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1.
J Invest Dermatol ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901775

RESUMEN

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

2.
Ann Plast Surg ; 92(5S Suppl 3): S320-S326, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38689413

RESUMEN

PURPOSE: Resection of sacral neoplasms such as chordoma and chondrosarcoma with subsequent reconstruction of large soft tissue defects is a complex multidisciplinary process. Radiotherapy and prior abdominal surgery play a role in reconstructive planning; however, there is no consensus on how to maximize outcomes. In this study, we present our institution's experience with the reconstructive surgical management of this unique patient population. METHODS: We conducted a retrospective review of patients who underwent reconstruction after resection of primary or recurrent pelvic chordoma or chondrosarcoma between 2002 and 2019. Surgical details, hospital stay, and postoperative outcomes were assessed. Patients were divided into 3 groups for comparison based on reconstruction technique: gluteal-based flaps, vertical rectus abdominus myocutaneous (VRAM) flaps, and locoregional fasciocutaneous flaps. RESULTS: Twenty-eight patients (17 males, 11 females), with mean age of 62 years (range, 34-86 years), were reviewed. Twenty-two patients (78.6%) received gluteal-based flaps, 3 patients (10.7%) received VRAM flaps, and 3 patients (10.7%) were reconstructed with locoregional fasciocutaneous flaps. Patients in the VRAM group were significantly more likely to have undergone total sacrectomy (P < 0.01) in a 2-stage operation (P < 0.01) compared with patients in the other 2 groups. Patients in the VRAM group also had a significantly greater average number of reoperations (2 ± 3.5, P = 0.04) and length of stay (29.7 ± 20.4 days, P = 0.01) compared with the 2 other groups. The overall minor and major wound complication rates were 17.9% and 42.9%, respectively, with 17.9% of patients experiencing at least 1 infection or seroma. There was no association between prior abdominal surgery, surgical stages, or radiation therapy and an increased risk of wound complications. CONCLUSIONS: Vertical rectus abdominus myocutaneous flaps are a more suitable option for patients with larger defects after total sacrectomy via 2-staged anteroposterior resections, whereas gluteal myocutaneous flaps are effective options for posterior-only resections. For patients with small- to moderate-sized defects, local fasciocutaneous flaps are a less invasive and effective option. Paraspinous flaps may be used in combination with other techniques to provide additional bulk and coverage for especially long postresection wounds. Furthermore, mesh is a useful adjunct for any reconstruction aimed at protecting against intra-abdominal complications.


Asunto(s)
Cordoma , Procedimientos de Cirugía Plástica , Sacro , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Procedimientos de Cirugía Plástica/métodos , Anciano , Adulto , Anciano de 80 o más Años , Cordoma/cirugía , Sacro/cirugía , Condrosarcoma/cirugía , Colgajos Quirúrgicos , San Francisco , Neoplasias de la Columna Vertebral/cirugía
3.
Ann Plast Surg ; 92(5S Suppl 3): S331-S335, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38689414

RESUMEN

BACKGROUND: Incisional negative pressure wound therapy (iNPWT) is an adjunctive treatment that uses constant negative pressure suction to facilitate healing. The utility of this treatment modality on vascular operations for critical limb-threatening ischemia (CLTI) has yet to be elucidated. This study compares the incidence of postoperative wound complications between the Prevena Incision Management System, a type of iNPWT, and standard wound dressings for vascular patients who also underwent plastic surgery closure of groin incisions for CLTI. METHOD: We performed a retrospective cohort study of 40 patients with CLTI who underwent 53 open vascular surgeries with subsequent sartorius muscle flap closure. Patient demographics, intraoperative details, and wound complications were measured from 2015 to 2018 at the University of California San Francisco. Two cohorts were generated based on the modality of postoperative wound management and compared on wound healing outcomes. RESULTS: Of the 53 groin incisions, 29 were managed with standard dressings, and 24 received iNPWT. Patient demographics, comorbidities, and operative characteristics were similar between the 2 groups. Patients who received iNPWT had a significantly lower rate of infection (8.33% vs 31.0%, P = 0.04) and dehiscence (0% vs 41.3%, P < 0.01). Furthermore, the iNPWT group had a significantly lower rate of reoperation (0% vs 17.2%, P = 0.03) for wound complications within 30 days compared with the control group and a moderately reduced rate of readmission (4.17% vs 20.7%, P = 0.08). CONCLUSIONS: Rates of infection, reoperation, and dehiscence were significantly reduced in patients whose groin incisions were managed with iNPWT compared with standard wound care. Readmission rates were also decreased, but this difference was not statistically significant. Our results suggest that implementing iNPWT for the management of groin incisions, particularly in patients undergoing vascular operations for CLTI, may significantly improve clinical outcomes.


