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1.
J Surg Res ; 298: 201-208, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626717

RESUMO

INTRODUCTION: Adrenalectomy generally has favorable outcomes. It is unknown if patients with functional adrenal tumors experience different clinical outcomes than those with benign adrenal tumors, due to the presence of comorbid conditions secondary to the functional tumor. We investigated outcomes following open and laparoscopic adrenalectomy for benign nonfunctional (BNF) versus functional adrenal masses. METHODS: Patients undergoing adrenalectomy were identified in the 2015-2020 National Surgical Quality Improvement Program database, then categorized as BNF, hyperaldosteronism, hypercortisolism, and pheochromocytoma. The primary outcome of interest was 30-d morbidity and secondary outcomes included 30-d mortality, 30-d readmission, and postoperative length of stay (LOS). Subgroup analysis was performed based upon surgical approach. Univariate analysis was performed, followed by multivariable logistic regression for individual outcomes that differed significantly between patients with BNF and functional neoplasm, factoring in patient demographics and operative approach with statistical significance on univariate analysis. Descriptive statistics and outcomes were analyzed using Pearson's χ2 test and Mann-Whitney U-test as appropriate. RESULTS: There were 3291 patients with BNF while 484 had hyperaldosteronism, 263 hypercortisolism, and 46 pheochromocytomas. Within the laparoscopic group of 3615 (88.5%) of adrenalectomy patients, compared to BNF patients, patients with hyperaldosteronism had lower rates of postoperative morbidity (1.9% versus 5.2%, P < 0.001) and shorter LOS (1 d, interquartile range (IQR) [1-1] versus 1d IQR [1-2], P = 0.003); these persisted on multivariate analysis (OR 0.32, 95% confidence interval [CI] 0.14-0.74 and odds ratio 0.47, 95% CI 0.36-0.60, P < 0.001). Patients with hypercortisolism had higher morbidity (7.3% versus 5.2%, P < 0.001), 30-d readmission rates (5.3% versus 2.9%, P = 0.042) and longer LOS (2d, IQR [1-3] versus 1d, IQR [1-2, P < 0.001). On multivariate analysis, presence of hypercortisolism was independently associated with increased likelihood of readmission within 30 d (OR 2.20, 95% CI 1.11-2.99, P = 0.012) and longer LOS (>1 d) (OR 1.79, 95% CI 1.33-2.40, P < 0.001). Compared to BNF patients, patients with pheochromocytoma had higher rates of postoperative morbidity (6.2% versus 5.2%, P < 0.001). Within the open group of 469 (11.5% of adrenalectomy patients), there were no statistically significant differences in outcomes between patients with BNF and functional adrenal masses. CONCLUSIONS: Outcomes after adrenalectomy performed for functional neoplasms differ based on surgical indication.

2.
J Surg Res ; 296: 556-562, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340489

RESUMO

INTRODUCTION: The risk of adverse outcomes after adrenal metastasectomy is not well defined. Knowledge of these risks is essential to guide patient counseling. METHODS: The 2015-2020 National Surgical Quality Improvement Program datasets were combined. Patients who underwent adrenalectomy for secondary adrenal malignancy (SM) and benign nonfunctional (BNF) adrenal neoplasms were identified; BNF neoplasms were chosen as a comparison as functional neoplasms can contribute to comorbidity. Patients who had additional surgery at the time of adrenalectomy were excluded. Patient demographics, comorbidities, perioperative factors, and outcomes were compared between groups. Multivariable logistic regression analysis was performed. RESULTS: Of 3496 adrenalectomy patients, 332 had SM and 3164 had BNF neoplasms. Patients with SM were older (65 versus 54 y) and more often had chronic obstructive pulmonary disease (7.5% versus 4.4%), chronic steroid use (10.5% versus 3.8%), and bleeding disorders (4.5% versus 2.2%) than patients with BNF, respectively (P < 0.01 for all). Laparoscopic adrenalectomy was the most common operative approach for both groups (74.7% versus 88.3%). Rates of mortality, morbidity, reoperation, readmission, and nonhome discharge did not differ significantly between groups. Patients with SM had higher rates of postoperative bleeding than patients with BNF (6.3% versus 2.6%, P < 0.001). This persisted on multivariable regression analysis that adjusted for demographics, comorbidities, and operative approach (odds ratio 2.34, 95% confidence interval 1.19-4.64). CONCLUSIONS: Adrenalectomy for SM is associated with an increased risk of postoperative bleeding compared to adrenalectomy for BNF adrenal neoplasms. Patients with SM that meet criteria for adrenal metastasectomy should be counseled appropriately.


Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Adrenalectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Comorbidade , Morbidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Operatória/etiologia , Laparoscopia/efeitos adversos
3.
Membranes (Basel) ; 14(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38392674

RESUMO

Differential scanning calorimetry (DSC) was used to explore the interactions of isolated polyphenolic compounds, including (-)-epigallocatechin gallate ((-)-EGCg), tellimagrandins I and II (Tel-I and Tel-II), and 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG), with a model Gram-negative bacterial membrane with a view to investigating their antimicrobial properties. The model membranes comprised 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), fabricated to mimic the domain formation observed in natural membranes, as well as ideally mixed lipid vesicles for the interaction with (-)-EGCg. Polyphenols induced changes in lipid mixing/de-mixing depending on the method of vesicle preparation, as was clearly evidenced by alterations in the lipid transition temperatures. There was a distinct affinity of the polyphenols for the DPPG lipid component, which was attributed to the electrostatic interactions between the polyphenolic galloyl moieties and the lipid headgroups. These interactions were found to operate through either the stabilization of the lipid headgroups by the polyphenols or the insertion of the polyphenols into the membrane itself. Structural attributes of the polyphenols, including the number of galloyl groups, the hydrophobicity quantified by partition coefficients (logP), and structural flexibility, exhibited a correlation with the temperature transitions observed in the DSC measurements. This study furthers our understanding of the intricate interplay between the structural features of polyphenolic compounds and their interactions with model bacterial membrane vesicles towards the exploitation of polyphenols as antimicrobials.

4.
Alzheimers Dement ; 20(3): 2128-2142, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38248636

RESUMO

INTRODUCTION: We aimed to investigate associations between common infections and neuroimaging markers of dementia risk (brain volume, hippocampal volume, white matter lesions) across three population-based studies. METHODS: We tested associations between serology measures (pathogen serostatus, cumulative burden, continuous antibody responses) and outcomes using linear regression, including adjustments for total intracranial volume and scanner/clinic information (basic model), age, sex, ethnicity, education, socioeconomic position, alcohol, body mass index, and smoking (fully adjusted model). Interactions between serology measures and apolipoprotein E (APOE) genotype were tested. Findings were meta-analyzed across cohorts (Nmain  = 2632; NAPOE-interaction  = 1810). RESULTS: Seropositivity to John Cunningham virus associated with smaller brain volumes in basic models (ß = -3.89 mL [-5.81, -1.97], Padjusted  < 0.05); these were largely attenuated in fully adjusted models (ß = -1.59 mL [-3.55, 0.36], P = 0.11). No other relationships were robust to multiple testing corrections and sensitivity analyses, but several suggestive associations were observed. DISCUSSION: We did not find clear evidence for relationships between common infections and markers of dementia risk. Some suggestive findings warrant testing for replication.


Assuntos
Demência , Neuroimagem , Humanos , Estudos de Coortes , Demência/diagnóstico por imagem , Demência/epidemiologia , Demência/genética , Apolipoproteínas E/genética , Reino Unido/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
5.
J Vasc Surg ; 79(2): 412-417, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37952782

RESUMO

BACKGROUND: Practice consolidation by vertical and horizontal integration is a growing trend in surgery. Practice consolidation has not been previously examined in vascular surgery. METHODS: The Medicare Provider Enrollment, Chain, and Ownership System data were used to identify vascular providers and vascular surgery practices in the United States in 2015 and 2020. Practices were categorized as solo (1 surgeon), small (2), medium (3-5), and large (≥6). The number of providers and the number of practices in each size group were determined. The Hirfendahl-Hirshman index (HHI), a measure of market consolidation, was calculated. Provider count, practice size, and HHI were additionally analyzed by urban and rural regions. All values were calculated for each time point and compared. RESULTS: Vascular providers increased in number from 2929 to 3154 (7.7%) from 2015 to 2020. The number of practices decreased from 1351 to 1090 (19.3%). The number of large practices increased by 49.4%; the number of small or solo practices decreased by 42.1%. The mean HHI increased from 0.486 in 2015 to 0.498 in 2020. Both urban and rural regions had a decrease in solo practices (43.3% and 2.3%, respectively) and an increase in HHI (from 0.499 to 0.509 and 0.793 to 0.818, respectively). All changes were statistically significant. CONCLUSIONS: From 2015 to 2020, there is a trend toward vascular providers working in larger practice groups and a corresponding increase in measures of market consolidation.


Assuntos
Medicare , Procedimentos Cirúrgicos Vasculares , Idoso , Humanos , Estados Unidos
6.
Am J Surg ; 229: 111-115, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38065724

RESUMO

INTRODUCTION: Most adrenal incidentalomas are not appropriately evaluated. Reporting the mass in the radiology report summary and providing recommendations in the report can positively impact evaluation. This study evaluated the effect of reporting Hounsfield units(HU) on adrenal incidentaloma follow-up. METHODS: Patients with adrenal incidentalomas identified on noncontrast CT scan from 2015 to 2020 â€‹at a tertiary care institution were studied. Chart review was conducted. Patient and imaging characteristics were compared between patients who did and did not have HU reported. Outcomes of interest were 1)outpatient referral, 2)biochemical evaluation, and 3)dedicated imaging if appropriate. Multivariate analysis determined the impact of HU, reporting in the summary and provision of recommendations on the outcomes. RESULTS: 363 patients were studied, 36(9.9 â€‹%) had HU reported. When HU were used in addition to recommendations and reporting in the summary, the likelihood of outpatient referral increased from 10.1 to 32.6-fold (95%CI 7.7-138.1, p â€‹< â€‹0.001). Similarly, the likelihood of biochemical workup increased from 2.5 to 7.8-fold (95%CI 2.5-24.1, p â€‹< â€‹0.001). CONCLUSION: Recording adrenal incidentaloma HU on non-contrast CT scans was associated with increased rates of outpatient referral and biochemical workup.


Assuntos
Neoplasias das Glândulas Suprarrenais , Humanos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
7.
Prostate ; 84(3): 292-302, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37964482

RESUMO

BACKGROUND: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting. METHODS: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients. Five thousand patients will be screened through an online at-home germline testing to identify and enroll 500 patients with germline mutations, including: pathogenic or likely pathogenic variants and variants of uncertain significance in genes of interest. Patients will be followed for 15 years and clinical data with real time patient reported outcomes will be collected. Eligible patients will enter long-term follow-up (6-month PRO surveys and medical record retrieval). As a virtual study with patient self-enrollment, the PROMISE Registry may fill gaps in genetics services in underserved areas and for patients within sufficient insurance coverage. RESULTS: The PROMISE Registry opened in May 2021. 2114 patients have enrolled to date across 48 US states and 23 recruiting sites. 202 patients have met criteria for long-term follow-up. PROMISE is on target with the study's goal of 5000 patients screened and 500 patients eligible for long-term follow-up by 2026. CONCLUSIONS: The PROMISE Registry is a novel, prospective, germline registry that will collect long-term patient outcomes data to address current gaps in understanding resulting from recently FDA-approved treatments and updates to genetic testing recommendations for prostate cancer. Through inclusion of a broad nationwide sample, including underserved patients and those unaffiliated with major academic centers, the PROMISE Registry aims to provide access to germline genetic testing and to collect data to understand disease characteristics and treatment responses across the disease spectrum for prostate cancer with rare germline genetic variants.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias da Próstata , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Resultado do Tratamento , Sistema de Registros
8.
Pediatr Dev Pathol ; 27(3): 260-265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38098239

