Objective
There is no consensus on the treatment of progressive multifocal leukoencephalopathy (PML) occurring in multiple sclerosis (MS) patients treated with natalizumab (Nz). We report novel ...immune activating treatment with filgrastim of Nz‐associated PML in MS patients treated at Rush University Medical Center.
Methods
We retrospectively analyzed 17 Nz‐PML patients treated at this single tertiary referral center between 2010 and 2017. We reviewed the clinical symptoms, diagnostic methods, survival, outcome and MS modifying therapy (MSMT) after Nz‐PML.
Results
PML occurred after an average of 49 Nz infusions. To facilitate JCV elimination by accelerating immune reconstitution inflammatory syndrome (IRIS), all patients received subcutaneous filgrastim upon PML diagnosis and discontinuation of Nz; eight received plasma exchange (PLEX). Earlier than previously published, PML‐IRIS occurred in 15 of 17 (88.2%) patients within a mean of 57.4 days (SD 21.20) after the last Nz infusion. Seven patients recovered to or near baseline. There were no PML/IRIS–related fatalities but one patient committed suicide 2.5 years later. PLEX had no impact on PML outcome. Of 17 patients, 3 (18%) had MS relapses within 1 year after PML, and 5 (29%) beyond 1 year of PML onset, which is lower than expected in highly active MS patients. Eight patients started MSMTs after Nz‐PML on an average of 26 months after Nz withdrawal.
Interpretation
Our findings indicate that immunoactivation with filgrastim during PML and careful management of subsequent IRIS is likely beneficial in patients with Nz‐PML, without worsening MS. The clinical course of MS may be ameliorated by PML.
We present two natalizumab‐treated multiple sclerosis patients who developed glioblastoma multiforme (GBM) with variable outcomes. One patient had an isocitrate dehydrogenase (IDH)‐wildtype GBM with ...aggressive behavior, who declined treatment and died 13 weeks after symptoms onset. The other patient underwent resection of an IDH‐mutant secondary GBM that arose from a previously diagnosed grade II astrocytoma. He is still alive 5 years after the diagnosis of GBM. JC virus was not detected in either case. Whether natalizumab played a role in the development of GBM in those patients deserves further investigation.
Unfortunately, the given name and family name of first author was incorrectly tagged in the xml data, therefore it is abbreviated wrongly as “Morales FS” in Pubmed. The correct given name is Fabian ...and family name is Sierra Morales. Auhtor name should be abbreviated as Sierra Morales F.
We present the case of an HIV-2-infected patient who developed progressive multifocal leukoencephalopathy (PML) in the setting of immune reconstitution inflammatory syndrome (IRIS) presenting as ...Bell’s palsy. The brain MRI showed a single lesion in the facial colliculus considered initially to be ischemic in nature. This case report should alert clinicians that PML can occur in the setting of HIV-2 infection. It also illustrates the difficulty of establishing the diagnosis of PML.
Cyclophosphamide (CYC) may be an effective treatment in patients who fail first line therapy for severe central nervous system (CNS) inflammatory disorders including CNS vasculitis, neuromyelitis ...optica, autoimmune encephalitis, tumefactive and aggressive multiple sclerosis (MS). We performed a retrospective analysis of 46 patients treated with CYC after failing first line therapy for severe CNS inflammatory conditions. Primary outcomes included modified Rankin Scale (mRS) for patients classified into a non-MS group, Expanded Disability Status Score (EDSS) for MS patients, and Targeted Neurological Deficit score (TND) for all patients. Secondary outcome included neuroimaging studies following CYC treatment. By the second follow up period (average of 7 months) mRS in the non-MS group improved from 3.7 to 2.2 and EDSS in the MS group improved from 5.6 to 3.8. Average TND score at 7 months was 2.8 (mild-marked improvement). At first follow up (average 5.6 months), 76.2% (32/42) patients had either stable or improving imaging, and 83.3% (30/36) patients had stable or improving imaging at second follow up (average 13.6 months). Adverse events were reported by 31.9% of patients with most common being nausea and vomiting, headache, alopecia, and hyponatremia. Treatment with CYC can result in disease stabilization of severe CNS inflammatory diseases and is generally well tolerated.
