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Background: in Italy, Hepatitis-B-vaccine is advised and provided free-of-charge for subjects with chronic liver disease (CLD), including liver cirrhosis. Aims: to evaluate HB-vaccine-coverage and variables associated with lack of vaccination in cirrhotic patients with particular attention to cirrhosis' etiology. Methods: cirrhotic patients of any etiology (excluding HBsAg+) referring to 8 tertiary-centers were prospectively enrolled for a-six-months-period in 2019. Subjects were asked if they received HB-vaccine previously. Multiple-logistic-regression-analysis was performed to identify independent predictors of lack of vaccination. Results: 731 cases were recruited. Overall-vaccine-coverage was 16.3% (23.7% in those younger than 65y, 10.0% in those older than 64y; p64 y (OR: 4.27; CI 95%: 2.52-7.24), educational level

Background The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count p = 0.83). Conclusions Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.

Injury to the medial compartment of the knee is the most common ligament injury to this joint. The medial approach must consider the presence of associated anteromedial instability. Untreated injury of these instabilities can result in failure of the other reconstructed ligaments. As treatment is usually associated with other ligaments, it is relevant that the technique could save grafts and synthetic material. This article aims to describe a technique for the treatment of anteromedial instabilities through semimembranosus tendon tenodesis in a more anterior and distal position, promoting the tensioning of the posteromedial structures., Technique Video Video 1 Reconstruction of a posteromedial structure of a left knee. The patient is in a supine position. The medial approach starts over the medial epicondyle up to 7 cm distal to the joint interline in the medial tibia surface. At this moment, the semitendinosus and gracilis tendons are removed and prepared to serve as a graft for the (MCLs). The direct tibial insertion of the semimembranosus (SM) tendon is individualized and reinserted from the tibia. Anterodistalization of this tendon is carried out, and posterior oblique ligament is tensioned on this anchor with knee flexed at 5°, neutral rotation, and without adduction. Finally, the MCLs are reconstructed and fixed in 30° of flexion using interference screws.

Background. Vitamin D deficiency has been correlated with Multiple Sclerosis (MS) risk and disease activity. There is some controversy as to whether vitamin D could have an impact on depressive symptoms in people with MS (pwMS). The aim of this scoping review was to evaluate the association between vitamin D status and depressive symptoms in pwMS. Methods. We searched databases to include studies published up to March 2021 to provide an overview of the available evidence on the correlation between vitamin D status and depressive symptoms in pwMS. The eligibility criteria were as follows: studies evaluating the use of vitamin D measurement on depressive symptoms in patients suffering from MS, including randomized and non-randomized studies; studies written in English; and studies exploring an adult population over the age of 18. Results. Eleven studies met our inclusion criteria: two of them were abstracts only; the majority were cross-sectional studies; two were prospective longitudinal studies; one was a retrospective cohort study; and one was a randomized placebo-controlled trial (RCT). Of the eleven studies selected, seven showed a potential correlation between low vitamin D levels and depressive symptoms. Conclusion. Future RCT studies should include patients with greater severity of depressive symptoms and should consider confounding factors such as sun exposure and seasonal variation of vitamin D.

Liver injury has been reported in coronavirus disease 2019 (COVID-19) cases but the impact of pre-existing liver damage and related etiology have not been completely elucidated. Our research interests include the potential reciprocal influence of COVID-19 and pre-existing liver damage related to hepatitis C virus (HCV) infection, in particular. To this end, we have evaluated three cohorts of patients admitted at three Italian hospitals during the coronavirus pandemic; these included 332 patients with COVID-19 and 1527 patients with HCV who were from established real-world antiviral treatment study cohorts (sofosbuvir/velpatasvir), with either liver disease (various severities; n = 1319) or cirrhosis (n = 208). Among the COVID-19 patients, 10 had cirrhosis (3%), including 7 of metabolic origin and 3 of viral origin. Mortality among the COVID- 19 patients was 27.1%, with 70% of those with cirrhosis of metabolic etiology having died. Cirrhosis, older age, low white blood cell count and lymphocyte count being identified as risk predictors of death [odds ratio (OR) = 13.7, 95% confidence interval (CI): 2.59-83.01, P = 0.006; OR = 1.05, 95%CI: 1.03-1.08, P =0.0001; OR = 1.09, 95%CI: 1.36-1.16, P = 0.001; OR = 0.61, 95%CI: 0.39-0.93, P = 0.023, respectively]. In the two cohorts of HCV patients, COVID-19 diagnosis was made in 0.07% of those with liver disease and 1% of those with cirrhosis. Thus, the prevalence of HCV antibodies among COVID-19-infected patients was comparable to that currently reported for the general population in Italy. Amongst the COVID-19 patients, pre-existing metabolic cirrhosis appears to be associated with higher mortality, while HCV antibodies may be suggestive of “protection” against COVID-19.

