[Calciphylaxis, risk factors, treatment and outcomes. Retrospective study of 39 patients]. / Calcifilaxis, factores de riesgo, tratamiento y evolución. Estudio retrospectivo de 39 pacientes.

INTRODUCTION: Calciphylaxis is a serious vascular disorder characterized by calcification of tunica media, intimal hyperplasia, thrombosis, and skin necrosis. It was described in patients with renal failure (UC), although it can occur in its absence (NUC). Its risk factors are under study and its diagnosis can be complex. Over a decade ago, its mortality was estimated at 60-80%. Recent studies indicate that it has decreased (40%). METHODS: A retrospective study was carried out in the period between January 1, 2011 and December 31, 2019. The past medical record, clinical characteristics, laboratory and histopathological findings, and evolution of all patients with calciphylaxis evaluated at the Hospital Italiano de Buenos Aires were reviewed. RESULTS: Thirty-nine patients were included. Sixtyone percent were men and 39% were NUC cases. Eightytwo percent had arterial hypertension, 66% obesity and 46% diabetes. Of those, 49% received coumarin anticoagulants. All patients with NUC and 75% with UC presented ulcers with necrosis, located more frequently on the legs. In 72% of the cases the histological diagnosis was made with one biopsy. In all the treatment was multimodal and mortality at one year was 42%. CONCLUSION: We observed a high proportion of patients with NUC, in relation to what is reported in the literature, and that half received vitamin K antagonists. The histological diagnosis was made with one biopsy in most of the cases, as the surgical technique for taking the sample, the Von Kossa staining and the evaluation by an expert pathologist were the key of it.

Introducción: La calcifilaxis es un trastorno vascular grave caracterizado por depósito de calcio en túnica media arteriolar, trombosis y necrosis cutánea. Se describió en pacientes con insuficiencia renal (CU), aunque puede producirse en su ausencia (CNU). Sus factores de riesgo están en estudio y su diagnóstico puede ser complejo. Su mortalidad se estimaba en 60-80%, aunque trabajos recientes indican que ha disminuido (40%). Métodos: Estudio retrospectivo entre el 1/1/2011 y el 31/12/2019. Se revisaron los antecedentes, las características clínicas, los hallazgos de laboratorio e histopatológicos, y la evolución de todos los pacientes con diagnóstico de calcifilaxis evaluados en el Hospital Italiano de Buenos Aires. Resultados: Se incluyeron 39 pacientes. El 61.5% (24) eran hombres y 38.5% (15) fueron casos de CNU. De éstos, 82% presentaba hipertensión arterial, 66% obesidad y 46% diabetes. El 49% recibía anticoagulantes dicumarínicos. Todos los pacientes con CNU y 75% con CU presentaron úlceras de fondo necrótico, localizadas con mayor frecuencia en las piernas. En 72% de los casos el diagnóstico histológico se efectuó con una toma de biopsia. En todos, el tratamiento fue multimodal y la mortalidad al año fue de 42%. Conclusión: Observamos una elevada proporción de pacientes con CNU, en relación con lo comunicado en la literatura, y la mitad recibía anticoagulantes dicumarínicos. El diagnóstico histológico se efectuó por biopsia en la mayor parte de los casos, para lo cual la toma quirúrgica de la muestra, la tinción con Von Kossa y la evaluación por un patólogo experto fueron claves.

Active avoidance under social conditions recruits the anterior cingulate cortex in male and female rats.

