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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., (© 2021 Scandinavian Societies for Medical Microbiology and Pathology.)

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., (© 2020 Wiley-VCH GmbH.)

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., Competing Interests: Dr. Kerr disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

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., Competing Interests: Declaration of Competing Interest There are none., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

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., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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 H 2 S and health outcomes, using a residential cohort study design., Methods: Spatial variability of exposure to chronic levels of H 2 S 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 H 2 S 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 H 2 S 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 H 2 S 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 H 2 S exposure., Conclusions: The most consistent findings were reported for respiratory diseases. Associations with increased H 2 S 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

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., (© 2019 S. Karger AG, Basel.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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.

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.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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.

Background: Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC., Methods: The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion., Results: Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC., Conclusions: Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.

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., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

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 βS, 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., (Copyright © 2017 American Society for Microbiology.)

Objectives: To elucidate the epidemiology, complication profiles, hospital outcome, and predisposing factors of CNS complications occurring during venoarterial extracorporeal membrane oxygenation in adults., Design: Retrospective analysis of the Extracorporeal Life Support Organization registry., Setting: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers from 1992 to 2013., Patients: Patients more than 16 years old supported with a single-run of venoarterial extracorporeal membrane oxygenation., Interventions: None., Measurements and Main Results: We examined 4,522 adult patients supported with venoarterial extracorporeal membrane oxygenation and included in the Extracorporeal Life Support Organization registry. Venoarterial extracorporeal membrane oxygenation was used for cardiac dysfunction in 3,005 patients (66.5%), cardiopulmonary resuscitation in 877 patients (19.4%), and respiratory failure in 640 patients (14.1%), respectively. Multivariate logistic regression was performed to identify factors independently associated with CNS injury. Neurologic complications occurred in 682 patients (15.1%), and included brain death in 358 patients (7.9%), cerebral infarction in 161 patients (3.6%), seizures in 83 patients (1.8%), and cerebral hemorrhage in 80 patients (1.8%). Multiple CNS complications in the same patient occurred in 70 cases. Hospital mortality in patients with CNS complications was 89%, compared with 57% in patients without (p < 0.001). In a multivariable model, age, pre-extracorporeal membrane oxygenation cardiac arrest, the use of inotropes on extracorporeal membrane oxygenation, and post-extracorporeal membrane oxygenation hypoglycemia were shown to be associated with CNS complications., Conclusions: Neurologic complications in adult patients on venoarterial extracorporeal membrane oxygenation support are common and associated with poor survival. Further research should focus on better understanding and management of brain/extracorporeal membrane oxygenation interaction to avoid such catastrophic complications.

Exposure to organophosphates (OPs) often results in seizures and/or status epilepticus (SE) that produce neural damage within the central nervous system (CNS). Early control of SE is imperative for minimizing seizure-related CNS neuropathology. Although standard therapies exist, more effective agents are needed to reduce OP-induced SE and neuronal loss, particularly therapies with efficacy when administered 10's of minutes after the onset of SE. To evaluate novel antiseizure compounds, animal models should simulate the CNS effects of OP exposure observed in humans. We characterized in rats the effects of the OP, diisopropyl flourophosphate (DFP) as a function of dose and route of administration of supporting agents (pyridostigmine, 2-PAM, atropine); outcome measures were mortality, electrographic seizure activity during SE, and subsequent CNS neuropathology. Doses of DFP between 3 and 7mg/kg consistently caused SE, and the latency to behavioral tremors and to subsequent initiation of SE were dose related. In distinction, all doses of DFP that resulted in electrographic SE (3-7mg/kg) produced seizures of similar intensity and duration, and similar CNS neuropathology (i.e., the effects were all-or-none). Although SE was similar across doses, mortality progressively increased with higher doses of DFP. Mortality was significantly lower when the route of administration of therapeutic agents was intramuscular compared to intraperitoneal. This rodent model of OP poisoning demonstrates pathological characteristics similar to those observed in humans, and thus begins to validate this model for investigating potential new therapeutic approaches., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy., Patient Description: A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused., Conclusions: This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We report on the long-term survival of children initiated on invasive and noninvasive positive pressure ventilation (NiPPV) before the age of 1 to assess the safety and efficacy of long-term ventilation at home., Methods: A chart review was performed of children initiated on long-term home mechanical ventilation (LTHV) before the age of 1 year, at The Hospital for Sick Children (SickKids), Canada, between January 1991 and April 2014., Results: We report on 51 children. Twenty-five children (49%) received NiPPV and 26 (51%) received invasive mechanical ventilation via tracheostomy (IMV). There was one NiPPV initiation between 1991 and 2001, the rest were in subsequent years. Most children had a "musculoskeletal disorder" in the NiPPV cohort, n = 14 (56%) and a "central nervous system" disorder in the IMV cohort, n = 13 (50%). The pCO2 improved with the initiation of NiPPV, P = < 0.0001. Of the 25 subjects initiated on NiPPV, eight (32%) are currently being followed as compared to 22 (84%) in the IMV cohort. Seven (28%) of the NiPPV group were weaned off ventilation as compared to three (11.5%) in the IMV cohort. There were two NiPPV treatment failures. There were more deaths in the NiPPV cohort: eight (32%) versus two (7.6%) in the IMV cohort. Four of the deaths in the NiPPV cohort were in children in whom a palliative approach was taken. None were due to NiPPV technical failure., Conclusions: Based on this long-term follow-up study, NiPPV use in infants appears to be a viable long-term ventilation strategy., (© 2015 Wiley Periodicals, Inc.)

Red pandas ( Ailurus fulgens ) are managed as captive populations in both North America and Europe. Regular review of pathology reports is a useful tool for developing veterinary care and husbandry strategies for such populations. Though thorough pathology reviews have been conducted for the European studbook, the North American population has not been reviewed similarly until now. Complete gross and histopathology reports were requested from institutions holding red pandas that died during 1992 through 2012 (n = 530), and reports were received for 95.8% of the individuals, including full necropsy records for 366 red pandas. These reports were classified by subspecies, gender, and age, then reviewed for primary cause of death and secondary pathological findings. A substantial portion of the deaths (40.2%) were neonates (<30 days of age). In both neonatal and juvenile (age = 31-365 days) animals, pneumonia was the most common cause of death. In adult (age = 366 days-10 yr) and geriatric red pandas (age >10 yr), cardiovascular disease was the most common cause of death. Renal disease and gastrointestinal disease also were common pathologic findings in adult and geriatric animals. These findings suggest that stress associated with captivity and husbandry practices, including those associated with social, environmental, and nutritional conditions, may contribute to immune and cardiovascular pathologies, and other common necropsy findings.

Objective: To summarize the causes of death and to analyze the risk factors in a surgical intensive care unit (SICU)., Methods: The relevant information of patients died in the SICU of Xijing Hospital of Fourth Military Medical University in past 15 years (from December 1999 to February 2015) was retrospectively analyzed. The gender, age, reason and date of hospitalization, date of transfer SICU, past medical history, whether or not admitted directly from emergency department or transferred from other department, operated or not, date of death, the main cause of death, acute physiology and chronic health evaluation II (APACHE II) score, the history of undergoing mechanical ventilation, continuous renal replacement therapy (CRRT), or antifungal therapy, as well as the ratio of the patients with body temperature higher than 39 °C, white blood cell (WBC) count higher than 10 x 10⁹/L, platelet (PLT) count below 100 x 10⁹/L, albumin (Alb) below 35 g/L of two periods, namely from December 1999 to July 2007 (the first period), and from August 2007 to February 2015 (the second period) were compared. The above parameters were compared with those of 201 survivors in SICU, and the risk factors leading to death were analyzed by logistic regression., Results: From December 1999 to February 2015, 4 317 patients were taken care of in the SICU. Among them, the number of death was 186, and the mortality rate was 4.3%. In the first time period (from December 1999 to July 2007), the total number of patients was 1 356, and the number of death were 109 (the mortality rate was 8.0%). In the second period, i.e. from August 2007 to February 2015, the number of SICU patients was 2,961, and 77 died (the mortality rate was 2.6%). The difference of mortality rate between the two periods was statistically significant (χ² = 66.707, P = 0.001 ). The death rate of patients transferred directly from emergency department in the first period was 79.8% (87/109), and it was lower in the second period (51.9%, 40/77, χ² = 16.181, P = 0.001 ). The death rate of the patients with blood A1b below 35 g/L in the second period (59.7%, 46/77) was higher than that of the first period (41.3%, 45/109, χ² = 6.151, P = 0.017). The top three causes of death from December 1999 to February 2015 were sepsis (38.2%), trauma (16.7%), and operation for cancer (14.0%). In the first period, the top three causes of death were sepsis (35.8%), trauma (22.0%), and operation for cancer (13.8%). In the second period, the top three causes of death were sepsis (41.6%), damage of the central nervous system (16.9%), and operation for cancer (14.3%). Top three reasons for SICU admission were trauma (29.03%), abdominal pain (20.97%) and other reasons (18.82%). Top three departments from which the patients were transferred were the emergency department (19.35%), orthopedics department (17.20%), and hepatobiliary department (16.13%). Logistic regression analysis showed that age [odds ratio (OR) = 2.025, 95% confidence interval (95% CI) = 1.500-2.734, P = 0.000], mechanical ventilation (OR = 3.514, 95% CI = 1.701-7.259, P = 0.001), CRR T (OR = 5.604, 95% CI = 3.003-10.459, P = 0.000 ), body temperature higher than 39 °C (OR = 1.992, 95%CI = 1.052-3.771, P = 0.034) were the risk factors of death in SICU patients., Conclusion: Sepsis and severe trauma are the leading causes of death in severe SICU patients, to whom with risk factors of death enough attention should be given.

Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model., Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultant model was converted into an online calculator for ease of clinical use., Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death., Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes., (Published by Elsevier Inc.)

Artificial neural networks (ANNs) effectively analyze non-linear data sets. The aimed was A review of the relevant published articles that focused on the application of ANNs as a tool for assisting clinical decision-making in neurosurgery. A literature review of all full publications in English biomedical journals (1993-2013) was undertaken. The strategy included a combination of key words 'artificial neural networks', 'prognostic', 'brain', 'tumor tracking', 'head', 'tumor', 'spine', 'classification' and 'back pain' in the title and abstract of the manuscripts using the PubMed search engine. The major findings are summarized, with a focus on the application of ANNs for diagnostic and prognostic purposes. Finally, the future of ANNs in neurosurgery is explored. A total of 1093 citations were identified and screened. In all, 57 citations were found to be relevant. Of these, 50 articles were eligible for inclusion in this review. The synthesis of the data showed several applications of ANN in neurosurgery, including: (1) diagnosis and assessment of disease progression in low back pain, brain tumours and primary epilepsy; (2) enhancing clinically relevant information extraction from radiographic images, intracranial pressure processing, low back pain and real-time tumour tracking; (3) outcome prediction in epilepsy, brain metastases, lumbar spinal stenosis, lumbar disc herniation, childhood hydrocephalus, trauma mortality, and the occurrence of symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid haemorrhage; (4) the use in the biomechanical assessments of spinal disease. ANNs can be effectively employed for diagnosis, prognosis and outcome prediction in neurosurgery., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival., Methods: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival., Results: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%)., Conclusion: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Purpose: Few interventions have been proven to improve outcomes in neurocritical care patients. It is unknown whether outcomes in Canada have changed over time. We performed a cohort study in Southern Alberta to determine whether survival and discharge disposition have improved., Methods: Using prospectively collected data, we identified patients admitted to regional intensive care units (ICUs) over a more than 11-year period with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage, anoxic encephalopathy, central nervous system infection, or status epilepticus. Four sequential time periods of 2.8 years were compared, as were periods before and after various practice modifications were introduced. Logistic regression was used to adjust for patient age, Glasgow Coma Scale score, and case mix., Results: A total of 4,097 patients were assessed. The odds of death were lowest in the most recent time quartile (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.56 to 0.88, P < 0.01). The odds of being discharged home without the need for support services increased over time (OR 1.45, 95% CI 1.38 to 1.85, P = 0.003). Improvements were not the same for all diagnostic subgroups. They were statistically significant for patients with TBI and SAH. Neurocritical care consultative services, evidence-based protocols, and clustering of patients within a multidisciplinary ICU were associated with improved outcomes. Length of stay in an ICU increased among hospital survivors (4.6 vs 3.8 days, P < 0.01)., Conclusions: Mortality and discharge disposition of neurocritical care patients in Southern Alberta have improved over time. Practice modifications in the region were associated with positive outcome trends. Longer ICU length of stay may imply that intensivists are increasingly delaying decisions about withdrawing life-sustaining interventions.

