HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma.

Human herpesvirus 8 (HHV8)-associated lymphoid proliferations are uncommon and poorly characterized disorders mainly affecting immunosuppressed patients, especially with HIV infection. They encompass different diseases with overlapping features that complicate their classification. In addition, the role of HHV8 in reactive lymphoid hyperplasia is not well known. To analyze the clinicopathological spectrum of these lesions, we have reviewed 66 biopsies of 61 patients with HHV8 infection. All cases were also investigated for Epstein-Barr virus (EBV) and HIV infection. We identified 13 (20%) cases of HHV8-related reactive lymphoid hyperplasia, 2 (3%) HHV8 plasmablastic proliferations of the splenic red pulp, 28 (42%) multicentric Castleman disease, 6 (9%) germinotropic lymphoproliferative disorders, and 17 (26%) HHV8-related lymphomas. As expected, the pathologic subtype was predictive of overall survival (P<0.05). Forty-seven of our cases were HIV positive (77%). In addition to the classical presentation of the different entities, we identified novel and overlapping features. Reactive HHV8 proliferations were frequently associated with systemic symptoms but never progressed to overt HHV8-positive lymphoma. Two cases had a plasmablastic proliferation limited to spleen. Eight cases of multicentric Castleman disease had a previously unrecognized presentation shortly after the diagnosis of HIV infection, six cases had cavity effusions, and three showed plasmablast enriched proliferations. One germinotropic lymphoproliferative disorder was EBV negative and three occurred in HIV-positive patients, who had distinctive clinical and morphological features. Two of the HHV8-related lymphomas did not fulfill the criteria for previously recognized entities. All these findings expand the clinical and pathological spectrum of HHV8-related lymphoid proliferations, which is broader than current recognized.

Factors Associated with Hospitalization among Emergency Department Patients Referred for Quick Investigation of Iron-Deficiency Anemia.

BACKGROUND: Although patients with anemia are frequently seen in emergency departments (EDs), studies on patients presenting there with symptomatic chronic anemia--usually iron-deficiency anemia (IDA) caused by occult gastrointestinal bleeding--are lacking. Awareness of predictors of hospitalization could direct the ED triage to the appropriate diagnostic setting. OBJECTIVE: Based on initial observations that some patients with IDA were hospitalized after ED referral and initial evaluation at a quick diagnosis unit (QDU), a new cost-effective alternative to hospitalization for diagnostic workup, this study aimed to determine the patient factors associated with hospitalization after the first QDU visit. METHODS: An 8-year prospective cohort study of patients with IDA referred from the ED to the QDU of a third-level university hospital was conducted. Patients with a baseline hemoglobin level of <9 g/dL in the ED, proven iron deficiency, and no overt bleeding were included. The primary outcome was hospitalization after the initial QDU assessment. RESULTS: Two hundred eighty-four (7.7%) of 3692 patients were hospitalized. Inter-rater agreement of appropriateness of admissions was 90.6% (κ = 0.82). Overall, 90% of study patients presented to the ED with symptomatic anemia, and 87% were transfused there. On multivariate analysis, age ≥ 65 years, living alone, a post-transfusion hemoglobin level of <9 g/dL, higher age-adjusted overall comorbidity, heart failure, and poor physical health-related quality of life at first QDU visit independently predicted hospitalization. CONCLUSION: While these predictors do not necessarily reflect the need for hospitalization, they are easily evaluated during the initial ED visit and can guide the triage of similar IDA patients to the suitable setting for timely investigation.

Predictors of mortality in emergency department patients with sepsis scored 2 or 3 on the Quick Sequential Organ Failure Assessment scale. / Factores predictivos de mortalidad en los pacientes con sepsis y un valor del indicador 'Quick Sequential Organ Failure Assessment' (qSOFA) de 2 o 3 puntos atendidos en un servicio de urgencias.

OBJECTIVES: To identify predictors of mortality after implementation of a treatment protocol in the first 3 hours for patients who come to our emergency department with sepsis scored 2 or 3 on the Quick Sequential Organ Failure Assessment (qSOFA) scale. MATERIAL AND METHODS: Our team identified adult emergency department patients with a diagnosis of sepsis on starting the morning shift between September 2018 and March 2019. We selected patients whose qSOFA score on arrival was 2 or 3. Variables were explored statistically to identify factors associated with mortality. RESULTS: A total of 90 patients with a mean (SD) age of 72 (16) years were included. Thirty-three (37%) died. Univariate analysis detected that the only qSOFA indicator that was significantly associated with mortality was altered mentation (level of consciousness), which was noted in 79% of patients who died versus 54% of survivors (P=.02). Other variables associated with higher mortality were age 70 years or older, an order to limit therapeutic interventions in emergencies, and lactic acid levels on first and second extractions. The treatment protocol was completed in 42% of the cases and compliance was associated with a lower mortality rate of 21% versus 54% when the protocol was not fully implemented (P=.003). Multivariate Cox regression analysis showed that risk for death was higher when the full protocol was not implemented within 3 hours of arrival (hazard ratio, 2.67; 95% CI, 1.15-6.21; P=.02). CONCLUSION: Full implementation of the protocol within 3 hours of hospital arrival favors survival in patients with sepsis and qSOFA scores of 2 or 3 on arrival. We recommend that emergency departments organize ways to train staff in the use of a sepsis treatment protocol and improve compliance.

OBJETIVO: Determinar los factores predictivos de mortalidad de los pacientes que acuden a urgencias con sepsis y tiene un qSOFA de 2 o 3 puntos tras la implementación de un paquete de medidas a cumplimentar en las primeras 3 horas. METODO: De septiembre de 2018 a marzo de 2019 el equipo investigador identificó a los pacientes adultos que se encontraban en urgencias en el inicio del turno de mañana con el diagnóstico de sepsis. De estos pacientes se seleccionaron los que en el momento de su llegada tenían un qSOFA de 2 o 3 puntos. Se realizó análisis estadístico para establecer los factores relacionados con mortalidad. RESULTADOS: Se incluyeron 90 pacientes con una edad media de 72 (DE 16) años. La mortalidad global fue de 33 pacientes (37%). En el análisis univariado de mortalidad, el único indicador del qSOFA con significación estadística fue el nivel de consciencia (79% vs 54%, p = 0,02). Otras variables relacionadas con mayor mortalidad fueron: edad igual o mayor de 70 años, orden de limitación del esfuerzo terapéutico en urgencias y valor de la primera y de la segunda determinación de lactato. El cumplimiento del paquete de medidas fue del 42% y se asoció a una menor mortalidad (21% vs 54%, p = 0,003). En el análisis multivariado mediante regresión de Cox, los pacientes en los que no se cumplimentó el paquete de medidas en las primeras 3 horas tuvieron mayor riesgo de mortalidad al final del episodio (HR = 2,67; IC95% = 1,15-6,21; p = 0,02). CONCLUSIONES: En los pacientes con sepsis y un qSOFA de 2-3 puntos a su llegada a urgencias el cumplimiento del paquete de medidas en las primeras 3 horas mejora la supervivencia. Es recomendable hacer los esfuerzos organizativos y docentes necesarios para mejorar el cumplimiento.

Infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies.

INTRODUCTION: Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients. OBJECTIVES AND METHODS: The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies. RESULTS: We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein-Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively). CONCLUSIONS: In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended.