Low-intensity focused ultrasound to the human insular cortex differentially modulates the heartbeat-evoked potential: a proof-of-concept study.

Background: The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing. The insula and dorsal anterior cingulate cortex (dACC) are brain regions that may be involved in generating the HEP. Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique that can selectively target sub-regions of the insula and dACC to better understand their contributions to the HEP. Objective: Proof-of-concept study to determine whether LIFU modulation of the anterior insula (AI), posterior insula (PI), and dACC influences the HEP. Methods: In a within-subject, repeated-measures design, healthy human participants (n=16) received 10 minutes of stereotaxically targeted LIFU to the AI, PI, dACC or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was change in HEP amplitudes. Relationships between LIFU pressure and HEP changes were examined using linear mixed modelling. Peripheral indices of visceromotor output including heart rate and heart rate variability (HRV) were explored between conditions. Results: Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; this was partially explained by increased LIFU pressure. LIFU did not affect time or frequency dependent measures of HRV. Conclusions: These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations.

Wild Zebrafish Sentinels: Biological Monitoring of Site Differences Using Behavior and Morphology.

Environmental change poses a devastating risk to human and environmental health. Rapid assessment of water conditions is necessary for monitoring, evaluating, and addressing this global health danger. Sentinels or biological monitors can be deployed in the field using minimal resources to detect water quality changes in real time, quickly and cheaply. Zebrafish (Danio rerio) are ideal sentinels for detecting environmental changes due to their biomedical tool kit, widespread geographic distribution, and well-characterized phenotypic responses to environmental disturbances. Here, we demonstrate the utility of zebrafish sentinels by characterizing phenotypic differences in wild zebrafish between two field sites in India. Site 1 was a rural environment with flowing water, low-hypoxic conditions, minimal human-made debris, and high iron and lead concentrations. Site 2 was an urban environment with still water, hypoxic conditions, plastic pollution, and high arsenic, iron, and chromium concentrations. We found that zebrafish from Site 2 were smaller, more cohesive, and less active than Site 1 fish. We also found sexually dimorphic body shapes within the Site 2, but not the Site 1, population. Advancing zebrafish sentinel research and development will enable rapid detection, evaluation, and response to emerging global health threats.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina.

OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Macroprolactinoma appearing after resolution of hydrocephalus.

SUMMARY: The role of mechanical forces influencing the growth of a pituitary adenoma is poorly understood. In this paper we report the case of a young man with hyperprolactinaemia and an empty sella secondary to hydrocephalia, who developed a macroprolactinoma following the relief of high intraventricular pressure. LEARNING POINTS: The volume of a pituitary tumour may be influenced not only by molecular but also by local mechanical factors.Intratumoural pressure, resistance of the sellar diaphragm and intracranial liquid pressure may play a role in the final size of a pituitary adenoma.The presence of hydrocephalus may hide a pituitary macroadenoma.

Implementing a screening program for acromegaly in Latin America: necessity versus feasibility.

INTRODUCTION: Acromegaly is a rare disease with a large burden due its associated comorbidities and the life-long management required. Since the occurrence and severity of associated complications are related to length of exposure to the excess growth hormone seen in acromegaly, early diagnosis is imperative. The delay in diagnosis, however, can be long, and may be the result of a lack of disease awareness and screening programs. Since acromegaly is an uncommon disease, finding ways to increase recognition and diagnosis that would permit early detection in a logical and cost-effective manner could be a challenge. METHODS: We conducted a retrospective literature review for information relating to the screening and diagnosis of acromegaly using PubMed. The aim was to assess whether an acromegaly-screening program in Latin America (and elsewhere) would be both of use and be feasible. FINDINGS AND CONCLUSIONS: An earlier diagnosis allows earlier initiation of treatment, such as surgery and/or drugs, which leads to more successful disease management (biochemical control) and better outcomes. Since the delay in diagnosis can be long, we believe that clear opportunities exist for earlier (and increased) detection of acromegaly. This can be achieved by increasing disease awareness for earlier recognition of symptoms and by using targeted screening (rather than mass screening) programs.

