA) but, to date, PDUS/SWA has not been yet applied to the study of sacroiliac joints (SIJs) in children. Methods: A group of 20 children (13 F/7 M, mean age 14.2 y) with suspected juvenile SpA (jSpA) underwent PDUS/SWA and, subsequently, MRI of the SIJs. SIJs PDUS scoring and resistance index (RI) of the SIJs flows were recorded. The accuracy of PDUS/SWA for the diagnosis of active sacroiliitis was evaluated, with MRI as the gold standard. Results: PDUS signals were detected in 19 patients and 30 SIJs. Bone marrow edema (BME) lesions on MRI were detected in 12 patients (diagnosed as jSpA) and 22 SIJs. PDUS scoring on SIJs were higher in patients with a final diagnosis of jSpA (p = 0.003). On SWA, the mean RIs in patients with or without final diagnosis of active sacroiliitis were, respectively, 0.604 and 0.767 (p = 0.005) at joint level. A RI < 0.55 and PDUS > 1 showed the higher specificity for sacroiliitis (AUROC curve 0.854 for PDUS and 0.920 for RI). SIJs PDUS/SWA showed an overall concordance of 82.35%, with substantial agreement (k = 0.627) with MRI on the diagnosis of sacroiliitis. Conclusions: In children with sacroiliitis, PDUS demonstrates a rich vascularization into SIJs and low RIs (<0.55) have high specificity for this condition. SIJs PDUS/SWA could be useful as a screening method in children with suspected jSpA

Clinical, laboratory and ultrasonographic findings at baseline predict long-term outcome of polymyalgia rheumatica: a multicentric retrospective study : Polymyalgia rheumatica predicted by ultrasonographic findings polymyalgia rheumatica outcome predicted early by ultrasound

To assess the rate of PMR who, during the follow-up, undergo a diagnostic shift as well as to assess which clinical, laboratory and US findings are associated to a diagnostic shift and predict the long-term evolution of PMR. All PMR followed-up for at least 12 months were included. According to the US procedures performed at diagnosis, patients were subdivided into four subgroups. Clinical data from follow-up visits at 12, 24, 48 and 60 months, including a diagnostic shift, the number of relapses and immunosuppressive and steroid treatment, were recorded. A total of 201 patients were included. During the follow-up, up to 60% had a change in diagnosis. Bilateral LHBT was associated with persistence in PMR diagnosis, whereas GH synovitis and RF positivity to a diagnostic shift. Patients undergoing diagnostic shift had a higher frequency of GH synovitis, shoulder PD, higher CRP, WBC, PLT and Hb and longer time to achieve remission, while those maintaining diagnosis had bilateral exudative LHBT and SA-SD bursitis, higher ESR, lower Hb and shorter time to remission. Cluster analysis identified a subgroup of older patients, with lower CRP, WBC, PLT and Hb, lower PD signal or peripheral synovitis who had a higher persistence in PMR diagnosis, suffered from more flares and took more GCs. Most PMR have their diagnosis changed during follow-up. The early use of the US is associated with a lower dosage of GCs. Patients with a definite subset of clinical, laboratory and US findings seem to be more prone to maintain the diagnosis of PMR

Laparoscopic bariatric surgery is safe during phase 2-3 of COVID-19 pandemic in Italy: A multicenter, prospective, observational study

Background: Sars-Cov-2 epidemic in Italy caused one of the greatest 2020 European outbreaks, with suspension of elective bariatric/metabolic surgery (BMS). From May 2020 a significant decline of the epidemic has been observed (phase 2); National Health Service protocols permitted elective BMS' resumption. A new, more severe COVID-19 surge, the "second wave", started on October 2020 (phase 3).Aim: The primary end point was to analyze the outcomes of any Sars-Cov-2 infection and related morbidity/mortality within 30 POD after laparoscopic BMS during phase 2-3; secondary end points were readmission and reoperation rates.Methods: Study design prospective, multicenter, observational.Setting: Eight Italian high-volume bariatric centers. All patients undergoing BMS from July 2020 through January 2021 were enrolled according to the following criteria: no Sars-Cov-2 infection; primary procedures; no concomitant procedure; age > 18 < 60 years; compensated comorbidities; informed consent including COVID-19 addendum; adherence to specific admission, in-hospital and follow-up protocols. Data were collected in a prospective database. Patients undergone BMS during July-December 2019 were considered a control group.Results: 1258 patients were enrolled and compared with 1451 operated on in 2019, with no differences for demographics, complications, readmission, and reintervention rates. Eight patients (0.6%) tested positive for Sars-Cov-2 infection after discharge, as well as and 15 healthcare professionals, with no related complications or mortality.Conclusions: Introduction of strict COVID-19 protocols concerning the protection of patients and health-care professionals guaranteed a safe resumption of elective BMS in Italy. The safety profile was, also, maintained during the second wave of outbreak, thus allowing access to a cure for the obese population. (C) 2021 Elsevier B.V. All rights reserved

Baricitinib retention rate: ‘real-life’ data from a mono-centric cohort of patients affected by rheumatoid arthritis

ObjectivesThe aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection.Materials and methodsPatients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort’s demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks.ResultsNinety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p < 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation.ConclusionOur data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects