Data-driven phenotyping of preoperative functional decline patterns in patients undergoing lumbar decompression and lumbar fusion using smartphone accelerometry.

OBJECTIVE: Treatment of degenerative lumbar spine pathologies typically escalates to surgical intervention when symptoms begin to significantly impair patients' functional status. Currently, surgeons rely on subjective patient assessments through patient-reported outcome measures to estimate the decline in patient wellness and quality of life. In this analysis, the authors sought to use smartphone-based accelerometry data to provide an objective, continuous measurement of physical activity that might aid in effective characterization of preoperative functional decline in different lumbar spine surgical indications. METHODS: Up to 1 year of preoperative activity data (steps taken per day) from 14 patients who underwent lumbar decompression and 15 patients who underwent endoscopic lumbar fusion were retrospectively extracted from patient smartphones. A data-driven algorithm was constructed based on 10,585 unique activity data points to identify and characterize the functional decline of patients preceding surgical intervention. Algorithmic estimation of functional decline onset was compared with reported symptom onset in clinical documentation across patients who presented acutely (≤ 5 months of symptoms) or chronically (> 5 months of symptoms). RESULTS: The newly created algorithm identified a statistically significant decrease in physical activity during measured periods of functional decline (p = 0.0020). To account for the distinct clinical presentation phenotypes of patients requiring lumbar decompression (71.4% acute and 28.6% chronic) and those requiring lumbar fusion (6.7% acute and 93.3% chronic), a variable threshold for detecting clinically significant reduced physical activity was implemented. The algorithm characterized functional decline (i.e., acute or chronic presentation) in patients who underwent lumbar decompression with 100% accuracy (sensitivity 100% and specificity 100%), while characterization of patients who underwent lumbar fusion was less effective (accuracy 26.7%, sensitivity 21.4%, and specificity 100%). Adopting a less-permissive detection threshold in patients who underwent lumbar fusion, which rendered the algorithm robust to minor fluctuations above or below the chronically decreased level of preoperative activity in most of those patients, increased functional decline classification accuracy of patients who underwent lumbar fusion to 66.7% (sensitivity 64.3% and specificity 100%). CONCLUSIONS: In this study, the authors found that smartphone-based accelerometer data successfully characterized functional decline in patients with degenerative lumbar spine pathologies. The accuracy and sensitivity of functional decline detection were much lower when using non-surgery-specific detection thresholds, indicating the effectiveness of smartphone-based mobility analysis in characterizing the unique physical activity fingerprints of different lumbar surgical indications. The results of this study highlight the potential of using activity data to detect symptom onset and functional decline in patients, enabling earlier diagnosis and improved prognostication.

Development of an Intraoperative Pipeline for Holographic Mixed Reality Visualization During Spinal Fusion Surgery.

Objective. Holographic mixed reality (HMR) allows for the superimposition of computer-generated virtual objects onto the operator's view of the world. Innovative solutions can be developed to enable the use of this technology during surgery. The authors developed and iteratively optimized a pipeline to construct, visualize, and register intraoperative holographic models of patient landmarks during spinal fusion surgery. Methods. The study was carried out in two phases. In phase 1, the custom intraoperative pipeline to generate patient-specific holographic models was developed over 7 patients. In phase 2, registration accuracy was optimized iteratively for 6 patients in a real-time operative setting. Results. In phase 1, an intraoperative pipeline was successfully employed to generate and deploy patient-specific holographic models. In phase 2, the registration error with the native hand-gesture registration was 20.2 ± 10.8 mm (n = 7 test points). Custom controller-based registration significantly reduced the mean registration error to 4.18 ± 2.83 mm (n = 24 test points, P < .01). Accuracy improved over time (B = -.69, P < .0001) with the final patient achieving a registration error of 2.30 ± .58 mm. Across both phases, the average model generation time was 18.0 ± 6.1 minutes (n = 6) for isolated spinal hardware and 33.8 ± 8.6 minutes (n = 6) for spinal anatomy. Conclusions. A custom pipeline is described for the generation of intraoperative 3D holographic models during spine surgery. Registration accuracy dramatically improved with iterative optimization of the pipeline and technique. While significant improvements and advancements need to be made to enable clinical utility, HMR demonstrates significant potential as the next frontier of intraoperative visualization.

