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Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1- CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate-induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.
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Phenology refers to the seasonal timing patterns commonly exhibited by life on Earth, from blooming flowers to breeding birds to human agriculture. Climate change is altering abiotic seasonality (e.g., longer summers) and in turn, phenological patterns contained within. However, how phenology should evolve is still an unsolved problem. This problem lies at the crux of predicting future phenological changes that will likely have substantial ecosystem consequences, and more fundamentally, of understanding an undeniably global phenomenon. Most studies have associated proximate environmental variables with phenological responses in case-specific ways, making it difficult to contextualize observations within a general evolutionary framework. We outline the complex but universal ways in which seasonal timing maps onto evolutionary fitness. We borrow lessons from life history theory and evolutionary demography that have benefited from a first principles-based theoretical scaffold. Lastly, we identify key questions for theorists and empiricists to help advance our general understanding of phenology.
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Ecosistema , Rasgos de la Historia de Vida , Animales , Humanos , Estaciones del Año , Fitomejoramiento , Aves , Cambio ClimáticoRESUMEN
BACKGROUND: We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies. MATERIALS AND METHODS: We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). RESULTS: We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS. CONCLUSIONS: Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.
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BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.
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PURPOSE: We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS: Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION: In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.
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Neoplasias de la Mama , Neutropenia , Policétidos Poliéteres , Neoplasias de la Mama Triple Negativas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Ciclofosfamida/efectos adversos , Furanos/uso terapéutico , Cetonas/efectos adversos , Neutropenia/tratamiento farmacológico , Receptor ErbB-2 , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiologíaRESUMEN
PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women < 45 years with newly diagnosed stage 1-3 breast cancer. Patients completed a REDCap survey on fertility and family-building in the setting of hypothetical risk scenarios. Patient, tumor, and treatment characteristics were collected through surveys and medical record. RESULTS: Of 140 study patients [median age = 41.4 (range 23-45)], 71 (50.7%) were interested in having children. Women interested in future childbearing were younger than those who were not interested (mean = 35.2 [SD = 5.2] vs 40.9 years [3.90], respectively, p < 0.001), and more likely to be childless (81% vs 31%, p < 0.001). 54 women (77.1% of patients interested in future children) underwent/planned to undergo oocyte/embryo cryopreservation before chemotherapy. Interest in future childbearing decreased with increasing hypothetical recurrence risk, however 17% of patients wanted to have children despite a 75-100% hypothetical recurrence risk. 24.3% of patients wanted to conceive < 2 years from diagnosis, and 35% of patients with hormone receptor positive tumors were not willing to complete 5 years of hormone therapy. CONCLUSION: Many young women diagnosed with early-stage breast cancer prioritize childbearing. Interest in having a biologic child was not associated with standard prognostic risk factors. Interest decreased with increasing hypothetical recurrence risk, though some patients remained committed to future childbearing despite near certain hypothetical risk. Individual risk assessment should be included in family-planning discussions throughout the continuum of care as it can influence decision-making.
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Neoplasias de la Mama , Preservación de la Fertilidad , Infertilidad Femenina , Humanos , Femenino , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Estudios Prospectivos , FertilidadRESUMEN
Eleven patients (5 men, 6 women) with post-operative thoracic duct injuries and high output chylothorax were treated with thoracic duct embolization (TDE). Six patients underwent intraprocedural thoracic duct ligation at the time of original procedure. In all cases, the pleural fluid demonstrated high triglyceride levels (414 mg/dL; interquartile range [IQR], 345 mg/dL). Median daily (IQR) chest tube outputs before and after TDE were 900 mL (1,200 mL) and 325 mL (630 mL), respectively. Coil- or plug-assisted ethylene vinyl alcohol (EVOH) copolymer was used as embolic agent in all patients. Technical and clinical success rates were 100% and 82%, respectively. Nontarget venous embolization of EVOH copolymer was not identified on subsequent imaging.