Asunto(s)
Ingle , Isquemia , Terapia de Presión Negativa para Heridas , Cicatrización de Heridas , Humanos , Terapia de Presión Negativa para Heridas/métodos , Masculino , Estudios Retrospectivos , Femenino , Ingle/cirugía , Isquemia/cirugía , Isquemia/etiología , Anciano , Persona de Mediana Edad , Procedimientos Quirúrgicos Vasculares/métodos , Estudios de Cohortes , Complicaciones Posoperatorias/epidemiología
4.
Ann Plast Surg ; 92(5): 564-568, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38563574

RESUMEN

PURPOSE: The benefits of paraspinous flaps in adult complex spine surgery patients are established in the literature; however, their use in pediatric patients has not been well described. This study compares clinical outcomes with and without paraspinous muscle flap closure in pediatric patients who have undergone spine surgery. METHODS: We conducted a retrospective review of all pediatric spine surgeries at the University of California, San Francisco from 2011 to 2022. Patients were divided into 2 cohorts based on whether the plastic surgery service closed or did not close the wound with paraspinous muscle flaps. We matched patients by age, American Society of Anesthesiology classification, prior spinal surgical history, and diagnosis. Surgical outcomes were compared between the 2 cohorts. RESULTS: We identified 226 pediatric patients who underwent at least one spinal surgery, 14 of whom received paraspinous flap closure by plastic surgery. They were matched in a 1:4 ratio with controls (n = 56) that did not have plastic surgery closure. The most common indication for plastic surgery involvement was perceived complexity of disease by the spine surgeon with concern for inadequate healthy tissue coverage (78.6%), followed by infection (21.4%). Postoperative complications were similar between the two groups. The plastic surgery cohort had a higher rate of patients who were underweight (57.1% vs 14.3%, P < 0.01) and had positive preoperative wound cultures (28.6% vs 8.9%, P = 0.05), as well as a higher rate of postoperative antibiotic usage (78.6 vs 17.9%, P < 0.01). There was no difference in recorded postoperative outcomes. CONCLUSIONS: Spine surgeons requested paraspinous flap closure for patients with more complex disease, preoperative infections, history of chemotherapy, or if they were underweight. Patients with paraspinous flap coverage did not have increased postoperative complications despite their elevated risk profile. Our findings suggest that paraspinous muscle flaps should be considered in high-risk pediatric patients who undergo spine surgery.


Asunto(s)
Músculos Paraespinales , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Humanos , Estudios Retrospectivos , Femenino , Masculino , Niño , Adolescente , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/trasplante , Preescolar , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Enfermedades de la Columna Vertebral/cirugía
5.
JCI Insight ; 9(3)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38113104

RESUMEN

Hidradenitis suppurativa (HS) is a chronic skin condition affecting approximately 1% of the US population. HS skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu, the biology and the contribution of these cells in HS pathogenesis are unclear. We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Combining histological analysis, single-cell RNA sequencing, and spatial transcriptomics profiling of HS lesions, we defined the tissue microenvironment relative to B cell activity within this disease. Our findings identified tertiary lymphoid structures (TLSs) within HS lesions and described organized interactions among T cells, B cells, antigen-presenting cells, and skin stroma. We found evidence that B cells within HS TLSs actively underwent maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells were primed to support the formation of TLSs and facilitate B cell recruitment during HS. Our data definitively demonstrated the presence of TLSs in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed nonlymphoid tissue.


