Predictors of extended length of stay following outpatient reduction mammaplasty.

PURPOSE: Reduction mammaplasty has transitioned into a largely outpatient procedure in the United States. Following planned outpatient procedures, patients may still be admitted for additional inpatient care, incurring clinical and economic burden. Prior literature has not explored the preoperative and perioperative determinants of extended lengths of stay (LOS) after breast reduction surgery. METHODS: Patients who underwent scheduled outpatient reduction mammaplasty were identified via current procedural terminology code from the 2013 to 2021 National Surgical Quality Improvement Program databases. The primary outcome was extended LOS, defined as an LOS greater than 1 day. The most significant predictor variables were identified through bivariate association, and a binary logistic regression model was used to characterize predictive associations (p < 0.05). RESULTS: In this study, 33,924 patients were included in the final cohort of planned outpatient reduction mammaplasty cases. Among them 325 (1.0%) patients had extended LOS. Concurrent liposuction, body contouring, and increased operative time were the most significant predictors of extended LOS (p < 0.001), followed by older age, higher body mass index, bleeding disorder, history of diabetes, higher American Society of Anesthesiologists class, and White race (p < 0.05). When adjusted for other confounding variables, extended LOS was also a significant predictor of increased risk of postoperative complications after discharge (OR: 1.85, 95% confidence intervals: 1.27-2.69, p = 0.0012). CONCLUSION: Extended LOS after planned outpatient reduction mammaplasty is associated with specific comorbidities, and is a significant predictor of postoperative complications following hospital discharge. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are publicly available.

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core-Shell Silica Nanoparticles.

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

The impact of a shadowing program on medical students' interest in plastic surgery.

Given the lack of formal education on plastic surgery services during the preclinical years of medical school, many medical students commonly misunderstand the breadth and depth of the field. Shadowing is highly impactful in shaping students' desire to pursue surgery, but the impact of plastic surgery shadowing remains unexplored. The study design utilized an anonymous web-based survey containing questions surrounding prior interest in surgery, race, gender, medical school progress, and clinical versus OR shadowing. All medical students who participated in an ongoing, voluntary plastic surgery shadowing program over a two-year period were invited to complete the survey. Of the 54 students who shadowed during the study period, 43 (79.6%) returned the survey. Students reported an overall greater impact of OR shadowing than clinic shadowing on their interest in plastic surgery, approaching significance (p = 0.0527). On simple and multivariate regression, the number of times a student shadowed in the OR was the only statistically significant predictor of students' interest in plastic surgery (p = 0.0003). In general, the majority of students reported that their shadowing experience "significantly increased" (24.2%) or "somewhat increased" (45.5%) their interest in pursuing a career in plastic surgery. The impact of shadowing, particularly in the operating room, on students' interest in plastic surgery demonstrates the value of structured shadowing programs. Additionally, given the particularly influential effect of shadowing in the operating room, our results indicate that efforts may benefit most from facilitating student exposure to the hands-on aspects of the field.

National Legislative Favorability and Insurance Coverage for Adult and Adolescent Gender-Affirming Surgery.

BACKGROUND: Despite established medical necessity, laws prohibiting coverage discrimination, and increasing numbers of transgender and gender diverse patients seeking gender-affirming surgeries (GAS), cost and restrictive insurance policies continue to be the most common barriers. As recent legislation places further restrictions on GAS, this study aims to provide an updated review of insurance policies and assess the relationship between legislative favorability and coverage. METHODS: Insurance policies of groups representing 80% market coverage in each state were collected for gender-affirming chest, genital and facial surgery. Policies were categorized based on previously published methodologies: never-covered (N), case-by-case (CC), and preauthorization (PA). The relationship between established scores of legislative favorability and policy coverage in each state was analyzed and compared across regions. RESULTS: Of the 316 analyzed policies, coverage was preauthorized most often for genital (94.0%), masculinizing top (93%), feminizing top (74%), and facial reconstruction (24%), respectively. Higher legislative scores in the Northeast and West, as well as individual states were predictive of increased genital, facial, and all forms of adolescent GAS, but were not correlated to chest GAS. CONCLUSION: Compared to previous studies, our findings suggest that there is a growing acceptance of GAS as medically necessary. However, the correlation between legislative scores and genital, face, and adolescent GAS coverage may suggest increased reliance on sociopolitical factors for access in the absence of comprehensive medical guidelines, which are more established for chest reconstruction. Significantly higher coverage of masculinizing versus feminizing chest surgery suggests additional burden of proof for GAS with a cosmetic overlap.

Concordance of National Insurance Criteria with WPATH Standards of Care for Gender-Affirming Surgery.

BACKGROUND: Given that gender-affirming surgery (GAS) is considered medically necessary for transgender and gender diverse (TGD) individuals who desire it, the aim of this study is to assess the concordance of insurance criteria for GAS with the most recent World Professional Association for Transgender Health (WPATH) Standards of Care Version 8 (SOC-8). METHODS: Insurance policies for coverage of gender-affirming genital ("bottom surgery"), chest ("top surgery"), and facial reconstruction from companies representing 80% of the market coverage in each state were evaluated. Policies were classified into three categories: no-coverage (NC), case-by-case (CC), and preauthorization (PA). Among PA policies, criteria for coverage of specific surgeries were analyzed for adherence to WPATH SOC-8. RESULTS: Bottom surgery policies were most concordant for age and gender dysphoria criteria, and transmasculine top surgery policies were most concordant for hormone therapy, continuous living in a congruent gender role, and referral criteria. transfeminine top surgery criteria were more restrictive than transmasculine criteria. The most discordant criteria was for hormone therapy, being required for at least 12 months prior to surgery in the majority of surveyed policies. Many specific procedures and treatments were excluded, especially facial GAS with cosmetic overlap. Additionally, reversal and revisionary surgeries were covered in less than 25% of policies. CONCLUSION: Compared to previous literature, insurance coverage and criteria alignment are becoming more concordant with medical guidelines. However, significant barriers to care are still present for GAS.

