Granulation-embedded autologous skin grafting improves healing chronic wounds at high altitudes: a pilot study.

BACKGROUND: The management of chronic wounds presents a challenge for surgeons. In this pilot study, the authors established a novel auto-grafting approach for chronic wounds and evaluated its efficacy. PURPOSE: The objective of this pilot study was to observe the clinical efficacy of granulation-embedded skin grafting for the treatment of chronic wounds at high altitudes. METHODS: The data of 45 patients with chronic wounds were obtained from the medical records of the Yushu People's Hospital. Patients were divided into stamp skin-grafting and granulation-embedded skin-grafting groups. Skin graft survival rate, wound coverage rate, and wound-healing time were observed and recorded. The length of hospital stay and 1% total body surface area (TBSA) treatment cost were compared. RESULTS: Significant differences were noted in skin graft survival rate (94% ± 3% vs 86% ± 3%, P < .01), wound coverage rate on postoperative day 7 (61% ± 16% vs 54% ± 18%, P < .01), and wound-healing times (23 ± 2.52 days vs 31 ± 3.61 days, P < .05). The length of hospital stay and 1% TBSA treatment cost were significantly reduced in the granulation-embedded skin grafting group (P < .05). CONCLUSIONS: Granulation-embedded skin grafting can improve the healing of chronic wounds at high altitudes. These findings provide a new approach to the clinical treatment of chronic wounds.

National trends in revision procedures in post-mastectomy breast reconstruction: Autologous vs implant-based approaches.

BACKGROUND: Breast reconstruction involves collaborative decision-making between patients and surgeons, but the need for multiple revisions after the initial reconstructive surgery process can burden patients and the healthcare system. This study explored how the type of breast reconstruction (autologous [ABR], immediate implant-based reconstruction [IBR], or two-stage IBR) impacts postreconstruction revision rates. METHOD: Using MarketScan Databases, a retrospective database study (2007-2021) was conducted, identifying revision procedures through Current Procedural Terminology codes. Statistical analysis with linear models, adjusted for patient characteristics and surgical factors, used a significance threshold of p < 0.05. RESULTS: Among 58,264 patients, 6.2% of ABR patients, 3.8% of immediate IBR patients, and 3.6% of two-stage IBR patients underwent future revisions. IBR had a 51% lower incidence rate of revision operations than ABR (incidence rate ratio = 0.49, p < 0.001). Within IBR, there was no significant difference in the number of operations between immediate IBR (0.06 ± 0.32) and two-stage IBR (0.05 ± 0.32, p = 0.95). Immediate IBR demonstrated 12% (OR = 0.88, p = 0.0022) and 70% (OR = 0.30, p < 0.001) lower odds of requiring breast revision and fat grafting compared to ABR, respectively. Two-stage reconstruction had 66 % lower odds of requiring only fat grafting than ABR (OR = 0.34, p < 0.001). CONCLUSION: ABR necessitated a higher number of total revision procedures after completion of the initial reconstruction. These findings will better equip providers and patients to counsel patients in understanding their reconstructive journey, planning their reconstructions and timing, and provide more accurate estimates of the number of procedures that will be required to reach their aesthetic goals and final outcome.

Trends in Outcomes After Upfront Autologous Transplant for Multiple Myeloma Over Three Decades.

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront auto-SCT over the past three decades, including those with high-risk disease.

Cirugía de Ross en Chile: tasa libre de reoperación y supervivencia global en una cohorte de más de 10 años de seguimiento / Ross surgery in Chile: reoperation free and global survival rates after a 10 year follow up

