Multi-institutional analysis of outcomes in acute myeloid leukemia patients with central nervous system involvement.

We evaluated outcomes of AML patients with central nervous system (CNS) involvement at two academic institutions. Fifty-two adult patients were identified. Neurologic symptoms were reported in 69% of patients, with headache the most common (33%). 84% (n = 42) of patients cleared their cerebrospinal fluid (CSF), with a median number of one dose of intrathecal (IT) chemotherapy. Of these patients, 21% (n = 9) had a CSF relapse, with 67% (n = 6) of those experiencing CSF relapse also having concurrent bone marrow relapse. Of the 36 patients with baseline neurologic symptoms, 69% had improvement in symptoms post-IT therapy. The median overall survival was 9.3 months and 3.5 months for patients with CNS involvement diagnosed before/during induction and at relapse, respectively. In this study, IT therapy was rapidly effective in clearing CSF blasts and improving neurologic symptoms in most patients. Few patients experienced CSF relapse, which predominantly occurred in the setting of concomitant bone marrow relapse.

Case report: Invasive fungal infection in a patient with a rare CVID-causing gene (TNFRSF13B) mutation undergoing AML treatment.

Acute myeloid leukemia (AML) is a complex diagnosis that puts patients at a higher risk for developing infections, particularly invasive fungal infections (IFI). Mutations in TNFRSF13B have been shown to cause dysfunction in B-cell homeostasis and differentiation, making it a risk factor for developing immunodeficiency syndromes. In this case, a male patient in his 40s presented to our emergency department (ED) with symptoms leading to a diagnosis of AML with concurrent mucormycosis of the lungs and sinuses. Targeted next generation sequencing (NGS) of the patient's bone marrow showed, among other variants, a loss of function mutation in the TNFRSF13B gene. While most patients present with fungal infections after prolonged periods of neutropenia associated with AML treatment, this case presented with IFI at diagnosis without neutropenia suggesting an immunodeficiency syndrome. The concurrent IFI and AML diagnoses create a delicate balance between treatment of the infection and the malignancy. This case highlights the risk of infection in patients receiving chemotherapy, especially those with unrecognized immunodeficiency syndromes, and emphasizes the importance of NGS for prognosis and treatment.

Cryptococcal Neoformans and Varicella Zoster Meningitis in a Patient With Selective Innate Immunodeficiency: A Case Report.

Cryptococcal neoformans (C. neoformans) and varicella-zoster (VZV) meningitis are opportunistic infections that are primarily seen in immunocompromised patients, including those with HIV, cancer, or receiving transplants. Despite treatment, infection in immunocompromised patients can be lethal, including those with T-cell dysfunction or deficiency. Whether innate immunodeficiencies also predispose to these infections remains less clear. Here, we report a case of disseminated C. neoformans and VZV meningitis in a young male with idiopathic hypereosinophilic syndrome and hypocomplementemia and no history of HIV infection, malignancy, or transplant. The patient presented with a pulsating headache, myalgia, joint pain, insomnia, night sweats, and subjective fever, along with clusters of vesicular lesions on his neck and back. A lumbar puncture and an MRI of the brain confirmed C. neoformans and VZV meningitis. Vesicular skin lesions proved to be VZV, and blood culture confirmed fungemia, suggesting disseminated disease. We investigated his medical history further to determine the underlying cause of his prior hypereosinophilia and current meningitis. The patient had idiopathic hypereosinophilia with high IgE levels, low complement levels, high rheumatoid factor levels, and an intermittent rash dating back two years, which had been treated intermittently with prednisone and hydroxyurea, with the most recent admission three weeks prior to this admission. Prior to admission, the patient had a peak absolute eosinophil count of 18.6 x103/uL. The patient was discharged on a daily dose of 60 mg of prednisone without hydroxyurea. In further evaluating his immune status, we found he was HIV-negative, with a normal CD4 count and high IgE. We also tested lymphocyte subsets and proliferation, which showed a low CD16/56 level, suggesting possibly reduced natural killer (NK) cell quantity. The patient responded well to acyclovir, amphotericin, and flucytosine therapy. After follow-up cerebrospinal fluid (CSF) and blood cultures were negative, the patient was discharged with fluconazole as maintenance therapy.

Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I2 provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I2 = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I2 = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I2 = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph+ ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.

A Critical Appraisal and Targeted Intervention of the Oncology Experience in an Internal Medicine Residency.

Most oncology education is provided to residents on an inpatient oncology service, with limited outpatient exposure. There exists considerable need to develop effective education strategies to teach resident physicians basic concepts in oncology. We created a 2-hour small-group interactive workshop, using interactive cases, followed by a number of questions regarding curability, survival, and possible treatment options. All residents were asked to fill out optional questionnaires before and after this workshop. A total of 64 residents participated in this study with an average of 16 residents per session. Significant deficits in knowledge were identified, and prognosis was estimated correctly by 40% of residents when presented with a variety of clinical scenarios. We demonstrated an increase in comfort level in basic oncology concerns, comfort level at estimating prognosis, and managing toxicity based on pre- and post-level testing. Our results confirm that the oncology inpatient rotation may not be adequate in educating residents. The format of our workshop demonstrates that it is possible to create and implement a focused intervention with fairly limited resources. This can serve as a platform for evaluation of oncology medical education of internal medicine residents at other institutions.

Multi-Database Description of Primary Splenic Diffuse Large B-Cell Lymphoma.

BACKGROUND/AIM: Stage I splenic diffuse large B-cell lymphoma (DLBCL) is rare and there are few data to guide management. We sought to further define prognosis and outcomes. MATERIALS AND METHODS: We utilized the Surveillance, Epidemiology, and End Results registry to identify patients with stage I splenic DLBCL diagnosed 1973-2013. Patients were divided into two cohorts based on the year of diagnosis (1983-2005; 2006-2013) as rituximab was approved by the U.S. Food and Drug Administration in 2006 for first-line treatment of DLBCL. RESULTS: Utilization of splenectomy decreased after the approval of rituximab (82% pre- versus 72% rituximab-era). Disease-specific and overall survival were greater with splenectomy [hazard ratio (HR)=0.57, p=0.04; and HR=0.66, p=0.03, respectively], but this benefit was only seen in the pre-rituximab cohort, not in the rituximab-era cohort. There was a trend toward improved overall survival with the introduction of rituximab (HR=0.75, p=0.054). CONCLUSION: Utilization of splenectomy for stage I splenic DLBCL has decreased with the introduction of rituximab without compromising outcomes.

GABA and glutamate levels in occlusal splint-wearing males with possible bruxism.

OBJECTIVE: The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the pathophysiology of anxiety behavioural disorders such as panic disorder and post-traumatic stress disorder and is also implicated in the manifestation of tooth-grinding and clenching behaviours generally known as bruxism. In order to test whether the stress-related behaviours of tooth-grinding and clenching share similar underlying mechanisms involving GABA and other metabolites as do anxiety-related behavioural disorders, we performed a Magnetic Resonance Spectroscopy (MRS) study for accurate, in vivo metabolite quantification in anxiety-related brain regions. DESIGN: MRS was performed in the right hippocampus and right thalamus involved in the hypothalamic-pituitary-adrenal axis system, together with a motor planning region (dorsal anterior cingulate cortex/pre-supplementary motor area) and right dorsolateral prefrontal cortex (DLPFC). Eight occlusal splint-wearing men (OCS) with possible tooth-grinding and clenching behaviours and nine male controls (CON) with no such behaviour were studied. RESULTS: Repeated-measures ANOVA showed significant Group×Region interaction for GABA+ (p = 0.001) and glutamate (Glu) (p = 0.031). Between-group post hoc ANOVA showed significantly lower levels of GABA+ (p = 0.003) and higher levels of Glu (p = 0.002) in DLPFC of OCS subjects. These GABA+ and Glu group differences remained significant (GABA+, p = 0.049; Glu, p = 0.039) after the inclusion of anxiety as a covariate. Additionally, GABA and Glu levels in the DLPFC of all subjects were negatively related (Pearson's r = -0.75, p = 0.003). CONCLUSIONS: These findings indicate that the oral behaviours of tooth-grinding and clenching, generally known as bruxism, may be associated with disturbances in brain GABAergic and glutamatergic systems.

