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The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last decades. However, at relapse, overall survival (OS) ∼40% to 50% and is even lower for patients with chemorefractory disease. Effective and less-toxic therapies are urgently needed for these children. In the last years, immune-directed therapies such as chimeric antigen receptor (CAR)-T cells were introduced, which showed outstanding clinical activity against B-cell malignancies. CART therapies are being developed for AML on the basis of the results obtained for other hematologic malignancies. The biggest challenge of CART therapy for AML is to identify a specific target antigen, since antigens expressed in AML cells are usually shared with healthy hematopoietic stem cells. An overview of prospects of CART in pediatric AML, focused on the common antigens targeted by CART in AML that have been tested or are currently under investigation, is provided in this manuscript., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Psychotherapy is the cornerstone of the multidisciplinary treatment approach for eating disorders. This review examines recent evidence regarding effectiveness, predictors, and mechanisms of change of psychotherapy in eating disorders, providing a road map for clinicians and researchers., Recent Findings: Family-based treatments (FBT) are effective in adolescents with anorexia nervosa and bulimia nervosa. Evidence-based psychotherapies for anorexia nervosa have no evidence of superiority compared with treatment as usual (TAU) in adults with anorexia nervosa. Cognitive-behavioural therapy (CBT) is the first-choice psychotherapy recommended for adults with bulimia nervosa and binge-eating disorder (BED). Self-help interventions have some evidence of effectiveness in nonunderweight individuals with eating disorders. Early symptom improvement and adolescent age predict more favourable outcomes., Summary: Evidence-based psychotherapies can be suggested for eating disorders, although follow-up data are needed. Beyond anorexia nervosa, bulimia nervosa, and BED, there is no evidence of psychotherapy effectiveness in other eating disorders. The effectiveness of novel (e.g. 'third-wave') psychotherapies, treatment delivery modality (e.g. internet-delivered), and adjunctive interventions (e.g. virtual reality) needs to be further explored. A broader definition of recovery is recommended, including behavioural, physical, and psychological criteria. Predictors and mechanisms of changes have not been studied enough: quantitative and qualitative studies are needed to promote more tailored and individualized psychotherapy interventions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Background: Hemodynamic support using vasoactive agents is a mainstay in the management of patients with pediatric fluid-refractory septic shock (FRSS). However, evidence supporting the appropriate choice of vasoactive agent is limited. This study aimed to perform a systematic review and meta-analysis on the effect of different first-line vasoactive strategies on mortality in pediatric FRSS. Methods: MEDLINE, Embase, Scopus, CINAHL, Web of Science, the Cochrane Library, ClinicalTrials.gov , and the ISRCTN registry were searched up until December 2023. Randomized controlled trials and observational cohort studies reporting vasoactive agent-specific outcomes of children with FRSS were included. Mortality was assessed as primary outcome in studies on patients receiving dopamine, epinephrine, or norepinephrine as first-line. Random-effects meta-analyses were conducted. Prevalence ratio (PR) estimates were calculated between two drugs when was available in the same study. Findings: Of the 26,284 identified articles, 13 were included, for a total of 997 children. Twelve studies included 748 patients receiving a single vasoactive agent. Of these, 361 received dopamine, 271 epinephrine, and 116 norepinephrine. Overall pooled mortality for patients receiving a single vasoactive was 12% (95% CI 6%-21%) of which 11% (95% CI 3%-36%) for patients receiving dopamine, 17% (95% CI 6%-37%) for epinephrine, and 7% (95% CI 1%-48%) for norepinephrine. Four first-line dopamine (176 patients) and first-line epinephrine (142 patients): dopamine showed a tendency toward higher mortality (PR 1.38, 95% CI 0.81-2.38) and a significant higher need for mechanical ventilation (PR 1.12, 95% CI 1.02-1.22). Interpretation: Among children with FRSS receiving a single vasoactive agent, norepinephrine was associated with the lowest mortality rate. Comparing dopamine and epinephrine, patients receiving epinephrine needed less mechanical ventilation and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria., Methods: The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort., Results: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability., Conclusions: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Background: Increased lung-cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases., Methods: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits, and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects (NDE) and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately as well as by multiple quantitative bias analysis, using bootstrap to create 95% simulation intervals (SI)., Results: Mediation analysis of lung-cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung-cancer risk in the multiple bias analysis. Lung-cancer risks remained increased for lower SES groups, with higher risks in men [4th versus 1st (highest) SES quartile: CDE 1.50 (SI 1.32-1.69)] than women [CDE 1.20 (SI 1.01-1.45)]. NDE were similar to CDE, particularly in men., Conclusions: Bias adjustment lowered direct lung-cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures., Competing Interests: Competing interests: The authors do not declare any conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Physician modified endografts (PMEGs) have been widely used in the treatment of complex abdominal aortic aneurysm and thoracoabdominal aortic aneurysm, however, previous data are limited to small single center studies and robust data on safety and effectiveness of PMEGs are lacking. We aimed to perform an international multicenter study analyzing the outcomes of PMEGs in complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms., Methods: An international multicenter single-arm cohort study was performed analyzing the outcomes of PMEGs in the treatment of elective, symptomatic, and ruptured complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. Variables