Heart-Shaped Bilateral Medullary Pyramidal Infarction as a Pathognomonic Finding of Anterior Spinal Artery Occlusion.

BACKGROUND: Unilateral anterior spinal artery (ASA) occlusion resulting in bilateral medullary pyramidal (BMP) infarction is a rare and devastating stroke subtype. We present two cases highlighting the diagnostic and clinical challenges of BMP infarction. METHODS: Case reports and literature review. RESULTS: A 57-year-old man rapidly had severe vomiting and diarrhea 2 h after a meal. Examination revealed bulbar weakness and areflexic tetraplegia. Respiratory failure developed, requiring intubation and mechanical ventilation. Brain magnetic resonance imaging (MRI) showed a heart-shaped region of diffusion abnormality, characteristic of BMP infarction. Cerebral angiography showed an occluded left vertebral artery with unilateral left-sided origin of ASA. The patient required tracheostomy and percutaneous gastrostomy tube and was discharged to rehabilitation, with little improvement of his tetraplegia at 3-month follow-up. A 43-year-old woman presented to the emergency department with acute onset of lower-extremity paresthesia and history of upper respiratory infection 2 weeks prior. Initial examination findings included bulbar weakness, dysphagia, hyporeflexia, and generalized weakness. After admission, she had severe respiratory distress and required intubation. Lumbar puncture was evaluated for Guillain-Barré syndrome, but cerebrospinal fluid protein concentration was normal. Changes on diffusion-weighted MRI of the brain showed the characteristic heart-shaped BMP infarction, indicating occlusion of a unilateral ASA. She required tracheostomy and percutaneous gastrostomy tube placement, with no paralysis resolution. CONCLUSION: Acute BMP infarction may present with flaccid tetraplegia mimicking neuromuscular disorders. When the infarction is recognized early, intravenous thrombolysis can be considered to reduce morbidity of this rare stroke subtype.

Granulomatous Angiitis of the Central Nervous System Associated with Hodgkin's Lymphoma: Case Report and Literature Review.

Granulomatous angiitis of the central nervous system (GACNS) is a rare cerebrovascular disorder. It usually presents with multifocal neurologic symptoms symptoms including stroke, encephalopathy, and headache. A limited number of case reports describe neurological deficits resulting from GACNS as the manifesting symptoms of Hodgkin's lymphoma (HL). We describe the case of a patient with neurological symptoms from GACNS that led to the diagnosis of HL, as well as a literature review focusing on the association between GACNS and HL.

groEL is a suitable genetic marker for detecting Vibrio parahaemolyticus by loop-mediated isothermal amplification assay.

A groEL gene-based loop-mediated isothermal amplification (LAMP) assay was developed to detect Vibrio parahaemolyticus in contaminated seafood and water. The assay was optimized and conducted at 63°C for 40 min using Bacillus stearothermophilus (Bst) DNA polymerase, large fragment. Amplification was analysed via multiple detection methods, including opacity, formation of white precipitate, DNA intercalating dyes (ethidium bromide and SYBR Green I), metal ion-binding indicator dye, calcein, and 2% agarose gel electrophoresis. A characteristic ladder-like band pattern on agarose gel and the desired colour changes when using different dyes were observed in positive cases, and these were species-specific for V. parahaemolyticus when compared with other closely related Vibrio spp. The limit of detection (LoD) of this assay was 100 fg per reaction, 100-fold higher than that for conventional polymerase chain reaction (PCR). When tested on artificially contaminated seafood and seawater, the LoDs of the LAMP assay were 120 and 150 fg per reaction respectively, and those of conventional PCR were 120 and 150 pg per reaction respectively. Based on our results, the groEL gene-based LAMP assay is rapid, specific, sensitive, and reliable for detecting V. parahaemolyticus, and it could be used in field diagnosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The loop-mediated isothermal amplification (LAMP) assay using groEL gene (an abundant, highly conserved gene and member of the groESL chaperone gene family) provided rapid, species-specific and highly sensitive method for detecting Vibrio parahaemolyticus, the leading causal agent of seafood-borne diseases worldwide. Moreover, groEL LAMP revealed high efficiency than conventional PCR assay for V. parahaemolyticus using template both from pure culture and artificially contaminated seafood and water, which indicated the applicability in the field and environmental screening purpose for the organism.

Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis.

The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.

Mutational spectrum of Korean patients with corneal dystrophy.

Corneal dystrophy typically refers to a group of rare hereditary disorders with a heterogeneous genetic background. A comprehensive molecular genetic analysis was performed to characterize the genetic spectrum of corneal dystrophies in Korean patients. Patients with various corneal dystrophies underwent thorough ophthalmic examination, histopathologic examination, and Sanger sequencing. A total of 120 probands were included, with a mean age of 50 years (SD = 18 years) and 70% were female. A total of 26 mutations in five genes (14 clearly pathogenic and 12 likely pathogenic) were identified in 49 probands (41%). Epithelial-stromal TGFBI dystrophies, macular corneal dystrophy and Schnyder corneal dystrophy (SCD) showed 100% mutation detection rates, while endothelial corneal dystrophies showed lower detection rates of 3%. Twenty six non-duplicate mutations including eight novel mutations were identified and mutations associated with SCD were identified genetically for the first time in this population. This study provides a comprehensive characterization of the genetic aberrations in Korean patients and also highlights the diagnostic value of molecular genetic analysis in corneal dystrophies.

Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial.

The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were -0.78 % and -1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.

Vitamin D deficiency in Parkinson's disease patients with orthostatic hypotension.

OBJECTIVES: The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 (calcitriol) between the two groups. RESULTS: Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. CONCLUSIONS: Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.

An epidemiological study of androgenic alopecia in 3114 Korean patients.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

Identification of stringent response-related and potential serological proteins released from Bacillus anthracis overexpressing the RelA/SpoT homolog, Rsh Bant.

RelA and SpoT synthesize ppGpp, a key effector molecule that facilitates the adaptation of bacteria to nutrient starvation and other stresses, known as the stringent response. To investigate the role of Rsh Bant , a putative RelA/SpoT homolog (encoded by BAS4302) in Bacillus anthracis, we examined the alteration of the secretome profiles after the overexpression of a functional His-Rsh Bant protein in the B. anthracis strain Sterne at the stationary growth phase. In the ppGpp-deficient E. coli mutant strain CF1693, overexpression of Rsh Bant restored a ppGpp-dependent growth defect on minimal glucose media. The secretome profiles obtained using a two-dimensional electrophoresis (2-DE) analysis were altered by overexpression of Rsh Bant in B. anthracis. Among the 66 protein spots differentially expressed >1.5-fold, the 29 proteins were abundant for further identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Functional categorization of those proteins implicated their involvement in various biological activities. Taken together, our results imply that overexpression of a functional His-Rsh Bant can lead to the increased levels of intracellular ppGpp in B. anthracis, resulting in the significant changes in its secretome profiling. The stringent response-controlled proteins identified are likely useful as potential targets for serodiagnostic applications.

Charge distribution studies in the epi-cadmium neutron induced fission of 238Pu.

