Usefulness of Ultrasound in Assessing the Impact of Bariatric Surgery on Body Composition : a Pilot Study

Bariatric surgery (BS) has a significant impact on body composition. The purpose of the study is to evaluate the usefulness of musculoskeletal ultrasound (MUS) to bioelectrical impedance (BIA) in the follow-up of patients undergoing BS in terms of body composition and quality of life (QoL). This is a prospective pilot study including 32 subjects (75% female, mean age: 49.15 ± 1.9 years) who underwent BS. Fat mass (FM), lean mass (LM), and skeletal muscle index (SMI) were calculated by BIA. MUS measured subcutaneous fat (SF) and thigh muscle thickness (TMT) of the quadriceps. QoL was assessed by the Moorehead-Ardelt questionnaire. All these measurements were performed 1 month prior to BS and at 12-month follow-up. The mean BMI decreased by 6.63 ± 1.25 kg/m 2 (p =0.001). We observed significant reductions in FM (p =0.001) and SF (p =0.007) and in LM (p =0.001) but not in SMI and TMT. We found a correlation between the FM and SF (pre-surgical, r =0.42, p =0.01; post-surgical, r =0.52, p =0.003) and between SMI and TMT (pre-surgical, r =0.35, p =0.04; post-surgical, r =0.38, p =0.03). QoL test showed significant improvement (p =0.001). In addition, a correlation between the QoL questionnaire and TMT post-surgery (r =0.91, p =0.019) was observed. However, we did not find any statistically significant correlation between QoL assessment and SMI or LM. Our results suggest that MUS can be complementary to BIA for the evaluation and the follow-up of body composition after BS. TMT of quadriceps can provide relevant information about regional sarcopenia and has a significant correlation with QoL

Insuficiencia suprarrenal aguda por metástasis suprarrenales secundarias a melanoma cutáneo

Primary adrenal insufficiency is a vital emergency that requires a substitute treatment without delay. Clinically, it can present with nonspecific symptoms, so that its diagnostic suspicion can sometimes be a challenge. Bilateral adrenal metastases are well described but they uncommonly trigger adrenal insufficiency. We illustrate a case of malignant melanoma that required immediate emergency assistance with hydrocortisone.La insuficiencia suprarrenal primaria es una urgencia vital que requiere tratamiento sustitutivo sin demora. Clínicamente se puede presentar con síntomas inespecíficos, por lo que su sospecha diagnóstica en algunas ocasiones puede suponer un reto. Las metástasis suprarrenales bilaterales están bien descritas, pero raramente desencadenan insuficiencia suprarrenal. Ilustramos un caso de melanoma maligno que requirió asistencia inmediata en Urgencias con hidrocortisona

Is Trabecular Bone Score Valuable In Bone Microstructure Assessment After Gastric Bypass In Women With Morbid Obesity?

Introduction: The effects of bariatric surgery on skeletal health raise many concerns. Trabecular bone score (TBS) is obtained through the analysis of lumbar spine dual X-ray absorptiometry (DXA) images and allows an indirect assessment of skeletal microarchitecture (MA). The aim of our study was to evaluate the changes in bone mineral density (BMD) and alterations in bone microarchitecture assessed by TBS in morbidly obese women undergoing Roux-en-Y gastric bypass (RYGB), over a three-year follow-up. Material/Methods: A prospective study of 38 morbidly obese white women, aged 46.3 +/- 8.2 years, undergoing RYGB was conducted. Biochemical analyses and DXA scans with TBS evaluation were performed before and at one year and three years after surgery. Results: Patients showed normal calcium and phosphorus plasma concentrations throughout the study. However, 25-hydroxyvitamin D (25(OH)D-3) decreased, and 71% of patients had a vitamin D deficiency at three years. BMD at femoral neck and lumbar spine (LSBMD) significantly decreased 13.53 +/- 5.42% and 6.03 +/- 6.79%, respectively, during the three-year follow-up; however Z-score values remained above those for women of the same age. TBS was within normal ranges at one and three years (1.431 +/- 106 and 1.413 +/- 85, respectively), and at the end of the study, 73.7% of patients had normal bone MA. TBS at three years correlated inversely with age (r = -0.41, p = 0.010), body fat (r = -0.465, p = 0.004) and greater body fat deposited in trunk (r = -0.48, p = 0.004), and positively with LSBMD (r = 0.433, p = 0.007), fat mass loss (r = 0.438, p = 0.007) and lean mass loss (r = 0.432, p = 0.008). In the regression analysis, TBS remained associated with body fat ( = -0.625, p = 0.031; R-2 = 0.47). The fracture risk, calculated by FRAX((R)) (University of Sheffield, Sheffield, UK), with and without adjustment by TBS, was low. Conclusion: Women undergoing RYGB in the mid-term have a preserved bone MA, assessed by TBS

