Citations

Abstract Aim The aim of this review was to synthesise qualitative research evidence on factors influencing the implementation of patient reported outcome measures (PROMs) in surgical population. Methods The following databases were searched: MEDLINE, Embase, Emcare, Allied and Complementary Medicine, Global Health, Health and Psychosocial Instruments, Health Management Information Consortium, APA PsycInfo, PubMed and Web of Science. Searches were carried out between 21st and 23rd February 2024. “Best fit” framework analysis was selected for evidence synthesis, necessitating two systematic reviews. The “Models review” focused on relevant theory, framework or conceptual model relating to implementation of PROMs. The “Primary research review” focused on studies describing factors affecting the implementation of PROMs. Case reports, editorial, reviews, meta-analysis, protocols, or studies, conducted in non-surgical or paediatric population, were excluded. Results 3,714 studies were identified in the Models review, of which 7 underwent full-text review and 2 were included in the analysis. Two relevant implementation frameworks were identified: the Theoretical Domains Framework (TDF) and the Consolidated Framework for Implementation Research. TDF was selected as a priori framework for the coding of evidence. Primary research review identified 1,293 studies, of which 50 underwent full-text review and 18 were included in the analysis. Extracted data were coded against TDF, revealing multiple patient-, clinician- and provider-factors affecting the implementation of PROMs, including: beliefs about consequences and capabilities, environmental context and resources, knowledge, skills, social influences, decision processes, emotional and identity factors. Conclusions Successful implementation of PROMs into routine surgical practice requires careful consideration of patient-, clinician- and provider-factors.

Abstract Bispecific T-cell engagers (TCEs) targeting B-cell maturation antigen (BCMA) and CD3, induce deep hematologic responses in ∼60% of heavily pretreated patients with multiple myeloma (MM). We and others found that high tumor burden leads to resistance to TCE and novel strategies are urgently needed to improve responses in this setting. Ikaros degraders, including immunomodulatory drugs (IMiDs) and cereblon E3 ligase modulatory drugs (CELMoDs), represent logical partners for TCEs due to their direct anti-MM effects and additional immune-stimulatory activity; however, it is unclear how to optimally combine them with TCEs. Taking advantage of the immunocompetent IMiD-sensitive Vk∗MYChCRBN murine model of MM, we optimized strategies to overcome primary resistance to BCMA-TCEs and achieve sustained remission, while maintaining a manageable safety profile. The addition of anti–programmed cell death protein 1 (PD1) and pomalidomide reduced the T-cell exhaustion that occurs in response to TCEs in high tumor burden settings. This allowed for a higher degree of T-cell activation and significant improvement in response rates but also increased risk of lethal cytokine release syndrome (CRS). To moderate the response and prevent CRS, we evaluated Ikaros degraders and dexamethasone (DEX) with step-up–dosed TCEs. Pretreatment with iberdomide and DEX reshaped the bone marrow T-cell compartment, promoted infiltration of naïve T cells, and generated 100% response rates and the longest survival in subjects with high tumor burden. This was accompanied by more favorable T-cell profiling, with limited expansion of regulatory T cells and exhaustion. Overall, administering a TCE after DEX and iberdomide treatments provided deeper and more durable responses with a reduced risk of CRS.

Objective Preparation for a career in plastic and reconstructive surgery (PRS) begins long before the residency application process. Given the challenging nature of matching into integrated PRS, the expectations for competitive applicants, including research productivity and networking at conferences, incur significant expenses. Our study is the first to detail the comprehensive costs of pursuing PRS, highlighting many hidden expenses that precede the application process. Design and Setting A branched logic survey was created to inquire about respondents' demographics, personal finances, expenses related to education and research, and opinions on the comprehensive costs of pursuing PRS. Qualitative and quantitative data were collected and analyzed using descriptive statistics. Participants The survey was distributed to PRS residency applicants in the 2023–2024 cycle and to senior members of a virtual PRS research group. The survey achieved a 28.9% response rate. Results Most respondents were fourth-year medical students (57.3%) and attended a school without a home integrated residency program (42.7%). Of students who pursued a research year (37.1%), 40.7% were unpaid, and 53.3% reported living expenses exceeding their income. Most attended more than 5 PRS conferences (29.9%), corresponding to a median total cost of $2000 to $3000. Fourth-year students typically participated in 3 away rotations (40.0%) at a cost of $6000 to $9000. The financial burden of pursuing a career in PRS, including PRS-related extracurricular activities and application-associated costs, is estimated to be $33,400–$45,479. Nearly all respondents (96.6%) believed this cost was too high or excessively high; however, 93.3% determined that it was probably or definitely worth a career in PRS. Conclusions The lofty costs associated with pursuing PRS are unsustainable for many. Additional efforts should be made to reduce financial barriers for PRS applicants. Ensuring funding to all students pursuing a research year, diversifying scholarships for conference attendance and away rotations, increasing loan forgiveness opportunities, and expanding use of lower-cost application options such as the Plastic Surgery Common Application are potential solutions to offset the cost of pursuing PRS.

