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1.
Int J Mol Sci ; 24(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36768676

RESUMO

Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI -34.3% (OP) vs. -1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Humanos , Ratos , Animais , Derivação Gástrica/métodos , Metabolômica/métodos , Dieta , Redução de Peso , Obesidade Mórbida/metabolismo
3.
J Peripher Nerv Syst ; 22(3): 182-190, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28573768

RESUMO

Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls. Immunofluorescence of skin sections with antibodies against Caspr, neurofascin, sodium channels, and myelin basic protein was performed to assess paranodal/nodal architecture, segmental demyelination, and myelinated nerve fibers. Staining with antibodies against protein gene product 9.5 was used to quantify unmyelinated nerve fibers. There was an increase of elongated Ranvier nodes and a dispersion of neurofascin at the distal leg in patients with DM with and without neuropathy and at the finger in patients with DNP. An increased dispersion of Caspr was only found in biopsies of the finger in patients with DNP. Skin biopsy may be an appropriate tool to analyze nodes of Ranvier in patients with DM. Structural nodal changes are detectable in DNP and even in diabetic patients without neuropathy.


Assuntos
Diabetes Mellitus/patologia , Fibras Nervosas Mielinizadas/patologia , Nós Neurofibrosos/patologia , Pele/inervação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas
4.
Nutrients ; 16(16)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39203846

RESUMO

After bariatric surgery lifelong follow-up is recommended. Evidence of the consequences and reasons for being lost to follow-up (LTFU) is sparse. In this prospective study follow-up data of all patients who underwent bariatric surgery between 2008 and 2017 at a certified obesity centre were investigated. LTFU patients were evaluated through a structured telephone interview. Overall, 573 patients (female/male 70.9%/29.1%), aged 44.1 ± 11.2 years, preoperative BMI 52.1 ± 8.4 kg/m2 underwent bariatric surgery. Out of these, 33.2% had type 2 diabetes mellitus and 74.4% had arterial hypertension. A total of 290 patients were LTFU, of those 82.1% could be reached. Baseline characteristics of patients in follow-up (IFU) and LTFU were comparable, but men were more often LTFU (p = 0.01). Reported postoperative total weight loss (%TWL) and improvements of comorbidities were comparable, but %TWL was higher in patients remaining in follow-up for at least 2 years (p = 0.013). Travel issues were mentioned as the main reason for being LTFU. A percentage of 77.6% of patients reported to regularly supplement micronutrients, while 71.0% stated regular monitoring of their micronutrient status, mostly by primary care physicians. Despite comparable reported outcomes of LTFU to IFU patients, the duration of the in-centre follow-up period affected %TWL. There is a lack of sufficient supplementation and monitoring of micronutrients in a considerable number of LTFU patients.


Assuntos
Cirurgia Bariátrica , Perda de Seguimento , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Seguimentos , Redução de Peso , Diabetes Mellitus Tipo 2 , Obesidade Mórbida/cirurgia , Hipertensão , Obesidade/cirurgia
5.
Obes Facts ; 17(3): 311-324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38537612

RESUMO

INTRODUCTION: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term postoperative care. Since no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers. METHODS: ACHT is a multicenter, prospective, non-randomized control group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric bypass or sleeve gastrectomy (months 1-18 postoperatively), intervention group 2 begins the program 18 months after surgery (months 19-36 postoperatively). Intervention groups are compared to respective control groups that had surgery 18 and 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care. RESULTS: The primary endpoint to compare intervention and control groups is the adapted King's score, a composite tool evaluating physical, psychological, socioeconomic, and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the 3 years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period. CONCLUSIONS: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life, and the feasibility of such a program outside of specialized obesity centers.


Assuntos
Cirurgia Bariátrica , Qualidade de Vida , Humanos , Estudos Prospectivos , Alemanha , Adulto , Resultado do Tratamento , Feminino , Masculino , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Cuidados Pós-Operatórios/métodos , Pessoa de Meia-Idade
6.
Front Endocrinol (Lausanne) ; 14: 1244647, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027217

