Outcomes by sex in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial.

BACKGROUND: In the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial, among participants with stable coronary artery disease, the risk of cardiac events was similar between an invasive (INV) strategy of angiography and coronary revascularisation and a conservative (CON) strategy of initial medical therapy alone. Outcomes according to participant sex were not reported. AIMS: We aimed to analyse the outcomes of ISCHEMIA by participant sex. METHODS: We evaluated 1) the association between participant sex and the likelihood of undergoing revascularisation for participants randomised to the INV arm; 2) the risk of the ISCHEMIA primary composite outcome (cardiovascular death, any myocardial infarction [MI] or rehospitalisation for unstable angina, heart failure or resuscitated cardiac arrest) by participant sex; and 3) the contribution of the individual primary outcome components to the composite outcome by participant sex. RESULTS: Of 5,179 randomised participants, 1,168 (22.6%) were women. Female sex was independently associated with a lower likelihood of revascularisation when assigned to the INV arm (adjusted odds ratio 0.75, 95% confidence interval [CI]: 0.57-0.99; p=0.04). The INV versus CON effect on the primary composite outcome was similar between sexes (women: hazard ratio [HR] 0.96, 95% CI: 0.70-1.33; men: HR 0.90, 95% CI: 0.76-1.07; pinteraction=0.71). The contribution of the individual components to the composite outcome was similar between sexes except for procedural MI, which was significantly lower in women (9/151 [5.9%]) than men (67/519 [12.9%]; p=0.01). CONCLUSIONS: In ISCHEMIA, women assigned to the INV arm were less likely to undergo revascularisation than men. The effect of an INV versus CON strategy was consistent by sex, but women had a significantly lower contribution of procedural MI to the primary outcome.

Strong immunogenicity & protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functional polymer.

DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90 % along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted.

Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape.

Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-ß (TGF-ß) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.

Visualizing machine learning-based predictions of postpartum depression risk for lay audiences.

OBJECTIVES: To determine if different formats for conveying machine learning (ML)-derived postpartum depression risks impact patient classification of recommended actions (primary outcome) and intention to seek care, perceived risk, trust, and preferences (secondary outcomes). MATERIALS AND METHODS: We recruited English-speaking females of childbearing age (18-45 years) using an online survey platform. We created 2 exposure variables (presentation format and risk severity), each with 4 levels, manipulated within-subject. Presentation formats consisted of text only, numeric only, gradient number line, and segmented number line. For each format viewed, participants answered questions regarding each outcome. RESULTS: Five hundred four participants (mean age 31 years) completed the survey. For the risk classification question, performance was high (93%) with no significant differences between presentation formats. There were main effects of risk level (all P < .001) such that participants perceived higher risk, were more likely to agree to treatment, and more trusting in their obstetrics team as the risk level increased, but we found inconsistencies in which presentation format corresponded to the highest perceived risk, trust, or behavioral intention. The gradient number line was the most preferred format (43%). DISCUSSION AND CONCLUSION: All formats resulted high accuracy related to the classification outcome (primary), but there were nuanced differences in risk perceptions, behavioral intentions, and trust. Investigators should choose health data visualizations based on the primary goal they want lay audiences to accomplish with the ML risk score.

CONTRIBUTION FACTORS OF EFFECTIVE LENS POSITION, TILT, AND DECENTRATION DURING FLANGED SCLERAL FIXATION OF INTRAOCULAR LENS: A Model Eye Study.

PURPOSE: The authors aimed to elucidate the factors related to effective lens position, tilt, and decentration of scleral fixed intraocular lenses (IOLs) with a flanged haptic technique in an artificial eye model using anterior segment optical coherence tomography. METHODS: Two bent 27-gauge needles were passed through a 1.0- or 2.0-mm scleral tunnel, 2.0 mm posterior to the limbus and 180° apart. Both haptics of a three-piece IOL were docked with guide needles and externalized. Factors related to the IOL position were analyzed using anterior segment optical coherence tomography and a stereomicroscope. RESULTS: The 1.0-mm scleral tunnel induced a significantly longer effective lens position than the 2.0-mm tunnel and suture fixation ( P < 0.05 and P < 0.01, respectively). Discrepancy in scleral tunnel length induced higher decentration of the optic to the opposite side of the haptic-embedded shorter tunnel and tilt perpendicular to the fixed axis than that in the scleral tunnel of the same length ( P < 0.001 and P < 0.05, respectively). If the scleral fixation points of both haptics are not exactly 180° apart, the IOL may become decentered and tilted ( P < 0.01 and P < 0.05, respectively). CONCLUSION: In the flanged haptic technique, the length, balance, and position of both scleral tunnels determine IOL effective lens position, tilt, and decentration.

