Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study.

Background: Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. Objective: We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. Results: In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. Limitations: A retrospective study. Conclusions: Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Patterns of Perioperative Hormone Therapy for Gender-Affirming Surgery.

INTRODUCTION: There is no consensus regarding perioperative hormone replacement therapy (HRT) for gender-affirming surgery (GAS). Common concerns for continuing perioperative HRT included risk of deep vein thrombosis (DVT) or hematoma. However, discontinuing HRT is not risk free and may cause mood swing or increased anxiety. Our study aimed to investigate current patterns of HRT before GAS worldwide. METHODS: The first stage of Delphi technique was implemented by sending a 27-item survey to all surgeons (total n = 150; 94 plastic surgeon, 35 urologist, and 21 gynecologists) of the World Professional Association for Transgender Health who perform GAS. Survey themes included the hormone type, duration, and usage of DVT prophylaxis. RESULTS: Overall survey response rate was 34% (total n = 51; 8 urologists, 35 plastic surgeons, and 8 gynecologists). The majority of surgeons are US-based (n = 39, 76%). The most common HRTs are in injection form (n = 28, 55%). The majority of surgeons do not stop HRT before GAS and do provide DVT prophylaxis to all patients <1 week after GAS. The most common procedure that surgeons discontinue HRT is feminizing bottom surgery (43%). For surgeons who discontinue HRT before GAS, there is a wide variation on discontinuation schedule. CONCLUSIONS: There is considerable variation in perioperative HRT patterns for GAS. Further research is needed to develop a data-driven consensus guideline to provide high quality of care for transgender and nonbinary patients.

Radiology in the immune checkpoint inhibitor era.

The field of oncology has undergone rapid changes following the introduction of immunotherapies and biologics. However, these changes have also created new roles for radiology in both diagnosis and treatment. Our article addresses the evolving role of radiology in the immune checkpoint inhibitor era of oncology. With the progression of new immunotherapies for cancer, imaging paradigms and image guided therapy options have changed. Multidisciplinary oncology teams should be aware of these opportunities for collaboration.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.

IMPORTANCE: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma. OBJECTIVE: To determine the efficacy of adjuvant PD1 in resected AM or MM. DESIGN: An international, retrospective cohort study SETTING: Data up to November 2021 collected from 20 centres across 10 countries. PARTICIPANTS: One hundred and ninety four patients with resected stage III or IV1 AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis. MAIN OUTCOMES AND MEASURES: Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated. RESULTS: Forty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52-0.92, p = 0.0127)], DMFS [HR0.58 (0.38-0.89, p = 0.0134)] and OS [HR of 0.59 (0.38-0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69-2.68,p-value 0.3799], DMFS or OS. CONCLUSION AND RELEVANCE: After adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed.

Deaths of U.S. Citizens Undergoing Cosmetic Surgery - Dominican Republic, 2009-2022.

Although infections resulting from cosmetic surgery performed outside the United States have been regularly reported, deaths have rarely been identified. During 2009-2022, 93 U.S. citizens died after receiving cosmetic surgery in the Dominican Republic. The number of deaths increased from a mean of 4.1 per year during 2009-2018 to a mean of 13.0 during 2019-2022 with a peak in of 17 in 2020. A subset of post-cosmetic surgery deaths occurring during peak years was investigated, and most deaths were found to be the result of embolic events (fat emboli or venous thromboembolism) for which a high proportion of the patients who died had risk factors, including obesity and having multiple procedures performed during the same operation. These risk factors might have been mitigated or prevented with improved surgical protocols and postoperative medical care, including prophylactic measures against venous thromboembolism. U.S. citizens interested in receiving elective cosmetic surgery outside the United States should consult with their health care professionals regarding their risk for adverse outcomes. Public health authorities can support provider education on the importance of preoperative patient evaluation and the potential danger of performing multiple cosmetic procedures in one operation.

Vanderbilt Mini-PROM-Breast for Breast Reconstruction: A Short-Form, Patient-Reported Outcomes Measure.

BACKGROUND: Breast reconstruction procedures are among the most commonly performed plastic surgery operations. Although there are well-validated patient-reported outcomes measures (PROMs) for breast reconstruction, there are several patient-, provider-, and service-level barriers to their implementation in routine clinical settings. Therefore, we developed a short-form PROM to evaluate breast reconstruction outcomes. METHODS: Using a mixed-methods approach, the Vanderbilt Mini-PROM-Breast (VMP-B) was constructed and validated to assess patient-reported outcomes from breast reconstruction. Classic test theory methods were used to evaluate acceptability, reliability, and validity. External validation was subsequently performed using the BREAST-Q as a reference standard. RESULTS: The VMP-B is a 16-item instrument composed of three domains: quality of life, body image, and breast satisfaction. Psychometric properties including acceptability, reliability, and validity exceeded reference criteria. When tested with 104 patients, the authors found significant benefits of breast reconstruction on quality of life, body image, and breast satisfaction. These results were associated with sizeable effect sizes (g) (g = 0.421, g = 0.520, and g = 1.25) demonstrative of clinically meaningful results. When tested concurrently in 70 patients, the VMP-B and the BREAST-Q showed similar results, exhibiting excellent convergent validity. CONCLUSIONS: The VMP-B is a validated short-form PROM that reliably assesses breast reconstruction outcomes. As a short form, the VMP-B decreases both patient and provider burden, which allows for routine, point-of-care collection of breast reconstruction outcomes.

Defining access without excess: expanding appropriate use of antibiotics targeting multidrug-resistant organisms.

Antimicrobial resistance remains a significant global public health threat. Although development of novel antibiotics can be challenging, several new antibiotics with improved activity against multidrug-resistant Gram-negative organisms have recently been commercialised. Expanding access to these antibiotics is a global public health priority that should be coupled with improving access to quality diagnostics, health care with adequately trained professionals, and functional antimicrobial stewardship programmes. This comprehensive approach is essential to ensure responsible use of these new antibiotics.

Patient Perspectives on Selecting an Academic Aesthetic Surgeon: A Qualitative Analysis.

BACKGROUND: Growth of the aesthetic surgery marketplace has increased patient choice in provider selection. This study aimed to characterize how patients choose an aesthetic surgeon, identify knowledge gaps in this decision-making process, and understand why patients select academic aesthetic surgeons. METHODS: A qualitative interview study of aesthetic surgery patients from an academic center was conducted. Purposive sampling maximized representation regarding surgeon, surgery type, and patient demographics. An interview guide was developed in collaboration with content and methodology experts, then refined through pilot testing. Emergent themes were identified using a codebook constructed by grounded theory. RESULTS: Thematic saturation was achieved with 24 patients. When selecting a surgeon, participants valued bedside manner (24 of 24) and past patients' satisfaction (18 of 24). Most participants (16 of 24) ascribed low importance to board certification. Reasons given for choosing an academic practice included the institution's reputation (13 of 24) and the availability of medical records and other specialties if complications arise (8 of 24). Participants demonstrated knowledge gaps regarding medical training and licensure. No participant (0 of 24) was aware that any licensed physician can offer aesthetic surgery, and nearly all participants (23 of 24) expressed discomfort with this. CONCLUSIONS: Patients prioritize subjective elements when selecting an aesthetic surgeon, relying less on objective and meaningful qualifications like board certification and training background. Academic aesthetic practice is valued because of reputation and ability to function as a medical home. Given the lack of public understanding regarding physician training, initiatives promoting transparency are needed to ensure that patients can make safe, informed decisions.

Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers. Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity. Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs. Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

Case Report of Very-Low-Dose Fentanyl Causing Fentanyl-Induced Chest Wall Rigidity.

Wooden chest syndrome (WCS) is a rare phenomenon of opioid-induced skeletal muscle rigidity causing respiratory failure and inability to ventilate. The most common opioid associated with WCS is the synthetic opioid fentanyl. Fentanyl has been called the deadliest drug in America. With the use of fentanyl in critical care units and operation rooms, it is important to better understand fentanyl's side effects and predisposing factors of WCS. The symptoms of WCS are often seen in lower fentanyl doses than what would cause apnea. In this case report, we present a case of WCS with an extremely low dose of fentanyl, i.e., 50 µcg (0.49 µcg/kg), in an 80-year-old patient with a medical history significant for chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS).

Multidimensional Assessment of Patient-Reported Outcomes After Gender-Affirming Surgeries Using a Validated Instrument.

