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Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [ 18 F]FDG PET (PET) in follicular lymphoma patients., Methods: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS)., Results: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003)., Conclusion: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 10 6 PBSC/kg, 2.6% (n = 7) mobilized < 4 × 10 6 PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 10 6 /kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes., (© 2024. The Author(s).)

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background : The treatment of displaced intra-articular calcaneal fractures (DIACF) is debated. This study compares open reduction and internal fixation (ORIF) with minimally invasive osteosynthesis (MIOS). Methods : We conducted a retrospective study on 70 patients with DIACF treated between January 2018 and September 2022, divided into ORIF ( n = 50) and MIOS ( n = 20) groups. Functional outcomes were assessed using the Maryland Foot Score (MFS) and the Creighton-Nebraska Health Foundation Assessment Scale (CNHFAS). Radiographic outcomes, complication rates, and reintervention rates were evaluated. A chi-square analysis examined the correlation between Sanders classification and treatment choice. Results : The chi-square analysis indicated no significant correlation between the complexity of the fracture and the type of treatment chosen (χ 2 = 0.175, p = 0.916). Additionally, the Cochran-Armitage test for trend showed no significant trend in the choice of treatment based on fracture complexity (statistic = 0.048, p = 0.826). A Kaplan-Meier analysis showed a longer time to reintervention for MIOS ( p = 0.029). Complication rates were similar, with specific complications varying between groups. Quality-of-life outcomes were comparable. Conclusions : ORIF is preferable for high-demand patients due to better anatomical outcomes, while MIOS suits high-risk patients by reducing reinterventions and complications. Further randomized trials are needed to confirm these findings.

Zinc is essential for animals, playing a vital role in enzyme systems and various biochemical reactions. It is crucial to ensure a sufficient intake of zinc through the diet to maintain efficient homeostasis. Only few studies on zinc effect in cow lactating diet evaluated the effects on milk and cheese quality, with conflicting findings. 24 cows of the Friesian breed were divided into two groups (CTR: control and TRT: treated group). Cows were selected for age, body weight, parity and phase of lactations (mid lactation, 140-160 days). CTR diet contained 38 mg/kg of Zn and TRT diet was supplied with 120 mg/kg of complete feed for 60 days. The objective of current investigation was to evaluate the impact of a dietary Zinc Oxide (ZnO) integration of lactating Friesian cows on chemical composition, zinc content, fatty acid and proteic profile, ammine content, pH, a w , texture, and sensory profile of cheese and to improve the chemical-nutritional quality of milk and cheese. The results showed that ZnO supplementation reduced mesophilic aerobic bacteria and Presumptive Pseudomonas spp. growth, proteolysis, biogenic amines content, lipid oxidation, odour intensity and sour and increased hardness, gumminess, chewiness, elasticity of cheese. Biogenic amines are considered an important aspect of food safety. ZnO integration in cow diet could represent a promising strategy for improving the quality, the safety and shelf-life of caciotta cheese.

Augmented reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications has driven new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify their value and impact in the medical-scientific field, especially in the improvement of diagnostics in complex fractures. Acetabular fractures have always been a challenge in orthopedics, due to their volumetric complexity and low diagnostic reliability. Background/Objectives : The goal of this study was to determine whether these methods could improve the learning aspect and diagnostic accuracy of complex acetabular fractures compared to gold-standard CT (computed tomography). Methods : Orthopedic residents of our department were selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum were included in the study, and details of these were provided as CT scans, 3DP models, and AR models displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results : Twenty residents (JUN = 10, SEN = 10) classified five fractures. Overall DA was 26% (CT), 18% (3DP), and 29% (AR). AR-DA was superior to 3DP-DA ( p = 0.048). DA means (JUN vs. SEN, respectively): CT-DA was 20% vs. 32% ( p < 0.05), 3DP-DA was 12% vs. 24% ( p = 0.08), and AR-DA was 28% vs. 30% ( p = 0.80). Overall RT was 61.2 s (±24.6) for CT, 35.8 s (±20.1) for 3DP, and 46.7 s (±20.8) for AR. R was fairly poor between methods and groups. Overall, 3DPs had superior C (65%). Conclusions : AR had the same overall DA as CT, independent of experience, 3DP had minor differences in DA and R, but it was the fastest method and the one in which there was the most confidence. Intra- and inter-observer R between methods remained very poor in residents.

Background : Olecranon fractures are common injuries of the upper limb in adults. Simple displaced trasverse fractures are generally surgically treated with tension-band wiring (TBW) or plate fixation (PF). The purpose of this retrospective study is to compare the clinical-functional outcome, complications and reoperation rates between TBW and PF for Mayo IIA fractures. Methods : 72 patients treated with PF or TBW at our institution, completed our survey and clinical evaluation and their demographic and clinical data were recorded and analysed. The clinical-functional outcomes were evaluated assessing ROMs and three validated scoring systems: the Disabilities of the Arm, Shoulder, and Hand (DASH), the Mayo Elbow Performance Score (MEPS) and the Patient American Shoulder and Elbow Surgeons Standardized Elbow Assessment score (pASES-e). Results : 38 patients (53%) underwent TBW and 34 (47%) PF. The mean DASH, MEPS and pASES-e scores were respectively 14.5 ± 17.2, 80.5 ± 14.7 and 83.6 ± 12.4 in the TBW group and 21 ± 21.7, 75.6 ± 15.3 and 75.1 ± 19.2 in the PF group ( p = 0.16, p = 0.17 and p = 0.03). The mean duration of surgery and hospitalisation period were longer in the PF group ( p = 0.002, p = 0.37) whereas the complication and reoperation rates were higher after TBW ( p = 0.15, p = 0.24). Conclusions : According to the literature, both TBW and PF resulted comparable valid surgical options for the treatment of simple isolated displaced olecranon fractures. Our results corroborate previous findings, showing good/excellent outcomes without significant differences.

Rubeosis Iridis (RI) is characterized by an increase in neovascularization and inflammation factors in the iris. During angiogenesis, the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a pivotal role in extracellular matrix remodeling, where uPAR regulates endothelial cell migration and proliferation through assembly with transmembrane receptors. Here, in the context of hypoxia-induced angiogenesis, the uPA/uPAR system blockage was investigated by using UPARANT in a novel ex vivo human iris organotypic angiogenesis assay. The effects of uPA/uPAR system antagonism in the humanized model of ocular pathologic angiogenesis were analyzed by sprouting angiogenesis and protein assays (western, dot blots, and co-immunoprecipitation) and correlated to vascular endothelial growth factor (VEGF) inhibition. Phosphoprotein and co-immunoprecipitation assay illustrated an unidentified antagonism of UPARANT in the interaction of uPAR with the low-density lipoprotein receptor-related protein-1 (LRP-1), resulting in inhibition of β-catenin-mediated angiogenesis in this model. The effects of uPA/uPAR system inhibition were focal to endothelial cells ex vivo. Comparison between human iris endothelial cells and human retinal endothelial revealed an endothelial-specific mechanism of β-catenin-mediated angiogenesis inhibited by uPA/uPAR system blockage and not by VEGF inhibition. Collectively, these findings broaden the understanding of the effects of the uPA/uPAR system antagonism in the context of angiogenesis, revealing non-canonical β-catenin downstream effects mediated by LRP-1/uPAR interaction., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Periprosthetic joint infection (PJI) poses a challenging complication for many patients undergoing arthroplasty, and the literature identifies numerous risk factors. A comprehensive understanding of the primary risk and protective factors for PJI is valuable for surgeons. This article aims to compile and summarize the key risk factors for PJI documented in the literature. Some risk factors are related to the nutritional status of patients, with obesity, weight loss, hypovitaminosis, and malnutrition being frequently reported. Pathologies affecting patients also contribute to PJI risk, including septic arthritis, hepatitis, diabetes, urinary tract infections, anemia, hypothyroidism, osteoporosis, and dental pathologies. Unhealthy habits, such as tobacco and drug abuse, are significant factors. Previous corticosteroid injections may also play a role in infection development. A few protective factors are also reported in the literature (use of statins, preoperative decolonization, and preadmission skin preparation). The identification of risk factors and the implementation of evidence-based preoperative protocols are essential steps in reducing the incidence of PJI., Competing Interests: The authors declare no conflicts of interest.

Study Question: Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?, Summary Answer: Aneuploid embryo-derived EVs contain transcripts of PPM1J , LINC00561 , ANKRD34C , and TMED10 with differential abundance from euploid embryo-derived EVs and induce upregulation of MUC1 transcript in dESCs., What Is Known Already: We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown., Study Design Size Duration: Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy., Participants/materials Setting Methods: EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs., Main Results and the Role of Chance: Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes PPM1J (log2fc = -5.13, P  = 0.011), LINC00561 (log2fc = -7.87, P  = 0.010), and ANKRD34C (log2fc = -7.30, P  = 0.017) and more abundant in TMED10 (log2fc = 1.63, P  = 0.025) compared to EVs of euploid embryos. Decidualization per se induced downregulation of MUC1 (log2fc = -0.54, P  = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of MUC1 transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, P  = 0.0201)., Large Scale Data: Raw data have been uploaded to GEO (accession number GSE234338)., Limitations Reasons for Caution: The findings of the study will require validation utilizing a second cohort of EV samples., Wider Implications of the Findings: The discovery that the transcriptomic profile of EVs secreted from aneuploid cleavage stage embryos differs from that of euploid embryos supports the possibility to develop a non-invasive methodology for PGT-A. The upregulation of MUC1 in dESCs following aneuploid embryo EV treatment proposes a new mechanism underlying implantation failure., Study Funding/competing Interests: The study was supported by a Marie Skłodowska-Curie Actions fellowship awarded to SM by the European Commission (CERVINO grant agreement ID: 79620) and by a BIRTH research grant from Theramex HQ UK Ltd. The authors have no conflicts of interest to declare., Competing Interests: None to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Endometriosis was claimed to negatively affect the intrafollicular environment, hindering oocyte competence. Previous studies evaluated expression levels of cytochrome P450 aromatase (CYP19A) in granulosa and cumulus oophorus cells collected from endometriosis women, but results are controversial. To further investigate the intrafollicular environment whose alteration may potentially disturb ovarian steroidogenesis in endometriosis, gene expression of CYP19A and of its upstream enzymes, StAR and 3βHSD was assessed in luteinized granulosa cells isolated from follicular fluids (FF) collected during Assisted Reproduction Technology (ART) procedures in women with stage III-IV disease and from subjects without the condition. In a subgroup of patients, cumulus oophorus cells (COCs) were also assessed for CYP19A, StAR and 3βHSD gene expression. No difference in mRNA expression of CYP19A1, StAR and 3βHSD in both granulosa cells and COCs was observed between the two groups of patients. No significant difference was also found between estradiol FF levels detected in endometriosis patients (median=873, IQR=522-1221 ng/ml)) and control patients (median=878, IQR=609-1137 ng/ml). To gain more insight into the intrafollicular regulation of CYP19A in patients with endometriosis, associations between expression of the analyzed genes, systemic and follicular 17β-estradiol levels and ART outcomes were assessed. While in the control group, levels of CYP19A1, StAR and 3βHSD transcripts significantly correlated with follicular estradiol levels (adjusted R² of 0.60), no significant association was detected in affected women (adjusted R² of 0.23). After stratification of the populations based on the presence of the disease, CYP19A1 expression was shown to correlate with the number of oocytes retrieved [β:- 1.214;95%CI: - 2.085 - (-0.343); p = 0.007] in the control group while this association was not present in patients with endometriosis [β:- 0.003; 95%CI:- 0.468-0.461; p = 0.988)]. These results do not support data from the literature indicating a reduced aromatase expression in granulosa cells of affected women, but they highlight a potential subtle mechanism affecting the ovulation process in these women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Evaluation of the optimal number of embryos, their quality, and the precise timing for transfer are critical determinants in reproductive success, although still remaining one of the main challenges in assisted reproduction technologies (ART). Indeed, the success of in vitro fertilization (IVF) treatments relies on a multitude of events and factors involving both the endometrium and the embryo. Despite concerted efforts on both fronts, the overall success rates of IVF techniques continue to range between 25% and 30%. The role of the endometrium in implantation has been recently recognized, leading to the hypothesis that both the "soil" and the "seed" play a central role in a successful pregnancy. In this respect, identification of the molecular signature of endometrial receptivity together with the selection of the best embryo for transfer become crucial in ART. Currently, efforts have been made to develop accurate, predictive, and personalized tests to identify the window of implantation and the best quality embryo. However, the value of these tests is still debated, as conflicting results are reported in the literature. The purpose of this review is to summarize and critically report the available criteria to optimize the success of embryo transfer and to better understand current limitations and potential areas for improvement.

Introduction: Corticosteroid injections have demonstrated short-term benefits for shoulder pain. This symptomatic treatment method is used in various inflammatory conditions that affect the shoulder joint. Corticosteroid joint injections are not without risks and complications. Adverse effects have been documented, including damage to the articular cartilage, tendon rupture, and attenuation of the subject's immune response. The aim of this study was to examine the timing of preoperative corticosteroid injections on infectious outcomes of shoulder arthroscopies and shoulder arthroplasty., Materials and Methods: In accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the PubMed, Cochrane, and Science Direct databases were systematically reviewed by two independent authors in January 2024. After full-text reading and checking the reference lists, 11 article were included., Results: Patients who received a shoulder injection within three months prior to undergoing shoulder arthroplasty exhibited a markedly elevated incidence of infection. In addition, a significantly increased risk of periprosthetic joint infection (PJI) at 90 days postoperatively in patients who received CSIs (corticosteroid injections) within 1 month prior to shoulder arthroplasty was found. Different authors consider CSI injections within the 2 weeks prior to shoulder arthroscopy surgery principally associated with an increased risk of postoperative infection., Discussion: There is still no consensus on the correct timing of preoperative CSIs in both arthroscopic and arthroplasty procedures. The literature does not identify whether the number of preoperative injections could increase the risk of periprosthetic infection. Obesity, sex, and smoking did not have a significant effect on PJIs; alcohol abuse could be considered as a risk factor for PJIs with CSIs. Both in prosthetic surgeries and in arthroscopy procedures, modifiable and unmodifiable factors play secondary roles. The risk of postoperative infection is greater within 3 months, although it is almost comparable at one- and two-year follow-ups.