Asunto(s)
Hidradenitis Supurativa , Estructuras Linfoides Terciarias , Humanos , Hidradenitis Supurativa/patología , Estructuras Linfoides Terciarias/patología , Piel/patología , Linfocitos B/patología , Linfocitos T/patología
6.
bioRxiv ; 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36824918

RESUMEN

Background: Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear. Objective: We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Methods: We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease. Results: Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS. Conclusion: Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue.

7.
Plast Reconstr Surg Glob Open ; 10(11): e4665, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36438470

RESUMEN

The use of muscle flaps, such as the sartorius muscle, for groin coverage in high-risk vascular patients has been shown to reduce complication rates. However, it remains unknown whether earlier postoperative ambulation is associated with improved postoperative outcomes for groin muscle flaps following infrainguinal vascular surgery. Methods: We performed a pilot randomized trial to analyze the effect of early ambulation on postoperative outcomes in patients who had groin reconstruction with sartorius muscle flaps following infrainguinal vascular surgery at our academic institution. Results: Fourteen patients were randomized to standard ambulation (on postoperative day 6), and 14 patients were randomized to early ambulation (on postoperative day 2). The treatment arms were similar with respect to age, body mass index, risk category, smoking status, and comorbidities. Median length of stay was 6 days in the early group versus 7 days in the standard group. Immediate and long-term physical function and general health were better in the early group There were slightly more wound complications in the standard (57.1%) versus the early group (42.9%), and the early group had more lymphatic complications (35.7% versus 14.3%). Conclusions: The decision to ambulate a patient after this surgery continues to be a decision between the vascular and plastic surgeons. However, this pilot trial has shown the safety profile of early ambulation and that it should be considered for specific patients. Additionally, this trial has provided valuable information for performing a larger scale randomized controlled trial to determine the optimal postoperative protocol for patients with these reconstructions.

9.
Ann Vasc Surg ; 78: 77-83, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34433093

RESUMEN

BACKGROUND: Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin. METHODS: A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone. RESULTS: A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, P = 0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, P < 0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, P = 0.02). Other rates of complications were not statistically different between groups. CONCLUSIONS: In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.


Asunto(s)
Ingle/cirugía , Complicaciones Posoperatorias/prevención & control , Colgajos Quirúrgicos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Aneurisma/cirugía , Arteriopatías Oclusivas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Herida Quirúrgica
10.
Ann Vasc Surg ; 82: 197-205, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34902473

RESUMEN

INTRODUCTION: Lymphatic complications following vascular procedures involving the groin require prompt treatment to limit morbidity. Several treatments have been described, including conservative management, aspiration, sclerotherapy, and direct lymphatic ligation with or without a muscle flap have been described. To date, there is no data indicating which treatment results in the shortest time to recovery. We sought to address this gap by conducting a retrospective cohort study. METHODS: We reviewed all patients who developed a lymphatic complication after undergoing an open revascularization procedure in the groin between 2014 and 2020 in which plastic surgery was involved in the closure. A control group consisted of patients from the same timespan who did not develop a lymphatic complication. Demographics, comorbidities, operative details, and outcomes were compared between these groups. For cases identified with a lymphatic complication, the method of diagnosis, culture data, and treatment details were collected, and outcomes were compared for surgical management versus sclerotherapy. RESULTS: There were 27 lymphatic complications and 60 control patients. The complication group had a higher incidence of aortofemoral bypass (25.8% vs. 8.3%, P = 0.04), and a lower incidence of femoral-to-distal bypass (11.1% vs. 45.0%, P < 0.01). Daily drain output volume from postoperative days 1-5, and days 6-10, was significantly higher in the complication group than in the controls (194.0 vs. 44.0, P < 0.01; and 429.5 vs. 35.0, P < 0.01, respectively). In the lymphatic leak group, 16 patients (59.3%) had surgical treatment and six (22.2%) had sclerotherapy. Of those who had surgery, 71.4% had successful outcomes without the need for an additional intervention, whereas all of the patients analyzed who were treated with sclerotherapy had successful outcomes without further intervention. The average time to resolution was significantly shorter for surgery than for sclerotherapy (38.7 vs. 86.0 days, P = 0.03). CONCLUSIONS: Daily postoperative drain volume can assist with early diagnosis of a lymphatic leak in the groin following an open revascularization procedure. Sclerotherapy and surgery were each successful, but surgery resulted in significantly shorter times to resolution. In the appropriate candidates, surgery should be considered first line management of a lymphatic leak.