Aims To evaluate the prevalence of clinical and ultrasonographic musculoskeletal involvement in Italian patients with inflammatory bowel disease (IBD). Methods In this cross-sectional multicenter study, 148 consecutive patients with IBD were evaluated by a gastroenterologist and a rheumatologist. All patients underwent a B-mode and power Doppler ultrasonographic examination of 6 pairs of entheses and of knee and ankle joints. Results A positive history for at least one musculoskeletal manifestation was reported by 40.5% of patients, more frequently in ulcerative colitis (UC) (p = 0.033). Inflammatory back pain was reported by 13.5% of patients, and a past history of peripheral arthritis by 14.9%, entheseal inflammation by 14.2% and dactylitis by 2.7%. At clinical examination, arthritis was observed in 19.6% of patients and enthesitis in 33%. Oligoarthritis and enthesitis at clinical examination were more frequently observed in UC than in Crohn disease (CD). 37.8% of total IBD patients fulfilled ASAS classification criteria for axial and/or peripheral spondyloarthritis, 8.1% ASAS classification criteria for axial spondyloarthritis, and 29.7% ASAS classification criteria for peripheral spondyloarthritis. With ultrasonographic examination, signs of entheseal involvement were observed in 87.8% of patients, while at power Doppler, ≥1 abnormality was observed in 27.1%. ASAS+ patients compared to those ASAS- had a significantly higher frequency at ultrasonography of acute entheseal abnormalities, power Doppler entheseal positivity and joint involvement. These abnormalities at ultrasonography were also observed in 34%, 13% and 12% of ASAS- patients. Conclusions Musculoskeletal manifestations occur frequently in patients with IBD. Ultrasonographic entheseal and joint involvement were also observed in asymptomatic patients.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P&nbsp

Graphical abstract, Introduction Hepatitis D Virus (HDV) infection is vanishing in Italy. It is therefore believed that hepatitis D is no longer a medical problem in the domestic population of the country but remains of concern only in migrants from HDV-endemic areas. Objectives To report the clinical features and the medical impact of the residual domestic HDV infections in Italy. Methods From 2010 to 2019, one hundred ninety-three first-time patients with chronic HDV liver disease attended gastroenterology units in Torino and San Giovanni Rotondo (Apulia); 121 were native Italians and 72 were immigrants born abroad. For this study, we considered the 121 native Italians in order to determine their clinical features and the impact of HDV disease in liver transplant programs. Results At the last observation the median age of the 121 native Italians was 58 years. At the end of the follow-up, the median liver stiffness was 12.0 kPa (95% CI 11.2–17.4), 86 patients (71.1%) had a diagnosis of cirrhosis; 80 patients (66.1%) remained HDV viremic. The ratio of HDV to total HBsAg transplants varied from 38.5% (139/361) in 2000–2009 to 50.2% (130/259) in 2010–2019, indicating a disproportionate role of hepatitis D in liver transplants compared to the minor prevalence of HDV infections in the current scenario of HBsAg-positive liver disorders in Italy. Conclusion Though HDV is vanishing in Italy, a legacy of ageing native-Italian patients with advanced HDV liver disease still represents an important medical issue and maintains an impact on liver transplantation.

Background En bloc pediatric kidney (EBPK) allografts represent one potential solution to increase the number of organs available in the donor pool, thus facilitating transplantation of kidneys from young donors into adult recipients. However, EBPK transplantation has been traditionally considered suboptimal because of concerns for perioperative complications. Methods An extensive reconstruction and successful transplantation of an EBPK allograft using same pediatric donor vascular grafts and a bladder patch aiming to avoid postoperative complications is presented in this report. Results The warm ischemia time was 25 minutes. No surgical drainage or ureteral stent were used. Postoperative Doppler ultrasound showed laminar blood flow and normal parameters in both the external iliac and graft arteries, no collections, and no signs of obstructive uropathy. The patient had an uneventful recovery showing a creatinine level of 0.86 mg/dL and 0.85 mg/dL at 1 month and 3 months, respectively. Conclusions A refined back-table reconstruction of these allografts is crucial to avoid mishaps in the postoperative period.