RESUMO

Context: Although renal long-term complications are acknowledged in chronic hypoparathyroidism (HPT), standardized investigations are scarce. Objective: To systematically investigate renal complications and their predictors in hypoparathyroid patients compared to matched individuals. Design: Prospective observational study in 161 patients with chronic HPT. Methods: Patients received renal ultrasound, clinical and laboratory assessments. An individual 1:3 matching with participants from the German population-based Study of Health in Pomerania was performed. Results: Of 161 patients (92% postoperative HPT), prevalence of eGFR <60ml/min/1.73m2 was 21%, hypercalciuria 41%. Compared to healthy individuals, HPT patients had a significantly lower eGFR (74.2 vs. 95.7 ml/min/1.73m², p<0.01). Renal ultrasound revealed calcifications in 10% (nephrocalcinosis in 7% and calculi in 3%). Patients with renal calcifications had higher levels of 24-hour urine calcium excretion (8.34 vs. 5.08 mmol/d, p=0.02), spot urine calcium excretion (4.57 vs. 2.01 mmol/L, p=0.01) and urine calcium-to-creatinine ratio (0.25 vs. 0.16, p<0.01) than patients without calcifications. Albumin-corrected calcium, phosphate, calcium-phosphate product, 25-hydroxyvitamin D in serum, eGFR, daily calcium intake or disease duration were not significantly different between these two groups. Including patients receiving rhPTH therapy, a lower serum phosphate concentration (odds ratio 1.364 [95% confidence interval (CI) 1.049-1.776], p<0.05) and a longer disease duration of HPT (odds ratio 1.063 [95% CI 1.021-1.106], p<0.01) were significant predictors for renal calcifications. Excluding patients receiving rhPTH therapy, a higher 24-hour urine calcium excretion (odds ratio 1.215 [95% CI 1.058-1.396], p<0.01) was a significant predictor for renal calcifications but not serum magnesium or disease duration. Conclusions: Prevalence of impaired renal function among patients with chronic HPT is increased and independent from visible renal calcifications. Depending on exclusion of patients with rhPTH therapy, regression analysis revealed disease duration and serum phosphate or disease duration and 24-hour urinary calcium excretion as predictors for renal calcifications. Clin Trials Identifier: NCT05585593.


Assuntos
Calcinose , Hipoparatireoidismo , Nefrocalcinose , Humanos , Cálcio , Estudos Transversais , Rim/fisiologia , Hipoparatireoidismo/complicações , Hipoparatireoidismo/epidemiologia , Nefrocalcinose/epidemiologia , Nefrocalcinose/etiologia , Fosfatos
7.
Metabolism ; 147: 155655, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37393945

RESUMO

OBJECTIVE: Randomized evidence comparing the cardiovascular effects of surgical and conservative weight management is lacking. PATIENTS & METHODS: In this single-center, open-label randomized trial, obese patients with indication for Roux-en-Y gastric bypass (RYGB) and able to perform treadmill cardiopulmonary exercise testing (CPET) were included. After a 6-12 month run-in phase of multimodal anti-obesity treatment, patients were randomized to RYGB or psychotherapy-enhanced lifestyle intervention (PELI) and co-primary endpoints were assessed 12 months later. Thereafter, PELI patients could opt for surgery and patients were reassessed 24 months after randomization. Co-primary endpoints were mean change (95 % confidence intervals) in peak VO2 (ml/min/kg body weight) in CPET and the physical functioning scale (PFS) of the Short Form health survey (SF-36). RESULTS: Of 93 patients entering the study, 60 were randomized. Among these (median age 38 years; 88 % women; mean BMI 48·2 kg/m2), 46 (RYGB: 22 and PELI: 24) were evaluated after 12 months. Total weight loss was 34·3 % after RYGB vs. 1·2 % with PELI, while peak VO2 increased by +4·3 ml/min/kg (2·7, 5·9) vs +1·1 ml/min/kg (-0·2, 2·3); p < 0·0001. Respective improvement in PFS score was +40 (30, 49) vs +10 (1, 15); p < 0·0001. 6-minute walking distance also favored the RYGB group: +44 m (17, 72) vs +6 m (-14, 26); p < 0·0001. Left ventricular mass decreased after RYGB, but not with PELI: -32 g (-46, -17) vs 0 g (-13,13); p < 0·0001. In the non-randomized follow-up, 34 patients were assessed. Favorable changes were sustained in the RYGB group and were repeated in the 15 evaluated patients that opted for surgery after PELI. CONCLUSIONS: Among adults with severe obesity, RYGB in comparison to PELI resulted in improved cardiopulmonary capacity and quality of life. The observed effect sizes suggest that these changes are clinically relevant.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Adulto , Humanos , Feminino , Masculino , Obesidade Mórbida/cirurgia , Qualidade de Vida , Obesidade/complicações , Obesidade/cirurgia , Estilo de Vida , Resultado do Tratamento , Estudos Retrospectivos
8.
Metabolism ; 138: 155341, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341838

