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ObjectivesHow brain MRI lesions associate with outcomes in pediatric anti-NMDA receptor encephalitis (pNMDARE) is unknown. In this study, we correlate T2-hyperintense MRI brain lesions with clinical outcomes in pNMDARE.MethodsThis was a multicenter retrospective cohort study from 11 institutions. Children younger than 18 years with pNMDARE were included. One-year outcomes were assessed by the modified Rankin Score (mRS) with good (mRS ≤2) and poor (mRS ≥3) outcomes.ResultsA total of 175 pNMDARE subjects were included, with 1-year mRS available in 142/175 (81%) and 60/175 (34%) had abnormal brain MRIs. The most common T2-hyperintense lesion locations were frontal, temporal, and parietal. MRI features that predicted poor 1-year outcomes included abnormal MRI, particularly T2 lesions in the frontal and occipital lobes. After adjusting for treatment within 4 weeks of onset, improvement within 4 weeks, and intensive care unit admission, MRI features were no longer associated with poor outcomes, but after multiple imputation for missing data, T2 frontal and occipital lesions associated with poor outcomes.DiscussionAbnormal frontal and occipital lesions on MRI may associate with 1-year mRS in pNMDARE. MRI of the brain may be a helpful prognostication tool that should be examined in future studies.

Since emergence of the highly pathogenic avian influenza virus (HPAIV) H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage in 1996, successors continue to circulate in waves around the world, leading to massive losses in [...]

Abstract Objective To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. Methods A multicenter, retrospective, case–control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10–30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. Results In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p

In a 1-year survey of wild terrestrial predators in northern Germany, we found that 5 of 110 foxes were infected with contemporary avian influenza A(H5N1) viruses, forming a temporal cluster during January‒March 2023. Encephalitis and strong cerebral virus replication but only sporadic mammalian-adaptive viral polymerase basic 2 protein E627K mutations were seen.

Abstract Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9–12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush–Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2 = 11.82, P = 0.001), abnormal MRI (χ 2 = 7.78, P = 0.005), and abnormal LP (χ 2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P

Abstract Introduction Infectious diseases (ID) consultations have been demonstrated to improve patient outcomes in the treatment of severe infections. However, ID consultation is often unavailable to patients that live in rural communities. Little is known regarding the treatment of infections in rural hospitals with no coverage from an ID specialist. We characterized the outcomes of patients cared for in hospitals without coverage from an ID physician. Methods Patients aged 18 years or older admitted to eight community hospitals without access to ID consultation during a 6.5-month period were assessed. All patients had received at least three days of continuous antimicrobial therapy. The primary outcome was the need for transfer to a tertiary facility for ID services. The secondary outcome was the characterization of antimicrobials received. Antimicrobial courses were evaluated independently by two board-certified ID physicians. Results 3706 encounters were evaluated. Transfers for ID consultation occurred in 0.01% of patients. The ID physician would have made modifications in 68.5% of patients. Areas for improvement included treatment of chronic obstructive pulmonary disease exacerbations, broad-spectrum treatment of skin and soft tissue infection, long courses of azithromycin, and management of Staphylococcus aureus bacteremia, including choice and length of therapy, as well as obtaining echocardiography. Patients evaluated received 22,807 days of antimicrobial therapy. Conclusions Patients hospitalized in community hospitals are rarely transferred for ID consultation. Our work demonstrates a need for ID consultation in community hospitals, identifying opportunities to enhance patient care by modifying antimicrobial regimens to improve antimicrobial stewardship and avoid inappropriate antimicrobials. Efforts to expand the ID workforce to include coverage at rural hospitals will likely improve antibiotic utilization.

This study proposes a unified, dynamic framework based on turnover event theory to evaluate the effects of dismissals, layoff announcements, and voluntary turnover on subsequent work-unit voluntary turnover. Applying our approach to 1,620 retail stores over 22 months, we show that modeling exit events as a dynamic and interdependent system adds to our ability to predict subsequent human capital outflow. Dismissals had the weakest total effect on subsequent voluntary turnover, layoff announcements had the strongest and most immediate effects, and voluntary turnovers had moderate but lasting effects. We also find that these three exit reasons each exhibit a distinct pattern of subsequent turnover intensity and longevity. Based on characteristics of work units in our setting, our results correspond to a cumulative worker-level average effect of 0.17 quits following dismissals, 0.23 quits following quits, and 2.2 quits following a layoff. We find that these "multiplier" effects are concentrated among workers of similar performance: high performer exits beget high performer quits, just as low-performer exits beget low-performer quits. Our findings suggest analyses offering individual-level estimates of turnover will generally underestimate the broader, work-unit level consequences of individual exit events on similar workers. [ABSTRACT FROM AUTHOR]

Abstract Background Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. Methods A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. Results Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04–1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64–37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88–9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. Conclusions This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.

Fingolimod is a disease-modifying treatment utilized in the treatment of relapsing-remitting multiple sclerosis. Fingolimod has been associated with an increased risk in herpes simplex and varicella infection in clinical trials. We report a case of cerebral venous thrombosis secondary to cryptococcus in a patient receiving fingolimod. A 61-year-old male with multiple sclerosis treated with fingolimod presented with a 2-week history of headache, chills, and night sweats. An MRI of the brain revealed a left transverse and sigmoid sinus thrombosis. Two blood cultures revealed Cryptococcus neoformans; a serum cryptococcal antigen was also positive. HIV testing was negative. A lumbar puncture was deferred as the patient was placed on heparin and, subsequently, warfarin for the cerebral venous thrombosis. The patient received antifungal therapy for 14 days with liposomal amphotericin B and flucytosine, followed by oral fluconazole for 8 weeks. He was subsequently readmitted 60 days later with bilateral papilledema; his anticoagulation was reversed, and a lumbar puncture revealed a negative cryptococcal antigen and an intracranial pressure of 20. A repeat MRI revealed worsening superior sagittal sinus thrombosis, thought to be the cause of the papilledema; his anticoagulation was reinitiated. He received a brief course of intravenous methylprednisolone, but as his multiple sclerosis was well-controlled, further therapy was deferred. His symptoms had resolved at a 3-month follow-up appointment. This is the first report of a multiple sclerosis patient treated with fingolimod to develop cerebral venous thrombosis secondary to cryptococcal fungemia. The risks of opportunistic infections should be considered in patients managed with fingolimod.