38.3 Primary Immunodeficiencies: When is it not just "JIA".

Juvenile Idiopathic Arthritis (JIA) is sometimes considered a diagnosis of exclusion as the name signifies that no cause is evident for this form of arthritis. Despite this JIA has some classical clinical features and many categories are defined based on the phenotype. Since there is no diagnostic test for JIA, diseases that can mimic JIA, including Primary Immunodeficiencies (PID) can sometimes be misdiagnosed as JIA. The clues to suspecting PIDs are early age of onset, presence of family history, increased susceptibility to infections, unusual features like urticaria, interstitial lung disease, sensorineural hearing loss and poor response to conventional therapy, amongst others. This review will highlight the basics of PIDs and will discuss PIDs that can present with arthritis and hence can be confused with JIA.

Caregiver burden in families of children with juvenile idiopathic arthritis in India.

Juvenile Idiopathic Arthritis (JIA) causes caregiver burden on families with children affected with it. Our study aimed to explore this multifaceted burden in the Indian context. In this cross-sectional study, we administered the Hindi translated CAREGIVER questionnaire to adult caregivers in the families of JIA patients ≤ 18 years. The responses to the 28 items were used to calculate the burden scores in various dimensions. The relationship of the global burden scores with demographic and socioeconomic factors were analysed. Non parametric tests were used. Two hundred twenty-one caregivers participated with a median age of 39 years (IQR 32-45). This included 116 fathers, 50 mothers, 32 brothers, 18 uncles, three grandfathers, one sister, and one grandmother. The JIA patients had a median age of 15 (12-17) years, and the male-to-female ratio was 3.2:1. Enthesitis-related arthritis was the predominant subtype (72.4%). Most caregivers (70.6%) expressed sadness at diagnosis, and 29.9% continued to express sadness. Nearly two-thirds (65.6%) had to borrow money from others. More than half (59.3%) of the caregivers neglected their health, and 9.0% became sick. Male gender of the child, systemic JIA subtype, low socioeconomic status, high disease activity, extra-articular damage, high parent-reported disease activity and poor quality of life were associated with higher global caregiver burden. JIA has a significant emotional, social, economic, and labour impact on caregivers. Economic and psychosocial support needs to be given to family caregivers caring for children with JIA.

Individualized stress detection using an unmodified car steering wheel.

In-car passive stress sensing could enable the monitoring of stress biomarkers while driving and reach millions of commuters daily (i.e., 123 million daily commuters in the US alone). Here, we present a nonintrusive method to detect stress solely from steering angle data of a regular car. The method uses inverse filtering to convert angular movement data into a biomechanical Mass Spring Damper model of the arm and extracts its damped natural frequency as an approximation of muscle stiffness, which in turn reflects stress. We ran a within-subject study (N = 22), in which commuters drove a vehicle around a closed circuit in both stress and calm conditions. As hypothesized, cohort analysis revealed a significantly higher damped natural frequency for the stress condition (P = .023, d = 0.723). Subsequent automation of the method achieved rapid (i.e., within 8 turns) stress detection in the individual with a detection accuracy of 77%.

Supervision of a self-driving vehicle unmasks latent sleepiness relative to manually controlled driving.

Human error has been implicated as a causal factor in a large proportion of road accidents. Automated driving systems purport to mitigate this risk, but self-driving systems that allow a driver to entirely disengage from the driving task also require the driver to monitor the environment and take control when necessary. Given that sleep loss impairs monitoring performance and there is a high prevalence of sleep deficiency in modern society, we hypothesized that supervising a self-driving vehicle would unmask latent sleepiness compared to manually controlled driving among individuals following their typical sleep schedules. We found that participants felt sleepier, had more involuntary transitions to sleep, had slower reaction times and more attentional failures, and showed substantial modifications in brain synchronization during and following an autonomous drive compared to a manually controlled drive. Our findings suggest that the introduction of partial self-driving capabilities in vehicles has the potential to paradoxically increase accident risk.

A Suite of Mobile Conversational Agents for Daily Stress Management (Popbots): Mixed Methods Exploratory Study.

BACKGROUND: Approximately 60%-80% of the primary care visits have a psychological stress component, but only 3% of patients receive stress management advice during these visits. Given recent advances in natural language processing, there is renewed interest in mental health chatbots. Conversational agents that can understand a user's problems and deliver advice that mitigates the effects of daily stress could be an effective public health tool. However, such systems are complex to build and costly to develop. OBJECTIVE: To address these challenges, our aim is to develop and evaluate a fully automated mobile suite of shallow chatbots-we call them Popbots-that may serve as a new species of chatbots and further complement human assistance in an ecosystem of stress management support. METHODS: After conducting an exploratory Wizard of Oz study (N=14) to evaluate the feasibility of a suite of multiple chatbots, we conducted a web-based study (N=47) to evaluate the implementation of our prototype. Each participant was randomly assigned to a different chatbot designed on the basis of a proven cognitive or behavioral intervention method. To measure the effectiveness of the chatbots, the participants' stress levels were determined using self-reported psychometric evaluations (eg, web-based daily surveys and Patient Health Questionnaire-4). The participants in these studies were recruited through email and enrolled on the web, and some of them participated in follow-up interviews that were conducted in person or on the web (as necessary). RESULTS: Of the 47 participants, 31 (66%) completed the main study. The findings suggest that the users viewed the conversations with our chatbots as helpful or at least neutral and came away with increasingly positive sentiment toward the use of chatbots for proactive stress management. Moreover, those users who used the system more often (ie, they had more than or equal to the median number of conversations) noted a decrease in depression symptoms compared with those who used the system less often based on a Wilcoxon signed-rank test (W=91.50; Z=-2.54; P=.01; r=0.47). The follow-up interviews with a subset of the participants indicated that half of the common daily stressors could be discussed with chatbots, potentially reducing the burden on human coping resources. CONCLUSIONS: Our work suggests that suites of shallow chatbots may offer benefits for both users and designers. As a result, this study's contributions include the design and evaluation of a novel suite of shallow chatbots for daily stress management, a summary of benefits and challenges associated with random delivery of multiple conversational interventions, and design guidelines and directions for future research into similar systems, including authoring chatbot systems and artificial intelligence-enabled recommendation algorithms.