Actively avoiding potential threats is necessary for survival. Most research has focused on the behavioral and neurobiological processes when individuals avoid potential threats alone, under solitary conditions. Therefore, little is known about how social context affects active avoidance. Using a modified version of the platform-mediated avoidance task, we investigated whether the presence of a social partner attenuates freezing responses and promotes greater avoidance learning compared to avoidance learned under solitary conditions. Rats spent a similar percentage of time avoiding during the conditioned tone under both conditions; however, rats trained under social conditions exhibited greater freezing during the tone and lower pressing for food reward compared to solitary rats. Under solitary conditions, we observed greater avoidance in female compared to male rats, which was not present in rats under social conditions. To gain greater mechanistic insight, we optogenetically inactivated glutamatergic projection neurons in the anterior cingulate cortex (ACC) following avoidance training. Photoinactivation of ACC neurons impaired avoidance expression under social conditions both in the presence and absence of the partner. Under solitary conditions, photoinactivation of ACC delayed avoidance in males but blocked avoidance in females. Our findings suggest that avoidance is mediated by the ACC, regardless of social context, and may be dysfunctional in those suffering from trauma-related disorders. Furthermore, sex differences in prefrontal circuits mediating active avoidance warrant further investigation, given that females experience a higher risk of developing anxiety disorders.

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy.

INTRODUCTION AND AIM: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. METHODS: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. RESULTS: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range -1.6 to -2.0. The summary of findings was analyzed and put to a vote. CONCLUSIONS: With more than 80% agreement of the voting expert panel, a T-score≤-1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy / Umbral densitométrico de densidad mineral ósea para considerar tratamiento en pacientes mujeres posmenopáusicas y hombres mayores de 50 años en tratamiento con glucocorticoids

Introduction and aim: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. Methods: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. Results: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range −1.6 to −2.0. The summary of findings was analyzed and put to a vote. Conclusions: With more than 80% agreement of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.(AU)

Introducción y objetivo: Los umbrales del T-score de densidad mineral ósea (DMO) podrían influir en el tratamiento de pacientes bajo terapia con glucocorticoides (GC). Se han descrito diferentes umbrales, pero no existe un consenso internacional. El objetivo de este trabajo fue encontrar un umbral que ayude en la decisión terapéutica en la población bajo tratamiento con GC. Métodos: Se convocó un grupo de trabajo en representación de tres sociedades científicas de Argentina. El primer equipo estuvo formado por especialistas con experiencia en osteoporosis inducida por glucocorticoides (OIG), quienes estuvieron a cargo de la votación basada en la evidencia. El segundo equipo estuvo a cargo de la metodología coordinando y supervisando cada etapa. Realizamos dos revisiones sistemáticas: la primera incluyó ensayos de fármacos utilizados en OIG para analizar el T-score considerado como criterio de inclusión. En la segunda, analizamos la evidencia sobre umbrales densitométricos para la discriminación de pacientes fracturados y no fracturados bajo tratamiento con GC. Resultados: En la primera revisión se incluyeron 31 artículos donde se halló que más de 90% de los ensayos incluyeron pacientes independientemente del T-score o en el rango de osteopenia. En la segunda revisión se incluyeron cuatro artículos donde observamos que más de 80% de los valores de T-score se encontraban entre -1,6 y -2,0. Conclusiones: Con un acuerdo superior a 80% del panel de expertos, un T-score ≤ -1,7 se consideró el más adecuado para el tratamiento en mujeres posmenopáusicas y hombres mayores de 50 años bajo tratamiento con GC. Este estudio podría ayudar en la decisión terapéutica en pacientes bajo tratamiento con GC sin fracturas, pero ciertamente deberían considerarse otros factores de riesgos de fracturas complementarios.(AU)

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

A Novel Insular/Orbital-Prelimbic Circuit That Prevents Persistent Avoidance in a Rodent Model of Compulsive Behavior.