Summary Background Despite guidelines describing the optimal diagnostic and therapeutic procedures for patients with suspected cardiac implantable electronic device (CIED) infections, their management is often challenging. Aims To describe our diagnostic and therapeutic practices for suspected CIED infection, and to compare them with European Heart Rhythm Association (EHRA) guidelines. Methods Patients hospitalized in the tertiary care Nancy University Hospital for suspected CIED infection from 2014 to 2019 were included retrospectively. We applied the EHRA classification of CIED infection, and compared diagnostic and therapeutic management with the EHRA guidelines. Results Among 184 patients (mean age 72.3 ± 12.4 years), 137 had a proven infection of the lead (by transthoracic echocardiography/transoesophageal echocardiography, 18F-fluorodesoxyglucose positron emission tomography/computed tomography or positive culture of the lead) or an isolated pocket infection without proof of lead infection, and 47 had no proof of CIED infection. According to the EHRA classification, CIED infection was considered as definite in 145 patients and possible in 31 and was excluded in eight patients. Regarding recommended diagnostic procedures, blood cultures were performed in 90.8%, transthoracic echocardiography in 97.8%, transoesophageal echocardiography in 85.9%, 18F-fluorodesoxyglucose positron emission tomography/computed tomography in 50.5% and imaging for embolisms in 78.3% of the patients. Compared with therapeutic recommendations for the 145 cases of definite CIED infection, device removal was performed in 96 patients (66.2%) and antibiotic therapy was prescribed in 130 (89.7%), with a duration equal to or longer than that recommended in 105 (72.4%) of the patients. Conclusion This study underlines the difficulties in following theoretical guidelines in daily practice, where both technical and human considerations interfere with their strict appliance.

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

Resumen Introduccion y objetivos El trasplante renal se asocia a un mayor riesgo de cancer de vejiga; sin embargo, no existen directrices sobre el tratamiento del cancer de vejiga tras el trasplante renal. Materiales y metodos Se realizo una revision sistematica de la literatura utilizando PubMed y siguiendo las directrices PRISMA para identificar estudios relacionados con la prevalencia y la supervivencia del cancer de vejiga despues del trasplante de rinon. Tambien se revisaron y discutieron los factores de riesgo y el tratamiento de la enfermedad en este contexto. Resultados Se identificaron un total de 41 estudios publicados entre 1996 y 2018, que incluian datos primarios sobre el cancer de vejiga despues del trasplante de rinon. Se observo una marcada heterogeneidad en terminos de la prevalencia del cancer vesical, el tiempo hasta el diagnostico, la prevalencia del cancer vesical no musculoinvasivo/musculoinvasivo, y la supervivencia. Se identificaron 4 estudios, publicados entre 2003 y 2017, que incluian datos primarios sobre el cancer de vejiga tratado con el bacilo de Calmette-Guerin (BCG) despues del trasplante de rinon. La supervivencia libre de enfermedad, la supervivencia especifica del cancer y la supervivencia global, fueron similares entre los estudios de BCG (75-100%). Conclusiones La exposicion a carcinogenos causante de ERET, VBK y VPH, los agentes inmunosupresores y el estado de inmunosupresion probablemente contribuyen a un mayor riesgo de cancer de vejiga despues del trasplante renal. La enfermedad no musculoinvasiva debe tratarse con reseccion transuretral. La BCG puede utilizarse con seguridad en los receptores de trasplante y probablemente mejore la evolucion de la enfermedad. La enfermedad musculo invasiva debe ser tratada con cistectomia radical, tomando en especial consideracion la diseccion y la eleccion de la derivacion urinaria. La quimioterapia y los inhibidores de puntos de control inmunitario pueden utilizarse de forma segura y con un beneficio potencial en los casos de cancer de vejiga con diseminacion regional. Los inhibidores de mTOR pueden disminuir el riesgo de desarrollar cancer de vejiga, y los medicamentos inmunosupresores se deben reducir en caso de desarrollo de una neoplasia.

Background HCV‐related extra‐hepatic complications include peripheral neuropathies, with important prevalence and impact. A recent metanalysis of previous intervention trials concluded for insufficient data to support evidence‐based treatments for this complication. In this longitudinal study, we assessed for the first time prevalence and outcome of neuropathy in a cohort of patients with chronic HCV, before and after direct‐acting antiviral agent (DAA) treatment. Method Ninety‐four patients (mean age 58.5 ± 9.9, infection duration 22.2 ± 6.3 years) without systemic and metabolic diseases, underwent neurological examination and electroneurography studies before (T0) and 10.4 ± 1.7 months after the end of DAA therapy (T1), and cryoglobulins (CG) assessment. Muscle strength was evaluated by Medical Research Council (MRC) score; neuropathic pain, sensory function, disability, quality of life were assessed by validated questionnaires (DN4, NPSI, SSS, INCAT and Euro‐QoL). Results At T0, sensory‐motor neuropathy was detected in 22 patients (23%), reflexes were depressed in 32 (34%) with no association with infection duration, viral load, age, CG. Neuropathic pain (DN4 ≥4) was present in 37 patients (39%). At T1, out of the 22 patients with altered electroneurography, 3 had died or developed HCC, 4 showed normal electroneurography, and nerve amplitude parameters tended to improve in the whole group. Only 11 patients (12%) had depressed reflexes and 10 (11%) DN4 ≥4 (P