RESUMO

Wilms tumor (WT) is the commonest cause of renal cancer in children. In Europe, a diagnosis is made for most cases on typical clinical and radiological findings, prior to pre-operative chemotherapy. Here, we describe a case of a young boy presenting with a large abdominal tumor, associated with raised serum alpha-fetoprotein (AFP) levels at diagnosis. Given the atypical features present, a biopsy was taken, and histology was consistent with WT, showing triphasic WT, with epithelial, stromal, and blastemal elements present, and positive WT1 and CD56 immunohistochemical staining. During pre-operative chemotherapy, serial serum AFP measurements showed further increases, despite a radiological response, before a subsequent fall to normal following nephrectomy. The resection specimen was comprised of ~55% and ~45% stromal and epithelial elements, respectively, with no anaplasia, but immunohistochemistry using AFP staining revealed positive mucinous intestinal epithelium, consistent with the serum AFP observations. The lack of correlation between tumor response and serum AFP levels in this case highlights a more general clinical unmet need to identify WT-specific circulating tumor markers.


Assuntos
Biomarcadores Tumorais , Neoplasias Renais , Tumor de Wilms , alfa-Fetoproteínas , Humanos , Tumor de Wilms/diagnóstico , Tumor de Wilms/patologia , Tumor de Wilms/sangue , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Masculino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/sangue , Nefrectomia
9.
Cancer Res Commun ; 4(1): 55-64, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38108490

RESUMO

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales. SIGNIFICANCE: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals.


Assuntos
Dor do Câncer , Neoplasias da Próstata , Humanos , Masculino , Negro ou Afro-Americano , Estudos Prospectivos , Neoplasias da Próstata/complicações , Qualidade de Vida , Estados Unidos/epidemiologia , Brancos , Taxa de Sobrevida
10.
Phys Med ; 116: 103169, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37989042

RESUMO

PURPOSE: This study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6-24 months after radiotherapy for oropharynx cancer. METHODS: The treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. RESULTS: Xerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58-0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. CONCLUSIONS: Based on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2-3 the risk for radiation induced xerostomia that is observed at 6-24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6-24 months post-RT by 2.0-2.3 times.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Dosagem Radioterapêutica , Xerostomia/etiologia , Xerostomia/diagnóstico , Xerostomia/patologia , Neoplasias Orofaríngeas/radioterapia , Glândula Parótida , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias de Cabeça e Pescoço/complicações , Probabilidade
11.
Endocrinol Metab Clin North Am ; 52(4): 689-703, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37865482

RESUMO

The significant volume-outcome relationship has triggered interest in improving quality of care by directing patients to high-volume centers and surgeons. However, significant disparities exist for different racial/ethnic, geographic, and socioeconomic groups for thyroid, parathyroid, adrenal, and pancreatic neuroendocrine surgical diseases disease.


Assuntos
Cirurgiões , Glândula Tireoide , Humanos , Estados Unidos
12.
J Surg Res ; 291: 527-535, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37540970

RESUMO

INTRODUCTION: Surgical residents make decisions that may have a dramatic impact on career earnings based off conceptions regarding future income potential. This study examines the effect of debt burden, repayment plan, and practice setting on a general surgeon's career value. METHODS: Debt levels, repayment plans, and practice setting were considered to model a surgeon's career value using net present value (NPV) across 35 scenarios. The NPV was calculated using salary, education debt, yearly spending, and a discount rate of 5%. Salary data were obtained from the Medical Group Management Association, student debt information from the Association of American Medical Colleges, and tax and household spending data from U.S. government records. Assumptions included no gaps in training, no prior debt, single-person household, and career duration of 35 y. RESULTS: A general surgeon's salary adequately repays debt burdens from $100,000-$300,000 over 10-25 y, regardless of repayment plan or practice setting. Practice setting decreased career value for academic surgeons when debt burden and repayment plan were held constant: the NPV for an academic surgeon was $382,000 compared to $500,000 for a nonacademic surgeon with the same debt and repayment plan. Debt burden repaid through unsubsidized and income-based repayment plans reduced NPV for all surgeons, while subsidized plans increased NPV. The projected NPV for all scenarios ranged $2.35M-$2.87 M. CONCLUSIONS: Though the modeled scenarios do not account for prior debt burden, major expenditures, or increases in yearly household spending beyond national averages, surgery residents should be aware that general surgery remains a financially feasible career.


Assuntos
Internato e Residência , Cirurgiões , Humanos , Escolha da Profissão , Renda , Salários e Benefícios
13.
Am J Surg ; 226(5): 652-659, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37453804

RESUMO

BACKGROUND: Racial disparities in care exist for diseases with heterogeneous treatment guidelines. The impact of these disparities on outcomes after parathyroidectomy for secondary(2HPT) and tertiary hyperparathyroidism(3HPT) was explored. METHODS: The 2015-2019 NSQIP datasets were used. Patients who underwent parathyroidectomy for 2HPT and 3HPT were identified and analyzed separately. Patients were stratified by race (white vs. non-white); demographics, comorbidities, and outcomes were compared. Studied outcomes included 30-day morbidity, mortality, unplanned reoperation, readmission, and postoperative length of stay(LOS). RESULTS: There were 1,150 patients with 2HPT and 262 with 3HPT. For 2HPT, 65.5% were non-white; morbidity, reoperation, and prolonged LOS(>3days) occurred disproportionately more often in non-white patients. Non-white race was independently associated with morbidity; higher ASA class and alkaline phosphatase levels were associated with prolonged LOS. For 3HPT, 53.1% were non-white; a prolonged LOS(>1day) occurred disproportionately more often in non-white patients. Higher alkaline phosphatase levels were independently associated with prolonged LOS. CONCLUSION: Race and markers of advanced disease negatively impact outcomes after parathyroidectomy for 2HPT and 3HPT. Attention to racial disparities and earlier referral may positively impact outcomes.


Assuntos
Hiperparatireoidismo Secundário , Hiperparatireoidismo , Humanos , Paratireoidectomia , Fosfatase Alcalina , Hiperparatireoidismo/cirurgia , Morbidade , Reoperação , Hiperparatireoidismo Secundário/cirurgia , Estudos Retrospectivos
14.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37497183

RESUMO

Goldenhar Syndrome is a rare congenital disorder characterized by hemifacial microsomia. Although select mutations have been mapped for this disorder, the genetic etiologies in the majority of cases remain unknown. A recent clinical report of a Goldenhar Syndrome patient identified a homozygous missense mutation in FRK , a gene associated with various types of cancer. In this work, we precisely modeled the disease-associated missense mutation in the C. elegans FRK ortholog src-2 , using CRISPR/Cas9 gene editing, and investigated the physiological role of this mutation and the src-2 gene. In addition, we generated a conserved variant in src-1 ( FYN ortholog) to assess the functional redundancy of the conserved variant. The putative pathogenic variants src-1 (Val190Ile) or src-2 (Val170Ile) caused only subtle phenotypes, suggesting that these mutations alone are not sufficient to explain the facial deformities observed in the Goldenhar Syndrome patient. However, the src-2 (Val170Ile) mutant exhibited reduced brood size and moderately enhanced embryonic developmental phenotypes, including epidermal and neuronal patterning defects, in the src-1 (RNAi) condition, indicating that the src-2 (Val170Ile) locus could play a supportive role during developmental processes. Overall, however, these studies showed that src-1 /FYN is essential for regulating embryogenesis and morphogenesis, while src-2 /FRK is largely dispensable for normal embryonic development, suggesting FYN , not FRK , is the dominant non-receptor protein kinase during embryonic development in C. elegans .

15.
Molecules ; 28(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37446937

RESUMO

Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic resistance. While tannins have been shown to exhibit these activities on their own, one approach would be to use them as complementary nutrients alongside commercial anthelmintics. So far, research on the interactions between tannins and anthelmintics is limited, and few studies have reported both synergistic and antagonistic effects depending on the type of tannin and the method used. These interactions could either strengthen or weaken the efficacy of commercial anthelmintics, especially if tannin-rich diets are combined with anthelmintics used as oral drenches. To study these interactions, a series of hydrolysable tannins (HTs) was selected, and their direct interactions with thiabendazole (TBZ) were evaluated by isothermal titration calorimetry (ITC), which allowed the detection of the exothermic interaction but also the roles and significances of different structural features of HTs in these interactions. Our results show that HTs can have a direct interaction with the benzimidazole anthelmintic TBZ and that the interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of HTs.