Chronic Refractory Cough: Long-Term Outcomes Following Cough Suppression Therapy.

OBJECTIVE: This study aimed to determine the long-term outcomes of patients with chronic refractory cough (CRC) following treatment for cough suppression therapy (CST). Currently, there is a lack of objective data regarding the long-term outcome of behavioral treatment for CRC. METHODS: From the charts of 106 adult patients diagnosed with CRC, 24 patients were identified as having long-term data at least 3 months post-CST in the form of otolaryngologic examination, Voice Handicap Index-10 (VHI-10), and Cough Severity Index (CSI) scores. Patients underwent otolaryngologic evaluation and completed the VHI-10 and CSI assessments during pretreatment, posttreatment, and long-term follow-up visits. Patients were also divided into two groups based on their number of comorbidities. RESULTS: Twenty of the 24 patients had significant reduction in cough severity after completing CST (P < 0.001). A significant difference was also found in CSI scores from pretherapy to the long-term follow-up visits (P = 0.001). No significant difference was found in CSI scores from posttherapy to long-term follow-up visits (P = 0.93). No significant difference was found in VHI-10 scores over time (P = 0.83). No correlation was found between changes in cough and voice severity and number of comorbidities at the tested level. CONCLUSIONS: Findings of no significant change in CRC over the long term compared to posttherapy measures suggest that patients were able to maintain improvement in cough over the long term despite various comorbidities. The current results suggest that CST represents a satisfactory approach to treating CRC and provides patients with an ongoing tool to maintain reduced cough severity. No significant correlations between number of comorbidities and mean CSI or VHI-10 scores were found over the long term.

Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012-2016.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

Neurocognitive Effect of Biased µ-Opioid Receptor Agonist Oliceridine, a Utility Function Analysis and Comparison with Morphine.

BACKGROUND: Oliceridine (Olinvyk) is a µ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. This study was designed to determine the utility function of oliceridine versus morphine based on neurocognitive tests and cold pressor test. METHODS: The study had a randomized, double-blind, placebo-controlled, partial block three-way crossover design. Experiments were performed in 20 male and female volunteers. The subjects received intravenous oliceridine (1 or 3 mg; cohorts of 10 subjects/dose), morphine (5 or 10 mg; cohorts of 10 subjects/dose), or placebo on three separate occasions. Before and after dosing, neurocognitive tests, cold pressor test, and plasma drug concentrations were obtained at regular intervals. Population pharmacokinetic-pharmacodynamic analyses served as the basis for construction of a utility function, which is an objective function of probability of benefit minus probability of harm. Antinociception served as the measure of benefit, and slowing of saccadic peak velocity and increased body sway as the measures of neurocognitive harm. RESULTS: The oliceridine and morphine C50 values, i.e., the effect-site concentrations causing 50% effect, were as follows: antinociception, 13 ± 2 and 23 ± 7 ng/ml; saccadic peak velocity, 90 ± 14 and 54 ± 15 ng/ml; and body sway, 10 ± 2 and 5.6 ± 0.8 ng/ml, respectively. The ratio oliceridine/morphine of the therapeutic indices, C50(benefit)/C50(harm), were 0.34 (95% CI, 0.17 to 0.7; P < 0.01) for saccadic peak velocity and 0.33 (0.16 to 0.50; P < 0.01) for body sway. The oliceridine utility was positive across the effect-site concentration 5 to 77 ng/ml, indicative of a greater probability of benefit than harm. The morphine utility was not significantly different from 0 from 0 to 100 ng/ml. Over the concentration range 15 to 50 ng/ml, the oliceridine utility was superior to that of morphine (P < 0.01). Similar observations were made for body sway. CONCLUSIONS: These data indicate that over the clinical concentration range, oliceridine is an analgesic with a favorable safety profile over morphine when considering analgesia and neurocognitive function.

