Secondary hypogammaglobulinemia in adults—A large retrospective cohort study / Hipogammaglobulinemia secundaria en adultos: estudio de cohorte retrospectiva

Background and objective: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. Methods: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels – with a disease-related SHG or treatment that reduces serum immunoglobulins. Results: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2–8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. Conclusion: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.(AU)

Antecedentes y objetivos: La IgG sustitutiva ha cambiado radicalmente la evolución de las inmunodeficiencias primarias, mientras que la información sobre hipogammaglobulinemia secundaria (HGS) es insuficiente y discordante. El objetivo del estudio es describir las características clínicas, evolución y tratamiento de pacientes con HGS. Métodos: Cohorte retrospectiva dinámica entre enero de 2001 y julio de 2021 de adultos con proteinograma y fracción de gammaglobulina <0,6g/dL y dosaje disminuido de IgG, con enfermedad o tratamiento que produzcan HGS. Resultados: Se incluyó a 1.012 pacientes con HGS con una mediana de seguimiento de 5 años (IIC 2-8). El 95% tenía enfermedad hematológica y el 61% recibió fármacos asociados a HGS. El 65% tenía más de un factor etiológico asociado con HGS. El 69% presentó infecciones de cualquier tipo, el 48% infecciones respiratorias y el 17%, infecciones graves. Hubo asociación significativa entre infecciones respiratorias y graves entre los subgrupos de mieloma múltiple, linfoma y rituximab. Los pacientes con MGUS tuvieron menor frecuencia de infecciones y muerte comparados con otros factores etiológicos. El 18,7% de los pacientes recibió IgG sustitutiva y el 4,6% de forma crónica, con intervalos variables. Los últimos tuvieron disminución significativa de infecciones de cualquier tipo e infecciones respiratorias con IgG sustitutiva (p<0,001), que se mantuvo en los subgrupos con mieloma múltiple, linfoma y todos los niveles de IgG. Conclusión: La HGS asoció más de un factor etiológico y alta frecuencia de infecciones. La indicación de IgG sustitutiva fue irregular, pero, aún así, efectiva. Se plantea considerar el dosaje de inmunoglobulinas, monitoreo y la adecuada indicación de IgG sustitutiva.(AU)

Secondary hypogammaglobulinemia in adults-A large retrospective cohort study.

BACKGROUND AND OBJECTIVE: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. METHODS: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels - with a disease-related SHG or treatment that reduces serum immunoglobulins. RESULTS: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2-8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. CONCLUSION: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.

Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status

ABSTRACT Introduction: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. Methods: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. Results: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. Conclusion: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status.

INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. METHODS: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. RESULTS: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. CONCLUSION: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

Determination and Management of Risks for Practices and Procedures in the Elderly (DRIPP): the impact of a comprehensive geriatric evaluation in elderly with diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) treatment in older patients is challenging. The Determination and Management of Risks for Practices and Procedures in the Elderly (DRIPP) is a multidimensional evaluation program that involves patients undergoing oncological treatments. OBJECTIVE: We aimed to evaluate the overall survival and progression-free survival (PFS) of patients evaluated and those not evaluated by the DRIPP. MATERIALS AND METHODS: Retrospective cohort study, patients > 65 years with DLBCL were included. They were divided into 3 groups: patients with a diagnosis prior to the DRIPP implementation (pre-DRIPP), patients with the DRIPP (DRIPP) and patients with a diagnosis after the DRIPP implementation, but who did not undergo the evaluation (non-DRIPP). RESULTS: A total of 125 patients were analyzed. Fourteen (11%) patients in the pre-DRIPP group, 74 (59%) in the DRIPP group, and 37 (30%) in the non-DRIPP group. In 43 (58%) patients of the DRIPP group, some drug dose adjustments were made vs. 19 (15%) in the non-DRIPP (p = 0.03). There were no significant differences in terms of discontinuation of treatment or hematological toxicity between groups. The OS and PFS in one year was 64% (95%CI 34-83) and 50% (95%CI 23-72) for the pre-DRIPP group, 82% (95%CI 71-89) and 72% (95%CI 60-81) for the DRIPP group, 58% (95% CI 41-72) and 56% (95% CI 38-70) for the non-DRIPP group, (p = 0.08). The analysis was adjusted for probable confounders and no differences were found. CONCLUSIONS: This is the first study to evaluate the DRIPP as a decision-making tool in patients with lymphoma and showed a trend towards improvement in the OS in evaluated patients.