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Quilotórax , Embolización Terapéutica , Traumatismos Torácicos , Masculino , Humanos , Femenino , Quilotórax/diagnóstico por imagen , Quilotórax/etiología , Quilotórax/terapia , Embolización Terapéutica/métodos , Conducto Torácico/diagnóstico por imagen , Estudios Retrospectivos , Traumatismos Torácicos/terapia , Resultado del TratamientoRESUMEN
OBJECTIVES: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. STUDY DESIGN: Retrospective observational study; review of patient records in fifteen Australian institutions. SETTING, PARTICIPANTS: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. MAIN OUTCOME MEASURES: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. RESULTS: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. CONCLUSION: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Masculino , Adulto , Humanos , Anciano , Femenino , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios de Cohortes , Australia/epidemiologíaRESUMEN
BACKGROUND: Epinephrine is recommended without an apparent ceiling dosage during cardiac arrest. However, excessive alpha- and beta-adrenergic stimulation may contribute to unnecessarily high aortic afterload, promote post-arrest myocardial dysfunction, and result in cerebral microvascular insufficiency in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This was a retrospective cohort study of adults (≥ 18 years) who received ECPR at large academic ECMO center from 2018 to 2022. Patients were grouped based on the amount of epinephrine given during cardiac arrest into low (≤ 3 mg) and high (> 3 mg) groups. The primary endpoint was neurologic outcome at hospital discharge, defined by cerebral performance category (CPC). Multivariable logistic regression was used to assess the relationship between cumulative epinephrine dosage during arrest and neurologic outcome. RESULTS: Among 51 included ECPR cases, the median age of patients was 60 years, and 55% were male. The mean cumulative epinephrine dose administered during arrest was 6.2 mg but ranged from 0 to 24 mg. There were 18 patients in the low-dose (≤ 3 mg) and 25 patients in the high-dose (> 3 mg) epinephrine groups. Favorable neurologic outcome at discharge was significantly greater in the low-dose (55%) compared to the high-dose (24%) group (p = 0.025). After adjusting for age, those who received higher doses of epinephrine during the arrest were more likely to have unfavorable neurologic outcomes at hospital discharge (odds ratio 4.6, 95% CI 1.3, 18.0, p = 0.017). CONCLUSION: After adjusting for age, cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurologic outcomes after ECPR and require further investigation.
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Reanimación Cardiopulmonar , Epinefrina , Oxigenación por Membrana Extracorpórea , Paro Cardíaco , Humanos , Epinefrina/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Reanimación Cardiopulmonar/métodos , Oxigenación por Membrana Extracorpórea/métodos , Paro Cardíaco/terapia , Anciano , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Resultado del TratamientoRESUMEN
PURPOSE: Craniotomies for tumor resection can at times result in wound complications which can be devastating in the treatment of neuro-oncological patients. A cranial stair-step technique was recently introduced as an approach to mitigate these complications, especially in this patient population who often exhibit additional risk factors including steroids, chemoradiation, and VEGF inhibitor treatments. This study evaluates our cranial stair-step approach by comparing its postoperative complications using propensity score matching with those of a standard craniotomy wound closure. METHODS: A retrospective chart review was conducted on patients with intracranial neoplasms undergoing primary craniotomy at a single institution. Patients with prior craniotomies and less than three months of follow-up were excluded. Analyses were performed using R Studio. RESULTS: 383 patients were included in the study, 139 of whom underwent the stair-step technique while the rest underwent traditional craniotomy closures. The stair-step cohort was older, had higher ASA classes, and had a higher prevalence of coronary artery disease. The stair-step patients were administered fewer steroids before (40.29% vs. 56.56%, p < 0.01) and after surgery (87.05% vs. 94.26%, p = 0.02), fewer immunotherapy (12.95% vs. 20.90%, p = 0.05), but they received more radiation preoperatively (15.11% vs. 8.61%, p = 0.05). They also underwent fewer operations for recurrences and residuals (0.72% vs. 10.66%, p = 0.01). On propensity score matching, we found 111 matched pairs with no differences except follow-up duration (p < 0.01). The stair-step group had fewer soft tissue infections (0% vs. 3.60%, p = 0.04), fewer total wound complications (0% vs. 4.50%, p = 0.02), was operated on less for these complications (0% vs. 3.60%, p = 0.04), and had a shorter length of stay (6 vs. 9 days, p < 0.01). Notably, the average time to wound complication in our cohort was 44 days, well within our exclusion criteria and follow-up duration. CONCLUSION: The cranial stair-step technique is safe and effective in reducing rates of wound complications and reoperation for neuro-oncologic patients requiring craniotomy.
