Liver findings in patients with Carney complex, germline PRKAR1A pathogenic variants, and link to cardiac myxomas.

This study aimed to evaluate liver involvement in patients with Carney complex (CNC) based on a large cohort and to analyze any germline PRKAR1A genotype-phenotype association of liver disease. The study included 83 patients with CNC, followed between 1995 and 2018 at a tertiary research center. We reviewed liver images, recorded types and number of lesions and analyzed per genotype: all patients were sequenced for the PRKAR1A gene. A total of 29/83 patients (24.0%) had liver radiological findings. Patients with liver lesion had a significantly higher rate of pathogenic variants detected in the PRKAR1A gene (72.4 vs 38.9%, P = 0.005, respectively). Patients with a pathogenic variant detected on germline PRKAR1A analysis had a higher risk for having a liver lesion compared with patients with wild-type (WT) PRKAR1A alleles (21/42 (50.0%) vs 8/41 (19.5%), respectively, P = 0.004). Among patients with liver lesions, those with a nonsense PRKAR1A pathogenic-variant had more liver lesions (7/7) than among those with other pathogenic-variant types (8/22, P = 0.001). In multivariable analysis, detection of liver lesion(s) was associated with an odds ratio of 5.2 for cardiac myxomas (95% CI 1.55-17.49, P = 0.008). In conclusion, patients with CNC, particularly with a PRKAR1A pathogenic variant, have a higher rate of liver lesions. Additionally, liver lesions are associated with a high risk for cardiac myxomas in this population.

Failure to Thrive in the Context of Carney Complex.

BACKGROUND/AIMS: Carney complex (CNC) is a rare syndrome associated with multiple tumors and several other unique manifestations. We describe the clinical, genetic, and laboratory findings in a cohort of patients with CNC and failure to thrive (FTT). METHODS: A retrospective case series of pediatric patients with CNC presenting with FTT. RESULTS: We describe a patient with infantile Cushing syndrome (CS) who presented with severe FTT and liver disease; the patient was subsequently diagnosed with CNC. This led to the realization that at least 10 other patients with CNC and FTT have been investigated in the last 22 years at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Four of those had primary pigmented nodular adrenocortical disease (PPNAD), 2 had cardiac myxomas, and 3 had liver disease. CONCLUSION: Pediatric patients with CNC may present with FTT whose primary cause is variable and includes CS due to PPNAD, hepatic involvement, and other manifestations of CNC. FTT due to liver disease and/or other causes is a unique new presentation of this rare syndrome with which clinicians need to be familiar.

[Extremely elevated erythrosedimentation in an adult population in the City of Buenos Aires]. / Eritrosedimentación extremadamente elevada en una población de adultos en la ciudad de Buenos Aires.

BACKGROUND: An extremely elevated erythrosedimentation rate (ESR), defined as equal or higher than 100 mm/h, has been linked to serious underlying conditions, such as infections, connective tissue and oncologic disease. AIM: To analyze a group of patients in order to determine the underlying diagnosis and the characteristics associated with extremely elevated ESR in our environment. METHODS: Cross-sectional study of adult patients, who presented with at least one ESR equal or higher than 100 mm/h at Hospital Italiano, in Buenos Aires (Buenos Aires, Argentina) between January 2002 and August 2014. RESULTS: During the previously stated period of time, we analyzed the results of 879 patients. All patients were over 18 years of age. The median for the ESR results was 111 mm/h (interquartile range 105-120). The most prevalent etiology of an elevated ESR was infectious (41.64%), followed by malignancies (21.62%) and autoimmune / inflammatory diseases (12.97%). The most frequent individual diagnosis found was pneumonia (11.49%), followed by undetermined causes (5.92%). CONCLUSION: When comparing inpatient versus outpatient populations, the most frequent cause was infectious in the former group, while malignancies were the most frequent diagnosis in the latter.

Eritrosedimentación extremadamente elevada en una población de adultos en la ciudad de Buenos Aires / Extremely elevated erythrosedimentation in an adult population in the City of Buenos Aires

Resumen Introducción: Una velocidad de eritrosedimentación (VHS) extremadamente elevada, definida como mayor o igual a 100 mm/h, se ha asociado a condiciones graves subyacentes como enfermedades infecciosas, enfermedades del colágeno u oncológicas. Objetivo: Analizar un grupo de pacientes para determinar los diagnósticos de base y las características que se asocian con valores de VHS mayores a 100 mm/h en nuestro medio. Pacientes y Métodos: Estudio tipo observacional de corte transversal, con recolección retrospectiva de datos de pacientes adultos con al menos un valor de VHS mayor o igual a 100 mm/h, registrado en el laboratorio entre enero de 2002 y agosto de 2014 en el Hospital Italiano de Buenos Aires. Resultados: Durante el período evaluado se analizaron 879 pacientes mayores de 18 años. La mediana de los valores de VHS fue 111 mm/h (Rango intercuartil 105-120). La etiología prevalente de VHS elevada fueron las enfermedades infecciosas (41,6%), seguida de malignidad (21,6%) y de autoinmune/inflamatoria (12,9%). El diagnóstico individual más frecuente fue el de neumonía (11,4%), seguido por causa indeterminada (5,9%). Conclusión: En pacientes internados, la causa más frecuente de VHS ≥ 100 mm/h fue las enfermedades infecciosas, mientras que en pacientes ambulatorios la causa más frecuente fue la malignidad.