Worldwide, more than 4 million patients with end-stage kidney disease require hemodialysis through an arteriovenous fistula (AVF). AVFs fail because of venous neointimal hyperplasia (VNH) resulting in venous stenosis formation. A phase 1 randomized trial in patients undergoing upper extremity AVF placement was performed to evaluate the safety and efficacy of autologous adipose–derived mesenchymal stem cells (MSCs) in improving AVF function. The mechanism of action by which MSCs exert their beneficial effects was investigated using AVFs created in mice and pigs treated with allogenic MSCs and xenotransplant using patient MSCs in CD1- Foxn1nu mice. At a median follow-up of 42 months, patients with MSC-treated AVFs had reduced time to maturation with an increase in the vein diameter compared with controls. AVFs treated with allogenic MSCs in mice and pigs had an increase in M2- and M1-like macrophages with a decrease in VNH. Transcriptomic analysis of AVFs treated with allogenic MSCs in mouse and MSC xenotransplants of patients with successful AVFs showed decreased peroxisome proliferator–activated receptor gamma ( Ppar γ) and leptin receptor ( Lepr ) and increased latent transforming growth factor–beta–binding protein 2 ( Ltbp2 ). PPARγ was reduced in CD68 (+) cells from successful AVFs and allogenic MSC-treated mouse AVFs. Venous stenosis and VNH formation were mitigated in AVFs of mice with Ppar γ ablation in immune cells. Conditioned medium from MSCs of responders versus nonresponders had decreased proinflammatory genes, senescence-associated proteins, and monocyte-to-macrophage differentiation induced by phorbol 12-myristate-13-acetate. Periadventitial delivery of MSCs to AVFs promoted positive vascular remodeling through decreased inflammatory responses.

This cohort study examines trends in patient access of radiology imaging results after implementation of the 21st Century Cures Act in different clinical settings.

ImportanceIndia’s goal of measles elimination remains unmet, as evidenced by significant recent outbreaks.ObjectiveTo identify seroprevalence rates among vaccinated children and to examine demographic factors that influence antibody responses.Design, Setting, and ParticipantsThis cross-sectional study included a highly vaccinated cohort of Indian children from the states of Kerala and Tamil Nadu between 2018 and 2023. Eligible children had received at least 2 doses of measles-containing vaccines; their mothers were recruited from various community settings, including local nursery and secondary schools, residential associations, and hospitals.ExposureMeasles-specific antibodies were quantified in serum samples.Main Outcomes and MeasuresMeasles-specific immunoglobulin G (IgG) and neutralizing antibodies were quantified in both children and mothers. Measles-specific IgM was also measured in children.ResultsThe total cohort comprised 684 children (median age, 9 years [range, 4-18 years]; 348 male [50.1%]) and 544 mothers. All children received at least 2 doses of measles-containing vaccines; 435 children (63.6%) received a third dose, and 7 (1.0%) received a fourth dose. Among the children, 621 (90.8%) had positive measles-specific IgG, and 623 (91.5%) had protective neutralizing antibodies titers, with a strong correlation between measles-specific IgG and neutralizing antibodies (r = 0.73; P < .001). Female children exhibited significantly higher titers of both measles-specific IgG and neutralizing antibodies compared with male children. While IgG and neutralizing antibody titers remained stable over time and were not associated with the number of vaccine doses in children, neutralizing antibody titers increased with age in mothers, likely due to repeated viral exposure. Notably, in 20 families with at least 2 children, differential measles-specific IgM profiles were observed between siblings despite high IgG and neutralizing antibody titers, suggesting ongoing breakthrough infections.Conclusions and RelevanceIn this cross-sectional study, substantial measles immunity gaps were found despite high vaccine coverage with evidence of breakthrough infections, posing significant challenges to India’s measles elimination efforts. These results underscore the urgent need to strengthen India’s immunization program and investigate the mechanisms driving suboptimal responses to measles vaccination; without addressing these immune response deficiencies, achieving measles elimination through increased vaccine coverage alone may remain unattainable in India.

Importance Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a substantial burden. Standardized global prevalence estimates and data on associated sociodemographic and risk factors are lacking. Objective To estimate the global prevalence of HS and study differences in prevalence by age, sex, geographical location, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, gross domestic product (GDP), and Human Development Index (HDI). Data Sources and Study Selection Included studies were conducted using the standardized Global Hidradenitis Suppurativa Atlas methodology with finalized data collection before May 19, 2023. Studies were required to use a population-based sampling method and conduct clinical confirmation of HS diagnosis following a screening questionnaire. Data Extraction and Synthesis Data were independently extracted from relevant studies by 2 reviewers (D.B. and C.E.M.) using a standardized form. Extracted variables included geographic location, age, sex, BMI (median and BMI >30), smoking status, HS prevalence estimates (with 95% CIs), GDP, and HDI. A proportional meta-analysis using a random-effects model was conducted on the included studies. Main Outcomes and Measures The primary outcome was the point prevalence of HS, confirmed by clinical examination. Secondary outcomes included differences in HS prevalence by sex, age, BMI category, smoking status, and country-level socioeconomic indicators (GDP and HDI). All outcomes were prespecified before data analysis. Results The sample included 22 743 participants, identifying 247 patients with HS, across 25 studies in 23 countries spanning 6 continents. The median proportion of female patients with HS was 55.6%, and the median age was 34.5 years. While the prevalence estimates showed considerable inconsistency ( I 2 > 75%; τ 2 = 0.747), the overall random-effects global prevalence of HS was 0.99% (95% CI, 0.67%-1.46%). Female sex was the only factor observed to be associated with the prevalence estimates (β = 1.02; 95% CI, 1.01-1.03). Conclusions and Relevance In this meta-analysis, an estimated global prevalence of HS between 0.67% and 1.46% surpassed previous global estimates. Substantial global variations in HS prevalence were also observed. Female sex was the only factor associated with prevalence in this sample. Future studies assessing genetic, environmental, and etiological factors are warranted to explain the heterogeneity in prevalence.