Working with a post-secondary student with intellectual disability, an adapted alternating treatments design was used to compare sight-word acquisition across three computer-delivered learning trial interventions: one with fixed 5-s response intervals, another with fixed 1-s response intervals, and a third with self-determined intervals. Visual analysis of session-series graphs suggest that all three interventions increased sight-word acquisition with the 5-s and self-determined interventions causing more steady and consistent learning per session than the 1-s intervention. Analysis of the time-series graph suggests that the self-determined intervention caused superior learning rates to the other interventions. From an applied perspective, the self-determined intervention is the most appropriate remedial procedure for this student because it resulted in the most rapid learning. Discussion focuses on the value of making relative-effectiveness decisions based on measures of learning as a function of time spent learning (learning speed) versus measures of learning as a function of sessions or trials.

In the popular imaginary, cocoa-derived products, like chocolate, represent a panacea for mood and affectivity. However, whether this is a myth or a fact has yet to be clarified. A systematic review and meta-analysis were conducted according to the PRISMA guidelines to investigate the effect of cocoa-derived food on depressive and anxiety symptoms, positive and negative affect. We searched Web of Knowledge

Background Two-dimensional fluoroscopy-guided percutaneous pedicle screw placement is currently the most widely applied instrumentation for minimally invasive treatment of spinal injuries requiring stabilization. Although this technique has advantages over open instrumentation, it also presents new challenges and specific complications. The objective of this study was to provide recommendations developed from the experience of several spinal surgeons at different minimally invasive spine surgery reference centers to solve specific problems and prevent complications during the learning curve of this technique. Methods An AO Spine Latin America minimally invasive spine surgery study group analyzed the most frequent complications and challenges occurring during the placement of >14,000 two-dimensional fluoroscopy–guided percutaneous pedicle screws at different centers over 15 years. Twenty tips considered most relevant to performing this technique, excluding problems directly related to specific brands of instruments, were presented. Results The 20 tips included the following: (1) positioning; (2) clean and painless; (3) fewer x-rays; (4) check the clock; (5) beveled tip; (6) transverse-rib-pedicle; (7) double Jamshidi; (8) hammer the Kirschner wire; (9) bent tip; (10) too loose, too tight; (11) new trajectory; (12) manual control; (13) start over; (14) Kirschner wire first; (15) adhesive drape control; (16) bend the rod; (17) lower rods; (18) freehand inner; (19) posterior fusion; (20) revision. Conclusions Implementation of these tips might improve performance of this technique and reduce the complications related to percutaneous pedicle screw placement.

Diagnosis and treatment of renal cell carcinoma with venous tumor thrombosis remains a challenge today, requiring multidisciplinary teams, mainly in tumor thrombus levels III-IV. Our objective is to present the various diagnostic techniques used and its controversies. A review of the most relevant related articles between January 2000 and August 2020 has been carried out in PubMed, EMBASE and Scielo. Continuous technological development has allowed progress in its detection, in the approximation of the histological subtype, and in the determination of tumor thrombus level. Regardless of the imaging technique used for its diagnosis (CT, MRI, TEE, ultrasound with contrast), the time elapsed until treatment is vitally important to reduce the risk of complications, some of them fatal, such as pulmonary thromboembolism.

Resumen El diagnostico y tratamiento del carcinoma de celulas renales asociado con trombosis venosa tumoral sigue suponiendo un reto en la actualidad, requiriendo de equipos multidisciplinares, fundamentalmente en niveles del trombo III y IV. Nuestro objetivo es la exposicion de las distintas tecnicas diagnosticas empleadas y de las controversias asociadas. Para ello se ha llevado a cabo una revision de los articulos relacionados mas relevantes entre enero del 2000 y agosto de 2020 en PubMed, EMBASE y Scielo. El continuo desarrollo tecnologico, ha permitido avanzar en su deteccion, en la aproximacion del subtipo histologico y en la determinacion del nivel del trombo tumoral. Independientemente de la tecnica de imagen utilizada para su diagnostico (TC, RMN, ETE, ecografia con contraste), es de vital importancia el tiempo transcurrido hasta su tratamiento con el fin de disminuir el riesgo de complicaciones, algunas de ellas fatales como la tromboembolia pulmonar.

