ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy.

INTRODUCTION: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. METHODS: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). RESULTS: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). CONCLUSIONS: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.

Ultra-High Frequency UltraSound (UHFUS) Assessment of Barrier Function in Moderate-to-Severe Atopic Dermatitis during Dupilumab Treatment.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient's reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

Assessment and Monitoring of Nail Psoriasis with Ultra-High Frequency Ultrasound: Preliminary Results.

Psoriatic onychopathy is one of the clinical presentations of psoriasis and a well-known risk factor for the development of psoriatic arthritis. High-frequency ultrasounds (HFUS > 20 MHz) have recently been used to evaluate the nail apparatus of healthy and psoriatic subjects. The aim of our study was to detect by means of ultra-high-frequency ultrasound (UHFUS 70-100 MHz) alterations of the nail bed and matrix in patients with psoriatic onychopathy and to monitor these parameters during the treatment with monoclonal antibody (mAb). We enrolled 10 patients with psoriatic onychopathy and naive to previous biologic therapies. Patients were evaluated at baseline, after 1 month and after 3 months from the beginning of mAb therapy by a complete clinical assessment and US evaluation. A UHFUS examination with a 70 MHz probe was performed on the thumbnail (I), the index fingernail (II) and the nail with greater clinical impairment (W). The following measurements were analyzed: nail plate thickness (A), nail bed thickness (B), nail insertion length (C), nail matrix length (D) and nail matrix thickness (E). Among the various parameters analyzed, some measures showed a statistically significant decrease with p-value < 0.05 (t0 WA = 0.52 mm vs. t2 WA = 0.42 mm; t0 WB = 2.8 mm vs. t2 WB = 2.4 mm; t0 WE = 0.76 mm vs. t2 WE = 0.64 mm; t0 IIA = 0.49 mm vs. t2 IIA = 0.39 mm). In conclusion, UHFUS could represent a viable imaging technique for the real-time evaluation and monitoring of psoriatic onychopathy, thus supporting the clinical parameters and revealing any subclinical signs of early drug response.

Relapsed/Refractory Chronic Lymphocytic Leukemia Patients Treated with Fixed Duration Venetoclax-Rituximab: Assessment of Response with Ultrasound, and Relationship with Minimal Residual Disease.

A fixed duration of venetoclax-rituximab (VenR) resulted in a significant benefit of both PFS and in the attainment of an undetectable minimal residual disease (uMRD) compared with bendamustine-rituximab in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients. The 2018 International Workshop on CLL guidelines, outside the context of clinical trials, suggested ultrasonography (US) as a possible imaging technique to evaluate visceral involvement, and palpation to evaluate superficial lymph nodes (SupLNs). In this real-life study we prospectively enrolled N = 22 patients. Patients were assessed by US, to determine nodal and splenic response in R/R CLL patients treated with a fixed duration VenR. We found an overall response rate, complete remission, partial remission, and stable disease, of 95.4%, 68%, 27.3%, and 4.5%, respectively. Responses were also correlated with risk categories. The time to response, and the time to clearance of the disease in the spleen, in abdominal LN (AbdLNs), and in SupLNs were discussed. Responses were independent from LN size. The correlation between response rate with MRD were also investigated. US allowed to detect a substantial CR rate correlated with uMRD.

A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy.

Background. In IWCLL guidelines, progressive splenomegaly and lymphadenopathy are signs of active disease. In this study, we have tested the hypotheses if US could be a reliable tool for both superficial lymphnodes (SupLNs) and splenic assessment in chronic lymphocytic leukemia (CLL) patients. Methods. We enrolled N = 75 patients. SupLN and the spleen were assessed by two independent physicians (M1 and M2) by palpation and by a third physician (M3) with ultrasound sonography (US) using two different sonographers (US1 and US2). The results of M1 vs. M2 assessment, US1 vs. US2, palpation vs. US were compared. The echostructure of N = 1037 SupLN and of the spleen was also investigated. Results. The dimensions of SupLNs assessed by MD1 vs. MD2 were statistically discordant. Splenic size was concordant. There was concordance between US1 and US2 SupLN and splenic assessment. US found a higher number of pathological SupLN (Cohen's Kappa < 0.1) than palpation, which misses remarkable-sized SupLNs. LN echostructure and splenic involvement patterns were described. Conclusions. US is a reliable, radiation-free tool useful in clinical practice to assess SupLN and splenic involvement in CLL.

Usefulness of MRI-based radiomic features for distinguishing Warthin tumor from pleomorphic adenoma: performance assessment using T2-weighted and post-contrast T1-weighted MR images.