Antecedentes: El autoinjerto de válvula pulmonar (VP) u operación de Ross (OpR) tiene excelentes resultados a largo plazo. Es superior a otros tipos de reemplazo valvular en jóvenes adultos, aunque no el estándar de primera línea. Un tiempo quirúrgico prolongado o alta morbimortalidad son importantes preocupaciones. Objetivos: Establecer la morbimortalidad asociada a la OpR por un período >10 años, considerando el tiempo quirúrgico, tasa de reoperación y supervivencia global (SG). Métodos: Cohorte prospectiva (1996-2012), en seguimiento hasta agosto-2023. La SG fue estimada desde la OpR hasta la última consulta o deceso. Mediante regresión de Cox (Hazard Ratio, HR) se estimaron factores asociados a la SG. Resultados: La serie consta de 161 pacientes: 118 de etiología congénita (73.3%), 17 infecciosa (10.6%), 26 reumática (16.1%). La lesión fue estenótica en 79 (49.1%), insuficiencia en 40 (24.8%), mixta en 42 (26.1%). La OpR fue urgente en 11 (6.8%). The median time of ECC and the operation was 149 y 232 minutos, respectivamente. Veintisiete pacientes requirieron reoperación (16.8%). Con una mediana de 19.7 años (17.2-22.2), 23 pacientes fallecieron (14.3%): 1/23 asociado a OpR, 17/23 por causa cardiovascular y 5/23 por causas no cardiovasculares. La lesión mixta se asoció a mayor mortalidad (HR 3.07; IC 95% 1.11-8.47; p=.029). Conclusiones: La OpR es un procedimiento con baja morbimortalidad. La lesión mixta es un factor de riesgo independiente de mayor mortalidad. Sin embargo, la mediana de tiempo de CEC y quirúrgico es prolongado frente a otras técnicas de reemplazo valvular.

Background: Pulmonary valve (PV) autograftor reoperation or Ross surgery (RS), presents excellent long-term results. It is superior to other types of PV replacement in young adults, although it is not the first-line gold standard. A longer operative time or high morbidity and mortality rates are important concerns. Aim: To establish the morbidity and mortality associated with RS for >10 years, considering operative time, reoperation rate and overall survival (OS). Methods: Prospective cohort (1996-2012), with a follow-up until August/2023. The OS was estimated from RS to the last consultation/death. Factors associated to OS were estimated using Cox regression (Hazard Ratio, HR) Results: 161 patients were included: the etiology was congenital (118, 73%), infectious (17, 10.6%), and rheumatic (26,16.1%). The lesion was stenotic in 79 (49.1%), heart failure in 40 (24.8%), mixed in 42 (26.1%). RS was urgent in 11 (6.8%). Extracorporeal circulation (ECC) and operative times were 149 and 232 minutes, respectively. Twenty-seven patients required reoperation (16.8%). With a median follow up of 19.7 years (17.2-22.2), 23 patients died (14.3%): 1/23 associated with RS, 17/23 due to cardiovascular causes, and 5/23 due to non-cardiovascular causes. Mixed injury was associated with higher mortality (HR 3.07; 95% CI 1.11-8.47; p=.029). Conclusions: RS is a procedure with low morbidity and mortality. Mixed injury is an independent risk factor for increased mortality. However, the median ECC and operative times were higher compared to other valvular replacement techniques.

Oncological Safety of Autologous Fat Grafting in Breast Reconstruction after Mastectomy for cancer: A case-control study.

OBJECTIVE: The use of autologous fat grafting in the context of breast reconstruction is still a matter of controversy. The objective of this study was to compare the local relapse rate in women who had a fat grafting session in the context of breast reconstruction after breast cancer management, to those who had breast reconstruction without fat grafting. METHODS: We performed a retrospective, monocentric, case-control study from January 2007 to December 2017 in our hospital. The cases included women who underwent breast reconstruction with autologous fat grafting and controls, undergoing breast reconstruction without fat grafting. We compared survival and local recurrence between the two groups. RESULTS: 412 women were included: 109 (26.5%) in the lipofilling group and 303 women (73.5%) in the "no lipofilling" group. In the overall study population, lipofilling did not appear to be a predictive factor for recurrence, HR = 1.39 [0.63 - 3.06], p = 0.41; or a predictive factor for overall survival, HR = 0.84 [0.23 - 3.02], p = 0.79, or for distant metastases, HR = 1.10 [0.43 - 2.79], p = 0.84. In contrast, in the subgroup of women treated for invasive cancer, the multivariate analysis showed that lipofilling in this context was an independent predictive factor for local recurrence (HR= 5.06 [1.97 - 10.6], p = 0.04). CONCLUSION: we found an increased risk of local recurrence after lipofilling in women who were managed for invasive breast cancer. This suggests that special consideration should be given to women who have had invasive breast cancer before lipofilling.