and outcomes were defined according to the Society for Vascular Surgery reporting standards. Device modification and procedure details were collected and analyzed. Efficacy outcomes included technical success and safety outcomes included major adverse events and 30-day mortality. Follow-up outcomes included reinterventions, endoleaks, target vessel patency rates and overall and aortic-related mortality. Multivariable analysis was performed aiming at identifying predictors of technical success, 30-day mortality, and major adverse events., Results: Overall, 1274 patients were included in the study from 19 centers. Median age was 74 (IQR, 68-79), and 75.7% were men; 45.7% were complex abdominal aortic aneurysms, and 54.3% were thoracoabdominal aortic aneurysms; 65.5% patients presented electively, 24.6% were symptomatic, and 9.9% were ruptured. Most patients (83.1%) were submitted to a fenestrated repair, 3.6% to branched repair, and 13.4% to a combined fenestrated and branched repair. Most patients (85.8%) had ≥3 target vessels included. The overall technical success was 94% (94% in elective, 93.4% in symptomatic, and 95.1% in ruptured cases). Thirty-day mortality was 5.8% (4.1% in elective, 7.6% in symptomatic, and 12.7% in ruptured aneurysms). Major adverse events occurred in 25.2% of cases (23.1% in elective, 27.8% in symptomatic, and 30.3% in ruptured aneurysms). Median follow-up was 21 months (5.6-50.6). Freedom from reintervention was 73.8%, 61.8%, and 51.4% at 1, 3, and 5 years; primary target vessel patency was 96.9%, 93.6%, and 90.3%. Overall survival and freedom from aortic-related mortality was 82.4%/92.9%, 69.9%/91.6%, and 55.0%/89.1% at 1, 3, and 5 years., Conclusions: PMEGs were a safe and effective treatment option for elective, symptomatic, and ruptured complex aortic aneurysms. Long-term data and future prospective studies are needed for more robust and detailed analysis., Competing Interests: The following authors declare conflicts of interest regarding consulting, research grants, advisory boards and/or any compensation fees from the mentioned companies. N. Tsilimparis (Proctor fees, speaking fees and institutional research support), D.J. Adam (speaking, research and proctor fees), L. Mendes Pedro (speaking and proctor fees), L. Bertoglio (speaking and proctor fees), T. Kölbel (speaking and proctor fees, institutional research support, royalties and consulting), and G. Panuccio (proctor and speaking fees) are supported by Cook Medical. R. Gouveia e Melo is supported by Cook Medical (speaking fees), Cordis (speaking fees), and Abbott Laboratories (travel and accommodation for congress). S. Scali is supported by Medtronic Inc, Boston Scientific Corporation, and Cook Medical (food and beverage). B. Mendes is supported by WL Gore & Associates Inc, Cook Medical (consulting, speaker and research fees, all proceeds towards Mayo Clinic), Medtronic Inc (aortic advisory board); and Bolton Medical Inc (food and beverage). S. Han is supported by WL Gore & Associates Inc, Cook Medical, Bolton Medical Inc (research support and consulting with all proceeds towards University of San Diego); Medtronic Inc (travel and lodging); Artivion Inc (food and beverage), Guard Medical Inc (consulting fees), Bolton Medical Inc (food and beverage), Endologix LLC (food and beverage), Silk Road Medical Inc (food and beverage), and Viz.ai Inc(food and beverage). M. Schermerhorn is supported by WL Gore & Associates Inc, Silk Road Medical Inc (travel and lodging), Shape Memory Medical Inc and Medtronic Inc (food and beverage). M. Farber is supported by Cook Medical (research support, honoraria and clinical trial support), Centerline Biomedical Inc, WL Gore & Associates Inc and Merck Sharp & Dohme LLC (consulting), Medtronic Inc and Getinge USA Sales LLC (food and beverage). B. Starnes is supported by Bolton Medical Inc, Terumo Aortic (consulting and travel and lodging), Surmodics Inc, Abbott Laboratories and Medtronic Inc and Cook Medical(food and beverage). D. Branzan is supported by Artivion, Bentley InnoMed, Cook Medical, Endologix, Getinge, and Medtronic (consulting and research support).C. Timaran is supported by Cook Medical, WL Gore & Associates Inc, and Philips Healthcare (research support and consulting). F. Verzini is supported by Cook Medical, WL Gore & Associates Inc, and Medtronic (proctor and speaking fees). A.W. Beck is supported by Artivion, Cook Medical, Medtronic, Philips Healthcare, Terumo, and WL Gore & Associates (research and consulting fees with all proceeds towards the University of Alabama). J. Chait is supported by WL Gore & Associates, Bard Peripheral Vascular, and Medtronic Inc (food and beverage). A. Pyun is supported by Silk Road Medical Inc (food and beverage) and Medtronic Inc (education). G. Magee is supported by Silk Road Medical Inc (consulting, travel and lodging, food and beverage), Medtronic Inc (consulting fees, travel and lodging), WL Gore & Associates (consulting fees, food and beverage), ShockWave Medical Inc (travel and lodging and food and beverage), Penumbra Inc, Boston Scientific Inc and Bolton Medical Inc (food and beverage). N. Swerdlow is supported by Silk Road Medical Inc and Shape Memory Medical Inc (food and beverage). M. Juszczak is supported by Cook Medical (research support) and Terumo (research grant). A. Barleben is supported by Cook Medical (consulting; travel and lodging fees), Endologix LLC (consulting; food and beverage), WL Gore & Associates (food and beverage), Silk Road Medical Inc (food and beverage), Penumbra Inc (consulting; travel and lodging), Musculoskeletal Transplant Foundation Inc (food and beverage), Abbott Laboratories (food and beverage), Surmodics Inc (food and beverage), and Cagent Vascular Inc (food and beverage). R. Patel is supported by Silk Road Medical Inc (food and beverage). M.P. Sweet is supported by Artivion Inc and Bolton Medical Inc (food and beverage). S.L. Zettervall is supported by WL Gore & Associates Inc, Bolton Medical Inc, Cook Medical, and Terumo Aortic (consulting and research support), Silk Road Medical Inc and Artivion Inc (food and beverage). G.S. Oderich is supported by Cook Medical (consulting, travel and lodging, speaking fees), WL Gore & Associates (consulting, travel and lodging, education, food and beverage), GE HealthCare (speaking fees, food and beverage), Centerline Biomedical Inc (consulting), Atrium Medical Corporation, Silk Road Medical Inc, Bard Peripheral Vascular Inc, Medtronic Inc (food and beverage). The remaining authors have no conflict of interest to declare.