BACKGROUND: A common symptom of obsessive-compulsive disorder is the persistent avoidance of cues incorrectly associated with negative outcomes. This maladaptation becomes increasingly evident as subjects fail to respond to extinction-based treatments such as exposure-with-response prevention therapy. While previous studies have highlighted the role of the insular-orbital cortex in fine-tuning avoidance-based decisions, little is known about the projections from this area that might modulate compulsive-like avoidance. METHODS: Here, we used anatomical tract-tracing, single-unit recording, and optogenetics to characterize the projections from the insular-orbital cortex. To model exposure-with-response prevention and persistent avoidance in rats, we used the platform-mediated avoidance task followed by extinction-with-response prevention training. RESULTS: Using tract-tracing and unit recording, we found that projections from the agranular insular/lateral orbital (AI/LO) cortex to the prefrontal cortex predominantly target the rostral portion of the prelimbic (rPL) cortex and excite rPL neurons. Photoinhibiting this projection induced persistent avoidance after extinction-with-response prevention training, an effect that was still present 1 week later. Consistent with this, photoexcitation of this projection prevented persistent avoidance in overtrained rats. This projection to rPL appears to be key for AI/LO's effects, considering that there was no effect of photoinhibiting AI/LO projections to the ventral striatum or basolateral amygdala. CONCLUSIONS: Our findings suggest that projections from the AI/LO to the rPL decreases the likelihood of avoidance behavior following extinction. In humans, this connectivity may share some homology of projections from lateral prefrontal cortices (i.e., ventrolateral prefrontal cortex, orbitofrontal cortex, and insula) to other prefrontal areas and the anterior cingulate cortex, suggesting that reduced activity in these pathways may contribute to obsessive-compulsive disorder.

Alliance for the development of the Argentinian Hip Fracture Registry.

Age expectancy has significantly increased over the last 50 years, as well as some age-related health conditions such as hip fractures. The development of hip fracture registries has shown enhanced patient outcomes through quality improvement strategies. The development of the Argentinian Hip Fracture Registry is going in the same direction. INTRODUCTION: Age expectancy has increased worldwide in the last 50 years, with the population over 64 growing from 4.9 to 9.1%. As fractures are an important problem in this age group, specific approaches such as hip fracture registries (HFR) are needed. Our aim is to communicate the Argentinian HFR (AHFR) development resulting from an alliance between Fundación Trauma, Fundación Navarro Viola, and the Argentinian Network of Hip Fracture in the elderly. METHODS: Between October 2020 and May 2021, an iterative consensus process involving 5 specialty-focused meetings and 8 general meetings with more than 20 specialists was conducted. This process comprised inclusion criteria definitions, dataset proposals, website deployment with data protection and user validation, the definition of hospital-adjusted registry levels, implementation planning, and sustainability strategies. RESULTS: By June 2021, we were able to (1) outline data fields, including epidemiological, clinical, and functional dimensions for the pre-admission, hospitalization, discharge, and follow-up stages; (2) define three levels: basic (53 fields), intermediate (85), and advanced (99); (3) identify 21 benchmarking indicators; and (4) make a correlation scheme among fracture classifications. Simultaneously, we launched a fundraising campaign to implement the AHFR in 30 centers, having completed 18. CONCLUSION: AHFR development was based on four pillars: (1) representativeness and support, (2) solid definitions from onset, (3) committed teams, and (4) stable funding. This tool may contribute to the design of evidence-based health policies to improve patient outcomes, and we hope this experience will help other LMICs to develop their own tailored-to-their-needs registries.

Representation of Expression and Identity by Ventral Prefrontal Neurons.

Evidence has suggested that the ventrolateral prefrontal cortex (VLPFC) processes social stimuli, including faces and vocalizations, which are essential for communication. Features embedded within audiovisual stimuli, including emotional expression and caller identity, provide abundant information about an individual's intention, emotional state, motivation, and social status, which are important to encode in a social exchange. However, it is unknown to what extent the VLPFC encodes such features. To investigate the role of VLPFC during social communication, we recorded single-unit activity while rhesus macaques (Macaca mulatta) performed a nonmatch-to-sample task using species-specific face-vocalization stimuli that differed in emotional expression or caller identity. 75% of recorded cells were task-related and of these >70% were responsive during the nonmatch period. A larger proportion of nonmatch cells encoded the stimulus rather than the context of the trial type. A subset of responsive neurons were most commonly modulated by the identity of the nonmatch stimulus and less by the emotional expression, or both features within the face-vocalization stimuli presented during the nonmatch period. Neurons encoding identity were found in VLPFC across a broader region than expression related cells which were confined to only the anterolateral portion of the recording chamber in VLPFC. These findings suggest that, within a working memory paradigm, VLPFC processes features of face and vocal stimuli, such as emotional expression and identity, in addition to task and contextual information. Thus, stimulus and contextual information may be integrated by VLPFC during social communication.

