Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients [Formula: see text] 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients. A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit. A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively. Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52. This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.

This study underscores the pressing need for unified recommendations to improve nutritional care and potentially enhance outcomes for pediatric cancer patients. • The assessment and support of nutrition are gaining interest in the overall care of children with cancer. • The assessment and management of nutritional needs in pediatric cancer patients, including those undergoing hematopoietic cell transplantation, currently lack a systematic approach. • There is considerable variability in the nutritional assessment and support among Italian centers treating pediatric patients with cancer. • To enhance nutritional assessment and support for pediatric cancer patients, it is essential to establish shared national and international guidelines.

Abstract Background: Three-dimensional (3D) printing technology has impacted many clinical applications across medicine. However, 3D printing for Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) has not yet been reported in the peer-reviewed literature. The current observational cohort study aimed to evaluate the impact of half scaled (50% scale) 3DP anatomic models in the pre-procedural planning of MIDCAB. Methods: Retrospective analysis included 12 patients who underwent MIDCAB using 50% scale 3DP between March and July 2020 (10 males, 2 females). Distances measured from CT scans and 3DP anatomic models were correlated with Operating Room (OR) measurements. The measurements were compared statistically using Tukey’s test. The correspondence between the predicted (3DP &amp; CT) and observed best InterCostal Space (ICS) in the OR was recorded. Likert surveys from the 3D printing registry were provided to the surgeon to assess the utility of the model. The OR time saved by planning the procedure using 3D printed anatomic models was estimated. Results: All 12 patients were successfully grafted. The 3DP model predicted the optimal ICS in all cases (100%). The distances measured on the 3DP model corresponded well to the distances measured in OR. The measurements were significantly different between the CT and 3DP (p &lt; 0.05) as well as CT and OR (p &lt; 0.05) groups, but not the 3DP and OR group. The Likert responses suggested high clinical utility of 3D printing. The mean estimated OR time saved was 40 minutes. Conclusion: The 50% scaled 3DP anatomic models demonstrated high utility for MIDCAB and saved OR time while being resource efficient. The subjective benefits over routine care that used 3D visualization for surgical planning warrants further investigation.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100µg every 2weeks for 2years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5years. During the first 2years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3years, and the probability of drug survival after a median of 3.15years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than threebloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6months post-diagnosis.

ABSTRACT Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a multifunctional protein with roles beyond biomarker status, influencing critical processes. This study aimed to assess dipstick test for NGAL (NGALds), a novel dipstick test, against the established laboratory-based NGAL (NGALlab) method for early peritonitis detection, focusing on peritoneal fluid analysis to provide a rapid and cost-effective diagnostic tool for peritonitis management. Methods: Conducted at San Bortolo Hospital, Italy, this retrospective study collected samples from suspected or confirmed peritonitis cases between May 1, 2021, and December 31, 2021. Samples included peritoneal dialysate effluents (PDE) and underwent white blood cell counts, NGALds, NGALlab, and effluent culture. Results: The study analyzed 27 peritonitis cases, involving 133 PDE samples from 22 patients. NGALds exhibited a strong correlation (Rs = 0.732, P &lt; 0.05) with NGALlab, particularly for medium to high-risk peritonitis cases, with a 98% accuracy rate. Conclusion: NGALds effectively aligns with NGALlab for peritonitis diagnosis, offering a valuable diagnostic tool, particularly suitable for point-of-care and resource-limited healthcare settings. Further research should investigate its correlation with neutrophil levels in PDE, solidifying NGALds as an accessible and efficient resource for peritonitis management.

ABSTRACT Introduction Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD. Similar results were reported in a phase 3 trial in adolescents (aged ≥12 years). Areas covered We review the role of IL-13 in AD and discuss the value of tralokinumab for treating moderate-to-severe AD, comparing efficacy and safety results derived from clinical trials and real-life data. Expert opinion The role of IL-13 in AD supports a targeted therapeutic approach. Tralokinumab has proven efficacious and well-tolerated in a large proportion of patients confirming its value for treating moderate-to-severe AD from age 12 years onwards; it quickly improves itching and can maintain a high-level of response over time; it can be administered with flexible dosing schedules. Future studies will further clarify the role of IL-13 pathway and which patients would be best suited to tralokinumab, shifting AD treatment into an era of precision medicine.

