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Background: Early adverse experiences are assumed to affect fundamental processes of reward learning and decision making. However, computational neuroimaging studies investigating these circuits in the context of adversity are sparse and limited to studies conducted in adolescent samples, leaving the long-term effects unexplored., Methods: Using data from a longitudinal birth cohort study (n = 156; 87 female), we investigated associations between adversities and computational markers of reward learning (i.e., expected value, prediction errors). At age 33 years, all participants completed a functional magnetic resonance imaging-based passive avoidance task. Psychopathology measures were collected at the time of functional magnetic resonance imaging investigation and during the COVID-19 pandemic. We applied a principal component analysis to capture common variations across 7 adversity measures. The resulting adversity factors (factor 1: postnatal psychosocial adversities and prenatal maternal smoking; factor 2: prenatal maternal stress and obstetric adversity; factor 3: lower maternal stimulation) were linked with psychopathology and neural responses in the core reward network using multiple regression analysis., Results: We found that the adversity dimension primarily informed by lower maternal stimulation was linked to lower expected value representation in the right putamen, right nucleus accumbens, and anterior cingulate cortex. Expected value encoding in the right nucleus accumbens further mediated the relationship between this adversity dimension and psychopathology and predicted higher withdrawn symptoms during the COVID-19 pandemic., Conclusions: Our results suggested that early adverse experiences in caregiver context might have a long-term disruptive effect on reward learning in reward-related brain regions, which can be associated with suboptimal decision making and thereby may increase the vulnerability of developing psychopathology., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate 1) whether having a vascular comorbidity (i.e., hypertension, hyperlipidemia, heart disease, and diabetes) was associated with self-reported issues with functional activities among persons with multiple sclerosis (MS) and 2) if certain contributing factors (i.e., disability, depression, and fatigue) might explain the observed relationships., Materials and Methods: Participants ( n  = 263) completed the Functional Status Index (FSI), which assessed five domains: gross mobility, hand activities, personal care, home chores, and social/role activities. After bivariate analyses, individual linear regressions were conducted for each FSI domain, controlling for demographics. Follow-up mediation analyses were done for each of the three mediators., Results: Participants with vascular comorbidities endorsed more issues on all five domains, with the demographic-adjusted associations with gross mobility ( b  = 0.34, p  = 0.002), hand activities ( b  = 0.15, p  = 0.006), home chores ( b  = 0.44, p  = 0.003), and social/role activities ( b  = 0.32, p  = 0.024) remaining significant. Disability fully mediated the effects of vascular comorbidities on these domains, with partial and full mediations observed with depression and fatigue. Diabetes emerged as a significant individual comorbidity in several models., Conclusions: Vascular comorbidities, diabetes in particular, are associated with persons with MS endorsing worse ratings on functional outcomes, with disability, depression, and fatigue explaining these associations.

Background and Study Aims: Piecemeal EMR of large (≥20mm) non-pedunculated colorectal polyps (LNPCPs) is succeeded by a 6-month surveillance endoscopy to evaluate the post-EMR scar for recurrence. Data from expert centers suggest that routine tattoo placement and scar biopsies can be omitted, but data from community hospitals are lacking., Patients and Methods: In a post-hoc analysis of the STAR-LNPCP study (NTR7477), containing prospective data on 6-month post-pEMR scar assessments in 30 Dutch community hospitals (October 2019 to May 2022), the agreement between optical assessment and histological confirmation by routine biopsies was evaluated. Documentation of optical characteristics, imaging, and biopsies of the post-EMR scar were performed according to a standardized protocol., Results: In 1277 post-EMR scar assessments, identification of the scar was achieved in 1215/1277 (95%). Tattoo placement did not influence scar identification. Scar biopsy was performed in 1050/1215 cases (86%). Recurrences were seen in 200/1050 cases (19%). There was a good agreement between optical assessment of recurrence and histological confirmation (Cohen's kappa 0.78 [0.73-0.83]). The NPV was 98% [97-99%] and the PPV was 74% [68-80%]. Higher false positive rate was seen after prior use of clips (11% vs. 5%, p=0.017). Dedicated endoscopists identified the scar more often (96% vs. 88%, p<0.001), and showed a lower optical recurrence miss rate (1%vs. 3%, p=0.111) compared to non-dedicated endoscopists., Conclusion: Based on this multicenter community hospital study, routine tattoo placement and scar biopsies of the post-EMR scar can be omitted. Assessment of post-EMR scars by dedicated endoscopists is advised., Competing Interests: P. Siersema received grants or speaker’s fees from Pentax Japan, The E-Nose Company The Netherlands, Microtech China, Lucid Diagnostics USA, Magentiq Eye Israel, Norgine UK/The Netherlands, and Motus GI USA. M. Pellisé has received speaker’s fees from Norgine Iberia (2018-2023), Casen Recordati (2016 – 2019), Olympus (2018, 2022), Jansen (2018), Medtronic (2022), Fujifilm (2022); a consultancy fee GI Supply (2019), Fujifilm Europe (2022) and research funding from Fujifilm (2019-2021), Casen Recordati (2020); Ziuz (2021); 3-DMatrix (2021); her department has received loan material from Fujifilm (2017- ongoing), a consultancy service with Olympus (2022-ongoing); She is Board member of ESGE and AEG; and has received a fee from Thieme as an Endoscopy Co-Editor (2015-2021). She has shared actions of MiWendo. M. Bourke received research support for ethics-approved studies from Boston Scientific, Cook Medical, and Olympus Medical. A. Masclee received research grants from the Dutch Cancer Society (KWF) and the Dutch Organization for Health Research and Innovation (ZonMW). L. Moons acts as a consultant for Boston Scientific. The other authors disclose no competing interests., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Aim: To determine how gestational age at birth and postnatal growth relate to body composition in childhood., Methods: We calculated conditional growth (birth-2 years, 2 years-6 years) and measured body composition at 2 and 6 years using bioelectrical impedance in cohorts of New Zealand children born very preterm (VPT; 23-31 weeks), late preterm (LPT; 35- <37 weeks) and term (≥37 weeks). We explored the relationships between growth and fat mass (FM) index and fat-free mass (FFM) index at 6 years using multivariable linear regression., Results: Of 1125 children (51% male), 202 were VPT, 114 LPT and 809 Term. Compared to Term, VPT but not LPT were lighter and shorter at 2 and 6 years and had lower FM index and FFM index. The association between weight growth from 2 to 6 years and both FM index and FFM index at 6 years was stronger than for weight growth from birth to 2 years or height growth at any period in all gestational age groups., Conclusions: Size and body composition at 2 and 6 years are different between infants born VPT, but not LPT, and at term. Later weight growth is more strongly associated with childhood body composition than earlier growth., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Twisted bilayer graphene (TBG) represents a highly tunable, strongly correlated electron system. However, understanding the single-particle band structure alone has been challenging due to a lack of spectroscopic measurements over a broad energy range. Here, we probe the band structure of TBG around the magic angle using infrared spectroscopy and reveal spectral features that originate from interband transitions. In combination with quantum transport, we connect spectral features over a broad energy range (10-700 meV) and track their evolution with the twist angle. We compare our data with calculations of the band structures obtained via the continuum model and find good agreement only when considering a variation of interlayer/intralayer tunneling parameters with the twist angle. Our analysis suggests that the magic angle also shifts due to lattice relaxation and is better defined for a wide angular range of 0.9-1.1°. Additionally, our measurements offer an optical fingerprint of the magic angle for screening heterostructures before nanofabrication.