INTRODUCTION: Limited literatures used validated instruments to evaluate patient-reported outcomes (PROs) for transgender and gender-diverse population undergoing gender-affirming surgeries (GASs). This study aimed to evaluate PROs using a newly validated psychometric instrument, Vanderbilt Mini Patient-Reported Outcome Measures-Gender (VMP-G). METHODS: Vanderbilt Mini Patient-Reported Outcome Measures-Gender assesses 4 scales: quality of life, self-concept, satisfaction, and gender dysphoria. Scores range from 20 to 100, with higher scores representing superior PROs. Descriptive analysis was performed, and outcomes were compared in different races/ethnicities, gender identities, age, types of GAS, and time. Patients seeking GAS at Vanderbilt University Medical Center from October 11, 2021, to October 11, 2022, were included. Data were collected anonymously via the Research Electronic Data Capture survey tool at preoperative or postoperative clinic visits. RESULTS: A total of 207 patients completed VMP-G. Average age was 31.8 years (SD, ±11.5 years). Fifty-three percent of patients were postoperative GAS. In bivariate and linear regression analyses, postoperative patients scored higher on all scales compared with preoperative patients ( P < 0.001). After adjustment, postoperative patients scored 12.5 higher on VMP-G compared with preoperative patients ( P < 0.01). In subset analyses, GAS was associated with improved PROs in White, non-White, binary, and nonbinary and patients younger than 21 years ( P < 0.05). After GAS, patients younger than 21 years reported similar outcomes, compared with patients older than 21 years ( P > 0.05). No PROs differences were reported between patients who underwent top versus bottom surgery ( P = 0.2). Postoperative patients reported low rates of regret (2.8%). Scores on the VMP-G were sustained even 1 year after GAS. Each month after GAS was associated with a score improvement of 0.02 in the gender dysphoria domain after adjusting for patient demographics ( P = 0.02). CONCLUSIONS: Using a validated GAS-specific measure, we found that surgery sustainably improves patients' self-reported outcomes including gender dysphoria.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Comparison of Complication Rates Between Subpectoral vs Prepectoral Techniques in Prosthetic Breast Reconstruction.

BACKGROUND: The location of tissue expanders in implant-based breast reconstruction remains controversial due to variation in surgical techniques and devices. OBJECTIVES: The aim of this study was to provide a comprehensive assessment of early and late complication rates between prepectoral and subpectoral placement of tissue expanders. METHODS: A retrospective cohort study was conducted of all adult female patients who had undergone 2-stage implant-based breast reconstruction between 2013 and 2019 in our institution. Early complication was defined as complications that occurred within 30 days after surgery. Time-to-event analyses were performed and Cox proportional hazard models were used to adjust for confounders. RESULTS: In total, 854 patients were included; 76% of patients underwent a subpectoral tissue expander placement. After the first-stage procedure, the early complication rate was 34% and the late complication rate was 36.4%. After the second-stage procedure, the early complication rate was 16.3% and the late complication rate was 16.1%. Location of the tissue expander did not predict either overall early or late complication rates, regardless of the stages of reconstruction, after adjusting for confounders. Tissue expanders placed in prepectoral plane were associated with a higher hazard ratio (HR) for developing early and late infection after the first stage of reconstruction (HR, 2.1 and 2.4, respectively) as well as late infection after the second stage of reconstruction (HR, 5.3; all P < .05). CONCLUSIONS: Location of tissue expanders did not predict risk of complication. However, the prepectoral group was associated with an increased risk of developing infection.

Impact of Tissue Expander Surface Texture on Two-Stage Breast Reconstruction Outcomes: A Combined Analysis of Incidence, Timing, and Severity.

