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1.
Nat Immunol ; 25(5): 902-915, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38589618

RESUMEN

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.


Asunto(s)
Factor Nuclear 1-alfa del Hepatocito , Hipersensibilidad , Factor de Unión 1 al Potenciador Linfoide , Células Madre Multipotentes , Factor 1 de Transcripción de Linfocitos T , Células Th2 , Humanos , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Factor de Unión 1 al Potenciador Linfoide/genética , Células Th2/inmunología , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Factor Nuclear 1-alfa del Hepatocito/genética , Hipersensibilidad/inmunología , Células Madre Multipotentes/metabolismo , Células Madre Multipotentes/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Diferenciación Celular , Citocinas/metabolismo , Linfopoyetina del Estroma Tímico , Animales , Células Cultivadas , Ratones
2.
Plast Reconstr Surg Glob Open ; 12(4): e5747, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38645629

RESUMEN

Patients undergoing extensive lymph node dissection and radiation are at high risk for not only lymphedema but also painful contracture. In a standard lymphadenectomy, immediate lymphatic reconstruction using a lymphovenous bypass is effective in reconstructing the lymphatic defect. However, a more aggressive nodal clearance leaves the patient with a large cavity and skeletonized neurovascular structures, often resulting in severe contracture, pain, cosmetic deformity, and venous stricture. Adjuvant radiotherapy to the nodal bed can lead to severe and permanent disability despite physical therapy. Typically, these patients are referred to us after the fact, where surgery will rarely restore the patient to normal function. In an effort to avoid lymphedema and contracture, we have been reconstructing both the lymphatic and soft tissue defect during lymphadenectomy, using vascularized omentum lymphatic transplant (VOLT). A total of 13 patients underwent immediate reconstruction with VOLT at the time of axillary (n = 8; 61.5%) or groin (n = 5; 38.5%) dissection. No postoperative complications were observed. The mean follow-up time was 15.1 ±â€…12.5 months. Only one lower extremity patient developed mild lymphedema (11% volume differential), with excellent scores in validated patient-reported outcomes. All patients maintained full range of motion with no pain. None of the 13 patients required a compression garment. Immediate lymphatic reconstruction with VOLT is a promising procedure for minimizing the risk of lymphedema and contracture in the highest risk patients undergoing particularly extensive lymph node dissection and radiotherapy.

4.
JAMA Surg ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38536186

RESUMEN

Importance: Higher lymphedema rates after axillary lymph node dissection (ALND) have been found in Black and Hispanic women; however, there is poor correlation between subjective symptoms, quality of life (QOL), and measured lymphedema. Additionally, racial and ethnic differences in QOL have been understudied. Objective: To evaluate the association of race and ethnicity with long-term QOL in patients with breast cancer treated with ALND. Design, Setting, and Participants: This cohort study enrolled women aged 18 years and older with breast cancer who underwent unilateral ALND at a tertiary cancer center between November 2016 and March 2020. Preoperatively and at 6-month intervals, arm volume was measured by perometer and QOL was assessed using the Upper Limb Lymphedema-27 (ULL-27) questionnaire, a validated tool for assessing lymphedema that evaluates how arm symptoms affect physical, psychological, and social functioning. Data were analyzed from November 2016 to October 2023. Exposures: Breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. Main Outcomes and Measures: Scores in each domain of the ULL-27 were compared by race and ethnicity. Factors impacting QOL were identified using multivariable regression analyses. Results: The study included 281 women (median [IQR] age, 48 [41-58] years) with breast cancer who underwent unilateral ALND and had at least 6 months of follow-up. Of these, 30 patients (11%) self-identified as Asian individuals, 57 (20%) as Black individuals, 23 (8%) as Hispanic individuals, and 162 (58%) as White individuals; 9 individuals (3%) who did not identify as part of a particular group or who were missing race and ethnicity data were categorized as having unknown race and ethnicity. Median (IQR) follow-up was 2.97 (1.96-3.67) years. The overall 2-year lymphedema rate was 20% and was higher among Black (31%) and Hispanic (27%) women compared with Asian (15%) and White (17%) women (P = .04). Subjective arm swelling was more common among Asian (57%), Black (70%), and Hispanic (87%) women than White (44%) women (P < .001), and lower physical QOL scores were reported by racial and ethnic minority women at nearly every follow-up. For example, at 24 months, median QOL scores were 87, 79, and 80 for Asian, Black, and Hispanic women compared with 92 for White women (P = .003). On multivariable analysis, Asian race (ß = -5.7; 95% CI, -9.5 to -1.8), Hispanic ethnicity (ß = -10.0; 95% CI, -15.0 to -5.2), and having Medicaid (ß = -5.4; 95% CI, -9.2 to -1.7) or Medicare insurance (ß = -6.9; 95% CI, -10.0 to -3.4) were independently associated with worse physical QOL (all P < .001). Conclusions and Relevance: Findings of this cohort study suggest that Asian, Black, and Hispanic women experience more subjective arm swelling after unilateral ALND for breast cancer compared with White women. Black and Hispanic women had higher rates of objective lymphedema than their White counterparts. Both minority status and public medical insurance were associated with worse physical QOL. Understanding disparities in QOL after ALND is an unmet need and may enable targeted interventions to improve QOL for these patients.