Characterization of Google Search Volumes and Trends From 2004 to 2021 for Diagnosis and Treatment of Locally Advanced Prostate Cancer.

Introduction and objective The purpose of this study is to better characterize at which point during the course of diagnosis and treatment of locally advanced prostate cancer the internet is utilized and to evaluate the search trends over time. Methods Monthly Google Trends data were collected from 2004 to 2021 for prostate cancer-specific terms. Temporal trends were analyzed by comparing average search volume indexes (aSVI) and analysis with joinpoint software of six-month percent change (6mPC). Chloropleths were created for geographic pattern comparisons. Results Search terms associated with interventions demonstrated the highest aSVI with terms such as "prostate biopsy" (aSVI: 33.59), "prostatectomy" (aSVI: 31.6), and "prostate radiation" (aSVI: 16.45). Terms associated with treatment side effects increased at a high rate with "radiation side effects" (21.4 6mPC, p<0.05) and "prostatectomy side effects" (14.4 6mPC, p<0.05). Prostate-specific antigen (PSA)-related search terms demonstrated a strong positive trend on joinpoint analysis with search terms "What is PSA?" (8.9 6mPC, p<0.05), and "What is normal PSA?" (15.1, p<0.05). Geographic patterns demonstrated higher search volumes in regard to screening and diagnostic terms in the northeast, while the southern regions demonstrated relatively higher search volumes for treatment and interventions. Conclusions The internet continues to be a growing part of the dynamics of prostate cancer management with more men utilizing the internet each year to help understand their diagnosis. Specifically, we found that the internet is used more for searches pertaining to PSA, procedures, and interventions affecting the quality of life.

Validation of a multidisciplinary virtual reality (VR) robotic surgical curriculum.

The objective is to identify whether trainees demonstrate improvement in a standardized knot-tying task as assessed by Global Evaluative Assessment of Robotic Skills (GEARS) score after completion of a virtual reality (VR) robotic curriculum. An IRB-exempt prospective study was conducted with surgical trainees from August 2021 to February 2023. Participants initially performed a baseline robotic suturing task in which they were instructed to tie interrupted square knots in 10 min. Participants then completed a virtual reality simulation curriculum involving 23 exercises until they achieved 90% proficiency on all tasks. Participants then repeated the suturing task. Pre- and post-curriculum suturing tasks were recorded, de-identified, and scored by expert graders using a GEARS score. Trainees from three academic centers were invited to participate. Medical students (MS1-MS3) and surgical residents from gynecology, urology, and general surgery were invited to participate. Twenty-five trainees completed the pre-curriculum suturing task, the VR curriculum, and the post-curriculum suturing task. Trainees demonstrated significant improvement in their post-test GEARS score by 2.43 points (p < 0.05) and were able to tie three additional knots within 10 min after completion of the curriculum (p < 0.05). Trainees also demonstrated a faster time to complete first knot (114 s improvement, p < 0.05) after completion of the curriculum. All participants agreed or strongly agreed that completion of the robotic curriculum helped them feel more comfortable using the robotic console, and improved their robotic surgical skills. Surgical trainees and medical students with limited prior robotic surgical experience demonstrated objective improvement after completion of a standardized VR curriculum.

Adaptive designs for IVPT data with mixed scaled average bioequivalence.

In vitro permeation tests (IVPT) offer accurate and cost-effective development pathways for locally acting drugs, such as topical dermatological products. For assessment of bioequivalence, the FDA draft guidance on generic acyclovir 5% cream introduces a new experimental design, namely the single-dose, multiple-replicate per treatment group design, as IVPT pivotal study design. We examine the statistical properties of its hypothesis testing method-namely the mixed scaled average bioequivalence (MSABE). Meanwhile, some adaptive design features in clinical trials can help researchers make a decision earlier with fewer subjects or boost power, saving resources, while controlling the impact on family-wise error rate. Therefore, we incorporate MSABE in an adaptive design combining the group sequential design and sample size re-estimation. Simulation studies are conducted to study the passing rates of the proposed methods-both within and outside the average bioequivalence limits. We further consider modifications to the adaptive designs applied for IVPT BE trials, such as Bonferroni's adjustment and conditional power function. Finally, a case study with real data demonstrates the advantages of such adaptive methods.

