Prognostic implications of the tumor immune microenvironment and immune checkpoint pathway in primary central nervous system diffuse large B-cell lymphoma in the North Indian population.

Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and the PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 expression in the PCNSL and evaluated their prognostic significance. All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1, and PD-L1 was performed on the tissue microarray. Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male-to-female ratio of 0.91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, an increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells were significantly associated with the longer OS (p = 0.037) and DFS (p = 0.023). TAMs (68CD and CD163 positive) showed an inverse relationship with OS and DFS but did not reach statistical significance (p > 0.05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p = 0.037). The TME plays a significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1-expressing immune cells is associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against the TME and immune check point inhibitors in this disease.

CNS Complications in Adult Patients Treated With Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the incidence and outcomes of radiologically confirmed acute CNS complications in extracorporeal membrane oxygenation patients at an Australian extracorporeal membrane oxygenation referral center and identify associated patient characteristics. DESIGN: Retrospective cohort study. SETTING: Single-center tertiary institution. PATIENTS: Four-hundred twelve consecutive adult patients supported with extracorporeal membrane oxygenation from 2009 to 2017. RESULTS: Fifty-five patients (13.3%) had a CNS complication confirmed by CT or MRI, including ischemic stroke (7.0%), intracerebral hemorrhage (3.4%), hypoxic ischemic encephalopathy (3.6%), and spinal cord injury (1.2%). CNS complication rates in the venoarterial, venovenous, and veno-pulmonary artery extracorporeal membrane oxygenation subgroups were 18.0%, 4.6%, and 13.6%, respectively. Neurologic complications were independently associated with the use of venoarterial extracorporeal membrane oxygenation (p = 0.002) and renal replacement therapy (p = 0.04). Sixty-five percent of patients with a neurologic complication died during their hospital admission compared with 32% of patients without this complication (p < 0.001). Venoarterial extracorporeal membrane oxygenation, renal replacement therapy, and days of extracorporeal membrane oxygenation support were also associated with hospital mortality and remained so after adjustment in a multivariable regression model (p = 0.01, p < 0.001, and p = 0.003, respectively). CONCLUSIONS: CNS complications appear to occur more frequently in patients requiring circulatory as opposed to respiratory support on extracorporeal membrane oxygenation and are independently associated with mortality. It remains unclear if these complications are causative of a poor outcome or a marker of severity of the underlying condition. Further research is required to better elucidate modifiable or preventable aspects through better patient selection and change in ongoing care.

Treatment and mortality outcomes in patients with other extrapulmonary cryptococcal disease compared with central nervous system disease.

BACKGROUND: Determining the extent of cryptococcal disease (CD) is key to therapeutic management. Treatment with fluconazole is only recommended for localised pulmonary disease. Induction therapy with amphotericin B (AmB) and flucytosine is recommended for disease at other sites, irrespective of central nervous system (CNS) involvement, but this is not often followed in patients without meningitis. In this study, we compared treatment and mortality between patients with CD of the CNS and other extrapulmonary (OE) sites. METHODS: This is a retrospective, single-centre study of all hospitalised patients with nonpulmonary cryptococcal infection from 2002 to 2015 who underwent lumbar puncture. Demographics, predisposing factors, comorbidities, clinical presentation, laboratory values, antifungal treatment and mortality data were collected to evaluate 90-day mortality and treatment differences between patients with OE and CNS CD. Survival analysis was performed using multivariable Cox regression analysis. RESULTS: Of 193 patients analysed, 143 (74%) had CNS CD and 50 (26%) had OE CD. Ninety-day mortality was 23% and similar between the OE and CNS CD groups (22% vs 23%, p = .9). In the comorbidity-adjusted multivariable Cox regression model, mortality risk was similar in the OE and CNS groups. Fewer patients with OE CD received induction therapy with AmB and flucytosine compared to those with CNS disease (28% vs 71.3%, p < .001). CONCLUSION: Patients with OE CD had similar 90-day mortality compared to those with CNS disease. Despite current guideline recommendations, patients with OE disease were less likely to receive appropriate induction therapy with AmB and flucytosine compared to patients with CNS disease.