Humoral and cellular responses to repeated COVID-19 exposure in multiple sclerosis patients receiving B-cell depleting therapies: a single-center, one-year, prospective study.

Multiple sclerosis patients treated with anti-CD20 therapy (aCD20-MS) are considered especially vulnerable to complications from SARS-CoV-2 infection due to severe B-cell depletion with limited viral antigen-specific immunoglobulin production. Therefore, multiple vaccine doses as part of the primary vaccination series and booster updates have been recommended for this group of immunocompromised individuals. Even though much less studied than antibody-mediated humoral responses, T-cell responses play an important role against CoV-2 infection and are induced efficiently in vaccinated aCD20-MS patients. For individuals with such decoupled adaptive immunity, an understanding of the contribution of T-cell mediated immunity is essential to better assess protection against CoV-2 infection. Here, we present results from a prospective, single-center study for the assessment of humoral and cellular immune responses induced in aCD20-MS patients (203 donors/350 samples) compared to a healthy control group (43/146) after initial exposure to CoV-2 spike antigen and subsequent re-challenges. Low rates of seroconversion and RBD-hACE2 blocking activity were observed in aCD20-MS patients, even after multiple exposures (responders after 1st exposure = 17.5%; 2nd exposure = 29.3%). Regarding cellular immunity, an increase in the number of spike-specific monofunctional IFNγ+-, IL-2+-, and polyfunctional IFNγ+/IL-2+-secreting T-cells after 2nd exposure was found most noticeably in healthy controls. Nevertheless, a persistently higher T-cell response was detected in aCD20-MS patients compared to control individuals before and after re-exposure (mean fold increase in spike-specific IFNγ+-, IL-2+-, and IFNγ+/IL-2+-T cells before re-exposure = 3.9X, 3.6X, 3.5X/P< 0.001; after = 3.2X, 1.4X, 2.2X/P = 0.002, P = 0.05, P = 0.004). Moreover, cellular responses against sublineage BA.2 of the currently circulating omicron variant were maintained, to a similar degree, in both groups (15-30% T-cell response drop compared to ancestral). Overall, these results highlight the potential for a severely impaired humoral response in aCD20-MS patients even after multiple exposures, while still generating a strong T-cell response. Evaluating both humoral and cellular responses in vaccinated or infected MS patients on B-cell depletion therapy is essential to better assess individual correlations of immune protection and has implications for the design of future vaccines and healthcare strategies.

Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and COVID-19 vaccination. Here, the humoral and cellular responses are analyzed in a group of aCD20-MS patients (n=43) compared to a healthy control cohort (n=34) during the first 6 months after a 2-dose cycle mRNA-based COVID-19 vaccination. Both IgG antibodies recognizing receptor binding domain (RBD) from CoV-2 spike protein and their blocking activity against RBD-hACE2 binding were significantly reduced in aCD20-MS patients, with a seroconversion rate of only 23.8%. Interestingly, even under conditions of severe B-cell depletion and failed seroconversion, a significantly higher polyfunctional IFNγ+ and IL-2+ T-cell response and strong T-cell proliferation capacity were detected compared to controls. Moreover, no difference in T-cell response was observed between forms of disease (relapsing remitting- vs progressive-MS), anti-CD20 therapy (Rituximab vs Ocrelizumab) and type of mRNA-based vaccine received (mRNA-1273 vs BNT162b2). These results suggest the generation of a partial adaptive immune response to COVID-19 vaccination in B-cell depleted MS individuals driven by a functionally competent T-cell arm. Investigation into the role of the cellular immune response is important to identifying the level of protection against SARS-CoV-2 in aCD20-MS patients and could have potential implications for future vaccine design and application.

Ultrasmall, Bright, and Photostable Fluorescent Core-Shell Aluminosilicate Nanoparticles for Live-Cell Optical Super-Resolution Microscopy.

Stochastic optical reconstruction microscopy (STORM) is an optical super-resolution microscopy (SRM) technique that traditionally requires toxic and non-physiological imaging buffers and setups that are not conducive to live-cell studies. It is observed that ultrasmall (<10 nm) fluorescent core-shell aluminosilicate nanoparticles (aC' dots) covalently encapsulating organic fluorophores enable STORM with a single excitation source and in a regular (non-toxic) imaging buffer. It is shown that fourfold coordinated aluminum is responsible for dye blinking, likely via photoinduced redox processes. It is demonstrated that this phenomenon is observed across different dye families leading to probes brighter and more photostable than the parent free dyes. Functionalization of aC' dots with antibodies allows targeted fixed cell STORM imaging. Finally, aC' dots enable live-cell STORM imaging providing quantitative measures of the size of intracellular vesicles and the number of particles per vesicle. The results suggest the emergence of a powerful ultrasmall, bright, and photostable optical SRM particle platform with characteristics relevant to clinical translation for the quantitative assessment of cellular structures and processes from live-cell imaging.