Abstract: The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. A total of 306 of 474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD negativity, 185 of 306 (60%) patients were still MRD negative and progression free, 118 (39%) lost their MRD-negative status, and 3 patients (1%) died without progression. Amp1q vs normal (4-year CI, 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs 0 (4-year CI, 59% vs 33%), circulating tumor cells at baseline (high vs low at 4-year CI, 62% vs 32%), and time-to-reach MRD negativity postconsolidation vs preconsolidation (4-year CI, 46% vs 35%) were associated with a higher risk of unsustained MRD negativity in a multivariate Fine-Gray model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs lenalidomide alone had a lower risk of unsustained MRD negativity (4-year CI, 20% vs 33%)., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Proximal humerus fractures account for about 5% of fragility fractures. These involve a significant burden of disability and a reduced quality of life. This study aims to compare functional results and surgical outcomes (closed reduction and internal fixation with the internal closure system of the proximal humerus) and the conservative management of proximal humerus fractures by 2-, 3-, 4-parts, in patients older than 55 years. Between January 2017 and April 2019, 65 patients with 2, 3 or 4-part fractures were retrospectively analyzed: 29 patients (5 males and 24 females) with an average age of 70.8 ± 9.9 years treated non-surgically (conservative group (CG)) and 36 patients (11 males and 25 females) with an average age of 66.2 ± 7.1 years treated surgically with plate fixation (operating group (OG)). Using different evaluation scores, we compared the OG and the CG. Through the DASH score we have seen how at 12 months there is a satisfactory result in patients with conservative treatment (p = 0.0019). Constant-Murley scale shows no difference between the two treatments (p = 0.2300). BARTHEL scale and SST score did not give statistically satisfactory results. Also, after one year of follow-up, patients treated with conservative therapy had a higher improvement in their Range of Motion (ROM) values than patients treated with surgical treatment. The results in terms of pain in NPRS at 3, 6, 12 months are better for conservative groups (p = 0,0000). Our findings suggest that conservative treatment in proximal humeral fractures, particularly in multi-fragmented fractures in patients over 55 years of age, designs an excellent alternative to the surgical option., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marco Sapienza reports article publishing charges was provided by University of Catania Faculty School of Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Sport-specific adaptations of the glenohumeral joint may arise in adolescent overhead athletes who begin high-performance sports early in life. Research mainly addresses overuse injuries, leaving gaps in prevention, with adults studied more than youths., Objective: This study aims to investigate sport-adaptations of the glenohumeral joint in asymptomatic adolescent volleyball players to identify potential shoulder injury risk factors., Design: Observational study., Setting: Clinical screening campaign conducted at the Physical Medicine and Rehabilitation Unit of Policlinic Hospital in Catania, Italy., Participants: Forty asymptomatic under-16 athletes were evaluated., Interventions: Shoulder internal rotation (IR) and external rotation (ER), range of motion (ROM), total-rotation ROM, glenohumeral IR deficit (GIRD), general joint laxity using Beighton score, apprehension, relocation, O'Brian tests, and ultrasound (US) glenohumeral distance were tested bilaterally. Variables such as the player's position, the age they began the sport, limb dominance, weight, and height were also considered., Results: The median US glenohumeral distance was at 0.42 ± 0.26 cm, which is consistent with the range found in non-dislocated shoulders of a healthy non-athletic population. The ER ROM was significantly greater in the dominant shoulder than the contralateral one (P = 0.0001), and there was a significant correlation between the ER ROM of attackers and their US glenohumeral distance (P = 0.0413). Furthermore, shoulder IR ROM and US glenohumeral distance were not significantly different between the dominant and contralateral limbs (P = 0.05). None of the athletes presented GIRD. Other tests, including the Beighton score, apprehension, and relocation tests, yielded no significant differences between the dominant and contralateral limbs., Conclusions: Despite an increased shoulder ER in the dominant limb, the glenohumeral joint remains stable, suggesting that greater ROM in ER does not equate to instability in overhead athletes without hyperlaxity. Nevertheless, increased ER impacts glenohumeral distance in attacker volleyball players. This finding suggests that the shoulder morphological adaptation process starts early in attackers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

This paper aims to investigate the effectiveness and the outcomes of the association between different types of biofeedback techniques and therapeutic exercises in the conservative treatment of patellar femoral pain (PFP). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines have been used and followed the Cochrane Handbook for Systematic Reviews of Interventions. Between April and June 2023, the following electronic databases were searched: PubMed, ScienceDirect, BIOMED Central, Cochrane Library, and PEDro. Only randomized controlled trials (RCTs) were selected. Following the search, 414 records were found, and after using strict inclusion and exclusion criteria, 12 RCTs were retrieved to include in this systematic review, assessing 513 patients. The association between biofeedback and therapeutic exercise may be beneficial for pain, function (AKPS), extensor muscle strength, reduction of the dynamic knee valgus and vastus medialis (VM) and vastus lateralis (VL) (EMG) optimization. All these results were valued in the short term. Regarding the intervention type, it was possible to correlate the EMG biofeedback with the benefits of the knee extensor strength and the EMG activity of VM and VL. Conversely, using mirror, verbal, and somesthetic (hands and band) feedback seems to be linked to the reduction of the knee dynamic valgus.

Background: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance., Patients and Methods: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group)., Results: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189)., Conclusions: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hereby, we describe the first case of latent mastocytosis triggered by mRNA-based vaccine to prevent COVID-19 infection., Case Presentation: In a 42-year-old Arabian man affected by slight, undiagnosed mastocytosis, the second dose of the COVID-19 vaccine made more blatant his latent disease. The postvaccination diagnostic iter is illustrated and the potential reasons causing the onset of the cutaneous mastocytosis are discussed., Conclusion: Clinicians should keep a longer follow-up of their patients after the COVID-19 vaccination, not related to few hours, for the risk of immediate-type adverse events only., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: The main aim of the study is to assess clinical and functional outcomes of arthroscopic outside-in repair of isolated radial tears of the midbody of lateral meniscus in professional athletes and to evaluate the return to the sport activity after surgery., Methods: A retrospective data collection on professional athletes with isolated complete lesion of the midbody of lateral meniscus, treated with arthroscopic outside-in repair was carried out. Outcome measures included functional assessment, Limb Symmetry Index (LSI) and Hamstring Quadriceps Ratio (HQR) and Lysholm score collected before surgery and at 4-month follow-up. Data on return to sport practice and re-injury were also retrieved., Results: Fourteen patients satisfied the selection criteria. Full return to professional sport activity (Tegner 10) was registered in the 86% of the cohort at 4 months after the surgery. Functional testing of the athletes showed a return of the LSI and HQR to the pre-surgical condition, demonstrating a full recovery of the functional ability and muscle strength. Similarly, clinical evaluation through Lysholm score showed an improvement, reaching an average of 97.7 points at 4 months follow-up., Conclusion: A good functional recovery and a high rate of return to play has been observed in a population of professional athletes, at 4 months after outside-in repair., (© 2022. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL&#95;ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool. Patients were administered a maximum of 6 28-day cycles of 20 mg oral lenalidomide from days 2 to 22 and IV rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients with partial response or complete response (CR) at cycle 6 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary end point was the overall response rate (ORR) after cycle 6; the coprimary end point was the rate of grade 3 or 4 extrahematological toxicity. The ORR was 50.8%, with 27.7% CR. After a median follow-up of 24 months, the median progression-free survival was 14 months, and the 2-year duration of response was 64%. Thirty-four patients experienced extrahematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3. The activity of the R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach in frail older patients with DLBCL. This trial was registered at EudraCT as #2015-003371-29 and clinicaltrials.gov as #NCT02955823., (© 2023 by The American Society of Hematology.)