Assuntos
Anti-Helmínticos , Taninos , Taninos/farmacologia , Taninos/química , Anti-Helmínticos/química , Extratos Vegetais/química , Taninos Hidrolisáveis , Tiabendazol , Calorimetria/métodos
16.
Surgery ; 174(4): 819-827, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460336

RESUMO

BACKGROUND: Adrenalectomy is well tolerated with low complication rates. It is unclear if these excellent outcomes are consistent across all age groups. METHODS: The 2015-2020 American College of Surgeons National Surgical Quality Improvement Program datasets were used. Patients who underwent adrenalectomy were identified and grouped based on age: ≤60, 61 to 70, 71 to 80, and >80 years. Patient characteristics, surgical indications, operative characteristics, and postoperative outcomes were compared between age groups. Primary outcome measures were mortality, morbidity, postoperative length of stay, non-home discharge, and unplanned readmission. Multivariable logistic regression analysis was performed. RESULTS: Adrenalectomy was performed on 6,114 patients. Younger patients more frequently had surgery for non-functional benign neoplasms compared with older (55.7% vs 52.8% vs 45.9% vs 45.3%, for patients ≤60, 61 to 70, 71 to 80, and >80 years, respectively, P < .001), and less frequently had surgery for malignancy (8.8% vs 14.4% vs 22.5% vs 24.5%, P < .001). The median length of stay for patients ≤60 was 1 day compared with 2 days for patients 61-70, 71-80, and >80 (P < .001). The overall mortality rate was <1% and did not differ based on age (P = .18). Morbidity occurred less frequently in the younger age groups (7.3% vs 8.9% vs 11.2% vs 16.0%, P < .001) compared with older. Similar trends were seen for non-home discharge (1.4% vs 2.5% vs 4.8% vs 17.0%, P < .001). On multivariable analysis, patients aged >80 had a 2-fold increased likelihood of morbidity and a 9-fold increased likelihood of non-home discharge compared to patients aged ≤60. CONCLUSION: Older age is associated with morbidity and non-home discharge after adrenalectomy. Knowledge of these risks is critical when counseling an aging surgical population.


Assuntos
Adrenalectomia , Neoplasias Encefálicas , Humanos , Idoso , Idoso de 80 Anos ou mais , Adrenalectomia/efeitos adversos , Morbidade , Fatores de Risco , Envelhecimento , Readmissão do Paciente , Neoplasias Encefálicas/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação , Estudos Retrospectivos
17.
Med Clin North Am ; 107(2): 371-384, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36759103

RESUMO

Gender identity is a deeply felt internal sense of self, which may correspond (cisgender) or not correspond (transgender) with the person's assigned sex at birth. Transgender, nonbinary, and gender diverse people may choose to affirm their gender in any number of ways including medical gender affirmation. This is a primer on the medical care of transgender individuals which covers an introduction to understanding a common language, history of transgender medical care, creating a welcoming environment, hormone therapy, surgical therapies, fertility considerations, and cancer screening in transgender people.


Assuntos
Pessoas Transgênero , Recém-Nascido , Humanos , Masculino , Feminino , Identidade de Gênero
18.
JCO Glob Oncol ; 8: e2200154, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36332173

RESUMO

PURPOSE: To describe a newly established international registry recruiting diverse patients with advanced prostate cancer across academic and community practices to address unmet needs in this population. PATIENTS AND METHODS: Initiated in 2017, IRONMAN (International Registry for Men with Advanced Prostate Cancer) is a prospective cohort of patients with advanced prostate cancer. The study will enroll 5,000 patients with metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC), recruited from Australia, the Bahamas, Barbados, Brazil, Canada, Ireland, Jamaica, Kenya, Nigeria, Norway, South Africa, Spain, Sweden, Switzerland, the United Kingdom, and the United States. The study is collecting datatypes to study variation in care and treatment of advanced prostate cancer across countries and across academic, community-based, and government practices with a focus on clinical outcomes, patient-reported outcomes, epidemiologic data, biologic subtypes, and clinician questionnaires. RESULTS: Through July 2022, 2,682 eligible patients were enrolled in 11 of 12 active countries. Sixty-six percent of patients have mHSPC, and 34% have CRPC. On the basis of self-report, 11% of patients are Black and 9% are Hispanic. Five Veterans Affairs Medical Centers are enrolling patients. Globally, 23% of patients report being veterans of military service. CONCLUSION: To our knowledge, this is the first international cohort of people newly diagnosed with advanced prostate cancer designed to describe variations in patient management, experiences, and outcomes. IRONMAN aims to identify optimal treatment sequences to improve survival, understand patient-reported outcomes, and explore novel biomarkers to understand treatment resistance mechanisms. Insights from IRONMAN will inform and guide future clinical management of people with mHSPC and CRPC. This cohort study will provide real-world evidence to facilitate a better understanding of the survivorship of people with advanced prostate cancer.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos de Coortes , Estudos Prospectivos , Sistema de Registros , Espanha
19.
J Surg Res ; 280: 501-509, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36081309

