Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.

PURPOSE: To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies. METHODS: This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated. RESULTS: A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management. CONCLUSIONS: Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.

Naps reliably estimate nocturnal sleep spindle density in health and schizophrenia.

Sleep spindles, defining oscillations of non-rapid eye movement stage 2 sleep (N2), mediate memory consolidation. Spindle density (spindles/minute) is a stable, heritable feature of the sleep electroencephalogram. In schizophrenia, reduced spindle density correlates with impaired sleep-dependent memory consolidation and is a promising treatment target. Measuring sleep spindles is also important for basic studies of memory. However, overnight sleep studies are expensive, time consuming and require considerable infrastructure. Here we investigated whether afternoon naps can reliably and accurately estimate nocturnal spindle density in health and schizophrenia. Fourteen schizophrenia patients and eight healthy controls had polysomnography during two overnights and three afternoon naps. Although spindle density was lower during naps than nights, the two measures were highly correlated. For both groups, naps and nights provided highly reliable estimates of spindle density. We conclude that naps provide an accurate, reliable and more scalable alternative to measuring spindle density overnight.

The cerebellar cognitive affective/Schmahmann syndrome scale.

Cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome) is characterized by deficits in executive function, linguistic processing, spatial cognition, and affect regulation. Diagnosis currently relies on detailed neuropsychological testing. The aim of this study was to develop an office or bedside cognitive screen to help identify CCAS in cerebellar patients. Secondary objectives were to evaluate whether available brief tests of mental function detect cognitive impairment in cerebellar patients, whether cognitive performance is different in patients with isolated cerebellar lesions versus complex cerebrocerebellar pathology, and whether there are cognitive deficits that should raise red flags about extra-cerebellar pathology. Comprehensive standard neuropsychological tests, experimental measures and clinical rating scales were administered to 77 patients with cerebellar disease-36 isolated cerebellar degeneration or injury, and 41 complex cerebrocerebellar pathology-and to healthy matched controls. Tests that differentiated patients from controls were used to develop a screening instrument that includes the cardinal elements of CCAS. We validated this new scale in a new cohort of 39 cerebellar patients and 55 healthy controls. We confirm the defining features of CCAS using neuropsychological measures. Deficits in executive function were most pronounced for working memory, mental flexibility, and abstract reasoning. Language deficits included verb for noun generation and phonemic > semantic fluency. Visual spatial function was degraded in performance and interpretation of visual stimuli. Neuropsychiatric features included impairments in attentional control, emotional control, psychosis spectrum disorders and social skill set. From these results, we derived a 10-item scale providing total raw score, cut-offs for each test, and pass/fail criteria that determined 'possible' (one test failed), 'probable' (two tests failed), and 'definite' CCAS (three tests failed). When applied to the exploratory cohort, and administered to the validation cohort, the CCAS/Schmahmann scale identified sensitivity and selectivity, respectively as possible exploratory cohort: 85%/74%, validation cohort: 95%/78%; probable exploratory cohort: 58%/94%, validation cohort: 82%/93%; and definite exploratory cohort: 48%/100%, validation cohort: 46%/100%. In patients in the exploratory cohort, Mini-Mental State Examination and Montreal Cognitive Assessment scores were within normal range. Complex cerebrocerebellar disease patients were impaired on similarities in comparison to isolated cerebellar disease. Inability to recall words from multiple choice occurred only in patients with extra-cerebellar disease. The CCAS/Schmahmann syndrome scale is useful for expedited clinical assessment of CCAS in patients with cerebellar disorders.awx317media15678692096001.

Percutaneous Image-Guided Cryoablation of Hepatic Tumors: Single-Center Experience With Intermediate to Long-Term Outcomes.