Background: Flexible flatfoot (FFF) is a very common condition in children, but no evidence-based guidelines or assessment tools exist. Yet, surgical indication is left to the surgeon's experience and preferences., Aim: To develop a functional clinical score for FFF [Catania flatfoot (CTF) score] and a measure of internal consistency; to evaluate inter-observer and intra-observer reliability of the CTF Score; to provide a strong tool for proper FFF surgical indication., Methods: CTF is a medically compiled score of four main domains for a total of twelve items: Patient features, Pain, Clinical Parameters, and Functionality. Each item refers to a specific rate. Five experienced observers answered 10 case reports according to the CTF. To assess inter- and intra-observer reliability of the CTF score, the intra-class correlation coefficients' (ICCs) statistics test was performed, as well as to gauge the correlation between the CTF score and the surgical or conservative treatment indication. Values of 75% were chosen as the score cut-off for surgical indication. Sensitivity, specificity, positive likelihood ratio (PLHR), negative likelihood ratio (NLHR), positive predictive value (PPV), and negative predictive value (NPV)., Results: Overall interobserver reliability ICC was 0.87 [95% confidence interval (CI): 0.846-0.892; P < 0.001]. Overall intra-observer reliability ICC was 0.883 (95%CI: 0.854-0.909; P < 0.001). A direct correlation between the CTF score and surgical treatment indication [Pearson correlation coefficient = 0.94 ( P < 0.001)] was found. According to the 75% cut-off, the sensitivity was 100% (95%CI: 83.43%-100%), specificity was 85.71% (95%CI: 75.29%-92.93%), PLHR was 7 (95%CI: 3.94-12.43), NLHR was 0 (95%CI: 0-0), PPV was 75% (95%CI: 62.83%-84.19%) and NPV was 100% (95%CI: 100%-100%)., Conclusion: CTF represents a useful tool for orthopedic surgeons in the FFF evaluation. The CTF score is a quality questionnaire to reproduce suitable clinical research, survey studies, and clinical practice. Moreover, the 75% cut-off is an important threshold for surgical indication and helps in the decision-making process., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The knowledge on the anatomy, function and biomechanics and the role of surgical procedures on the anterolateral ligament (ALL) of the knee is still controversial. Only a few papers have examined the ALL in children. The aim of this review is to analyze all the available literature about ALL in the pediatric population. Following the PRISMA criteria, the literature was systematically reviewed, examining all the articles about ALL in pediatric patients. Eight articles were involved in this study. Five cadaveric studies, two diagnostic studies, and one cross-sectional study were found. The identification of the ALL is not always possible in diagnostic studies using magnetic resonance (MRI) or in dissecting specimens. A high variability in the presence of the ligament and in its origin and insertion were found among the studies. It is more difficult to identify the ligament in younger patients than in older children, suggesting that its presence may develop at some point during the growth. Further studies are needed for a detailed knowledge of the ALL.

Over the last decades, much effort has been devoted to the construction of protein and peptide-based metalloporphyrin catalysts capable of promoting difficult transformations with high selectivity. In this context, mechanistic studies are fundamental to elucidate all the factors that contribute to catalytic performances and product selectivity. In our previous work, we selected the synthetic peptide-porphyrin conjugate MnMC6*a as a proficient catalyst for indole oxidation, promoting the formation of a 3-oxindole derivative with unprecedented selectivity. In this work, we have evaluated the role of the metal ion in affecting reaction outcome, by replacing manganese with iron in the MC6*a scaffold. Even though product selectivity is not altered upon metal substitution, FeMC6*a shows a lower substrate conversion and prolonged reaction times with respect to its manganese analogue. Experimental and theoretical studies have enabled us to delineate the reaction free energy profiles for both catalysts, indicating different thermodynamic limiting steps, depending on the nature of the metal ion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Regulations governing assisted reproduction control the degree to which gamete donation is legal and how people providing genetic material are selected and compensated. The United States and Spain are both global leaders in fertility treatment with donor oocytes. Yet both countries take different approaches to how egg donation is regulated. The US model reveals a hierarchically organized form of gendered eugenics. In Spain, the eugenic aspects of donor selection are more subtle. Drawing upon fieldwork in the United States and Spain, this article examines (1) how compensated egg donation operates under two regulatory settings, (2) the implications for egg donors as providers of bioproducts, and (3) how advances in oocyte vitrification enhances the commodity quality of human eggs. By comparing these two reproductive bioeconomies we gain insight into how different cultural, medical, and ethical frameworks intersect with egg donor embodied experiences., (© 2023 The Authors. Medical Anthropology Quarterly published by Wiley Periodicals LLC on behalf of American Anthropological Association.)

Oxidases and peroxidases have found application in the field of chlorine-free organic dye degradation in the paper, toothpaste, and detergent industries. Nevertheless, their widespread use is somehow hindered because of their cost, availability, and batch-to-batch reproducibility. Here, we report the catalytic proficiency of a miniaturized synthetic peroxidase, Fe-Mimochrome VI*a, in the decolorization of four organic dyes, as representatives of either the heterocyclic or triarylmethane class of dyes. Fe-Mimochrome VI*a performed over 130 turnovers in less than five minutes in an aqueous buffer at a neutral pH under mild conditions.

Background: Septic arthritis (SA) in children is an acute inflammatory disease of the joints. If not treated promptly, it could become a surgical emergency. The incidence of the disease in children in Europe is approximately 2-7 per 100,000 children. The aim of this systematic review was to investigate which of these treatments-arthrocentesis, arthrotomy, and arthroscopy-provides better results in children and when to use them., Methods: Three independent authors conducted a systematic review of PubMed, ScienceDirect, and MEDLINE databases to assess studies with any level of evidence that reported the surgical outcome of SA. Two senior investigators evaluated and approved each stage's findings., Results: A total of 488 articles were found. After screening, we chose 24 articles that were suitable for full-text reading based on the inclusion and exclusion criteria. The results of our analysis showed that there are no numerically significant differences reported in the literature on clinical and radiographic outcomes by surgical technique., Conclusions: We developed an algorithm that could be used if septic arthritis is suspected. Based on our results, the surgical technique to be used will depend on the operator who will perform it.

Physical and psychological health concerns have been raised due to either spine deformity or orthotic treatment in adolescents with idiopathic scoliosis. To determine whether orthotic bracing duration affects psychological stress and health-related quality of life, a sample of 46 patients (8M, 38F, aged 11-17 years, regularly treated with bracing) with moderate or moderate to severe idiopathic scoliosis were separated into two groups based on whether their treatment duration was up to six months or longer. The brace-related levels of stress and quality of life were investigated in both groups by using the Bad Sobernheim Stress Questionnaire and the Italian Spine Youth Quality of Life, respectively. The questionnaire scores were categorized as low, mean, and high. Our statistical analysis considered the proportion of patients falling into the three categories and the difference in crude score rates between the two groups. Values were considered significant at p < 0.05. The proportion of patients with brace-related stress and impaired quality of life was significantly lower in the group treated longer compared to the group that had only received treatment for up to six months (chi-square test, p < 0.0001). Overall, mean ± SD BSSQ scored 8.72 ± 4.91 and 12.89 ± 4.65 in group 1 and group 2, respectively (Mann-Whitney U test, p = 0.008), while ISYQoL scored 19.94 ± 8.21 and 16.07 ± 6.12, respectively. We argue that the differences could depend on both the physical and psychological adaptation patients make to their brace and that more support should be provided to patients when they start to wear their brace.