Introduction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), has led to a significant increase of morbidity worldwide. A recent meta-analysis showed a high case fatality rate in hospitalized patients with hematological malignancies and published reports indicated high rates also in chronic lymphocytic leukemia patients (CLL) patients. The aim of our study was to evaluate the impact of COVID-19 in CLL patients treated with venetoclax. Methods. The retrospective multicenter study included CLL patients treated since 2017 with venetoclax single agent until progression or toxicity or venetoclax plus anti-CD20 antibody (mainly rituximab as part of VR protocol for 24 months in relapsed/refractory patients or obinutuzumab as part of VO protocol for 12 months in untreated patients). Results. We found 128 infections from SARS-CoV-2 in 104 patients out of 287 patients with CLL who received venetoclax. Basal characteristics of the 104 patients who experienced COVID-19 were compared to those of the 183 patients who did not experience the infection (Table 1). Patients of the first group did not show more comorbidities in terms of CIRS, nor renal and pulmonary impairment. Unexpectedly patients without COVID-19 experienced more previous infections in the 12 months before the beginning of venetoclax but a similar low rate of previous SARS-CoV-2 infection. They received a median of 2 different previous lines of treatment whereas patients with COVID-19 were exposed to a median of a single line of therapy. No significant differences were noted for prophylaxis with immunoglobulin, antiviral and antibacterial drugs. In the group of COVID-19 a higher rate of patients received venetoclax plus anti-CD20 antibody (62.9% vs 38.5% of the group without COVID-19, p&amp;lt;0.001). The rate of vaccination was higher than 66% in both the groups with a median of 3 doses each. Prophylaxis with tixagevimab/cilgavimab was administered in less than 20% of the patients. Analyzing the characteristics of the 128 infections we distinguished 73 grade 1-2 COVID-19 and 55 grade 3-4 COVID-19. Patients with grade 1-2 COVID-19 were positive for a median time of 10 days (range 5-97). No treatment was administered in 29.1% of the cases, nirmatrelvir/ritonavir was used in 23.6%, remdesivir in 18.2%. Regarding patients with grade 3-4 COVID-19 resulted positive for a median time of 21 days (range 5-120). Remdesivir was chosen as treatment in 48.9%, nirmatrelvir/ritonavir in 21.3%. Univariate and multivariate analysis found that association to anti-CD20 was a risk factor for COVID-19 of any grade (OR 1.93) and of grade 3-4 (OR 2.96), conversely previous infection in the 12 months before the beginning of venetoclax was a protective factor for COVID-19 any grade (OR 0.42) and grade 1-2 (OR 0.32). During COVID-19 Venetoclax was withdrawn in 38 (36.5%) patients, in 32 of whom venetoclax was administered together to anti-CD20 antibody; in 25/38 the discontinuation was only temporary. Thirty-five (33.6%) patients required hospitalization due to COVID-19, the median time of recovery was 15 days, and 8 (7.7%) patients needed intensive care unit admission. Among the 104 patients with COVID-19, 18 patients died, 10 deaths were due to COVID-19: 7 were exposed to anti-CD20 antibody, 3 had a previous grade 1-2 COVID-19, but none experienced a SARS-CoV-2 infection before treatment with venetoclax. All were vaccinated with at least 3 doses except one patient who was not vaccinated but was infected and died in 2020. The rate of mortality due to COVID-19 was 9.6% considering patients who were infected by SARS-CoV-2, but 18.2% among patients with severe grade 3-4 COVID-19. Conclusions. This is a real-life study on 287 patients affected by CLL treated with venetoclax with the aim to describe COVID-19 in this cohort. The analysis found over a third of patients infected by SARS-CoV-2, in 57% of the cases the infection was grade 1-2 with a mortality rate of almost 10%, but higher if COVID-19 was of grade 3-4 (18.2%). We confirmed the association of anti-CD20 antibody to venetoclax as a risk factor for SARS-CoV-2 infection and mortality rate in patients with CLL and severe COVID-19.