Sarcoidosis of the central nervous system: Safety and efficacy of treatment, and experience of biological therapies.

OBJECTIVES: Neurological complications of sarcoidosis are uncommon and the natural history and optimal treatments under-researched. With the advent of biological therapies, it is important to define the clinical characteristics and immunopathology of the disease. PATIENTS AND METHODS: Patients referred to and treated within the Centre for Neurosarcoidosis over a 15 year period who had biopsy proven "highly probable" disease of the central nervous system were studied prospectively. RESULTS: Corticosteroids were used effectively in all patients, immunosuppression in 79 % and TNFα antagonists in 23 %. Treatment with steroids alone inevitably led to relapse, and low dose immunosuppression was ineffective in those with severe forms of the disease. Use of biological therapies substantially improved outcome. Patients with cranial neuropathy had an excellent outcome. Those with pachymeningitis had marked radiological abnormalities but less disablement. Those with leptomeningitis had an invasive, destructive disease which responded well to treatment but with residual neurological impairments. Treatment was required for many years, but the risk of relapse following treatment withdrawal was low. Infective complications arose in six. There were two deaths, neither directly related to the neurological disease, nor its treatment. CONCLUSIONS: This prospective study of the natural history and treatment response in neurosarcoidosis provides evidence that the use of high dose immunosuppression and early and prolonged use of biological therapies is associated with greatly improved outcomes and lower mortality. The data may be used to plan further studies and treatment trials, and provide class IV evidence for the effectiveness of biological agents in the treatment of Neurosarcoidosis.

Relationship between Use of Rehabilitation Resources and ICU Readmission and ER Visits in ICU Survivors: the Korean ICU National Data Study 2008-2015.

BACKGROUND: Despite the increasing importance of rehabilitation for critically ill patients, there is little information regarding how rehabilitation therapy is utilized in clinical practice. Our objectives were to evaluate the implementation rate of rehabilitation therapy in the intensive care unit (ICU) survivors and to investigate the effects of rehabilitation therapy on outcomes. METHODS: A retrospective nationwide cohort study with including > 18 years of ages admitted to ICU between January 2008 and May 2015 (n = 1,465,776). The analyzed outcomes were readmission to ICU readmission and emergency room (ER) visit. RESULTS: During the study period, 249,918 (17.1%) patients received rehabilitation therapy. The percentage of patients receiving any rehabilitation therapy increased annually from 14% in 2008 to 20% in 2014, and the percentages for each type of therapy also increased over time. The most common type of rehabilitation was physical therapy (91.9%), followed by neuromuscular electrical stimulation (29.6%), occupational (28.6%), respiratory, (11.6%) and swallowing (10.3%) therapies. After adjusting for confounding variables, the risk of 30-day ICU readmission was lower in patients who received rehabilitation therapy than in those who did not (P < 0.001; hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.65-0.75). And, the risk of 30-day ER visit was also lower in patients who received rehabilitation therapy (P < 0.001; HR, 0.83; 95% CI, 0.77-0.88). CONCLUSION: In this nationwide cohort study in Korea, only 17% of all ICU patients received rehabilitation therapy. However, rehabilitation is associated with a significant reduction in the risk of 30-day ICU readmission and ER visit.

PROGNOSTIC INDICATORS FOR SURVIVAL OF ORPHANED NEONATAL AND JUVENILE EASTERN COTTONTAIL RABBITS (SYLVILAGUS FLORIDANUS): 1,256 CASES (2012-17).

