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1.
Ann Surg ; 279(2): 340-345, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37389888

RESUMO

OBJECTIVE: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. BACKGROUND: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. METHODS: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. RESULTS: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). CONCLUSIONS: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.


Assuntos
Hiperparatireoidismo Primário , Neoplasia Endócrina Múltipla Tipo 1 , Humanos , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/complicações , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Glândulas Paratireoides , Paratireoidectomia , Recidiva
2.
Langenbecks Arch Surg ; 407(6): 2489-2498, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35596781

RESUMO

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.


Assuntos
Hipercalcemia , Hiperparatireoidismo Secundário , Hiperparatireoidismo , Transplante de Rim , Calcimiméticos/uso terapêutico , Cálcio , Cinacalcete/uso terapêutico , Humanos , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/cirurgia , Hiperparatireoidismo Secundário/cirurgia , Rim , Transplante de Rim/efeitos adversos , Hormônio Paratireóideo , Paratireoidectomia
3.
Ann Surg ; 274(5): 851-858, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34353986

RESUMO

OBJECTIVE: The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy. SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice. METHODS: The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms. RESULTS: A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%). CONCLUSIONS: Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication.


Assuntos
Hipoparatireoidismo/etiologia , Saúde Mental , Qualidade de Vida , Tireoidectomia/efeitos adversos , Voz/fisiologia , Autoavaliação Diagnóstica , Feminino , Humanos , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Autoavaliação (Psicologia)
4.
Nutr Metab Cardiovasc Dis ; 31(4): 981-996, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33612382

RESUMO

AIMS: Primary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English. DATA SYNTHESIS: In the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting. CONCLUSIONS: PTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Tomada de Decisão Clínica , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/mortalidade , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Ann Surg Oncol ; 27(10): 3831-3839, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32246313

RESUMO

BACKGROUND: Persistent primary hyperparathyroidism (PHPT) occurs in 2.5% to 15% of cases after parathyroidectomy. Few studies have evaluated the best pre-reoperative imaging approaches for persistent sporadic PHPT. This retrospective multicenter study aimed to evaluate the benefit of a second pre-reoperative 99mTc-methoxy-isobutyl-isonitrile (MIBI) scintigraphy for patients with persistent PHPT who had a 99mTc-MIBI before their initial surgery. METHODS: The study enrolled 50 patients with persistent sporadic PHPT who had reoperation between 2006 and 2016 in three French University Hospitals (Angers, Nantes, and La Pitié Salpêtrière-Paris). Preoperative 99mTc-MIBI scan was performed before each operation. RESULTS: After the reoperation, 42 patients (84%) were cured. By the second 99mTc-MIBI, 31 patients (62%) had a removed gland identified. A new pathologic gland was identified by a second 99mTc-MIBI in 25 patients (50%), and this imaging permitted correction of an initial surgical error in six patients (12%). A second 99mTc-MIBI showed a sensitivity of 63%, a specificity of 89%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 80%. A concordant second 99mTc-MIBI and ultrasonography (17 patients) showed a sensitivity of 70%, a specificity of 81%, a PPV of 70%, and an NPV of 81%. CONCLUSIONS: Performing a second 99mTc-MIBI scan permitted 62% of the persistent PHPT patients to be cured, allowing identification of new pathologic glands in 50% of the cases and correction of an initial surgical error in 12% of the cases, with high specificity and PPV. These results reinforce the fact that a second 99mTc-MIBI scan should be performed at first intention before reoperation of patients with persistent PHPT, regardless of the result from the initial 99mTc-MIBI scan.


Assuntos
Hiperparatireoidismo Primário , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Glândulas Paratireoides , Cintilografia , Compostos Radiofarmacêuticos , Reoperação , Estudos Retrospectivos , Tecnécio Tc 99m Sestamibi
6.
Proc Natl Acad Sci U S A ; 114(18): E3689-E3698, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28416698