Aim: To determine whether there were "quality gaps" in the provision of care during pregnancies that resulted in a perinatal death due to congenital abnormality., Method: Perinatal deaths from congenital cardiovascular, central nervous system or chromosomal abnormality in 2010 were identified retrospectively. Data were extracted by retrospective clinical note review and obtained by independent review of ultrasound scans., Results: There were 137 perinatal deaths due to a congenital cardiovascular (35), central nervous system (29) or chromosomal abnormality (73). First contact with a health professional during pregnancy was predominantly with a general practitioner. First contact occurred within 14 weeks in 85% of pregnancies and there was often a significant delay before booking. Folate supplements were taken by 7% pre-conceptually and 54% of women in the antenatal period. There were 20 perinatal deaths from neural tube defects that could potentially have been prevented through the use of pre-conceptual folate. Antenatal screening was offered to 75% of the women who presented prior to 20 weeks and 84% of these undertook at least one of the available antenatal screening tests. Review of ultrasound images found five abnormalities could have been detected earlier., Conclusion: Delay in booking or failure to offer screening early were the most common reasons for delay in diagnosis of screen detectable abnormalities. The preventative value and timing of (pre-conceptual) folate needs emphasis.

The problem of unexpected death is challenging for many medical disciplines including forensic medicine. In 2011 the ratio of violent to non-violent deaths was 1:1.7. The structure of non-violent mortality changed due to the rise in the number of deaths from cerebrovascular diseases. International epidemiological studies demonstrated that stroke presently holds the second or third place in the structure of overall mortality in the world's population. The lethality rate attributable to hemorrhagic stroke is estimated at 79.5%. Of special interest for both forensic medical experts and general practitioners is the combination of cerebrovascular disease and the preceding craniocerebral injury. The discrepancy between clinical and pathologo-anatomical diagnoses amounts to 46.5%. According to the data collected by the Russian Centre of Forensic Medical Expertise in 2010, cerebrovascular pathology remained unrecognized in 62.4% of the cases and was erroneously diagnosed as a cerebrocranial injury in 52.2% of the patients. It is believed that forensic medical experts can render assistance to health facilities as regards the improvement of the quality of medical aid and preventive measures provided to the population by means of analysis of available information and the development of relevant recommendations.