Purpose: To describe the medial-sided pathoanatomy and ligament injuries in acute MLKIs with medial-sided involvement andlook forassociated injury patterns based upon location of ligamentous injury., Methods: Patients who underwent treatment for MLKI at two level-1 trauma centers were identified between January 2001 and May 2023. Only cases involvingcomplete disruption of the superficial medial collateral ligament (sMCL) were included. Zone of injury to the sMCL, the posterior oblique ligament (POL), the medial patellofemoral ligament (MPFL), the vastus medialis oblique (VMO) was recorded, as well as demographics,injury details, neurovascular status, and mechanism of injury.Data was summarized usingdescriptive statistics., Results: A total of 92 patientswere included, with a mean age of 37.8 ± 12.7 years. Forty-four (47.8%) patients had a high velocity injury. Within sMCL tears, 39% were proximal avulsions, 29% were midsubstance tears, and 32% were distal avulsions. The medial-sided injury patterns were: 31 (33.7%) isolated sMCL tears, 24 (27.3%) combined sMCL, POL, and MPFL tears, 23 (25%) combined sMCL and MPFL tears, and 11 (12%) combined sMCL and POL tears. Most common location of sMCL injury varied based upon the number of associated medial knee ligaments injured: isolated sMCL (even distribution), sMCL & POL (distal), sMCL-MPFL (proximal), sMCL-POL-MPFL (proximal)., Conclusion: Medial-sided ligament injuries seen MLKIs were found to occur in four injury patterns ranging from isolated sMCL or combined injury patterns of the adjacent medial structures. Additionally, location of sMCL injury varied based upon the number of medial-sided ligaments injured., 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 © 2024 Elsevier B.V. All rights reserved.)

Objectives: To describe maternal and perinatal outcomes in patients with BMI ≥30 kg/m 2 by BMI class and gestational weight gain., Methods: Retrospective review of singleton pregnancies with pre-pregnancy BMI ≥30 kg/m 2 who received care at our institution between January 1, 2016 and December 31, 2021. Patients were divided into three categories based on BMI (kg/m 2 ): Class I (BMI 30.0-34.9), Class II (BMI 35-39.9), and Class III (BMI≥40) obesity. For gestational weight gain analysis, pregnancies were stratified into three groups: <11 pounds, 11-20 pounds, and >20 pounds. Maternal demographics and outcomes were compared using chi-square analysis, analysis of variance, nonparametric tests, and multivariable regression analysis., Results: Of 641 patients included, 299 (46.6 %) were in Class I, 209 (32.6 %) in Class II, and 133 (20.7 %) in Class III. Readmission within 6 weeks postpartum, the only outcome found to have a significant difference between BMI categories, was higher in the Class III group (p=0.01). One hundred sixty-two (25.3 %) patients gained <11 pounds, 164 (25.6 %) gained 11-20 pounds, and 313 (48.8 %) gained ≥20 pounds. Greater gestational weight gain was associated with increased rates of cesarean delivery (p<0.001), higher quantitative blood loss (p=0.006), longer length of hospitalization (p=0.03), and higher birthweights (p<0.001)., Conclusions: This represents a unique and actionable opportunity for clinicians to counsel and support their patients in adhering to optimal weight gain targets throughout their pregnancy. Future studies are needed to determine the optimal gestational weight gain recommendations for obese patients., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background Structural and functional MRI studies have revealed brain alterations associated with opioid use disorder (OUD). However, previous research has been limited by small sample sizes, few female participants, and single-modality analyses. Purpose To identify structural and functional brain alterations in individuals with OUD using whole-brain data-driven methods to analyze T1-weighted MRI and resting-state functional MRI (rsfMRI). Materials and Methods This secondary analysis of the Collaboration Linking Opioid Use Disorder and Sleep study compared participants with OUD (data collection February 2021 to February 2023) receiving methadone treatment with healthy control participants (data collection February 2018 to May 2023). T1-weighted MRI and rsfMRI were analyzed using tensor-based morphometry and intrinsic connectivity distribution, respectively. Primary outcome measures included regional brain volumes and functional connectivity. Voxel-wise linear regression was used to assess group differences, with family-wise error correction. Pearson partial correlations were used to examine structure-function relationships. Results Compared with healthy control participants ( n = 105; median age, 27 years [IQR, 23-37 years]; 58 female), participants with OUD ( n = 103; median age, 37 years [IQR, 31.5-46 years]; 62 male) showed smaller volumes (corrected P < .05) in the thalamus (β = -17.42 [95% CI: -26.56, -8.27]) and right medial temporal lobe (β = -8.02 [95% CI: -12.25, -3.78]). Larger volumes (corrected P < .05) were seen in the brainstem (pons and medulla, β = 15.21 [95% CI: 7.03, 23.40]; midbrain, β = 13.04 [95% CI: 6.61, 19.47]) and cerebellum (right, β = 14.96 [95% CI: 7.25, 22.67]; left, β = 14.88 [95% CI: 7.32, 22.43]). An interaction between sex and group was found for medial prefrontal cortex volume (β = -19.38, corrected P < .05), with female participants having smaller volumes than male participants in the OUD group. Increased functional connectivity (corrected P < .05) was noted in the thalamus (β = 0.50 [95% CI: 0.25, 0.75]), right medial temporal lobe (β = 0.43 [95% CI: 0.21, 0.66]), right cerebellum (β = 0.46 [95% CI: 0.21, 0.71]), and brainstem (β = 0.48 [95% CI: 0.22, 0.74]) in the OUD group. Structure and function were positively correlated in the cerebellum (Pearson r = 0.32 [95% CI: 0.17, 0.44], P < .001) and brainstem (Pearson r = 0.23 [95% CI: 0.09, 0.37], P = .002). Conclusion Individuals with OUD showed overlapping structural and functional brain alterations in opioid receptor-dense regions compared with healthy control participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Messina in this issue.

Introduction: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with inflammatory complications. There are no known placental histopathological features, which are unique to PE. It is often pooled with the fetal growth restriction (FGR) under a single umbrella pathophysiology, the maternal vascular malperfusion (MVM). The aim of this study is to assess the villous trophoblast and the villous tree quantitatively in PE placentas and to identify morpholgical correlates unique to PE., Methods: 20 PE placentas (10 female and 10 male) and 20 Control placentas (10 female and 10 male) were included in the study. The villous trophoblast and the villous tree were assessed quantitatively by Stereology and 3D Microscopy. For Stereology measurements, the villous tree was classified in contractile and non-contractile parts based on immunohistochemical detection of perivascular myofibroblasts., Results: The density of proliferative trophoblast nuclei is increased, whereas the density of non-proliferative trophoblast nuclei is decreased in female PE placentas. The male PE placentas do not show this effect. Though no significant difference in the diffusion distance was observed, the non-contractile villi and the fetal vessels inside show a significantly reduced volume in PE placentas. The branching index of the villous tree is lower in PE placentas in general. However, in female PE placentas the deviation is accentuated., Conclusion: In PE, the villous trophoblast shows a sexually dimorphic alteration in the density of proliferative and non-proliferative nuclei, which is inherently different from FGR., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Second-order superlattices form when moiré superlattices with similar periodicities interfere with each other, leading to larger superlattice periodicities. These crystalline structures are engineered using two-dimensional materials such as graphene and hexagonal boron nitride, and the specific alignment plays a crucial role in facilitating correlation-driven topological phases. Signatures of second-order superlattices have been identified in magnetotransport experiments; however, real-space visualization is still lacking. Here we reveal the second-order superlattice in magic-angle twisted bilayer graphene closely aligned with hexagonal boron nitride through electronic transport measurements and cryogenic nanoscale photovoltage measurements and evidenced by long-range periodic photovoltage modulations. Our results show that even minuscule strain and twist-angle variations as small as 0.01° can lead to drastic changes in the second-order superlattice structure. Our real-space observations, therefore, serve as a 'magnifying glass' for strain and twist angle and can elucidate the mechanisms responsible for the breaking of spatial symmetries in twisted bilayer graphene., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Importance: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care., Objective: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce., Evidence Review: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions., Findings: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology., Conclusions and Relevance: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients., (© 2024. The Author(s).)