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM To identify risk factors associated with delayed graft function (DGF). METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

Background and Aims The MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. Patients and Methods Achievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naive and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity and Activity Impairment) were also evaluated. Results The SVR12 rate was 99.4% (319/321; 95% CI: 97.8–99.8%) in the core population with sufficient follow-up (n = 321), 99.7% (289/290) in 8-week treated patients, and high (>96%) across subgroups. Only three patients (0.9%) had treatment-related adverse events that led to treatment discontinuation. In total, 30.1% of patients showed an improvement of ≥2.5 points in the Physical Component Summary of the SF-36 from baseline to the end of treatment, and this figure raised to 37.5% with the achievement of SVR12. Corresponding values for MCS were 42.2% and 42.8%, respectively. Conclusion Glecaprevir/pibrentasvir is safe and effective across subpopulations who are underserved in clinical trials.

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N=91/15) and glecaprevir (G)/pibrentasvir (P) (N=9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D±RBV (Paritaprevir/r+Ombitasvir+Dasabuvir, N=15), SOF+Simeprevir (SIM) (N=1) or SOF/Ledipasvir (LDV)±RBV (N=4). RAS prevalence was 15.8% in DAA-naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF-failures. In NS5A-failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA-naïve, P&nbsp

OBJECTIVE To describe a series of 3 cases of renal cell carcinoma that developed a metachronic recurrence in the form of inferior vena cava tumor thrombus after a first attempt of curative intent by means of radical nephrectomy. METHODS A complete work-up consisting of total body computed tomography and transesophagic echocardiography was performed in all cases. After extensive counseling a decision for surgical excision was made. We used a transplant-based approach to eliminate every vestige of visible neoplastic tissue including the tumor thrombus in all cases. Three different approaches, including tangential and circumferencial excision of the inferior vena cava with or without caval replacement by prosthetic vascular graft were used for caval management after thrombectomy. RESULTS Estimated blood loss ranged between 500 and 2000 cc. Transfusion requirements varied from 1-9 red blood cell packed units. Complete thrombectomy along with excision of all visible neoplastic lesions was achieved in all cases. One of the patients experimented a cardiac arrest on postoperative day 7 without fatal consequences that increased de length of stay (range 7-30 days). No other major complications were registered. None of the patients died in the first 30 days after the procedure. CONCLUSION The transplant-based surgical approach to thrombectomy in these cases provides for excellent exposure and vascular control, thus minimizing the complication rate and resulting a safe treatment option for the patient.

Renal cell carcinoma is no longer considered a monolithic disease, but a group of different entities exhibiting unique molecular alterations requiring a tailored systemic approach. One of the remaining challenges is the identification of the best candidate for a particular therapeutic regimen.: Current literature regarding the recent advances and treatment options in systemic therapy for metastatic RCC, and issues pertaining to the available biomarkers tested to date for a correct treatment stratification.: Underlying biology of RCC will still drive the development of new treatment agents/combinations that will be tested in earlier stages of the disease, and probably prove to have a role in the neoadjuvant/adjuvant settings. The correct characterization of the tumor microenvironment through transcriptomic analysis should help to overcome the issues related to tumor heterogeneity. Preclinical ex-vivo models will enlarge our current knowledge regarding the potential immune-escape mechanisms exhibited by RCC, and facilitate a better monitoring of the response to therapy. New tracers, image modalities, and tests aimed at detecting and analyzing tumor-circulating cells will improve our clinical performance through a better identification of the metastatic site locations and their variable histologic patterns, and ultimately their behavior in response to treatment.

BackgroundEpidermolysis bullosa (EB) comprises a heterogeneous group of rare genetic diseases associated with skin blistering caused by minimal trauma. A major and common EB subtype, recessive dystrophic EB (RDEB), is characterized by altered wound healing, inflammatory dysbalance and fibrotic changes associated with reduced to absent collagen VII. Because of its exposed position and its continued use in daily activities, the hand is constantly at risk of microtrauma and is therefore one of the organs most affected by the disease with highly disabling deformities that represent a challenging field in hand surgery practice.MethodsThe authors present their experience in the microsurgical treatment of pseudosyndactylies comparing the classic dressing with vaseline gauze with an innovative “glove protocol” using Integra®dermal regeneration template. The endpoints analyzed were: healing times, hospital stay time, discomfort for the patient, free-recurrence interval, follow-up range and major complications.ResultsA total of 34 procedures were performed on 24 RDEB patients with hand deformities. Compared with the dressing with vaseline gauze, microsurgery followed by application of dermal regeneration template gloves allowed a significant reduction of hospital stay, healing time, and dressing pain as well as an increased recurrence-free interval.ConclusionsThe microsurgical approach followed by our new protocol described in the study has been beneficial in providing consistent and successful long-term results for these patients.

