Predictive modeling of ambulatory outcomes after spinal cord injury using machine learning.

STUDY DESIGN: Retrospective multi-site cohort study. OBJECTIVES: To develop an accurate machine learning predictive model using predictor variables from the acute rehabilitation period to determine ambulatory status in spinal cord injury (SCI) one year post injury. SETTING: Model SCI System (SCIMS) database between January 2000 and May 2019. METHODS: Retrospective cohort study using data that were previously collected as part of the SCI Model System (SCIMS) database. A total of 4523 patients were analyzed comparing traditional models (van Middendorp and Hicks) compared to machine learning algorithms including Elastic Net Penalized Logistic Regression (ENPLR), Gradient Boosted Machine (GBM), and Artificial Neural Networks (ANN). RESULTS: Compared with GBM and ANN, ENPLR was determined to be the preferred model based on predictive accuracy metrics, calibration, and variable selection. The primary metric to judge discrimination was the area under the receiver operating characteristic curve (AUC). When compared to the van Middendorp all patients (0.916), ASIA A and D (0.951) and ASIA B and C (0.775) and Hicks all patients (0.89), ASIA A and D (0.934) and ASIA B and C (0.775), ENPLR demonstrated improved AUC for all patients (0.931), ASIA A and D (0.965) ASIA B and C (0.803). CONCLUSIONS: Utilizing artificial intelligence and machine learning methods are feasible for accurately classifying outcomes in SCI and may provide improved sensitivity in identifying which individuals are less likely to ambulate and may benefit from augmentative strategies, such as neuromodulation. Future directions should include the use of additional variables to further refine these models.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Study Registration for the Field of Prevention Science: Considering Options and Paths Forward.

The practice of prospectively registering the details of intervention studies in a public database or registry is gaining momentum across disciplines as a strategy for increasing the transparency, credibility, and accessibility of study findings. In this article, we consider five registries that may be relevant for registration of intervention studies in the field of prevention science: ClinicalTrials.gov, the American Economic Association Registry of Randomized Controlled Trials (AEA RCT Registry), the Open Science Framework Preregistration (OSF Preregistration), the Registry for International Development Impact Evaluations (RIDIE), and the Registry of Efficacy and Effectiveness Studies (REES). We examine the five registries in terms of substantive focus, study designs, and contents of registry entries. We consider two paths forward for prospective registration of intervention studies in the field of prevention science: Path A: register all studies in ClinicalTrials.gov and Path B: allow individual researchers to select the registry with the "best fit." Lastly, we consider how the field might begin to establish norms around registration.

Sepsis in Traumatic Brain Injury: Epidemiology and Outcomes.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Risk factors for in-hospital mortality include older age, co-morbidity, and TBI severity. Few studies have investigated the role of sepsis in individuals with TBI. METHODS: We studied adult patients with TBI admitted to intensive care over a 5-year period. Patient characteristics were identified by linking clinical and administrative databases. Charts of individuals with TBI and sepsis were manually reviewed. Predictors of ICU and hospital mortality were identified using logistic regression modeling. RESULTS: Four hundred eighty-six individuals with TBI were admitted to intensive care. Sixteen (3.3%) developed sepsis. Pneumonia was the most common source (94%). Staphylococcus aureus was the most common pathogen (75%). ICU lengths of stay (LOS) (12.2 days [interquartile range (IQR) 4.4-23.5] versus 3.7 days [IQR 1.7-8.2]; p < 0.001) and hospital LOS (28.0 days [IQR 11.8-41.4] versus 15.3 days [IQR 5.0-30.9]; p = 0.017) were longer in patients with TBI and sepsis. Sepsis was not associated with ICU (adjusted odds ratio [aOR] 0.51; 95%CI 0.12-2.27; p = 0.38) or hospital (aOR 0.78; 95% CI 0.21-2.96; p = 0.78) mortality, though age (aOR 1.02; 95% CI 1.00-1.04; p = 0.014 for hospital mortality), severe TBI (aOR 3.71; 95% CI 1.52-9.08; p = 0.004 for ICU mortality and 4.10; 95% CI 1.95-8.65; p < 0.001 for hospital mortality), and APACHE II score (aOR 1.19; 95% CI 1.11-1.28; p < 0.001 for ICU mortality and 1.22; 95% CI 1.14-1.31; p < 0.001 for hospital mortality) were. CONCLUSION: Sepsis in patients with TBI was not associated with mortality; however, sepsis was associated with increased health care utilization (ICU and hospital LOS).

Oophorectomy in NMDA receptor encephalitis and negative pelvic imaging.

Ovarian teratomas are found in one-third of females presenting with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. When a teratoma is detected on imaging, its removal is first-line therapy. Even with multiple imaging modalities, occasionally, the teratoma is found only on subsequent imaging, long after initial presentation. Very rarely, patients have undergone oophorectomy despite negative imaging, with pathology demonstrating teratoma, and resulting clinical improvement. We present a patient in whom removal of a teratoma, not visible on conventional imaging, resulted in marked clinical improvement. Such cases present a major clinical challenge, needing to consider the risks of oophorectomy, including sterilisation and early menopause, versus the possibility of death in the absence of response to first-line (eg, corticosteroids, plasma exchange, intravenous immunoglobulin), second-line (eg, rituximab) and third-line (eg, bortezomib) immunosuppression. This decision is made more difficult as patients are usually females of childbearing age who at the time lack capacity to make medical decisions. This case also highlights the lack of consensus and guidelines for imaging modalities used to detect teratoma and when to pursue oophorectomy.