RESUMO

Anti-MAG (myelin-associated glycoprotein) neuropathy is a disabling autoimmune peripheral neuropathy caused by monoclonal IgM autoantibodies that recognize the carbohydrate epitope HNK-1 (human natural killer-1). This glycoepitope is highly expressed on adhesion molecules, such as MAG, present in myelinated nerve fibers. Because the pathogenicity and demyelinating properties of anti-MAG autoantibodies are well established, current treatments are aimed at reducing autoantibody levels. However, current therapies are primarily immunosuppressive and lack selectivity and efficacy. We therefore hypothesized that a significant improvement in the disease condition could be achieved by selectively neutralizing the pathogenic anti-MAG antibodies with carbohydrate-based ligands mimicking the natural HNK-1 glycoepitope 1. In an inhibition assay, a mimetic (2, mimHNK-1) of the natural HNK-1 epitope blocked the interaction of MAG with pathogenic IgM antibodies from patient sera but with only micromolar affinity. Therefore, considering the multivalent nature of the MAG-IgM interaction, polylysine polymers of different sizes were substituted with mimetic 2. With the most promising polylysine glycopolymer PL84(mimHNK-1)45 the inhibitory effect on patient sera could be improved by a factor of up to 230,000 per epitope, consequently leading to a low-nanomolar inhibitory potency. Because clinical studies indicate a correlation between the reduction of anti-MAG IgM levels and clinical improvement, an immunological surrogate mouse model for anti-MAG neuropathy producing high levels of anti-MAG IgM was developed. The observed efficient removal of these antibodies with the glycopolymer PL84(mimHNK-1)45 represents an important step toward an antigen-specific therapy for anti-MAG neuropathy.


Assuntos
Anticorpos Neutralizantes , Autoanticorpos/imunologia , Antígenos CD57/imunologia , Glicoproteína Associada a Mielina/imunologia , Polirradiculoneuropatia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Bovinos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Polirradiculoneuropatia/tratamento farmacológico , Polirradiculoneuropatia/imunologia , Polirradiculoneuropatia/patologia
7.
Biochim Biophys Acta Mol Basis Dis ; 1864(5 Pt A): 1596-1608, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29454073

RESUMO

Ketogenic diet (KD) which combined carbohydrate restriction and the addition of ketone bodies has emerged as an alternative metabolic intervention used as an anticonvulsant therapy or to treat different types of neurological or mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation. The broad success of KD is due to multiple beneficial mechanisms with distinct effects of very low carbohydrates and ketones. To evaluate the metabolic part of carbohydrate restriction, transmitochondrial neuronal-like cybrid cells carrying the m.3243A > G mutation, shown to be associated with a severe complex I deficiency was exposed during 3 weeks to glucose restriction. Mitochondrial enzyme defects were combined with an accumulation of complex I (CI) matrix intermediates in the untreated mutant cells, leading to a drastic reduction in CI driven respiration. The severe reduction of CI was also paralleled in post-mortem brain tissue of a MELAS patient carrying high mutant load. Importantly, lowering significantly glucose concentration in cell culture improved CI assembly with a significant reduction of matrix assembly intermediates and respiration capacities were restored in a sequential manner. In addition, OXPHOS protein expression and mitochondrial DNA copy number were significantly increased in mutant cells exposed to glucose restriction. The accumulation of CI matrix intermediates appeared as a hallmark of MELAS pathophysiology highlighting a critical pathophysiological mechanism involving CI disassembly, which can be alleviated by lowering glucose fuelling and the induction of mitochondrial biogenesis, emphasizing the usefulness of metabolic interventions in MELAS syndrome.


Assuntos
Complexo I de Transporte de Elétrons/metabolismo , Glucose/metabolismo , Síndrome MELAS/enzimologia , Mitocôndrias/enzimologia , Neurônios/enzimologia , Mutação Puntual , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Síndrome MELAS/genética , Síndrome MELAS/patologia , Masculino , Mitocôndrias/genética , Mitocôndrias/patologia , Neurônios/patologia , Fosforilação Oxidativa
8.
Biochim Biophys Acta Mol Basis Dis ; 1863(1): 284-291, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27815040