Post-transplantation lymphoproliferative disorders (PTLD) localized to the central nervous system (CNS) is a rare but potentially fatal side-effect of immunosuppression for organ transplantation. Till now, to the best of our knowledge, the total number of such cases reported worldwide is less than 100. In this survey, we collected the data of PTLD localized to the CNS (CNS-PTLD) and compared this data with other PTLD patients with localizations to other areas serving as the control group. A comprehensive search was performed for studies reporting CNS-PTLD data in the Pubmed and Google scholar search engines. Finally, international data from 21 different studies were included in the analysis. Overall, 367 patients were entered into analysis. Organ recipients with CNS-PTLD had comparable gender make up, lymphoma cell types, Epstein-Barr virus infection rate, remission and mortality rates, with PTLD patients having other localizations. Multiorgan involvement as well as disseminated lymphoma were significantly more prevalent in the control group (P <0.05). At the last follow-up, 192 (60%) patients were dead (47 missing data). Irrespective of whether the overall death or only death due to PTLD was used as the final outcome, we found that the survival rates were similar for patients of the two groups (P = 0.895). Renal transplant recipients are at greater risk for developing CNS involvement by PTLD, while heart and liver recipients represent significant lower risks for the same. This study showed that PTLD patients who had CNS presentation have quite a comparable outcome compared with those with other areas of localization. However, further prospective studies are needed for reaffirming our findings.

Hyponatremia is prevalent before liver transplantation and generally corrected immediately after transplantation. However, the clinical significance of correction rate of hyponatremia is not well investigated. The prognostic impact of pre-transplant serum sodium concentrations and post-transplant correction rate of hyponatremia were assessed. A total of 512 patients who received orthotopic liver transplants were enrolled. The correction rate of hyponatremia (delta sodium, ΔNa) was calculated based on the data collected during the first 48 hours following liver transplantation. Outcomes, including in-hospital mortality, delirium, neurological complications, acute kidney injury, and infections, were compared according to the serum sodium levels (sNa < 125, 125-135, and ≥ 135 mmol/L), and the risk factors for in-hospital mortality and neurological complications were analyzed using multivariate logistic regression methods. Patients with severe hyponatremia (sNa < 125 mmol/L) had higher rates of in-hospital mortality (9.6%, P = 0.010), delirium (54.8%, P = 0.003), neurological complications (24.7%, P = 0.003), and acute kidney injury (57.5%, P = 0.005). In multivariate analysis, serum sodium levels (OR = 0.975, P = 0.402) and delta sodium (OR = 1.097, P = 0.066) were not independent risk factors for in-hospital mortality. However, delta sodium (OR = 1.093, P = 0.003) and fast correction rate of hyponatremia (ΔNa ≥ 12 mmol/L/24h, OR = 3.397, P = 0.023) were significantly associated with post-transplant neurological complications. Pre-transplantation hyponatremia was not independently associated with clinical outcomes. However, rapid correction of hyponatremia is an independent risk factor for the development of post-transplant neurological complications.

Hepatoma-derived growth factor (HDGF), a potential predictive and prognostic marker in several human cancers, is the firstly reported member of the HDGF family of proteins containing a well-conserved N-terminal amino acid sequence. HDGF is implicated in tumorigenesis by direct angiogenic activity, and its expression is correlated with aggressive biological ability of cancer cells including proliferation and angiogenesis. So, we propose that HDGF may be a valuable factor in progression and prognosis for primary central nervous system lymphoma (PCNSL) through its angiogenic and proliferative activity. So, HDGF, CD31 and Ki67 expression in the specimens of 60 patients suffering from PCNSL was investigated by immunohistochemistry in this study. Their correlations with clinicopathologic features and prognosis were evaluated to determine whether HDGF, CD31 and Ki67 expression levels correlate with the prognosis of the 60 patients suffering from PCNSL. We found that all PCNSL specimens showed HDGF, CD31 and Ki67 expression with different expression levels. Statistical analysis showed that HDGF had a positive correlation with CD31, but not with Ki67. Patients with higher HDGF and CD31 expression level had poorer overall survival rates than those with lower expression levels of HDGF and CD31, while Ki67 expression level did not correlate with overall survival. Multivariate analysis revealed that postoperative adjuvant chemotherapy and high expression of HDGF was independent prognostic indicator of patient survival.