OBJECTIVE: The purpose of this article is to report our intermediate to long-term outcomes with image-guided percutaneous hepatic tumor cryoablation and to evaluate its technical success, technique efficacy, local tumor progression, and adverse event rate. MATERIALS AND METHODS: Between 1998 and 2014, 299 hepatic tumors (243 metastases and 56 primary tumors; mean diameter, 2.5 cm; median diameter, 2.2 cm; range, 0.3-7.8 cm) in 186 patients (95 women; mean age, 60.9 years; range, 29-88 years) underwent cryoablation during 236 procedures using CT (n = 126), MRI (n = 100), or PET/CT (n = 10) guidance. Technical success, technique efficacy at 3 months, local tumor progression (mean follow-up, 2.5 years; range, 2 months to 14.6 years), and adverse event rates were calculated. RESULTS: The technical success rate was 94.6% (279/295). The technique efficacy rate was 89.5% (231/258) and was greater for tumors smaller than 4 cm (93.4%; 213/228) than for larger tumors (60.0%; 18/30) (p < 0.0001). Local tumor progression occurred in 23.3% (60/258) of tumors and was significantly more common after the treatment of tumors 4 cm or larger (63.3%; 19/30) compared with smaller tumors (18.0%; 41/228) (p < 0.0001). Adverse events followed 33.8% (80/236) of procedures and were grade 3-5 in 10.6% (25/236) of cases. Grade 3 or greater adverse events more commonly followed the treatment of larger tumors (19.5%; 8/41) compared with smaller tumors (8.7%; 17/195) (p = 0.04). CONCLUSION: Image-guided percutaneous cryoablation of hepatic tumors is efficacious; however, tumors smaller than 4 cm are more likely to be treated successfully and without an adverse event.

Interreader Agreement of Prostate Imaging Reporting and Data System Version 2 Using an In-Bore MRI-Guided Prostate Biopsy Cohort: A Single Institution's Initial Experience.

OBJECTIVE: The purpose of this study is to determine the interobserver agreement of the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for diagnosing prostate cancer using in-bore MRI-guided prostate biopsy as the reference standard. MATERIALS AND METHODS: Fifty-nine patients underwent in-bore MRI-guided prostate biopsy between January 21, 2010, and August 21, 2013, and underwent diagnostic multiparametric MRI 6 months or less before biopsy. A single index lesion per patient was selected after retrospective review of MR images. Three fellowship-trained abdominal radiologists (with 1-11 years' experience) blinded to clinical information interpreted all studies according to PI-RADSv2. Interobserver agreement was assessed using Cohen kappa statistics. RESULTS: Thirty-eight lesions were in the peripheral zone and 21 were in the transition zone. Cancer was diagnosed in 26 patients (44%). Overall PI-RADS scores were higher for all biopsy-positive lesions (mean ± SD, 3.9 ± 1.1) than for biopsy-negative lesions (3.1 ± 1.0; p < 0.0001) and for clinically significant lesions (4.2 ± 1.0) than for clinically insignificant lesions (3.1 ± 1.0; p < 0.0001). Overall suspicion score interobserver agreement was moderate (κ = 0.45). There was moderate interobserver agreement among overall PI-RADS scores in the peripheral zone (κ = 0.46) and fair agreement in the transition zone (κ = 0.36). CONCLUSION: PI-RADSv2 scores were higher in the biopsy-positive group. PI-RADSv2 showed moderate interobserver agreement among abdominal radiologists with no prior experience using the scoring system.

Spectrally encoded confocal microscopy for diagnosing breast cancer in excision and margin specimens.

A large percentage of breast cancer patients treated with breast conserving surgery need to undergo multiple surgeries due to positive margins found during post-operative margin assessment. Carcinomas could be removed completely during the initial surgery and additional surgery avoided if positive margins can be determined intraoperatively. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to rapidly image the entire surgical margin at subcellular resolution and accurately determine margin status intraoperatively. In this study, in order to test the feasibility of using SECM for intraoperative margin assessment, we have evaluated the diagnostic accuracy of SECM for detecting various types of breast cancers. Forty-six surgically removed breast specimens were imaged with an SECM system. Side-by-side comparison between SECM and histologic images showed that SECM images can visualize key histomorphologic patterns of normal/benign and malignant breast tissues. Small (500 µm × 500 µm) spatially registered SECM and histologic images (n=124 for each) were diagnosed independently by three pathologists with expertise in breast pathology. Diagnostic accuracy of SECM for determining malignant tissues was high, average sensitivity of 0.91, specificity of 0.93, positive predictive value of 0.95, and negative predictive value of 0.87. Intra-observer agreement and inter-observer agreement for SECM were also high, 0.87 and 0.84, respectively. Results from this study suggest that SECM may be developed into an intraoperative margin assessment tool for guiding breast cancer excisions.

High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion.

