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1.
Clin Exp Rheumatol ; 42(6): 1215-1223, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38966946

RESUMEN

OBJECTIVES: The pathogenesis of fibromyalgia (FM), characterised by chronic widespread pain and fatigue, remains notoriously elusive, hampering attempts to develop disease modifying treatments. Mitochondria are the headquarters of cellular energy metabolism, and their malfunction has been proposed to contribute to both FM and chronic fatigue. Thus, the aim of the current pilot study, was to detect structural changes in mitochondria of peripheral blood mononuclear cells (PBMCs) of FM patients, using transmission electron microscopy (TEM). METHODS: To detect structural mitochondrial alterations in FM, we analysed PBMCs from seven patients and seven healthy controls, using TEM. Patients were recruited from a specialised Fibromyalgia Clinic at a tertiary medical centre. After providing informed consent, participants completed questionnaires including the widespread pain index (WPI), symptoms severity score (SSS), fibromyalgia impact questionnaire (FIQ), beck depression inventory (BDI), and visual analogue scale (VAS), to verify a diagnosis of FM according to ACR criteria. Subsequently, blood samples were drawn and PBMCs were collected for EM analysis. RESULTS: TEM analysis of PBMCs showed several distinct mitochondrial cristae patterns, including total loss of cristae in FM patients. The number of mitochondria with intact cristae morphology was reduced in FM patients and the percentage of mitochondria that completely lacked cristae was increased. These results correlated with the WPI severity. Moreover, in the FM patient samples we observed a high percentage of cells containing electron dense aggregates, which are possibly ribosome aggregates. Cristae loss and possible ribosome aggregation were intercorrelated, and thus may represent reactions to a shared cellular stress condition. The changes in mitochondrial morphology suggest that mitochondrial dysfunction, resulting in inefficient oxidative phosphorylation and ATP production, metabolic and redox disorders, and increased reactive oxygen species (ROS) levels, may play a pathogenetic role in FM. CONCLUSIONS: We describe novel morphological changes in mitochondria of FM patients, including loss of mitochondrial cristae. While these observations cannot determine whether the changes are pathogenetic or represent an epiphenomenon, they highlight the possibility that mitochondrial malfunction may play a causative role in the cascade of events leading to chronic pain and fatigue in FM. Moreover, the results offer the possibility of utilising changes in mitochondrial morphology as an objective biomarker in FM. Further understanding the connection between FM and dysfunction of mitochondria physiology, may assist in developing both novel diagnostic tools as well as specific treatments for FM, such as approaches to improve/strengthen mitochondria function.


Asunto(s)
Fibromialgia , Mitocondrias , Humanos , Fibromialgia/patología , Fibromialgia/fisiopatología , Proyectos Piloto , Mitocondrias/ultraestructura , Mitocondrias/patología , Femenino , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Masculino , Microscopía Electrónica de Transmisión , Leucocitos Mononucleares/ultraestructura , Leucocitos Mononucleares/patología , Índice de Severidad de la Enfermedad , Dimensión del Dolor
3.
Am J Surg ; : 115794, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38879356

RESUMEN

BACKGROUND: The role of immune-oncology (IO) therapy in soft tissue sarcoma (STS) is underexplored. This study characterized IO use in STS. METHODS: This is a retrospective analysis of patients with a soft tissue mass in the National Cancer Database, 2011-2021. Patients were categorized by IO receipt status. Groupwise testing and proportional trend tests were performed with Chi-squared tests. Multivariate logistic regression was performed to assess factors associated with IO receipt. RESULTS: Of the 103,092 patients with STS, 1935 (1.9 â€‹%) received or were recommended IO therapy. IO use increased 10-fold (0.24 â€‹%-2.5 â€‹% from 2011 to 2021; p â€‹< â€‹0.0001). Patients had higher odds of receiving IO when having higher grade tumors and metastatic disease, and when treated at an academic research center (all p â€‹< â€‹0.001). CONCLUSIONS: IO use in STS is low but increasing and primarily used in the metastatic setting. Future studies should identify biomarkers of IO response and facilitators for treatment receipt.

4.
Sci Rep ; 14(1): 11599, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773296

RESUMEN

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.