Asunto(s)
Ingle , Cirugía Plástica , Ingle/cirugía , Humanos , Extremidad Inferior/irrigación sanguínea , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Resultado del Tratamiento
11.
Plast Reconstr Surg ; 148(5): 764e-768e, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34705780

RESUMEN

SUMMARY: Treatment of boutonniere Dupuytren disease is rare and is resistant to treatment because of altered tendon dynamics. The authors used a small dose of collagenase clostridium histolyticum for an enzymatic tenotomy of the distal interphalangeal joint and showed that hyperextension at the distal interphalangeal joint improved significantly. Fifteen patients with boutonniere Dupuytren disease with severe proximal interphalangeal joint contractures averaging -69 degrees of extension were included in the study. Ten patients had at least one previous intervention, including surgical fasciectomy, Digit Widget treatment, and needle aponeurotomy. Collagenase clostridium histolyticum enzymatic tenotomy was performed in-office as a wide-awake procedure. All patients received varying doses of collagenase clostridium histolyticum for volar Dupuytren disease enzymatic fasciotomy and 0.1 mg of collagenase clostridium histolyticum into the distal extensor tendon for tenotomy to treat boutonniere deformity at the same time. Collagenase clostridium histolyticum enzymatic tenotomy significantly improved total active motion of the finger by 41.0 degrees (p = 0.001). Loss of extension at both the metacarpophalangeal joint and the proximal interphalangeal joint also improved with gains of 11.7 (p = 0.04) and 20.7 degrees (p = 0.0005) of extension, respectively. The average distal interphalangeal joint hyperextension was improved from 29.7 degrees to 14.0 degrees (p = 0.002). The authors show that collagenase injection led to significant average improvement in joint contracture at all finger joints and significantly increased the arc of motion at the proximal interphalangeal joint and metacarpophalangeal joint. Although collagenase has been previously used for flexion contractures in Dupuytren disease, we believe it has a role in treating the distal interphalangeal joint hyperextension deformity associated with boutonniere deformity in Dupuytren disease as well. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Asunto(s)
Contractura de Dupuytren/cirugía , Colagenasa Microbiana/administración & dosificación , Tendones/efectos de los fármacos , Tenotomía/métodos , Anciano , Anciano de 80 o más Años , Contractura de Dupuytren/fisiopatología , Femenino , Articulaciones de los Dedos/fisiopatología , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del Tratamiento
12.
JBJS Case Connect ; 11(3)2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-34319917

RESUMEN

CASE: A 37-year-old man presented with an absent right elbow joint secondary to trauma, subsequent ankylosis, total elbow arthroplasty (TEA), and TEA explantation after infection. The patient also had a contralateral complete brachial plexus injury, but an intact elbow joint. Given that the patient had a functional right hand/wrist, composite vascularized autograft elbow transplant was performed from left to right upper extremity. Four years postoperatively, the patient could independently complete activities of daily living. CONCLUSION: This case is the first to report composite vascularized autograft elbow transplant. Although indications are limited, this case illuminates novel uses of standard techniques for a difficult problem.