RESUMO

Ketogenic Diet used to treat refractory epilepsy for almost a century may represent a treatment option for mitochondrial disorders for which effective treatments are still lacking. Mitochondrial complex I deficiencies are involved in a broad spectrum of inherited diseases including Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome leading to recurrent cerebral insults resembling strokes and associated with a severe complex I deficiency caused by mitochondrial DNA (mtDNA) mutations. The analysis of MELAS neuronal cybrid cells carrying the almost homoplasmic m.3243A>G mutation revealed a metabolic switch towards glycolysis with the production of lactic acid, severe defects in respiratory chain activity and complex I disassembly with an accumulation of assembly intermediates. Metabolites, NADH/NAD+ ratio, mitochondrial enzyme activities, oxygen consumption and BN-PAGE analysis were evaluated in mutant compared to control cells. A severe complex I enzymatic deficiency was identified associated with a major complex I disassembly with an accumulation of assembly intermediates of 400kDa. We showed that Ketone Bodies (KB) exposure for 4weeks associated with glucose deprivation significantly restored complex I stability and activity, increased ATP synthesis and reduced the NADH/NAD+ ratio, a key component of mitochondrial metabolism. In addition, without changing the mutant load, mtDNA copy number was significantly increased with KB, indicating that the absolute amount of wild type mtDNA copy number was higher in treated mutant cells. Therefore KB may constitute an alternative and promising therapy for MELAS syndrome, and could be beneficial for other mitochondrial diseases caused by complex I deficiency.


Assuntos
Complexo I de Transporte de Elétrons/metabolismo , Corpos Cetônicos/farmacologia , Síndrome MELAS/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Linhagem Celular , Respiração Celular/efeitos dos fármacos , Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/genética , Dieta Cetogênica , Complexo I de Transporte de Elétrons/deficiência , Humanos , Síndrome MELAS/genética , Síndrome MELAS/metabolismo , Síndrome MELAS/patologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Mitocondriais/complicações , Neurônios/metabolismo , Neurônios/patologia
10.
Ann Endocrinol (Paris) ; 85(2): 136-141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246417

RESUMO

Amiodarone is the most widely prescribed antiarrhythmic drug worldwide, but induces thyrotoxicosis or hypothyroidism in 15 to 20% of patients. Hyperthyroidism is less frequent than hypothyroidism, and two types of thyrotoxicosis are distinguished according to presence of underlying thyroid disease. Diagnosis is made in case of low TSH and high levels of T3 and T4. Initial treatment is based on anti-thyroid drugs and/or glucocorticoids. Some patients do not respond to medication, which increases the time spent with hyperthyroidism. A long interval between diagnosis and euthyroidism and low left ventricular ejection fraction (LVEF) are predictive of major adverse cardiovascular events. Here, after describing the current state of knowledge of amiodarone-induced thyrotoxicosis, we analyze the literature on the impact of surgery. We suggest that early surgery should be the first option in case of ineffective medical treatment or LVEF<40%. In expert centers, surgical morbidity is no longer different than in other indications for thyroidectomy.


Assuntos
Amiodarona , Hipertireoidismo , Hipotireoidismo , Tireotoxicose , Humanos , Volume Sistólico , Função Ventricular Esquerda , Amiodarona/efeitos adversos , Tireotoxicose/induzido quimicamente , Hipotireoidismo/tratamento farmacológico
11.
Surgery ; 175(1): 172-179, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935599

RESUMO

BACKGROUND: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. METHODS: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. RESULTS: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). CONCLUSION: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.


Assuntos
Doenças Ósseas Metabólicas , Hiperparatireoidismo Primário , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Densidade Óssea , Estudos Prospectivos , Hiperparatireoidismo Primário/cirurgia , Paratireoidectomia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/cirurgia , Biomarcadores , Cálcio
12.
J Clin Endocrinol Metab ; 109(6): 1494-1504, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38152848

RESUMO

CONTEXT: Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. OBJECTIVE: To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. DESIGN: In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. SETTING: Referral center. PATIENTS: A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: BMD change between before and 1 year after parathyroidectomy. RESULTS: Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. CONCLUSION: Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas , Hiperparatireoidismo Primário , Paratireoidectomia , Humanos , Feminino , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Pessoa de Meia-Idade , Doenças Ósseas Metabólicas/cirurgia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/sangue , Idoso , Estudos Prospectivos , Remodelação Óssea , Biomarcadores/sangue , Absorciometria de Fóton , Seguimentos , Resultado do Tratamento
13.
Obesity (Silver Spring) ; 32(1): 91-106, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37875256