RESUMO

OBJECTIVE: The hypothalamus is the main integrator of peripheral and central signals in the control of energy homeostasis. Its functional relevance for the effectivity of bariatric surgery is not entirely elucidated. Studying the effects of bariatric surgery in patients with hypothalamic damage might provide insight. SUMMARY BACKGROUND DATA: Prospective study to analyze the effects of bariatric surgery in patients with hypothalamic obesity (HO) vs. matched patients with common obesity (CO) with and without bariatric surgery. METHODS: 65 participants were included (HO-surgery: n = 8, HO-control: n = 10, CO-surgery: n = 12, CO-control: n = 12, Lean-control: n = 23). Body weight, levels of anorexic hormones, gut microbiota, as well as subjective well-being/health status, eating behavior, and brain activity (via functional MRI) were evaluated. RESULTS: Patients with HO lost significantly less weight after bariatric surgery than CO-participants (total body weight loss %: 5.5 % vs. 26.2 %, p = 0.0004). After a mixed meal, satiety and abdominal fullness tended to be lowest in HO-surgery and did not correlate with levels of GLP-1 or PYY. Levels of PYY (11,151 ± 1667 pmol/l/h vs. 8099 ± 1235 pmol/l/h, p = 0.028) and GLP-1 (20,975 ± 2893 pmol/l/h vs. 13,060 ± 2357 pmol/l/h, p = 0.009) were significantly higher in the HO-surgery vs. CO-surgery group. Abundance of Enterobacteriaceae and Streptococcus was increased in feces of HO and CO after bariatric surgery. Comparing HO patients with lean-controls revealed an increased activation in insula and cerebellum to viewing high-caloric foods in left insula and cerebellum in fMRI. CONCLUSIONS: Hypothalamic integrity is necessary for the effectiveness of bariatric surgery in humans. Peripheral changes after bariatric surgery are not sufficient to induce satiety and long-term weight loss in patients with hypothalamic damage.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Doenças Hipotalâmicas , Humanos , Estudos Prospectivos , Estudos Transversais , Redução de Peso/fisiologia , Obesidade/cirurgia , Peptídeo 1 Semelhante ao Glucagon , Hipotálamo
9.
Atheroscler Plus ; 53: 6-15, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37434912

RESUMO

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

10.
Clin Nutr ESPEN ; 50: 238-246, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35871930

RESUMO

BACKGROUND AND AIMS: Severe obesity (BMI ≥60 kg/m2) in multimorbid patients can be acutely life-threatening. While emergency weight-loss surgery is urgently needed to preserve life, most patients are in an inoperable state. Pre-surgical bridging therapy is required to achieve technical operability through weight reduction. Standard bridging using an intragastric balloon (IB) can achieve operability in 6 months but is unsuitable for some patients in a critical condition. A non-invasive fast-track rescue therapy to achieve very rapid operability is urgently needed. We investigated whether a rescue weight reduction therapy (RWR) consisting of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, a leucine-rich amino acid infusion and a hypocaloric diet, can accelerate readiness for emergency surgery in patients with acutely life-threatening severe obesity. METHODS: In this proof-of-concept study, prospective data from patients treated with RWR (intervention group 1, n = 26) were mathematically matched with retrospective biometric data of 26 patients with severe obesity (historic control group 2) who underwent standard 6-month bridging with IB. A rating scale was developed to identify patients needing urgent fast-track bridging. RESULTS: Rapid weight loss was observed in all patients on the RWR therapy. All achieved operability after a mean RWR bridging duration of 20.7 ± 6.9 days. Baseline weight was 236.3 ± 35.8 kg in group 1 compared with 230.1 ± 32.7 kg in group 2. Mean body weight loss during RWR was 27.5 ± 14.1 kg, compared with 20.9 ± 10.5 kg in group 2 (P = 0.0629). CONCLUSIONS: Pre-operative bridging using liraglutide in combination with a leucine-rich amino acid infusion and hypocaloric diet was effective in all cases of acutely life-threatening severe obesity, achieving technical operability within only ca. 2-4 weeks. This therapy has potential as a life-saving rescue therapy for multimorbid patients with severe obesity who were previously untreatable. This study is registered at ClinicalTrials.gov (identifier: NCT02616003).