Asunto(s)
Abuso Sexual Infantil , Fibromialgia , Oxigenoterapia Hiperbárica , Humanos , Fibromialgia/terapia , Oxigenoterapia Hiperbárica/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Abuso Sexual Infantil/psicología , Estudios Prospectivos , Clorhidrato de Duloxetina/uso terapéutico , Pregabalina/uso terapéutico , Resultado del Tratamiento , Encuestas y Cuestionarios , Tomografía Computarizada de Emisión de Fotón Único , Analgésicos/uso terapéutico
5.
Foot Ankle Spec ; : 19386400241235389, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38450616

RESUMEN

Pin tract infections are virtually universal complications with the use of external fixation. While most are superficial and respond to oral antibiotics and local care, septic loosening may occur at the bone-pin interface, which may lead to instability of the fixator, catastrophic failure, fracture, and long-term osteomyelitis. Classification systems and prevention protocols have been developed to address this ubiquitous complication. Treatment of severe pin tract infections often requires debridement, parenteral antibiotics, and removal of the offending pin or the entire external fixator. In cases of osteomyelitic pin tracks, a sizable cavity is often present. We describe a simple technique for treatment of deep bone pin tract infection through the use of debridement, irrigation, and an antibiotic "sparkler," which is a specially prepared percutaneous implant of antibiotic laden bone cement.Levels of Evidence: Level 5.

6.
Pediatr Transplant ; 28(3): e14708, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38553812

RESUMEN

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Adulto , Humanos , Niño , Estudios Prospectivos , Biomarcadores , Rechazo de Injerto , Donantes de Tejidos
7.
Cancer Rep (Hoboken) ; 7(1): e1929, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37884691

RESUMEN

BACKGROUND: The burden of oral cancer in Nigeria is increasing. Different studies have shown how public education on oral cancer have increased knowledge of oral cancer across populations, however, it is not known if these practices are adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. AIMS: To investigate the patient oral cancer education strategies adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. METHODS: This study adopted an analytical cross-sectional study design. This study surveyed practicing oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. An e-questionnaire was used for this study. The data were analyzed using the SPSS Version 20 software, and a p-value of <.05 was used to determine the level of statistical significance. RESULTS: The study's response rate was 46.6% (75/161). The 75 participants were from the six geopolitical zones in Nigeria responded to the survey questionnaire. Even though more than half (43/75, 57.3%) of the respondents have never received any training since their post-bachelor's degree qualification on the strategies that can be used in educating patients on oral cancer, majority (54/75, 72.0%) of them knew at least one education strategy; also, the most known (36/54, 66.7%) and utilized (33/54, 61.3%) strategy among those respondents who were aware of patient education strategy was health talk. Only 38.7% (29/75) of the respondents reported that health learning materials (posters, leaflets, fliers, and flipcharts) are available in their clinics, all of which were in insufficient quantities. Also, 93.3% (70/75) of the respondents opined that it is worthwhile that dental clinics/hospitals in Nigeria invest in the provision of oral cancer learning materials for patient use. Inferential statistical analysis did not reveal any significant relationship between the respondents' characteristics and their awareness and practice on patient oral cancer education strategies. CONCLUSION: This study identified that many oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria lack the needed capacity to educate their patients on oral cancer. There is a need to strengthen their capacity by giving them training on patient oral cancer education strategies, and by providing them with good quality and enough teaching aids.


Asunto(s)
Neoplasias de la Boca , Médicos , Humanos , Cirujanos Oromaxilofaciales , Estudios Transversales , Patólogos , Educación del Paciente como Asunto
8.
Oncologist ; 29(2): e237-e247, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37756655

RESUMEN

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.