Background: Long-term outcomes for children who survive on tracheostomy and positive-pressure ventilation (TPPV) at home are not well known., Methods: A retrospective review of 20 years of clinical data at a single institution was performed. Outcome measures included 5-year survival, decannulation rate, and neurocognition., Results: A total of 91 children were categorized under neuromotor dysfunction (52%), chronic lung disease (29%), and congenital anomalies (20%). The 5-year survival rates for these categories were 89% (95% confidence interval [CI] = 80%-99%), 76% (95% CI = 57%-100%), and 94% (95% CI = 83%-100%), respectively. Overall, the 5-year decannulation rate was 25% (95% CI = 14%-35%), with children with chronic lung disease having the highest rate (51%). It was found that 14% were extremely delayed in neurocognition., Conclusion: Most children on TPPV at home survive beyond 5 years, and a significant number are decannulated. Primary care physicians and communities should be prepared to accommodate the increasing number of children on TPPV at home.

Background: Alterations in the central nervous system in patients with acute liver failure (ALF) present unique challenges in the perioperative period. In this retrospective study, we examined pretransplant neurological presentation and the incidence, clinical presentation, and risk factors associated with severe posttransplant brain injury (BI) in ALF patients undergoing orthotopic liver transplantation (OLT)., Methods: After institutional review board approval, ALF patients who underwent OLT between 2004 and 2010 at our center were reviewed. Pretransplant neurological presentation and severe posttransplant BI were examined. Risk factors for the latter were identified., Results: During the study period, 90 (67 adults and 23 children) ALF patients underwent primary OLT. Preoperatively, all patients developed encephalopathy, 6 had seizure activity, 32 had radiological evidence of cerebral edema, and 11 had severe cerebral edema. After OLT, 7 patients developed severe posttransplant BI. Of these 7 patients, 4 had brain death, and 3 had irreversible injury that precluded them from living independently. Severe pretransplant cerebral edema and a higher posttransplant international normalized ratio (odds ratios and 95% confidence intervals: 50.2, 5.8-433.5 [P<0.001] and 3.1, 1.1-8.8 [P=0.031], respectively) were risk factors associated with severe posttransplant BI., Conclusions: Pretransplant neurological complications were prevalent, and severe posttransplant BI occurred at a rate of 7.8% and was significantly associated with severe pretransplant cerebral edema and postoperative international normalized ratio. Our findings support the use of pretransplant computed tomography. If severe pretransplant cerebral edema is confirmed, efforts should be made to aggressively control intracranial pressure and select a proper donor to minimize the risk of severe posttransplant BI and futile transplantation.

We describe the process of establishing a large database for the investigation of craniotomy infection and the preliminary results of this database. The initial results have been used to generate a cost analysis for craniotomy infection. The craniotomy infections database prospectively registers craniotomy cases taking place in the John Radcliffe Hospital. In order to achieve this, each patient's details are registered at the time of operation and followed up to identify cases of infection. Infection was defined strictly according to Centre for Disease Control criteria and validated by at least two members of clinical staff. The first 10 months of data are presented here which identifies a total of 245 craniotomies and 20 verified craniotomy infections. An overall infection rate of 8% is identified, and the cost incurred by the neurosurgery department as a result of craniotomy infections is estimated at £1 85 660 for the 10-month period studied. This amounts to a cost per case of infection of £9283.

Background: According to the regulations of the National Health Act, all 'sudden and unexpected' deaths in South Africa should be referred to Forensic Pathology Services (FPS) for further investigation., Objectives: We aimed to determine the final outcomes of forensic postmortem examinations in 'sudden and unexpected' adult deaths referred to Tygerberg FPS between 2001 and 2005., Methods: The study was a retrospective descriptive study. Demographic and autopsy data from adult cases of 'sudden and unexpected deaths' referred to Tygerberg FPS were collected and analysed. Results. Some 816 adult cases of 'sudden' deaths were studied. The presumed manner of death was natural in 645 (79.0%) cases, unnatural in 99 (12.2%), and undetermined in 72 (8.8%). Diseases of the cardiovascular, respiratory and central nervous systems accounted for the majority of natural deaths. Infectious diseases accounted for most deaths in the youngest age group studied (18 - 29 years); however, ischaemic heart disease was the most prevalent cause of death in the total study population., Conclusions: This study highlighted the lack of useful pre-autopsy information and therefore the performance of 'unnecessary' medicolegal autopsies in a resource-limited country. Clinicians could ease the burden by giving useful information when referring cases to FPS. Feedback should be given to family members, especially where the cause of death may have an impact on surviving family members.