[Ectopic mediastinal parathyroid adenoma. Detection with a radioisotopic probe and resolution with videothoracoscopy]. / Adenoma paratiroideo ectópico mediastinal. Diagnóstico por sonda de detección gamma y resección por videotoracoscopia.

We report a 66 years old woman with a diagnosis of primary hyperparathyroidism. Localization to mediastinum was obtained with parathyroid scintigraphy using 99mtc-methoxy-isobutyl-isonitrite (Tc99-MIBI). The patient was successfully operated upon by means of a videothora-coscopic approach. During the procedure serum parathormone was measured before and 10 minutes after adenomectomy, showing a more than 50% reduction from the basal level. An attempt to detect the precise site of the adenoma with a Tc99-MIBI probe was unsuccessful because of its proximity to the myocardium, but radioactivity was confirmed on the surgical specimen after resection. The patient's calcemia and parathormone levels became normal during the postoperative course and she remains normocalcemic 9 months after the procedure. In our case, preoperative localization and intraoperative parathormone measurements were both very useful for confirming surgical success; the intraoperative localization with a radioactive probe was not useful, but radioactivity was confirmed after resection on the surgical specimen. The endoscopic surgical procedure with videothoracoscopy was well tolerated, less painful than a thoracotomy, and it shortened the hospitalization period.

Adenoma paratiroideo ectopico mediastinal: diagnostico por sonda de deteccion gamma y reseccion por videotoracoscopia / Ectopic mediastinal parathyroid adenoma: detection with a radioisotopic probe and resolution with videothoracoscopy

Presentamos el caso de una mujer de 66 años con diagnóstico de hiperparatiroidismo primariopor adenoma paratiroideo ectópico mediastinal realizado por gammagrafía paratiroidea con 99mtcmetoxi-isobutil-isonitrito (Tc99-MIBI). Fue intervenida exitosamente mediante la técnica de videotoracoscopia.Durante el procedimiento se utilizó la medición de parathormona y a los 10 minutos de extirpado el adenoma seobtuvo un descenso mayor del 50% del basal. La sonda de detección gamma no fue efectiva in situ por la superposicióndel radioisótopo con el miocardio pero confirmó la radioactividad dentro del quirófano una vez extirpadoel adenoma. La paciente normalizó los valores de calcemia y parathormona en el postoperatorio y permaneciónormocalcémica luego de 9 meses de seguimiento. En nuestro caso, la localización prequirúrgica y elmonitoreo de parathormona intraoperatoria fueron de gran utilidad para el éxito quirúrgico, la sonda detectora marcada con Tc99-MIBI no fue efectiva in situ pero confirmó la radioactividad una vez extirpado el adenoma. El tratamiento quirúrgico endoscópico por videotoracoscopia fue bien tolerado, menos doloroso que la toracotomía y acortó el tiempo de internación

We report a 66 years old woman with a diagnosis of primary Hyperparathyroidism. Localization to mediastinum was obtained with parathyroid scintigraphy using 99mtc-methoxyisobutyl-isonitrite (Tc99-MIBI). The patient was successfully operated upon by means of a videothora-coscopicapproach. During the procedure serum parathormone was measured before and 10 minutes after adenomectomy,showing a more than 50% reduction from the basal level. An attempt to detect the precise site of the adenomawith a Tc99-MIBI probe was unsuccessful because of its proximity to the myocardium, but radioactivity was confirmed on the surgical specimen after resection. The patient’s calcemia and parathormone levels became normalduring the postoperative course and she remains normocalcemic 9 months after the procedure. In our case,preoperative localization and intraoperative parathormone measurements were both very useful for confirming surgical success; the intraoperative localization with a radioactive probe was not useful, but radioactivity was confirmedafter resection on the surgical specimen. The endoscopic surgical procedure with videothoracoscopy waswell tolerated, less painful than a thoracotomy, and it shortened the hospitalization period