Alessandro Mancini and Luca De Carolis are Co-first authors. Nicodemo Baffa, Brunangelo Falini and Enrico Tiacci are Co-last authors. INTRODUCTION HCL is an indolent BRAF-mutated leukemia usually presenting with cytopenias, splenomegaly, little or no lymphadenopathy, heavy bone marrow (BM) infiltration and few circulating leukemic cells. Imaging exams for staging include abdominal echography and computed tomography (CT), while the role of PET is largely unknown. METHODS 84 patients (pts) with relapsed/refractory HCL participating to our clinical trials of BRAF inhibitor-based therapies prospectively underwent PET/CT pre- and post-treatment, in addition to usual examinations for response assessment. Since FDG uptake is normally higher in liver than spleen, BM and lymph nodes, uptake in the latter tissues was considered abnormal if equal to or higher than the liver. Splenomegaly was defined by a longest spleen diameter &amp;gt;13 cm on PET/CT. The standard definition of complete remission (CR) in HCL just requires no palpable splenomegaly on physical examination, in addition to resolution of cytopenias as well as no hairy cells visible in the blood smear and the BM biopsy by non-immunological stains. RESULTS Pre-therapy, 58/77 (75%) non-splenectomized pts showed abnormal splenic FDG uptake (maximal standardized uptake value/SUVmax: median 4.8, vs 3.9 for the liver), which was always diffuse without focal lesions. Conversely, focal splenic uptake is not infrequent in splenic marginal zone lymphoma (18%, 7/39 pts - Abdom Radiol 2018;43:2721; vs of 0/58 HCL pts, p=0.0003), which may aid in the differential diagnosis with this HCL-mimicker. Moreover, 14/58 (24%) HCL pts. with a PET+ spleen did not have splenomegaly, and splenic uptake returned to normal in 10/11 evaluable cases (91%) achieving at least a partial response post-therapy, which suggests leukemic spleen involvement even without splenomegaly. Abnormal diffuse BM uptake was observed in 41/82 evaluable pts (50%; median SUVmax 5, vs 3.4 for the liver). In these cases, leukemic involvement in the BM biopsy was greater (median 80%) than in the other 41 pts (median 65%; p-value &amp;lt;0.01), pointing to HCL infiltration as the cause of abnormal BM uptake rather than to reactive hyperplasia of non-involved BM. Post-therapy, pathologic spleen uptake normalized in 46/51 evaluable pts (90%), and their CR rate was higher (32/46 pts, 70%) than in the other 5 pts remaining PET+ (1/5, 20%; p=0.047). Among the 46 PET- cases, 31 (67%) were not splenomegalic while 15 (33%) had residual splenomegaly (up to 17 cm; Fig. 1A); interestingly, within PET- cases relapse-free survival (RFS) was similar not only in conventionally defined CR cases with (n=8) vs without (n=24) residual non-palpable splenomegaly (p=0.84 after a median follow-up of 19 months), but also when the 6 cases meeting all conventional CR criteria except for still palpable splenomegaly were added to the 8 CR pts with residual non-palpable splenomegaly (p=0.7 after a median follow-up of 20.5 months - Fig. 1B). These findings suggest that metabolic status reflects splenic HCL involvement more reliably than spleen size or palpability, a concept that could improve the current definition of CR in HCL. Abnormal BM uptake resolved after treatment in 34/37 evaluable pts (92%), and their CR rate was again higher (23/34, 68%) than in the other 3 pts remaining PET+ (0/3; p=0.047). Leukemic infiltration of the BM biopsy was lower in the 34 PET- vs the 3 PET+ pts (median 5% vs 70%-80%, respectively; p=0.0004), indicating that BM abnormal uptake reflects HCL infiltration load rather than reactive BM hyperplasia post-therapy. Finally, abnormal lymph node uptake was observed pre-therapy in 9/84 (11%) pts (median SUVmax 7.1, vs 3.4 for the liver) and normalized after treatment in 7/8 evaluable pts (88%), including one case with residual lymph node enlargement (2.2 cm); all these 7 pts had achieved a CR while the remaining pt had no response to therapy. CONCLUSIONS PET is potentially useful in the differential diagnosis with splenic marginal zone lymphoma and may aid in the clinical management of HCL pts by detecting metabolic involvement of the main disease sites even in the absence of organomegaly. Importantly, PET signal tracks with response to therapy even in case of persistent organomegaly, which may lead to refine the definition of CR in HCL.