Assuntos
Cirurgia Bariátrica , Balão Gástrico , Obesidade Mórbida , Dieta Redutora , Humanos , Leucina , Liraglutida , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudo de Prova de Conceito , Estudos Prospectivos , Estudos Retrospectivos , Redução de Peso
11.
Endocr Connect ; 11(2)2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35015697

RESUMO

Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled Würzburg Adipositas Studie (WAS) trial compares the effects of Roux-en-Y gastric bypass (RYGB) vs psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and the quality of life (QoL) (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6-12 months. Thereafter, the patients were randomized and followed through month 12 to collect the primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac MRI), functional brain MRI, psychometric scales, and endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m2) exhibiting a relevantly compromised exercise capacity (median peakVO2 18.3 mL/min/kg) and the QoL (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on the cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB.

12.
N Engl J Med ; 356(23): 2372-80, 2007 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-17554118

RESUMO

BACKGROUND: Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. METHODS: We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. RESULTS: Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients. CONCLUSIONS: Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/cirurgia , Antineoplásicos Hormonais/efeitos adversos , Quimioterapia Adjuvante , Humanos , Mitotano/efeitos adversos , Análise Multivariada , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Análise de Sobrevida
13.
Obes Surg ; 30(5): 1704-1711, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31974866

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is the most frequent 30-day complication in patients with morbid obesity undergoing bariatric surgery. Therefore, there is a need for optimized low molecular weight heparin (LMWH) thromboprophylaxis dosing strategies in order to avoid VTE-associated morbidity and mortality in this patient population. OBJECTIVE: The primary goal was to evaluate if a pre-specified enoxaparin dosing regimen in patients undergoing bariatric surgery reaches anti-factor Xa (aFXa) levels in the defined target range (0.2-0.4 U/ml). Second, we aimed to identify biometric and laboratory parameters that might influence the aFXa value. METHODS: A prospective database of 236 patients with obesity who received thromboprophylaxis with enoxaparin was established. These patients were divided into two weight-adjusted groups (group 1 < 150 kg, group 2 ≥ 150 kg). Enoxaparin was administered twice daily; dosing was determined by weight (group 1, 2 × 40 mg/day; group 2, 2 × 60 mg/day). In both groups, the peak aFXa serum level was evaluated 3 days after initiating the thromboprophylaxis. RESULTS: In group 1 (body mass index (BMI) 42.94 ± 6.84 kg/m2, weight of 121.7 ± 17.49 kg), seventy-one of the included 124 patients (57.25%) reached the aFXa target range of 0.2 to 0.4 U/m. In group 2 (BMI 63.21 ± 10.05 kg/m2, weight of 191.66 ± 33.37 kg), 68 of 112 (60.71%) patients scored prophylactic aFXa range. Multiple regression of the biometric and laboratory parameters showed significance for weight, waist-to-hip ratio, glomerular filtration rate (GFR), creatinine, and HbA1c exclusively in group 1. There was no case of VTE within 3 months after surgery and no case of severe perioperative bleeding in those patients who underwent surgery. CONCLUSIONS: Measurement of the aFXa level helps to define the real prophylactic thromboprophylaxis status in patients with obesity, especially in those with a weight above 150 kg. In patients at risk, the measurement of aFXa should be considered in routine clinical practice.


Assuntos
Obesidade Mórbida , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Estudos de Coortes , Esquema de Medicação , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Padrões de Referência , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
14.
Artigo em Inglês | MEDLINE | ID: mdl-32478671

RESUMO

SUMMARY: Standard treatment of hypoparathyroidism consists of supplementation of calcium and vitamin D analogues, which does not fully restore calcium homeostasis. In some patients, hypoparathyroidism is refractory to standard treatment with persistent low serum calcium levels and associated clinical complications. Here, we report on three patients (58-year-old male, 52-year-old female, and 48-year-old female) suffering from severe treatment-refractory postsurgical hypoparathyroidism. Two patients had persistent hypocalcemia despite oral treatment with up to 4 µg calcitriol and up to 4 g calcium per day necessitating additional i.v. administration of calcium gluconate 2-3 times per week, whereas the third patient presented with high frequencies of hypocalcemic and treatment-associated hypercalcemic episodes. S.c. administration of rhPTH (1-34) twice daily (40 µg/day) or rhPTH (1-84) (100 µg/day) only temporarily increased serum calcium levels but did not lead to long-term stabilization. In all three cases, treatment with rhPTH (1-34) as continuous s.c. infusion via insulin pump was initiated. Normalization of serum calcium and serum phosphate levels was observed within 1 week at daily 1-34 parathyroid hormone doses of 15 µg to 29.4 µg. Oral vitamin D and calcium treatment could be stopped or reduced and regular i.v. calcium administration was no more necessary. Ongoing efficacy of this treatment has been documented for up to 7 years so far. Therefore, we conclude that hypoparathyroidism that is refractory to both conventional treatment and s.c. parathyroid hormone (single or twice daily) may be successfully treated with continuous parathyroid hormone administration via insulin pump. LEARNING POINTS: Standard treatment of hypoparathyroidism still consists of administration of calcium and active vitamin D. Very few patients with hypoparathyroidism also do not respond sufficiently to standard treatment or administration of s.c. parathyroid hormone once or twice daily. In those cases, continuous s.c. administration of parathyroid hormone via insulin pump may represent a successful treatment alternative.