Asunto(s)
Lesiones de Codo , Articulación del Codo , Actividades Cotidianas , Adulto , Autoinjertos , Codo/cirugía , Articulación del Codo/cirugía , Humanos , Masculino , Articulación de la Muñeca
14.
BMJ Case Rep ; 14(7)2021 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-34301699

RESUMEN

A mycotic aneurysm of the distal radial artery following access for cardiac catheterisation is a rare complication that has not been described in the literature. We present the case of an 84-year-old man who developed bacteraemia and cellulitis over his left first dorsal webspace 2 days after undergoing cardiac catheterisation through the distal radial artery at the anatomic snuffbox. Ultrasound scanning and CT imaging were concerning for a possible pseudoaneurysm at that location. Once we confirmed that the patient had adequate flow through his hand with angiography and an Allen's test, we explored his left hand and found a mycotic aneurysm of the distal radial artery with surrounding frank purulence. We resected the aneurysm and ligated the artery. Pathology confirmed that this was a mycotic aneurysm. The patient quickly recovered from his infection after this definitive treatment.


Asunto(s)
Aneurisma Falso , Aneurisma Infectado , Anciano de 80 o más Años , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Aneurisma Infectado/diagnóstico por imagen , Aneurisma Infectado/etiología , Aneurisma Infectado/cirugía , Cateterismo Cardíaco/efectos adversos , Mano , Humanos , Masculino , Arteria Radial/diagnóstico por imagen , Arteria Radial/cirugía
15.
Semin Plast Surg ; 35(1): 3-9, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33994871

RESUMEN

Wound complications occur in up to 19% of patients undergoing complex spine surgery. The role of the plastic surgeon in complex and redo spine surgery is important and evolving. Classically, plastic surgeons have been involved in the management of patients who develop wound complications following surgery. This involves reconstruction of posterior trunk defects with locoregional fasciocutaneous, muscle, and free tissue transfers. There has also been an increasing role for plastic surgeons to become involved in prophylactic closures of complex and/or redo spine surgeries for high-risk populations. Identification of patients with comorbidities and likelihood for multiple reoperations who are prophylactically treated with complex closure with or without local muscle flaps could significantly decrease the postoperative wound complications.

16.
Oper Neurosurg (Hagerstown) ; 20(5): 508-512, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33616164

RESUMEN

BACKGROUND: Solid arthrodesis is the long-term goal of most spinal reconstruction surgeries. A multitube of biologics as well as autograft is commonly used to augment the bony fusion. Medial scapular vascularized bone grafts (S-VBGs) are a novel approach to supplement cervicothoracic arthrodesis in patients at high risk for failed fusion. OBJECTIVE: To discuss the benefits of using a vascularized scapular graft, pedicled to the rhomboid minor, compared to both nonvascularized bone grafts and free vascularized bone grafts, as well as the surgical technique, feasibility, and nuances of the surgical experience with an S-VBG. METHODS: The anatomic feasibility of this procedure has been established in cadaver studies. This technical note details the operative steps and presents the first surgery in which a vascularized scapular graft was used to supplement cervicothoracic arthrodesis. RESULTS: A single patient with complex cervical deformity was successfully treated with this novel arthrodesis approach. CONCLUSION: Vascularized scapula grafts, pedicled on the rhomboid minor, provides both structural support and a source of vascularized autograft to a cervicothoracic arthrodesis. It leverages the benefits of a free-flap bone with less operative time and morbidity.


Asunto(s)
Fusión Vertebral , Trasplante Óseo , Cadáver , Humanos , Escápula/cirugía , Trasplante Autólogo
17.
Stem Cells ; 39(3): 331-344, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33326654

RESUMEN

Irreversible denervation atrophy remains an unsolved clinical problem, and the role of skeletal muscle stem cell (MuSC, satellite cell) depletion in this process is unclear. We investigated the ability of MuSCs to regenerate muscle in the context of denervation. Three to 12 months following sciatic denervation in mice, MuSC number, size, EdU uptake, rate of division, and mitochondrial activity were increased. Following acute myotoxin injury, denervated muscles formed new muscle fibers in situ. MuSCs isolated via flow cytometry from denervated mouse muscle, or from atrophic denervated gluteus maximus muscles of humans with complete spinal cord injuries two decades prior, formed new muscle fibers and reoccupied the anatomic niche after transplantation into uninjured muscle. Our results show unequivocally that, even after prolonged denervation, MuSCs retain intrinsic regenerative potential similar to that of uninjured MuSCs. Treatment of denervation atrophy will require elucidating the non-MuSC environmental changes in muscle that prevent functional regeneration.