Studies on charge distribution have been carried out in the epi-cadmium neutron induced fission of 238Pu for the first time. Experimentally fractional cumulative yields (FCY) and independent yields (IY) of various fission products have been measured by using an off-line γ-ray spectrometric technique. From the FCY values, the charge distribution parameters such as the isobaric width parameter (σZ), most probable charge (ZP) and the charge polarization (ΔΖEXPT) as a function of fragment mass were obtained. On the other hand, from the measured IY values, isotopic width parameter (σA), the most probable mass (AP) and the elemental yields (YZ) of Sn, Sb, Te, I, Xe, Cs, Ba, La, Ce and Pr were determined by using a non-linear fit. From the YZ values, the proton even-odd effect (δp) was obtained for the first time. The isobaric and isotopic charge distribution parameters in the 238Pu(nf, f) reaction were compared with the similar data in the thermal neutron induced fission of 238Pu and other actinides to examine the role of excitation energy.

Independent isomeric yield ratios of fission products in the epi-cadmium neutron induced fission of 239Pu.

Measurement of independent isomeric yield ratios (IR) of 128,130,132Sb, 131,133Te, 132.134,136I, 135Xe and 138Cs have been carried out for the first time in the epi-cadmium neutron induced fission of 239Pu by using an off-line gamma-ray spectrometric technique. The average neutron energy () of the epi-cadmium reactor neutron spectrum is 1.9 MeV. From the IR values, root mean square fragment angular momenta (JRMS) were deduced by using spin dependent statistical model analysis. Effect of nuclear structure on JRMS values was examined. The present data in the epi-cadmium neutron induced fission of 239Pu were compared with the similar data in the thermal neutron induced fission of 239Pu to examine the role of excitation energy on JRMS values.

Charge distribution studies in the epi-cadmium neutron induced fission of 235U.

For the first time, charge distribution studies have been carried out in the epi-cadmium neutron induced fission of 235U by measuring the fractional cumulative yields (FCY) and independent yields (IY) of various fission products. An off-line γ-ray spectrometric technique was used for the measurements. The average energy of the epi-cadmium neutron spectrum is 1.9 MeV. From the FCY values, the isobaric width parameter (σZ), most probable charge (ZP) and the charge polarization (ΔΖEXPT) as a function of fragment mass were obtained. Similarly, from the IY values, isotopic width parameter (σA), the most probable mass (AP) and the elemental yields (YZ) of Sn, Sb, Te, I, Xe, Cs, Ba, La, Ce and Pr were determined by using a non-linear fit. From the YZ values, the proton even-odd effect (δp) was obtained for the first time. The present data in the 235U(n, f) reaction were compared with the similar data in the 235U(nth, f) and 238U(n, f) reactions as well as of other actinides to examine the role of excitation energy and pairing effect.

Independent isomeric yield ratios of fission products in the epi-cadmium neutron induced fission of 235U.

In the epi-cadmium neutron induced fission of 235U, independent isomeric yield ratios (IR) of fission products 130,132Sb, 131,133Te, 134,136I, 135Xe and 138Cs have been measured by using an off-line gamma-ray spectrometric technique. The average neutron energy of the epi-cadmium reactor neutron spectrum is 1.9 MeV. From the IR values, the root mean square fragment angular momenta (JRMS) were deduced by using spin dependent statistical model analysis. The IR and JRMS values of considered fission products in the epi-cadmium neutron induced fission of 235U were compared with the literature data in the thermal neutron induced fission of 235U to examine the influence of excitation energy on nuclear structure effect.

Independent isomeric yield ratios of fission products in the epi-cadmium neutron induced fission of 233U.

The independent isomeric yield ratios (IR) of 128,130,132Sb, 131,133Te, 132,134,136I, 135Xe and 138Cs have been measured in the epi-cadmium neutron induced fission of 233U by using an off-line gamma-ray spectrometric technique. The average neutron energy of the epi-cadmium reactor neutron spectrum is 1.9 MeV. The root mean square fragment angular momenta (JRMS) were deduced from the IR values by using spin dependent statistical model analysis. The IR and JRMS values of considered fission products in the epi-cadmium neutron induced fission of 233U were compared with the literature data in the thermal neutron induced fission of 233U to examine the influence of excitation energy on nuclear structure effect.

Tick-borne pathogens isolated from ticks, rodents, and a shrew in Gangwon and Gyeonggi provinces in the Republic of Korea.

The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.