Adenoma paratiroideo ectopico mediastinal: diagnostico por sonda de deteccion gamma y reseccion por videotoracoscopia / Ectopic mediastinal parathyroid adenoma: detection with a radioisotopic probe and resolution with videothoracoscopy

Presentamos el caso de una mujer de 66 años con diagnóstico de hiperparatiroidismo primariopor adenoma paratiroideo ectópico mediastinal realizado por gammagrafía paratiroidea con 99mtcmetoxi-isobutil-isonitrito (Tc99-MIBI). Fue intervenida exitosamente mediante la técnica de videotoracoscopia.Durante el procedimiento se utilizó la medición de parathormona y a los 10 minutos de extirpado el adenoma seobtuvo un descenso mayor del 50% del basal. La sonda de detección gamma no fue efectiva in situ por la superposicióndel radioisótopo con el miocardio pero confirmó la radioactividad dentro del quirófano una vez extirpadoel adenoma. La paciente normalizó los valores de calcemia y parathormona en el postoperatorio y permaneciónormocalcémica luego de 9 meses de seguimiento. En nuestro caso, la localización prequirúrgica y elmonitoreo de parathormona intraoperatoria fueron de gran utilidad para el éxito quirúrgico, la sonda detectora marcada con Tc99-MIBI no fue efectiva in situ pero confirmó la radioactividad una vez extirpado el adenoma. El tratamiento quirúrgico endoscópico por videotoracoscopia fue bien tolerado, menos doloroso que la toracotomía y acortó el tiempo de internación (AU)

We report a 66 years old woman with a diagnosis of primary Hyperparathyroidism. Localization to mediastinum was obtained with parathyroid scintigraphy using 99mtc-methoxyisobutyl-isonitrite (Tc99-MIBI). The patient was successfully operated upon by means of a videothora-coscopicapproach. During the procedure serum parathormone was measured before and 10 minutes after adenomectomy,showing a more than 50% reduction from the basal level. An attempt to detect the precise site of the adenomawith a Tc99-MIBI probe was unsuccessful because of its proximity to the myocardium, but radioactivity was confirmed on the surgical specimen after resection. The patientãs calcemia and parathormone levels became normalduring the postoperative course and she remains normocalcemic 9 months after the procedure. In our case,preoperative localization and intraoperative parathormone measurements were both very useful for confirming surgical success; the intraoperative localization with a radioactive probe was not useful, but radioactivity was confirmedafter resection on the surgical specimen. The endoscopic surgical procedure with videothoracoscopy waswell tolerated, less painful than a thoracotomy, and it shortened the hospitalization period (AU)

Adenoma paratiroideo ectopico mediastinal: diagnostico por sonda de deteccion gamma y reseccion por videotoracoscopia / Ectopic mediastinal parathyroid adenoma: detection with a radioisotopic probe and resolution with videothoracoscopy

Presentamos el caso de una mujer de 66 años con diagnóstico de hiperparatiroidismo primariopor adenoma paratiroideo ectópico mediastinal realizado por gammagrafía paratiroidea con 99mtcmetoxi-isobutil-isonitrito (Tc99-MIBI). Fue intervenida exitosamente mediante la técnica de videotoracoscopia.Durante el procedimiento se utilizó la medición de parathormona y a los 10 minutos de extirpado el adenoma seobtuvo un descenso mayor del 50% del basal. La sonda de detección gamma no fue efectiva in situ por la superposicióndel radioisótopo con el miocardio pero confirmó la radioactividad dentro del quirófano una vez extirpadoel adenoma. La paciente normalizó los valores de calcemia y parathormona en el postoperatorio y permaneciónormocalcémica luego de 9 meses de seguimiento. En nuestro caso, la localización prequirúrgica y elmonitoreo de parathormona intraoperatoria fueron de gran utilidad para el éxito quirúrgico, la sonda detectora marcada con Tc99-MIBI no fue efectiva in situ pero confirmó la radioactividad una vez extirpado el adenoma. El tratamiento quirúrgico endoscópico por videotoracoscopia fue bien tolerado, menos doloroso que la toracotomía y acortó el tiempo de internación (AU)