Competing Interests: The authors report no financial relationships with commercial interests.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors. Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations. Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p  < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p  = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p  = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning. Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Objectives: Methylene blue exerts its vasopressor properties by inhibiting nitric oxide-mediated vasodilation. Recent studies have advocated the use of methylene blue as a rescue therapy for patients with septic shock. The primary aim was to investigate the effect of methylene blue on the mean arterial pressure among adult patients with septic shock., Methods: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their inception date until October 2023. Randomized Clinical Trials (RCT) comparing methylene blue and placebo in adults with septic shock were included., Results: Our systematic review included 5 studies (n = 257) for data analysis. As compared to the placebo, our pooled analysis showed that methylene blue significantly increased mean arterial pressure (MD: 1.34 mmHg, 95% CI 0.15 to 2.53, p = 0.03, level of evidence: very low). Patients who were given methylene blue were associated with statistically lower mortality rate (OR = 0.49, 95% CI 0.27 to 0.88, p = 0.02, level of evidence: low), reduced serum lactate levels (MD: -0.76 mmoL.L -1 , 95% CI -1.22 to -0.31, p = 0.0009, level of evidence: low), reduced length of hospital stay (MD: -1.94 days, 95% CI -3.79 to -0.08, p = 0.04, level of evidence: low), and increased PaO 2 /FiO 2 (MD: 34.78, 95% CI 8.94 to 60.61, p = 0.008, level of evidence: low)., Conclusions: This meta-analysis demonstrated that methylene blue administration was associated with an increased in mean arterial pressure and PaO 2 /FiO 2 ratio, along with a reduction in mortality rates, serum lactate levels, and length of hospital stay. However, substantial degree of heterogeneity and inadequate number of studies with low level of evidence warrant future adequately powered RCTs to affirm our results., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported. No funding was received in support of this project., (Copyright © 2024. Published by Elsevier España S.L.U.)

Background and Purpose: Lower limb (LL) weakness and gait impairment are prevalent among persons with multiple sclerosis (PwMS) and can impede functional independence and impact health-related quality of life (HR-QoL). The purpose of this study was to examine the mediation effect of walking speed and perceived walking ability on the relationship between LL weakness and HR-QoL in ambulatory PwMS., Methods: Participants (n = 175) were PwMS in this secondary analysis of a cross-sectional study. Demographics, pain (visual analog scale), fatigue (5-item Modified Fatigue Impact Scale), LL strength (hip extensors [HE] and flexors [HF], knee extensors [KE] and flexors [KF], and ankle plantarflexors [APF] and dorsiflexors [ADF]), Timed 25-Foot Walk, 12-item MS Walking Scale, and HR-QoL (MS Impact Scale-Physical [MSIS-29-Phys] and Psychological [MSIS-29-Psych]) were collected. Bivariate and mediation analyses using Hayes' PROCESS were performed to determine if LL strength had an indirect effect through walking speed or perceived walking ability on physical and psychological HR-QoL while controlling for fatigue and pain., Results: There were significant (P < 0.01) correlations for all strength measures with the MSIS-29-Phys and for HF, KE, KF, and APF with the MSIS-29-Psych. In the mediation analyses, LL strength indirectly influenced PwMS' MSIS-29-Phys through walking speed and perceived walking ability. There was only partial mediation between HE, HF, KF, ADF, and MSIS-29-Phy when walking speed was in the model. LL strength did not influence MSIS-29-Psych., Discussion and Conclusions: LL strength impacts physical HR-QoL through walking but does not indirectly affect PwMS' perceived psychological HR-QoL. These findings may prompt physical therapists to create individualized care plans that address LL weakness and walking impairments with the goal of promoting optimal outcomes and improving HR-QoL., Video Abstract Available: for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A504)., (Copyright © 2024 Academy of Neurologic Physical Therapy, APTA.)

Purpose: The aim of this article is to review the current literature regarding the use of bone marrow aspirate concentrate (BMAC) in rotator cuff repair (RCR) surgery to determine variations in the preparation and administration of BMAC, assess the healing rates with the use of BMAC in terms of post-operative range of motion (ROM), patient reported outcomes (PROMs), and retear rates, and finally to analyze the safety of using BMAC., Methods: A PRISMA-S compliant search was performed. Two independent authors screened all suitable studies for their inclusion, obtained the data, and assessed risk of bias. The types of studies included in the analysis were human studies of randomized control trials, prospective cohort, case-control, and case-series., Results: 7 studies reported PROMs: 4/7 studies reported statistically significant improvements in at least 4 different scores with 2/7 studies reporting general improvements in the BMAC groups (with no statistical analysis provided). Of the two comparative studies, neither was able to show a difference in PROMs between the control and biologic groups. Post-operative range of motion was reported in 5 studies: 3/5 studies showed statistically significant improvement in ROM, 1 study showed general improvement (with no statistical analysis provided), and 1 study showed no difference in post-operative ROM between a BMAC and control group. Retear rates were mixed, with one study reporting rates between the concentrated Bone Marrow Aspirate (cBMA) and control group did not differ (p=0.964), while another found that the MSC augmentation improved healing both short (6 months) and long-term (10 years). There were no complications associated with the use of BMAC in rotator cuff repairs in any of the papers included., Conclusion: This systematic review demonstrates that bone marrow aspirate concentrate as an intervention in rotator cuff repair has not been associated with increased complication rates. In the available literature, there is significant heterogeneity among the included studies in terms of study design, patient demographics, surgical techniques, and methods of BMAC preparation and application as well as reported measures and follow up periods. Some studies suggest that BMAC may enhance healing rates, pain relief, and functional improvements for both short and long-term outcomes., Level of Evidence: Level IV, Systematic review of Level I to IV studies., (Copyright © 2024. Published by Elsevier Inc.)

Background: Low back pain (LBP) presents with diverse manifestations, necessitating personalized treatment approaches that recognize various phenotypes within the same diagnosis, which could be achieved through precision medicine. Although prediction strategies have been explored, including those employing artificial intelligence (AI), they still lack scalability and real-time capabilities. Digital care programs (DCPs) facilitate seamless data collection through the Internet of Things and cloud storage, creating an ideal environment for developing and implementing an AI predictive tool to assist clinicians in dynamically optimizing treatment., Objective: This study aims to develop an AI tool that continuously assists physical therapists in predicting an individual's potential for achieving clinically significant pain relief by the end of the program. A secondary aim was to identify predictors of pain nonresponse to guide treatment adjustments., Methods: Data collected actively (eg, demographic and clinical information) and passively in real-time (eg, range of motion, exercise performance, and socioeconomic data from public data sources) from 6125 patients enrolled in a remote digital musculoskeletal intervention program were stored in the cloud. Two machine learning techniques, recurrent neural networks (RNNs) and light gradient boosting machine (LightGBM), continuously analyzed session updates up to session 7 to predict the likelihood of achieving significant pain relief at the program end. Model performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), precision-recall curves, specificity, and sensitivity. Model explainability was assessed using SHapley Additive exPlanations values., Results: At each session, the model provided a prediction about the potential of being a pain responder, with performance improving over time (P<.001). By session 7, the RNN achieved an ROC-AUC of 0.70 (95% CI 0.65-0.71), and the LightGBM achieved an ROC-AUC of 0.71 (95% CI 0.67-0.72). Both models demonstrated high specificity in scenarios prioritizing high precision. The key predictive features were pain-associated domains, exercise performance, motivation, and compliance, informing continuous treatment adjustments to maximize response rates., Conclusions: This study underscores the potential of an AI predictive tool within a DCP to enhance the management of LBP, supporting physical therapists in redirecting care pathways early and throughout the treatment course. This approach is particularly important for addressing the heterogeneous phenotypes observed in LBP., Trial Registration: ClinicalTrials.gov NCT04092946; https://clinicaltrials.gov/ct2/show/NCT04092946 and NCT05417685; https://clinicaltrials.gov/ct2/show/NCT05417685., (©Anabela C Areias, Robert G Moulder, Maria Molinos, Dora Janela, Virgílio Bento, Carolina Moreira, Vijay Yanamadala, Steven P Cohen, Fernando Dias Correia, Fabíola Costa. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.11.2024.)