Purpose of Review: Anaphylaxis is a severe, and potentially life-threatening hypersensitivity reaction whose diagnosis is based on clinical signs and symptoms and their prompt recognition. The presence of mimics and unusual presentations necessitate a careful evaluation and expertise in the field, due to potential diagnostic errors and hence a delay in the treatment.The aim of this review is to analyze and make an overview of the potential differential diagnosis of anaphylaxis, focusing on the clinical challenges of recognizing these conditions effectively among similar others., Recent Findings: The presence of mimics and unusual presentations of anaphylaxis necessitate a careful evaluation, emphasizing the importance of a comprehensive diagnostic approach.Tryptase is well known marker of mast cells activation, and a useful tool assisting the diagnosis of anaphylaxis, helping to differentiate it from atypical mimickers., Summary: The differential diagnosis of anaphylaxis comprises a very wide setting, and a systematic approach assessing different categories of cardiovascular, skin, respiratory airway, neuropsychiatric, and hematologic systems, can facilitate recognition of the correct diagnosis of this complex and life-threatening condition., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO., Design: Retrospective observational cohort study., Setting: Thirty-four centers from 16 countries between January 2000 and December 2020., Patients: Adults requiring post PC ECMO between 2000 and 2020., Interventions: None., Measurements and Main Results: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days ( n = 649 [32.1%]), 4-7 days ( n = 776 [38.3%]), 8-10 days ( n = 263 [13.0%]), and greater than 10 days ( n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days ( n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support ( n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival., Conclusions: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration., Competing Interests: Dr. Wiedemann received funding from Xenios, Fresenius, and Abbott. Dr. Whitman received funding from Avania, LLC. Dr. Miranda received funding from Resuscitec. Dr. Lorusso’s institution received funding from Medtronic, LivaNova, Eurosets, Abiomed, Xenios, Hemocue, ChinaBridge Medical, and Getinge. Dr. MacLaren is the president of the Extracorporeal Life Support Organization. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Abstract: In patients on oral anticoagulant (OAC) therapy undergoing percutaneous coronary intervention (PCI) with stent, international guidelines endorse the use of direct oral anticoagulants (DOAC) rather than vitamin K antagonists (VKA) and dual antithrombotic therapy (DAT) rather than triple antithrombotic therapy (TAT). The aim of this study was to evaluate contemporary real-world data on antithrombotic regimens and outcome in patients on OAC undergoing PCI with stent. Consecutive patients on OAC undergoing PCI were enrolled in the multicenter, prospective, observational PERSEO registry (NCT03392948). Primary end point was net adverse clinical events (NACE) with VKA versus DOAC, whereas a secondary prespecified end point was NACE with DAT versus TAT both at 1-year follow-up. From February 2018 to February 2022; in total, 1234 consecutive patients were included. The main indication for OAC was atrial fibrillation (86%), and the mean CHA 2 DS 2 VASc and HAS-BLED scores were 4 ± 2 and 3.6 ± 1, respectively. Of the 1228 patients discharged alive, 222 (18%) were on VKA and 1006 (82%) on DOAC ( P < 0.01). DAT was employed in 197 patients whereas TAT in 1028. At follow-up, NACE rate was significantly higher than VKA compared with DOAC (23% vs. 16%, P = 0.013) and confirmed after propensity score adjustment. TAT and DAT did not differ as regards NACE rate (17% vs. 19%, P = 0.864) although, compared with TAT, DAT was associated with less major bleedings (2% vs. 5%, P = 0.014), confirmed after propensity score adjustment. In conclusion, in patients on OAC undergoing PCI, DOAC, compared with VKA, was associated with a significantly lower occurrence of NACE and DAT reduced bleedings compared with TAT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments., Background: Robotic liver surgery has been gaining prominence over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated., Methods: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis., Results: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P<0.001), decreased blood transfusion (3.1% vs. 5.4%, P=0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P=0.004), lower proportion of open conversion (1.2% vs. 4.5%, P<0.001), shorter post operative stay (4 days vs. 5 days, P<0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P=0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR., Conclusion: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The psychopathological manifestations associated with substance use, including induced psychotic experiences, are increasingly relevant but not well-understood within the medical community. Novel psychoactive substances and potentiated old compounds like cannabis and cocaine have emerged as a global concern, especially among adolescents and young adults. Transition rates from substance-induced psychosis (SIP) to persistent psychosis are significant, particularly in cases of cannabis-induced psychosis. Scientific inquiry into induced psychotic phenomena has revealed differences between SIP and primary psychotic disorders, highlighting the risk factors associated with each. The concept of exogenous psychosis, including its toxic variant known as lysergic psychoma, provides valuable insights into the role of external factors in psychosis development. A phenomenological approach characterizes this disruption in perception as a shift in temporal and spatial dimensions, leading to auditory and visual hallucinations. The "twilight state" of consciousness plays a crucial role in the transition from substance use to psychosis, with implications for spatiality, intersubjectivity, and temporality. This complex path to psychosis challenges traditional diagnostic models and underscores the need for a more nuanced understanding of substance-induced psychopathological experiences., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evidence suggests that drug-coated balloons may benefit in-stent restenosis (ISR) treatment. However, the efficacy of new-generation sirolimus-coated balloon (SCB) compared with the latest generation drug-eluting stents (DESs) has not been studied in this setting., Methods: All patients in the EASTBORNE (The All-Comers Sirolimus-Coated Balloon European Registry) and DEB-DRAGON (DEB vs Thin-DES in DES-ISR: Long Term Outcomes) registries undergoing percutaneous coronary intervention for DES-ISR were included in the study. The primary study end point was target lesion revascularization at 24 months. Secondary end points were major adverse cardiovascular events, all-cause death, myocardial infarction, and target vessel revascularization at 24 months. Our