Online teaching has resulted in university students adopting a sedentary lifestyle. Prolonged sitting and reduced physical activity due to pandemic restrictions have led to musculoskeletal pain in various body areas, significantly impacting students' quality of life. This study aims to investigate the effects of remote learning on Sicilian physiotherapy students during the COVID-19 pandemic, specifically focusing on the occurrence of musculoskeletal pain. An observational study was conducted using an online survey administered through Google Forms. The survey consisted of 26 multiple-choice questions and was distributed to students enrolled in physiotherapy programs at the universities of Catania, Messina, and Palermo. Participants were contacted via social channels or email, and data collection spanned 5 weeks. The collected data were analyzed using R software. A total of 128 questionnaires were collected. At the time of compilation, most respondents ( n = 103/201, 51.2%) were enrolled in the third year of the course of study in physiotherapy at the universities of Catania, Messina, and Palermo. Their ages ranged between 22 and 25 years (43.3%), and most were female ( n = 104/201, 51.7%). More than half of the students (51.6%) reported dedicating 15-22 h per week to distance learning for a duration of 6-12 months (50%). Regarding study location, most students preferred studying at a desk (82.8%), and slightly over half (57.8%) adopted a backrest while studying remotely. Analysis of the students' posture during study hours revealed common positions, including tilting the head forward by more than 20 degrees (47.8%), leaning the trunk forward by more than 20 degrees (71.9%), hunching both shoulders forward (57.0%), wrists positioned above the level of the elbows (46.1%), thighs pointing upwards (41.4%), and one or both feet in a downward or dorsiflexed position (69.5%). In conclusion the questionnaire responses indicate that the lifestyle of university students, influenced by online teaching, has deteriorated, leading to musculoskeletal pain, including myofascial pain. These results are primarily influenced by the adopted posture and the duration of time spent in these positions. Additionally, research is needed to identify the most effective therapeutic approaches for managing musculoskeletal pain.

Background: Non-operative treatment with immobilization is the gold-standard for paediatric clavicular fractures. Purpose of this study is to evaluate functional outcomes and efficacy of non-operative treatment of clavicular fractures in a succession of 131 children., Methods: Between 2006 and 2012, we treated non-surgically 131 children for a clavicular fracture. All fractures have been classified according to Robinson classification. Clavicle shortening, range of movements and muscular strength through the Medical Research Council (MRC) Scale were evaluated. To assess the outcomes, QuickDASH questionnaire, dividing the sample in 3 age-related group, was administered., Results: The average follow-up was 26 months (8-84 months). Clavicle shortening at the time of injury occurred in 18 cases. All fractures reached union. Average time to union was 34 days. Mean time return to activity was 12.6 weeks. No cases of nonunion or delayed union were reported. Complications occurred in 21 cases. A shortening persisted in 2 cases. Only one patient had a slight functional restriction. Average QuickDASH Score was 6.2±1.1 (range 4.3-9.4). All patients recovered to an MRC Score of 5, except for one patient with a score of 4. Best QuickDASH Scores were observed in the group aged under 8 years and in non-comminuted and lateral third fractures of the clavicle., Conclusions: Observing results, clavicle fractures have a satisfactory clinical healing as shown by the good scores at QuickDASH and MRC Scale. Younger children under 8 years can achieve the best results with a conservative treatment in terms of bone healing and activity level.

Background: Syndesmotic injuries are common lesions associated with ankle fractures. Static and dynamic fixation are frequently used in syndesmotic injury-associated ankle fractures. The purpose of this study is to compare short- and mid-term quality of life, clinical outcomes, and gait after static stabilization with a trans-syndesmotic screw or dynamic stabilization with a suture button device., Methods: Here, 230 patients were enrolled in a retrospective observational study. They were divided in two groups according to the fixation procedure (Arthrex TightRope ® , Munich, Germany) synthesis vs. osteosynthesis with a 3.5 mm trans-syndesmotic tricortical screw). They then underwent clinical assessment using the American Foot and Ankle Score (AOFAS) at 1, 2, 6, 12, and 24 months after surgery. Quality of life was assessed according to the EuroQol-5 Dimension (EQ-5D) at 2 and 24 months after surgery in the follow-up; gait analysis was performed 2 and 24 months postoperatively., Results: Significant differences were found at a two-month follow-up according to the AOFAS ( p = 0.0001) and EQ-5D ( p = 0.0208) scores. No differences were noted in the other follow-ups ( p > 0.05) or gait analysis., Conclusion: The dynamic and static fixation of syndesmotic injuries in ankle fracture are both efficacious and valid procedures for avoiding ankle instability. The suture button device was comparable to the screw fixation according to functional outcomes and gait analysis.

The development of artificial enzymes for application in sustainable technologies, such as the transformation of environmental pollutants or biomass, is one of the most challenging goals in metalloenzyme design. In this work, we describe the oxidation of mono-, di-, tri- and penta-halogenated phenols catalyzed by the artificial metalloenzyme Fe-MC6*a. It promoted the dehalogenation of 4-fluorophenol into the corresponding 1,4-benzoquinone, while under the same experimental conditions, 4-chloro, 4-bromo and 4-iodophenol were selectively converted into higher molecular weight compounds. Analysis of the 4-chlorophenol oxidation products clarified that oligomers based on C-O bonds were exclusively formed in this case. All results show that Fe-MC6*a holds intriguing enzymatic properties, as it catalyzes halophenol oxidation with substrate-dependent chemoselectivity.

Designing metal sites into de novo proteins has significantly improved, recently. However, identifying the minimal coordination spheres, able to encompass the necessary information for metal binding and activity, still represents a great challenge, today. Here, we test our understanding with a benchmark, nevertheless difficult, case. We assemble into a miniature 28-residue protein, the quintessential elements required to fold properly around a FeCys 4 redox center, and to function efficiently in electron-transfer. This study addresses a challenge in de novo protein design, as it reports the crystal structure of a designed tetra-thiolate metal-binding protein in sub-Å agreement with the intended design. This allows us to well correlate structure to spectroscopic and electrochemical properties. Given its high reduction potential compared to natural and designed FeCys 4 -containing proteins, we exploit it as terminal electron acceptor of a fully artificial chain triggered by visible light., (© 2023. The Author(s).)

Slipped capital femoral epiphysis (SCFE) is the most common hip disorder affecting children and adolescents aged between 9 and 16 years, affecting approximately 10 per 100,000 children per year. The diagnosis of SCFE is often delayed, leading to an increased risk of complications. This study aims to provide the latest evidence concerning the causes of diagnostic delay and risk factors for SCFE and to educate general practitioners and paediatricians to help reduce delays in diagnosis and provide earlier therapeutic intervention. A literature search was conducted in the ScienceDirect and PubMed databases according to the PRISMA statement. Suitable studies for this systematic review included 22 articles discussing the aetiology of SCFE, risk factors, and causes of late diagnosis. Causes of delayed diagnosis include underestimation by patients, initial diagnostic approach by a non-orthopaedic professional, inadequate imaging, failure to recognize morphological changes, and variation in symptomatic presentation. The underlying risk factors for SCFE are likely part of a multifactorial process which involves anatomical variations and the metabolism of leptin, growth hormone, insulin, and other metabolic parameters. This review highlights the importance of early recognition and diagnosis of SCFE and proposes an algorithm for physicians to approach children who may have this condition.