5.
Plast Reconstr Surg ; 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38546540

RESUMEN

BACKGROUND: Following passage of the Women's Health and Cancer Rights Act (WHCRA), a steady rise in breast reconstruction rates was reported; however, a recent update is lacking. This study aimed to evaluate longitudinal trends in breast reconstruction (BR) rates in the U.S. and relevant sociodemographic factors. METHODS: Mastectomy cases with/without BR from 2005 through 2017 were abstracted from the National Surgical Quality Improvement Program (NSQIP), Surveillance, Epidemiology, and End Results (SEER) Program, and National Cancer Database (NCDB). BR rates were examined using Poisson regression. Multivariable logistic regression analysis of NCDB data was used to identify predictors of reconstruction. Race and insurance distributions were evaluated over time. RESULTS: Of 1,554,381 mastectomy patients, 507,631 (32.7%) received BR. Annual reconstruction rates per 1000 mastectomies increased from 2005 to 2012 (NSQIP: Incidence Rate Ratio (IRR) 1.077; SEER: 1.090; NCDB: 1.092) and stabilized from 2013 to 2017. NCDB data showed that patients who were younger (≤59 years), privately insured, had fewer comorbidities, and underwent contralateral prophylactic mastectomy were more likely to undergo BR (all p<0.001). Over time, the increase in BR rates was higher among Black (252.3%) and Asian (366.4%) patients than White patients (137.3%). BR rates increased more among Medicaid (418.6%) and Medicare (302.8%) patients than privately insured (125.3%) patients. CONCLUSIONS: This analysis demonstrates stabilization in immediate BR rates over the last decade; reasons behind this stabilization are likely multifactorial. Disparities based on race and insurance type have decreased, with a more equitable distribution of BR rates.

6.
J Invest Dermatol ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38548256

RESUMEN

Allergic contact dermatitis is a common inflammatory skin disease comprising 2 phases. During sensitization, immune cells are activated by exposure to various allergens, whereas repeated antigen exposure induces local inflammation during elicitation. In this study, we utilized mouse models lacking lymphatics in different skin regions to characterize the role of lymphatics separately in the 2 phases, using contact hypersensitivity as a model of human allergic inflammatory skin diseases. Lymphatic-deficient mice exhibited no major difference to single antigen exposure compared to controls. However, mice lacking lymphatics in both phases displayed reduced inflammation after repeated antigen exposure. Similarly, diminished immune response was observed in mice lacking lymphatics only in sensitization, whereas the absence of lymphatics only in the elicitation phase resulted in a more pronounced inflammatory immune response. This exaggerated inflammation is driven by neutrophils impacting regulatory T cell number. Collectively, our results demonstrate that skin lymphatics play an important but distinct role in the 2 phases of contact hypersensitivity. During sensitization, lymphatics contribute to the development of the antigen-specific immunization, whereas in elicitation, they moderate the inflammatory response and leukocyte infiltration in a neutrophil-dependent manner. These findings underscore the need for novel therapeutic strategies targeting the lymphatics in the context of allergic skin diseases.