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors

Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. We found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. NF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET

Data mining analyses for precision medicine in acromegaly: a proof of concept

Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL. We took advantage of a multicenter study of 71 acromegaly patients and we used advanced mathematical modelling to predict SRL response combining molecular and clinical information. Different models of patient stratification were obtained, with a much higher accuracy when the studied cohort is fragmented according to relevant clinical characteristics. Considering all the models, a patient stratification based on the extrasellar growth of the tumor, sex, age and the expression of E-cadherin, GHRL, IN1-GHRL, DRD2, SSTR5 and PEBP1 is proposed, with accuracies that stand between 71 to 95%. In conclusion, the use of data mining could be very useful for implementation of personalized medicine in acromegaly through an interdisciplinary work between computer science, mathematics, biology and medicine. This new methodology opens a door to more precise and personalized medicine for acromegaly patients

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to = 3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.Results: In all, 30 patients were responders and 17 were non-responders. GH(2h) was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH(2h) = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH(2h) = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH(2h) than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 +/- 4.2 vs 3.3 +/- 2.1; p=0.01).Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

IntroductionWe previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .MethodsA total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs’ response. Those patients whose IGF1 decreased to &lt;3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.ResultsIn all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p&lt;0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p&lt;0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01).ConclusionThe sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly

Usefulness of Muscle Ultrasound to Study Sarcopenic Obesity: A Pilot Case-Control Study

Background and objectives: Sarcopenic obesity (SO) is an emerging problem, especially in candidates for bariatric surgery (BS). We hypothesized that musculoskeletal ultrasound (MUS), a simple and accessible method, could be a reliable index of SO. Materials and Methods: A cross-sectional pilot study including 122 subjects (90 cases and 32 controls, 73% female, mean age: 51.2 years) who underwent BS was conducted at University Hospital M&uacute;tua Terrassa. The lean mass (LM) was calculated by bioelectrical impedance analysis (BIA) and the thigh muscle thickness (TMT) by MUS. To identify the subjects with SO by BIA, we used skeletal muscle index (SMI). The validity of MUS was determined using the ROC curve. Results: The mean BMI in the obesity group was 44.22 kg/m2. We observed a correlation between the LM and SMI assessed by BIA and the TMT assessed by MUS (R = 0.46, p &lt; 0.001). This correlation was maintained at significant levels in the SO group (n = 40): R = 0.79; p = 0.003). The TMT assessed by MUS was able to predict SMI using BIA (AUC 0.77; 95% CI: 0.68242 to 0.84281). The optimal cut-off point for maximum efficiency was 1.57 cm in TMT (sensitivity = 75.6% and specificity = 71.1%). Conclusions: The TMT of the quadriceps assessed by US is a useful tool for identifying subjects with SO. Larger studies to validate this simple low-cost screening strategy are warranted