Asunto(s)
Desnervación , Fibras Musculares Esqueléticas/citología , Músculo Esquelético/fisiología , Mioblastos/citología , Animales , Desnervación/métodos , Ratones Endogámicos C57BL , Factores de Tiempo
18.
JCI Insight ; 5(19)2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-32841223

RESUMEN

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.


Asunto(s)
Biomarcadores/análisis , Regulación de la Expresión Génica , Hidradenitis Supurativa/tratamiento farmacológico , Linfocitos T Reguladores/inmunología , Transcriptoma/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Estudios de Casos y Controles , Redes Reguladoras de Genes , Hidradenitis Supurativa/inmunología , Hidradenitis Supurativa/patología , Humanos , Transducción de Señal , Análisis de la Célula Individual/métodos , Linfocitos T Reguladores/efectos de los fármacos
19.
J Surg Res ; 230: 34-39, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30100037

RESUMEN

BACKGROUND: Current surgical management of retroperitoneal masses involving major vessels now includes complete en bloc resection with in situ venous, arterial, or combined reconstruction. No studies have investigated preresection arterial bypass for continuous lower extremity perfusion during definitive resection. Here, we characterize and compare the outcomes of surgery for retroperitoneal masses with major vascular involvement by a two-stage approach (femoral-femoral bypass preceding resection) and the traditional one-stage approach (consecutive resection and in situ vascular reconstruction). MATERIALS AND METHODS: We retrospectively reviewed patients who underwent resection of retroperitoneal masses and reconstruction of major arterial or venous structures from 2004 to 2016. Outcomes were compared with unpaired t-tests, chi-squared tests, and Kaplan-Meier analysis. RESULTS: Eight patients underwent a two-stage procedure, and seven underwent a one-stage procedure for retroperitoneal masses with vascular involvement. Mean (±SD) oncologic resection time (443 ± 215 versus 648 ± 128 min, P = 0.047) and postoperative ICU stay (0.9 ± 1.3 versus 4.4 ± 2.9 d, P = 0.018) were significantly shorter for the two-stage approach. CONCLUSIONS: To our knowledge, this is the first report of a two-stage approach for resection of retroperitoneal masses with major vessel involvement. Femoral-femoral arterial bypass before definitive resection could be a viable option for improving intraoperative vascular control and decreasing perioperative complications in these complex procedures.


Asunto(s)
Recuperación del Miembro/métodos , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Injerto Vascular/métodos , Adulto , Anciano , Arterias/diagnóstico por imagen , Arterias/cirugía , Angiografía por Tomografía Computarizada , Supervivencia sin Enfermedad , Femenino , Humanos , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología , Recuperación del Miembro/efectos adversos , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Tempo Operativo , Periodo Perioperatorio/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/patología , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Sarcoma/mortalidad , Sarcoma/patología , Factores de Tiempo , Injerto Vascular/efectos adversos , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/cirugía
20.
Stem Cell Reports ; 10(3): 1160-1174, 2018 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-29478895

RESUMEN

Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC) pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs.


Asunto(s)
Células Satélite del Músculo Esquelético/citología , Animales , Separación Celular/métodos , Células Cultivadas , Distrofina/metabolismo , Humanos , Ratones , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Regeneración/fisiología , Células Satélite del Músculo Esquelético/metabolismo , Trasplante de Células Madre/métodos , Células Madre/citología , Células Madre/metabolismo , Trasplante Heterólogo/métodos
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