Background Transplantation of kidneys with vascular anatomical variants remains a challenge. Due to its varying success in regard to graft function after transplantation, these organs have been frequently discarded assuming in advance an unaffordable rate of vascular complications. Patients and methods We performed three kidney transplants using organs from deceased donors harboring vascular variants (multiple arteries and short veins), including an unsplittable horseshoe kidney. Different grafts harvested from the same donor aorta, common iliac artery, and inferior vena cava, were used to reconstruct the initial vascular configuration by creating single arterial and venous conduits aimed to simplify the vascular anastomoses in the recipient. Results No post-operative complications were recorded. Warm ischemia times remained comparable to single artery renal allografts. No delayed graft function was noted in any case, and every patient regained normal renal function after transplantation. Conclusions Vascular reconstruction using arterial and venous grafts harvested from the same deceased donor may result a helpful tool to simplify vascular anastomoses during transplantation surgery, thus avoiding their discard in advance, minimizing perioperative complications, and enabling normal graft function rates in the long-term follow-up. The successful outcome obtained by using this approach would help to expand the donor criteria for the inclusion of organs containing vascular anatomical variants.

Resumen Antecedentes El trasplante renal con variantes anatomicas vasculares sigue siendo un desafio. Debido a su exito variable en lo que respecta a la funcion del injerto despues del trasplante, estos organos se descartan frecuentemente, asumiendo de antemano una tasa inasequible de complicaciones vasculares. Pacientes y metodos Realizamos 3 trasplantes de rinon utilizando organos de donantes fallecidos que presentaban variantes vasculares (arterias multiples y venas cortas), incluyendo un rinon en herradura indivisible. Se utilizaron diferentes injertos extraidos de la aorta, la arteria iliaca comun y la vena cava inferior del mismo donante para reconstruir la configuracion vascular inicial mediante la creacion de conductos arteriales y venosos individuales, con el fin de simplificar la anastomosis vascular en el receptor. Resultados No se registraron complicaciones postoperatorias. Los tiempos de isquemia caliente fueron comparables con los de aloinjertos renales de una sola arteria. En ningun caso se observo un retraso en la funcion del injerto y todos los pacientes recuperaron la funcion renal normal despues del trasplante. Conclusiones La reconstruccion vascular mediante injertos arteriales y venosos del mismo donante fallecido puede ser un recurso util para simplificar la anastomosis vascular durante la cirugia de trasplante, evitando asi su descarte de antemano, reduciendo al minimo las complicaciones perioperatorias y permitiendo tasas normales de funcion de los injertos en el seguimiento a largo plazo. El resultado satisfactorio obtenido mediante la utilizacion de este enfoque ayudaria a ampliar los criterios de donantes para incluir organos que presentan variantes anatomicas vasculares.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammation of axial joints and the pelvis. It is known that intestinal dysbiosis may exert direct pathogenic effects on gut homeostasis and may act as a triggering factor for the host innate immune system to activate and cause inflammation in extraintestinal sites in the so-called “gut-joint axis”, contributing to AS pathogenesis. However, although the intestinal microbiota’s influence on the clinical manifestation of AS is widely accepted, the mechanisms mediating the cross-talk between the intestinal lumen and the immune system are still not completely defined. Recent evidence suggests that the metabolism of microbial species may be a source of metabolites and small molecules participating in the complex network existing between bacteria and host cells. These findings may give inputs for further research of novel pharmacological targets and pave the way to applying dietary interventions to prevent the onset and ameliorate the clinical presentation of the disease. In this review, we discuss the role of some of the biological mediators of microbial origin, with a particular focus on short-chain fatty acids, tryptophan and vitamin B derivatives, and their role in barrier integrity and type 3 immunity in the context of AS.

BackgroundLimited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI).AimsTo compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI.MethodsRetrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting.Results'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments.ConclusionsOverall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