La ecografía : una nueva herramienta para el estudio de la obesidad sarcopénica

Aquesta tesi doctoral es presenta com a compendi de 3 publicacions en revistes d'alt impacte que segueixen una coherència temàtica ja que exploren l'utilitat de l'ecografia en la valoració de la sarcopènia en pacients amb obesitat i candidats a cirurgia bariàtrica tant en la fase pre- (Simó-Servat et al. J Clin Med. 2022;11:2886) com post-cirurgia (Simó-Servat et al. Obes Surg 2023; 33:1211-1217), així com en pacients de més de 70 anys amb diabetis i fragilitat, la majoria també amb obesitat (Simó-Servat et al. Biology 2023;12:884). Les troballes de la tesi obren noves perspetives a l 'hora d 'avançar en l 'estudi de la composició corporal en els pacients amb obesitat sarcopènica. La utilitat de l'ecografia músculoesqueletètica pel diagnòstic de la obesitat sarcpènica és el que els tres articles de la tesis present intenten validar i demostrar, proporcionant bones correlacions entre ela paràmetres que ens ofereix la bioimpedància elèctrica (un mètode gold estandar per l'estudi de composició corporal) i la distància del greix subcutani i el gruix muscular. Per tant, les principals aportacions d'aquest treball és el valor que té l'ecografia muscular (concretament del quàdriceps) com mètode de cribratge per identificar els pacients amb obesitat sarcopènica i com eina per monitoritzar els canvis que hi ha en la composició corporal després de la cirurgia bariàtrica. Alhora es demostra també la seva utilitat per informar-nos de la capacitat funcional en pacients fràgils d'edat avançada amb diabetis, que es relaciona amb els tests de qualitat de vida. Des del punt de vista d'aplicació pràctica dels resultats, aquesta tesi es paradigmàtica ja que pot canviar el procediment diagnòstic i de seguiment d'una condició cada vegada més freqüent com és l'obesitat sarcopènica. Val a dir que la simplicitat i innocuïtat de l'ecografia son clarament un avantatge respecte a les altres tècniques per l'estudi de la composició corporal. El punts forts de la tesi és que s'ha comparat amb la BIA (mètode estàndard) demostrant que son mètodes complementaris però al ser estudis pilot caldrà confirmar-ho en d'altres estudis on s'incloguin més pacients. A partir dels resultats obtinguts en aquesta tesi s obren noves línies d investigació que acabaran repercutint en un millor diagnòstic i tractament personalitzat: - Establir punts de tall per al diagnòstic d obesitat sarcopènica adaptats a diferents poblacions - Protocolitzar i estandarditzar el mètode de medició de l ecografia per tal d establir un diagnòstic més precís d'obesitat sarcopènica - Treballar en la detecció de canvis qualitatius en l estructura muscular mitjançant ecografia que permeti un diagnòstic més precoç i contribuir a modificar el pronòstic de la malaltia Com a punts febles a destacar que es tracta d un estudi pilot i que per tant els resultats han de ser validats en sèries més àmplies. També la falta d una definició i punts de tall estandaritzats, però tal i com s ha comentat en el paràgraf anterior, això obre noves vies de treball per continuar avançant en aquesta línia. D altra banda, a la versió final de la tesi es va decidir eliminar la part de deteriorament cognitiu i la seva relació amb l obesitat sarcopènica, com estava inicialment previst en el projecte. Això es va fer per centrar els esforços i resultats en la validació de l ecografia com a mètode diagnòstic de l obesitat sarcopènica. El deteriorament cognitiu és una entitat complexa que requereix un estudi en profunditat per separat. Els tres treballs publicats en revistes revisades per parells i amb factor d'impacte reconegut ja parla en favor de la solidesa del treball efectuat. Les línies de futur plantejades també donaran de ben segur els seus fruits que es traduiran en d'altres publicacions, motiu pel quan treballarem.Esta tesis doctoral se presenta como una recopilación de 3 publicaciones en revistas de alto impacto que siguen una coherencia temática, ya que exploran la utilidad de la ecografía en la evaluación de la sarcopenia en pacientes con obesidad y candidatos a cirugía bariátrica, tanto en la fase preoperatoria (Simó-Servat et al. J Clin Med. 2022; 11:2886) como en la postoperatoria (Simó-Servat et al. Obes Surg 2023; 33:1211-1217), así como en pacientes mayores de 70 años con diabetes y fragilidad, la mayoría de ellos también con obesidad (Simó-Servat et al. Biology 2023; 12:884). Los hallazgos de la tesis abren nuevas perspectivas para avanzar en el estudio de la composición corporal en pacientes con obesidad sarcopénica. La utilidad de la ecografía musculoesquelética para diagnosticar la obesidad sarcopénica es lo que los tres artículos de la tesis intentan validar y demostrar, proporcionando fuertes correlaciones entre los parámetros proporcionados por la impedancia bioeléctrica (un método estándar de oro para estudiar la composición corporal) y el grosor de la grasa subcutánea y el grosor muscular. Por lo tanto, las principales contribuciones de este trabajo radican en el valor de la ecografía muscular (específicamente del cuádriceps) como método de detección para identificar a pacientes con obesidad sarcopénica y como herramienta para monitorear los cambios en la composición corporal después de la cirugía bariátrica. También se demuestra su utilidad para informarnos sobre la capacidad funcional de pacientes ancianos y frágiles con diabetes, lo que se correlaciona con pruebas de calidad de vida. Desde una perspectiva de aplicación práctica, esta tesis es innovadora, ya que puede cambiar