Asunto(s)
COVID-19 , Pandemias , Adulto , Masculino , Humanos , Oncología Médica , Centros Médicos Académicos , COVID-19/epidemiología , Internet
9.
Artículo en Inglés | MEDLINE | ID: mdl-38065238

RESUMEN

BACKGROUND: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk. METHODS: Metabolomic profiling was performed on serial samples of ex situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, nonesterified fatty acids [NEFA], ketones, and 3-hydroxybutyrate). We tested for change over time in injury biomarkers and metabolites, along with differential changes by recovery strategy (donation after circulatory death [DCD] vs donation after brain death [DBD]). We examined associations between metabolites, injury biomarkers, and primary graft dysfunction (PGD). Analyses were performed using linear mixed models adjusted for recovery strategy, assay batch, donor-predicted heart mass, and time. RESULTS: A total of 176 samples from 92 ex situ perfusion runs were taken from donors with a mean age of 35 (standard deviation 11.3) years and a median total ex situ perfusion time of 234 (interquartile range 84) minutes. Lactate trends over time differed significantly by recovery strategy, while TnI increased during ex situ perfusion regardless of DCD vs DBD status. We found fuel substrates were rapidly depleted during ex situ perfusion, most notably the branched-chain amino acids leucine/isoleucine, as well as ketones, 3-hydroxybutyrate, and NEFA (least squares [LS] mean difference from the first to last time point -1.7 to -4.5, false discovery rate q < 0.001). Several long-chain acylcarnitines (LCAC), including C16, C18, C18:1, C18:2, C18:3, C20:3, and C20:4, increased during the perfusion run (LS mean difference 0.42-0.67, q < 0.001). Many LCACs were strongly associated with lactate and TnI. The change over time of many LCACs was significantly different for DCD vs DBD, suggesting differential trends in fuel substrate utilization by ischemic injury pattern. Changes in leucine/isoleucine, arginine, C12:1-OH/C10:1-DC, and C16-OH/C14-DC were associated with increased odds of moderate-severe PGD. Neither end-of-run nor change in lactate or TnI was associated with PGD. CONCLUSIONS: Metabolomic profiling of ex situ normothermic perfusion solution reveals a pattern of fuel substrate utilization that correlates with subclinical and clinical allograft dysfunction. This study highlights a potential role for interventions focused on fuel substrate modification in allograft conditioning during ex situ perfusion to improve allograft outcomes.

10.
Am J Clin Exp Urol ; 11(5): 420-428, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37941646

RESUMEN

INTRODUCTION: The objective of this study is to conduct a thorough investigation of the risk factors associated with blood loss during PCNL, within the setting of a US urban tertiary care center. MATERIALS AND METHODS: We conducted a retrospective analysis of our endourology database to identify adult patients who underwent PCNL for stone extraction at our tertiary stone center between October 2014 and December 2022. Patients were categorized into two groups based on the extent of blood loss: significant blood loss (SBL) and no significant blood loss (NSBL). The cut-off value for SBL was determined as the median change in hematocrit levels from preoperative to postoperative among patients who required postoperative transfusions. Several factors were evaluated, including stone dimensions, operative details, the presence of preoperative drains, patient position, type of access, access site, number of accesses, tract size, tract length, stone location, number of stones, operative time, and the S.T.O.N.E. Nephrolithometry Scoring System. RESULTS: Our analysis included a total of 695 procedures performed on 674 distinct patients who met our inclusion criteria. Of these, 102 patients (14.7%) were included in the SBL group. Patients in the SBL group had a higher mean number of accesses (1.57 vs. 1.29, P<0.001), were positioned prone more often (96.0% vs. 88.6%, P = 0.025), and underwent fluoroscopic-guided access more frequently (89.9% vs. 64.8%, P<0.001). Additionally, significant differences were observed in stone morphology, with the SBL group having higher rates of complete staghorn stones (42.2% vs. 27.0%, P = 0.019) and lower rates of partial staghorn stones (27.7% vs. 36.8%, P = 0.019). A larger proportion of patients in the SBL group required a 16 French nephrostomy tube for postoperative drainage (13.3% vs. 10.4%, P = 0.041). Lastly, the SBL group had a longer mean operative time compared to the NSBL group (P<0.001). Multiple logistic regression analysis identified stone volume (P = 0.039), number of accesses (P = 0.047), and operative time (P = 0.006) as independent risk factors associated with SBL status. CONCLUSION: Surgical complexity factors such as stone volume, number of accesses, and operative time are linked to a higher risk of SBL during PCNL. Stone volume and the requirement for multiple accesses can usually be estimated with reasonable accuracy before surgery.