Sarcocystis myopathy in a patient with HIV-AIDS.

Sarcocystosis is a zoonotic infection that causes intestinal and muscular illnesses in humans. Sarcocystosis was until recently considered rare in humans. To complete their life cycle, Sarcocystis species require both a definitive and an intermediate host. Humans are the definitive host when infected by one of two species: Sarcocystis hominis (from eating undercooked beef) or Sarcocystis suihominis (from eating uncooked pork). Infection with either of these species results in intestinal sarcocystosis, causing a self-limited disease characterized by nausea, abdominal pain, and diarrhea. Humans act as the intermediate host when infected by Sarcocystis nesbitti, resulting in the markedly different clinical picture of muscular sarcocystosis. Most documented cases of muscular sarcocystosis were assumed to be acquired in Malaysia, in addition to other regions of Southeast Asia and India. Published cases of muscular sarcocystosis from the Middle East, Central and South America, and Africa are all rare. Although the clinical presentation of muscular sarcocystosis remains to be fully characterized, fever, myalgia, and headache are among the most common symptoms. Here, we report a patient from sub-Saharan Africa with chronic Sarcocystis myopathy and well-controlled HIV-AIDS.

Rituximab in refractory myasthenia gravis: Extended prospective study results.

INTRODUCTION: Rituximab appears to be beneficial in treatment-refractory myasthenia gravis (MG); however, prospective, long-term durability data are lacking. METHODS: In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 nicotinic acetylcholine receptor, 9 muscle-specific tyrosine kinase, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B-cell counts were serially monitored. RESULTS: At mean follow-up of 28.8 ± 19.0 months (range, 6-66), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (P < 0.0001). Mean prednisone dosage declined from 25.2 ± 15.1 to 7.3 ± 7.1 mg/d (P = 0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range, 9-23). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B-cell depletion (range, 24-45 months) after 1 cycle. DISCUSSION: Sustained clinical improvement was associated with rituximab after 1 cycle, with prolonged time to relapse and reduction in steroid dosage. Muscle Nerve 58: 453-456, 2018.

Improvement in the Prognosis of Cerebral Venous Sinus Thrombosis over a 22-Year Period.

BACKGROUND: Cerebral venous thrombosis is a rare cause of stroke, with a number of well-defined risk factors. However, there exist few studies that describe trends in the prognosis of this disease over time. METHODS: A retrospective study was performed on patients diagnosed with cerebral venous thrombosis at the University of Alberta Hospital during two time periods: 1988-1998 (21 patients) and 1999-2009 (40 patients). Signs and symptoms, risk factors, imaging findings, etiologies, treatment modalities, and status at discharge were examined. RESULTS: Headache, nausea and vomiting, focal motor deficit, and seizure were the most common signs and symptoms, and active hormonal contraception was the most commonly identified risk factor between the two cohorts. Hematoma and hyperdense sinuses were the most commonly identified CT findings between groups. Thrombophilia and the use of hormonal contraception were the most frequently identified etiologies between the two cohorts. Treatment was similar, with the majority of patients in both cohorts receiving unfractionated heparin as first-line therapy. Patients in the 1999-2009 cohort were significantly less likely to have a severe deficit or be dead at discharge (odds ratio [OR]=0.178; 95% confidence interval [CI 95%]=0.051, 0.625) and were more likely to have a favorable modified Rankin Scale score of 0 or 1 at discharge (OR=7.98; CI 95%=1.79, 35.71). CONCLUSIONS: Our data indicate a reduction in severe residual symptoms at discharge and improved functional status at discharge for patients presenting with cerebral venous thrombosis from 1999 to 2009, as compared with 1988-1998.

A neuropathic pain syndrome associated with hantavirus infection.

Hantaviruses are a group of single-stranded RNA viruses of the Bunyaviridae family. "New World" hantaviruses cause hantavirus cardiopulmonary syndrome (HCPS) in North America. HCPS carries with it significant mortality and those patients who survive the disease are often left with substantial morbidity. Neurologic complications of hantavirus infections are rare, with only sparse cases of central nervous system involvement having been documented in the literature. To our knowledge, there are no reports of hantavirus infection contributing to peripheral nervous system dysfunction. Here we report a case of possible small fiber neuropathy associated with hantavirus infection, in a patient who survived HCPS. Persistent and treatment-resistant neuropathic pain may be a prominent feature in hantavirus-associated peripheral neuropathy.

Neurological Nuance: Hodgkin lymphoma presenting with Guillain-BarrÉ syndrome.