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Neoplasias Encefálicas , Craneotomía , Complicaciones Posoperatorias , Puntaje de Propensión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Craneotomía/métodos , Craneotomía/efectos adversos , Estudios Retrospectivos , Neoplasias Encefálicas/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Anciano , AdultoRESUMEN
INTRODUCTION: Malnutrition is associated with increased mortality in patients with head and neck (H&N) cancer. Because albumin levels are used as a surrogate for nutritional status, the purpose of this study is to assess whether malnutrition is associated with adverse postoperative outcomes in H&N free flap reconstruction. MATERIALS AND METHODS: The 2006-2018 National Surgical Quality Improvement Program Database was queried for patients undergoing flap procedures of the H&N based on Current Procedure Terminology codes. Patients were included if they were operated on by an otolaryngologist or when the primary surgical site was H&N. Nutritional status was categorized as malnourished (preoperative albumin level <3.5 g/dL) or normal (preoperative albumin level ≥3.5 g/dL). Major complications included pulmonary complications, cardiac complications, deep vein thrombosis/pulmonary embolism, and sepsis/septic shock. Minor complications included surgical infection, urinary tract infection, bleeding, and dehiscence. Data were analyzed via univariate chi-square and multivariate regression analyses. RESULTS: Of the patients, 2532 (83.3%) had normal albumin and 506 (16.7%) had hypoalbuminemia. Patients with hypoalbuminemia were more likely to have smoking history (P = 0.008), pulmonary comorbidity (P < 0.001), renal comorbidity (P = 0.018), disseminated cancer (P < 0.001), steroid use (P < 0.001), recent weight loss (P < 0.001), bleeding disorder (P = 0.023), and preoperative transfusion (P < 0.001). After adjustment for preoperative variance, malnourished patients were more likely to experience death (P < 0.001), return to operating room (P < 0.001), free flap failure (P = 0.008), pulmonary complication (P < 0.001), deep vein thrombosis/pulmonary embolism (P = 0.019), wound disruption (P = 0.042), intraoperative transfusion (P < 0.001), minor complication (P < 0.001), major complication (P < 0.001), and extended length of stay (P < 0.001). Of the patients with normal albumin, 2.1% experienced flap failure compared with 6.3% of patients with hypoalbuminemia. It should be noted that malnourished patients were 3.370 times more likely to experience flap failure (95% confidence interval, 1.383-8.212; P = 0.008) and 3.975 times more likely to experience death (95% confidence interval, 1.700-9.626; P = 0.001) than those with normal albumin. CONCLUSION: Malnutrition is associated with death, flap failure, minor complications, and other major complications following H&N free flap surgery, even after controlling for preoperative variance. Optimizing preoperative nutrition status before free flap procedures may ameliorate morbidity and mortality in H&N patients.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Hipoalbuminemia , Desnutrición , Embolia Pulmonar , Trombosis de la Vena , Humanos , Hipoalbuminemia/complicaciones , Estudios Retrospectivos , Desnutrición/complicaciones , Desnutrición/epidemiología , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Trombosis de la Vena/complicaciones , Albúminas , Factores de RiesgoRESUMEN
BACKGROUND: Gender-affirming top surgery is becoming increasingly common, with greater diversity in the patients receiving top surgery. The purpose of this study was to examine national trends in patient demographics, characteristics, wound complication rates, and concurrent procedures in patients receiving gender-affirming top surgeries. METHODS: Patients with gender dysphoria who underwent breast procedures, including mastectomy, mastopexy, breast augmentation, or breast reduction by a plastic surgeon between 2013 and 2022, were identified from the American College of Surgeons National Surgical Quality Improvement Program database. These procedures were considered to be gender-affirming "top surgery." Univariate analyses were performed to examine trend changes in the patient population and types of additional procedures performed over the last decade. RESULTS: There was a 38-fold increase in the number of patients who received top surgery during the most recent years compared to the first 2 years of the decade. Significantly more individuals receiving top surgery in recent years were nonbinary (P < 0.01). There was a significant decrease in percentage of active smokers (P < 0.01) while there was an increase in percentage of patients with diabetes (P = 0.03). While there was a significant increase in the number of obese patients receiving top surgery (P < 0.01), there were no differences in postoperative wound complications between the years. Significantly more patients received additional procedures (P < 0.01) and had about a 9-fold increase in distinct number of additional CPT codes from 2013-2014 to 2021-2022. CONCLUSIONS: Our study found that there has been (1) a significant increase in the number of top surgery patients from 2013 to 2022 overall and (2) a particular increase in patients with preoperative comorbidities, such as a higher body mass index and diabetes. Understanding current and evolving trends in patients undergoing surgical treatment for gender dysphoria can inform individualized care plans that best serve the needs of patients and optimize overall outcomes.