los procedimientos de diagnóstico y seguimiento de una afección cada vez más común, como la obesidad sarcopénica. Cabe destacar que la simplicidad y seguridad de la ecografía son ventajas claras en comparación con otras técnicas para estudiar la composición corporal. Las fortalezas de la tesis radican en la comparación con la impedancia bioeléctrica (el método estándar), demostrando que son métodos complementarios, pero se necesita una mayor validación en estudios más amplios. Basándonos en los resultados obtenidos en esta tesis, se abren nuevas líneas de investigación que finalmente conducirán a un mejor diagnóstico y tratamiento personalizado: Establecimiento de puntos de corte para el diagnóstico de la obesidad sarcopénica adaptados a diferentes poblaciones. Estandarización y protocolización del método de medición por ecografía para un diagnóstico más preciso de la obesidad sarcopénica. Trabajo en la detección de cambios cualitativos en la estructura muscular mediante ecografía que permita un diagnóstico más temprano y contribuya a modificar el pronóstico de la enfermedad. En cuanto a las debilidades, es importante señalar que se trata de un estudio piloto y, por lo tanto, los resultados deben validarse en cohortes más grandes. Además, la falta de definiciones y puntos de corte estandarizados, pero como se mencionó en el párrafo anterior, esto abre nuevas vías para trabajos futuros. Por otro lado, en la versión final de la tesis, se omitió la parte sobre el deterioro cognitivo y su relación con la obesidad sarcopénica, como se había planeado inicialmente en el proyecto. Esto se hizo para centrar los esfuerzos y resultados en la validación de la ecografía como método de diagnóstico de la obesidad sarcopénica. El deterioro cognitivo es una entidad compleja que requiere un estudio en profundidad por separado. Los tres trabajos publicados en revistas revisadas por expertos con factores de impacto reconocidos hablan de la solidez del trabajo realizado. Las direcciones futuras propuestas sin duda darán sus frutos, que se traducirán en más publicaciones y más trabajo por delante.This doctoral thesis is presented as a compilation of 3 publications in high-impact journals that follow a thematic coherence, as they explore the utility of ultrasound in the assessment of sarcopenia in patients with obesity and candidates for bariatric surgery, both in the pre-surgery phase (Simó-Servat et al. J Clin Med. 2022;11:2886) and post-surgery (Simó-Servat et al. Obes Surg 2023; 33:1211-1217), as well as in patients over 70 years of age with diabetes and frailty, most of whom also have obesity (Simó-Servat et al. Biology 2023;12:884). The findings of the thesis open new perspectives for advancing the study of body composition in patients with sarcopenic obesity. The utility of musculoskeletal ultrasound for diagnosing sarcopenic obesity is what the three articles in the thesis attempt to validate and demonstrate, providing strong correlations between the parameters provided by bioelectrical impedance (a gold standard method for studying body composition) and subcutaneous fat thickness and muscle thickness. Therefore, the main contributions of this work lie in the value of muscular ultrasound (specifically of the quadriceps) as a screening method to identify patients with sarcopenic obesity and as a tool to monitor changes in body composition after bariatric surgery. It also demonstrates its utility in informing us about the functional capacity of elderly, frail patients with diabetes, which correlates with quality of life tests. From a practical application perspective, this thesis is groundbreaking, as it can change the diagnostic and monitoring procedures for an increasingly common condition such as sarcopenic obesity. It's worth noting that the simplicity and safety of ultrasound are clear advantages over other techniques for studying body composition. The strengths of the thesis lie in the comparison with BIA (the standard method), demonstrating that they are complementary methods, but further validation is needed in larger studies. Based on the results obtained in this thesis, new lines of research are opening up that will ultimately lead to better diagnosis and personalized treatment: Establishing cutoff points for the diagnosis of sarcopenic obesity adapted to different populations Standardizing and protocolizing the ultrasound measurement method for a more precise diagnosis of sarcopenic obesity Working on the detection of qualitative changes in muscle structure through ultrasound that allows for earlier diagnosis and contributes to modifying the disease's prognosis. As for weaknesses, it's worth noting that this is a pilot study, and therefore, the results need to be validated in larger cohorts. Also, the lack of standardized definitions and cutoff points, but as mentioned in the previous paragraph, this opens up new avenues for further work. On the other hand, in the final version of the thesis, the part on cognitive impairment and its relationship with sarcopenic obesity, as initially planned in the project, was omitted. This was done to focus efforts and results on the validation of ultrasound as a diagnostic method for sarcopenic obesity. Cognitive impairment is a complex entity that requires separate in-depth study. The three published works in peer-reviewed journals with recognized impact factors speak to the strength of the work carried out. The future directions proposed will undoubtedly yield their results, which will translate into further publications, giving us more to work on