Central nervous system relapse in diffuse large B lymphoma: a retrospective cohort study / [Recaída en sistema nervioso central en linfoma difuso de células B grandes: estudio de cohorte retrospectiva]

Introduction: CNS relapse in patients with LDCGB is a poor prognosis event. The incidence of relapse is variable according to the literature. Data in Latin America is lacking. Methods: In order to establish the incidence of CNS relapse in our cohort, time to CNS relapse and the impact of CNS relapse risk factors, a retrospective cohort study was performed, from January 2012 to June 2017. Results: One hundred and forty seven patients were analyzed. The median age was 66 years (ICR 56-76); 76 patients (51.70%) were men. The IPI was low or intermediate/low in 115 (78.2%) cases. The CNS IPI was intermediate in 77 (52.4%) and high in 14 (9.5%) of cases. Thirty-five (23.81%) patients received intrathecal prophylaxis. No patient received systemic prophylaxis. During the follow-up, 8 (4.59%) patients had CNS relapse, none of them with high IPI. The median time to relapse was 6.5 months (ICR 5.5-10). Seven (87.5%) patients relapsed within the year of diagnosis. We found no risk factors for CNS involvement in the bivariate analysis. The incidence of relapse was 2.7% (CI 0.2% -4.6%), 4.8% (CI 1.8% -8.9%) and 5.4% (CI 4.5- 8.9%) at 6, 12 and 24 months, respectively. Discussion: The incidence of CNS relapse was similar to that described in the international series. Our study confirms that the majority of patients relapse during the first year of follow up. We must carry out broader collaborative work to better establish the risk factor for CNS relapse.

Introducción: La recaída del SNC en pacientes con LDCBG en un evento de mal pronóstico. La incidencia de recaída  es variable según la bibliografía. Los datos en América Latina son escasos. Metodología: Para establecer la incidencia de recaída en SNC, el tiempo a la recaída en SNC y el impacto de los factores de riesgo de recaída del SNC, se realizó un estudio de cohorte retrospectiva, de enero del 2012 a junio del 2017. Resultados: Se analizaron 147 pacientes. La mediana de edad fue de 66 años (IIC 56-76); 76 pacientes (51,70%) fueron hombres. El IPI fue bajo o intermedio/bajo en 115 (78,2%) casos. El CNS IPI fue intermedio en 77 (52,4%) y alto en 14 (9,5%) casos. Treinta y cinco (23.81%) pacientes recibieron profilaxis intratecal del SNC, ninguno profilaxis sistémica. Durante el seguimiento, 8 (4,59%) pacientes tuvieron recaída del SNC. La mediana de tiempo a la recaída fue de 6,5 meses (IIC 5,5 - 10). Siete (87,5%) pacientes recayeron dentro del año. No encontramos factores de riesgo para el compromiso del SNC en el análisis bivariado. La incidencia de recaída fue del 2,7% (IC 0,2%-4,6%), 4,8% (IC 1,8%-8,9%) y 5,4% (IC 4,5-8,9%) a los 6, 12 y 24 meses, respectivamente. Discusión: La incidencia de recaída del SNC fue similar a la descrita en las series internacionales. Nuestro estudio confirma que la mayoría de los pacientes que recaen, lo hacen dentro del primer año del diagnóstico. Debemos realizar trabajos colaborativos más amplios para establecer mejor factores de riesgo asociados.

EBER+ extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia.

Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the immunosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon association of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months.

La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndrome, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Complete remission and proviral load negativization after allogeneic-SCT in a patient with Adult T-cell lymphoma: Case report.

Adult T-cell lymphoma is an aggressive and poor prognosis HTLV1-associated lymphoma. There is no standard treatment, but it is known that intensive chemotherapy regimens are necessary, with or without concomitant antiretroviral therapy, plus consolidation with allogeneic stem cell transplantation. Our case report shows a favorable outcome after 2 cycles of chemotherapy and allogeneic stem cell transplantation without antiretroviral agents, achieving complete remission, and a negative proviral load.

[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.

[Associated factors with the presence of secondary neoplastic cells in the cerebrospinal fluid of patients with suspected carcinomatous meningitis]. / Factores asociados a presencia de células neoplásicas secundarias en el liquido cefalorraquideo de pacientescon sospecha de meningitis carcinomatosa.