Orphaned eastern cottontail rabbits (ECRs; Sylvilagus floridanus) often present to wildlife clinics within their geographic range and require considerable dedication of time and resources. The objective of this analytical cross-sectional study was to assess initial examination findings to be used as prognostic indicators for orphaned neonatal and juvenile ECRs. The medical records of the University of Illinois Wildlife Medical Clinic were searched for ECRs presenting between 2012 and 2018. This criterion identified 1,256 ECRs that were then classified as survivors (survived and released) or as nonsurvivors (euthanized or natural death) within 72 h of admission. Presenting weight, body system abnormalities, hydration status, intervention prior to presentation, and singleton versus group presentation were categorically recorded for each individual ECR. The data were modeled using a series of logistic regression models fitted using the general linear model. Individuals were significantly more likely to be nonsurvivors if they presented as singletons (P<0.0001), presented with moderate/severe (P<0.001) or mild integumentary signs (P=0.0261), presented with multi-organ disease (P<0.001), presented with neurologic signs (P<0.0003), or had treatment provided prior to presentation (P=0.031). Factors that did not predict survival status in ECRs included body weight (P=0.210), presence of respiratory signs (P=0.674), and presence of dehydration (P=0.356). These findings may be used at wildlife medical clinics to make triage criteria for euthanasia as well as dedicate limited funds and labor to cases with the best prognosis for survival.

Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III-IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention.

Health effects associated with chronic exposure to low-level hydrogen sulfide from geothermoelectric power plants. A residential cohort study in the geothermal area of Mt. Amiata in Tuscany.

BACKGROUND: Geothermal power plants for the production of electricity are currently active in Mt. Amiata, Italy. The present study aimed to investigate the association between chronic low-level exposure to H2S and health outcomes, using a residential cohort study design. METHODS: Spatial variability of exposure to chronic levels of H2S was evaluated using dispersion modelling. Cohorts included people residing in six municipalities of the geothermal district from 01/01/1998 to 31/12/2016. Residence addresses were georeferenced and each subject was matched with H2S exposure metrics and socio-economic status available at census tract level. Mortality and hospital discharge data for neoplasms and diseases of the respiratory, central nervous and cardiovascular systems were taken from administrative health databases. Cox proportional hazard models were used to test the association between H2S exposure and outcomes, with age as the temporal axis and adjusting for gender, socio-economic status and calendar period. RESULTS: The residential cohort was composed of 33,804 subjects for a total of 391,002 person-years. Analyses reported risk increases associated with high exposure to H2S for respiratory diseases (HR = 1.12 95%CI: 1.00-1.25 for mortality data; HR = 1.02 95%CI: 0.98-1.06 for morbidity data), COPD and disorders of the peripheral nervous system. Neoplasms were negatively associated with increased H2S exposure. CONCLUSIONS: The most consistent findings were reported for respiratory diseases. Associations with increased H2S exposure were coherent in both mortality and hospitalization analyses, for both genders, with evidence of exposure-related trends. No positive associations were found for cancer or cardiovascular diseases.

Noninfectious Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (P = .004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, n = 15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, n = 6 (4%), and myelopathy, n = 5 (3%). PNS complications (32%) included neuropathies, n = 25 (17%), and myopathies and neuromuscular junction disorders, n = 23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P < .00001), and extensive chronic GVHD (HR, 3.2; P = .0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P < .0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT.

Neuroscience Intermediate-Level Care Units Staffed by Intensivists: Clinical Outcomes and Cost Analysis.