Hyperglycosylation of prosaposin in tumor DCs promotes immune escape in cancer.

Tumors develop strategies to evade immunity by suppressing antigen presentation. Here, we show that prosaposin drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor DCs leads to cancer immune escape. We found that lysosomal prosaposin and its single saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, TGF-ß induced hyperglycosylation of prosaposin and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. In melanoma patients, we found similar prosaposin hyperglycosylation in tumor-associated DCs, and reconstitution with prosaposin rescued activation of tumor-infiltrating T cells. Targeting tumor DCs with recombinant prosaposin triggered cancer protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of prosaposin in tumor immunity and escape and introduce a novel principle of prosaposin-based cancer immunotherapy. One Sentence Summary: Prosaposin facilitates antigen cross-presentation and tumor immunity and its hyperglycosylation leads to immune evasion.

Women's perspectives on the use of artificial intelligence (AI)-based technologies in mental healthcare.

This study aimed to evaluate women's attitudes towards artificial intelligence (AI)-based technologies used in mental health care. We conducted a cross-sectional, online survey of U.S. adults reporting female sex at birth focused on bioethical considerations for AI-based technologies in mental healthcare, stratifying by previous pregnancy. Survey respondents (n = 258) were open to AI-based technologies in mental healthcare but concerned about medical harm and inappropriate data sharing. They held clinicians, developers, healthcare systems, and the government responsible for harm. Most reported it was "very important" for them to understand AI output. More previously pregnant respondents reported being told AI played a small role in mental healthcare was "very important" versus those not previously pregnant (P = .03). We conclude that protections against harm, transparency around data use, preservation of the patient-clinician relationship, and patient comprehension of AI predictions may facilitate trust in AI-based technologies for mental healthcare among women.

Role of Sex in Participation During Virtual Grand Rounds in Ophthalmology.

Importance: Sex disparities exist in academia. Female attendees consistently ask fewer questions in scientific meetings than male attendees, even when they constitute half of the audience. Objective: To assess the role of sex in participation during virtual grand rounds (GR) at a major academic center. Design, Setting, and Participants: In this prospective cohort study, attendees of the Department of Ophthalmology at the University of California, San Francisco, GR from April 2020 to April 2021 were included. All GR were held via a synchronous live video communication platform. During each GR session, a predesignated attendee collected the sex of all attendees, sex of the GR speaker, and sex of each individual who asked a question to the GR speaker in order of inquiry. The GR speakers and audience were unaware of the study. Data were analyzed from June 2021 to April 2023. Main Outcome and Measures: The main analysis assessed the association between being female and asking one of the first 3 questions. Results: A total of 31 virtual ophthalmology GR sessions were observed. The sex of the GR speaker was female in 13 of 31 sessions (42%). The mean (SD) percentage of audience sex at each of the GR sessions was 47% (0.05) female, 45% (0.06) male, and 8% (0.03) unknown. Male attendees were more likely to ask one of the first 3 questions compared with female attendees (prevalence ratio, 3.1; 95% CI, 2.1-4.5; P < .001). Conclusions and Relevance: Male attendees were more likely to ask questions during virtual ophthalmology GR compared with female attendees at an academic medical center. Strategies to encourage equal participation of sex in academic discourse should be encouraged.

Impact of Obstructive Sleep Apnea Syndrome on Time to Complete Recovery of Continence After Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Analysis.