•Neuroinflammatory diseases of the central nervous system cause severe morbidity and mortality despite first line therapy.•This study analyzes the agent cyclophosphamide as a second line therapy in neuroinflammatory disorders.•Most patients made clinical and radiologic improvement after cyclophosphamide treatment.•Overall, cyclophosphamide was well tolerated with expected adverse events.
Objectives
To identify risk factors for DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MS patients.
Methods
We performed a retrospective analysis of 194 RRMS patients ...treated with DMF at the Beth Israel Deaconess Medical Center (BIDMC) over a median of 17 months. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined included age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymphopenia was defined as grade 1: absolute lymphocytes count (ALC) 800–999/μl; grade 2: ALC 500–799/μl; grade 3: ALC 200–499/μl; and grade 4: ALC < 200/μl.
Results
Of 194 DMF-treated patients, 73 (38%) developed lymphopenia and reached an ALC nadir after a median of 504 days (range 82–932). Risk of developing DMF-induced lymphopenia increased with BMI 25–30, older age, white ethnicity, non-smoking status, and lowest quartile baseline ALC. Prior exposure to natalizumab or concomitant steroid, opiates or carbamazepine/oxcarbamazepine use was not associated with lymphopenia. Compared to baseline levels, CD8 T cells were significantly more reduced than CD4 cells. CD8 counts were more commonly reduced with age or white ethnicity. Subjects with BMI 25–30 was associated with a higher risk of abnormal CD4 cell count reductions. In contrast, non-smokers were more likely to experience reductions in both CD4 and CD8 counts while on DMF.
Conclusions
Patients with low baseline lymphocyte counts, with intermediate BMI, with white ethnicity, with advanced age, or with no tobacco use, had a significantly higher incidence of lymphopenia on DMF. Intermediate BMI or lowest quartile baseline ALC predicted low CD4 levels, while advanced age or white ethnicity predicted low CD8 levels from DMF exposure.
The development of a novel small-scale electrical power source technology is essential in the design of microelectronic devices. In this sense, this study presents the optimization of the sputtering ...deposition parameters to grow a LiFePO4 cathode, a candidate material for the development of solid-state lithium batteries. Specifically, it was evaluated the effect of argon deposition pressure on the electrochemical properties of LiFePO4 cathode. By combining X-ray photoelectron spectroscopy with electrochemical characterization methods, it was revealed that argon deposition pressure modulated the degree of the re-sputtering effects. In addition, it was found that high argon deposition pressure leads to the growth of LiFePO4 films with oxygen and phosphor deficiency. The absence of these atoms caused the decrease in the LiFePO4 electrochemical activity. Conversely, deposition parameters based on low argon sputtering pressure significantly reduced the degree of the re-sputtering effects, which in turn favored the growth of stoichiometric LiFePO4 films with an enhanced electrochemical activity.
The worldwide scarcity of psychiatrists makes the identification of the factors associated with the intention to choose this specialty an important issue. This study aims to evaluate the association ...between religious affiliation and the intention to choose psychiatry as a specialty among medical students from 11 Latin American countries. We conducted a cross-sectional, multi-country study that included first- and fifth-year students of 63 medical schools in 11 Latin-American countries between 2011 and 2012. The main outcome and measures were the intention to pursue psychiatry as a specialty over other specialties (yes/no) and religious affiliation (without: atheist/agnostic; with: any religion). A total of 8308 participants were included; 53.6% were women, and the average age was 20.4 (SD = 2.9) years. About 36% were fifth-year students, and 11.8% were not affiliated with any religion. Only 2.6% had the intention to choose psychiatry; the highest proportion of students with the intention to choose psychiatry was among students in Chile (8.1%) and the lowest among students in Mexico (1.1%). After adjusting for demographic, family, academic as well as personal and professional projection variable, we found that those who had no religious affiliation were more likely to report the intention to become a psychiatrist OR: 2.92 (95%CI: 2.14-4.00). There is a strong positive association between not having a religious affiliation and the intention to become a psychiatrist. The possible factors that influence this phenomenon must be evaluated in greater depth, ideally through longitudinal research.
Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic.
The objective of the study to describe the ...clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC).
We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020.
We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m
and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died.
Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.
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