11.
Aesthet Surg J ; 44(1): 95-101, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-37431878

RESUMEN

BACKGROUND: Aesthetic surgery fellowship applications were consolidated under the San Francisco Match in 2018. The impact of these changes on aesthetic program and applicant numbers had not yet been investigated. OBJECTIVES: In this study we sought to evaluate changes in programs, positions, applications, match rates, and fill rates since aesthetic surgery joined the San Francisco Match. We also aimed to compare these trends to craniofacial surgery, microsurgery, and hand surgery fellowships over this same time period. METHODS: San Francisco and National Resident Matching Program (NRMP) match data for aesthetic, craniofacial, microsurgery, and hand fellowships were obtained from 2018 to 2022, and the number of applications, positions, programs, and successful matches were evaluated. RESULTS: The number of aesthetic fellowship positions increased from 17 to 41 (141%) over the period studied. This resulted in increased match rates and more unfilled positions. Over the same period, fellowship positions for craniofacial, hand, and microsurgery increased by 3.4%, 6%, and 2.5% respectively. There was no increase in applications to any postgraduate subspecialty, nor was there any change in the number of residents pursuing fellowship. Similarly, there was no change in the percentage of fellowship-bound residents applying to any given discipline. CONCLUSIONS: The increase in aesthetic fellowship programs and positions did not generate an increase in applications. Applications to other plastic surgery subspecialties also failed to increase. Unlike aesthetic fellowships, their program numbers have remained stable. Given the limited fellowship applicant pool, our focus should be on enhancing the quality of existing aesthetic programs rather than continuing to increase the number of aesthetic positions.


Asunto(s)
Internado y Residencia , Procedimientos de Cirugía Plástica , Cirugía Plástica , Humanos , Estados Unidos , Cirugía Plástica/educación , Becas , Educación de Postgrado en Medicina
12.
Circulation ; 148(17): 1316-1329, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37401479

RESUMEN

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Insuficiencia Cardíaca , Humanos , Administración por Inhalación , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Epoprostenol/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/cirugía , Óxido Nítrico , Vasodilatadores
13.
Ann Surg ; 278(3): 417-425, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37334712

RESUMEN

OBJECTIVES: We aimed to report efficacy, safety, and health-related quality of life (HRQoL) outcomes of a multidisciplinary treatment approach including supraclavicular thoracic outlet decompression among patients with thoracic outlet syndrome (TOS). BACKGROUND: TOS is a challenging condition where controversy remains in diagnosis and treatment, primarily given a lack of data exploring various treatment approaches and associated patient outcomes. METHODS: Patients who underwent unilateral, supraclavicular thoracic outlet decompression, or pectoralis minor tenotomy for neurogenic, venous, or arterial TOS were identified from a prospectively maintained database. Demography, use of preoperative botulinum toxin injection, and participation in multidisciplinary evaluation were measured. The primary endpoints were composite postoperative morbidity and symptomatic improvement compared with baseline. RESULTS: Among 2869 patients evaluated (2007-2021), 1032 underwent surgery, including 864 (83.7%) supraclavicular decompressions and 168 (16.3%) isolated pectoralis minor tenotomies. Predominant TOS subtypes among surgical patients were neurogenic (75.4%) and venous TOS (23.4%). Most patients (92.9%) with nTOS underwent preoperative botulinum toxin injection; 56.3% reported symptomatic improvement. Before surgical consultation, few patients reported participation in physical therapy (10.9%). The median time from first evaluation to surgery was 136 days (interquartile range: 55, 258). Among 864 patients who underwent supraclavicular thoracic outlet decompression, complications occurred in 19.8%; the most common complication was chyle leak (8.3%). Four patients (0.4%) required revisional thoracic outlet decompression. At a median follow-up of 420 days (interquartile range: 150, 937) 93.3% reported symptomatic improvement. CONCLUSION: Based on low composite morbidity, need for very few revisional operations, and high rates of symptomatic improvement, a multidisciplinary treatment approach including primarily supraclavicular thoracic outlet decompression is safe and effective for patients with TOS.