INTRODUCTION: Hodgkin lymphoma (HL) is a common lymphoid malignancy rarely associated with Guillain-Barré syndrome (GBS). In most cases, GBS does not precede HL. METHODS: We describe a patient with acute inflammatory demyelinating polyneuropathy who fulfilled criteria for GBS that heralded undiagnosed HL. RESULTS: Cerebrospinal fluid (CSF) studies revealed albuminocytologic dissociation with significant protein elevation (250 mg/dl). The patient worsened during intravenous immunoglobulin (IVIg) therapy. Constitutional symptoms with elevated inflammatory markers prompted further investigation, and imaging revealed an anterior mediastinal mass confirmed on biopsy to be HL. Chemotherapy yielded early clinical improvement. CONCLUSIONS: GBS preceding HL is rare, and this case highlights the importance of considering HL in the setting of GBS. Marked elevations in CSF protein, ongoing deterioration despite administration of IVIg, and constitutional symptoms with elevated inflammatory markers may be clues to possible HL-induced GBS. Muscle Nerve 55: 601-604, 2017.

The expression pattern of a Cav3-Kv4 complex differentially regulates spike output in cerebellar granule cells.

The cerebellum receives sensory information by mossy fiber input from a multitude of sources that require differential signal processing. A compartmentalization of function begins with the segregation of mossy fibers across 10 distinct lobules over the rostrocaudal axis, with tactile receptor afferents prevalent in anterior lobules and vestibular input in caudal lobules. However, it is unclear how these unique signals might be differentially processed at the circuit level across the cerebellum. As granule cells receive mossy fiber input, they represent a key stage at which postsynaptic mechanisms could influence signal processing. Granule cells express an A-type current mediated by Kv4 potassium channels that modify the latency and frequency of spike output. The current study examined the potential for a Cav3 calcium-Kv4 channel complex to regulate the response of granule cells to mossy fiber input in lobules 2 and 9 of the rat cerebellum. Similar A-type currents were recorded in both regions, but the Cav3 calcium current was expressed at a substantially higher density in lobule 9 cells, acting to increase A-type current availability through its influence on Kv4 voltage for inactivation. The difference in excitability imparted by Cav3-Kv4 interactions proves to allow lobule 2 granule cells to respond more effectively to tactile stimulus-like burst input and lobule 9 cells to slow shifts in input frequency characteristic of vestibular input. The expression pattern of Cav3 channels and its control of Kv4 availability thus provides a novel means of processing widely different forms of sensory input across cerebellar lobules.

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells.

Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca(2+)-activated K(+) channels are known to control spike frequency in central neurons, Ca(2+)-activated K(+) channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca(2+) channels at the nanodomain level to support a previously undescribed transient voltage- and Ca(2+)-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca(2+) influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.

Does the Implementation of an Advanced Life Support Quick Response Vehicle (QRV) in an Integrated Fire/EMS System Improve Patient Contact Response Time?

BACKGROUND: The current Fire/Emergency Medical Services (EMS) model throughout the United States involves emergency vehicles which respond from a primary location (ie, firehouse or municipal facility) to emergency calls. Quick response vehicles (QRVs) have been used in various Fire/EMS systems; however, their effectiveness has never been studied. OBJECTIVES: The goal of this study was to determine if patient response times would decrease by placing an Advanced Life Support (ALS) QRV in an integrated Fire/EMS system. METHODS: Response times from an integrated Fire/EMS system with an annual EMS call volume of 3,261 were evaluated over the three years prior to the implementation of this study. For a 2-month period, an ALS QRV staffed by a firefighter/paramedic responded to emergency calls during peak call volume hours of 8:00 am to 5:00 pm. The staging of this vehicle was based on historical call volume percentages using respective geocodes as well as system requirements during multiple emergency dispatches. RESULTS: Prior to the study, the citywide average response time for the twelve months preceding was 5.44 minutes. During the study, the citywide average response time decreased to 4.09 minutes, resulting in a 27.62% reduction in patient response time. CONCLUSION: The implementation of an ALS QRV in an integrated Fire/EMS system reduces patient response time. Having a QRV that is not staged continuously in a traditional fire station or municipal location reduces the time needed to reach patients. Also, using predictive models of historic call volume can aid Fire and EMS administrators in reduction of call response times.

The Cav3-Kv4 complex acts as a calcium sensor to maintain inhibitory charge transfer during extracellular calcium fluctuations.

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.

Dentigerous cyst of mandible presenting as sepsis.

Dentigerous cysts are odontogenic cysts that develop by accumulation of fluid between reduced enamel epithelium and a crown of an unerupted tooth. Dentigerous cysts typically are slow growing and incidental findings on radiographic images [1]. These cysts are usually small but when they become large, they will cause a pathologic fracture. Occasionally, they can become painful when infected, which will cause swelling and erythema [1]. We present a rare case of a dentigerous cyst that presented as sepsis. Dentigerous cysts are the most common type of noninflammatory odontogenic cyst [2]. The atypical acute presentation and extent of this patient's soft tissue manifestations resulting in tracheal midline shift and sepsis make this a rare case for presentation.