Bosworth lesions are fracture-dislocations of the ankle and are characterized by entrapment of the proximal segment of the fibula behind the posterior tubercle of the distal tibia. Treatment is challenging, mainly due to failure of a closed reduction. The aim of this study was to review the literature concerning this type of injury. A total of 103 patients with Bosworth fractures were included in the study. The analyzed studies yielded a total of 103 cases, of which 68% (n = 70) were male and 32% (n = 33) were female. Bosworth fractures are mainly due to accidental trauma (58.2%), sports-related injuries (18.4%), and traffic accidents (18.4%). More than 76% of the patients presented a Danis-Weber B fracture, 8.7% a type C fracture, and only 0.97% presented a type A fracture. In 92.2% of the patients, the attempted closed reduction was unsuccessful. A definitive treatment with open reduction and internal fixation (ORIF) was used in 96 patients (93.2%). The most frequent complication was post-traumatic arthritis (10.7%). Bosworth fractures are challenging. The available literature lacks adequate information about this fracture, and an approved standardized algorithm for treating such fractures is not available.

Shoulder pain is one the most common musculoskeletal complaints. The most common pathological causes of shoulder pain in the general population are subacromial impingement syndrome and adhesive capsulitis, commonly referred to as "frozen shoulder". The purpose of this study was to evaluate the role of the scapulo-thoracic complex, particularly in scapular kinematic functions, in rehabilitative interventions for shoulder pain in patients suffering from these two common conditions. This systematic review was performed using the scientific search engines PubMed, PEDro and Cochrane Library, considering only randomized controlled clinical trials. Selected articles were evaluated according to the level of evidence and methodological quality. Thirteen randomized clinical trials were selected. Interventions have been divided into three macro-categories: (1) manual therapy in patients with subacromial impingement, (2) therapeutic exercise programs including interventions on the scapulothoracic complex in patients with subacromial impingement syndrome, and (3) therapeutic exercise programs including interventions on the scapulothoracic complex in patients with frozen shoulder. Following this, a qualitative analysis was performed according to outcomes such as pain, shoulder function, and scapular kinematics. Physiotherapy exercise programs that included scapular motor control training and scapular mobilizations, in particular, those of the scapulo-thoracic complex in scapular kinematic function, represent valid alternatives in the management of patients with subacromial impingement syndrome.

The demand for noninvasive methods to assess postural defections is increasing because back alterations are more common among the healthy population. We propose a combined infrared method of rasterstereography and thermography to assess the back without harmful effects. This study aims to provide reference data on rasterstereography and thermography to evaluate the back of a healthy population and to further study the correlation between these two methods. This cross-sectional research involved 175 healthy individuals (85 males and 90 females) aged 22 to 35 years. There is a large Cohen's d effect size in the cervical depth (males = 43.77 ± 10.96 mm vs. females = 34.29 ± 7.04 mm, d = 1.03), and in the lumbar lordosis angle (males = 37.69 ± 8.89° vs. females = 46.49 ± 8.25°, d = - 1.03). The back temperature was different for gender in the cervical area (males = 33.83 ± 0.63 °C vs. females = 34.26 ± 0.84 °C, d = - 0.58) and dorsal area (males = 33.13 ± 0.71 °C vs. females = 33.59 ± 0.97 °C, d = - 0.55). Furthermore, in the female group there was a moderate correlation of lumbar temperature with lumbar lordosis angle (r = - 0.50) and dorsal temperature with shoulders torsion (r = 0.43). Males showed a moderate correlation for vertebral surface rotation RMS with cervical (r = - 0.46), dorsal (r = - 0.60), and lumbar (r = - 0.50) areas and cervical temperature with shoulders obliquity (r = 0.58). These results highlight a possible correlation between rasterstereography and thermography, which may elucidate the underlying mechanics of spinal alterations and thermal muscle response. Our findings may represent reference data for other studies using noninvasive methods to assess postural alterations., (© 2023. The Author(s).)

The aim of this study was to retrospectively evaluate the clinical, functional, and radiographic outcomes of displaced C-shaped intercondylar fractures of the humerus in children and adolescents, and evaluate upper-extremity function with the short version of the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (Quick DASH). We retrospectively reviewed the data of nine children with displaced C-intercondylar fractures that were treated surgically. Age, sex, laterality, mechanism of injury, amount of displacement, type of treatment, fixation method, and outcome were recorded. The outcome of C-shaped fractures was compared with that of T-intercondylar fractures published by the same surgeons in a previous study. A total of nine consecutive patients (median age, 12 years; range, 9-14 years) with displaced C-intercondylar fractures of the humerus (3 females) were included; in six cases (67%), the left side was affected. Median follow-up was 2 years (range, 2-6). All patients underwent open reduction and internal fixation by screws ( n = 5), Kirschner-wires ( n = 3), or both ( n = 1). Overall, four out of nine patients developed a total of five complications (55.5%): one case of secondary displacement, one case of fishtail deformity, two cases extension deficit, and one case of limited flexion/extension requiring release. The median Quick DASH score at last follow-up visit was 0 (range, 0-4.5). C-intercondylar fractures should be added as a class to complete the Tnoniolo and Wilkin's classification. The prognosis is similar to that of T-intercondylar fractures because, in both cases, fractures are intra-articular and require open reduction and internal fixation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing., Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%)., Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients ( P  < 0.001); more active diseases at the time of SCT ( P  < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 ( P  < 0.001) or a good Karnofsky performance status ( P  = 0.025); increased use of peripheral blood stem cells as graft sources ( P  < 0.001); and greater use of reduced intensity conditioning regimens ( P  = 0.013) and of haploidentical donors ( P  < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P  = 0.0003). This was not observed in the TREO-based group., Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Extracapsular femoral neck fractures (eFNF) are the third most common type of fracture in traumatology. Intramedullary nailing (IMN) is one of the most frequently used ortho-pedic treatments for eFNF. Blood loss is one of the main complications of this treatment. This study aimed to identify and evaluate the perioperative risk factors that lead to blood transfusion in frail patients with eFNF who undergo IMN., Methods: From July 2020 to December 2020, 170 eFNF-affected patients who were treated with IMN were enrolled and divided into two groups according to blood transfusion: NBT (71 patients who did not need a blood transfusion), and BT (72 patients who needed blood transfusion). Gender, age, BMI, pre-operative hemoglobin levels, in-ternational normalized ratio (INR) level, number of blood units transfused, length of hospital stay, surgery duration, type of anesthesia, pre-operative ASA score, Charlson Comorbidity Index, and mortality rate were assessed., Results: Cohorts differed only for pre-operatively Hb and surgery time ( p < 0.05)., Conclusion: Patients who have a lower preoperative Hb level and longer surgery time have a high blood-transfusion risk and should be closely followed peri-operatively., Competing Interests: The authors declare no conflict of interest.

Background and Objectives : Supracondylar fractures of the humerus (SCHF) make up about one-third of pediatric fractures and are the most common elbow fractures in children. Reduction and fixation of SC fractures can be performed with the patient in the prone or supine position. However, the role of the patient's position during surgery is still unclear. The purpose of this systematic review is to evaluate, based on data from the literature, the role of patient position during closed reduction and fixation of pediatric SCHFs. Materials and Methods : A systematic review of the current literature from 1951 to 2021 was conducted according to PRISMA guidelines. Articles were identified from 6 public databases. Articles were screened and abstracted by two investigators and the quality of included publications ( n = 14) was assessed (MINORS criteria). Statistical analyses were performed using R studio 4.1.2. Results : The systematic literature review identified 114 articles, from which, according to inclusion and exclusion criteria, 14 studies were identified. A total of 741 children were treated in the prone position and 538 in the supine position. The results of the systematic review showed that there were no statistical differences between the two positions with regard to clinical, radiographic, and complication outcomes. Conclusions: : The functional and radiographic outcome of displaced SCHFs is generally excellent regardless of the position, prone or supine, in which the patient is positioned for surgery. The choice of how to position the patient depends on the habit and experience of the surgeon and anesthesiologist performing the surgery.

Checkpoint inhibitors have significantly changed the prognosis of patients with relapsing refractory classical Hodgkin's lymphoma (cHL), demonstrating excellent results in heavily pretreated patients. However, there is still limited data on the real-world experience with PD-1 inhibitors in cHL. Within the context of the Apulian hematological network (Rete Ematologica Pugliese, REP), we performed a retrospective, multicenter analysis of 66 patients with relapsing refractory cHL who had received PD-1 inhibitors in the non-trial setting. Forty-three patients (65%) were treated with nivolumab and 23 (35%) with pembrolizumab. Thirty-one (47%) and 8 (12%) patients underwent autologous or allogeneic stem cell transplantation prior to checkpoint inhibitor therapy, respectively. The median number of lines of treatment attempted prior to PD-1 inhibitor therapy was 4 (range, 3 to 7). All patients had received brentuximab vedotin prior to checkpoint inhibitor therapy. The overall response rate to PD-1 inhibitors therapy was 70% (47% complete remission (CR) and 23% partial remission (PR)). Twenty-four immune-related adverse events (19 (80%) grades 1-2; 5 (20%) grades 3-4) were documented (4 gastrointestinal, 4 hepatic, 6 fever, 4 hematological, 3 dermatological, 3 allergic rhinitis). Toxicity resolved in all patients, and there were no deaths attributed to checkpoint inhibitor therapy. After a median follow-up of 26 months (range 3-72 months), 54 patients (82%) are alive, and 12 (18%) died. The cause of death was attributed to disease progression in 9 patients and sepsis in 3 patients. After PD-1 inhibitor therapy, 22 patients (33%) relapsed or progressed. The overall survival and progression-free survival at 5 years were 65% and 54%, respectively. This study confirms the efficacy and tolerability of PD-1 inhibitor therapy in relapsed refractory cHL in a real-world setting, demonstrating similar clinical outcomes and toxicity profiles compared to clinical studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The various mechanisms involved in peripheral nerve regeneration, induced by exercise and electrical nerve stimulation, are still unclear., Objective: The aim of this review was to summarize the influence of physical exercise and/or electrical stimulation on peripheral nerve repair and regeneration and the variation of impact of intervention depending on timing, as well as kind and dosage of the intervention. A literature survey was conducted on PubMed, Scopus, and Web of Science, between February 2021 to July 2021, with an update in September 2022., Methodology: The literature search identified 101,386 articles with the keywords: "peripheral nerve" OR "neuropathy" AND "sprouting" OR "neuroapraxia" OR "axonotmesis" OR "neurotmesis" OR "muscle denervation" OR "denervated muscle" AND "rehabilitation" OR "physical activity" OR "physical exercise" OR "activity" OR "electrical stimulation". A total of 60 publications were included. Eligible studies were focused on evaluating the process of nerve repair (biopsy, electromyographic parameters or biomarker outcomes) after electrical stimulation or physical exercise interventions on humans or animals with peripheral sensory or motor nerve injury., Synthesis: This study shows that the literature, especially regarding preclinical research, is mainly in agreement that an early physical program with active exercise and/or electrical stimulation promotes axonal regenerative responses and prevents maladaptive response. This was evaluated by means of changes in electrophysiological recordings of CMAPs for latency amplitude, and the sciatic functional index (SFI). Furthermore, this type of activity can cause an increase in weight and in muscle fiber diameter. Nevertheless, some detrimental effects of exercising and electrical stimulation too early after nerve repair were recorded., Conclusion: In most preclinical studies, peripheral neuropathy function was associated with improvements after physical exercise and electrical stimulation. For humans, too little research has been conducted on this topic to reach a complete conclusion. This research supports the need for future studies to test the validity of a possible rehabilitation treatment in humans in cases of peripheral neuropathy to help nerve sprouting.

Early life stress (ELS) refers to harmful environmental events (i.e., poor maternal health, metabolic restraint, childhood trauma) occurring during the prenatal and/or postnatal period, which may cause the 'epigenetic corruption' of cellular and molecular signaling of mental and physical development. While the impact of ELS in a wide range of human diseases has been confirmed, the ELS susceptibility to bone diseases has been poorly explored. In this review, to understand the potential mediating pathways of ELS in bone diseases, PRISMA criteria were used to analyze different stress protocols in mammal models and the effects elicited in dams and their progeny. Data collected, despite the methodological heterogeneity, show that ELS interferes with fetal bone formation, also revealing that the stress type and affected developmental phase may influence the variety and severity of bone anomalies. Interestingly, these findings highlight the maternal and fetal ability to buffer stress, establishing a new role for the placenta in minimizing ELS perturbations. The functional link between ELS and bone impairments will boost future investigations on maternal stress transmission to the fetus and, parallelly, help the assessment of catch-up mechanisms of skeleton adaptations from the cascading ELS effects.