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BACKGROUND: The popularity of cosmetic tourism may increase unnecessary risks for patients as postoperative care is variable. However, little is known about the current trends and public perception of this growing phenomenon. This study compares interest in cosmetic tourism in popular medical tourism destinations relative to the US. METHODS: Google Trends was queried from October 2017 to September 2023, examining trends over the full period and dissecting changes between 2017-2020 and 2020-2023. Search volume data were retrieved for the top international countries and the US for each of the top five cosmetic procedures, according to the ISAPS 2022 Global Survey. A p value < 0.05 was used for statistical significance. RESULTS: Searches for liposuction, blepharoplasty, breast augmentation, mastopexy, and abdominoplasty were compared between the US, Mexico, Turkey, Thailand, and Colombia. Google Trends data mirrored the prevalence of the two most common procedures, liposuction, and breast augmentation. Differences in interest regarding liposuction were greatest in Mexico, Thailand, and Turkey compared to the US (p < 0.05). Medical tourism for blepharoplasty had the highest search interest scores for Turkey and Thailand from 2017 to 2023 (p < 0.05). Significant differences were also consistent across all time intervals for breast augmentation, mastopexy, and abdominoplasty, with higher interest in Mexico and Turkey (p < 0.05). CONCLUSIONS: Google Trends analysis serves as an insightful tool for understanding cosmetic tourism. Changing trends bring the potential to assess worldwide versus country-specific procedure interest. These observed trends may foreshadow future international aesthetic procedure trends. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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BACKGROUND: Surgical chest masculinization procedures, especially gender-affirming top surgery (GATS), are becoming increasingly prevalent in the USA. While a variety of surgical techniques have been established as both safe and effective, there is limited research examining ideal aesthetic nipple appearance and incision scar pattern. This study employs patient images to understand the public's perception on top surgery outcomes when adjusting for BMI ranges and Fitzpatrick skin types. METHODS: Images from RealSelf modified via Adobe Photoshop depicted various scar types and nipple-areolar complex (NAC) sizes/positions. A Qualtrics survey was distributed utilizing Amazon Mechanical Turk. Statistical analysis was performed through JMP Pro 17 for ordinal and categorical values, with a p value less than or equal to 0.05 statistically significant. RESULTS: A moderately sized and laterally placed NAC was preferred. A transverse scar that resembles the pectoral border between the level of the inframammary fold and pectoral insertion was deemed most masculine and aesthetic. Majority of results demonstrated that this is unaffected by Fitzpatrick skin types. Increased BMI images impacted public preferences, as a nipple placed farther from the transverse incision (p = 0.04) and a transverse scar position closer to the IMF was preferred in higher BMI patients. CONCLUSIONS: An understanding of the most popular NAC and scar choices, as well as how these factors may differ when considering a Fitzpatrick skin type or BMI categorization was attained. This validates the importance of patient-centered approach when employing surgical techniques in GATS. Future studies intend to obtain reports from actual patients considering GATS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable.
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BACKGROUND: Plastic and reconstructive surgeons are often presented with reconstructive challenges as a sequela of complications in high-risk surgical patients, ranging from exposure of hardware, lymphedema, and chronic pain after amputation. These complications can result in significant morbidity, recovery time, resource utilization, and cost. Given the prevalence of surgical complications managed by plastic and reconstructive surgeons, developing novel preventative techniques to mitigate surgical risk is paramount. METHODS: Herein, we aim to understand efforts supporting the nascent field of Preventive Surgery, including (1) enhanced risk stratification, (2) advancements in postoperative care. Through an emphasis on four surgical cohorts who may benefit from preventive surgery, two of which are at high risk of morbidity from wound-related complications (patients undergoing sternotomy and spine procedures) and two at high risk of other morbidities, including lymphedema and neuropathic pain, we aim to provide a comprehensive and improved understanding of preventive surgery. Additionally, the role of risk analysis for these procedures and the relationship between microsurgery and prophylaxis is emphasized. RESULTS: (1) medical optimization and prehabilitation, (2) surgical mitigation techniques. CONCLUSION: Reconstructive surgeons are ideally placed to lead efforts in the creation and validation of accurate risk assessment tools and to support algorithmic approaches to surgical risk mitigation. Through a paradigm shift, including universal promotion of the concept of "Preventive Surgery," major improvements in surgical outcomes may be achieved.