RESUMO

OBJECTIVE: The objective of this study was to compare the general and metabolic impact of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) with Roux-en-Y gastric bypass (RYGB) in an obese (ob/ob) mouse model. METHODS: 10-week-old male ob/ob mice underwent either SADI-S, RYGB, or laparotomy surgery (Sham group). General and metabolic parameters were assessed during a 5-week period thereafter. RESULTS: SADI-S induced a deeper weight loss ([mean ± SEM] -41.2% ± 3.3%) than RYGB (-5.6% ± 3.5%, p < 0.001) compared with the Sham group (+6.3% ± 1.0%, p < 0.05). A significant food restriction was observed after SADI-S only (-31%, 117.4 ± 10.3 g vs. 170.2 ± 5.2 g of food at day 35 in Sham group mice, p < 0.001). Random-fed glycemia and glucose tolerance were more improved after SADI-S than RYGB. SADI-S decreased plasma cholesterol concentration by 60% (0.49 ± 0.04 g/L vs. 1.40 ± 0.10 g/L in the Sham group at day 35, p < 0.01), significantly more than RYGB (1.04 ± 0.14 g/L, p = 0.018). Plasma sitosterol/cholesterol and campesterol/cholesterol ratios were decreased after SADI-S, suggesting a reduced intestinal cholesterol absorption. SADI-S increased exogenous plasma cholesterol-D7 clearance and fecal elimination, also indicating an increased plasma cholesterol excretion. Studying a pair-fed group demonstrated that calorie restriction alone did not explain the beneficial impact of SADI-S. CONCLUSIONS: SADI-S is associated with a greater improvement in lipid and glucose homeostasis than RYGB in ob/ob mice.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Animais , Masculino , Camundongos , Colesterol , Gastrectomia , Glucose , Homeostase , Lipídeos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Camundongos Obesos
14.
Transl Res ; 272: 151-161, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38471633

RESUMO

The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema. Furthermore, specific PCSK9 inhibition during the elicitation steps of allergic process was sufficient to ensure anti-allergic effects in mice. Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.

15.
J Vis Exp ; (192)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36847386

RESUMO

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, cardiovascular events, and cancers) through restrictive and malabsorptive mechanisms. Understanding the mechanisms by which these procedures allow such improvements often require their transposition into animals, especially in mice, because of the ease of generating genetically modified animals. Recently, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has emerged as a procedure that uses both restrictive and malabsorptive effects, which is being used as an alternative to gastric bypass in case of major obesity. Thus far, this procedure has been associated with strong metabolic improvements, which has led to a marked increase in its use in daily clinical practice. However, the mechanisms underlying these metabolic effects have been poorly studied as a result of a lack of animal models. In this article, we present a reliable and reproducible model of SADI-S in mice, with a special focus on perioperative management. The description and use of this new rodent model will be helpful for the scientific community to better understand the molecular, metabolic, and structural changes induced by the SADI-S and to better define the surgical indications for clinical practice.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Camundongos , Animais , Obesidade Mórbida/cirurgia , Derivação Gástrica/métodos , Obesidade/cirurgia , Obesidade/complicações , Duodeno/cirurgia , Gastrectomia/métodos , Anastomose Cirúrgica/métodos , Estudos Retrospectivos
16.
Surgery ; 173(1): 146-153, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167701

RESUMO

BACKGROUND: Altered glomerular filtration rate is a controversial indication for parathyroidectomy in patients with primary hyperparathyroidism. The objective of this study was to evaluate the estimated glomerular filtration rate change 12 months after parathyroidectomy for primary hyperparathyroidism according to preoperative kidney function. METHOD: Patients who underwent parathyroidectomy for primary hyperparathyroidism between 2016 and 2021 (n = 381) were enrolled in a monocentric prospective cohort. Patients without 1-year follow-up or with missing data were excluded (n = 135, 35%). Patients were dichotomized according to their baseline estimated glomerular filtration rate: <60 mL/min (group 1) and ≥60 mL/min (group 2). Parameters were measured before and then at 6 and 12 months after parathyroidectomy. RESULTS: Out of 246 included patients, 27 (11%) were assigned to group 1 and 219 (89%) to group 2. The mean baseline estimated glomerular filtration rate was 46.8 ± 11.5 and 87.3 ± 14.7 mL/min in groups 1 and 2, respectively. Group 1 patients were older (P = .0006) and had a higher median serum parathyroid hormone level (P = .021). At 6 months postoperative, 224 patients (91%) were normocalcemic. The estimated glomerular filtration rate raw change after parathyroidectomy was significantly higher in group 1 than in group 2 (4.2 ± 7.8 vs -2.2 ± 9.1 mL/min, P = .0004). In group 1, 13/27 patients (48%) improved their chronic kidney disease stage after parathyroidectomy, including 6/13 (46%) with postoperative estimated glomerular filtration rate ≥60 mL/min, whereas 2/27 (7%) worsened. The baseline estimated glomerular filtration rate <60 mL/min and elevated serum calcium level were associated with postoperative estimated glomerular filtration rate improvement in multivariable analysis (P = .0023 and .039, respectively). CONCLUSION: Parathyroidectomy for primary hyperparathyroidism is more likely to improve kidney function in patients with preoperative estimated glomerular filtration rate <60 mL/min. These results strengthen the current guidelines for surgery.


