A multi-institutional comparison of mitoxantrone,etoposide, and cytarabine vs high-dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia

Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC) and mitoxantrone and high-dose Ara-C (Ara-C couplets). We analyzed 155 patients treated at three academic institutions between 1998 and 2017; 87 patients received MEC and 68 received Ara-C couplets. The primary endpoint was overall response (OR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and nonhematologic toxicities, and success in proceeding to alloSCT. Baseline characteristics of the cohorts were well matched, though patients receiving Ara-C couplets had more co-morbidities (48.5% vs 33%; P = .07). OR was achieved in 43.7% of MEC and 54.4% of Ara-C couplets patients (P = .10). Ara-C couplets patients also trended towards a longer OS and PFS, more frequently proceeded to alloSCT (31% vs 54.4%; P = .003), and experienced less febrile neutropenia (94% vs 72%; P < .001) and grade 3/4 gastrointestinal toxicities (17.2% vs 2.94%; P = .005). No significant differences in other toxicities or median duration of hospitalization were noted. This is the first multi-institutional study directly comparing these regimens in a racially diverse population of R/R AML patients. Although these regimens have equivalent efficacy in terms of achieving OR, Ara-C couplets use is associated with significant reductions in toxicities, suggesting it should be used more frequently in these patients.     

Lumbar puncture requirement in acute hemiparesis: Diagnosis of tuberculous meningitis after hemiparesis in a child

Background

Infections are an important acquired cause of cerebral arteriopathy. Tuberculous (TB) meningitis leading to infectious cerebral vasculopathy is a rare cause of acute hemiparesis.

Case report

A 14-year-old male patient was examined after acute hemiparesis developing within 1 day. Neurological examination revealed total hemiplegia on the left side. Brain MRI findings showed bilateral focal T2-weighted signal hyperintensity in the subcortical and deep white matter regions. There were also areas of restricted diffusion in the right basal ganglia. Although the father had a history of pulmonary TB, the patient had not been given TB prophylaxis because of PPD negativity. At lumbar puncture, opening cerebrospinal fluid (CSF) pressure was 50 cm/H20, CSF protein 66.9 mg/dL, and glucose 54 mg/dL (concurrent blood glucose 93 mg/dL); 170 polymorphonuclear leukocytes per cubic millimeter were present in CSF. Following tests for TB, treatment was started immediately with four anti-TB drugs. TB PCR of CSF and acid-fast bacteria (AFB) staining in gastric aspirate were positive. At clinical follow-up, the patient was able to walk with support at the end of the first month.

Conclusion

Various infectious agents have been reported as causes of cerebral vasculopathy. TB, which affects a significant number of patients worldwide, should be kept in mind in terms of cerebral vascular complications. Lumbar puncture is essential in order to diagnose TB meningitis.     

Quantitative Positron Emission Tomography Studies of the Serotonin Transporter in Humans Previously Treated with the Appetite Suppressants Fenfluramine or Dexfenfluramine

Purpose The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [¹¹C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters. Procedures Subjects previously treated with fenfluramines for weight loss (N = 15) and age-matched controls (N = 17) underwent PET studies with [¹¹C] McN5652. Global and regional distribution volumes (DVs) of [¹¹C] McN5652 were compared in the two subject groups using parametric statistical analyses. Results Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [¹¹C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation. Conclusions These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.     