BACKGROUND: With ongoing investigations of the impact of device texturing on breast implant-related anaplastic large cell lymphoma (BIA-ALCL), studies have begun comparing complications profiles of tissue expanders. However, there is a paucity of timing and severity data of complications. The aim of this study is to provide a comparative survival analysis of post-operative complications between smooth (STE) and textured tissue expanders (TTE) in breast reconstruction. METHODS: A single institution experience with tissue expander breast reconstruction was reviewed for complications up to 1 year post 2nd stage reconstruction from 2014-2020. Demographics, comorbidities, operation-related variables, and complications were evaluated. Kaplan-Meier curves, cox proportional hazard models, and a consensus based ordinal logistic regression model were used to compare complication profiles. RESULTS: Of 919 ttal patients, 65.3% (n=600) received TTEs and 34.7% (n=319) received STEs. There was increased risk of infection (p<0.0001), seroma (p=0.046), expander malposition (p<0.0001), and wound dehiscence (p=0.019) in STEs compared to TTEs. However, there were also decreased risk of capsular contracture (p=0.005) in STEs compared to TTEs. Failure of breast reconstruction (p<0.001) and wound dehiscence (p=0.018) occurred significantly earlier in STEs compared to TTEs. Predictors for significantly higher severity complications included: smooth tissue expander use (p=0.007), shorter time to complication (p<0.0001), higher BMI (p=0.005), smoking history (p=0.025), and nipple sparing mastectomy (p=0.012). CONCLUSIONS: Differences in the timing and severity of complications contribute to the safety profiles of tissue expanders. STEs are associated increased odds of higher severity and earlier complications. Therefore, tissue expander selection may depend on underlying risk factors and severity predictors.

Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations.

Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management. Here, we conducted a multi-institution analysis of all patients with stage III/IV melanoma who developed RirAEs after being treated with ICIs (anti-PD-1/L1, anti-CTLA-4, and combination PD-1/CTLA-4 blockade) at three institutions (Vanderbilt University Medical Center, Massachusetts General Hospital, and Melanoma Institute of Australia). RirAEs were defined as those occurring in approximately <1% of patients treated with anti-PD-1 or <2% with combination. Of 2834 patients who received ICIs, 82 developed RirAEs and were more common with combination PD-1/CTLA-4 blockade (4.6%) vs. anti-PD-1/L1 agents (2.8%). Overall median time from ICI start to RirAE was 86 days (interquartile range 42-235 days) with significantly earlier onset in combination therapy (p < 0.001). The spectrum of RirAEs spanned across several organ systems. Most RirAEs were grade 2 (57 [41.3%]) and grade 3 (40 [29.0%]) with relatively few grade 4 (11 [8.0%]) or 5 (5 [3.6%]) events. Steroid re-escalation (21.4%) or additional immunosuppression (13.8%) were commonly required. RirAE recurrence occurred in 22.6% with ICI rechallenge; 37.1% had new irAEs with rechallenge. In conclusion, RirAEs associated with ICIs in melanoma patients occurred, in aggregate, in 2-5% of patients treated with anti-PD-1-based therapy. Steroid re-escalation and alternative immunosuppression use were frequently required but fatal irAEs were fairly uncommon.

Infection Prevention and Control Initiatives to Prevent Healthcare-Associated Transmission of SARS-CoV-2, East Africa.

The coronavirus disease pandemic has highlighted the need to establish and maintain strong infection prevention and control (IPC) practices, not only to prevent healthcare-associated transmission of SARS-CoV-2 to healthcare workers and patients but also to prevent disruptions of essential healthcare services. In East Africa, where basic IPC capacity in healthcare facilities is limited, the US Centers for Disease Control and Prevention (CDC) supported rapid IPC capacity building in healthcare facilities in 4 target countries: Tanzania, Ethiopia, Kenya, and Uganda. CDC supported IPC capacity-building initiatives at the healthcare facility and national levels according to each country's specific needs, priorities, available resources, and existing IPC capacity and systems. In addition, CDC established a multicountry learning network to strengthen hospital level IPC, with an emphasis on peer-to-peer learning. We present an overview of the key strategies used to strengthen IPC in these countries and lessons learned from implementation.

Acute Dystonic Reaction in the Upper Extremity Following Anesthesia.

We present a case of an 83-year-old female who underwent carpal tunnel release with intravenous regional anesthesia (Bier block) and monitored anesthesia care (MAC). After surgery, the patient developed an abnormal motion of her upper extremity, which was treated as an acute dystonic reaction. Dystonic reactions can occasionally be seen as a post-anesthetic complication, but they are most often associated with antidopaminergic medications. Limbs are rarely affected by dystonic reactions, as they usually affect the head and neck. Acute dystonic reactions can be easily treated with diphenhydramine or benzodiazepines to prevent other extrapyramidal symptoms from occurring. The differential, in this case, was widely varied and inappropriate treatment would have been detrimental to patient care.