goal was to evaluate the efficacy and safety of SCB versus thin-struts DES in ISR at long-term follow-up., Results: A total of 1545 patients with 1679 ISR lesions were included in the pooled analysis, of whom 621 (40.2%) patients with 621 lesions were treated with thin-strut DES and 924 (59.8%) patients with 1045 lesions were treated with SCB. The unmatched cohort showed no differences in the incidence of target lesion revascularization (10.8% versus 11.8%; P =0.568); however, there was a trend toward lower rates of myocardial infarction (7.4% versus 5.0%; P =0.062) and major adverse cardiovascular events (20.8% versus 17.1%; P =0.072) in the SCB group. After propensity score matching (n=335 patients per group), there were no significant differences in the rates of target lesion revascularization (11.6% versus 11.8%; P =0.329), target vessel revascularization (14.0% versus 13.1%; P =0.822), myocardial infarction (7.2% versus 4.5%; P =0.186), all-cause death (5.7% versus 4.2%; P =0.476), and major adverse cardiovascular event (21.5% versus 17.6%; P =0.242) between DES and SCB treatment., Conclusions: In patients with ISR, angioplasty with SCB compared with thin-struts DES is associated with comparable rates of target lesion revascularization, target vessel revascularization, myocardial infarction, all-cause death, and major adverse cardiovascular events at 2 years., Competing Interests: None.

Purpose: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy., Methods: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis., Results: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018)., Conclusion: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

Purpose of Review: The purpose of this review is to discuss the value of blood and CSF biomarkers in primary CNS tumors., Recent Findings: Several analytes can be assessed with liquid biopsy techniques, including circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free RNA, circulating proteins and metabolites, extracellular vesicles and tumor-educated platelets. Among diffuse gliomas of the adult, ctDNA in blood or CSF has represented the most used analyte, with the detection of molecular alterations such as MGMT promoter, PTEN, EGFRVIII, TERT promoter mutation and IDH R132H mutation. In general, CSF is enriched for ctDNA as compared with plasma. The use of MRI-guided focused ultrasounds to disrupt the blood-brain barrier could enhance the level of biomarkers in both blood and CSF. The detection of MYD88 L265P mutation with digital droplet PCR and the detection of ctDNA with next generation sequencing represent the best tools to diagnose and monitoring CNS lymphomas under treatment. In meningiomas, the low concentration of ctDNA is a limiting factor for the detection of driver mutations, such as NF2, AKTs, SMO, KLF4, TRAF7, SMARCB1, SMARCE1, PTEN, and TERT; an alternative approach could be the isolation of ctDNA through circulating extracellular vesicles. Liquid biopsies are being used extensively for diagnosis and surveillance of diffuse midline gliomas, in particular with the detection of the driver mutation H3K27M. Last, specific methylome patterns in CSF may allow the distinction of glioblastomas from CNS lymphomas or meningiomas., Summary: This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the probability of being cured of pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery., Background: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease., Methods: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multi-institutional database. A nonmixture statistical cure model was applied to compare disease-free survival to the survival expected for a matched general population., Results: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life expectancy (and tumor-free) as the matched general population was 20.4% (95% CI: 18.3, 22.5). Cure likelihood reached the 95% of certainty (time to cure) after 5.3 years (95% CI: 4.7, 6.0). A preoperative model was developed based on tumor stage at diagnosis ( P =0.001), radiologic size ( P =0.001), response to chemotherapy ( P =0.007), American Society of Anesthesiology class ( P =0.001), and preoperative Ca19-9 ( P =0.001). A postoperative model with the addition of surgery type ( P =0.015), pathologic size ( P =0.001), tumor grading ( P =0.001), resection margin ( P =0.001), positive lymph node ratio ( P =0.001), and the receipt of adjuvant therapy ( P =0.001) was also developed., Conclusions: Patients operated for PDAC can achieve a life expectancy similar to that of the general population, and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15 ., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in STEMI patients between 2012 and 2017 by comparing purchased tablets to expected ones at one year through pharmacy registries. Optimal adherence was defined ≥80%. Primary outcomes included all-cause and cardiovascular death, while secondary outcomes were myocardial infarction, major/minor bleeding events, and ischemic stroke The study included 4688 patients discharged on beta-blockers. Mean age was 64 ± 12.3 years, 76% were male, and mean LVEF was 49.2 ± 8.8%. Mean adherence at one year was 87.1%. Optimal adherence was associated with lower all-cause (adjHR 0.62, 95%CI 0.41-0.92, p 0.02) and cardiovascular mortality (adjHR 0.55, 95%CI 0.26-0.98, p 0.043). In LVEF ≤40% patients, optimal adherence was linked to reduced all-cause and cardiovascular mortality but this was not found either in patients with preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in all-comers STEMI patients reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect is confirmed only in patients with reduced LVEF (< 40%) at hospital discharge., Competing Interests: Conflicts of interest: none, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology., Recent Findings: Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection., Summary: While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: HIV-associated neurocognitive disorders (HAND) still affects persons with HIV (PWH) and their pathogenesis is not completely understood. We aimed to explore the association between plasma and cerebrospinal fluid (CSF) markers of blood-brain barrier (BBB) impairment and HAND in untreated PWH., Design: Cross-sectional study., Methods: We enrolled untreated PWH, who underwent blood examinations and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, tight junction proteins: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria)., Results: Twenty-one patients (21/78, 26.9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4 + T cells and increased CD4 + T-cell exhaustion (lower CD4 + CD127 + and CD4 + CD45RA + T-cell percentages), in comparison to individuals without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15) but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules were not associated with HAND but with a poor performance in different cognitive domains., Conclusion: By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PWH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Importance: The diagnostic accuracy of focused cardiac ultrasound (FoCUS) performed in patients presenting to the emergency department (ED) with chest pain is currently unknown., Objective: The objective of this study was to assess the diagnostic accuracy of regional wall motion abnormalities detected with FoCUS for non-ST-elevation acute coronary syndrome (NSTE-ACS) diagnosis., Design: A Single-center prospective observational study conducted in 2022 in the ED of the University Hospital Careggi, Italy., Setting and Participants: Adult patients presenting to the ED with acute nontraumatic chest pain were enrolled, irrespective of the presence of previous regional wall motion abnormalities. Patients with ST-segment elevation myocardial infarctions and patients with hemodynamic instability were excluded. FoCUS was performed at presentation by a trained ED physician., Outcome Measures and Analysis: The final diagnosis of NSTE-ACS vs. alternative diagnosis was adjudicated by an ED physician blinded to FoCUS results after a 30-day follow-up. To assess if regional wall motion abnormalities were an independent predictor of NSTE-ACS, a multivariable logistic regression model was built. Diagnostic performance measures were calculated. A sensitivity analysis considering only type-1 NSTEMIs (i.e. plaque rupture/thrombosis) was conducted., Main Results: Among 686 patients, NSTE-ACS was adjudicated in 106 (15.5%) patients, 67 of which were NSTEMIs. A total of 87 (12.7%) patients had regional wall motion abnormalities detected by FoCUS, which were an independent predictor of NSTE-ACS in the multivariable logistic regression analysis. Regional wall motion abnormalities had a sensitivity of 42.5% (33.0-51.9), a specificity of 92.8% (90.6-94.9), a negative predictive value of 89.8% (87.4-92.2), and a positive predictive value of 51.7% (41.2-62.2), for NSTE-ACS. Results were consistent in the sensitivity analysis., Conclusions: In ED patients with chest pain and no ST elevation, the detection of regional wall motion abnormalities was a predictor of NSTE-ACS. Despite a high specificity, which indicated a possible role of FoCUS in the rule-in of NSTE-ACS, sensitivity was too low to allow a safe rule-out using FoCUS results alone., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity., Methods: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters., Results: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure ( P =0.043), hepatic injury ( P =0.049), and suspected/definite infection ( P =0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P =0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P =0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; P adj =0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; P adj <0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; P adj =0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; P adj =0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; P adj =0.008)., Conclusions: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality., Competing Interests: None.

Purpose of Review: The worldwide spread of novel psychoactive substances (NPS) in the illicit drug market and their continuous increase in number and type, for the purpose of bypassing controlled substance legislation, represents a continuing challenge for forensic scientists, clinicians and enforcement authorities. We aim to provide information regarding the most urgent harms related to NPS consumption in different world regions and the current state of the art for NPS analysis., Recent Findings: Unfortunately, the identification of NPS in biological samples is controversial, especially when samples are limited, or the drug is promptly and extensively metabolized. This causes a lack of information on their real diffusion in different parts of the world and in different populations. New technologies and instrumental detection of NPS in alternative samples are offering comprehensive information about NPS use., Summary: The lack of detection and underreporting of NPS in biological samples makes it difficult to obtain complete qualitative and quantitative information about NPS prevalence. The most innovative strategies that have been proposed in the last 2 years to assist NPS analysis and possibly facilitate the understanding of the NPS diffusion around the world are presented., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) enrolled 1445 older (aged ≥75 years) patients with myocardial infarction and multivessel disease in Italy, Spain, and Poland. Patients were randomized to physiology-guided complete revascularization or treatment of the only culprit lesion. Physiology-guided complete revascularization significantly reduced ischemic adverse events at 1 year. This prespecified analysis investigated the changes between the 2 study groups in angina status, quality of life, physical performance, and frailty., Methods: Patients underwent validated scales at hospital discharge (baseline) and 1 year later. Angina status was evaluated using the Seattle Angina Questionnaire, health-related quality of life by EQ visual analog scale, physical performance by short physical performance battery, and frailty by the clinical frailty scale. Mixed models for repeated measures analysis were used to study the association between the treatment arms, time, and scales., Results: Baseline and 1-year Seattle Angina Questionnaire, EQ visual analog scale, short physical performance battery, and clinical frailty scale were collected in around two-thirds of the entire FIRE study population. The mean age was 80.9±4.6 years (female sex, 35.9%). Overall, 35.3% were admitted for ST-segment-elevation myocardial infarction, whereas the others were admitted for non-ST-segment-elevation myocardial infarction. Physiology-guided complete revascularization, compared with culprit-only revascularization, was associated with greater improvement in terms of angina status (Seattle Angina Questionnaire summary score, 7.3 [95% CI, 6.1-8.6] points), health-related quality of life (EQ visual analog scale, 6.2 [95% CI, 4.4-8.1] points), and physical performance (short physical performance battery, 1.1 [95% CI, 0.9-1.3] points). After 1 year, patients randomized to culprit-only revascularization experienced a deterioration in frailty status (clinical frailty scale, 0.2 [95% CI, 0.1-0.3] points), which was not observed in patients randomized to physiology-guided complete revascularization., Conclusions: The present analysis suggested that a physiology-guided complete revascularization is associated with consistent benefits in terms of angina status, quality of life, physical performance, and the absence of further deterioration of the frailty status., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03772743., Competing Interests: Dr Campo received research grants and personal fees from Abbott Vascular and personal fees from Menarini, Amgen, and Sanofi, outside the submitted work. Dr Biscaglia received personal fees from Abbott Vascular, outside the submitted work. The other authors report no conflicts.

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)., Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking., Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines., Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ )., Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings., Background: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined., Methods: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+., Results: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance., Conclusions: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS., Competing Interests: M.A.H. and M.G.B. received grants from Medtronic GmbH, Intuitive Surgical Inc., and Johnson & Johnson Medical GmbH for investigator-initiated studies. S.L.B. reported received fees from Baxter, Olympus, and Johnson & Johnson. M.S. reported received fees from Merck Serono GmbH, Bayer AG, ERBE Elektromedizin GmbH, Amgen Inc., AstraZeneca, Avateramedical GmbH, Johnson & Johnson Medical GmbH, TakedaPharmaceutical Limited, Olympus K.K., Medtronic GmbH, Intuitive Surgical Inc., Corzamedical, Baxter Int Inc. A.A.F. reported speaker’s honoraria from Bayer and Olympus. F.R. reported speakers' honoraria from Olympus. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To gain insight into the global practice of robot-assisted minimally invasive gastrectomy (RAMIG) and evaluate perioperative outcomes using an international registry., Background: The techniques and perioperative outcomes of RAMIG for gastric cancer vary substantially in the literature., Methods: Prospectively registered RAMIG cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia, and South-America. Techniques for resection, reconstruction, anastomosis, and lymphadenectomy were analyzed and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group., Results: Between 2020 and 2023, 759 patients underwent total (n=272), distal (n=465), or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%), or D2+ (12%). Median nodal harvest yielded 31 nodes (interquartile range: 21-47) after total and 34 nodes (interquartile range: 24-47) after distal gastrectomy. R0 resection rates were 93% after total and 96% distal gastrectomy. The hospital stay was 9 days after total and distal gastrectomy, and was median 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%., Conclusions: This large multicenter study provided a worldwide overview of current RAMIG techniques and their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG, and can be considered an international reference for surgical standardization., Competing Interests: J.R.: Consulting or Advisory Role: Intuitive Surgical. R.v.H.: Consulting or Advisory Role: Intuitive Surgical, Medtronic. T.K.: honorarium for lectures for Intuitive Surgical, Medtronic, Johnson & Johnson, and Olympus. E.K.: Consulting or Advisory Role: Intuitive Surgical. M.v.D.: Consulting or Advisory Role: Intuitive Surgical. J.P.H.: Consulting or Advisory Role: Intuitive Surgical. P.R.: Consulting or Advisory Role: Intuitive Surgical. O.S.-M.: Consulting or Advisory Role: Intuitive Surgical. The remaining authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess the success of the short-term location of the heavy silicone oil (Densiron 68, HSO) as endotamponade after pars plana vitrectomy for rhegmatogenous complex retinal redetachment., Methods: Consecutive, retrospective, nonrandomized, pilot study was conducted. Twenty-two eyes of 22 patients with complex inferior retinal redetachment previously tamponade with gas (SF6 or C3F8) or 1000 cSt standard silicone oil (SSO) were selected. All were treated with HSO endotamponade, and its removal was performed after 1 month. The main outcomes were best-corrected visual acuity and postoperative complications after the HSO removal., Results: Of the 22 eyes, 10 were treated with SSO endotamponade, 3 with fluorinated gas 14% C3F8, and 9 with 20% SF6 at first surgery. In all eyes, a complex inferior retinal redetachment was observed after the first surgery, in 1 month to 3 months after silicone oil removal or gas endotamponade introduction. In 10 eyes, the proliferative vitreoretinopathy (Grade B or C 1-3) was found. The main best-corrected visual acuity before HSO removal was 0.55 ± 0.20 the logarithm of the minimum angle of resolution (range 0.4-0.7) and after the HSO removal, it was 0.32 ± 0.29 the logarithm of the minimum angle of resolution (0.1-0.4). Among the postoperative complications, only in four eyes the macular edema was found (medically resolved), in four eyes an increase of intraocular pressure, and none of these developed the epiretinal membrane., Conclusion: The main purpose of this study is to establish a short-term HSO endotamponade in eyes with complex retinal detachment recurrences, reducing the possible postoperative complications and having a better prognosis for visual acuity outcomes.

Objective: We aimed to establish global benchmark outcomes indicators for L-RPS/H67., Background: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted., Methods: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff., Results: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively., Conclusions: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Abnormal encoding of somatosensory modalities (ie, mechanical, cold, and heat) are a critical part of pathological pain states. Detailed phenotyping of patients' responses to these modalities have raised hopes that analgesic treatments could one day be tailored to a patient's phenotype. Such precise treatment would require a profound understanding of the underlying mechanisms of specific pain phenotypes at molecular, cellular, and circuitry levels. Although preclinical pain models have helped in that regard, the lack of a unified assay quantifying detailed mechanical, cold, and heat pain responses on the same scale precludes comparing how analgesic compounds act on different sensory phenotypes. The conflict avoidance assay is promising in that regard, but testing conditions require validation for its use with multiple modalities. In this study, we improve upon the conflict avoidance assay to provide a validated and detailed assessment of all 3 modalities within the same animal, in mice. We first optimized testing conditions to minimize the necessary amount of training and to reduce sex differences in performances. We then tested what range of stimuli produce dynamic stimulus-response relationships for different outcome measures in naive mice. We finally used this assay to show that nerve injury produces modality-specific sex differences in pain behavior. Our improved assay opens new avenues to study the basis of modality-specific abnormalities in pain behavior., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The training and preferences of surgeons influence the type of surgical treatment for mandibular fractures. This multicentre prospective study analyzed the current treatment strategies and outcomes for mandibular fractures with open reduction and internal fixation (ORIF)., Material and Methods: This prospective study included patients aged ≥16 years who underwent ORIF for mandibular fractures in 12 European maxillofacial centers. Age, sex, pretrauma dental status, fracture cause, site and type, associated facial fractures, surgical approach, plate number and thickness (≤1.4 or ≥1.5 mm), duration of postoperative maxillomandibular fixation, occlusal and infective complications at 6 weeks and 3 months, and revision surgeries were recorded., Results: Between May 1, 2021 and April 30, 2022, 425 patients (194 single, 182 double, and 49 triple mandibular fractures) underwent ORIF for 1 or more fractures. Rigid osteosynthesis was performed for 74% of fractures and was significantly associated with displaced ( P =0.01) and comminuted ( P =0.03) fractures and with the number of nonsurgically treated fracture sites ( P =0.002). The angle was the only site associated with nonrigid osteosynthesis ( P <0.001). Malocclusions (5.6%) and infective complications (5.4%) were not associated with osteosynthesis type., Conclusion: Rigid osteosynthesis was the most frequently performed treatment at all fracture sites, except the mandibular angle, and was significantly associated with displaced and comminuted fractures and the number of nonsurgically treated fracture sites. No significant differences were observed regarding postoperative malocclusion or infections among osteosynthesis types., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Purpose of Review: Oligometastatic (om) cancer is considered as a transitional state in between locally confined disease and widespread metastases, accessible to a multimodal treatment, combining systemic and local therapy. In urothelial bladder cancer (BCa), the definitions and the approaches to this condition are poorly standardised and mainly based on retrospective data. We aim to portray the framework for uro-oncologic terminology in omBCa and go through the latest evidence and the future perspectives., Recent Findings: Retrospective and registry data support the potential benefits of multimodality treatment for carefully selected omBCa patients, especially following a good response to systemic treatment. In 2023, a Delphi consensus has defined omBCa, allowing maximum three metastatic lesions, theoretically amenable to radical local treatment. In de-novo omBCa, surgical treatment of primary tumour might improve overall survival (OS), according to a matched registry analysis; also, consolidative radiotherapy was associated with better OS in two recent cohorts. Furthermore, metastasis-directed therapy (MDT) has shown high local control rates and promising OS (14.9-51 months) in a meta-analysis; benefits might be more pronounced for single-site omBCa and nodal or lung lesions., Summary: From a clinical perspective, in de-novo omBCa, the local treatment of primary and metastatic sites might improve disease control and survival, in selected patients; in the oligorecurrent setting, MDT achieves good local symptom control with limited side effects; in selected cases, it could convey a survival benefit, too. From a research perspective, well designed prospective evidence is eagerly awaited, based on recently adopted shared definitions for omBCa., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa)., Recent Findings: Evidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa.Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life., Summary: MDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Patients with IDH1/2 -mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory., Methods: We retrospectively included patients with IDH1/2 -mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence., Results: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH -mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH -mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037)., Discussion: This study analyzed seizure control in patients with IDH1/2- mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH -mutant lower-grade glioma.

Background and Objectives: Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD., Methods: Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk., Results: In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results., Discussion: This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.

Background: Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis., Methods: Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography., Results: Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS., Conclusions: Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis., Competing Interests: Disclosures None.

Purpose: To assess the intersession repeatability of reading performance measures in patients with previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen)., Methods: Ninety-one patients (91 eyes) with a diagnosis of previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen) were prospectively enrolled. Reading performance metrics were assessed using Radner charts, and these measurements were repeated after 7 days to obtain the intersession repeatability. To test repeatability, we calculated the intraclass correlation coefficient, the 95% coefficient of repeatability, and the coefficient of variation for each reading parameter: 1) reading acuity (RA-LogRAD); 2) maximal reading speed-words per minute; 3) RA score (RA score-LogRAD); and 4) critical print size-LogRAD., Results: Mean ± standard deviation best-corrected visual acuity was 0.13 ± 0.01 logMAR [range: 0.00-0.30 logMAR]. The intraclass correlation coefficient values indicated a good reliability for all the analyzed metrics (0.901 for RA; 0.859 for max reading speed; 0.906 for RA score; and 0.868 for critical print size). The coefficient of repeatability was 0.2 LogRAD for RA, 63.2 words per minute for max reading speed, 0.2 LogRAD for RA score, and 0.2 LogRAD for critical print size. Coefficient of variation was 5.5% for RA, 8.9% for max reading speed, 5.8% for RA score, and 6.9% for critical print size., Conclusion: Reading performance metrics are characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. Our findings may grant the employment of such measures in trials assessing the visual outcome in these patients.

Competing Interests: The authors have no conflicts of interest to report.