Asunto(s)
Toxinas Botulínicas , Síndrome del Desfiladero Torácico , Humanos , Resultado del Tratamiento , Calidad de Vida , Descompresión Quirúrgica/efectos adversos , Síndrome del Desfiladero Torácico/cirugía , Síndrome del Desfiladero Torácico/diagnóstico , Síndrome del Desfiladero Torácico/etiología , Estudios Retrospectivos
15.
Radiat Res ; 199(5): 439-451, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37237442

RESUMEN

Radiation models, such as whole thorax lung irradiation (WTLI) or partial-body irradiation (PBI) with bone-marrow sparing, have shown that affected lung tissue displays a continual progression of injury, often for months after the initial insult. Undoubtably, a variety of resident and infiltrating cell types either contribute to or fail to resolve this type of progressive injury, which in lung tissue, often develops into lethal and irreversible radiation-induced pulmonary fibrosis (RIPF), indicating a failure of the lung to return to a homeostatic state. Resident pulmonary epithelium, which are present at the time of irradiation and persist long after the initial insult, play a key role in the maintenance of homeostatic conditions in the lung and have often been described as contributing to the progression of radiation-induced lung injury (RILI). In this study, we took an unbiased approach through RNA sequencing to determine the in vivo response of the lung epithelium in the progression of RIPF. In our methodology, we isolated CD326+ epithelium from the lungs of 12.5 Gy WTLI C57BL/6J female mice (aged 8-10 weeks and sacrificed at regular intervals) and compared irradiated and non-irradiated CD326+ cells and whole lung tissue. We subsequently verified our findings by qPCR and immunohistochemistry. Transcripts associated with epithelial regulation of immune responses and fibroblast activation were significantly reduced in irradiated animals at 4 weeks postirradiation. Additionally, alveolar type-2 epithelial cells (AEC2) appeared to be significantly reduced in number at 4 weeks and thereafter based on the diminished expression of pro-surfactant protein C (pro-SPC). This change is associated with a reduction of Cd200 and cyclooxygenase 2 (COX2), which are expressed within the CD326 populations of cells and function to suppress macrophage and fibroblast activation under steady-state conditions, respectively. These data indicate that either preventing epithelial cell loss that occurs after irradiation or replacing important mediators of immune and fibroblast activity produced by the epithelium are potentially important strategies for preventing or treating this unique injury.


Asunto(s)
Lesión Pulmonar , Fibrosis Pulmonar , Animales , Ratones , Femenino , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , Ratones Endogámicos C57BL , Pulmón/efectos de la radiación , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/metabolismo , Inflamación/patología
16.
Neurosci Biobehav Rev ; 151: 105235, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37207842

RESUMEN

Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fibromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the understanding, assessment, and intervention for fibromyalgia.


Asunto(s)
Fibromialgia , Modelos Biopsicosociales , Humanos
17.
JCO Oncol Pract ; 19(8): 577-585, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37216627

RESUMEN

PURPOSE: Acute care events (ACEs), comprising emergency department visits and hospitalizations, are a priority area for reduction in oncology. Prognostic models are a compelling strategy to identify high-risk patients and target preventive services, but have yet to be broadly implemented, partly because of challenges with electronic health record (EHR) integration. To facilitate EHR integration, we adapted and validated the previously published PRediction Of Acute Care use during Cancer Treatment (PROACCT) model to identify patients at highest risk for ACEs after systemic anticancer treatment. METHODS: A retrospective cohort of adults with a cancer diagnosis starting systemic therapy at a single center between July and November 2021 was divided into development (70%) and validation (30%) sets. Clinical and demographic variables were extracted, limited to those in structured format in the EHR, including cancer diagnosis, age, drug category, and ACE in prior year. Three logistic regression models of increasing complexity were developed to predict risk of ACEs. RESULTS: Five thousand one hundred fifty-three patients were evaluated (3,603 development and 1,550 validation). Several factors were predictive of ACEs: age (in decades), receipt of cytotoxic chemotherapy or immunotherapy, thoracic, GI or hematologic malignancy, and ACE in the prior year. We defined high-risk as the top 10% of risk scores; this population had 33.6% ACE rate compared with 8.3% for the remaining 90% in the low-risk group. The simplest Adapted PROACCT model had a C-statistic of 0.79, sensitivity of 0.28, and specificity of 0.93. CONCLUSION: We present three models designed for EHR integration that effectively identify oncology patients at highest risk for ACE after initiation of systemic anticancer treatment. By limiting predictors to structured data fields and including all cancer types, these models offer broad applicability for cancer care organizations and may offer a safety net to identify and target resources to this high risk.