7.
Ann Surg Oncol ; 31(5): 3377-3386, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38355780

RESUMEN

BACKGROUND: Electronic patient-reported outcome measures (ePROMs) for real-time remote symptom monitoring facilitate early recognition of postoperative complications. We sought to determine whether remote, electronic, patient-reported symptom-monitoring with Recovery Tracker predicts 30-day readmission or reoperation in outpatient mastectomy patients. METHODS: We conducted a retrospective review of breast cancer patients who underwent outpatient (< 24-h stay) mastectomy with or without reconstruction from April 2017 to January 2022 and who received the Recovery Tracker on Days 1-10 postoperatively. Of 5,130 patients, 3,888 met the inclusion criteria (2,880 mastectomy with immediate reconstruction and 1,008 mastectomy only). We focused on symptoms concerning for surgical complications and assessed if symptoms reaching prespecified alert levels-prompting a nursing call-predicted risk of 30-day readmission or reoperation. RESULTS: Daily Recovery Tracker response rates ranged from 45% to 70%. Overall, 1,461 of 3,888 patients (38%) triggered at least one alert. Most red (urgent) alerts were triggered by pain and fever; most yellow (less urgent) alerts were triggered by wound redness and pain severity. The 30-day readmission and reoperation rates were low at 3.8% and 2.4%, respectively. There was no statistically significant association between symptom alerts and 30-day reoperation or readmission, and a clinically relevant increase in risk can be excluded (odds ratio 1.08; 95% confidence interval 0.8-1.46; p = 0.6). CONCLUSIONS: Breast cancer patients undergoing mastectomy with or without reconstruction in the ambulatory setting have a low burden of concerning symptoms, even in the first few days after surgery. Patients can be reassured that symptoms that do present resolve quickly thereafter.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Neoplasias de la Mama/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación , Estudios Retrospectivos
8.
Ann Surg Oncol ; 31(6): 3684-3693, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38388930

RESUMEN

BACKGROUND: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways. PATIENTS AND METHODS: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure. RESULTS: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal. CONCLUSIONS: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations.


Asunto(s)
Anestesia de Conducción , Neoplasias de la Mama , Disparidades en Atención de Salud , Mamoplastia , Mastectomía , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Anestesia de Conducción/métodos , Mamoplastia/métodos , Estudios de Seguimiento , Adulto , Bloqueo Nervioso/métodos , Pronóstico , Anciano , Dispositivos de Expansión Tisular
10.
Ann Surg Oncol ; 31(4): 2766-2776, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38245651

RESUMEN

BACKGROUND: Prepectoral implant placement for postmastectomy breast reconstruction has increased in recent years. Benefits of prepectoral reconstruction may include lack of animation deformities and reduced postoperative pain, but its complication profile is currently unclear. This study aimed to examine the complication profile of prepectoral tissue expanders (TEs) to determine factors associated with TE loss. METHODS: A retrospective review was performed to identify all patients who underwent immediate prepectoral TE reconstruction from January 2018 to June 2021. The decision to use the prepectoral technique was based on mastectomy skin quality and patient comorbidities. Patient demographics, comorbidities, and operative details were evaluated. Outcomes of interest included TE loss, seroma, hematoma, infection/cellulitis, mastectomy skin flap necrosis requiring revision, and TE exposure. Logistic regression analysis was performed to identify factors associated with TE loss. RESULTS: The study identified 1225 TEs. The most frequent complications were seroma (8.7%, n = 106), infection/cellulitis (8.2%, n = 101), and TE loss (4.2%, n = 51). Factors associated with TE loss in the univariate analysis included ethnicity, history of smoking, body mass index, mastectomy weight, and neoadjuvant chemotherapy. In the multivariate regression analysis, only mastectomy weight had a positive association with TE loss (odds ratio, 1.001; p = 0.016). CONCLUSION: Prepectoral two-stage breast reconstruction can be performed safely with an acceptable early complication profile. The study data suggest that increasing mastectomy weight is the most significant factor associated with TE loss. Further research examining the quality of the soft tissue envelope and assessing patient-reported outcomes would prove beneficial.


Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Dispositivos de Expansión Tisular/efectos adversos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Celulitis (Flemón)/complicaciones , Celulitis (Flemón)/cirugía , Seroma/cirugía , Mamoplastia/efectos adversos , Mamoplastia/métodos , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Implantes de Mama/efectos adversos , Implantación de Mama/efectos adversos , Implantación de Mama/métodos
11.
Plast Reconstr Surg ; 153(2): 262e-272e, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37104467

RESUMEN

BACKGROUND: Increased understanding of breast implant-associated anaplastic large-cell lymphoma has led to a shift away from textured breast devices. A few small studies have compared the complication rates of textured and smooth tissue expanders (TEs). The aim of this study was to compare complication profiles in patients undergoing two-stage postmastectomy breast reconstruction with either textured or smooth TEs. METHODS: The authors performed a retrospective review of female patients who underwent immediate breast reconstruction with textured or smooth TEs from 2018 to 2020 at their institution. Rates of seroma, infection/cellulitis, malposition/rotation, exposure, and TE loss were analyzed in the overall cohort and subgroups undergoing prepectoral and subpectoral TE placement. A propensity score-matched analysis was used to decrease the effects of confounders comparing textured and smooth TEs. RESULTS: The authors analyzed 3526 TEs (1456 textured and 2070 smooth). More frequent use of acellular dermal matrix, SPY angiography, and prepectoral TE placement was noted in the smooth TE cohort ( P < 0.001). Univariate analysis suggested higher rates of infection/cellulitis, malposition/rotation, and exposure in smooth TEs (all P < 0.01). Rates of TE loss did not differ. After propensity matching, no differences were noted in infection or TE loss. Prepectoral smooth expanders had increased rates of malposition/rotation. CONCLUSIONS: TE surface type did not affect rates of TE loss, although increased rates of expander malposition were noted in the smooth prepectoral cohort. Further research is needed to examine breast implant-associated anaplastic large-cell lymphoma risk with temporary textured TE exposure to improve decision-making. CLINICAL QUESTION/LEVEL OF EVIDENCW: Therapeutic, III.


Asunto(s)
Implantes de Mama , Neoplasias de la Mama , Linfoma Anaplásico de Células Grandes , Mamoplastia , Femenino , Humanos , Dispositivos de Expansión Tisular/efectos adversos , Celulitis (Flemón)/etiología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Linfoma Anaplásico de Células Grandes/epidemiología , Linfoma Anaplásico de Células Grandes/etiología , Mastectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Mamoplastia/efectos adversos , Implantes de Mama/efectos adversos , Estudios Retrospectivos
12.
Plast Reconstr Surg ; 153(1): 245-255, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37092977

RESUMEN

BACKGROUND: Surgical treatment of lymphedema has outpaced coding paradigms. In the setting of ambiguity regarding coding for physiologic procedures [lymphovenous bypass (LVB) and vascularized lymph node transplant (VLNT)], we hypothesized that there would be variation in commercial reimbursement based on coding pattern. METHODS: The authors performed a cross-sectional analysis of 2021 nationwide hospital pricing data for 21 CPT codes encompassing excisional (direct excision, liposuction), physiologic (LVB, VLNT), and ancillary (lymphangiography) procedures. Within-hospital ratios (WHRs) and across-hospital ratios (AHRs) for adjusted commercial rates per CPT code quantified price variation. Mixed effects linear regression modeled associations of commercial rate with public payer (Medicare and Medicaid), self-pay, and chargemaster rates. RESULTS: A total of 270,254 commercial rates, including 95,774 rates for physiologic procedures, were extracted from 2863 hospitals. Lymphangiography codes varied most in commercial price (WHR, 1.76 to 3.89; AHR, 8.12 to 44.38). For physiologic codes, WHRs ranged from 1.01 (VLNT; free omental flap) to 3.03 (LVB; unlisted lymphatic procedure), and AHRs ranged from 5.23 (LVB; lymphatic channel incision) to 10.36 (LVB; unlisted lymphatic procedure). Median adjusted commercial rates for excisional procedures ($3635.84) were higher than for physiologic procedures ($2560.40; P < 0.001). Commercial rate positively correlated with Medicare rate for all physiologic codes combined, although regression coefficients varied by code. CONCLUSIONS: Commercial payer-negotiated rates for physiologic procedures were highly variable both within and across hospitals, reflective of variation in CPT codes. Physiologic procedures may be undervalued relative to excisional procedures. Consistent coding nomenclature should be developed for physiologic and ancillary procedures.