Assuntos
Hiperparatireoidismo Primário , Rim , Paratireoidectomia , Humanos , Cálcio , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Rim/patologia , Hormônio Paratireóideo , Paratireoidectomia/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Testes de Função Renal
17.
J Visc Surg ; 160(3S): S95-S109, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37211443

RESUMO

Postoperative hypoparathyroidism, resulting from removal and/or devascularization of one or more parathyroid glands, is a feared complication of total thyroidectomy. Two forms, which are distinguished by their frequency, their time to onset and their duration as well as by their presentation, must be individualized: early postoperative hypocalcemia, often secondary to early hypoparathyroidism is a frequent and often transient situation occurring within the first days after surgery; permanent hypoparathyroidism, which is rarer, manifests when parathyroid function remains impaired for more than six months after surgery. Because of their severity, these conditions must be known and ideally prevented during total thyroidectomy. The objective of this article is to provide surgeons with practical recommendations for the prevention, diagnosis, and treatment of hypoparathyroidism after total thyroidectomy. These recommendations, which are the fruit of a medico-surgical consensus, were developed by the Francophone Association of Endocrine Surgery (AFCE), the French Society of Endocrinology (SFE) and the French Society of Nuclear Medicine and Molecular Imaging. (SFMN). The content, grade and level of evidence for each recommendation was decided after consultation within a panel of experts, based on an analysis of recent literature.


Assuntos
Hipocalcemia , Hipoparatireoidismo , Medicina Nuclear , Humanos , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Complicações Pós-Operatórias/etiologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/prevenção & controle , Glândulas Paratireoides/diagnóstico por imagem
18.
Otolaryngol Head Neck Surg ; 169(6): 1542-1549, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37317630

RESUMO

OBJECTIVE: To report cardiac outcomes after total thyroidectomy for amiodarone-induced thyrotoxicosis according to the baseline left ventricular ejection fraction in a tertiary referral center. STUDY DESIGN: Retrospective, monocentric. SETTING: The tertiary health care system. METHODS: Patients who underwent total thyroidectomy for amiodarone-induced thyrotoxicosis between 2010 and 2020 with age >18 and available preoperative left ventricular ejection fraction were included in this study. Patients were dichotomized into: group 1 with left ventricular ejection fraction ≥40% (mildly reduced/normal ejection fraction), and group 2 with left ventricular ejection fraction <40% (reduced ejection fraction). RESULTS: There were 34 patients in group 1 and 17 to group 2. The latter were younger (median 58.4 [Q1-Q3 48.0-64.9] vs. 69.8 years in group 1 [59.8-78.3], p = .0035) and they presented more cardiomyopathy (58.8 vs. 26.5%, p = .030). Overall, the median time until surgery referral was 3.1 [1.9-7.1] months and 47.1% underwent surgery after restoration of euthyroidism. Surgical complications accounted for 7.8%. In group 2, the median left ventricular ejection fraction was significantly improved after surgery (22.5 [20.0-25.0] vs. 29.0% [25.3-45.5], p = .0078). Five-year cardiac mortality was significantly higher in group 2 (p < .0001): 47.0% died of cardiac causes versus 2.9% in group 1. A baseline left ventricular ejection fraction <40% and a longer time until surgery referral were significantly associated with cardiac mortality (multivariable Cox regression analysis, p = .015 and .020, respectively). CONCLUSION: These results reinforce the idea that surgery, if chosen, should be performed quickly in patients with left ventricular ejection fraction <40%.


