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OBJECTIVE: To compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases. MATERIALS AND METHODS: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRIspine), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRIWB), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CTWB). Per-patient and per-lesion detection rates were calculated. Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all functional and anatomic imaging served as an imaging comparator. The McNemar test compared detection rates between the scans. Two-sided p values were reported. RESULTS: Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33). Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator. [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 377/382 (98.7%) which was superior compared to [18F]FDG (72.0%, 275/382, p < 0.001), MRIspine (80.6%, 308/382, p < 0.001), MRIWB (55.3%, 136/246, p < 0.001), and CTWB (44.8%, 132/295, p < 0.001). The per-patient detection rate of [68Ga]DOTATATE PET/CT was 41/41 (100%) which was higher compared to [18F]FDG PET/CT (90.2%, 37/41, p = 0.13), MRIspine (97.6%, 40/41, p = 1.00), MRIWB (95.7%, 22/23, p = 1.00), and CTWB (81.8%, 27/33, p = 0.03). CONCLUSIONS: [68Ga]DOTATATE PET/CT should be the modality of choice in PPGL-related spinal bone metastases due to its superior detection rate. CLINICAL RELEVANCE STATEMENT: In a prospective study of 43 pheochromocytoma/paraganglioma participants with spinal bone metastases, [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% (377/382), compared to [18F]FDG PET/CT (p < 0.001), MRI of the spine (p < 0.001), whole-body CT (p < 0.001), and whole-body MRI (p < 0.001). KEY POINTS: ⢠Data regarding head-to-head comparison between functional and anatomic imaging modalities to detect spinal bone metastases in pheochromocytoma/paraganglioma are limited. ⢠[68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with pheochromocytoma/paraganglioma compared to other imaging modalities: [18]F-FDG PET/CT, MRI of the spine, whole-body CT, and whole-body MRI. ⢠[68Ga]DOTATATE PET/CT should be the modality of choice in the evaluation of spinal bone metastases associated with pheochromocytoma/paraganglioma.
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OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Bases de Datos FactualesRESUMEN
OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Cese del Hábito de Fumar , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Complicaciones Posoperatorias/epidemiologíaRESUMEN
OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Estudios Retrospectivos , Pulmón , Neumonectomía/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management.
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OBJECTIVE: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12âmonths and for 12âmonths after explantation. SUMMARY BACKGROUND DATA: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12âmonths. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24âmonths. RESULTS: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12âmonths [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12âmonths (OR 8.3, 95% CI: 1.8-39; Pâ=â.007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
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Diabetes Mellitus Tipo 2/cirugía , Duodeno/cirugía , Derivación Yeyunoileal , Yeyuno/cirugía , Obesidad/cirugía , Adulto , Femenino , Humanos , Derivación Yeyunoileal/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND. Recent professional society guidelines for radionuclide imaging of sporadic pheochromocytoma (PHEO) recommend 18F-fluorodihydroxyphenylala-nine (18F-FDOPA) as the radiotracer of choice, deeming 68Ga-DOTATATE and FDG to be second- and third-line agents, respectively. An additional agent, 18F-fluorodopamine (18F-FDA), remains experimental for PHEO detection. A paucity of research has performed head-to-head comparison among these agents. OBJECTIVE. The purpose of this study was to perform an intraindividual comparison of 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, CT, and MRI in visualization of sporadic primary PHEO. METHODS. This prospective study enrolled patients referred with clinical suspicion for sporadic PHEO. Patients were scheduled for 68Ga-DOTATATE PET/CT, FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, whole-body staging CT (portal venous phase), and MRI within a 3-month period. PET/CT examinations were reviewed by two nuclear medicine physicians, and CT and MRI were reviewed by two radiologists; differences were resolved by consensus. Readers scored lesions in terms of confidence in diagnosis of PHEO (1-5 scale; 4-5 considered positive for PHEO). Lesion-to-liver SUVmax was computed using both readers' measurements. Interreader agreement was assessed using intraclass correlation coefficients (ICCs) for SUVmax. Analysis included only patients with histologically confirmed PHEO on resection. RESULTS. The analysis included 14 patients (eight women, six men; mean age, 52.4 ± 16.8 [SD] years) with PHEO. Both 68Ga-DOTATATE PET/CT and FDG PET/CT were completed in all 14 patients, 18F-FDOPA PET/CT in 11, 18F-FDA PET/CT in 7, CT in 12, and MRI in 