Purpose: Differentiating Warthin tumor (WT) from pleomorphic adenoma (PA) is of primary importance due to differences in patient management, treatment and outcome. We sought to evaluate the performance of MRI-based radiomic features in discriminating PA from WT in the preoperative setting. Methods: We retrospectively evaluated 81 parotid gland lesions (48 PA and 33 WT) on T2-weighted (T2w) images and 52 of them on post-contrast fat-suppressed T1-weighted (pcfsT1w) images. All MRI examinations were carried out on a 1.5-Tesla MRI scanner, and images were segmented manually using the software ITK-SNAP (www.itk-snap.org). Results: The most discriminative feature on pcfsT1w images was GLCM_InverseVariance, yielding area under the curve (AUC), sensitivity and specificity of 0.9, 86 % and 87 %, respectively. Skewness was the feature extracted from T2w images with the highest specificity (88 %) in discriminating WT from PA. Conclusion: Radiomic analysis could be an important tool to improve diagnostic accuracy in differentiating PA from WT.

Local Management of Malignant and Unresectable Fungating Wounds: PEBO Assessment.

Malignant fungating wounds (MFWs) represent a major problem for public health. The most common symptoms associated with MFWs are pain, exudate, bleeding and odor. The aim of the study was to optimize the local management and dressing of MFWs. We developed a standardized 4- step approach to MFWs based on Pain, Exudate, Bleeding and Odor management in a case series of 24 patients: we call this the PEBO approach. We analyzed etiologies, localization, Quality of Life (QoL), pain and clinical signs and symptoms. We assessed the ulcers at baseline, after two weeks and after one month. In our study, most patients showed an improvement in the QoL using PEBO approach, although some experienced a deterioration in their general clinical conditions. Non-cytolesive cleansing, atraumatic dressings were applied to allow pain relief. Non-adherent dressings were combined with a secondary dressing in the case of exudate. Achieving hemostasis with dressing or medication is a priority in MFW management. Antibacterial dressings and odor absorbent dressings were used for odor absorption. Surgical debridement, adherent dressing and occlusive dressings were avoided. Dressing changes were programmed twice a week for four weeks. PEBO simplified the complex aspects of this type of ulcer, and could help physicians, nurses, and also the rest of the team, including the patients themselves and their family, in the multidisciplinary palliative care of MFWs.

Hand-assisted laparoscopic surgery versus endovascular repair in abdominal aortic aneurysm treatment.

OBJECTIVE: Hand-assisted laparoscopic surgery (HALS) for the treatment of abdominal aortic aneurysm (AAA) has shown promising initial results compared with traditional surgery, but its efficacy remains highly debated. The aim of this monocentric, retrospective study was to investigate differences in morbidity, mortality, and reintervention rates between endovascular aneurysm repair (EVAR) and HALS, in the medium- and long-term follow-up in a highly selected population. METHODS: We treated 977 patients consecutively for nonurgent AAA from January 2006 to December 2013; among them, 615 (62.9%) underwent open surgery, 173 (17.7%) HALS, and 189 (19.3%) EVAR. For this study, only patients treated with HALS or EVAR were considered. A subsequent selection process was carried out to identify the patients with clinical characteristics and aneurysm morphology amenable to either of these treatments. The final study cohort included 229 patients; 92 (40.2%) underwent HALS and 137 (69.8%) received EVAR. The two populations were homogeneous for clinical and demographic characteristics. RESULTS: The mean duration of follow-up was 57 ± 28 months (50 ± 24 months in the EVAR group and 67 ± 29 months in the HALS group; range, 2-110 months). No deaths and no statistically significant differences in severe complications or reinterventions were observed over the perioperative period (30 days). Length of stay was significantly shorter after EVAR, because the need for and length of stay in the intensive care unit were decreased. Three postoperative deaths (in-hospital mortality >30 days: HALS, 2.2%; EVAR, 0.7%; P = .7268) occurred owing to respiratory failure (two patients, one in each group) and multiorgan failure secondary to a bowel ischemia (one patient in the HALS group). Other deaths in the study population were not related to the procedure. In both groups, the major causes of death were cancer (24 cases [36.9%]), cardiovascular causes unrelated to AAA (16 [24.6%]), and chronic obstructive lung disease (10 [15.4%]). In the long-term follow-up period, there was a difference in the overall survival in favor of HALS when compared with EVAR (P = .011). CONCLUSIONS: This retrospective, single-center study shows that, within a population of similar clinical and anatomic characteristics, treatment of AAA with EVAR or HALS does not result in significant differences in early morbidity and mortality. EVAR presents significantly shorter hospital and intensive care unit length of stay, whereas HALS presents a lower aneurysm-related reintervention rate and lower perioperative cost. The strict patient selection in this trial, as is generally the case with AAA treatment, is likely the key to success for both of these techniques.

Multiple high-grade gliomas: epidemiology, management, and outcome. A systematic review and meta-analysis.