Motor control of jaw movements: An fMRI study of parafunctional clench and grind behavior.

Jaw-clenching and tooth-grinding associated with bruxism can contribute to abnormal tooth wear and pain in the masticatory system. Clench and tooth-grinding jaw-movement tasks were evaluated in a block-design fMRI study comparing a dental-control (DC) group with a tooth-grinding (TG) group. Group classification was made prior to imaging based upon self-reported parafunctional clench and grind behavior and clinical evidence of abnormal tooth wear. Group differences in brain activation patterns were found for each task compared to the resting baseline. The DC group showed a more widely distributed pattern; more extensive activity in the supplementary motor area (SMA) proper that extended into the pre-SMA; and, for clench, activity in the left inferior parietal lobule (IPL). The DC group activated more than the TG subjects the left IPL for clench, and pre-SMA for grind. Neither task elicited more activity in the TG than DC subjects. Our group findings suggest that jaw-movement tasks executed by the TG group elicited (1) more efficient brain activation pattern consistent with other studies that found less extensive activity with executing "over-learned" tasks; (2) "underactive" SMA activity that underlies reduced motor planning; (3) decreased inferior parietal activity that is associated with lesser motor-attentional demands. Thus orofacial parafunctional habits may influence brain circuits recruited for jaw movements, providing a possible basis for understanding involuntary jaw movements in bruxism and oral movement disorders in general.

Postoperative readmissions following laparoscopic and abdominal hysterectomy: a comparison.

OBJECTIVE: To quantify the readmission rates for total laparoscopic and total abdominal hysterectomy, as well as identify preoperative, intraoperative, and postoperative risk factors for readmission within 6 weeks of surgery. METHODS: A retrospective comparative study was performed using a departmental database to identify all readmissions following total laparoscopic and total abdominal hysterectomy and to assemble a control group. For each patient, the following data were systematically collected: surgery date, age, parity, body mass index, indications for surgery, type of procedure performed, uterine size, number of prior cesarean sections, number of prior laparoscopic abdominal surgeries, number of prior open abdominal surgeries, presence of adhesions at time of hysterectomy, diabetic status, operative time, postoperative hematocrit, intraoperative and postoperative complications, surgeon, use of postoperative antibiotics, postoperative day readmitted, reason for readmission, length of readmission, and whether the patient returned to the operating room during the readmission. RESULTS: From January 1, 2000 to April 1, 2007, 1,576 total abdominal and 1,198 total laparoscopic hysterectomies were performed at Ochsner Medical Center. Of these, 19 abdominal and 31 laparoscopic hysterectomy patients were readmitted within 6 weeks of surgery. Our control groups consisted of 84 laparoscopic and 53 abdominal hysterectomy patients. A statistically significant difference in readmission rates (1.2% following abdominal hysterectomy vs. 2.7% following laparoscopic hysterectomy) was identified. No correlation between readmission and operative time, adhesive disease, diabetic status, prior cesarean sections, prior open or laparoscopic procedures, postoperative antibiotic use or postoperative hematocrit could be identified. Compared to those undergoing abdominal hysterectomy, those undergoing laparoscopic hysterectomy had more readmissions due to cuff dehiscence and cuff cellulitis for (p  =  0.0146), which is a previously recognized complication of total laparoscopic hysterectomy. We were unable to identify any significant difference in postoperative day of readmission, length of readmission, or return to operating room. CONCLUSION: Further investigation would benefit from an expanded study group, which may result in identification of some significance of the studied factors that were not able to be identified in this study.