INTRODUCTION:: With an aging population and increasing numbers of intensive care unit admissions, novel ways of providing quality care at reduced cost are required. Closed neurointensive care units improve outcomes for patients with critical neurological conditions, including decreased mortality and length of stay (LOS). Small studies have demonstrated the safety of intermediate-level units for selected patient populations. However, few studies analyze both cost and safety outcomes of these units. This retrospective study assessed clinical and cost-related outcomes in an intermediate-level neurosciences acute care unit (NACU) before and after the addition of an intensivist to the unit's care team. METHODS:: Starting in October 2011, an intensivist-led model was adopted in a 16-bed NACU unit, including daytime coverage by a dedicated intensivist. Data were obtained from all patients admitted 1 year prior to and 2 years after this intervention. Primary outcomes were LOS and hospital costs. Safety outcomes included mortality and readmissions. Descriptive and analytic statistics were calculated. Individual and total patient costs were calculated based on per-day NACU and ward cost estimates and significance measured using bootstrapping. RESULTS:: A total of 2931 patients were included over the study period. Patients were on average 59.5 years and 53% male. The most common reasons for admission were central nervous system (CNS) tumor (27.6%), ischemic stroke (27%), and subarachnoid hemorrhage (11%). Following the introduction of an intensivist, there was a significant reduction in NACU and hospital LOS, by 1 day and 3 days, respectively. There were no differences in readmissions or mortality. Adding an intensivist produced an individual cost savings of US$963 in NACU and US$2687 per patient total hospital stay. CONCLUSION:: An intensivist-led model of intermediate-level neurointensive care staffed by intensivists is safe, decreases LOS, and produces cost savings in a system increasingly strained to provide quality neurocritical care.

Causes of Troponin Elevation and Associated Mortality in Young Patients.

BACKGROUND: While increased serum troponin levels are often due to myocardial infarction, increased levels may also be found in a variety of other clinical scenarios. Although these causes of troponin elevation have been characterized in several studies in older adults, they have not been well characterized in younger individuals. METHODS: We conducted a retrospective review of patients 50 years of age or younger who presented with elevated serum troponin levels to 2 large tertiary care centers between January 2000 and April 2016. Patients with prior known coronary artery disease were excluded. The cause of troponin elevation was adjudicated via review of electronic medical records. All-cause death was determined using the Social Security Administration's death master file. RESULTS: Of the 6081 cases meeting inclusion criteria, 3574 (58.8%) patients had a myocardial infarction, while 2507 (41.2%) had another cause of troponin elevation. Over a median follow-up of 8.7 years, all-cause mortality was higher in patients with nonmyocardial infarction causes of troponin elevation compared with those with myocardial infarction (adjusted hazard ratio [HR] 1.30; 95% confidence interval [CI], 1.15-1.46; P < .001). Specifically, mortality was higher in those with central nervous system pathologies (adjusted HR 2.21; 95% CI, 1.85-2.63; P < .001), nonischemic cardiomyopathies (adjusted HR 1.66; 95% CI, 1.37-2.02; P < .001), and end-stage renal disease (adjusted HR 1.36; 95% CI, 1.07-1.73; P = .013). However, mortality was lower in patients with myocarditis compared with those with an acute myocardial infarction (adjusted HR 0.43; 95% CI:, 0.31-0.59; P < .001). CONCLUSION: There is a broad differential for troponin elevation in young patients, which differs based on demographic features. Most nonmyocardial infarction causes of troponin elevation are associated with higher all-cause mortality compared with acute myocardial infarction.

A comparison between oral chemotherapy combined with radiotherapy and radiotherapy for newly diagnosed glioblastoma: A systematic review and meta-analysis.

The prognosis of glioblastoma (GBM), a major subtype of grade IV glioma, is rather poor nowadays. The efficiency of chemotherapy serving as the adjunct to radiotherapy (RT) for treating GBM is still controversial. In this study, we aim to investigate the overall survival (OS) and progression-free survival (PFS) in patients with newly diagnosed GBM received RT plus chemotherapy or with RT alone.Literatures were searched from the PubMed, Embase, and Cochrane Library between January 2001 and June 2015. Study selection was conducted based on the following criteria: randomized clinical trial (RCT) of adjuvant RT plus chemotherapy versus RT alone; studies comparing OS and/or PFS; and studies including cases medically confirmed of newly diagnosed GBM.Five RCTs (1655 patients) were eligible in this study. The meta-analysis showed a significant improvement in OS of patients treated with RT plus oral chemotherapy compared with that of RT alone (hazard ratio 0.70; 95% confidence interval, 0.56-0.88, P = .002).Adjuvant chemotherapy confers a survival benefit in patients newly diagnosed with GBM.

Association of Prognostic Factors and Immunosuppressive Treatment With Long-term Outcomes in Neurosarcoidosis.

Importance: Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear. Objectives: To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS. Design, Setting, and Participants: In this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years). Main Outcomes and Measures: All neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015). Results: The 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months. Conclusions and Relevance: This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Survival and medical utilization of children and adolescents with prolonged ventilator-dependent and associated factors.

Over the course of a year, more than 20,000 patients in Taiwan require prolonged mechanical ventilation (PMV). Data from the National Health Insurance Research Database for patients between 2005 and 2011 were used to conduct a retrospective analysis on ventilator dependence. The study subjects were PMV patients aged <17 years in Taiwan. A multiple regression model employing general estimating equations was applied to investigate the factors affecting the use of medical resources by children and adolescent PMV patients. A Cox proportional hazard model was incorporated to explore the factors affecting the survival of these patients. Data were collected for a total of 1,019 children and adolescent PMV patients in Taiwan. The results revealed that the average number of outpatient visits per subject was 32.1 times per year, whereas emergency treatments averaged 1.56 times per year per subject and hospitalizations averaged 160.8 days per year per subject. Regarding average annual medical costs, hospitalizations accounted for the largest portion at NT$821,703 per year per subject, followed by outpatient care at NT$123,136 per year per subject and emergency care at NT$3,806 per year per subject. The demographic results indicated that the patients were predominately male (61.24%), with those under 1 year of age accounting for the highest percentage (36.38%). According to the Kaplan-Meier curve, the 1-year and 5-year mortality rates of the patients were approximately 32% and 47%, respectively. The following factors affecting the survival rate were considered: age, the Charlson Comorbidity Index (CCI), diagnosis type necessitating ventilator use, and whether an invasive ventilator was used. This study investigated the use of medical resources and the survival rates of children and adolescent PMV patients. The findings of this study can serve as a reference for the National Health Insurance Administration in promoting its future integrated pilot projects on ventilator dependency.

Complications of miliary tuberculosis: low mortality and predictive biomarkers from a UK cohort.

BACKGROUND: Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS: Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust. Multivariable logistic regression was used to assess factors independently associated with the need for critical care intervention. Receiver operator characteristics (ROC) were calculated to assess the discriminatory ability of admission blood tests to predict clinical outcomes. RESULTS: Fifty-two patients were identified with miliary tuberculosis, of whom 29% had confirmed central nervous system (CNS) involvement. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture for detecting CNS disease. Severe complications were frequent, with 15% requiring critical care intervention with mechanical ventilation. This was independently associated with admission hyponatraemia and elevated alanine aminotransferase (ALT). Having an admission sodium ≥125 mmol/L and an ALT <180 IU/L had 82% sensitivity and 100% specificity for predicting a favourable outcome with an area under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications, one-year mortality was low at 2%. CONCLUSIONS: Although severe complications of miliary tuberculosis were frequent, mortality was low with timely access to critical care intervention, anti-tuberculous therapy and possibly corticosteroid use. Clinical outcomes could accurately be predicted using routinely collected biochemistry data.

Epidemiology and Characteristics of Neurosurgical Conditions at Mbarara Regional Referral Hospital.

BACKGROUND: The unmet surgical need, specifically neurosurgical need, in Uganda is significant, yet only 2 public hospitals currently perform neurosurgery in the country. This study examines the epidemiology and outcomes of neurosurgical conditions presenting to 1 of 12 regional referral hospitals in Uganda, in an effort to understand the neurosurgical needs of this population. METHODS: The study was conducted at Mbarara Regional Referral Hospital (MRRH), in southwestern Uganda. Demographics, clinical characteristics, and outcomes were retrospectively collected for all patients who presented to MRRH with a neurosurgical condition between January 2012 and September 2015. RESULTS: During the study period, 1854 patients presented to MRRH with a neurosurgical condition. More than half of the patients were between 19 and 40 years old, and the majority were males (76.1%). The overall median length of stay was 5 days (interquartile range: 2.5-10). The majority of admissions were due to trauma (87%), with almost 60% due to road traffic incidents. The overall mortality rate was 12.8%. A multivariable Cox proportional hazards model revealed that age, closed head injury, and admission Glasgow Coma Scale have a strong positive correlation with mortality while getting a diagnostic image and neurosurgical procedure were negatively correlated with mortality. CONCLUSION: Traumatic brain injury represented the majority of neurosurgical admissions at MRRH, disproportionately affecting young males. Age, closed head injury, admission Glasgow Coma Scale, getting a diagnostic image, and neurosurgical procedure were all independent predictors of mortality. Resource appropriate interventions throughout the health system are needed to meet the demand and improve outcomes.

Neurologic Complications of Influenza B Virus Infection in Adults, Romania.

We characterized influenza B virus-related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014-15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis.

Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils.

Misfolded α-synuclein (αS) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 αS transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of αS fibrils by comparing various peripheral sites of inoculations with different αS protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83+/+) mice, robust αS pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of αS fibrils in hemizygous M83 transgenic (M83+/-) mice resulted in CNS αS pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated αS resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 αS, human ßS, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of αS fibrils also induced CNS αS pathology in another αS transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of αS fibrils was more efficient in inducing CNS αS pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated αS in M83+/- mice also induced paralysis and CNS αS pathology, although less efficiently. These results further demonstrate the prion-like characteristics of αS and reveal its efficiency to invade the CNS via multiple routes of peripheral administration. IMPORTANCE: The misfolding and accumulation of α-synuclein (αS) inclusions are found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Similar characteristics have been observed between the infectious prion protein and αS, including its ability to spread from the peripheral nervous system and along neuroanatomical tracts within the central nervous system. In this study, we extend our previous results and investigate the efficiency of intravenous (i.v.), intraperitoneal (i.p.), and intramuscular (i.m.) routes of injection of αS fibrils and other protein controls. Our data reveal that injection of αS fibrils via these peripheral routes in αS-overexpressing mice are capable of inducing a robust αS pathology and in some cases cause paralysis. Furthermore, soluble, nonaggregated αS also induced αS pathology, albeit with much less efficiency. These findings further support and extend the idea of αS neuroinvasion from peripheral exposures.

Benefit in long-term response and mortality of treatment with intravenous immunoglobulin prior to plasmapheresis in peripheral polyneuropathies.

OBJECTIVES: The benefits of plasmapheresis (PA) for neurologic autoimmune diseases have been widely demonstrated. Little is known about the long-term neurologic prognosis and course after PA and immunosuppressive (IS) and/or intravenous immunoglobulin (IVIG) treatment. We aimed to analyse features associated with short-term response and long-term outcome and prognosis (neurologic status and mortality) of peripheral polyneuropathy (PP) and central nervous system acute inflammatory disease (CNSAID) treated with PA. PATIENTS AND METHODS: A descriptive, retrospective single-centre study from January 2005 to December 2012. RESULTS: There were 26 episodes, which included 16 CNSAID and 10 PP cases. First line therapy included PA (n=4), IS drugs (n=15), and IVIG (n=7). Responses were achieved in 80% and 50% of PP and CNSAID cases, respectively. For PP, first line treatment with IVIG and no IS treatment prior to or during PA were variables associated with short-term response (P=0.067), good or stable neurologic status at the end of follow-up (P=0.008), and lower mortality rate (P=0.008). For CNSAID, initial EDSS score≥7 (P=0.019) was related to long-term good or stable neurologic status. During the study period, 177 sessions were conducted; 3.4% had technical complications and 8.5% clinical complications. However, these incidents were all minor and no PA session had to be discontinued. CONCLUSION: The response rates achieved in our patients were similar to those of other research. PA has a safe profile but double-blind, controlled studies are needed to evaluate the synergy of sequential treatment with IGIV followed by PA and the possible benefit for long-term outcome.