15.
J Clin Endocrinol Metab ; 93(8): 2991-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18477658

RESUMO

BACKGROUND: The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e.g. >100 mOsm/kg), clinical euvolemia, and a urinary sodium (Na) excretion (U-Na) more than 30 mmol/liter. However, in hyponatremic patients taking diuretics, this definition is unreliable due to the natriuretic effect of diuretics. Here, we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD, regardless of the use of diuretics. METHODS: A total of 86 consecutive hyponatremic patients (serum Na <130 mmol/liter) was classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, and fractional excretion (FE) of Na, urea, and uric acid (UA) were measured in all subjects. The accuracy to diagnose SIAD was assessed using receiver operating characteristic analysis. RESULTS: A total of 31 patients (36%) had a diagnosis of SIAD, and 55 (64%) were classified as non-SIAD. There were 57 patients (68%) who were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the receiver operating characteristic curve 0.96; 0.92-1.02). However, in patients on diuretics, the diagnosis was unreliable (area under the curve 0.85; 0.73-0.97). There, FE-UA performed best compared with all other markers tested (area under the curve 0.96; 0.92-1.12), resulting in a positive predictive value of 100% if a cutoff value of 12% was used. CONCLUSION: FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagnostic accuracy in hyponatremic patients with and without diuretic treatment.


Assuntos
Diuréticos/uso terapêutico , Hiponatremia/diagnóstico , Ácido Úrico/urina , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Hiponatremia/tratamento farmacológico , Hiponatremia/urina , Síndrome de Secreção Inadequada de HAD/diagnóstico , Masculino , Pessoa de Meia-Idade , Curva ROC , Sódio/urina , Ureia/urina
17.
J Clin Endocrinol Metab ; 92(10): 3912-22, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17684047

RESUMO

BACKGROUND: There is mounting evidence that current replacement regimens fail to restore health-related subjective health status fully in patients with adrenal insufficiency (AI). Here we evaluated the subjective health status in primary and secondary AI and the effect of concomitant disease. METHODS: In a cross-sectional study, all AI patients registered with the University Hospital Wuerzburg (n = 148) or with the German Self-Help Network (n = 200) were contacted by mail. Underlying diagnoses and comorbidities were verified by review of medical records. Patients were asked to complete three validated self-assessment questionnaires [Short Form 36 (SF-36), Giessen Complaint List (GBB-24), Hospital Anxiety and Depression Scale (HADS)]. Results were compared to sex- and age-matched controls drawn from the questionnaire-specific reference cohorts. RESULTS: We identified 348 patients, and 256 agreed to participate. Completed questionnaire sets were available from 210 patients [primary AI (n = 132), secondary AI (n = 78)]. Seven of eight SF-36 dimensions, all five GBB-24 scales, and the HADS anxiety score reflected significant impairment of subjective health status in both AI cohorts (all P < 0.001). Even after exclusion of all patients with any concomitant disease, subjective health status remained significantly impaired in five SF-36 subscales and four GBB-24 subscales. Secondary AI patients were slightly more compromised than primary AI, significant with regard to two SF-36 scales (P < 0.05) and the HADS depression score (P < 0.001). A total of 18.3% of the AI patients were out of work, compared to 4.1% in the general population. CONCLUSION: Patients with AI on current standard replacement suffer from significantly impaired health-related subjective health status, irrespective of origin of disease or concomitant disease. Future studies will have to assess whether more physiological glucocorticoid replacement strategies in AI will ameliorate these impairments.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/epidemiologia , Glucocorticoides/uso terapêutico , Nível de Saúde , Atividades Cotidianas , Insuficiência Adrenal/psicologia , Adulto , Idoso , Ansiedade/epidemiologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Feminino , Terapia de Reposição Hormonal , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações , Psicometria , Inquéritos e Questionários
18.
J Clin Endocrinol Metab ; 92(7): 2784-92, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17426081

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma. MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed. RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype. CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.