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period., Methodology/principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1% of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age <65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8% vs. 27.5%, p = 0.502). However, among patients <65 years old and a Charlson index ≤ 1, the 2-year mortality was significantly higher in those with than without complications (18.6% vs. 11.8%, p = 0.001)., Conclusions/significance: Physicians should recognize that catastrophic disability due to ocular or neurological complications from PLA could lead to a poor long-term prognosis, and should follow-up these patients more closely.

Study Design: Retrospective study of a prospectively assembled cohort., Objective: To characterize the survival from subsequent spine surgery and the life survival of patients treated surgically for severe spinal deformity due to neuropathic diseases., Summary of Background Data: Survivorship analysis is widely used to study the natural history of disease processes and of treatments provided, but has very seldom been used to study patients' course after surgery for spinal deformity associated with neuropathic diseases., Methods: Patients with neuropathic spinal deformity treated with primary posterior instrumentation and arthrodesis from 1989 through 2002 were identified and studied by review of charts and radiographs, and by mail survey. Subsequent spine surgery and death events, and the time interval from surgery were identified. Fifteen variables possibly influencing survivorship were studied., Results: There were no perioperative deaths, spinal cord injuries, or acute wound infections in the 117 eligible patients. Reoperation and life survival statuses were available for 110 patients (94%) at an average follow-up of 11.89 years (±5.3; range: 2-20.9 yr). Twelve patients (11%) had subsequent spine surgery. Survival from subsequent spine surgery was 91% at 5 years, 90% at 10 and 15 years, and 72% at 20 years. Proximal fixation problems occurred in 4 patients. Twenty-two patients (20%) had died from 4 to 20 years postoperative. Life survival was 98% at 5 years, 89% at 10 years, 81% at 15 years, and 56% at 20 years. The only variable associated with life survival was the occurrence of one or more perioperative complications, P = 0.0032. The younger half of the series at operation (<13.75 yr) was significantly more likely to have one or more perioperative complications, P = 0.0068. Spinal deformity type and magnitude were similar for the younger and older halves of the patients. Life survival of the patients with cerebral-palsy and not-cerebral-palsy upper motor neuron disease was not different. One-hundred-two of 105 were at least satisfied or would have the surgery again for the same condition., Conclusion: Survival from subsequent spine operation was similar to adolescent idiopathic scoliosis series studied in the same manner. Life survival decline began at 4 years postoperative and was significantly associated with the occurrence of one or more perioperative complications. Even after successful spine deformity surgery, this population's health status is often precarious.

Background: Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions., Methods: A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response., Results: The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events., Conclusion: VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.

Background: The goal of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology., Methods and Results: A university center audit was done of 523 consecutive patients (median age, 64 years; interquartile range, 56-71 years) between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients) was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2% (P<0.001). Neurological injury was observed in 16.9% of patients with acute type A aortic dissection (chronic ascending aortic aneurysms, 7.9%; P=0.002). Multivariable regression analysis revealed hypothermic circulatory arrest >40 minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60-11.06; P=0.004) and redo surgery (OR, 3.44; 95% CI, 1.11-10.64; P=0.03) but not age (OR, 1.98; 95% CI, 0.73-5.38; P=0.18) as independent predictor of mortality. Emergency surgery (OR, 3.27; 95% CI, 1.31-8.15; P=0.01) and extracardiac arteriopathy (OR, 2.38; 95% CI, 1.26-4.50; P=0.008) but not age (OR, 1.80; 95% CI, 0.93-3.48; P=0.08) were independent predictors of neurological injury., Conclusions: Age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality, whereas emergency surgery and extracardiac arteriopathy predict neurological injury.