Background: Patients with newly diagnosed multiple myeloma and high-risk cytogenetic abnormalities (HRCA) represent an unmet medical need. In the FORTE trial, lenalidomide and dexamethasone plus carfilzomib (KRd) induction resulted in a higher proportion of patients with at least a very good partial response as compared with carfilzomib, cyclophosphamide, and dexamethasone (KCd), and carfilzomib plus lenalidomide maintenance prolonged progression-free survival compared with lenalidomide maintenance. In this prespecified analysis of the FORTE trial, we described the outcomes of enrolled patients according to their cytogenetic risk., Methods: The UNITO-MM-01/FORTE was a randomised, open-label, phase 2 trial done at 42 Italian academic and community practice centres, which enrolled transplant-eligible patients with newly diagnosed multiple myeloma aged 18-65 years. Eligible patients had newly diagnosed multiple myeloma based on standard International Myeloma Working Group criteria, a Karnofsky performance status of at least 60%, and had not received any previous treatment with anti-myeloma therapy. At enrolment, patients were stratified according to International Staging System stage (I vs II/III) and age (<60 years vs 60-65 years) and randomly assigned (1:1:1) to KRd plus autologous stem-cell transplantation (ASCT; four 28-day induction cycles with KRd, melphalan at 200 mg/m 2 and ASCT [MEL200-ASCT], followed by four 28-day KRd consolidation cycles), 12 28-day KRd cycles, or KCd plus ASCT (four 28-day induction cycles with KCd, MEL200-ASCT, and four 28-day KCd consolidation cycles), using a web-based system (block randomisation, block size of 12). Carfilzomib was administered at 20 mg/m 2 on days 1 and 2 of cycle 1, followed by 36 mg/m 2 intravenously administered on days 8, 9, 15, and 16 of cycle 1, and then 36 mg/m 2 intravenously administered for all subsequent doses on days 1, 2, 8, 9, 15, 16; lenalidomide 25 mg was administered orally on days 1-21; cyclophosphamide 300 mg/m 2 was administered orally on days 1, 8, and 15; and dexamethasone 20 mg was administered orally or intravenously on days 1, 2, 8, 9, 15, 16, 22, and 23. After the consolidation phase, patients were stratified according to induction-consolidation treatment and randomly assigned (1:1; block size of 8) to maintenance treatment with carfilzomib plus lenalidomide or lenalidomide alone. Carfilzomib 36 mg/m 2 was administered intravenously on days 1-2 and days 15-16, every 28 days for up to 2 years, and lenalidomide 10 mg was administered orally on days 1-21 every 28 days until progression or intolerance in both groups. The primary endpoints were the proportion of patients with at least a very good partial response after induction with KRd versus KCd and progression-free survival with carfilzomib plus lenalidomide versus lenalidomide alone as maintenance treatment. In this preplanned analysis, we included patients enrolled in the FORTE trial with complete cytogenetic data on del(17p), t(4;14), t(14;16), del(1p), gain(1q) (3 copies), and amp(1q) (≥4 copies) assessed by fluorescence in-situ hybridisation analysis on CD138-positive sorted cells. We assessed progression-free survival, overall survival, minimal residual disease negativity, and 1-year sustained minimal residual disease negativity according to the presence of zero, one, and two or more HRCA across treatment groups. The FORTE trial is ongoing, and registered with ClinicalTrials.gov, NCT02203643., Findings: Between Feb 23, 2015, and April 5, 2017, 477 patients were enrolled, of whom 396 (83%) had complete cytogenetic data and were analysed (176 [44%] of whom were women and 220 [56%] were men). The median follow-up from first randomisation was 51 months (IQR 46-56). 4-year progression-free survival was 71% (95% CI 64-78) in patients with zero HRCA, 60% (95% CI 52-69) in patients with one HRCA, and 39% (95% CI 30-50) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of progression or death was similar in patients with one HRCA (hazard ratio [HR] 1·33 [95% CI 0·90-1·97]; p=0·15) and higher in patients with two or more HRCA (HR 2·56 [95% CI 1·74-3·75]); p<0·0001) across the induction-intensification-consolidation groups. Moreover, the risk of progression or death was also higher in patients with two or more HRCA versus those with one HRCA (HR 1·92 [95% CI 1·34-2·76]; p=0·0004). 4-year overall survival from the first randomisation was 94% (95% CI 91-98) in patients with zero HRCA, 83% (95% CI 76-90) in patients with one HRCA, and 63% (95% CI 54-74) in patients with two or more HRCA. Compared with patients with zero HRCA, the risk of death was significantly higher in patients with one HRCA (HR 2·55 [95% CI 1·22-5·36]; p=0·013) and two or more HRCA (HR 6·53 [95% CI 3·24-13·18]; p<0·0001). Patients with two or more HRCA also had a significantly higher risk of death than those with one HRCA (HR 2·56 [95% CI 1·53-4·28]; p=0·0004). The rates of 1-year sustained minimal residual disease negativity were similar in patients with zero HRCA (53 [35%] of 153] and with one HRCA (57 [41%] of 138) and were lower in patients with two or more HRCA (25 [24%] of 105). The median duration of follow-up from second randomisation was 37 months (IQR 33-42). 3-year progression-free survival from the second randomisation was 80% (95% CI 74-88) in patients with zero HRCA, 68% (95% CI 59-78) in patients with one HRCA, and 53% (95% CI 42-67) in patients with two or more HRCA. The risk of progression or death was higher in patients with one HRCA (HR 1·68 [95% CI 1·01-2·80]; p=0·048) and two or more HRCA (2·74 [95% CI 1·60-4·69], p=0·0003) than in patients with zero HRCA., Interpretation: This preplanned analysis of the FORTE trial showed that carfilzomib-based induction-intensification-consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death and therefore represent an unmet medical need., Funding: Amgen and Celgene/Bristol Myers Squibb., Competing Interests: Declaration of interests RM has received honoraria from Janssen, Celgene, Takeda, and Amgen; has served on the advisory boards for Janssen, Celgene, Takeda, Bristol Myers Squibb, and Amgen; and has received consultancy fees from Janssen, Takeda, and Sanofi. PM has received honoraria from Celgene, Janssen, Takeda, Bristol Myers Squibb, Amgen, Novartis, Gilead, Jazz, Sanofi, AbbVie, and GlaxoSmithKlin; and has served on scientific advisory boards for Celgene, Janssen, Takeda, Bristol Myers Squibb, Amgen, Jazz, Sanofi, AbbVie, and GlaxoSmithKline. LP has received honoraria from Celgene, Takeda, Amgen, Bristol Myers Squibb, and Janssen; has served on the advisory boards for Celgene, Bristol Myers Squibb, Amgen, and Janssen; and has received consultancy fees from Janssen. BG has received honoraria from Amgen, Bristol Myers Squibb, Janssen, and Takeda; and has served on the advisory boards for Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda. AP has served on the advisory board for Amgen; has received support for meeting fees, travel, and lodging expenses from Amgen, Celgene, and Janssen; and has received non-financial support from Celgene, Janssen, Roche, Takeda, and Amgen. NG has received research grants from Celgene and Janssen Pharmaceutical; has received sponsorship for clinical studies from Janssen Pharmaceutical and Millennium Pharmaceutical; has served on the advisory boards for Celgene, Takeda, and Janssen Pharmaceutical; and has received support for attending meetings from Janssen Pharmaceutical, Celgene, and Bristol Myers Squibb. AG has received honoraria from Celgene, Takeda, Amgen, and Janssen; and has served on the advisory boards for Takeda and Janssen. MC has received advisory fees from Celgene, Janssen, and Takeda; and has received research funding from Celgene. SB has received honoraria from Sanofi, Celgene, Takeda, and Janssen. EZ has received honoraria from and served on the advisory boards for Janssen, Bristol Myers Squibb, Takeda, Sanofi, Amgen, GlaxoSmithKline, and Oncopeptides. AB has served on the advisory boards for Amgen, Janssen, Celgene, GlaxoSmithKline, and Takeda. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; has served on the advisory boards for Janssen and GlaxoSmithKline; and has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Mundipharma. FG has received honoraria from Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, and GlaxoSmithKline; and has served on the advisory boards for Amgen, Celgene, Janssen, Takeda, Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Roche, Adaptive Biotechnologies, Oncopeptides, bluebird bio, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To evaluate the reasons for inadequate adherence to osteoporosis therapy and to describe the strategies for improving adherence to and persistence with regular medications, we conducted a review of the literature. The primary outcome of the study was the determination of the factors adverse to the onset and maintenance of anti-osteoporosis therapies. Secondly, we focused on studies whose efforts led to finding different strategies to improve adherence and persistence. We identified a total of 26 articles. The most recurrent and significant factors identified were aging, polypharmacy, and smoking habits. Different strategies to guide patients in their osteoporosis care have been identified, such as monitoring and follow-up via telephone calls, email, and promotional meetings, and proactive care interventions such as medication monitoring, post-fracture care programs, and decision aids. Changes in the drugs regimen and dispensation are strategies tried to lead to better adherence and persistence, but also improved satisfaction of patients undergoing anti-osteoporosis treatment. Patient involvement is an important factor to increase medication persistence while using a flexible drugs regimen.

In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression-free survival (PFS) was 22 months, and the 2-year probability of PFS was 47.6%. Creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2-year probability of OS was 63.5%. At multivariate analysis, creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice., (© 2022 John Wiley & Sons Ltd.)