Assuntos
Mutação em Linhagem Germinativa , Perda de Heterozigosidade , Neurofibromatose 1/genética , Neurofibromina 1/genética , Feocromocitoma/genética , Adolescente , Adulto , Idoso , Feminino , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/epidemiologia , Feocromocitoma/epidemiologia , Índice de Gravidade de Doença
19.
J Clin Endocrinol Metab ; 91(11): 4501-4, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16895957

RESUMO

CONTEXT: Local tumor recurrence is common in adrenocortical carcinoma (ACC) and is the most frequent cause for reoperation. Although radiotherapy is often considered ineffective in the treatment of ACC, the limited number of available studies does not support this statement. OBJECTIVE: The objective of the study was investigation of adjuvant tumor bed irradiation in the treatment of ACC. DESIGN: We performed a retrospective analysis. PATIENTS: The German ACC Registry (n = 285) was screened for patients who had received tumor bed radiotherapy in an adjuvant setting (no macroscopic evidence for residual disease after surgery). Fourteen patients without distant metastases (World Health Organization stage I, one patient; stage II, seven; stage III, three; and stage IV, three) were matched with 14 patients for resection status, adjuvant mitotane treatment, stage, and tumor size. Median follow-up of patients still alive (n = 15) was 37 months. MAIN OUTCOME MEASURE: Survival without local recurrence and disease-free survival was the main outcome measure. RESULTS: Local recurrence was observed in two of 14 patients in the radiotherapy group and in 11 of 14 control patients. The probability to be free of local recurrence 5 yr after surgery differed significantly [79% (95% confidence interval, 53-100) vs. 12% (0-30); P < 0.01]. However, disease-free and overall survival were not significantly different between the two groups. Acute adverse events related to radiotherapy were mostly mild. One patient developed a partial Budd-Chiari syndrome. CONCLUSION: These data from the largest series of ACC patients treated with adjuvant tumor bed irradiation suggest that radiotherapy is effective in reducing the high rate of local recurrence in ACC. A randomized trial in high-risk patients is needed to further evaluate the efficacy of radiotherapy as an adjuvant treatment option in ACC.


Assuntos
Neoplasias do Córtex Suprarrenal/radioterapia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/radioterapia , Carcinoma Adrenocortical/cirurgia , Recidiva Local de Neoplasia/radioterapia , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/mortalidade , Adulto , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Mitotano/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Radioterapia/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
J Clin Endocrinol Metab ; 91(9): 3478-81, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16787982

RESUMO

BACKGROUND: Pheochromocytoma is a rare manifestation in patients with neurofibromatosis type 1 (NF 1). The 57-exon susceptibility gene NF1 has so far not been systematically scanned for unexpected germline mutations in individuals with sporadic pheochromocytoma. METHODS: Twenty-seven patients with bilateral adrenal and/or extraadrenal abdominal pheochromocytoma not carrying germline mutations of the genes VHL, RET, SDHB, and SDHD were selected from the European-American pheochromocytoma registry. All 57 exons and flanking intronic regions of the NF1 gene were PCR amplified using newly designed primer pairs to exclude the amplification of pseudogenes. Intragenic mutation scanning was performed using denaturing HPLC and bidirectional direct sequencing. RESULTS: Of the 27 apparently sporadic cases, one (4%) was found to have a pathogenic germline NF1 mutation, Leu303Arg. Clinical reevaluation of this individual, who had bilateral pheochromocytoma, revealed classic, but very mild, features of NF 1, one cutaneous neurofibroma, axillary freckling, and Lisch nodules of the iris as well as a few café-au-lait spots. CONCLUSIONS: In the absence of germline mutations in VHL, RET, SDHD, and SDHB, patients with pheochromocytoma, especially with bilateral disease, should be checked thoroughly for clinical lesions suggestive of underlying syndromes such as the cutaneous and ophthalmological features characteristic of NF 1.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Neurofibromatose 1/genética , Feocromocitoma/genética , Adolescente , Adulto , Idoso , Criança , Análise Mutacional de DNA , DNA de Neoplasias/genética , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
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