Background: An extremely elevated erythrosedimentation rate (ESR), defined as equal or higher than 100 mm/h, has been linked to serious underlying conditions, such as infections, connective tissue and oncologic disease. Aim: To analyze a group of patients in order to determine the underlying diagnosis and the characteristics associated with extremely elevated ESR in our environment. Methods: Cross-sectional study of adult patients, who presented with at least one ESR equal or higher than 100 mm/h at Hospital Italiano, in Buenos Aires (Buenos Aires, Argentina) between January 2002 and August 2014. Results: During the previously stated period of time, we analyzed the results of 879 patients. All patients were over 18 years of age. The median for the ESR results was 111 mm/h (interquartile range 105-120). The most prevalent etiology of an elevated ESR was infectious (41.64%), followed by malignancies (21.62%) and autoimmune / inflammatory diseases (12.97%). The most frequent individual diagnosis found was pneumonia (11.49%), followed by undetermined causes (5.92%). Conclusion: When comparing inpatient versus outpatient populations, the most frequent cause was infectious in the former group, while malignancies were the most frequent diagnosis in the latter.

[Hemophagocytic lymphohistiocytosis. Experience in 27 patients]. / Características clínicas y mortalidad de pacientes adultos con síndrome hemafagocítico, estudio de cohorte retrospectiva.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. MATERIAL AND METHODS: Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. RESULTS: Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7-70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2-9.9, p =0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p = 0.046). CONCLUSIONS: The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.

Características clínicas y mortalidad de pacientes adultos con síndrome hemafagocítico, estudio de cohorte retrospectiva / Hemophagocytic lymphohistiocytosis: experience in 27 patients

Background: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. Material and Methods: Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. Results: Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7-70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2-9.9, p =0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p = 0.046). Conclusions: The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.

[Hyponatremia induced by high-dose cyclophosphamide therapy: a retrospective cohort study Cyclophosphamide and Hyponatremia]. / Hiponatremia inducida por Ciclofosfamida en altas dosis: estudio de cohorte retrospectiva.

Cyclophosphamide-associated hyponatremia is an uncommon adverse effect. Published reports are inconclusive regarding patients under high-dose therapy. OBJECTIVE: To determine the incidence of hyponatremia in patients under high-dose cyclophosphamide therapy. METHODS: Retrospective cohort of adult patients who received high-dose cyclophosphamide therapy between 2010 and 2014 at the Hospital Italiano de Buenos Aires. The primary end-point was hyponatremia (defined as plasma sodium levels < 135 mEq/L), and secondary end-points were symptomatic hyponatremia, severe hyponatremia (plasma sodium levels < 120 mEq/L). RESULTS: A total of 96 patients received high-dose cyclophosphamide therapy during the study period. 27 patients met exclusion criteria and accounted for 28.1% , so that 69 patients were included in the primary analysis. Study population mean age was 56.5 years (SD 12.8) and 37.6% were female. The cumulative incidence were as follows: 52% (CI 95% 39¬­64) for hiponatremia, 5.8% (CI 95 % 0 ­12) for severe hyponatremia, and 8.7% (CI 95% 1.3­16) for symptomatic hyponatremia. The only independent variable associated with the development of hyponatremia was female gender (OR 3.89, CI 95% 1.02­8.55, p=0.04). Cumulative incidence found in this study appears higher than in previous reports, probably because only patients under high-dose cyclophosphamide therapy were included. Cumulative incidence of severe and symptomatic hyponatremia were lower

La hiponatremia asociada al uso de Ciclofosfamida es un efecto adverso infrecuente. Los estudios publicados no son concluyentes, especialmente respecto de los pacientes sometidos a dosis altas de dicho fármaco. Objetivos: Determinar la incidencia de hiponatremia en una subpoblación de pacientes que realizaron tratamiento con dosis altas de Ciclofosfamida. Materiales y Métodos: Estudio de cohorte retrospectivo de pacientes adultos que recibieron Ciclofosfamida a altas dosis en el período 2010-2014 en el Hospital Italiano de Buenos Aires. El evento primario fue la hiponatremia (definida como sodio plasmático menor a 135 meq/L) mientras que como eventos secundarios se tomaron la hiponatremia sintomática y la hiponatremia severa (valor menor 120 meq/L). Resultados: 96 pacientes recibieron altas dosis de Ciclofosfamida durante el período estudiado. Se excluyó un 27.4% de los pacientes por cumplir con los criterios de exclusión y se analizaron los datos de 69 pacientes. La edad media de la población fue de 56.5 años (DS 12.8) y un 37.7% de los pacientes eran mujeres. La incidencia de hiponatremia fue de 52% (IC95% 39-64), hiponatremia severa 5.8% (IC95% 0-12) y sintomática 8.7% (IC95% 1.3-16). La única variable asociada independientemente al desarrollo de hiponatremia fue el sexo femenino (OR: 3.89, IC95% 1.02-8.55, p=0.04). Si bien la incidencia observada resulta mayor a la observada en reportes previos, probablemente se deba a que solo consideramos la infusión de Ciclofosfamida a altas dosis. La hiponatremia severa y sintomática fue menor, aunque un 20% de los pacientes debieron prolongar su internación por esta causa.