BACKGROUND: Improvement in oncologic therapy has increased survival in oncologic patients. There has been a concomitant increase in the incidence of secondary meningeal involvement. Early diagnosis is mandatory. OBJECTIVE: To identify factors associated with the presence of secondary neoplastic cells in cerebrospinal fluid of patients with suspected carcinomatous meningitis (CM) Methods: Cross-sectional study involving adult patients with solid cancer diagnosis and suspected CM between 2004 and 2014 at Hospital Italiano de Buenos Aires. All included patients had at least one lumbar puncture with cerebrospinal fluid (CSF) analysis. CM cases were defined by the presence of neoplastic cells in CFS. We evaluated the association of each factor (cancer characteristics, clinical engagement of central nervous system, CSF analysis) with CM using a logistic regression model. RESULTS: We included 77 patients: mean age was 62 years (SD 13.1), 58.4% (45) were female. The most common oncologic disease was lung cancer 29.9% (23), followed by breast 23.4% (18) cancer. CM was detected in 23.4% (18) patients. In univariate analysis, glychorrachia, the CSF leukocyte count, the meningeal involvement on MRI, headache and delirium were significantly associated with MC. In the multivariate model that included the variables significantly associated in the crude analysis, the only variable that remained significantly associated with MC was the glychorrachia (OR 0.93 95%CI 0.9 - 0.97, p <0.001). DISCUSSION: These results suggest that as the glychorrachia increases, the probability of having MC decreases. These findings are consistent with previous studies.

Pyoderma gangrenosum: clinical characteristics, associated diseases, and responses to treatment in a retrospective cohort study of 31 patients.

OBJECTIVE: The aim of this study was to describe the clinical characteristics of patients with pyoderma gangrenosum (PG) and to evaluate the association between these characteristics, the treatment followed, and the patient responses, relapses, and mortality rates. MATERIAL AND METHODS: This retrospective cohort study identified adults diagnosed with pyoderma gangrenosum over the duration of 10 years. RESULTS: Thirty-one patients were evaluated; 58% were women and 55% were older than 65 years, 87% presented with the ulcerative type, and 77% showed lower limb compromise. Approximately 74% of the cases were associated with systemic disease. The most frequent were inflammatory bowel disease (32%) and hematologic malignancies (22%). Pyoderma gangrenosum preceded the associated disease in 26% of the patients, all of them were younger than 50 years old (P = 0.059). In 83% of the latter, the diagnosis of associated disease followed the cutaneous lesions within 24 months. Among the 10 patients with inflammatory bowel disease, six required biologic agents to control the pyoderma gangrenosum (P = 0.002). CONCLUSION: Despite the advances that have been made in the treatment of patients with pyoderma gangrenosum, we are still unclear as to the optimal way in which patients should be followed up once the diagnosis is made. The results of our study underline the importance of doing screening tests to detect potential disease, emphasizing patients younger than 50 years old, for a minimum time lapse of 24 months. It is essential to design randomized-controlled trials to understand the most appropriate and effective ways of following up patients with pyoderma gangrenosum.

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.

[Development of AIDS-related malignancies and infections after starting HAART]. / Desarrollo de neoplasias e infecciones definitorias de sida después de iniciar la terapia antirretroviral de alta eficacia.

In order to evaluate the incidence rate and possible risk factors associated with AIDS-related malignancies and infections (ARMI) we performed data analysis of clinical charts of HIV patients in two hospital cohorts, that started high activity antiretroviral therapy (HAART) between July 2003 and October 2007. Trimethoprim-sulfamethoxazole and Azithromycin prophylaxis was provided according to current guidelines. We evaluated development of ARMI six months after-starting HAART and its association with clinical and epidemiological variables. Of 235 patients analyzed -118 women (50.2%) and 117 men (49.8%)- 11 presented ARMI: 3 pulmonary TB and 3 lymph nodes TB cases, 3 cases with meningeal Cryptococcus, one Chagas's disease presenting brain mass and one with non-Hodgkin lymphoma. ARMI incidence: 4.7%. A CD4 cell count < 100/150 was associated with risk of developing ARMI. The mean CD4 cell count was 73 in patients who developed ARMI and 143 in those who did not. No association was found with the other analyzed variables. In the CD4 cell count < 150 group one out of 4 patients with reactive serology presented Chagas's disease causing brain mass; none of the 46 patients with reactive serology presented toxoplasmosis encephalitis. The incidence rate of ARMI was 4.7%. TB in first place and cryptococcosis in second were the AIDS events more frequently observed. A low CD4 cell count was the only observed risk factor statistically associated with development of ARMI. The role of prophylaxis in this population should be re-evaluated.