Background: Multiple sclerosis (MS) disease factors, such as cognitive impairment, can cause disruptions in meaningful activities, also known as illness intrusiveness. Although the association between specific objective measures of cognition and illness intrusiveness has been documented in MS, the contributions of individuals' perceptions of their cognition or whether any psychological factors can buffer the relationship have yet to be explored. This study aimed to (1) simultaneously examine objective processing speed and subjective cognition as disease factors contributing to illness intrusiveness and (2) explore whether resilience moderates the relationship between cognition and illness intrusiveness., Methods: Participants (N = 112) were individuals with MS who completed the Illness Intrusiveness Ratings Scale (IIRS), Symbol Digit Modalities Test (SDMT), Perceived Deficits Questionnaire (PDQ), and MS Resiliency Scale (MSRS) as part of a larger cross-sectional study. A hierarchical linear regression was done, followed by individual moderation analyses., Results: Both the PDQ ( b = .43, P = .001) and SDMT ( b = -4.17, P = .003) were independent predictors of the IIRS. There was no evidence of moderation in either model, although the MSRS independently contributed to the IIRS., Conclusions: Among individuals with MS, objective processing speed and subjective cognition were independently associated with illness intrusiveness, highlighting the importance of considering both cognitive performance and perceptions as contributing factors to life disruptions., (© 2024 Consortium of Multiple Sclerosis Centers.)

Background: It is recommended that healthcare providers and persons with multiple sclerosis (MS) have discussions prior to discontinuing a disease modifying therapy (DMT). However, if these appointments missed, either as a no show (NS) or short-notice cancellation (SNC), these discussions do not take place and may result in premature discontinuation. This study aimed to explore whether appointment non-attendance was predictive of DMT persistence the following year., Methods: Electronic health record data from Veterans with MS (n = 3,742) in the Department of Veterans Affairs (VA) MS Center of Excellence Data Repository were examined during two time frames: January 2013 - December 2013 (Year 1) and January 2014 - December 2014 (Year 2). DMT non-persistence was defined as discontinuing a DMT and not restarting another one within 90 days. The proportion of each type of missed appointment in Year 1 was calculated by dividing the number of NS and SNC by the total number of scheduled appointments during that time frame, respectively. Logistic regressions were run for each appointment non-attendance behavior, with Year 2 non-persistence as the outcome and age, sex, race, number of comorbidities, time since initial DMT, and Year 1 non-persistence as covariates., Results: Veterans who were non-persistent in Year 2 (n = 563) had a higher proportion of NS (6.5 % vs. 4.6 %, p < .001) and SNC (6.7 % vs 5.7 %, p = .002) in Year 1. After adjusting for demographics and DMT history, both the proportion of NS (aOR = 5.01, 95 % CI: 1.82, 13.29, p = .001) and SNC (aOR = 3.86, 95 % CI: 1.09, 12.90, p = .032) in Year 1 were significantly associated with non-persistence the following year., Conclusions: Appointment non-attendance was associated with DMT non-persistence the following year, with both higher proportions of NS and SNC being significant contributors after controlling for demographics and DMT history. These findings highlight the potential effects of disruption to care for persons with MS., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Published by Elsevier B.V.)

Repeat blood cultures are common in children after an initial positive culture. However, in contrast to adults, there are little data to help guide clinicians when a repeat culture is necessary to assess for persistent bacteremia. This study identifies factors associated with persistent bloodstream infections (BSI) in children to inform diagnostic stewardship. This cross-sectional study of children less than 18 years with at least one positive blood culture over a 5-year period utilized a generalized linear equation model to predict patient and microbial factors associated with persistent BSI defined as a positive blood culture with the same organism >48 hours after the index culture. Four hundred and five patients had 502 positive blood cultures yielding 556 organisms. Sixty-seven (13.2%) cultures were persistently positive. Anaerobic organisms (0/37) and Streptococcus species (0/104) were never recovered from repeat cultures. Staphylococcus aureus (OR 9.45, CI 5.15-17.35) and yeast (OR 78.18, CI 9.45-646.6) were statistically associated with persistent BSI. Patients with prior positive cultures (OR 1.44, CI 1.12-1.84) or a central venous catheter (OR 2.20, 95% CI 1.04-3.92) were also at risk for persistence. Immune dysfunction and elevated inflammatory markers at the time of the index blood culture were not significantly associated with persistence. Yeast or S. aureus were associated with persistent BSI, while anaerobes and Streptococcus species were never persistent. Patient characteristics at the time of blood draw did not predict persistence other than having previous positive blood cultures or a central venous catheter. These data can inform when repeat blood cultures have clinical value and reduce the risk of unnecessary blood draws in children., Importance: We identify factors associated with bloodstream infection persistence in children. Our findings can help guide blood culture stewardship efforts in pediatric patients, especially in light of blood culture supply shortages., Competing Interests: D.R.P. has received research funding from Hologic, Inc.. and honoraria from Beckton Dickinson.

Background: In this review, the complicated landscape of breast cancer management is explored with a focus on the promising synergies between ribociclib and endocrine therapy. Ribociclib mainly acts as a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, which disrupts cell cycle progression necessary for tumor growth. This, in combination with endocrine therapy, aims to produce hormone receptor-positive breast cancers, which is a very relevant subtype with challenging therapeutics., Methods: A comprehensive review was conducted using multiple databases, PubMed, Embase, Scopus, Cochrane Library, and Web of Science, covering the period from January 1990 to May 2024., Results: Pharmacokinetic studies underscore the efficacy and tolerability of ribociclib, thus providing vital information for dose adjustments, particularly among patients with renal and hepatic impairments. Ribociclib's value in extending progression-free survival and improving overall survival has been shown by clinical trials such as the MONALEESA series. Quality of life considerations and patient-reported outcomes from these trials indicate that ribociclib has a broader effect on the well-being of the patients. However, despite the success experienced by this drug in clinical practice, it still has some side effects, including hematologic toxicity, hepatotoxicity, and thromboembolism associated with it. Ribociclib resistance mechanisms are multifaceted mixtures comprising genetic variations or mutations, compensatory signaling pathways, and epigenomic changes. While overcoming resistance remains challenging, ongoing research seeks to reconcile., Conclusion: Ribociclib combined with endocrine therapy represents a significant advancement in breast cancer treatment, albeit with challenges that necessitate ongoing research and holistic patient care approaches., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study presents a description of a new stick insect species belonging to the genus Trychopeplus Shelford, 1909, discovered by the authors in the Chocó ecoregion of northwestern Ecuador. Trychopeplusmashpiensis sp. nov. is described and illustrated based on males, females, and eggs. The distinctive features of this new species, such as its unique body ornamentation and the morphology of its egg structure without fringes, clearly differentiate it from other known species within the genus. Photographs of the new species are provided, along with an updated key and distribution map for all Trychopeplus species. These findings enhance our understanding of the genus's diversity., Competing Interests: The authors have declared that no competing interests exist., (Oskar V. Conle, Pablo Valero, Frank H. Hennemann.)

