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1.
Cureus ; 16(3): e57109, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38681455

RESUMO

While Ewing sarcoma is traditionally a malignant tumor of bone, it may uncommonly present extra-skeletally, leading to an array of puzzling presentations depending on the tissue involved. Here, we describe the case of a 66-year-old man who presented to the primary care office for evaluation of intermittent melena. He ultimately underwent capsule endoscopy and developed a secondary small bowel obstruction, unveiling his neoplasm. The tumor was then resected and managed with surveillance only, and the patient remains without evidence of disease after four years of follow-up.

2.
ACS Omega ; 8(14): 13252-13264, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37065048

RESUMO

Mycobacterium tuberculosis has a complex life cycle transitioning between active and dormant growth states depending on environmental conditions. LipN (Rv2970c) is a conserved mycobacterial serine hydrolase with regulated catalytic activity at the interface between active and dormant growth conditions. LipN also catalyzes the xenobiotic degradation of a tertiary ester substrate and contains multiple conserved motifs connected with the ability to catalyze the hydrolysis of difficult tertiary ester substrates. Herein, we expanded a library of fluorogenic ester substrates to include more tertiary and constrained esters and screened 33 fluorogenic substrates for activation by LipN, identifying its unique substrate signature. LipN preferred short, unbranched ester substrates, but had its second highest activity against a heteroaromatic five-membered oxazole ester. Oxazole esters are present in multiple mycobacterial serine hydrolase inhibitors but have not been tested widely as ester substrates. Combined structural modeling, kinetic measurements, and substitutional analysis of LipN showcased a fairly rigid binding pocket preorganized for catalysis of short ester substrates. Substitution of diverse amino acids across the binding pocket significantly impacted the folded stability and catalytic activity of LipN with two conserved motifs (HGGGW and GDSAG) playing interconnected, multidimensional roles in regulating its substrate specificity. Together this detailed substrate specificity profile of LipN illustrates the complex interplay between structure and function in mycobacterial hormone-sensitive lipase homologues and indicates oxazole esters as promising inhibitor and substrate scaffolds for mycobacterial hydrolases.

3.
Am J Surg ; 221(4): 804-808, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32682499

RESUMO

BACKGROUND: Thyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well differentiated thyroid cancer. We aimed to determine factors associated with thyroid stimulating hormone over goal (TH) following lobectomy. METHODS: We performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. TH was defined as need for thyroid hormone in accordance with guidelines. Univariate and multivariate logistic regression analysis was performed. RESULTS: One hundred patients were included and 47% developed. TH: 73% of those with cancer, 38% with benign pathology (p = 0.002). Patients with TH were more likely to have thyroiditis 26% versus 3.8% (p = 0.002); higher preoperative TSH: mean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003). CONCLUSIONS: After thyroid lobectomy, TH is associated with preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal.


Assuntos
Hormônios Tireóideos/administração & dosagem , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireotropina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
4.
Am J Surg ; 220(5): 1169-1173, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32684294

RESUMO

BACKGROUND: Thyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well-differentiated thyroid cancer. We aimed to determine factors associated with need for thyroid hormone supplementation following thyroid lobectomy. METHODS: We performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. Thyroid hormone supplementation was assessed postoperatively based on guidelines for thyroid stimulating hormone (TSH) level goal for benign (0.5-4.5mIU/L) or malignant (<2mIU/L) final pathology. Univariate and multivariate logistic regression analysis was performed. RESULTS: One hundred patients were included and overall 47% required thyroid hormone supplementation after thyroid lobectomy: 73% of those with cancer, 38% with benign pathology (p = 0.002). Patients requiring thyroid hormone supplementation were more likely to have thyroiditis 26% versus 3.8% of those who remained euthyroid (p = 0.002); have a higher preoperative TSH: mean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and have a smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003). CONCLUSIONS: After thyroid lobectomy, the need for thyroid hormone supplementation is associated with higher preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy on final pathology. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal. For patients with benign pathology after thyroid lobectomy the majority will not require thyroid hormone supplementation to achieve TSH goal.


Assuntos
Terapia de Reposição Hormonal/estatística & dados numéricos , Hormônios Tireóideos/uso terapêutico , Tireoidectomia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidite/cirurgia , Tireotropina/sangue
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