RESUMO

INTRODUCTION: In 2019, Centers for Medicare and Medicaid Services (CMS) established a new requirement that all hospitals publish information on the standard costs of services provided. Increased price transparency allows patients to compare healthcare costs and make informed decisions about their care. We investigated compliance with this rule with regards to laparoscopic cholecystectomy, a commonly performed operation and one of the 70 shoppable services (SSs) included in the CMS requirement, among prominent hospitals in the United States. METHODS: The 2021-2022 US News "Best Hospitals for Gastroenterology and GI Surgery" was used to identify the top 50 hospitals for gastrointestinal surgery. Each hospital's website was assessed for the presence of a machine-readable file (MRF) as required by CMS. Each MRF was then evaluated for inclusion of all seven required elements: description of item/service, gross charge, payer-specific negotiated charge, deidentified minimum and maximum negotiated charges, discounted cash price, and billing code. The presence of a consumer-friendly display of SSs was also evaluated. The Current Procedural Terminology code 47562 (removal of gallbladder with an endoscope) was used to search for all six required elements: payer-specific negotiated charge, discounted cash price, de-identified minimum and maximum negotiated charges, campus location of the SS, and billing code. The SS display was further evaluated for provision of additional information on ancillary charges, which are recommended but not required. The MRF and SS were also evaluated for accessibility and date of last update. Hospitals were analyzed according to rank. Compliance with CMS requirements was compared between hospitals. RESULTS: Fifty one hospitals were included. Of these 51 hospitals, one (2%) provided all the required information for both MRF and SS, 44 (86%) did not provide all necessary components of both the MRF and SS, six (12%) had all necessary elements of an MRF only, and two (4%) had all necessary elements of the SS only. The MRF was accessible in 80% (41) of studied hospitals and 76% (39) provided a gross charge but just 35% (18) of hospitals included the discounted cash price. The SS specified location for all hospitals, indicated a billing code in 96% (49), and provided a payer-specific charge in 96% (48), but less often provided de-identified minimum (30; 59%) and maximum (30; 59%) charges. Thirty nine (76%) hospitals reported that the listed price included an ancillary charge. There was no significant difference between hospitals in having all required elements of both the MRF and SS or the MRF only or SS only. CONCLUSIONS: Hospitals are providing healthcare consumers with standard charge information, although with significant variation in what is disclosed. There is no association between hospital reputation and provision of standard charge information.


Assuntos
Colecistectomia Laparoscópica , Medicare , Humanos , Idoso , Estados Unidos , Hospitais , Centers for Medicare and Medicaid Services, U.S. , Custos de Cuidados de Saúde
20.
Pediatr Dermatol ; 39(5): 757-760, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35657009

RESUMO

Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare type of epidermal nevus, commonly arising in childhood. We present a case of a 13-year-old female with Blaschkoid psoriasiform plaques extending from her left foot to the scalp, sparing the right side of the body. While treatment options historically show variable success, we trialed an IL-17a receptor inhibitor as studies have shown increased levels of IL-17 receptor expression in ILVEN keratinocytes. At both 3 and 6 months after treatment initiation there was found to be significant improvement. We propose brodalumab as an effective treatment option for widespread ILVEN.


Assuntos
Nevo Sebáceo de Jadassohn , Nevo , Neoplasias Cutâneas , Adolescente , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Interleucina-17 , Nevo Sebáceo de Jadassohn/tratamento farmacológico , Receptores de Interleucina-17
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