Single cell cloning of free-living amoebae with isolated square agar.

An alternative amoeba cloning technique is described. The amoebic cells were scraped from the agar and inoculated in a new agar medium separated in isolated squares, preventing a cell from invading the space of another cell, increasing the reliability of cloning, and providing an efficient quality control of technique.

Genotype distribution of Acanthamoeba in keratitis: a systematic review.

Acanthamoeba spp. are among the most worldwide prevalent protozoa. It is the causative agent of a disease known as Acanthamoeba keratitis, a painful and severe sight-threatening corneal infection that can lead to blindness. In recent years, the prevalence of Acanthamoeba keratitis has rapidly increased, growing its importance to human health. This systematic review aims to assess the distribution of Acanthamoeba sp. genotypes causing keratitis around the world, considering the sample collected type and the used identification method. Most of the cases were found in Asia and Europe. Not surprisingly, the T4 genotype was the most prevalent worldwide, followed by T3, T15, T11, and T5. Furthermore, the T4 genotype contains a higher number of species. Given the differences in pathology, susceptibility to treatment, and clinical outcome between distinct genotypes, it is essential to genotype isolates from Acanthamoeba keratitis cases to help to establish a better correlation between in vitro and in vivo activities, resulting in better drug therapies and successful treatment in cases of this important ocular infection.

Divergent projections of the prelimbic cortex bidirectionally regulate active avoidance.

The prefrontal cortex (PFC) integrates incoming information to guide our actions. When motivation for food-seeking competes with avoidance of danger, the PFC likely plays a role in selecting the optimal choice. In platform-mediated active avoidance, rats avoid a tone-signaled footshock by stepping onto a nearby platform, delaying access to sucrose pellets. This avoidance requires prelimbic (PL) PFC, basolateral amygdala (BLA), and ventral striatum (VS). We previously showed that inhibitory tone responses of PL neurons correlate with avoidability of shock (Diehl et al., 2018). Here, we optogenetically modulated PL terminals in VS and BLA to identify PL outputs regulating avoidance. Photoactivating PL-VS projections reduced avoidance, whereas photoactivating PL-BLA projections increased avoidance. Moreover, photosilencing PL-BLA or BLA-VS projections reduced avoidance, suggesting that VS receives opposing inputs from PL and BLA. Bidirectional modulation of avoidance by PL projections to VS and BLA enables the animal to make appropriate decisions when faced with competing drives.

Prolonged social lockdown during COVID-19 pandemic and hip fracture epidemiology.

PURPOSE: To analyse the impact of prolonged mandatory lockdown due to COVID-19 on hip fracture epidemiology. METHODS: Retrospective case-control study of 160 hip fractures operated upon between December 2019 and May 2020. Based on the date of declaration of national lockdown, the cohort was separated into two groups: 'pre-COVID time' (PCT), including 86 patients, and 'COVID time' (CT), consisting of 74 patients. All CT patients tested negative for SARS-CoV-2. Patients were stratified based on demographic characteristics. Outcome measures were 30-day complications, readmissions and mortality. A logistic regression model was run to evaluate factors associated with mortality. RESULTS: Age, female/male ratio, body mass index and American Society of Anaesthesia score were similar between both groups (p > 0.05). CT patients had a higher percentage of Charlson ≥ 5 and Rockwood Frailty Index ≥ 5 scores (p < 0.05) as well as lower UCLA and Instrumental Activities of Daily Living scores (p < 0.05). This translated into a higher hemiarthroplasty/total hip arthroplasty ratio during CT (p = 0.04). Thromboembolic disease was higher during CT (p = 0.02). Readmissions (all negative for SARS-CoV-2) were similar between both groups (p = 0.34). Eight (10.8%) casualties were detected in the CT group, whereas no deaths were seen in the control group. Logistic regression showed that frailer (p = 0.006, OR 10.46, 95%CI 8.95-16.1), less active (p = 0.018, OR 2.45, 95%CI 1.45-2.72) and those with a thromboembolic event (p = 0.005, OR 30, 95%CI 11-42) had a higher risk of mortality. CONCLUSION: Despite testing negative for SARS-CoV-2, CT patients were less active and frailer than PCT patients, depicting an epidemiological shift that was associated with higher mortality rate.