12. Mean conspicuity score for PHEO was 5.0 ± 0.0 for 18F-FDOPA PET/CT, 4.7 ± 0.5 for MRI, 4.6 ± 0.8 for 18F-FDA PET/CT, 4.4 ± 1.0 for 68Ga-DOTATATE PET/CT, 4.3 ± 1.0 for CT, and 4.1 ± 1.5 for FDG PET/CT. The positivity rate for PHEO was 100.0% (11/11) for 18F-FDOPA PET/CT, 100.0% (12/12) for MRI, 85.7% (6/7) for 18F-FDA PET/CT, 78.6% (11/14) for FDG PET/CT, 78.6% (11/14) for 68Ga-DOTATATE PET/CT, and 66.7% (8/12) for CT. Lesion-to-liver SUVmax was 10.5 for 18F-FDOPA versus 3.0-4.2 for the other tracers. Interreader agreement across modalities ranged from 85.7% to 100.0% for lesion positivity with ICCs of 0.55-1.00 for SUVmax measurements. CONCLUSION. Findings from this small intraindividual comparative study support 18F-FDOPA PET/CT as a preferred first-line imaging modality in evaluation of sporadic PHEO. CLINICAL IMPACT. This study provides data supporting current guidelines for imaging evaluation of suspected PHEO. TRIAL REGISTRATION. ClinicalTrials.gov NCT00004847.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Imagen por Resonancia Magnética/métodos , Feocromocitoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Glándulas Suprarrenales/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Octreótido/análogos & derivados , Compuestos Organometálicos , Estudios Prospectivos , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: In January 2018, the Centers for Medicare and Medicaid Services removed total knee arthroplasty (TKA) from the Inpatient Only (IPO) list. This study aimed to compare patient-level payments in TKA cases with a length of stay (LOS) <2 midnights before and after removal of TKA from IPO list. METHODS: In this retrospective cohort study, all Medicare patients who received a primary elective TKA from 2016-2019 with a LOS <2 midnights at an academic tertiary center were identified. Total and itemized charges and patient-level payments were compared between eligible TKA cases performed in 2016-2017 and those in 2018-2019. There were 351 eligible TKA cases identified: 151 in 2016-2017 and 200 in 2018-2019. RESULTS: The percentage of patients making any out-of-pocket payment increased in 2018-2019 from 2016-2017 (51.0% versus 10.6%), as did median patient-level payment ($7.30 [range, $0.00-$3,389] versus $0.00 [range, $0.00-$1,248], P < .001 for both). A greater proportion of patients in 2018-2019 paid $1-$50 than in 2016-2017 (37.5% versus 1.3%, P < .001) with no change in the proportion of patients who made payments >$50. Total charges were less in 2018-2019 than in 2016-2017 (P = .001). Charges for drugs, laboratory tests, admissions/floor, and therapies decreased in 2018-2019, whereas charges for the operating room and radiology increased (P < .001 for all). CONCLUSION: Patients receiving outpatient TKA in 2018-2019 were more likely to have out-of-pocket payments than patients with comparable hospital stay who were designated as inpatients, although most of these payments were less than $50.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Anciano , Centers for Medicare and Medicaid Services, U.S. , Humanos , Pacientes Internos , Tiempo de Internación , Medicare , Estudios Retrospectivos , Estados UnidosRESUMEN
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and non-glycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 "tumor enriched" proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.
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Neoplasias de las Glándulas Suprarrenales/genética , Antígenos de Superficie/genética , Glutamato Carboxipeptidasa II/genética , Paraganglioma/genética , Feocromocitoma/genética , Proteoma/genética , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Humanos , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Nanomedicina TeranósticaRESUMEN
The main aim of the research was to synthesize amphiphilic cyclodextrin (AMCD) by substituting C12 alkyl chain to a ß-cyclodextrin (ßCD) in a single step and to study its self-assembly in an aqueous medium. The drug delivery application of the AMCD was also evaluated by encapsulating tamoxifen citrate as a model hydrophobic drug. AMCD was able to self-assemble in aqueous media, forming nanovesicles of size < 200 nm, capable of encapsulating tamoxifen citrate (TMX). Molecular docking and MD simulation studies revealed the interaction between TMX and AMCD which formed a stable complex. TEM and AFM studies showed that nanovesicles were perfectly spherical having a smooth surface and a theoretical AMCD bilayer thickness of ~ 7.2 nm as observed from SANS studies. XRD and DSC studies revealed that TMX was amorphized and molecularly dispersed in AMCD bilayer which was released slowly following Fickian diffusion. AMCD has excellent hemocompatibility as opposed to ßCD and no genotoxicity. IC50 of TMX against MCF-7 cell lines was significantly reduced from 11.43 to 7.96 µg/ml after encapsulation in nanovesicle because of nanovesicles being endocytosed by the MCF-7 cells. AMCD was well tolerated by IV route at a dose of > 2000 mg/kg in rats. Pharmacokinetic profile of TMX after encapsulation was improved giving 3-fold higher AUC; extended mean residence time is improving chances of nanovesicle to extravasate in tumor via EPR effect.
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Ciclodextrinas/administración & dosificación , Ciclodextrinas/síntesis química , Sistemas de Liberación de Medicamentos/métodos , Tamoxifeno/administración & dosificación , Tamoxifeno/síntesis química , Administración Oral , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células MCF-7 , Masculino , Ratones , Simulación del Acoplamiento Molecular/métodos , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Intradural transection of the filum terminale (FTI) is often used to treat tethered cord syndrome. Recently, some have proposed that the extradural part of the filum terminale (FTE) can be sectioned with equal results but with fewer complications. Therefore, the present cadaveric study aimed to evaluate the anatomical foundation of such procedures. METHODS: A posterior lumbosacral approach was performed on five fresh-frozen cadaveric specimens to expose both the FTI and FTE. Tension was then applied to the FTE and observations and measurements made of any movement of the FTI. Other morphological measurements (e.g., length, diameter) of the FTI and FTE were also made. RESULTS: Although very minimal movement of the FTI was seen in the majority of specimens following tension on the FTE, no specimen was found to have more cranial movement of the conus medullaris or cauda equina. The mean length and diameter of the FTI was 52.2 and 0.38 mm, respectively. The mean length and diameter of the FTE was 77 and 0.60 mm, respectively. The force necessary to move the FTI with tension applied to the FTE had a mean of 0.03 N. The average distance that the FTI moved with distal FTE tension was 1.33 mm. All specimens had a thecal sac that terminated at the S2 vertebral level. And no specimen had a low-lying conus medullaris, cutaneous stigmata of occult spinal dysraphism, or grossly visible adipose tissue in either the FTI or FTE. CONCLUSIONS: Based on our studies, tension placed on the FTE has very little effect on the FTI and no obvious effect on the conus medullaris or cauda equina. Therefore, isolated transection of the FTE for a patient with tethered cord syndrome is unlikely to have significant effect. To our knowledge, this is the first study to quantitate the distal forces needed on the FTE to move the FTI.
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Cauda Equina/patología , Cauda Equina/cirugía , Defectos del Tubo Neural/patología , Defectos del Tubo Neural/cirugía , Médula Espinal/patología , Médula Espinal/cirugía , Anciano , Cadáver , Femenino , Humanos , Región Lumbosacra/patología , Región Lumbosacra/cirugía , Masculino , Persona de Mediana EdadRESUMEN
The inferior gluteal nerve has been traditionally described as a solely motor branch innervating the gluteus maximus. However, during routine dissection of the gluteal region, a cutaneous branch of the inferior gluteal nerve was identified. As the gluteal region is vulnerable to the development of pressure ulcers and iatrogenic injury with for example, surgical approaches and injection therapies, a comprehensive understanding of its cutaneous innervation is important. Therefore, the aim of this study was to elucidate the anatomy of this cutaneous branch of the inferior gluteal nerve in a series of cadavers. Twelve sides from six fresh-frozen cadaveric specimens were dissected. When a cutaneous branch was identified piercing the gluteus maximus, its origin from the inferior gluteal nerve was verified and the diameter and length of it measured. Additionally, for localization, the distance from the midline to the exit point of the cutaneous branch from the gluteus maximus was measured. One to two cutaneous branches were identified as arising from the inferior gluteal nerve on nine sides (75%). The branch(es) were usually located in the lower outer quadrant of the gluteus maximus. These branches had a mean distance of 12.5 cm from the midline. Their mean diameter and length was 0.7 mm and 28.6 cm, respectively. On all sides with a cutaneous branch of the inferior gluteal nerve, the skin over the posterior aspect of the greater trochanter was innervated by superior and inferior cluneal nerves and supplemented by cutaneous branch(es) of the inferior gluteal nerve. Side or sex was not a predictor of the presence of a cutaneous branch of the inferior gluteal nerve. To our knowledge, a cutaneous branch derived from the inferior gluteal nerve has not been previously described. Based on our cadaveric findings, the majority of individuals will have the area of skin over the greater trochanter innervated by this nerve. Therefore, surgeons and pain specialists should be aware of its presence and might develop surgical procedures that help avoid it or develop technical advances that target it for various pain syndromes in this area. We propose naming these cutaneous branches the lateral cluneal nerves, which would necessitate renaming the middle cluneal nerves to medial cluneal nerves. Clin. Anat. 31:937-941, 2018. © 2018 Wiley Periodicals, Inc.