We have evaluated flu vaccine coverage and variables associated with the lack of vaccination in cirrhotic subjects with particular attention to the cirrhosis etiology. Cirrhotic subjects consecutively referring to eight Italian centers were prospectively enrolled for a 6-month period in 2019. Subjects were asked if they had received a flu vaccine in the last 12 months. Multiple logistic regression analysis was performed to identify independent predictors of lack of vaccination. A total of 818 cases were recruited. The overall vaccine coverage was 39.6% (26.9% in those younger than 65 years and 51.9% in those older than 64 years; p < 0.001). Age < 65 years (odds ratio [OR] = 2.38; 95% confidence interval [CI] = 1.68–3.36), alcoholic etiology (OR = 2.40; 95% CI = 1.49–3.85), birth abroad (OR = 2.7; 95% CI = 1.10–6.61), and residence in South/Sardinia island (OR = 1.66; 95% CI = 1.14–2.42) all resulted independent predictors of the likelihood of lack of vaccination. The lack of information regarding the vaccine as the reason for no vaccination was reported by 71.4% of foreigners and by 34.7% of natives (p < 0.001). In conclusion, much work still should be done to improve coverage among groups at higher risk of lack of vaccination identified in this survey. The ongoing SARS-CoV-2 pandemic may represent one more alert for improving seasonal flu vaccine coverage to avoid further stress to the National Health System.

The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25–5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02–2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9–4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Context: Though palliative sedation has been recognized as an acceptable practice in Canada for many years now, there is a lack of clinical research and guidelines pertaining to its use as a treatment of existential refractory symptoms in the terminally ill. Objectives: This scoping review aimed to survey the literature surrounding palliative sedation and existential suffering and to inform research, policy, and practice. Methods: To address the main research question: Is palliative sedation an acceptable intervention to treat existential refractory symptoms in adults aged 65 and older? a scoping review following Arksey and O’Malley’s framework was performed, spanning electronic databases of the peer reviewed and grey literature. Articles were screened for inclusion, and a thematic content analysis allowed for a summary of key findings. Results: Out of 427 search results, 71 full text articles were obtained, 20 of which were included. Out of these articles, four themes were identified as key findings. These included: (1) Ethical considerations; (2) The role of the health care provider; looking specifically at the impact on nurses; (3) The need for multidisciplinary care teams; and (4) Existential suffering’s connection to religiosity and spirituality. Conclusion: Palliative sedation to treat existential refractory symptoms was labelled a controversial practice. A shortage of evidence-based resources limits the current literature’s ability to inform policy and clinical practice. There is a need for both qualitative and quantitative multi-center research so health care professionals and regional-level institutions have firm roots to establish proper policy and practice.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Since the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic outbreak, vaccines gained a growing role. Possible vaccine-related side effects range from minor local events to more prominent systemic manifestations up to anaphylactic reactions. A heterogeneous spectrum of cutaneous reactions has been reported, ranging from local injection site reactions to urticarial and morbilliform eruptions, pernio/chilblains and zoster flares. Here, we describe a case of varicella zoster virus reactivation following mRNA coronavirus 2019 vaccine and discuss the available literature upon the topic published so far.

Background Despite guidelines describing the optimal diagnostic and therapeutic procedures of patients with suspected infection of cardiac implantable electronic device (CIED), the management of such patients is often challenging. Purpose The aim of this study was to describe our diagnostic and therapeutic practices for suspected CIED infection and to compare them to European Heart Rhythm Association (EHRA) guidelines. Methods Patients hospitalized in our tertiary care hospital for suspected CIED infection from 2014 to 2019 were retrospectively included. We applied the EHRA classification and compared diagnostic and therapeutic management to EHRA guidelines. Results Among 184 patients (mean age 72.3±12.4 years), 137 had a proven infection of the lead (either by TTE/TEE, by [18F]FDG PET/CT, or by positive culture of the lead) or an isolated pocket infection without proof of lead infection and 47 had no proof of infection of CIED. According to EHRA classification, CIED infection was considered as definite in 145 patients, possible in 31 and excluded in 8. Regarding recommended diagnostic procedures, blood cultures were performed in 90.8%, TTE in 97.8%, TEE in 85.9%, [18F]FDG PET/CT in 50.5% and imaging for embolisms in 78.3% of the patients. Compared to therapeutic recommendations for the 145 cases of definite CIED infection, device removal was performed in 96 patients (66.2%), antibiotic therapy was prescribed in 130 (89.7%), with a duration equal or superior to the one recommended in 105 (72.4%) of the patients. One-year survival rate was 66.3% and was better in patients with device removal than in patients without, both in the whole population (respectively 77.7% and 48.6%) and in the patients with definite CIED infection (80.0% vs 49.0%). After adjustement on age and Charlson's score, patients without device removal had a significantly higher risk of 1-year mortality (HR=3.40 [1.84–6.26], p=0.0001). Conclusion Suspicion of CIED infection are difficult situations. The use of theoretical classification helps to define the different types of cases and the resultant therapeutic approach. In daily practice, our study shows that the strict adherence to these guidelines is not always possible. This study shows a relatively good use of diagnostic procedures. However, theoretical advice for medical therapy and removal procedures are not always properly followed. To improve patients' prognosis, infected device removal must be systematically discussed in multidisciplinary endocarditis team, weighing the benefit-risk ratio of the strict appliance of the guidelines. Funding Acknowledgement Type of funding sources: None. Diagnostic comparisonTherapeutic comparison