Factors Associated With State-Specific Medicaid Expansion and Receipt of Autologous Breast Reconstruction Among Patients Undergoing Mastectomy.

Importance: Despite demonstrated psychosocial benefits, autologous breast reconstruction remains underutilized. An analysis of the association between Medicaid expansion and autologous breast reconstruction has yet to be performed. Objective: To compare autologous breast reconstruction rates and determine the association between Medicaid expansion and breast reconstruction. Design, Setting, and Participants: A retrospective cross-sectional study was performed using the State Inpatient Database from January 1, 2012, through September 30, 2015, and included 51 340 patients. Patients were identified using the International Classification of Diseases, Ninth Revision, codes for breast cancer, mastectomy, and autologous breast reconstruction. Data from states that expanded Medicaid (New Jersey, New York, and Washington) were compared with states that did not expand Medicaid (Florida, North Carolina, and Wisconsin). Data were analyzed from June 1, 2020, through February 28, 2021. Exposures: The Patient Protection and Affordable Care Act's Medicaid expansion was implemented in 2014; the preexpansion period ranged from 2012 to 2013 (2 years), whereas the postexpansion period ranged from 2014 to 2015 quarter 3 (1.75 years). Main Outcomes and Measures: Primary outcomes included use of autologous breast reconstruction before and after expansion. Independent covariates included patient demographics, comorbidities, and state of residence. Results: Among 45 850 patients who underwent mastectomy and 9215 patients who received autologous breast reconstruction, 36 777 (67%) were White and 32 205 (59%) had private insurance. The use of immediate or delayed autologous reconstruction increased from 18.1% (4951 of 27 290) to 23.0% (4264 of 18 560) throughout the study period. Compared with 2012, the odds of reconstruction were 64% higher in 2015 (odds ratio [OR], 1.64; 95% CI, 1.48-1.80; P < .001). African American (OR, 1.43; 95% CI, 1.33-1.55; P < .001) and Hispanic (OR, 1.44; 95% CI, 1.31-1.60; P < .001) patients had higher odds of reconstruction compared with White patients regardless of state of residence. However, Medicaid expansion was associated with a 28% decrease in the odds of reconstruction (OR, 0.72; 95% CI, 0.61-0.87; P < .001) for African American patients, a 40% decrease (OR, 0.60; 95% CI, 0.50-0.74; P < .001) for Hispanic patients, and 20% decrease (OR, 0.80; 95% CI, 0.67-0.96; P = .01) for patients with Asian, Native American, or other minority race/ethnicity. Medicaid expansion was not associated with changes in the odds of reconstruction for White patients. Conclusions and Relevance: In this cross-sectional study, although the odds of receiving autologous breast reconstruction increased annually, Medicaid expansion was associated with decreased odds of reconstruction for African American patients, Hispanic patients, and other patients of color.

Operative treatments for osteochondral lesions of the talus in adults: A systematic review and meta-analysis.

PURPOSE: This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT). MATERIALS AND METHODS: The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3. RESULTS: Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant. CONCLUSIONS: Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Mortality from Multiple Myeloma Within One Year Following Autologous Stem Cell Transplantation: Defining an Ultra-high Risk Population.

Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within 1 year of transplant (EM post-ASCT). Such patients tend to have few comorbidities suggesting their EM is owing to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed multiple myeloma (MM) treated with first-line ASCT. Patients who died within 1 year of ASCT were matched for age, sex, and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1, 2007, and May 1, 2019, 41 patients (4.3%) died within 1 year of ASCT from MM-related causes. In a multivariate analysis, anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase were associated with EM post-ASCT. Forty patients (97.6%) received at least 1 novel agent. Most patients with EM post-ASCT received second-line chemotherapy (80.5%), although survival from initiation of second-line chemotherapy was only 2.1 months. The primary reason for not receiving second-line therapy was rapid relapse. Clinical parameters reflecting disease burden, as well as high-risk cytogenetics, are associated with EM post-ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra-high risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma.