Uric acid (UA) is an antioxidant that has been reported to be a neuroprotective compound for injuries and diseases, and specifically, diseases of the central nervous system. However, uric acid is highly insoluble in aqueous solutions, and high levels in the serum lead to gout, which limits its use in humans. Here, we develop a novel drug delivery platform that will release uric acid in a sustained manner for application to neural tissue. We demonstrate that one-step incorporation of UA into an electrospun gelatin/hyaluronic acid nanofiber mat results in controlled release of UA in culture medium. Taking a unique approach, we made solutions of 12% gelatin and 1% hyaluronic acid in a formic acid solvent and added UA for production of nanofiber mats. We then dehydrothermally crosslinked the mats and tested for release of UA into physiological cell culture medium. To test whether the mats have any detrimental effects on healthy nervous system tissue, we cultured spinal cord explants on the mats extended and assessed extensions from the explants. We observed that comparable numbers and lengths of dendrites are extended from the spinal cord tissue, regardless of the amount UA content in the mats. Our results suggest that electrospun gelatin/hyaluronic acid nanofibers can be used as a platform for sustained uric acid delivery to neural tissue without detrimental effects., (© 2024 American Institute of Chemical Engineers.)

Background: The United Republic of Tanzania has had a 41.4% mortality rate in the intensive care unit. In Tanzania, the Ministry of Health and Social Welfare has implemented quality improvement (QI), yet the Tanzanian health sector continues to face resource constraints, unsustainable projects and gaps in knowledge and skills, contributing to unacceptably high mortality rates for Tanzanian patients. This research aims to determine if a Critical Care Training Program incorporating QI concepts can improve technical competence and self-efficacy of providers in a critical care setting in Tanzania., Methods: A 2-day Critical Care Training Program was developed for providers. It included the following modules: vital signs directed therapy (VSDT), cardiopulmonary and brain resuscitation (CPBR), blood glucose monitoring, introduction to critical care concepts and the QI concept of change management. For analysis, data were collected from pretests and post-tests and reported in REDCap. Descriptive statistics and paired t-tests were performed (alpha=0.05)., Results: A total of 77 nurses and three providers attended the training. The overall score changes among participants for CPBR and VSDT were significant (p<0.001). Six out of 10 questions in CPBR demonstrated significant improved change (p<0.001). All questions in the VSDT training showed significant improvement (p<0.001). Based on hospital guidelines, 63 (95.5%) passed the CPBR evaluation and 62 (95.2%) passed VSDT., Conclusion: A pre/post analysis demonstrated improvement in knowledge, skills and increased confidence towards emergencies. This study suggests a Critical Care Training Program significantly improves the knowledge among providers and that QI impacts culture of change. This research exemplifies a systematic approach to strengthening capacity of critical care delivery in limited resource settings, with implications for further innovation in other low- and middle-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases., Objectives: We aimed to characterize respiratory dysfunction in mild to moderate PD., Methods: In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON-medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing F I O 2 from 0.209 (room air) to 0.127, which was compared to eight age- and sex-matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45-min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF-medication to assess breathing responses., Results: At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038-0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45-min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (-0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079)., Conclusions: Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Controlling excitons at the nanoscale in semiconductor materials represents a formidable challenge in the quantum photonics and optoelectronics fields. Monolayers of transition metal dichalcogenides (TMDs) offer inherent 2D confinement and possess significant exciton binding energies, making them promising candidates for achieving electric-field-based confinement of excitons without dissociation. Exploiting the valley degree of freedom associated with these confined states further broadens the prospects for exciton engineering. Here, we show electric control of light polarization emitted from one-dimensional (1D) quantum-confined states in MoSe 2 . Building on previous reports of tunable trapping potentials and linearly polarized emission, we extend this understanding by demonstrating how nonuniform in-plane electric fields enable in situ control of these effects and highlight the role of gate-tunable valley hybridization in these localized states. Their polarization is entirely engineered through either the 1D confinement potential's geometry or an out-of-plane magnetic field. Controlling nonuniform in-plane electric fields in TMDs enables control of the energy (up to five times its line width), polarization state (from circular to linear), and position of 1D confined excitonic states (5 nm V -1 ).

Background and Objective: Our understanding of homicide-suicide (H-S), a rare yet tragic event, is sparse. While the phenomenon has been studied in the West for many years, only limited literature is available from Asia and none to our knowledge from Pakistan. There is evidence of complexity of the interaction between cultural, societal, and psychological mechanisms underlying this phenomenon; therefore, research findings from the Western countries cannot be directly applied in non-Western societies. Our objective was to study homicide-suicides in Pakistan, describe the characteristics of offenders and victims, determine the types of H-S, and examine possible motives and any events prior to the offense., Methods: In the absence of any official data on homicide-suicides, we used newspaper surveillance approach of four most widely circulated Pakistani newspapers (one Urdu and three English Daily) for two years (1 st January 2019 to 31 st December 2020). Each case was categorized using the modified Marzuk et al., Tardiff, and Hirsch's classification of homicide-suicides. Descriptive statistics were used to analyze the data that was then compared with published literature., Results: There were 114 H-S incidents with 198 victims of homicide during the study period, reported in the newspapers. Familial H-S particularly filicide-suicide were predominant, followed by spousal/ consortial H-S. Forty-one (36%) H-S involved multiple victims. The perpetrators across all categories of H-S were predominantly male (67%); the victims were predominantly women and children. Firearms were used in most incidents. The primary motive for the majority of H-S cases was familial, financial, and social stressors., Conclusions: The study highlights several unique patterns (predominance of familicide, multiple victims including high proportion of children) and a series of vulnerabilities (incidents related mostly to familial/ financial and social stressors) that overlap each other and ultimately lead to this tragic end. There is need to increase our understanding and develop effective evidence-based prevention strategies for H-S in Pakistan. It is also very important to have a national surveillance network and national violent death reporting system in the country for studying H-S cases, and for evaluating the impact of prevention programs., (Copyright: © Pakistan Journal of Medical Sciences.)

With the rising incidence of hepatocellular carcinoma, there has been increasing use of local-regional therapy (LRT) to downstage or bridge to transplant, for definitive treatment, and for palliation. The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Assessment (TRA) algorithm provides guidance for step-by-step tumor assessment after LRT and standardized reporting. Current evidence suggests that the algorithm performs well in the assessment of tumor response to arterial embolic and loco-ablative therapies and fair when assessing response to radiation-based therapies, with limited data to validate the latter. Both evidence-based and expert-based refinements of the algorithm are needed to improve its diagnostic accuracy after varying types of LRT. This review provides an overview of the challenges and limitations of the LI-RADS TRA algorithm version 2017 and discusses the refinements introduced in the updated 2024 LI-RADS algorithm for CT/MRI., (© RSNA, 2024.)

Background CT plays an important role in the opportunistic identification of hepatic steatosis. CT performance for steatosis detection has been inconsistent across various studies, and no clear guidelines on optimum thresholds have been established. Purpose To conduct a systematic review and meta-analysis to assess CT diagnostic accuracy in hepatic steatosis detection and to determine reliable cutoffs for the commonly mentioned measures in the literature. Materials and Methods A systematic search of the PubMed, Embase, and Scopus databases (English-language studies published from September 1977 to January 2024) was performed. Studies evaluating the diagnostic accuracy of noncontrast CT (NCCT), contrast-enhanced (CECT), and dual-energy CT (DECT) for hepatic steatosis detection were included. Reference standards included biopsy, MRI proton density fat fraction (PDFF), or NCCT. In several CECT and DECT studies, NCCT was used as the reference standard, necessitating subgroup analysis. Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I 2 statistic, and meta-regression to explore potential sources of heterogeneity. When available, mean liver attenuation, liver-spleen attenuation difference, liver to spleen attenuation ratio, and the DECT-derived fat fraction for hepatic steatosis diagnosis were assessed. Results Forty-two studies (14 186 participants) were included. NCCT had a sensitivity and specificity of 72% and 88%, respectively, for steatosis (>5% fat at biopsy) detection and 82% and 94% for at least moderate steatosis (over 20%-33% fat at biopsy) detection. CECT had a sensitivity and specificity of 66% and 90% for steatosis detection and 68% and 93% for at least moderate steatosis detection. DECT had a sensitivity and specificity of 85% and 88% for steatosis detection. In the subgroup analysis, the sensitivity and specificity for detecting steatosis were 80% and 99% for CECT and 84% and 93% for DECT. There was heterogeneity among studies focusing on CECT and DECT. Liver attenuation less than 40-45 HU, liver-spleen attenuation difference less than -5 to 0 HU, and liver to spleen attenuation ratio less than 0.9-1 achieved high specificity for detection of at least moderate steatosis. Conclusion NCCT showed high performance for detection of at least moderate steatosis. © RSNA, 2024 Supplemental material is available for this article.

Venetoclax synergizes with low-intensity regimens such as hypomethylating agents (HMAs) and low-dose cytarabine (LDAC). However, less is known about the clinical activity of venetoclax combined with HMAs or LDAC. Therefore, the current study focused on assessing the clinical efficacy, safety, and predictive factors for response to these venetoclax-based regimens in elderly patients with acute myeloid leukemia (AML). A comprehensive search for literature related to our study objective was performed on PubMed, Embase, Web of Science, and Google Scholar databases. The statistical analyses were performed using Review Manager or the Comprehensive Meta-Analysis software. In addition, methodological quality evaluation of nonrandomized studies was conducted using the Newcastle Ottawa Scale, while bias assessment of randomized studies was performed with Cochrane's risk of bias tool. Twelve studies, including 1432 elderly AML patients treated with venetoclax-based regimens, were identified for review and analysis. The pooled analysis showed that the rate of complete response with or without incomplete blood count recovery (CR/CRi) and overall response rate (ORR) among patients treated with venetoclax and HMAs was 59% and 64%, respectively. On the other hand, an CR/CRi of 50% was observed in patients treated with venetoclax and LDAC. Furthermore, venetoclax combined with HMAs demonstrated a significant survival benefit over HMAs alone and intensive chemotherapy (HR: 0.57; 95% CI: 0.47-0.68; P < .00001). The most common grade ≥ 3 hematologic disorder, nonhematological event, and infection in AML patients treated with venetoclax and HMAs were febrile neutropenia (39%), hypokalemia (12%), and pneumonia (19%), respectively. Conversely, thrombocytopenia, hypokalemia, and pneumonia were more common in patients treated with venetoclax and LDAC (41%, 15%, and 12%, respectively). Venetoclax combined with HMAs or LDAC has good clinical activity and a manageable safety profile in elderly patients with AML., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population., Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data., Results: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis., Conclusions: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2- breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety., Methods: Adhering to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2- advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis., Results: Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P = 0.005; I2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P = 0.11; I2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I2 = 61%)., Conclusion: SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2- advanced breast cancer., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Breast milk (BM) enhancement is often used to meet the nutritional needs of preterm infants after hospital discharge to achieve optimal growth. This study compared growth at 18-28 months corrected age (CA) among very preterm (VP) and very low birth weight (VLBW) infants discharged from the neonatal intensive care units (NICUs) on two BM enhancements., Methods: We conducted a retrospective chart review study of infants born between January 1, 2013 and December 31, 2017, with gestational age < 32 weeks or birthweight < 1500 g, discharged from the NICU on BM enhancements; fortification of BM with infant formula additives (BM-F) or unfortified BM supplemented with bottle feeds of infant formula (BM-S). BM enhancements were nonrandomized and determined by the medical team. A linear mixed model regression analysis with propensity score matching was used to estimate the adjusted associations between the nutrition plan at discharge and growth outcomes at 18-28 months CA follow-up., Results: Two hundred and fifty-one VLBW/VP infants were included. Compared with BM-S, infants discharged on BM-F were more likely to continue receiving BM at 8-12 months CA, and had lower head circumference, weight-for-length z scores, and higher incidence of moderate malnutrition (p ≤ 0.01). After adjusting for confounders, discharge on BM-F was associated with a lower incidence of overweight/obesity at 18-28 months CA (odds interval: 0.45; confidence interval: 0.21-0.96; p = 0.04)., Conclusions: This retrospective study suggests that VLBW/VP infants discharged on BM-F received BM longer, had lower growth parameter and were less likely to be overweight/obese at 18-28 months CA. Further studies are needed to evaluate the role of postdischarge nutrition on preterm born children's growth, metabolic disease, and neurodevelopmental outcomes., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Both age-associated hearing loss (AAHL) and peripheral neuropathy (PN) are common in older patients, and both are associated with impaired balance, falls, and premature mortality. The objectives of this study were to document the prevalence and severity of AAHL in older primary care patients, and to explore associations between AAHL, PN, balance, falls, and mortality., Methods: We analyzed information obtained in 1999 from 793 primary care patients recruited from practices participating in the Oklahoma Longitudinal Assessment of the Health Outcomes of Mature Adults (OKLAHOMA) Studies. Available data included demographic and health information, history of falls and hospitalizations, audiometry, balance testing, examination of the peripheral nerves, 50 foot timed gait, and dates of death up to 22 calendar years and 8106 person-years of follow-up. Proportionate hazards (PH) and structural equation modeling (SEM) were used to examine associations between AAHL, PN, balance, gait time, and mortality., Results: 501 of the 793 participants (63%) had AAHL. Another 156 (20%) had low frequency and 32 (4%) had unilateral deficits. Those with moderate or severe AAHL and the 255 (32%) with PN had impaired balance (p < 0.0001), increased gait time (p = 0.0001), and reduced survival time (p < 0.0001). In the PH model, both AAHL and PN were associated with earlier mortality (H.Rs. [95% C.I.]: 1.36 [1.13-1.64] and 1.32 [1.10-1.59] respectively). The combination of moderate or severe AAHL and PN, present in 24% of participants, predicted earlier mortality than predicted by either deficit alone (O.R. [95% C.I.I] 1.55 [1.25-1.92]). In the SEM models, the impacts of both moderate or severe AAHL and PN on survival were mediated, in part, through loss of balance., Conclusions: Hearing loss and PN, both common in older patients, appear to be independently and additively associated with premature mortality. Those associations may be mediated in part by impaired balance. The Mechanisms are likely multiple and complex., (© 2024 The American Geriatrics Society.)

Background: Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children., Methods: Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded., Results: A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss., Conclusions: Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema., 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 © 2024 Elsevier Inc. All rights reserved.)