Background: Postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) represents a bothersome side effect, which may permanently affect patient's quality of life. Several studies have demonstrated that obstructive sleep apnea syndrome (OSAS) is associated with urinary symptoms such as urge incontinence, overactive bladder, and nocturia. In this study, we sought to further explore the effect of OSAS on urinary continence after RARP. Methods: We queried our prospectively collected institutional RARP database and identified 82 patients with OSAS and 131 controls, which were matched for age and body mass index (BMI), with available follow-up data for continence. To minimize selection bias, we conducted a propensity score-matched analysis. Patient's characteristics and urinary continence outcomes were compared between the two groups before and after propensity-score matching. Kaplan-Meier curves were constructed to assess the difference in continence between the two groups. Results are presented as means with standard deviations and percentages with 95% confidence intervals (CIs). Results: A total of 213 patients were included in the analysis, of whom 82 with OSAS and 131 with non-OSAS (control group). The mean age of the total cohort was 61.7 ± 6.96 years, the mean BMI was 30.4 ± 5.36, and 52% of the cohort were classified as obese (BMI ≥30). In post-propensity score-matched analyses, there was no significant difference in baseline demographics and tumor characteristics between the two groups (included 82 cases in each group). The median time to continence was 6.6 months for the control group as compared with 13.0 months for the OSAS group (p < 0.001). At 12 months the continence rate for the OSAS group was 41.2% (95% CI: 28.9%-51.4%) as compared with 61.7% (95% CI: 28.5%-71.5%) for the control group. At 24 months the continence rate for the OSAS group was 68.7% (95% CI: 56%-77.7%) as compared with 90.8% (95% CI: 79%-96%) for the control group. Conclusion: On matched analysis, we found that patients with OSAS tended to demonstrate worse urinary continence recovery as compared with patients without OSAS. Additional investigation will be necessary to confirm these initial findings.

GARP on hepatic stellate cells is essential for the development of liver fibrosis.

BACKGROUND & AIMS: Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-ß docking molecule. While the immune regulatory properties of GARP on blood cells have been studied, the function of GARP on tissue stromal cells remains unclear. Here, we investigate the role of GARP expressed on hepatic stellate cells (HSCs) in the development of liver fibrosis. METHODS: The function of GARP on HSCs was explored in toxin-induced and metabolic liver fibrosis models, using conditional GARP-deficient mice or a newly generated inducible system for HSC-specific gene ablation. Primary mouse and human HSCs were isolated to evaluate the contribution of GARP to the activation of latent TGF-ß. Moreover, cell contraction of HSCs in the context of TGF-ß activation was tested in a GARP-dependent fashion. RESULTS: Mice lacking GARP in HSCs were protected from developing liver fibrosis. Therapeutically deleting GARP on HSCs alleviated the fibrotic process in established disease. Furthermore, natural killer T cells exacerbated hepatic fibrosis by inducing GARP expression on HSCs through IL-4 production. Mechanistically, GARP facilitated fibrogenesis by activating TGF-ß and enhancing endothelin-1-mediated HSC contraction. Functional GARP was expressed on human HSCs and significantly upregulated in the livers of patients with fibrosis. Lastly, deletion of GARP on HSCs did not augment inflammation or liver damage. CONCLUSIONS: GARP expressed on HSCs drives the development of liver fibrosis via cell contraction-mediated activation of latent TGF-ß. Considering that systemic blockade of TGF-ß has major side effects, we highlight a therapeutic niche provided by GARP and surface-mediated TGF-ß activation. Thus, our findings suggest an important role of GARP on HSCs as a promising target for the treatment of liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis represents a substantial and increasing public health burden globally, for which specific treatments are not available. Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-ß docking molecule. Here, we show that GARP expressed on hepatic stellate cells drives the development of liver fibrosis. Our findings suggest GARP as a novel target for the treatment of fibrotic disease.

Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.

OBJECTIVE: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. SUMMARY BACKGROUND DATA: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. METHODS: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. RESULTS: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. CONCLUSION: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.

A Case of Wellens' Syndrome.

This is a clinical case of a 43-year-old male with a past medical history notable for tobacco use disorder who presented to the emergency department for evaluation of typical chest pain. ECG was consistent with Wellens' syndrome with deeply inverted T waves in the anteroseptal leads. Coronary angiography confirmed a proximal left anterior descending coronary artery lesion, alongside other areas of coronary artery disease, and the patient was treated with surgical revascularization. There are specific ECG findings consistent with Wellens' syndrome that are important for all physicians to recognize, as they are associated with a serious cardiovascular condition that necessitates early invasive cardiac catheterization.