Healthcare resource utilisation and sickness absence in newly diagnosed multiple myeloma patients who did not undergo autologous stem cell transplantation: Trends in Sweden with the changing treatment landscape.

OBJECTIVES: The introduction of novel drugs has significantly improved outcomes for multiple myeloma (MM) patients. This study describes survival, healthcare resource utilisation and sickness absence in association with the changing MM treatment landscape over time, focussing on patients who did not undergo autologous stem cell transplantation (ASCT). METHODS: Population-based, retrospective registry study in Sweden, where 7012 non-ASCT patients diagnosed between 2001 and 2015 were stratified into diagnosis periods 2001-2005 (n = 2053), 2006-2010 (n = 2372) and 2011-2015 (n = 2587). RESULTS: Median survival increased from 2.5 to 3.4 years from 2001-2005 to 2011-2015. During the first 3 years of follow-up, patients diagnosed during 2011-2015 spent 29% and 12% less time in health care (55 days; inpatient admissions and outpatient visits) than patients diagnosed during 2001-2005 (78 days) and 2006-2010 (63 days), respectively. This was associated with less inpatient and more outpatient healthcare usage. Average 3-year sickness absence (362 days) was 31% and 12% less than for patients diagnosed during 2001-2005 (522 days) and 2006-2010 (410 days), respectively. CONCLUSIONS: These findings of improved survival, reduced healthcare needs and greater productivity in non-ASCT MM patients with access to improved treatment practices and novel drugs provide important real-world cost-benefit insights for the continued development and introduction of treatments for MM.

Evaluating Race and Time to Transplantation in Multiple Myeloma: The Mount Sinai Hospital Experience.

BACKGROUND: Previous studies have found that Black patients with multiple myeloma undergo autologous stem-cell transplantation (ASCT) less frequently than their white counterparts, although the factors leading to decreased access and utilization have not been fully elucidated. PATIENTS AND METHODS: To identify whether racial differences in transplantation timing played a role in these disparities, we retrospectively analyzed 410 Black and white patients who received their first transplant at The Mount Sinai Hospital between 2011 and 2016 (260 white and 150 Black patients). We compared the time from initial diagnosis to stem-cell collection and the time from collection to transplantation between the 2 races while controlling for age, socioeconomic status, and functional status. RESULTS: Between Blacks and whites, time from diagnosis to collection was higher in Black patients (median 238, vs. 195 days, respectively, P = .051). Functional status, socioeconomic status, and age were also significantly associated with time to collection, and after controlling for these covariates, the effect of race was not significant (P = .0625). Conversely, time from collection to transplantation was increased in white patients compared to Black. CONCLUSION: Increased time from diagnosis to stem-cell collection for Black patients was driven in part by socioeconomic status and baseline functional status.

Does Up-front Autologous Stem-Cell Transplantation at First Relapse Improve Outcome in Transplant-Eligible Follicular Lymphoma Patients Whose Disease Relapses Within 24 Months?

BACKGROUND: In Canadian adults, follicular lymphoma (FL) is the most common subtype of non-Hodgkin lymphomas. Approximately 20% of patients with FL experience progression of disease within 2 years of first-line chemoimmunotherapy. Those patients have an expected overall survival of less than 5 years. The optimal second-line treatment for these high-risk patients is unclear. PATIENTS AND METHODS: We analyzed data from the Blood and Bone Marrow Transplantation Center at Ottawa Hospital to determine whether autologous stem-cell transplantation as up-front therapy for first relapse can improve outcomes in this high-risk FL subgroup. We identified 17 patients who underwent up-front autologous stem-cell transplantation between February 2012 and February 2019. RESULTS: The disease of all patients had relapsed within 24 months after receipt of their first rituximab-based chemotherapy. Overall survival at 2 and 5 years was 86.2% (95% confidence interval [CI], 55-96) and 71.8% (95% CI, 31-91), respectively. The progression-free survival at 2 and 5 years was 62.6% (95% CI, 35-81) and 53.6% (95% CI, 25-75), respectively. CONCLUSION: Overall survival is improved when receiving autologous hematopoietic stem-cell transplantation as up-front therapy at first relapse in transplant-eligible FL whose disease relapses within 24 months of first-line therapy. Data from our single center look promising, but the data need to be replicated with a larger sample size.

Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT.

Lymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and lifespan increase homeostatically when lymphocyte numbers are low and, vice versa, return to normal once cell numbers have normalized. This widely accepted concept is largely based on experiments in mice, but is hardly investigated in vivo in humans. Here we quantified lymphocyte production and loss rates in vivo in patients 0.5-1 year after their autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T- and B-cell subsets in autoHSCT-patients were two to eight times higher than in healthy controls, but went hand in hand with a threefold to ninefold increase in cell loss rates. Both rates also did not normalize when cell numbers did. This shows that increased lymphocyte production and loss rates occur even long after autoHSCT and can persist in the face of apparently normal cell numbers.

Transplantation of autologous cells and porous gelatin microcarriers to promote wound healing.

Definitive treatment to achieve wound healing in major burns frequently include skin transplantation, where split-thickness skin grafts is considered gold standard. This method is associated with several drawbacks. To overcome these hurdles, efforts have been made to develop tissue engineered skin substitutes, often comprised of a combination of cells and biomaterials. In the present study, we aimed to investigate transplantation of autologous keratinocytes and fibroblasts seeded on porous gelatin microcarriers using a porcine wound model. Pre-seeded microcarriers were transplanted to a total of 168 surgical full-thickness wounds (2cm diameter) on eight adult female pigs and covered with occlusive dressings. The experimental groups included wounds transplanted with microcarriers seeded with the combination of keratinocytes and fibroblasts, microcarriers seeded with each cell type individually, microcarriers without cells, each cell type in suspension, and NaCl control. Wounds were allowed to heal for one, two, four or eight weeks before being excised and fixated for subsequent histological and immunohistochemical analysis. In vitro, we confirmed that viable cells populate the surface and the pores of the microcarriers. In vivo, the microcarriers were to a large extent degraded after two weeks. After one week, all treatment groups, with the exception of microcarriers alone, displayed significantly thicker neo-epidermis compared to controls. After two weeks, wounds transplanted with microcarriers seeded with cells displayed significantly thicker neo-epidermis compared to controls. After four weeks there was no difference in the thickness of neo-epidermis. In conclusion, the experiments performed illustrate that autologous cells seeded on porous gelatin microcarriers stimulates the re-epithelialization of wounds. This method could be a promising candidate for skin transplantation. Future studies will focus on additional outcome parameters to evaluate long-term quality of healing following transplantation.

A Critical Examination of Length of Stay in Autologous Breast Reconstruction: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: This study aims to use the National Surgical Quality Improvement Program database to identify factors associated with extended postoperative length of stay after breast reconstruction with free tissue transfer. METHODS: Consecutive cases of breast reconstruction with free tissue transfer were retrieved from the National Surgical Quality Improvement Program (2005 to 2017) database using CPT code 19364. Extended length of stay (dependent variable) was defined as greater than 5 days. RESULTS: Nine thousand six hundred eighty-six cases were analyzed; extended length of stay was noted in 34 percent. On regression, patient factors independently associated with extended length of stay were body mass index (OR, 1.5; 95 percent CI, 1.2 to 1.9; p < 0.001), diabetes (OR, 1.3; 95 percent CI, 1.1 to 1.6; p = 0.003), and malignancy history (OR, 1.9; 95 percent CI, 1.22 to 3.02; p = 0.005). Operation time greater than 500 minutes (OR, 3; 95 percent CI, 2.73 to 3.28; p < 0.001) and immediate postmastectomy reconstruction (OR, 1.7; 95 percent CI, 1.16 to 2.48; p < 0.001) conferred risk for extended length of stay. Bilateral free tissue transfer was not significant. Operations performed in 2017 were at lower risk (OR, 0.2; 95 percent CI, 0.06 to 0.81; p = 0.02) for extended length of stay. Reoperation is more likely following operative transfusion and bilateral free tissue transfers, but less likely following concurrent alloplasty. Given a known operation time (minutes), postoperative length of stay (days) can be calculated using the following equation: length of stay = 2.559 + 0.003 × operation time. CONCLUSIONS: This study characterizes the risks for extended length of stay after free tissue transfer breast reconstruction using a prospective multicenter national database. The result of this study can be used to risk-stratify patients during surgical planning to optimize perioperative decision-making. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Postirradiation Capsular Contracture in Implant-Based Breast Reconstruction: Management and Outcome.