Asunto(s)
Vasos Linfáticos , Linfedema , Anciano , Humanos , Estados Unidos , Medicare , Consenso , Estudios Transversales , Linfedema/cirugía , Vasos Linfáticos/cirugía
13.
Plast Reconstr Surg ; 153(4): 786-793, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37220401

RESUMEN

BACKGROUND: Prepectoral tissue expander (TE) placement for two-stage postmastectomy reconstruction is usually performed in conjunction with insertion of acellular dermal matrix (ADM). However, the effects of ADM use on TE loss or other early complications remain unknown. Therefore, the aim of this study was to compare early postoperative complications in patients who underwent prepectoral breast implant reconstruction with or without ADM use. METHODS: The authors performed a retrospective cohort study of all patients at their institution who underwent prepectoral breast reconstruction from January of 2018 to June of 2021. The primary outcome was TE loss within 90 days of surgery; secondary outcomes included other complications such as infection, TE exposure, mastectomy skin flap necrosis requiring revision, and seroma. RESULTS: Data on 714 patients with 1225 TEs (1060 with ADM and 165 without) were analyzed. Baseline demographics did not differ by ADM use, although mastectomy breast tissue weight was higher in patients without ADM (750.3 g versus 540.8 g; P < 0.001). Rates of TE loss were similar in reconstructions with (3.8%) ADM and without (6.7%; P = 0.09). We also did not find differences in the rates of secondary outcomes between cohorts. CONCLUSIONS: ADM use had no statistically significant effect on early complication rates among patients undergoing breast reconstruction with prepectoral TEs. Still, this study was underpowered, and data trended toward statistical significance; thus, larger studies are required in the future. Additional research and randomized studies should focus on larger cohorts and examine long-term complications such as capsular contracture and implant malposition. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Asunto(s)
Dermis Acelular , Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Estudios Retrospectivos , Mamoplastia/efectos adversos , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
14.
Clin Cancer Res ; 30(4): 703-718, 2024 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-37695642

RESUMEN

PURPOSE: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans. PATIENTS AND METHODS: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion. RESULTS: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response. CONCLUSIONS: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649.


Asunto(s)
Aminopiridinas , Liposarcoma , Humanos , Aminopiridinas/farmacología , Aminopiridinas/uso terapéutico , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Liposarcoma/tratamiento farmacológico , Liposarcoma/patología , Senescencia Celular , Quinasa 4 Dependiente de la Ciclina , Microambiente Tumoral
16.
Ann Surg Oncol ; 31(1): 659-671, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37864119

RESUMEN

BACKGROUND: Frailty is associated with higher risk of complications following breast reconstruction, but its impact on long-term surgical and patient-reported outcomes has not been investigated. We examined the association of the five-item modified frailty index (MFI) score with long-term surgical and patient-reported outcomes in autologous breast reconstruction. PATIENTS AND METHODS: We conducted a retrospective cohort study of consecutive patients who underwent mastectomy and autologous breast reconstruction between January 2016 and April 2022. Primary outcome was any flap-related complication. Secondary outcomes were patient-reported outcomes and predictors of complications in the frail cohort. RESULTS: We identified 1640 reconstructions (mean follow-up 24.2 ± 19.2 months). In patients with MFI ≥ 2, the odds of surgical [odds ratio (OR) 2.13, p = 0.023] and medical (OR 17.02, p < 0.001) complications were higher than in nonfrail patients. We found no significant difference in satisfaction with the breast (p = 0.287), psychosocial well-being (p = 0.119), or sexual well-being (p = 0.314) according to MFI score. Chronic obstructive pulmonary disease was an independent predictor of infection (OR 3.70, p = 0.002). Tobacco use (OR 7.13, p = 0.002) and contralateral prophylactic mastectomy (OR 2.36, p = 0.014) were independent predictors of wound dehiscence. Dependent functional status (OR 2.36, p = 0.007) and immediate reconstruction (compared with delayed reconstruction; OR 3.16, p = 0.026) were independent predictors of skin flap necrosis. Dependent functional status was also independently associated with higher odds of reoperation (OR 2.64, p = 0.011). CONCLUSION: Frailty is associated with higher risk of complications in breast reconstruction, but there is no significant difference in long-term patient-reported outcomes. MFI should be considered in breast reconstruction to improve outcomes in high-risk frail patients.


Asunto(s)
Neoplasias de la Mama , Fragilidad , Mamoplastia , Humanos , Anciano , Femenino , Mastectomía/efectos adversos , Estudios Retrospectivos , Fragilidad/complicaciones , Neoplasias de la Mama/cirugía , Anciano Frágil , Mamoplastia/efectos adversos , Mamoplastia/psicología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Medición de Resultados Informados por el Paciente
17.
J Surg Oncol ; 128(8): 1235-1242, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37653689

RESUMEN

BACKGROUND: The lack of evidence-based guidelines for postoperative opioid prescriptions following breast reconstruction contributes to a wide variation in prescribing practices and increases potential for misuse and abuse. METHODS: Between August and December 2019, women who underwent outpatient breast reconstruction were surveyed 7-10 days before (n = 97) and after (n = 101) implementing a standardized opioid prescription reduction initiative. We compared postoperative opioid use, pain control, and refills in both groups. Patient reported outcomes were compared using the BREAST-Q physical wellbeing of the chest domain and a novel symptom Recovery Tracker. RESULTS: Before changes in prescriptions, patients were prescribed a median of 30 pills and consumed three pills (interquartile range [IQR: 1,9]). After standardization, patients were prescribed eight pills and consumed three pills (IQR: 1,6). There was no evidence of a difference in the proportion of patients experiencing moderate to very severe pain on the Recovery Tracker or in the early BREAST-Q physical wellbeing of the chest scores (p = 0.8 and 0.3, respectively). CONCLUSION: Standardizing and reducing opioid prescriptions for patients undergoing reconstructive breast surgery is feasible and can significantly decrease the number of excess pills prescribed. The was no adverse impact on early physical wellbeing, although larger studies are needed to obtain further data.


Asunto(s)
Analgésicos Opioides , Mamoplastia , Dolor Postoperatorio , Procedimientos de Cirugía Plástica , Femenino , Humanos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Mamoplastia/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/diagnóstico , Procedimientos de Cirugía Plástica/efectos adversos , Pautas de la Práctica en Medicina , Prescripciones de Medicamentos/normas , Prescripciones de Medicamentos/estadística & datos numéricos
18.
J Clin Invest ; 133(17)2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37655664

RESUMEN

The lymphatic system (LS) is composed of lymphoid organs and a network of vessels that transport interstitial fluid, antigens, lipids, cholesterol, immune cells, and other materials in the body. Abnormal development or malfunction of the LS has been shown to play a key role in the pathophysiology of many disease states. Thus, improved understanding of the anatomical and molecular characteristics of the LS may provide approaches for disease prevention or treatment. Recent advances harnessing single-cell technologies, clinical imaging, discovery of biomarkers, and computational tools have led to the development of strategies to study the LS. This Review summarizes the outcomes of the NIH workshop entitled "Yet to be Charted: Lymphatic System in Health and Disease," held in September 2022, with emphasis on major areas for advancement. International experts showcased the current state of knowledge regarding the LS and highlighted remaining challenges and opportunities to advance the field.