Multiple high-grade gliomas (M-HGGs) are well--separated tumors, differentiated as multifocal (MF) and multicentric (MC) by their MRI features. The authors performed a systematic review and meta-analysis of literature examining epidemiology, clinical and radiological characteristics, management, and the overall survival from M-HGGs. According to PRISMA guidelines, a comprehensive review of studies published between January 1990 and January 2017 was carried out. The authors identified studies that examined the prevalence rate, clinical and radiological characteristics, treatment, and overall survival from M-HGGs in patients with HGG. Data were analyzed using a random-effects meta-analysis model. Finally, we systematically reviewed demographic characteristics, lesion location, and surgical and adjuvant treatments. Twenty-three studies were included in this systematic review. The M-HGGs prevalence rate was 19% (95% CI 13-26%) and the hazard ratio of death from M-HGGs in the HGGs population was 1.71 (95% CI 1.49-1.95, p < 0.0001). The MC prevalence rate was 6% (CI 95% 4-10%), whereas MF prevalence rate was 11% (CI 95% 6-20%) (p < 0.0001). There were no statistically significant differences between MF and MC HGGs in gender, lesion location, histological type, and surgical treatment. Survival analysis of MC tumors showed that surgical resection (gross total resection or subtotal resection) is an independent predictor of improved outcome (HR 7.61 for biopsy subgroup, 95% CI 1.94-29.78, p = 0.004). The prevalence of M-HGGs is approximately 20% of HGGs. The clinical relevance of separating M-HGGs in MF and MC tumors remains questionable and its prognostic significance is unclear. When patient status and lesion characteristics make it safe and feasible, cytoreduction should be attempted in patients with M-HGGs because it improves overall survival.

Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: prevalence, risk of rupture, and management. A systematic review.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder associated with high incidences of intracranial aneurysms. We performed a systematic review with the purpose of clarifying the prevalence, risk of rupture, and appropriate management of intracranial aneurysms in the ADPKD population. METHOD: PRISMA guidelines were followed. We conducted a comprehensive literature search of three databases (PubMed, Ovid MEDLINE, and Ovid EMBASE) on all series reporting ADPKD patients with intracranial aneurysms. RESULTS: Our systematic review included 16 articles with a total of 563 patients with ADPKD and intracranial aneurysms. The prevalence of unruptured aneurysms was 11.5% (95% CI = 10.1-13%), whereas 1.9% (95% CI = 1.3-2.6%) of aneurysms were ruptured. Hypertension was present in 79.3% of patients with ADPKD and renal impairment in 65%. The mean size of ruptured aneurysms was slightly higher than unruptured (6 mm vs. 4.4 mm). The most common locations of unruptured and ruptured aneurysms were the ICA (40.5%) and MCA (45%), respectively. Asymptomatic patients studied with four-vessel angiography experienced 25% transient complications. Overall, 74% unruptured aneurysms were surgically treated with lower complication rates compared to endovascular treatment (11% vs. 27.7%). Among conservatively treated aneurysms, 2.9% ruptured at follow-up (rupture rate 0.4%/patient-year). Finally, the growth rate was 0.4% per patient-year, and the incidence of de novo aneurysm formation was 1.4% per patient-year. CONCLUSIONS: The prevalence of unruptured intracranial aneurysms in the ADPKD population is approximately 11%. Given the non-negligible rate of procedural complications, the management of these patients must be cautious and individualised. The rupture rate appears comparable to that of the general population. On the other hand, the 1.4% rate per patient-year of de novo aneurysms is non-negligible. These findings should be considered when counselling ADPKD patients regarding the appropriate management of intracranial aneurysms.

Surgical management of acute subdural haematomas in elderly: report of a single center experience.

OBJECTIVE: To evaluate the clinical outcome of patients over 70 years old who have received surgical treatment for traumatic acute subdural haematoma (aSDH) in our Neurosurgical Department. We also disclose related surgical and medical costs. METHODS: A retrospective analysis was performed by analyzing the medical records of patients older than 70 who had undergone surgery for evacuation of traumatic aSDH between June 2011 and December 2014. Through univariate and multivariate analyses, we correlated clinical and radiological pre-operatory features with outcome at one and six months after surgery. Overall costs for each patient were recorded. RESULTS: We observed 67 patients, 36 male and 31 female, with a median age of 80.5 years old (range 71-94). The mortality rate at one month and six months after surgery was respectively 55.1% and 67.2% while functional recovery was respectively 10.4% and 13.4%. Multivariate analysis age and Glasgow Coma Score (GCS) are the most significant parameters in relation to clinical outcome. Age greater than 90, shift midline >20 mm and volume of the haematoma >200 cu cm were independent parameters to predict mortality within 10 days of surgery. CONCLUSION: Our study confirms a poor outcome for patients of 70 years and over who received surgical treatment for traumatic aSDH.