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Plexo Lumbosacro/anatomía & histología , Músculo Esquelético/inervación , Nalgas/anatomía & histología , Nalgas/inervación , Cadáver , Disección , Articulación de la Cadera/cirugía , Humanos , Músculo Esquelético/anatomía & histología , Dolor Postoperatorio/prevención & control , Traumatismos de los Nervios Periféricos/prevención & controlRESUMEN
Demyelinating disorders are very common, but remains isolated to the part of nervous system they involve. However, infrequently, combined involvement of central and peripheral nervous system with demyelinating process have been described. We report one such rare case, with possible theories of common etiological basis. We present a middle aged male patient with Chronic Inflammatory Demyelinating Polyneuropathy(CIDP), who responded to immuno-modulation. Subsequently, he developed Acute Transverse Myelitis (ATM). Recently a common substrate protein, NF186 has been described as responsible for this rare clinical entity.
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Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades Desmielinizantes/complicaciones , Enfermedades del Sistema Nervioso Periférico/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Unlike general surgery patients, most of vascular and cardiac surgery patients receive therapeutic anticoagulation during operations. The purpose of this study was to report the incidence of deep venous thrombosis (DVT) among cardiac and vascular surgery patients, compared with general surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent surgical procedures from 2005 to 2010. Patients who developed DVT within 30 days of an operation were identified. The incidence of DVT was compared among vascular, general, and cardiac surgery patients. Risk factors for developing postoperative DVT were identified and compared among these patients. RESULTS: Of total 2,669,772 patients underwent surgical operations in the period between 2005 and 2010. Of all the patients, 18,670 patients (0.69%) developed DVT. The incidence of DVT among different surgical specialties was cardiac surgery (2%), vascular surgery (0.99%), and general surgery (0.66%). The odds ratio for developing DVT was 1.5 for vascular surgery patients and 3 for cardiac surgery patients, when compared with general surgery patients (P < 0.001). The odds ratio for developing DVT after cardiac surgery was 2, when compared with vascular surgery (P < 0.001). CONCLUSIONS: The incidence of DVT is higher among vascular and cardiac surgery patients as compared with that of general surgery patients. Intraoperative anticoagulation does not prevent the occurrence of DVT in the postoperative period. These patients should receive DVT prophylaxis in the perioperative period, similar to other surgical patients according to evidence-based guidelines.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Trombosis de la Vena/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Distribución de Chi-Cuadrado , Comorbilidad , Bases de Datos Factuales , Esquema de Medicación , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/prevención & control , Adulto JovenRESUMEN
Friedreich's ataxia (FRDA) is a common hereditary degenerative neuro-muscular disorder caused by expansions of the (GAA)n repeat in the first intron of the frataxin gene. The expanded repeats from parents frequently undergo further significant length changes as they are passed on to progeny. Expanded repeats also show an age-dependent instability in somatic cells, albeit on a smaller scale than during intergenerational transmissions. Here we studied the effects of (GAA)n repeats of varying lengths and orientations on the episomal DNA replication in mammalian cells. We have recently shown that the very first round of the transfected DNA replication occurs in the lack of the mature chromatin, does not depend on the episomal replication origin and initiates at multiple single-stranded regions of plasmid DNA. We now found that expanded GAA repeats severely block this first replication round post plasmid transfection, while the subsequent replication cycles are only mildly affected. The fact that GAA repeats affect various replication modes in a different way might shed light on their differential expansions characteristic for FRDA.
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Replicación del ADN , Ataxia de Friedreich/genética , Proteínas de Unión a Hierro/genética , Expansión de Repetición de Trinucleótido , Animales , Células COS , Línea Celular , Chlorocebus aethiops , ADN/química , Herpesvirus Humano 4/genética , Humanos , Plásmidos/genética , Origen de Réplica , Virus 40 de los Simios/genética , FrataxinaRESUMEN
Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors which have the potential to metastasize. For the management of patients with PPGLs, CT is the preferred modality of choice for precise localization and estimation of their progression. However, due to the myriad variations in size, morphology, and appearance of the tumors in different anatomical regions, radiologists are posed with the challenge of accurate detection of PPGLs. Since clinicians also need to routinely measure their size and track their changes over time across patient visits, manual demarcation of PPGLs is quite a time-consuming and cumbersome process. To ameliorate the manual effort spent for this task, we propose an automated method to detect PPGLs in CT studies via a proxy segmentation task. As only weak annotations for PPGLs in the form of prospectively marked 2D bounding boxes on an axial slice were available, we extended these 2D boxes into weak 3D annotations and trained a 3D full-resolution nnUNet model to directly segment PPGLs. We evaluated our approach on a dataset consisting of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. We obtained a precision of 70% and sensitivity of 64.1% with our proposed approach when tested on 53 CT studies. Our findings highlight the promising nature of detecting PPGLs via segmentation, and furthers the state-of-the-art in this exciting yet challenging area of rare cancer management.
RESUMEN
Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors that have metastatic potential. Management of patients with PPGLs mainly depends on the makeup of their genetic cluster: SDHx, VHL/EPAS1, kinase, and sporadic. CT is the preferred modality for precise localization of PPGLs, such that their metastatic progression can be assessed. However, the variable size, morphology, and appearance of these tumors in different anatomical regions can pose challenges for radiologists. Since radiologists must routinely track changes across patient visits, manual annotation of PPGLs is quite time-consuming and cumbersome to do across all axial slices in a CT volume. As such, PPGLs are only weakly annotated on axial slices by radiologists in the form of RECIST measurements. To ameliorate the manual effort spent by radiologists, we propose a method for the automated detection of PPGLs in CT via a proxy segmentation task. Weak 3D annotations (derived from 2D bounding boxes) were used to train both 2D and 3D nnUNet models to detect PPGLs via segmentation. We evaluated our approaches on an in-house dataset comprised of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. On a test set of 53 CT volumes, our 3D nnUNet model achieved a detection precision of 70% and sensitivity of 64.1%, and outperformed the 2D model that obtained a precision of 52.7% and sensitivity of 27.5% (p< 0.05). SDHx and sporadic genetic clusters achieved the highest precisions of 73.1% and 72.7% respectively. Our state-of-the art findings highlight the promising nature of the challenging task of automated PPGL detection.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Tomografía Computarizada por Rayos X , Humanos , Feocromocitoma/diagnóstico por imagen , Paraganglioma/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodosRESUMEN
OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Dibenzodioxinas Policloradas , Veteranos , Adulto , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Agente Naranja , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/análisis , Estudios Retrospectivos , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4,5-Triclorofenoxiacético/análisis , Dibenzodioxinas Policloradas/efectos adversos , Dibenzodioxinas Policloradas/análisis , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/epidemiologíaRESUMEN
BACKGROUND: Lung cancer screening guidelines were introduced in the United States in 2013, with variable implementation. This study aimed to evaluate temporal diagnostic trends in non-small cell lung cancer (NSCLC) diagnosis since the introduction of these guidelines. METHODS: This retrospective cohort analysis used the VA Corporate Data Warehouse and the National Cancer Database. We evaluated temporal trends in the distribution of NSCLC stage at the time of diagnosis, including differences based on insurance coverage type (including uninsured, privately insured, Medicare, Medicaid, and VA coverage) with adjustment for clinically relevant variables. RESULTS: Among 1,450,965 patients diagnosed from 2006-2020, the proportion of NSCLC cases diagnosed at Stage I increased in all insurance groups (by 12.74%, 2%, 0.25%, and 2.57% for the VA, Medicare, Private Insurance, and Medicaid, respectively). If all insurance systems achieved the unadjusted stage distribution seen in the Veterans Health Administration, an additional 45,684 patients would be diagnosed with Stage I NSCLC and 65,933 fewer patients would be diagnosed with stage IV disease. CONCLUSIONS: For patients with any form of insurance, there has been an increase in the proportion of early-stage NSCLC (Stage I and II) and a corresponding decrease in the proportion of Stage III and IV since the introduction of national lung cancer screening guidelines. As the largest integrated "single-payer" healthcare system in the US, the VA dramatically outperforms other insurance types, perhaps attributable to universal coverage and robust lung cancer screening programs.