Assuntos
Amiodarona , Hipertireoidismo , Tireotoxicose , Humanos , Volume Sistólico , Amiodarona/efeitos adversos , Antiarrítmicos/uso terapêutico , Antiarrítmicos/farmacologia , Função Ventricular Esquerda , Tireoidectomia/métodos , Estudos Retrospectivos , Tireotoxicose/induzido quimicamente , Tireotoxicose/cirurgia , Hipertireoidismo/cirurgia
19.
Surgery ; 174(3): 593-601, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37357098

RESUMO

BACKGROUND: The objective was to compare the outcomes of open mesh repair versus suture repair for small (≤1 cm in diameter) umbilical hernia. The primary endpoint was the 30-day outcomes including pain, and secondary endpoints were the 2-year outcomes including recurrences and patient-reported outcomes. METHODS: This propensity-matched, multicenter study was carried out on data collected prospectively in the Hernia-Club database between 2011 and 2021. A total of 590 mesh repairs and 590 suture repairs were propensity score matched (age, sex, body mass index) at a ratio of 1:1. Postoperative pain was assessed using the Verbal Rating Scale-4 and 0‒10 Numerical Rating Scale-11. RESULTS: Mesh insertion was intraperitoneal in 331 patients (56.1%), extraperitoneal in 249 (42.2%), and onlay in 10 (1.7%). The rate of 30-day complications and Numerical Rating Scale-11 pain scores on postoperative days 8 and 30 were similar between the groups, including surgical site occurrences (2.2 vs 1.4% after suture repair). At 1 month, postoperative discomfort (sensation of something different from before) was significantly (P < .0001) more frequent after mesh repair, whereas the rate of relevant (moderate or severe) pain (mesh repair: 1.1% vs suture repair: 2.6%) and the distribution of Numerical Rating Scale-11 scores did not differ between the groups. At the 2-year follow-up, mesh repair patients had fewer reoperated recurrences (0.2% vs 1.7%; P = .035) and no more pain or discomfort than suture repair patients. CONCLUSION: Both techniques are effective and safe. Mesh repair is likely to reduce the rate of recurrences. Concerns about postoperative pain and infection might not prevent the use of mesh in smallest umbilical hernias.


Assuntos
Hérnia Umbilical , Humanos , Hérnia Umbilical/cirurgia , Estudos de Coortes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Telas Cirúrgicas/efeitos adversos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Suturas/efeitos adversos , Recidiva , Técnicas de Sutura/efeitos adversos
20.
Int J Surg ; 109(3): 364-373, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36917123

RESUMO

BACKGROUND: The impact of parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) on long-term quality of life (QoL) remains controversial. The study evaluated QoL changes 1 and 3 years after PTX. MATERIALS AND METHODS: Patients undergoing PTX for PHPT between 2016 and 2022 ( n =329) were enrolled in this monocentric, prospective cohort study. QoL was evaluated using the SF-36 questionnaire before, 1 year, and 3 years after PTX and compared with an age-matched and sex-matched French reference population. Only patients with 1-year and 3-year follow-up and complete evaluation (serum calcium, phosphorus, parathyroid hormone) were included. RESULTS: A total of 159 patients were included (mean age: 62.6±12.7 years, 79.2% females). Mean serum calcium (2.66±0.20 mmol/l) and median parathyroid hormone (96.4 [76.9-126.4] pg/ml) levels improved significantly after PTX. Before surgery, PHPT patients had impaired physical (44.6±8.9 vs. 47.6±6.8 in the reference population, P <0.001) and mental (42.3±10.9 vs. 48.9±6.8, P <0.001) component scores. The mean physical component score increased significantly at 1 and 3 years and was no longer different from the reference population (ratio: 0.94±0.15 preoperatively vs. 0.99±0.15 at 3 years, P <0.01). The mean mental component score increased significantly at 1 and 3 years, but remained significantly lower than the reference population. Before surgery, a lower physical component score and younger age were significantly associated with a 3-year physical component score increase on multiple linear regression analysis. CONCLUSION: A significant improvement in QoL is associated with PTX for PHPT at 1 year and is sustained for at least 3 years after surgery.


Assuntos
Hiperparatireoidismo Primário , Paratireoidectomia , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Hiperparatireoidismo Primário/cirurgia , Cálcio , Qualidade de Vida , Estudos Prospectivos , Hormônio Paratireóideo
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