A novel Gram-negative pathogenic bacterium was discovered in second-stage juveniles (J2) of root-knot nematodes (Meloidogyne spp.). Mature bacteria showed a peculiar rod morphology characterized by four cells sequentially joined at septa. Mature rods measured 4–5 0.5–0.6 um, characterized by the emptying and tapering of both apical cells. Transmission electron microscopy data showed an electron-dense external matrix forming a coating capsule involved in host attachment. The rods were not motile and packed in parallel inside the J2 body. After host penetration by adhering, germinating cells, the bacterium proliferated until the body content was completely digested, producing a lethal disease. Parasitized hosts could be recognized using light microscopy by a pale creamy-brown color assumed at parasitism completion. At death, the whole nematode body was filled with cells and only a few sclerotized esophageal structures (i.e., stylet, median bulb) remained visible. The bacterium cells were quickly released at host body rupture, suggesting that J2 infection occurs through passive adhesion of cells dispersed in soil. The bacterium appeared fastidious, as attempts to obtain pure cultures on common nutritive media failed.

Atherosclerosis is common in patients with end-stage renal disease. Severe calcification of the iliac vessels is expected in the growing pool of kidney transplant candidates. Thus, transplant surgeons must constantly develop alternative operative strategies to deal with the technical challenges that this condition confers. This case report aims to highlight a reconstructive vascular technique to salvage a completely calcified recipient external iliac artery using a deceased donor's arterial iliac allograft from the same donor as the renal allograft in a 59-year-old man, as an effective method to decrease vascular complications. Keywords: Kidney transplantation, Vascular complications, Surgical technique, Arterial allograft, Arterial reconstruction, Atherosclerosis

Background Renal cell carcinoma (RCC) with tumor thrombus extending into the inferior vena cava (IVC) occurs in 4%-10% of cases. Within this subset, pulmonary tumor embolism (PTE) appears in approximately 0.9%-2.4% of cases. We wanted to review our experience in managing patients with RCC with IVC involvement and a preoperative diagnosis of PTE. Methods A total of seven patients presented at our center between January, 2005 and January, 2015 with RCC, IVC involvement, and PTE (diagnosed either by chest computerized tomography angiography or preoperative transesophageal echocardiogram). Each patient underwent a radical nephrectomy and tumor thrombectomy using an organ transplant-based approach. Results Surgical removal of the PTE was performed in three patients (tumor embolectomy in two cases, right lower lobe resection in one case); the PTEs in four patients were considered to be too small to undergo surgical resection. PTE pathology found neoplastic cells in each patient that had surgical removal. No postoperative complications were observed in any of the seven patients. All four patients who were metastasis-free preoperatively (with 2/4 having tumor embolectomy performed) developed distant metastasis; median time-to-developing metastatic disease was 6.5 months. With a median follow-up of 19 months, three deaths because the disease have occurred. Conclusion Although RCC with IVC tumor thrombus complicated by PTE may not be catastrophic in most cases, it appears to be associated with an increased risk of developing metastatic disease. In addition, as the PTEs appear to contain neoplastic cells, pulmonary artery embolectomy at the time of nephrectomy should be performed whenever possible.

Distal finger injuries are very common in Hand Surgery. The purpose of this paper is to describe our “Extreme Atasoy flap” technique in the reconstruction of apical lesions of the fingers. Twenty patients were treated with the “Extreme Atasoy flap” technique. The following variables were evaluated: age, sex, comorbidity, cause of amputation, Visual Analogue Scale for pain assessment to time 0 (VAS T0), VAS to time 30 days (VAS T30), hospitalization time (HT), time to heal (TH), major complications (MC), minor complications (mC), advancement flap (AF), and static 2-point discrimination test to assess sensitivity. In our case series, no major complications were present. The average healing time was 2.4 days, and the 2-point discrimination test regarding sensitivity was satisfactory. The patients reported good aesthetic and functional outcomes. Treatment of fingertip injuries is an important topic in Hand Surgery. Local flaps are common forms of treatment in these kinds of injuries. The surgical technique is similar to that described by Atasoy, but with some important differences: the preoperative design is different, the donor site is not closed with stitches but heals by secondary intention, and the vascular pedicles are extremely skeletonized. This technique has proven to be safe and simple to carry out and provides good coverage of the distal portions of the fingers. Level of Evidence: Level V, therapeutic study