Evaluation of customized peripheral sealing device acceptance for surgical/medical masks among dental professionals during early COVID-19 pandemic / Evaluación de la aceptación de dispositivos de sellado periférico personalizados para máscaras quirúrgicas/médicas entre dentistas durante la pandemia temprana de COVID-19

Abstract A 3-dimensional (3D) printed custom-frame can improve the peripheral seal of readily available surgical/medical masks. This study aimed to assess the acceptance of a 3D-printed custom-frame with the American Society for Testing and Materials (ASTM) surgical/medical masks and the use of a face shield. A total of 206 subjects from a dental school participated, who answered a multiple-choice questionnaire. Participants received an invitation through the institutional email of the school via Qualtrics platform. 3D printed custom-frames were fabricated for each participant. According to their response, participants were divided into 4 groups: mask only (M), mask and frame (MF), mask and face shield (MFS), and all 3 personal protective equipment (MFFS). Data was analyzed in absolute and relative frequency. The acceptance of a 3D-printed custom-frame in the group MFFS varied between ''poor''/''very poor'' (44.7%). It allowed ''good'' performance of routine procedures (40.3%), but ''poor'' visual quality (48.1%). Musculoskeletal tolerance and ease to perform movements were adequate. There was no interference in olfactory sensitivity (44.7%) or in the ability to breathe (34.5%). Finally, it showed "moderate pain" (48.1%) on the ear and "no pain" (38.9%) on the head. The 3D-printed custom-frame adapted to ASTM surgical/medical face masks showed reasonable tolerance. Side effects of ear pain ranging in degrees were noted. Further research is indicated to evaluate safety, comfort, compliance, side effects, and occupational hazards of long-term use of enhanced PPE recommendations.Avoiding the recurrent outbreaks of COVID-19, the use of PPE by the public is necessary. Improper PPE use is a major source of concern for human and environmental health. Preventing such activities can be done by following steps involved in PPE disposals or by getting a new way to re-use such as improving peripherical sealing. Our work highlights that a custom-frame can improve protection, without adverse effects.

Resumen El sellado periférico de las máscaras médicas/quirúrgicas puede ser mejorado fácilmente mediante un marco personalizado impreso en 3 dimensiones (3D). Este estudio tuvo como objetivo evaluar la aceptación de un marco personalizado impreso en 3D cuando usado en combinacion con máscaras médicas/quirúrgicas de la Sociedad Estadounidense para Pruebas y Materiales (ASTM) asi como con el uso de protector facial. Participaron un total de 206 sujetos de una facultad de odontología, quienes respondieron un cuestionario de opción múltiple. Los participantes recibieron una invitación a través del correo institucional de la escuela a través de la plataforma Qualtrics. Se fabricaron marcos personalizados impresos en 3D para cada participante. Según su respuesta, los participantes se dividieron en 4 grupos: solo máscara (M), máscara y marco (MF), máscara y protector facial (MFS) y los 3 equipos de protección personal (MFFS). Los datos se analizaron en frecuencia absoluta y relativa. La aceptación de un marco personalizado impreso en 3D en el grupo MFFS varió entre ''pobre''/''muy pobre'' (44,7%). Permitió un ''buen'' desempeño de los procedimientos de rutina (40,3%), pero una ''mala'' calidad visual (48,1%). La tolerancia musculoesquelética y la facilidad para realizar movimientos fueron adecuadas. No hubo interferencia en la sensibilidad olfativa (44,7%) ni en la capacidad de respirar (34,5%). Finalmente, mostró "dolor moderado" (48,1%) en el oído y "sin dolor" (38,9%) en la cabeza. El marco personalizado impreso en 3D adaptado a las máscaras faciales quirúrgicas/ médicas de ASTM mostró una tolerancia razonable. Se observaron efectos secundarios de dolor de oído que variaron en grados. Estudios futuros deben evaluar la seguridad, la comodidad, efectos secundarios y los riesgos laborales del uso a largo plazo para este tipo de combinación. Para evitar los brotes recurrentes de COVID-19, es necesario el uso de equipamento personal de protección (EPP) por parte del público. El uso inadecuado de EPP es una fuente importante de preocupación para la salud humana y ambiental. La prevención de tales actividades se puede hacer siguiendo los pasos involucrados en la eliminación de EPP o obteniendo una nueva forma de reutilización, como mejorar el sellado periférico. Nuestro trabajo resalta que un marco personalizado puede mejorar la proteccion, sin afectos adversos.