Asunto(s)
Neoplasias , Adulto , Humanos , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Factores de Riesgo , Pronóstico , Modelos Logísticos
18.
J Endourol ; 37(6): 660-666, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37051709

RESUMEN

Purpose: Retropulsion of stone fragments during ureteroscopic laser lithotripsy (URSLL) remains a challenge for urologists and is associated with increased operative time and reduced stone-free rate (SFR). In this study, we compared the rate of retropulsion of ureteral stones during URSLL between the standard dorsal lithotomy (SDL) position and dorsal lithotomy position with reverse Trendelenburg (RT). Materials and Methods: Patients with ureteral stones requiring surgical intervention between May 2019 and January 2022 were randomized to undergo URSLL in either SDL or RT positions. The primary outcome of this study was stone retropulsion. Secondary outcomes included retropulsion to the kidney, SFR, operative time, 30-day emergency department visits and complications, and the need for conversion from semirigid to flexible ureteroscope. Differences between groups were evaluated using the chi-square test, Fisher exact test, Kruskal-Wallis test, or t-test. Results: A total of 114 patients were included in the study, with 57 patients in each group. There were no differences between groups in terms of baseline demographics or stone characteristics. Retropulsion was significantly less frequent in the RT group (68.4% vs 10.5%, p < 0.01). Similarly, the RT group was favored for lower risk of retropulsion into the kidney (40.4% vs 5.3%, p < 0.01), operative time (43.5 vs 33.0 minutes, p = 0.02), and need for ureteroscope conversion (16.7% vs 2.2%, p = 0.04). There was no difference in the SFR (100% vs 95%, p = 0.49). Conclusions: RT positioning during URSLL for ureteral stones significantly decreases the rate of stone retropulsion, operative time, and the need for conversion from semirigid to flexible ureteroscope.


Asunto(s)
Litotripsia por Láser , Litotricia , Cálculos Ureterales , Humanos , Ureteroscopía , Estudios Prospectivos , Resultado del Tratamiento , Cálculos Ureterales/terapia
19.
Am J Transplant ; 23(7): 1048-1057, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37059177

RESUMEN

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.


Asunto(s)
Trasplante de Corazón , Corazón Auxiliar , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Trasplante de Corazón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología
20.
Plast Reconstr Surg ; 152(5): 987-999, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36877611

RESUMEN

BACKGROUND: Surgical festoon management often entails aggressive dissection, flaps, unsightly scars, prolonged recovery, and high recurrence rates. The authors present outcomes with subjective and objective evaluation of an office-based, novel, minimally invasive (1-cm incision) festoon repair: mini-incision direct festoon access, cauterization, and excision (MIDFACE). METHODS: Charts of 75 consecutive patients from 2007 to 2019 were evaluated. Photographs of 39 patients who met inclusionary criteria were evaluated by three expert physician graders for festoon and incision visibility (339 randomly scrambled preoperative and postoperative photographs taken with and without flash and from four different views: close-up, profile, full-frontal, and worm's eye) using paired t tests and Kruskal-Wallis tests for statistical evaluation. Surveys returned by 37 of 75 patients were evaluated for patient satisfaction and possible contributing factors to festoon formation or exacerbation. RESULTS: There were no major complications in the 75 patients who underwent MIDFACE. Physician grading of photographs of 39 patients (78 eyes, 35 women; four men; mean age, 58 ± 7.7 years) demonstrated statistically significant sustained improvement in festoon score postoperatively up to 12 years regardless of view or flash. Incision scores were the same preoperatively and postoperatively, indicating incisions could not be detected by photography. Average patient satisfaction score was 9.5 on a Likert scale of 0 to 10. Possible factors for festoon formation or exacerbation included genetics (51%), pets (51%), prior hyaluronic acid fillers (54%), neurotoxin (62%), facial surgery (40%), alcohol (49%), allergies (46%), and sun exposure (59%). CONCLUSION: MIDFACE repair results in sustained improvement of festoons with an office-based, minimally invasive procedure with high patient satisfaction, rapid recovery, and low recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Asunto(s)
Disección , Tiroidectomía , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Tiroidectomía/métodos , Cicatriz , Satisfacción del Paciente , Cauterización
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