Background: Previous studies of glycemic control in non-neurologic ICU patients have shown conflicting results. The purpose was to investigate whether intensive insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or conventional treatment to keep levels less than 151 mg/dl was associated with a reduction of mortality and improved functional outcome in critically ill neurologic patients., Methods: Within 24 h of ICU admission, mechanically ventilated adult neurologic patients were enrolled after written informed consent and randomized to intensive or conventional control of blood glucose levels with insulin. Primary outcome measure was death within 3 months. Secondary outcome measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital LOS., Results: 81 patients were enrolled. The proportion of deaths was higher among IIT patients but this was not statistically significant (36 vs. 25%, P = 0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0-2 versus 3-6, respectively, there was no difference in outcome between the two groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P = 0.0006; and 4 vs. 0%, P = 0.5, respectively)., Conclusion: There was no benefit to IIT in this small critically ill neurologic population. This is the first glycemic control study to specifically examine both critically ill stroke and traumatic brain injury (TBI) patients and functional outcome. Given these results, IIT cannot be recommended over conventional control.

Background: Primary central nervous system (CNS) post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare complication of solid organ transplantation. The objectives of this study were to define the clinical, radiologic, and pathologic features of this disease and to explore the impact of treatment on patient outcomes., Methods: The authors reviewed the databases of participating institutions of the International Primary CNS Lymphoma Collaborative Group for cases of PCNS-PTLD. Thirty-four patients who had pathologically confirmed PCNS-PTLD without evidence of systemic PTLD were investigated retrospectively., Results: The median time from transplantation to diagnosis of PCNS-PTLD was 4.4 years. Disease usually was multifocal and involved any location of the brain but was most common in the cerebral hemispheres, usually in the subcortical white matter or basal ganglia. Radiographically, all lesions enhanced either homogenously or in a ring-enhancing pattern. Cerebral biopsy was required to establish diagnosis in most patients. Most patients had monomorphic, Epstein-Barr virus (EBV)-positive disease of B-cell origin. Response rates were high regardless of treatment type, and the median survival was 47 months. Age was the only factor predictive of survival., Conclusions: The current study demonstrated that PCNS-PTLD is typically an EBV-induced B-cell lymphoma that is responsive to treatment with favorable survival in many patients. An aggressive approach to tissue confirmation of diagnosis and treatment with chemotherapy or radiotherapy should be strongly considered.

To understand the cause of death of 405 marine mammals stranded on Cape Cod and southeastern Massachusetts between 2000 and 2006, a system for coding final diagnosis was developed and categorized as (1) disease, (2) human interaction, (3) mass-stranded with no significant findings, (4) single-stranded with no significant findings, (5) rock and/or sand ingestion, (6) predatory attack, (7) failure to thrive or dependent calf or pup, or (8) other. The cause of death for 91 animals could not be determined. For the 314 animals that could be assigned a cause of death, gross and histological pathology results and ancillary testing indicated that disease was the leading cause of mortality in the region, affecting 116/314 (37%) of cases. Human interaction, including harassment, entanglement, and vessel collision, fatally affected 31/314 (10%) of all animals. Human interaction accounted for 13/29 (45%) of all determined gray seal Halichoerus grypus mortalities. Mass strandings were most likely to occur in northeastern Cape Cod Bay; 97/106 (92%) of mass stranded animals necropsied presented with no significant pathological findings. Mass strandings were the leading cause of death in 3 of the 4 small cetacean species: 46/67 (69%) of Atlantic white-sided dolphin Lagenorhynchus acutus, 15/21 (71%) of long-finned pilot whale Globicephala melas, and 33/54 (61%) of short-beaked common dolphin Delphinus delphis. These baseline data are critical for understanding marine mammal population health and mortality trends, which in turn have significant conservation and management implications. They not only afford a better retrospective analysis of strandings, but ultimately have application for improving current and future response to live animal stranding.