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BACKGROUND: Reduction mammaplasty can provide symptomatic relief to patients suffering from macromastia, however complications such as dehiscence are common. It is unknown if the presence of complications may affect patient reported outcomes. OBJECTIVES: This study aims to (1) determine risk factors for development of complications, and (2) to examine the correlation between postoperative complications and patient reported outcomes in reduction mammaplasty. METHODS: A single-center retrospective chart review was performed on patients who received reduction mammaplasties (CPT19318) between 1/17-2/23 by thirteen surgeons. Breast cancer cases and oncoplastic reconstructions were excluded. Patients with >1 complication were grouped into the complications cohort. BREAST-Q-survey was used to assess satisfaction. RESULTS: A total of 661 patients were included for analysis, and 131 patients developed at least one complication. Patients in the complication group had significantly higher average ages and body mass indexes, and a higher likelihood of hypertension and diabetes (p<0.01). Among 180 BREAST-Q responders, 41 had at least one complication. There were no significant differences between the two groups across survey outcomes. Although obese patients were more likely to develop infection and require revisions (p<0.01), no significant differences in subgroup analysis of patient-reported outcomes focusing on obese patients were observed. CONCLUSIONS: Obesity, hypertension, and diabetes were associated with postoperative complications of reduction mammaplasty. Patients with complications had similar postoperative Breast-Q satisfaction to patients without complications. While risk optimization is critical, patients and surgeons should be reassured that satisfaction may be achieved even in the event of a complication.
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BACKGROUND: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care. METHODS: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales. Participants aged 18 or older referred with non-specific symptoms or symptoms potentially due to gynaecological, lung, or upper or lower gastrointestinal cancers were included and gave a blood sample when they attended for urgent investigation. Participants were excluded if they had a history of or had received treatment for an invasive or haematological malignancy diagnosed within the preceding 3 years, were taking cytotoxic or demethylating agents that might interfere with the test, or had participated in another study of a GRAIL MCED test. Patients were followed until diagnostic resolution or up to 9 months. Cell-free DNA was isolated and the MCED test performed blinded to the clinical outcome. MCED predictions were compared with the diagnosis obtained by standard care to establish the primary outcomes of overall positive and negative predictive value, sensitivity, and specificity. Outcomes were assessed in participants with a valid MCED test result and diagnostic resolution. SYMPLIFY is registered with ISRCTN (ISRCTN10226380) and has completed follow-up at all sites. FINDINGS: 6238 participants were recruited between July 7 and Nov 30, 2021, across 44 hospital sites. 387 were excluded due to staff being unable to draw blood, sample errors, participant withdrawal, or identification of ineligibility after enrolment. Of 5851 clinically evaluable participants, 376 had no MCED test result and 14 had no information as to final diagnosis, resulting in 5461 included in the final cohort for analysis with an evaluable MCED test result and diagnostic outcome (368 [6·7%] with a cancer diagnosis and 5093 [93·3%] without a cancer diagnosis). The median age of participants was 61·9 years (IQR 53·4-73·0), 3609 (66·1%) were female and 1852 (33·9%) were male. The MCED test detected a cancer signal in 323 cases, in whom 244 cancer was diagnosed, yielding a positive predictive value of 75·5% (95% CI 70·5-80·1), negative predictive value of 97·6% (97·1-98·0), sensitivity of 66·3% (61·2-71·1), and specificity of 98·4% (98·1-98·8). Sensitivity increased with increasing age and cancer stage, from 24·2% (95% CI 16·0-34·1) in stage I to 95·3% (88·5-98·7) in stage IV. For cases in which a cancer signal was detected among patients with cancer, the MCED test's prediction of the site of origin was accurate in 85·2% (95% CI 79·8-89·3) of cases. Sensitivity 80·4% (95% CI 66·1-90·6) and negative predictive value 99·1% (98·2-99·6) were highest for patients with symptoms mandating investigation for upper gastrointestinal cancer. INTERPRETATION: This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms. FUNDING: GRAIL Bio UK.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Gales/epidemiología , Medicina Estatal , Neoplasias/diagnóstico , Neoplasias/epidemiología , Estudios de Cohortes , Inglaterra/epidemiologíaRESUMEN
BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. CONCLUSIONS: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. CLINICAL TRIAL REGISTR ATION: Clinicaltrials.gov (NCT03475251).
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Neoplasias del Colon , Neoplasias del Recto , Humanos , Piridinas , Compuestos de Fenilurea , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. METHODS: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. RESULTS: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). CONCLUSION: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Médula Ósea/patología , Molécula de Adhesión Celular Epitelial/uso terapéutico , Terapia Neoadyuvante , Citometría de Flujo , PronósticoRESUMEN
This case series describes a technique to protect nondiseased liver parenchyma during transarterial radioembolization (TARE) using microvascular plugs to occlude nontarget vessels temporarily and protect normal liver. This technique, defined as temporary vascular occlusion, was performed in 6 patients, with complete vessel occlusion obtained in 5 of the 6 patients and partial occlusion with flow reduction in 1 of the 6 patients. A statistically significant (P = .001) dose decrease of 5.7 ± 3.1 times was measured using postadministration yttrium-90 positron emission tomography/computed tomography in the protected zone compared with that in the treated zone.