We report a 66 years old woman with a diagnosis of primary Hyperparathyroidism. Localization to mediastinum was obtained with parathyroid scintigraphy using 99mtc-methoxyisobutyl-isonitrite (Tc99-MIBI). The patient was successfully operated upon by means of a videothora-coscopicapproach. During the procedure serum parathormone was measured before and 10 minutes after adenomectomy,showing a more than 50% reduction from the basal level. An attempt to detect the precise site of the adenomawith a Tc99-MIBI probe was unsuccessful because of its proximity to the myocardium, but radioactivity was confirmed on the surgical specimen after resection. The patientãs calcemia and parathormone levels became normalduring the postoperative course and she remains normocalcemic 9 months after the procedure. In our case,preoperative localization and intraoperative parathormone measurements were both very useful for confirming surgical success; the intraoperative localization with a radioactive probe was not useful, but radioactivity was confirmedafter resection on the surgical specimen. The endoscopic surgical procedure with videothoracoscopy waswell tolerated, less painful than a thoracotomy, and it shortened the hospitalization period (AU)

Cáncer de tiroides: experiencia hospitalaria en 20 años / Thyroid cancer: 20 years experience in a hospital

Se revisaron 117 casos de cáncer de tiroides resgistrados a lo largo de veinte años en el Hospital Privado de Comunidad de Mar del Plata, para analizar las variables que influyeron en su evolución y poder comparadas con otras casuísticas. Del análises de los datos se desprende un porcentaje similar a otras series para las variables histológicas, con un predominio del sexo feminino (4,2:1). Un tercio de los pacientes tenía algún antecedente tiroideo previo. La edad de presentación fue significativamente mayor en aquellos pacientes que recidivaron o fallecieron como consecuencia de la enfermidad. Adquirió importancia en la evolución el estado tumoral al momento deldiagnóstico y el subtipo histológico, no pudiendo confirmarse que el sexo, el tipo de cirurgía o el tratamiento hormonal suprersor tuvieran significación pronóstica. La punción aspiración con aguja fina mostró un elevado valor predictivo positivo (96 por ciento) con una sensibilidad moderada (75 por ciento). Se observó además una merma gradual de las complicaciones posquirúrgicas; el último caso de hipoparatiroidismo posoperatorio permanente se registró en 1986.

Cáncer de tiroides: experiencia hospitalaria en 20 años / Thyroid cancer: 20 years experience in a hospital

Se revisaron 117 casos de cáncer de tiroides resgistrados a lo largo de veinte años en el Hospital Privado de Comunidad de Mar del Plata, para analizar las variables que influyeron en su evolución y poder comparadas con otras casuísticas. Del análises de los datos se desprende un porcentaje similar a otras series para las variables histológicas, con un predominio del sexo feminino (4,2:1). Un tercio de los pacientes tenía algún antecedente tiroideo previo. La edad de presentación fue significativamente mayor en aquellos pacientes que recidivaron o fallecieron como consecuencia de la enfermidad. Adquirió importancia en la evolución el estado tumoral al momento deldiagnóstico y el subtipo histológico, no pudiendo confirmarse que el sexo, el tipo de cirurgía o el tratamiento hormonal suprersor tuvieran significación pronóstica. La punción aspiración con aguja fina mostró un elevado valor predictivo positivo (96 por ciento) con una sensibilidad moderada (75 por ciento). Se observó además una merma gradual de las complicaciones posquirúrgicas; el último caso de hipoparatiroidismo posoperatorio permanente se registró en 1986. (AU)