Usefulness of Muscle Ultrasound to Study Sarcopenic Obesity: A Pilot Case-Control Study

Background and objectives: Sarcopenic obesity (SO) is an emerging problem, especially in candidates for bariatric surgery (BS). We hypothesized that musculoskeletal ultrasound (MUS), a simple and accessible method, could be a reliable index of SO. Materials and Methods: A cross-sectional pilot study including 122 subjects (90 cases and 32 controls, 73% female, mean age: 51.2 years) who underwent BS was conducted at University Hospital Mútua Terrassa. The lean mass (LM) was calculated by bioelectrical impedance analysis (BIA) and the thigh muscle thickness (TMT) by MUS. To identify the subjects with SO by BIA, we used skeletal muscle index (SMI). The validity of MUS was determined using the ROC curve. Results: The mean BMI in the obesity group was 44.22 kg/m2. We observed a correlation between the LM and SMI assessed by BIA and the TMT assessed by MUS (R = 0.46, p n = 40): R = 0.79; p = 0.003). The TMT assessed by MUS was able to predict SMI using BIA (AUC 0.77; 95% CI: 0.68242 to 0.84281). The optimal cut-off point for maximum efficiency was 1.57 cm in TMT (sensitivity = 75.6% and specificity = 71.1%). Conclusions: The TMT of the quadriceps assessed by US is a useful tool for identifying subjects with SO. Larger studies to validate this simple low-cost screening strategy are warranted