Breast cancer is the second leading cause of women's cancer deaths after lung cancer. Risk factors such as environment, lifestyle, and genetics contribute to its development, including mutation in the breast cancer (BRCA) gene. Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) target these mutations, benefiting patients with advanced cancers. This review summarizes PARPi' safety and efficacy in the treatment of BRCA-mutated breast cancer. PubMed, The Cochrane Library for Clinical Trials, and Science Direct, were searched for articles from inception to April 2024. Eligible articles were analyzed, and data were extracted for meta-analysis using RevMan 5.4 software with a random-effect model. Out of 430 articles identified from online databases, only 6 randomized control trials including 3610 patients were included in the analysis. PARPi therapy improved progression-free survival (hazard ratio: 0.64; 95% CI: 0.56, 0.73; P < 0.00001) and overall survival (hazard ratio: 0.84; 95% CI: 0.73, 0.98 P = 0.02), according to the analysis. In our safety analysis, the risk of adverse events was not statistically different between PARPi versus chemotherapy (relative risk [RR]: 1.08; 95% CI: 0.44, 2.68; P = 0.86), and combined PARPi and standard chemotherapy (RR: 1.00; 95% CI: 0.93, 1.07; P = 0.80). The only statistically significant difference was observed in anemia, where PARPi increased the risk of developing anemia compared with standard chemotherapy (RR: 6.17; 95% CI: 2.44, 15.58; P = 0.0001). In BRCA-mutated breast cancer, PARPi treatment shows better overall survival and progression-free survival compared with standard chemotherapy or placebo. Furthermore, PARPi, either alone or in combination therapy, does not increase the risk of adverse events in these patients, as per the meta-analysis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Race/ethnicity and gender concordance between patients and providers is a potential strategy to improve health care interventions. In digital health, where human interactions occur both synchronously and asynchronously, the effect of concordance between patients and providers is unknown., Objective: This study aimed to evaluate the impact of race/ethnicity or gender concordance between patients and physical therapists (PTs) in engagement and the clinical outcomes following a digital care program (DCP) in patients with musculoskeletal (MSK) conditions., Methods: This secondary analysis of 2 prospective longitudinal studies (originally focused on assessing the acceptance, engagement, and clinical outcomes after a remote DCP) examined the impact of both race/ethnicity concordance and gender concordance between patients and PTs on outcomes for a digital intervention for MSK conditions. Outcomes included engagement (measured by the completion rate and communication, assessed by text interactions), satisfaction, and clinical outcomes (response rate, ie, percentage of patients achieving at least a minimal clinically important change in pain, measured by the Numerical Pain Rating Scale [NPRS]; anxiety, measured by the Generalized Anxiety Disorder 7-item scale [GAD-7]; depression, measured by the Patient Health Questionnaire 9-item [PHQ-9]; and daily activity impairment, measured by the Work Productivity and Activity Impairment [WPAI] questionnaire)., Results: Of 71,201 patients, 63.9% (n=45,507) were matched with their PT in terms of race/ethnicity, while 61.2% (n=43,560) were matched for gender. Concordant dyads showed a higher completion rate among White (adjusted odds ratio [aOR] 1.11, 95% CI 1.05-1.19, P<.001) and Hispanic (aOR 1.27, 95% CI 1.08-1.54, P=.009) groups, as well as women (aOR 1.10, 95% CI 1.06-1.18, P<.001), when compared to discordant dyads. High and similar levels of interaction between patients and PTs were observed across race/ethnicity and gender dyads, except for Asian concordant dyads (adjusted β coefficient 5.32, 95% CI 3.28-7.36, P<.001). Concordance did not affect satisfaction, with high values (>8.52, 95% CI 8.27-8.77) reported across all dyads. Response rates for pain, anxiety, and daily activity impairment were unaffected by race/ethnicity concordance. An exception was observed for depression, with White patients reporting a higher response rate when matched with PTs from other races/ethnicities (aOR 1.20, 95% CI 1.02-1.39, P=.02). In terms of gender, men had a slightly higher pain response rate in discordant dyads (aOR 1.08, 95% CI 1.01-1.15, P=.03) and a higher depression response rate in concordant dyads (aOR 1.23, 95% CI 1.05-1.47, P=.01)., Conclusions: Race/ethnicity and gender concordance between patients and PTs does not translate into higher satisfaction or improvement for most clinical outcomes, aside from a positive effect on treatment completion. These results highlight the importance of other PT characteristics, in addition to race/ethnicity or gender concordance, suggesting the potential benefit of experience, languages spoken, and cultural safety training as ways to optimize care., Trial Registration: ClinicalTrials.gov NCT04092946, NCT05417685; https://clinicaltrials.gov/study/NCT05417685, https://clinicaltrials.gov/study/NCT04092946., (©Anabela C Areias, Dora Janela, Maria Molinos, Virgílio Bento, Carolina Moreira, Vijay Yanamadala, Steven P Cohen, Fernando Dias Correia, Fabíola Costa. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.10.2024.)

Objective: Studies have suggested that aortic thrombus may be associated with adverse outcomes following endovascular repair of aortic aneurysms, while other reports have suggested higher rates of sac regression and reduced risk of endoleak. However, the effect of thrombus burden on outcomes following physician modified endografts (PMEGs) remains unknown. This study aimed to assess the volume and morphology of thrombus burden and the effect on outcomes following PMEG for juxtarenal abdominal aortic aneurysm., Methods: This was a retrospective cohort study of patients who underwent PMEG from 2009 to 2021 in a single centre, investigational device exemption trial. Thrombus burden was measured as a percentage of luminal volume using pre-operative computed tomography scans from the lowest renal artery to the level of the aortic bifurcation using centreline reconstructive software. Morphology was documented by the presence of finger like projections. Univariate and multivariate analyses evaluated the impact on peri-operative and long term outcomes., Results: Volumetrical and morphological measures of thrombus burden were assessed in 142 patients; 40.1% of the cohort were classified as having a high thrombus burden (≥ 50% luminal volume) on volumetrical assessment and 22.5% had finger like projections on morphological assessment. Type II endoleak was more frequently observed in those with low thrombus burden (60.0% vs. 33.3%; p = .008) and persisted after multivariate analysis (odds ratio 2.5, 95% confidence interval 1.1 - 5.8), but there were no other significant differences in peri-operative adverse events or late outcomes-including sac behaviour, freedom from re-intervention, and overall survival-when stratifying thrombus burden by quantitative or qualitative measures. There were no observed differences in operative characteristics or anatomical characteristics, including landing zone characteristics and rates of inferior mesenteric artery patency., Conclusion: While thrombus burden and morphology were not associated with adverse peri-operative events or survival, low thrombus burden was associated with an increase in type II endoleak. These findings suggest that thrombus burden should not deter treatment for patients requiring PMEG., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This meta-analysis evaluates the efficacy and safety of lenvatinib, both as monotherapy and in combination with other (tyrosine kinase inhibitors) TKIs, compared with other TKIs in metastatic renal cell carcinoma (RCC) treatment., Methods: We searched for relevant studies from inception to February 2024 using PubMed, Web of Science, Cochrane Library, and Scopus. Eligible studies reported on the efficacy and safety of lenvatinib alone or in combination with other TKIs versus other TKIs for metastatic RCC. Primary outcomes included progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), adverse events (AEs), and health-related quality of life (HRQOL)., Results: Seventeen studies met the inclusion criteria. Lenvatinib, especially in combination therapies, significantly improved PFS (HR: 0.46, 95% CI: 0.38-0.54, P<0.001) and OS (HR: 0.80, 95% CI: 0.70-0.91, P<0.001) compared with other TKIs. Quality of life analyses showed mixed results, with EQ-5D demonstrating significant improvement (HR: 1.21, 95% CI: 0.90-1.53, P<0.001), while EORTC QLQ-C30 was not statistically significant. ORR analysis indicated a higher likelihood of achieving a complete or partial response with lenvatinib (OR: 2.04, 95% CI: 1.15-2.93, P=0.00). The analysis of total AEs above grade 3 showed no significant difference between lenvatinib and other TKIs (OR: -0.08, 95% CI: -0.21 to 0.06, P=0.26)., Conclusions: Lenvatinib significantly enhances survival outcomes in metastatic RCC patients compared with other TKIs. While associated with various adverse events, its safety profile is comparable to other TKIs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Spine deformity surgery is a complex multi-step procedure that has a relatively high complication rate. The use of surgical safety checklists has been shown to reduce perioperative adverse events, but existing lists are varied and non-specific for spinal deformity surgery. Thus, the purpose of this study was to develop a comprehensive surgical checklist for complex spinal corrective surgery., Methods: An electronic survey consisting of 187 surgical checklist items that had been developed and used by a group of SRS members over a 5-year period was distributed to the Scoliosis Research Society Safety and Value Committee membership. The survey sections included: (1) pre-operative area, (2) initial operating room visit, (3) before turning, (4) positioning, (5) prepare and drape, (6) pre-incision timeout, (7) intraoperative, (8) finishing implant placement and confirming imaging, (9) final rods and locking, (10) prior to closure, (11) closure, (12) turn to supine, and (13) checkout/debriefing. Respondents graded each item on a five-point Likert scale based on their perceived importance and feasibility for inclusion in the checklist. Features graded as "moderately important" or "very important" to include by at least 70% of respondents were considered to meet the cutoff for inclusion-based standard Delphi practices. Study data were collated using REDCap., Results: A total of 25 surgeons completed the survey in its entirety. The overall checklist "package" was shortened to 9 individual checklist modules, with 2 to 16 items per checklist. In terms of individual checklist items, 40% of items (74 of 187) met the cutoff for inclusion; 17 of these items were graded as "very important," which included verifying the presence of implantable devices, reviewing the surgical plan and positioning with the surgical staff, securing the endotracheal tube, bite block confirmation, prone and lateral positioning, neuromonitoring baseline readings, double-checking that the implant screw caps were locked prior to closure, and confirming that the patient was moving bilateral lower extremities before leaving the operating room when possible., Conclusion: This study has led to the development of a specific spinal deformity surgical checklist of 74 (many specific to spine surgery) items that were considered important for inclusion; 17 were considered "very important"., (© 2024. The Author(s).)

