Epidemiology and Clinical Characteristics of Primary Amebic Meningoencephalitis Caused by Naegleria fowleri: A Global Review.

BACKGROUND: Primary amebic meningoencephalitis (PAM) is a rapidly progressive and often fatal condition caused by the free-living ameba Naegleria fowleri. To estimate the global occurrence, characterize the epidemiology, and describe the clinical features of PAM, we report a series of PAM cases published in the international literature and reported to the Centers for Disease Control and Prevention (CDC). METHODS: We performed a literature search of PAM case reports published through 2018. Additionally, we included cases reported through the CDC's Free-Living Ameba surveillance or diagnosed via CDC's Free-Living and Intestinal Amebas Laboratory. Cases were classified as confirmed, probable, or suspect on the basis of confirmatory testing, presentation, exposure, and disease course. RESULTS: A total of 381 PAM cases were identified. Seven reported survivors were classified as confirmed. The most commonly reported exposure associated with PAM was swimming/diving, and the most common class of water source was lakes/ponds/reservoirs. Patients were predominantly male (75%), with a median age of 14 years. Confirmed and probable cases were similar in their survival, course of illness, and cerebrospinal fluid (CSF) findings. CONCLUSIONS: PAM is a rare but deadly disease with worldwide occurrence. Improved clinician awareness, resulting in earlier diagnosis and treatment, may contribute to increased survival among PAM patients. The case definition of probable used in this study appears to capture cases of PAM, as evidenced by similarities in outcomes, clinical course, and CSF profile to confirmed cases. In the absence of confirmatory testing, clinicians could use this case definition to identify cases of PAM.

Targeting of the bone marrow microenvironment improves outcome in a murine model of myelodysplastic syndrome.

In vitro evidence suggests that the bone marrow microenvironment (BMME) is altered in myelodysplastic syndromes (MDSs). Here, we study the BMME in MDS in vivo using a transgenic murine model of MDS with hematopoietic expression of the translocation product NUP98-HOXD13 (NHD13). This model exhibits a prolonged period of cytopenias prior to transformation to leukemia and is therefore ideal to interrogate the role of the BMME in MDS. In this model, hematopoietic stem and progenitor cells (HSPCs) were decreased in NHD13 mice by flow cytometric analysis. The reduction in the total phenotypic HSPC pool in NHD13 mice was confirmed functionally with transplantation assays. Marrow microenvironmental cellular components of the NHD13 BMME were found to be abnormal, including increases in endothelial cells and in dysfunctional mesenchymal and osteoblastic populations, whereas megakaryocytes were decreased. Both CC chemokine ligand 3 and vascular endothelial growth factor, previously shown to be increased in human MDS, were increased in NHD13 mice. To assess whether the BMME contributes to disease progression in NHD13 mice, we performed transplantation of NHD13 marrow into NHD13 mice or their wild-type (WT) littermates. WT recipients as compared with NHD13 recipients of NHD13 marrow had a lower rate of the combined outcome of progression to leukemia and death. Moreover, hematopoietic function was superior in a WT BMME as compared with an NHD13 BMME. Our data therefore demonstrate a contributory role of the BMME to disease progression in MDS and support a therapeutic strategy whereby manipulation of the MDS microenvironment may improve hematopoietic function and overall survival.

Tumor Lysis Syndrome in a Low-Risk Pancreatic Cancer Patient.

Tumor lysis syndrome (TLS) is the most common hematologic emergency encountered during the treatment of high-grade malignancies. While it can lead to death, the prognosis is typically excellent if caught early on in the course. Risk stratification prior to treatment initiation is paramount in deciding the utility of prophylaxis and ultimately in reducing morbidity and mortality. The following case describes the development of TLS in a patient categorized as low risk and highlights the need for further elucidation of a unified risk stratification system.

The unusual case of babesiosis causing disseminated intravascular coagulation with hemophagocytic lymphohistiocytosis.

Babesiosis is increasing in the elderly due to an age-related decline in immunity. Prompt diagnosis with blood smear and PCR prevent life-threatening complications, like DIC and HLH. Studies focusing on pathophysiology and risk factors are needed.

The Management of Erythrodermic Psoriasis Complicated by Cyclosporine.

We present a 64-year-old woman with past medical history of psoriasis and alcoholic liver cirrhosis who presented with a diffuse, erythematous, and scaly rash. Pertinent medications included topical triamcinolone 0.1% cream. She was started on oral prednisone 40 milligrams (mg) and oral cyclosporine 150 mg daily and was continued on topical triamcinolone. After the administration of two doses of this regimen, the serum creatinine increased to 1.76 mg/dL, and serum potassium increased to 6.7 mEq/L. The serum creatinine continued to uptrend to 2.42 mg/dL, and the glomerular filtration rate (GFR) decreased to 20 mL/min. The patient was emergently hemodialyzed. The patient was placed on an extended steroid taper, alleviating the psoriatic rash. However, the patient needed to be placed on a steroid-sparing regimen. Because of its rarity and ensuing complications, erythrodermic psoriasis must be identified and managed promptly. Cyclosporine is currently the first-line treatment. However, initiation of this therapy in our patient resulted in an acute kidney injury (AKI). Even though a steroid taper assisted in alleviating erythroderma, a steroid-sparing regimen needed to be started. This led to the consideration of alternate methods of therapy for further management of erythrodermic psoriasis with renal impairment.

Bouveret syndrome as a rare cause of gastric outlet obstruction.

Biliary-enteric fistula is a rare complication of cholelithiasis that can lead to gallstone ileus. Gallstone impaction in the duodenum and pylorus is extremely rare and can lead to gastric outlet obstruction, a condition known as Bouveret syndrome. Bouveret syndrome needs to be diagnosed and managed in a timely fashion, as it has a high mortality rate. We describe a case of an elderly patient who presented with Bouveret syndrome secondary to impaction of the biliary calculus in the first part of duodenum.

The Chemokine CCL3 Regulates Myeloid Differentiation and Hematopoietic Stem Cell Numbers.

The chemokine CCL3 is frequently overexpressed in malignancies and overexpression leads to microenvironmental dysfunction. In murine models of chronic myelogenous leukemia (CML), CCL3 is critical for the maintenance of a leukemia stem cell population, and leukemia progression. With CCL3 implicated as a potentially viable therapeutic target, it is important to carefully characterize its role in normal hematopoietic homeostasis. CCL3-/- mice were used to evaluate the role of CCL3 in regulating hematopoietic stem and progenitor cell (HSPC) populations. CCL3-/- mice had loss of mature myeloid populations, while myeloid progenitors and HSPCs were increased, and microenvironmental populations were unchanged. These data show that CCL3 promotes myeloid lineage differentiation and the size of the HSPC pool independent of the supportive bone marrow microenvironment. Our results demonstrate a previously unrecognized role of CCL3 in the maintenance of homeostatic hematopoiesis that should be evaluated when targeting CCL3 signaling for the treatment of hematologic malignancy.