Asunto(s)
Sistema Linfático , Vasos Linfáticos
19.
J Surg Oncol ; 128(8): 1416-1427, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37563928

RESUMEN

BACKGROUND: Limb salvage has better functional outcomes than amputation in the upper extremity. This can however be challenging after bony tumor resections. METHODS: This is a retrospective case series of patients who underwent humerus, ulna, or radius reconstruction with a fibula free flap. Data were collected on demographics, oncologic history, surgical details, and complications. Functional outcome measures included the patient's ability to perform activities of daily living (ADL), presence of pain, and musculoskeletal tumor society (MSTS) score. RESULTS: Over a 25-year period, 38 reconstructions were performed. The flap success rate was 97.5%. Bony union was obtained in 19 of 19 (100%) forearm reconstructions and in 15 of 19 (79%) humerus reconstructions (p = 0.10). All 19 forearm reconstruction patients and 18/19 humerus reconstruction patients were able to perform ADLs with no pain or only occasional pain. The MSTS scores were not significantly different between the humerus and forearm cohorts (27.1 vs. 27.3, p = 0.68). Functional outcomes were significantly better in limbs that achieved union (p < 0.001). Recipient and donor site complications occurred in 10 (26.3%) and 5 (13%) patients, respectively. CONCLUSIONS: Oncologic upper-extremity reconstruction with fibula free flaps has excellent functional outcomes. Bone union is a predictor of superior limb function.


Asunto(s)
Neoplasias Óseas , Colgajos Tisulares Libres , Enfermedades Musculoesqueléticas , Neoplasias de los Tejidos Conjuntivo y Blando , Humanos , Estudios Retrospectivos , Actividades Cotidianas , Neoplasias Óseas/cirugía , Extremidad Superior/cirugía , Dolor , Resultado del Tratamiento , Trasplante Óseo
20.
Aesthet Surg J ; 43(12): 1491-1498, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37551639

RESUMEN

BACKGROUND: Acellular dermal matrix (ADM) is frequently utilized in prepectoral breast reconstruction, but few studies have examined the role of ADM type in complication risk. OBJECTIVES: This study was performed to determine the impact of ADM type on early complication rates in 2-stage alloplastic prepectoral breast reconstruction. METHODS: We performed a cohort examination of all patients who underwent mastectomy with immediate 2-stage alloplastic prepectoral breast reconstruction with ADM support at Memorial Sloan Kettering Cancer Center from 2018 to 2021. ADM types utilized included AlloDerm (LifeCell Corporation, Branchburg, NJ), FlexHD (MTF Biologics, Edison, NJ), and SurgiMend (Integra LifeSciences Corporation, Princeton, NJ). Complication rates based on the number of tissue expanders (TEs) were determined for each ADM type. Performance of multivariate logistic regression determined the impact of ADM type on complication risk after accounting for confounders. RESULTS: Overall, 726 patients (1054 TEs: 194 AlloDerm, 93 FlexHD, 767 SurgiMend) were included. The 3 cohorts differed in terms of mastectomy type (nipple-sparing: 23.5% of AlloDerm, 33.3% of FlexHD, 19.1% of SurgiMend, P = .038); ADM perforation (perforated: 94.8% of AlloDerm, 98.2% of FlexHD, 100% of SurgiMend, P < .001); and ADM size (AlloDerm: 153.2 cm2 [37.6], SurgiMend: 198.7 cm2 [10.4], FlexHD: 223.7 cm2 [37.9], P < .001). On univariate examination, no differences existed between ADM types for seroma, infection, exposure, malposition, or TE loss. Additionally, after adjustment for confounders with multivariate regression, no ADM type had higher odds of TE loss. CONCLUSIONS: In this large cohort of prepectoral reconstruction patients, ADM type did not significantly affect the risk of complications. Additional prospective studies are warranted to better evaluate ADM choice for prepectoral breast reconstruction.


Asunto(s)
Dermis Acelular , Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Colágeno , Mamoplastia , Humanos , Femenino , Mastectomía/efectos adversos , Implantación de Mama/efectos adversos , Neoplasias de la Mama/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Mamoplastia/efectos adversos , Estudios de Cohortes , Implantes de Mama/efectos adversos
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