Hipofosfatasemia crónica persistente de causa no determinada y su repercusión músculo-esquelética / Persistent hypophosphatasemia and its musculoskeletal repercussion

La fosfatasa alcalina baja o hipofosfatasemia, ya sea debida a causas genéticas (hipofosfatasia) o secundarias, presenta correlato clínico. Nuestro objetivo es estimar la prevalencia de hipofosfatasemia crónica persistente y describir sus hallazgos osteometabólicos. Se realizó una búsqueda electrónica de afiliados adultos al Hospital Italiano de Buenos Aires, entre 2013 y 2017, con al menos 2 determinaciones de fosfatasa alcalina igual a 30 UI/l o menor y ninguna mayor de 30 UI/l (rango de referencia 30-100 UI/l). Se excluyeron aquellos con causas secundarias diagnosticadas y se analizaron los correlatos clínico y bioquímico. Se detectó hipofosfatasemia crónica persistente en 78 de 105.925, 0,07% (0,06-0,09) de los afiliados. Solo uno fue excluido por tener causa secundaria. Eran 61,1% mujeres de 44 (34-56) años, fosfatasa alcalina 24 (20-27) UI/L, fosfatemia 4,1 (3,8-4,6) mg/dl. Se observaron osteoartritis, calcificaciones vasculares y fracturas, menos frecuentemente litiasis renal, calcificación del ligamento longitudinal común anterior, pérdida dental y convulsiones. El 63,6% tenían al menos una de las características clínico-radiológicas evaluadas, pero en solo 5,2% fue mencionado el diagnóstico de hipofosfatasemia en la historia clínica. La densitometría evidenció algún grado de afección (osteopenia u osteoporosis) en 76,2%. Se constataron 19 fracturas, con predominio en radio. La prevalencia de hipofosfatasemia fue similar a lo previamente reportado. El reconocimiento fue bajo; sin embargo, se observaron variadas manifestaciones músculo-esqueléticas, similares a las descriptas en la hipofosfatasia del adulto, por lo cual ­ante una hipofosfatasemia sin causa secundaria­ se sugiere considerar este diagnóstico. (AU)

Low alkaline phosphatase (ALP) or hypophosphatasemia either due to genetic (hypophosphatasia) or secondary causes, presents a clinical correlate. Our objectives are to estimate the prevalence of persistent hypophosphatasemia and to describe the clinical findings. We performed a search using the electronic medical records of the members of the Hospital Italiano de Buenos Aires health care system, between 2013 and 2017. Adult members with ≥ 2 ALP ≤ 30 IU/l, no ALP >30 IU/l (normal range 30-100 UI/l) and without diagnosed secondary causes were analyzed. Persistent hypophosphatasemia was detected in 78 of 105.925, 0.07% (0.06-0.09) of members. Only one was excluded due to a secondary cause, 61.1% were women, 44 (34-56) year-old, ALP 24 (20-27) IU/l and phosphatemia 4.1 (3.8-4.6) mg/dl. Osteoarthritis, vascular calcifications and fractures were detected, and nephrolithiasis, DISH (Diffuse idiopathic skeletal hyperostosis), tooth loss, and seizures were less frequently observed. At least one of the mentioned characteristics were present in 63.6 %, but only 5.2% had hypophosphatasemia registered in their clinical record. Densitometry showed osteopenia or osteoporosis in 76.2%. There were 19 fractures, most of them in radius. The prevalence of hypophosphatasemia was similar to what has been previously reported. Hypophosphatasemia finding in medical records was low, but far from being asymptomatic, clinical manifestations were observed. In the presence of hypophosphatasemia without a secondary cause, adult hypophosphatasia should be uspected. (AU)

Hypercalcemia as an Early Finding of Opportunistic Fungal Pneumonia in Renal Transplantation: A Case Series Report.