Alterations in renal microperfusion play an important role in the development of acute kidney injury with long-term consequences. Here we used contrast-enhanced ultrasonography as a novel method for depicting intrarenal distribution of blood flow. After infusion of microbubble contrast agent, bubbles were collapsed in the kidney and postbubble destruction refilling was measured in various regions of the kidney. Local perfusion was monitored in vivo at 15, 30, 45, 60 minutes and 24 hours after 28 minutes of bilateral ischemia in 12 mice. High-resolution, pixel-by-pixel analysis was performed on each imaging clip using customized software, yielding parametric perfusion maps of the kidney, representing relative blood volume in each pixel. These perfusion maps revealed that outer medullary perfusion decreased disproportionately to the reduction in the cortical and inner medullary perfusion after ischemia. Outer medullary perfusion was significantly decreased by 69% at 60 minutes postischemia and remained significantly less (40%) than preischemic levels at 24 hours postischemia. Thus, contrast-enhanced ultrasonography with high-resolution parametric perfusion maps can monitor changes in renal microvascular perfusion in space and time in mice. This novel technique can be translated to clinical use in man.

Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of Inflammatory Strictures from Fibrotic Strictures in Crohn Disease.

PURPOSE: To retrospectively evaluate positron emission tomography (PET)/magnetic resonance (MR) enterography for the differentiation of fibrotic strictures from inflammatory strictures in patients with Crohn disease. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave their written informed consent for study enrollment. PET/MR enterography images were evaluated in 19 patients with Crohn disease who had strictures that underwent surgical resection with pathologic confirmation. Two radiologists and a nuclear medicine physician in consensus evaluated the following bowel wall PET/MR enterography biomarkers: signal intensity (SI) on T2-weighted images, apparent diffusion coefficient (ADC), PET maximum standardized uptake value (SUVmax), SI on T2-weighted images × SUVmax, and ADC × SUVmax values at levels that corresponded to pathologic specimens. MR, PET, and hybrid PET/MR biomarkers were compared, and the performance for differentiation of inflammatory strictures from fibrotic strictures was assessed. Mixed-model regression analysis was used to compare the mean imaging parameters between groups; the P values were corrected for the five comparisons by using the Bonferroni method. RESULTS: Three of the PET/MR enterography biomarkers, SUVmax, SI on T2-weighted images × SUVmax, and ADC × SUVmax, showed significant differences in the fibrosis group compared with the fibrosis with active inflammation group and the active inflammation only group. The best discriminator between fibrosis and active inflammation was the combined PET/MR enterography biomarker ADC × SUVmax cutoff of less than 3000, which was associated with accuracy, sensitivity, and specificity values of 0.71, 0.67, and 0.73, respectively. CONCLUSION: PET/MR enterography offers a potential noninvasive technique for the differentiation of purely fibrotic strictures from mixed or inflammatory strictures. A hybrid biomarker that incorporates both MR and PET information performed better for stricture evaluation than either modality alone.

Cerebellar Contribution to Social Cognition.

Emotion attribution (EA) from faces is key to social cognition, and deficits in perception of emotions from faces underlie neuropsychiatric disorders in which cerebellar pathology is reported. Here, we test the hypothesis that the cerebellum contributes to social cognition through EA from faces. We examined 57 patients with cerebellar disorders and 57 healthy controls. Thirty-one patients had complex cerebrocerebellar disease (complex cerebrocerebellar disease group (CD)); 26 had disease isolated to cerebellum (isolated cerebellar disease group (ID)). EA was measured with the Reading the Mind in the Eyes test (RMET), and informants were administered a novel questionnaire, the Cerebellar Neuropsychiatric Rating Scale (CNRS). EA was impaired in all patients (CD p < 0.001, ID p < 0.001). When analyzed for valence categories, both CD and ID missed more positive and negative stimuli. Positive targets produced the highest deficit (CD p < 0.001, ID p = 0.004). EA impairments correlated with CNRS measures of deficient social skills (p < 0.05) and autism spectrum behaviors (p < 0.005). Patients had difficulties with emotion regulation (CD p < 0.001, ID p < 0.001), autism spectrum behaviors (CD p < 0.049, ID p < 0.001), and psychosis spectrum symptoms (CD p < 0.021, ID p < 0.002). ID informants endorsed deficient social skills (CD p < 0.746, ID p < 0.003) and impaired attention regulation (CD p < 0.144, ID p < 0.001). Within the psychosis spectrum domain, CD patients were worse than controls for lack of empathy (CD p = 0.05; ID p = 0.49). Thus, patients with cerebellar damage were impaired on an EA task associated with deficient social skills and autism spectrum behaviors and experienced psychosocial difficulties on the CNRS. This has relevance for ataxias, the cerebellar cognitive affective/Schmahmann syndrome, and neuropsychiatric disorders with cerebellar pathology.

Evidence for brain glial activation in chronic pain patients.

Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.

Transperineal in-bore 3-T MR imaging-guided prostate biopsy: a prospective clinical observational study.

PURPOSE: To determine the detection rate, clinical relevance, Gleason grade, and location of prostate cancer ( PCa prostate cancer ) diagnosed with and the safety of an in-bore transperineal 3-T magnetic resonance (MR) imaging-guided prostate biopsy in a clinically heterogeneous patient population. MATERIALS AND METHODS: This prospective retrospectively analyzed study was HIPAA compliant and institutional review board approved, and informed consent was obtained. Eighty-seven men (mean age, 66.2 years ± 6.9) underwent multiparametric endorectal prostate MR imaging at 3 T and transperineal MR imaging-guided biopsy. Three subgroups of patients with at least one lesion suspicious for cancer were included: men with no prior PCa prostate cancer diagnosis, men with PCa prostate cancer who were undergoing active surveillance, and men with treated PCa prostate cancer and suspected recurrence. Exclusion criteria were prior prostatectomy and/or contraindication to 3-T MR imaging. The transperineal MR imaging-guided biopsy was performed in a 70-cm wide-bore 3-T device. Overall patient biopsy outcomes, cancer detection rates, Gleason grade, and location for each subgroup were evaluated and statistically compared by using χ(2) and one-way analysis of variance followed by Tukey honestly significant difference post hoc comparisons. RESULTS: Ninety biopsy procedures were performed with no serious adverse events, with a mean of 3.7 targets sampled per gland. Cancer was detected in 51 (56.7%) men: 48.1% (25 of 52) with no prior PCa prostate cancer , 61.5% (eight of 13) under active surveillance, and 72.0% (18 of 25) in whom recurrence was suspected. Gleason pattern 4 or higher was diagnosed in 78.1% (25 of 32) in the no prior PCa prostate cancer and active surveillance groups. Gleason scores were not assigned in the suspected recurrence group. MR targets located in the anterior prostate had the highest cancer yield (40 of 64, 62.5%) compared with those for the other parts of the prostate (P < .001). CONCLUSION: In-bore 3-T transperineal MR imaging-guided biopsy, with a mean of 3.7 targets per gland, allowed detection of many clinically relevant cancers, many of which were located anteriorly.

Age and Obesity Promote Methylation and Suppression of 5α-Reductase 2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia.

PURPOSE: In men with symptomatic benign prostatic hyperplasia 5α-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5α-reductase inhibitors. We have found that a third of adult prostate samples do not express 5α-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5α-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5α-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen. MATERIALS AND METHODS: Prostate samples from men undergoing transurethral prostate resection were used. We determined 5α-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, hypertension, hyperlipidemia, diabetes, prostate specific antigen and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: Body mass index and age significantly correlated with methylation of the 5α-reductase type 2 gene promoter (p <0.05) whereas prostate volume, prostate specific antigen or benign prostatic hyperplasia medication did not correlate. Methylation highly correlated with 5α-reductase protein expression (p <0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p <0.01). CONCLUSIONS: Increasing age and body mass index correlate with increased 5α-reductase type 2 gene promoter methylation and decreased protein expression in men with symptomatic benign prostatic hyperplasia. These results highlight the interplay among age, obesity and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic benign prostatic hyperplasia, which may be important to choose appropriate personalized treatment options.

Clinical impact of PET/MR imaging in patients with cancer undergoing same-day PET/CT: initial experience in 134 patients--a hypothesis-generating exploratory study.

PURPOSE: To compare the clinical impact of combined positron emission tomography (PET) and magnetic resonance (MR) imaging to that of combined PET and computed tomography (CT) performed on the same day in patients with cancer. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave written informed consent for study enrollment, including the possibility to use their imaging and clinical data in future evaluations. A total of 134 patients with cancer with a non-central nervous system primary neoplasm underwent same-day fluorodeoxyglucose (FDG) PET/CT and FDG PET/MR imaging. PET/CT and PET/MR studies were independently interpreted by teams of radiologists and nuclear medicine physicians. Four readers, divided into two teams composed of one radiologist and one nuclear medicine physician each, read all 134 studies. The referring physician classified discordance between PET/CT and PET/MR observations either as findings affecting clinical management or as findings not affecting clinical management. Data were compared with the χ(2) test. RESULTS: Findings affecting clinical management were noted for PET/CT studies but not for PET/MR studies in two (1.5%) of 134 patients and for PET/MR studies but not for PET/CT studies in 24 (17.9%) of 134 patients. The discrepancies between findings affecting clinical management detected with PET/MR imaging over those detected with PET/CT were significant (P < .001). CONCLUSION: In these patients, PET/MR imaging alone contributed to clinical management more often than did PET/CT alone. PET/MR imaging provides information that affects the care of patients with cancer and is unavailable from PET/CT. Online supplemental material is available for this article.

Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology.

Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = -0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.

Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography.

BACKGROUND AND PURPOSE: Early assessment of the likelihood of neurological recovery in comatose cardiac arrest survivors remains challenging. We hypothesize that quantitative noncontrast computed tomography (NCCT) combined with neurological assessments, are predictive of outcome. METHODS: We analyzed data sets acquired from comatose cardiac arrest patients who underwent CT within 72 hours of arrest. Images were semiautomatically segmented into anatomic regions. Median Hounsfield units (HU) were measured regionally and in the whole brain (WB). Outcome was based on the 6-month modified Rankin Scale (mRS) score. Logistic regression was used to combine Glasgow Coma Scale (GCS) score measured on Day 3 post arrest (GCS_Day3) with imaging to predict poor outcome (mRS>4). RESULTS: WB HU (P=0.02) and the ratio of HU in the putamen to the posterior limb of the internal capsule (PLIC) (P=0.004) from 175 datasets from 151 patients were univariate predictors of poor outcome. Thirty-three patients underwent hypothermia treatment. Multivariate analysis showed that combining median HU in the putamen (P=0.0006) and PLIC (P=0.007) was predictive of poor outcome. Combining WB HU and GCS_Day3 resulted in 72% [61% to 80%] sensitivity and 100% [73% to 100%] specificity for predicting poor outcome in 86 patients with measurable GCS_Day3. This was an improvement over prognostic performance based on GCS_Day3≤8 (98% sensitive but 71% specific). DISCUSSION: Combining density changes on CT with GCS_Day3 may be useful for predicting poor outcome in comatose cardiac arrest patients who are neither rapidly improving nor deteriorating. Improved prognostication with CT compared with neurological assessments can be achieved in patients treated with hypothermia.

Differences in cortical response to acupressure and electroacupuncture stimuli.

BACKGROUND: FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation. RESULTS: Evoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP. CONCLUSION: Both EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed.

A low-cost educational intervention to reduce unplanned extubation in low-resourced pediatric intensive care units.

INTRODUCTION: Unplanned extubation (UE) is orders of magnitude worse in low-income Pediatric Intensive Care Units (PICUs) than their high-income counterparts. Furthermore, a significant percent (20 %) of UEs result in a destabilizing event or cardiac collapse that negatively contributes to morbidity and mortality. As the principles of safe airway management are universal, we hypothesize that a multi-disciplinary educational intervention bundle which included provision of low-cost cuffed endotracheal tubes (ETT) and ETT tape will decrease the rate of unplanned extubation (UE) in a low-resourced PICU. METHODS: This is a pre-post interventional study powered to evaluate UE of intubated pediatric patients in an El Salvadorian PICU after a multi-disciplinary educational effort and provision of low-cost disposable materials. A multidisciplinary (otolaryngologists, intensivists, anesthesiologists, respiratory therapists, and nurses) educational curriculum involving hands on training, online video modules readily available via bedside QR codes, and pre- and post-testing was administered. The cost of the intervention materials was $1.32 per child. PICU mortality was evaluated as an exploratory outcome. RESULTS: Nine-hundred and fifty-seven (859 pre-intervention and 98 post-intervention) patients met inclusion criteria. Patients with one or more UEs decreased significantly from 29.4 % to 17.3 % post-intervention (p = 0.01; CI: 0.28-0.88) with an odds ratio of 0.51. The use of a cuffed ETT increased from 12 % to 36 % (p < 0.001; CI: 0.17-0.44; OR:3.74) and cuffed ETT use was associated with a reduction in UE with an odds ratio of 0.40 (p < 0.001; CI: 0.24-0.66). Finally, there was a 4.3 % decrease in pediatric mortality from 26.7 % to 22.4 % that equates to a number needed to treat to prevent a single child mortality of 23. Therefore, the ICER per mortality prevented is $30.7 and the ICER per Disability Adjusted Life Year (DALY) is $0.44. CONCLUSION: This multi-faceted intervention bundle is an accessible, scalable, cost-effective means to reduce UE and has implications in reducing global pediatric mortality.