Left Atrial Deformation Parameters Predict Left Atrial Appendage Function and Thrombus in Patients in Sinus Rhythm with Suspected Cardioembolic Stroke: A Speckle Tracking and Transesophageal Echocardiography Study

The aim of this study was to evaluate left atrial deformations using speckle tracking echocardiography for predicting left atrial appendage (LAA) thrombus in patients with suspected cardioembolic stroke who were in normal sinus rhythm. A total of 153 ischemic stroke patients (89 males, 64 females) in sinus rhythm who were suspected of having cardioembolism were included in the study. The patients underwent conventional two‐dimensional (2D) echocardiogram and 2D speckle tracking echocardiogram of the left atrium. Left atrial peak strain (LA‐4C‐RES) and left atrial precontraction strain (LA‐4C‐PUMP) were measured. Patients were divided into 2 groups according to the presence of thrombus in the LAA in transesophageal echocardiography. Both LA‐4C‐RES and LA‐4C‐PUMP values were found to be significantly lower in patients with LAA thrombus (11.8 ± 1.4% vs. 33 ± 12%, P < 0.001 and 5.8 ± 1.3% vs. 14.2 ± 5.3%, P < 0.001, respectively). A good inverse correlation was present between LA‐4C‐RES values and LAA morphologic parameters (with LAA area: r = ?0.70, P < 0.001, with LAA length: r = ?0.60, P < 0.001), and a good positive correlation was present with LAA emptying velocity with pulse Doppler (r = 0.74, P < 0.001). The area under the receiver‐operating characteristic curve of the LA‐4C‐RES was 0.94 (0.90–0.98, P < 0.001), for the LA‐4C‐PUMP, the area was 0.92 (0.87–0.96, P < 0.001) to predict LAA thrombus. Left atrial deformation parameters measured by 2D speckle tracking method was found to predict impaired LAA functions and the presence of LAA thrombus in ischemic stroke patients with suspected cardioembolism, but who are in sinus rhythm.     

Plasma Concentrations of Isoniazid and Rifampin Are Decreased in Adult Pulmonary Tuberculosis Patients with Diabetes Mellitus

Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol concentrations, were decreased by about 50% (P < 0.05) in diabetic pulmonary tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin, pyrazinamide, and ethambutol concentrations were 49% or 100% (P < 0.01), 66% or 100% (P < 0.05), 30% or 50% (P = 0.198), and 32% or 21% (P = 0.742) in nondiabetic or diabetic tuberculosis patients, respectively. These data show that plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic tuberculosis patients.     

Evaluation of capsular and acapsular strains of S. aureus in an experimental brain abscess model

Brain abscesses are mainly caused by either direct or indirect inoculation of gram positive bacteria including Stapylococcus aureus (S. aureus) or Streptococcus species into the central nervous system. In the present study, we aimed to compare potential changes in brain abscess pathogenesis induced by two different strains of S. aureus, namely the laboratory strain RN6390 and the clinical isolate Reynolds. Although the Reynolds strain was expected to be more resistant to eradication by the host, due to the existence of a polysaccharide capsule, and subsequently to be more virulent, instead we found parenchymal damage and mortality rates to be more prominent following RN6390 infection. In contrast, the Reynolds strain proliferated faster and induced early expression of the chemokine CXCL2, matrix metalloproteinase-9 (MMP-9), and complement 3a and C5. Furthermore, there were early and more abundant infiltration of PMNs, T cells and erythrocyte extravasation in brain abscesses induced by the Reynolds strain. However, several immune parameters were not different between the two strains during the later stages of the disease. These results suggest that capsular S. aureus can modulate innate immunity and complement system activation differently than the acapsular strain RN6390, and the early changes induced by Reynolds strain may have an important impact on survival.     

Spontaneous Infarction in a Fibroadenoma of the Breast

SUMMARY: BACKGROUND: Fibroadenomas are common neoplasms in young women but occur in a wide age range from adolescent females to octogenians. CASE REPORT: A 21-year-old female patient presented with a 10-week history of a mass in her breast. Ultrasound examination demonstrated a 3.5 × 3 cm, well-circumscribed, semisolid mass. An excisional biopsy but no fine needle aspiration was performed. The patient had no history of pregnancy or lactation, or trauma or infection to the area of the lesion. The histopathological examination showed a spontaneously infarcted fibroadenoma. CONCLUSIONS: Spontaneous infarction is an uncommon complication in fibroadenoma of the breast, and there are very few reported cases in the literature.