BACKGROUND: Pneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia. METHODS: We describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels. RESULTS: Mean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D. CONCLUSION: In kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia.

Recidiva del hiperparatiroidismo secundario a enfermedad renal crónica en diálisis luego de la paratiroidectomía / Recurrence of secondary hyper¬parathyroidism in dialysis patients after parathyroidectomy

La paratiroidectomía (PTX) es la terapia de elección en el hiperparatiroidismo secundario a enfermedad renal crónica (HPT-ERC) resistente al tratamiento médico. El objetivo del presente estudio fue evaluar el resultado de la PTX a largo plazo y sus factores predictores. Métodos: estudio unicéntrico retrospectivo observacional. Se incluyeron 92 pacientes con HPT-ERC en diálisis, en quienes se realizó la primera PTX en el Hospital Italiano de Buenos Aires entre 2006 y 2015 con seguimiento ≥ 6 meses. Se consideró persistencia del HPTERC con PTH > 300 pg/ml en el semestre posoperatorio, y recidiva con PTH > 500 pg/ml luego. Resultados: edad: 43,6±12,8 años, 50% mujeres, mediana 4,6 años de diálisis, PTH preoperatoria mediana 1639 pg/ml. A 39 se les realizó PTX subtotal (PTXS) y a 53 total con autoimplante (PTXT+AI). Se observó persistencia en 16 pacientes (17,4%). Presentaron recidiva 30 de 76 pacientes con adecuada respuesta inicial (39,5%; IC 95 28,5-50,5). La mediana de tiempo hasta la recidiva fue de 4,7 años (RIC 2,3-7,5). Los pacientes con recidiva presentaron mayor calcemia preoperatoria (mediana 9,9 vs. 9,3 mg/dl, p=0,035; OR ajustado 2,79) y menor elevación de fosfatasa alcalina en el posoperatorio (333 vs. 436 UI/l, p=0,031; OR ajustado 0,99). La recidiva se presentó más frecuentemente luego de la PTXT+AI (48,9%; OR ajustado 4,66), que en la PTXS (25,8%). Conclusiones: el tiempo en diálisis con inadecuado control metabólico constituye el principal factor para la recurrencia del HPT. Se postula que la mayor calcemia preoperatoria está relacionada con un HPT más severo y se asocia a recurrencia. Llamativamente, hallamos menores elevaciones de la fosfatasa alcalina durante el posoperatorio en pacientes con recurrencia. Hipotetizamos que esto pueda asociarse con menor mineralización en el posoperatorio e hiperfosfatemia sostenida, con consecuente estímulo paratiroideo. La menor recurrencia del HPT luego de la PTXS se vincula al sesgo generado en la selección del tipo de cirugía. (AU)

Parathyroidectomy is an effective therapy for refractory secondary hyperparathyroidism (sHPT). Continued dialysis represents risk for recurrent sHPT. The aim of this study was to estimate the proportion of recurrence and determine its predictors. Methods: We conducted a retrospective observational study of 92 adults in chronic dialysis, who underwent their first parathyroidectomy in this center between 2006 and 2015. We considered persistence of sHPT if PTH was > 300 pg/ml during the first postoperative semester, and recurrence if it was > 500 pg/ml afterwards. Results: Age 43.6+-12 y/o, 50% female, 4.6 years on dialysis, median preoperative PTH 1636 pg/ml (IQR 1226-2098). Subtotal parathyroidectomy (sPTX) was performed in 39, Total with autotransplantation (TA-PTX) in 53 patients. Persistence of sHPT occurred in 16 patients; relapse in 30 out of 76 with adequate initially response (39.5%; 95CI 28,5-50,5). Median time to recurrence: 4.7 y. Recurring patients had higher preoperative calcemia (9.9 vs 9.3 mg/dl; adj OR 2.79) and lower postoperative elevation of ALP (333 vs 436 UI/ml; adj OR 0.99). Recurrence presented more frequently in TA-PTX (48.9%; adj OR 4.66) than sPTX (25.8%). Conclusions: Time on dialysis with inadequate metabolic control remains the most important risk factor for sHPT recurrence. Higher preoperative levels of calcemia, related to sHPT severity, are associated with recurrence. Lower elevations of ALP during postoperative period in recurring patients are an interesting finding. We hypothesize that patients with less significant postoperative mineralization may have chronically higher levels of phosphatemia, stimulating parathyroid glands. Fewer recurrence in sPTX is associated to a bias in the procedure selection. (AU)

Know safety, no fear.

Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear responses. Such learning can last a lifetime but is not always beneficial for an organism. For an organism to thrive in its environment, it must know when to engage in defensive, avoidance behaviors and when to engage in non-defensive, approach behaviors. Fear should be suppressed in situations that are not dangerous: when a novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no longer predicts harm, or when there is an option to avoid harm. A cardinal feature of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for instance, learned fear is expressed inappropriately in safe situations and is resistant to extinction. In this review, we discuss mechanisms of suppressing fear responses during stimulus discrimination, fear extinction, and active avoidance, focusing on the well-studied tripartite circuit consisting of the amygdala, medial prefrontal cortex and hippocampus.

The study of active avoidance: A platform for discussion.

Traditional active avoidance tasks have advanced the field of aversive learning and memory for decades and are useful for studying simple avoidance responses in isolation; however, these tasks have limited clinical relevance because they do not model several key features of clinical avoidance. In contrast, platform-mediated avoidance (PMA) more closely resembles clinical avoidance because the response i) is associated with an unambiguous safe location, ii) is not associated with an artificial termination of the warning signal, and iii) is associated with a decision-based appetitive cost. Recent findings on the neuronal circuits of PMA have confirmed that amygdala-striatal circuits are essential for avoidance. In PMA, however, the prelimbic cortex facilitates the avoidance response early during the warning signal, perhaps through disinhibition of the striatum. Future studies on avoidance should account for additional factors such as sex differences and social interactions that will advance our understanding of maladaptive avoidance contributing to neuropsychiatric disorders.

Utilidad de la 18f-colina pet/tc en hiperparatiroidismo primario persistente o recurrente: experiencia inicial / Usefulness of 18f-choline pet / tc in persistent or recurrent primary hyperparathyroidism: initial experience

El hiperparatiroidismo persistente/recurrente representa un desafío en la localización del tejido paratiroideo hiperfuncionante. En esta subpoblación, los métodos convencionales ofrecen un menor rédito diagnóstico. La 18F-colina PET/TC podría ser una buena alternativa dada su mejor resolución espacial, capacidad de detectar glándulas ectópicas y la conjunción de la imagen molecular y anatómica. Sin embargo, la evidencia en este subgrupo de pacientes es escasa. Objetivo: evaluar la utilidad de la 18F-colina PET/TC como método de localización en el hiperparatiroidismo persistente o recurrente. Materiales y métodos: se analizaron los pacientes con 18F-colina PET/TC para hiperparatiroidismo entre diciembre de 2015 y enero de 2018 en un centro terciario de alto volumen. Se analizaron el número de lesiones, su localización, tamaño y el Standard Uptake Value máximo (SUV max) en las imágenes tempranas y tardías. Se compararon los resultados con los métodos convencionales. Resultados: 7 de 15 pacientes habían sido operados previamente (persistentes/recurrentes). La 18F-colina PET/TC detectó 6/7 casos (83,33%), la ecografía cervical 1/4 (25%) y el SPECT de paratiroides y la resonancia nuclear magnética 2/5 (40%). El SUV max obtenido fue variable, en la mitad de los casos a los 10 minutos y en los restantes a la hora; el tamaño promedio de las lesiones fue 8,61 mm (6-12 mm). Conclusiones: la 18F-colina PET/TC muestra una alta tasa de detección en los pacientes con hiperparatiroidismo persistente/recurrente. La combinación del comportamiento biológico del PET con los hallazgos morfológicos aportados por la TC con contraste endovenoso le ofrecería ventajas sobre otros estudios que podrían posicionarlo como método de primera línea en esta subpoblación. (AU)