BACKGROUND: Implant-based breast reconstruction is commonly avoided in the setting of radiation therapy, mainly because of risks of capsular contracture. Nevertheless, as breast reconstruction is becoming more available, more patients undergo both implant-based breast reconstruction and radiotherapy. The dilemma is how to manage capsular contracture if it does occur. The goal of this study was to examine the outcome of patients with implant-based breast reconstruction who developed postirradiation capsular contracture and were treated with capsulotomy or capsulectomy, with or without fat grafting. METHODS: The authors reviewed charts of patients who developed capsular contracture following alloplastic breast reconstruction followed by radiation therapy, between 2008 and 2018. The surgical treatment methods for capsular contracture were evaluated along with their outcomes. A follow-up of at least 1 year was required. RESULTS: Forty-eight breasts with postirradiation capsular contracture underwent surgical implant exchange with capsular release, of which 15 had combined fat grafting and 33 did not. Overall, 35 breasts (72.9 percent) showed long-term resolution of capsular contracture; 24 underwent a single procedure and 11 required an additional fat grafting procedure. Some patients [six breasts (12.5 percent)] were offered a consecutive round of fat grafting, and some [seven breasts (14.5 percent)] were offered autologous reconstruction because of lack of improvement. Fat grafting increased the success rate by more than 30 percent when it was initially and consecutively used. CONCLUSIONS: Postirradiation capsular contracture may be treated successfully by secondary procedures, sustaining implant-based breast reconstruction in over 70 percent of breasts. Fat grafting may elevate resolution rates even further, to 86 percent. Larger prospective studies are required to validate these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience.

INTRODUCTION: After failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients. PATIENTS AND METHODS: This retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen. RESULTS: Forty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88). CONCLUSION: Second-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.

Safety of Irradiated Homologous Costal Cartilage Graft in Cleft Rhinoplasty.

BACKGROUND: Autologous cartilage grafts have a low risk of infection and extrusion in cleft rhinoplasty. However, harvesting autologous cartilage involves donor-site morbidity and increased time under anesthesia. Irradiated homologous costal cartilage grafts may be an effective alternative. METHODS: A retrospective study was performed on patients with a history of cleft lip who underwent rhinoplasty for cleft nasal deformity at Johns Hopkins Hospital from 2009 to 2018. Patients were excluded if their rhinoplasty did not involve a cartilage graft. RESULTS: One hundred sixty-five cleft rhinoplasties (patient age, 2 to 72 years; 52 percent female) were performed. Median follow-up time was 256 days; 30 percent were revision operations. Ninety-six procedures (58 percent) used irradiated homologous costal cartilage grafts, with the remaining using autologous cartilage. Complications resulted from 18 procedures (11 percent), seven (10 percent) involving autologous cartilage and 11 (12 percent) involving irradiated homologous costal cartilage. Most autologous cartilage complications (86 percent) required operative intervention, versus seven of 11 (64 percent) for irradiated homologous costal cartilage. Complications associated with irradiated homologous costal cartilage included infection (n = 5), warping (n = 2), and extrusion (n = 1), while two patients with autologous cartilage experienced collapse and one each experienced resorption, warping, and hypertrophic donor-site scarring. There was no difference between groups regarding complication rate or complications requiring operative intervention (p = 0.3 and p = 0.5, respectively). CONCLUSIONS: Irradiated homologous costal cartilage grafts are equally safe and effective as autologous cartilage for use in cleft rhinoplasty. These grafts are readily available and eliminate donor-site morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9-9·7) months of panobinostat. In responders, T-lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non-responders. The reduction in the proportion of CD127+ CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre-transplant, in non-responders when compared to responders. Whole marrow RNA-seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.