Objective: HIV and Epstein-Barr virus (EBV) co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH)., Design: Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy ( n  = 70) or not., Methods: Serum and CSF anti-EBV viral capsid antigen immunoglobulin G (anti-EVI) and CSF EBV DNA were measured by commercial immunoassay and RT-PCR. Seventy-eight participants without neurological confounding factors underwent neurocognitive assessment (Global Deficit Score, GDS). CSF total tau and 181-phosphorylated-tau (ptau) were measured by immunoassays together with biomarkers of blood-brain barrier (BBB) integrity, immune activation, astrocytosis, and intrathecal synthesis. Logistic and linear regressions and moderation analysis were used to investigate the relationships between CSF anti-EVI, GDS, and biomarkers., Results: Twenty-one (17.1%) and 22 participants (17.9%) had detectable CSF anti-EVI (10.5-416.0 U/ml) and CSF EBV DNA (25-971 copies/ml). After adjusting for BBB integrity, age, and clinical factors, the presence of CSF anti-EVI was only associated with serum levels of anti-EVI, and not with CSF EBV DNA. CSF anti-EVI, tau and ptau showed reciprocal interactions affecting their associations with GDS. After adjusting for demographics and clinical parameters, higher CSF anti-EVI levels were associated with worse GDS (aβ 0.45, P  < 0.001), and CSF levels of tau and ptau had a moderation effect on the strength of this association (models' P  < 0.001)., Conclusion: Humoral immune responses against EBV within the central nervous system may contribute to NCI in PWH through mechanisms that involve neuronal injury., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The ability to respond to mechanical forces is a basic requirement for maintaining endothelial cell (ECs) homeostasis, which is continuously subjected to low shear stress (LSS) and high shear stress (HSS). In arteries, LSS and HSS have a differential impact on EC autophagy processes. However, it is still unclear whether LSS and HSS differently tune unique autophagic machinery or trigger specific autophagic responses in ECs., Methods: Using fluid flow system to generate forces on EC and multiscale imaging analyses on ApoE -/- mice whole arteries, we studied the cellular and molecular mechanism involved in autophagic response to LSS or HSS on the endothelium., Results: We found that LSS and HSS trigger autophagy activation by mobilizing specific autophagic signaling modules. Indeed, LSS-induced autophagy in endothelium was independent of the class III PI3K (phosphoinositide 3-kinase) VPS34 (vacuolar sorting protein 34) but controlled by the α isoform of class II PI3K (phosphoinositide 3-kinase class II α [PI3KCIIα]). Accordingly, reduced PI3KCIIα expression in ApoE -/- mice (ApoE -/- PI3KCIIα +/- ) led to EC dysfunctions associated with increased plaque deposition in the LSS regions. Mechanistically, we revealed that PI3KCIIα inhibits mTORC1 (mammalian target of rapamycin complex 1) activation and that rapamycin treatment in ApoE -/- PI3KCIIα +/- mice specifically rescue autophagy in arterial LSS regions. Finally, we demonstrated that absence of PI3KCIIα led to decreased endothelial primary cilium biogenesis in response to LSS and that ablation of primary cilium mimics PI3KCIIα-decreased expression in EC dysfunction, suggesting that this organelle could be the mechanosensor linking PI3KCIIα and EC homeostasis., Conclusions: Our data reveal that mechanical forces variability within the arterial system determines EC autophagic response and supports a central role of PI3KCIIα/mTORC1 axis to prevent EC dysfunction in LSS regions., Competing Interests: Disclosures None.

Purpose: To describe a case of a maxillofacial trauma that occurred during a mixed martial arts (MMA) match and to perform a literature review of maxillofacial injuries related to MMA match to determine whether preventive models are applicable., Methods: The authors described a maxillofacial injury with orbital and optic nerve involvement that happened during a professional MMA match. A literature review on maxillofacial trauma in MMA was conducted on Scopus and Pubmed with specific keywords., Results: Open reduction and internal fixation of the maxillofacial complex fractures with right eye optic neuropathy following an MMA match is described. Six articles were selected for the description of trauma in the maxillofacial complex associated with MMA fights., Discussion: Literature has paid little attention to injuries during MMA matches. The most common injury locations that emerged from the literature review were the head, face, and neck. Middle facial third injuries were the most common type. Frequently the injury involved the ophthalmic area., Conclusions: The timing of maxillofacial trauma in MMA is critical. Protective devices should be strongly promoted to prevent catastrophic consequences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

The main objective of this study was to retrospectively evaluate and compare the outcomes and complications of displaced closed tibial fractures in children treated by CRC (closed reduction and casting), elastic stable intramedullary nailing (ESIN) or external fixation (EF). One hundred twenty-three consecutive children were treated for displaced closed tibia shaft fracture from July 2014 and January 2020 at two different institutions. Seventy-five of them met the inclusion criteria and were included in the study: 30 (40%) patients were treated with CRC, 33 (44%) with ESIN, and 12 with EF (16%). All clinical and radiographic outcomes and complications were registered and compared. The three groups did not differ with regard to gender, affected side, fracture site and associated fibula fracture. The age at the time of treatment in the CRC group was statistically lower than in ESIN and EF groups (8.43 ± 3.52 years vs. 10.39 ± 2.56 years vs. 11.08 ± 3.55 years, respectively). Immobilization time and time to partial and total weight bearing were significantly reduced in ESIN and EF groups compared to CRC group (P < 0.05). Overall, no statistically significant differences were found between the three groups regarding complication rate and clinical and radiographic outcomes between the three groups. However, in CRC group, 3 patients (10%) had secondary fracture displacement and underwent ESIN. Surgical treatment is not contraindicated in children with displaced tibia shaft fractures. EF and ESIN provide earlier mobilization and weight-bearing recovery than CRC. However, apart from that, nonoperative treatment was as efficacious as surgical treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This article assesses work ability in a sample of blue-collar workers who often perform physically demanding tasks., Method: The data collected resulted in 354 validly completed questionnaires from 426 participants (response rate: approximately 90%)., Results: In this sample, the average score on WAI of workers is 37.42 (SD = 6.62), indicating good work ability. Regression analyses revealed that work ability was significantly associated skill discretion (β = 0.365, P = 0.001), home-work conflict (β = -0.199, P = 0.001), and work-home conflict (β = -0.320, P = 0.001)., Conclusions: Of the psychosocial factors examined in this study, skill discretion was the most important factor associated with work ability. Therefore, it is necessary to develop measures that support this component., Competing Interests: Conflict of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Purpose: The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab., Methods: This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded., Results: Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown., Conclusions: DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments., Background: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature., Methods: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias., Results: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset., Conclusions: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)