Persistent or recurrent hyperparathyroidism represents a challenge regarding the localization of the hyper-functioning parathyroid tissue. In this subpopulation of hyperpharathyroid patients, conventional methods have a low diagnostic yield. The 18F-choline PET /CT could be a good alternative given its better spatial resolution, ability to detect ectopic glands, and the conjunction of the molecular and anatomical image. However, the evidence in this subgroup of patients is limited. Objective: to evaluate the utility of 18F-choline PET/ CT as a localization method in persistent or recurrent hyperparathyroidism. Materials and methods: patients with 18F-choline PET / CT for hyperparathyroidism between December 2015 and January 2018 in a high-volume tertiary center were included. The number of lesions, and their location, size, and maximum Standard Uptake Value (SUV) in the early and late images were analyzed. The results were compared to conventional methods. Results: 7 of 15 patients had been previously operated (persistent/recurrent). 18F-choline PET / CT detected 6/7 cases (83,33%), cervical ultrasound 1/4 (25%) and parathyroid SPECT and magnetic resonance 2/5 (40%). The maximum SUV was variable, one half at 10 minutes and the other half at 60 minutes; the average size of the lesions was 8.61 mm (6-12 mm). Conclusions: 18F-Choline PET / CT shows a high detection rate in patients with persistent / recurrent hyperparathyroidism. The combination of the biological behavior of PET with the morphological findings provided by CT with intravenous contrast would offer advantages over other studies that could position it as a first line method in this subpopulation. (AU)

Servicio de enlace para pacientes con fracturas por osteoporosis / Osteoporotic fracture liaison service

Los pacientes con fracturas por fragilidad presentan elevadas tasas de morbimortalidad, lo que implica además un alto costo para el erario público. Luego de una fractura por osteoporosis, la mayoría de los pacientes no recibe una adecuada evaluación y tratamiento. Para suplir este vacío de atención médica se crearon distintas políticas; la mejor de ellas son los Servicios de Enlace de Pacientes con Fracturas (Fracture Liaison Service, en inglés). Estos programas tienen una vigencia internacional de más de diez años y son patrocinados por organismos internacionales. La finalidad de estos servicios es la prevención secundaria de fracturas. La modalidad de trabajo tiene como objetivo facilitar y asegurar la rápida identificación, el diagnóstico y la terapéutica de esta población en diferentes contextos asistenciales. La experiencia internacional demuestra que estos servicios son exitosos pues logran incrementar el inicio y la adherencia al tratamiento, disminuir las tasas de mortalidad, de morbilidad y de nuevas fracturas, y son costo-efectivos. En nuestro medio, el inicio de los Servicios de Enlace es reciente. El propósito de esta actualización es realizar una revisión de los fundamentos, características, modalidad operativa y los logros obtenidos por dichos programas. Las fracturas por fragilidad ósea constituyen un problema importante para la salud pública. Esta presentación tiene como objetivo alertar y motivar a la comunidad médica a intervenir de manera sistemática y dinámica para mejorar el cuidado habitual en esta población de pacientes. (AU)

Fragility fractures are associated with increased morbidity and mortality rates and higher costs. After a fracture, most patients do not receive adequate assessment and treatment. To fill this gap in medical care, different policies have been created; the best of them being the Fracture Liaison Services. These programs have been in place for over ten years worldwide and are sponsored by international organisms and societies. The purpose of the Fracture Liaison Services is secondary fracture prevention. Their goal is to ensure the rapid identification, diagnosis and treatment of this population in different clinical contexts. They increase treatment adherence and decrease mortality and morbidity rates and the incidence of new fractures. International experience shows that these services are successful and costeffective. (AU)