A current major topic of conversation in academic pharmacy is "curricular hoarding," the overloading of the curriculum due to the steady addition of required knowledge and skills without a concomitant subtraction of existing content. It can be tempting to consider addressing hoarding by just reducing content in the foundational biomedical and pharmaceutical sciences or by shifting some foundational content into prerequisites for admission into the Doctor of Pharmacy program. The health care education literature suggests that this approach would negatively impact the development of the critical and clinical thinking skills needed by a modern pharmacist. This commentary is intended to inform conversations on curricular hoarding by affirming and demonstrating the reliance of pharmacists' clinical and critical thinking on the scientific concepts of the biomedical and pharmaceutical science disciplines and reiterating the importance to the practicing pharmacist of a deep understanding of these concepts, conferred through a careful and intentional educational integration., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Phonon polaritons - quasiparticles formed by strong coupling of infrared (IR) light with lattice vibrations in polar materials - can be utilized for surface-enhanced infrared absorption (SEIRA) spectroscopy and even for vibrational strong coupling with nanoscale amounts of molecules. Here, we introduce and demonstrate a compact on-chip phononic SEIRA spectroscopy platform, which is based on an h-BN/graphene/h-BN heterostructure on top of a metal split-gate creating a p-n junction in graphene. The metal split-gate concentrates the incident light and launches hyperbolic phonon polaritons (HPhPs) in the heterostructure, which serves simultaneously as SEIRA substrate and room-temperature infrared detector. When thin organic layers are deposited directly on top of the heterostructure, we observe a photocurrent encoding the layer's molecular vibrational fingerprint, which is strongly enhanced compared to that observed in standard far-field absorption spectroscopy. A detailed theoretical analysis supports our results, further predicting an additional sensitivity enhancement as the molecular layers approach deep subwavelength scales. Future on-chip integration of infrared light sources such as quantum cascade lasers or even electrical generation of the HPhPs could lead to fully on-chip phononic SEIRA sensors for molecular and gas sensing., (© 2024. The Author(s).)

Purpose: To describe experiences of adolescents taking continuous drospirenone (DRSP-C) oral contraceptives, without placebo, for menstrual suppression, including breakthrough bleeding and other side-effects., Methods: This was a retrospective chart review of adolescents prescribed DRSP-C for menstrual suppression. Demographics and indications for DRSP-C were collected on the visit where DRSP-C was prescribed. Data through the final follow-up visit during the study period included documented effects and side-effects of DRSP-C and continuation of therapy. Statistical analyses were primarily descriptive., Results: Patients prescribed DRSP-C were included (n = 136). Dysmenorrhea was the most common indication for DRSP-C (58.8%, n = 80/136) followed by endometriosis (44.8%, n = 61/136). The median time on DRSP-C for the 116 patients who were able to initiate treatment was 12.3 months (interquartile range [IQR] 6.8, 17.4). Patients trialed, on average, 2 other forms of menstrual management before starting DRSP-C (IQR 1, 3). Pelvic pain or dysmenorrhea resolution or improvement was reported in 84.6% (44/52) of dysmenorrhea patients, and 77.8% (28/36) of pelvic pain patients. Almost half of patients reported breakthrough bleeding on DRSP-C (41.3%, n = 48/116); however, only 11 patients (42%, 11/26) discontinued DRSP-C because of it. Within the study period, 22.4% (n = 26/116) of patients discontinued DRSP-C, with a median treatment duration of 101 days (IQR 71, 157). Among patients who discontinued DRSP-C, the most common reason was breakthrough bleeding (42%, n = 11/26)., Discussion: DRSP-C for menstrual suppression was well tolerated in adolescents, with most patients reporting resolution or improvement of their indication for taking DRSP-C. Findings demonstrate DRSP-C is a viable option for menstrual suppression in adolescents., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine changes in health-related quality of life (HRQOL), this 2-year follow-up study reassessed the HRQOL of transgender and gender expansive (TG/GE) young people enrolled in a patient registry at the Gender Wellness Center (GWC) in upstate New York., Methods: Registry patients had to have a gender-affirming care follow-up visit at the GWC within a 2 year window (+6 months) of their baseline survey to complete follow-up. Youth <18 years of age completed the Child Health Questionnaire-Child Form 87 (CHQ-CF87); youth >18 years of age completed the Short Form-36v2 (SF-36v2). We analyzed change from baseline to follow-up for 11 CHQ-CF87 subscales and 8 SF-36v2 subscales. We compared follow-up HRQOL results to U.S. population standards. We abstracted receipt of gender-affirming care from GWC electronic medical records., Results: Among the 173 patients who completed HRQOL assessments at baseline, 108 completed follow-up (62% response rate) from May 2019 to March 2022. The mean age for those completing the CHQ-CF87 was 14.6±2.2 years (range 10-17) and for the SF-36v2 was 19.7±2.3 years (range 18-24). CHQ-CF87 Behavior and Role/Social Physical Functioning subscale scores improved significantly among youth 8-17 years of age from baseline. Follow-up SF-36v2 scores for patients 18-24 years of age did not change significantly. Follow-up HRQOL mental health scores remained statistically significantly lower than U.S. population standards for both age groups., Conclusions: Two year follow-up HRQOL data from TG/GE youth receiving gender-affirming care improved in two domains, but did not change among young adults (>18 years of age). Mental health remains suboptimal compared to national standards., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)