Erratum to: Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.

Peer reviewe

A User-Centered Chatbot (Wakamola) to Collect Linked Data in Population Networks to Support Studies of Overweight and Obesity Causes: Design and Pilot Study

[EN] Background: Obesity and overweight are a serious health problem worldwide with multiple and connected causes. Simultaneously, chatbots are becoming increasingly popular as a way to interact with users in mobile health apps. Objective: This study reports the user-centered design and feasibility study of a chatbot to collect linked data to support the study of individual and social overweight and obesity causes in populations. Methods: We first studied the users' needs and gathered users' graphical preferences through an open survey on 52 wireframes designed by 150 design students; it also included questions about sociodemographics, diet and activity habits, the need for overweight and obesity apps, and desired functionality. We also interviewed an expert panel. We then designed and developed a chatbot. Finally, we conducted a pilot study to test feasibility. Results: We collected 452 answers to the survey and interviewed 4 specialists. Based on this research, we developed a Telegram chatbot named Wakamola structured in six sections: personal, diet, physical activity, social network, user's status score, and project information. We defined a user's status score as a normalized sum (0-100) of scores about diet (frequency of eating 50 foods), physical activity, BMI, and social network. We performed a pilot to evaluate the chatbot implementation among 85 healthy volunteers. Of 74 participants who completed all sections, we found 8 underweight people (11%), 5 overweight people (7%), and no obesity cases. The mean BMI was 21.4 kg/m(2) (normal weight). The most consumed foods were olive oil, milk and derivatives, cereals, vegetables, and fruits. People walked 10 minutes on 5.8 days per week, slept 7.02 hours per day, and were sitting 30.57 hours per week. Moreover, we were able to create a social network with 74 users, 178 relations, and 12 communities. Conclusions: The Telegram chatbot Wakamola is a feasible tool to collect data from a population about sociodemographics, diet patterns, physical activity, BMI, and specific diseases. Besides, the chatbot allows the connection of users in a social network to study overweight and obesity causes from both individual and social perspectives.Moreover, the authors acknowledge the funding support for this study provided by the CrowdHealth Project (Collective Wisdom Driving Public Health Policies, 727560).Asensio-Cuesta, S.; Blanes-Selva, V.; Conejero, JA.; Frigola, A.; Portolés, MG.; Merino-Torres, JF.; Rubio Almanza, M.... (2021). A User-Centered Chatbot (Wakamola) to Collect Linked Data in Population Networks to Support Studies of Overweight and Obesity Causes: Design and Pilot Study. JMIR Medical Informatics. 9(4):1-14. https://doi.org/10.2196/17503S1149

Riesgo cardiovascular y cirugía bariátrica en pacientes con alteración del metabolismo hidrocarbonado

La tesis doctoral es un compendio de tres publicaciones científicas. El objetivo principal fue establecer si los pacientes con obesidad mórbida y prediabetes presentarían una reducción del riesgo cardiovascular similar a los pacientes con DM2 tras someterse a cirugía bariátrica.Además, se ha realizado una revisión del tratamiento farmacológico y quirúrgico en obesidad y DM2. Finalmente, se realizó un metaanálisis para valorar si la cirugía metabólica era efectiva en la remisión de la DM2 en pacientes con IMC < 30 kg/m2. Se observó que los pacientes con DM2 son los que más reducen su riesgo cardiovascular 12 meses tras cirugía, aunque los pacientes con prediabetes también mejoran. Actualmente se dispone de nuevos fármacos para el tratamiento de la obesidad y la DM2 que mejoran el riesgo cardiovascular, además de la cirugía. La cirugía metabólica puede ser efectiva en pacientes con DM2 sin obesidad, aunque son necesarios más estudios a largo plazo.The doctoral thesis is a compendium of three scientific publications. The main objective was to establish whether patients with morbid obesity and pre-diabetes would present a similar cardiovascular risk reduction to patients with T2DM after undergoing bariatric surgery. In addition, a review of pharmacological and surgical treatment has been carried out in obesity and T2DM. Finally, a meta-analysis was performed to assess whether metabolic surgery was effective in the remission of T2DM in patients with BMI <30 kg/m2. It was observed that patients with T2DM are those who reduce their cardiovascular risk the most 12 months after surgery, although patients with pre-diabetes also experience an improvement. Currently, new drugs are available for treatment of obesity and T2DM that improve cardiovascular risk, in addition to surgery. Metabolic surgery may be effective in patients with T2DM without obesity, although more long-term studies are necessary

Reproduction, smell, and neurodevelopmental disorders: genetic defects in different hypogonadotropic hypogonadal syndromes.

The neuroendocrine control of reproduction in mammals is governed by a neural hypothalamic network of nearly 1500 gonadotropin-releasing hormone (GnRH) secreting neurons that modulate the activity of the reproductive axis across life. Congenital hypogonadotropic hypogonadism (HH) is a clinical syndrome that is characterized by partial or complete pubertal failure. HH may result from inadequate hypothalamic GnRH axis activation, or a failure of pituitary gonadotropin secretion/effects. In man, several genes that participate in olfactory and GnRH neuronal migration are thought to interact during the embryonic life. A growing number of mutations in different genes are responsible for congenital HH. Based on the presence or absence of olfaction dysfunction, HH is divided in two syndromes: HH with olfactory alterations [Kallmann syndrome (KS)] and idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH). KS is a heterogeneous disorder affecting 1 in 5000 males, with a three to fivefold of males over females. KS is associated with mutations in KAL1, FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, NELF, and WDR11 genes that are related to defects in neuronal migration. These reproductive and olfactory deficits include a variable non-reproductive phenotype, including sensorineural deafness, coloboma, bimanual synkinesis, craniofacial abnormalities, and/or renal agenesis. Interestingly, defects in PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11 genes are also associated with normosmic IHH, whereas mutations in KISS1/KISSR, TAC3/TACR3, GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB, and LHB are only present in patients with normosmic IHH. In this paper, we summarize the reproductive, neurodevelopmental, and genetic aspects of HH in human pathology

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor.

Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia

Hypercalcémie refractaire et secretion de calcitone ectopique dans un tumeur pancreatique neuroendocrinienne maligne: effetcs hypocalcémiants du cinacalcet

Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments. Observation: In 2009, a well differentiated pancreatic neuroendocrine tumor (Ki-67= 2%) is diagnosed in a 52-year-old diabetic man. The tumor is revealed with a splenic and hepatic carcinomatosis. Plasmatic calcium was: 3.54 mmol/L (2.15 - 2.6). Biology showed hypophosphatemia, PTH < 4 ng/ml, high 1-25 OH VitD, calcitonin: 1016 ng/ml (< 12 ng/ml). He had hypercalciuria and hypophosphaturia. He received for two years several cycles of Streptozotocin-ADRIAMYCIN and FOLFOX, with partial control of the tumor mass and calcium levels. In 2012, calcitonin levels are 29 ng/ml whereas calcemia is 3.17 mmol/L. Hypercalcemia is refractory to hyperhydration, diuretics, corticosteroids, and bisphosphonates therapy. Cinacalcet (Mimpara) is prescribed up to 120 mg/day (PO). Calcemia decreases gradually from 3 to 2.87 and then 2.76 mmol/L. PTH and calcitonin-the tumor mass remain unchanged. After two months of Cinacalcet treatment, Sunitinib (Sutent) 37.5 mg per day was added. During the third month, calcium levels dropped to 2.09 mmol/L and PTH raised to 78 pg/ml, requiring discontinuation of Mimpara. Calcitonin normalized, with a further improvement over pancreatic and metastatic lesions. Conclusion: Cinacalcet is a Calcium Sensing Receptor oral agonist. Cinacalcet hypocalcemic effects have not been previously documented in pancreatic paraneoplastic hypercalcemia. In our patient, Cinacalcet has significantly improved cancer prognosis: this drug could be a new alternative in paraneoplastic hypercalcemia

Cardiovascular risk reduction over time in patients with diabetes or pre-diabetes undergoing bariatric surgery: data from a single-center retrospective observational study

Abstract Background Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities. Methods This is a retrospective observational study with 105 patients with type 2 diabetes (DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60 months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score. Results Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (p < 0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60 months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes. Conclusion Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI ≥ 35 kg/m2

Pan-European Economic Analysis to Identify Cost Savings for the Health Care Systems as a Result of Integrating Glucose Monitoring Based Telemedical Approaches Into Diabetes Management

BACKGROUND:: Self-monitoring of blood glucose supported by the diabetes-app OneTouch Reveal has demonstrated to improve HbA1c. We aimed at analyzing costs savings related the integration of telemedical features into diabetes management.METHODS:: Data from a randomized controlled trial were used to assess the 10-year risk of patients for fatal myocardial infarction (MI). On the basis of this risk assessments-also related to a 5% or 10% reduction of hypoglycemic episodes-cost savings for the health care systems of five European countries-France, Germany, Italy, Spain, and the United Kingdom-were modeled.RESULTS:: HbA1c reduction of 0.92% in insulin-treated type 2 diabetes patients (T2DM) was associated with a 2.3% decreased 10-year risk for fatal MI. In combination with a 10% reduction of hypoglycemic events this risk reduction led to cost savings of 16.1 million (France), 57.8 million (Germany), 30.9 million (Italy), 23.8 million (Spain), and 5.8 million (UK), considering all insulin-treated T2DM patients in the respective countries.CONCLUSION:: Improving metabolic control and thus risk for comorbidities like MI by combining the glucose meter with CRI with telemedical features has the potential to reduce costs for European health care systems

Budget Impact of Improved Diabetes Management by Utilization of Glucose Meters With a Color-Range Indicator-Comparison of Five European Healthcare Systems

Costs for the treatment of diabetes and its comorbidities are a major international issue. A recent randomized clinical trial showed that the introduction of color range indicator (CRI)-based glucose meters (GMs) positively affects the HbA1c of patients with type 1 and type 2 diabetes, when compared to GMs without a CRI. This budget impact analysis aimed to translate this beneficial effect of CRI-based GMs, OneTouch Verio Flex and OneTouch Verio, into potential monetary impact for the healthcare systems of five European countries, Germany, Spain, Italy, France, and the United Kingdom.; Data from a randomized controlled trial, evaluating the effect of CRI-based GMs, were used to estimate the ten-year risk of patients for fatal myocardial infarction (MI) as calculated by the UK Prospective Diabetes Study (UKPDS) risk engine. On the basis of assessed risks for MI, the potential monetary impact for the healthcare systems in five European countries was modeled.; Based on a mean HbA1c reduction of 0.36%, as demonstrated in a randomized controlled trial, the UKPDS risk engine estimated a reduction of 2.4% of the ten-year risk of patients for fatal MI. When applied to our economic model, substantial potential cost savings for the healthcare systems of five European countries were calculated: Euro547 472 (France), Euro9.0 million (Germany), Euro6.0 million (Italy), Euro841 799 (Spain), and Euro421 069 (United Kingdom) per year.; Improving metabolic control in patients with diabetes by the utilization of CRI-based GMs may have substantial positive effects on the expenditure of the healthcare systems of several European countries