Increased Rates of Septic Shock, Cardiac Arrest, and Mortality Associated With Chronic Steroid Use Following Anterior Cervical Discectomy and Fusion for Cervical Stenosis.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is an established treatment modality for cervical spondylosis. Many patients are on immunosuppressant therapy in the management of various inflammatory spinal pathologies and other comorbid conditions. The impact of chronic steroid use on postoperative complications has not been examined in cervical fusion procedures. The objective of this study was to identify specific postoperative complications associated with steroid/immunosuppressant use following ACDF for cervical stenosis. METHODS: A multi-institutional surgical registry was queried to identify 5377 patients with ACDF diagnosed with cervical stenosis. Patients were stratified into cohorts with a history of steroid/immunosuppressant use for chronic conditions (n = 198, 3.3%) versus those who did not (n = 5179, 96.7%). Propensity-score matching without replacement was implemented to control for preoperative demographics and comorbidities. Pearson χ2 and Fischer exact tests were used in comparing the prevalence of demographics, comorbidities, and complication rates. RESULTS: Upon propensity matching, increased rates of pulmonary embolisms (0.51% vs 0.00%, P = .025), cardiac arrest requiring resuscitation (1.01% vs 0.10%, P = .020), septic shock (0.51% vs 0.00%, P = .025), and mortality (1.52% vs 0.20%, P = .009) in the postoperative 30-day period in patients on chronic steroid/immunosuppressant use were observed. CONCLUSIONS: The results indicate that steroid use/immunosuppression in patients with ACDF has a higher associated rate of pulmonary embolisms, cardiac arrest, septic shock, and mortality. The risk of mortality and these other complications should be carefully considered prior to operative intervention. Future research may investigate steroid-tapering protocols that reduce the rate of infection and other postoperative complications in the subset of immunosuppressed ACDF patients. CLINICAL RELEVANCE: By elucidating the complication rates of ACDF patients on steroids for cervical stenosis, orthopedic surgeons can better stratify patients for risk of postoperative morbidity. Surgeons may have deeper risk-benefit discussions with these specific patients before they elect to have the operation.

Impact of diabetes mellitus on surgical complications in patients undergoing revision total knee arthroplasty: Insulin dependence makes a difference.

OBJECTIVES: Assessing the effects of diabetes mellitus (DM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-dependent diabetes mellitus (IDDM) on revision TKA (rTKA) has become increasingly imperative due to the increased rates of revisions associated with DM. This study sought to identify complications in rTKA that were independently associated with NIDDM/IDDM compared to non-diabetic (Non-DM) patients and whether IDDM was associated with specific postoperative complications compared to NIDDM. METHODS AND MATERIALS: 16,428 rTKA patients were identified from the ACS-NSQIP database from 2005 to 2016 and stratified into three separate cohorts. 12,922 (78.66%) were Non-DM, 2335 (14.21%) had NIDDM, and 1171 (7.13%) had IDDM. Univariate analyses were utilized to assess for differences in demographics, preoperative comorbidities, and postoperative complication rates. Multivariate logistic regression analyses were then employed to control for significant differences in patients characteristics to assess NIDDM and IDDM as independent risk factors for complications in comparison to Non-DM. IDDM was further analyzed as a risk factor in comparison to NIDDM for the purpose of elucidating the impact of insulin dependence on risk for postoperative complications. RESULTS: NIDDM was an independent risk factor for deep incisional surgical site infections (Odds Ratio (OR): 2.477) and urinary tract infections (UTI) (OR 1.862) (p < 0.05). Compared to NIDDM, IDDM was independently associated with greater risk for pneumonia (OR 2.603), septic shock (OR 6.597), blood transfusions (OR 1.326), and an extended length of stay (OR: 1.331) (p < 0.05). IDDM additionally increased the risk for acute renal failure (OR 3.269) and cardiac arrest (OR 3.268) (p < 0.05) when compared to Non-DM. DM patients overall had increased rates of worse outcomes and infectious complications. CONCLUSION: Although differences between diabetes and non-diabetes rTKA patients were seen, differences in complication rates between diabetes patients further divided based on insulin dependence status were also noted. Future work examining whether targeting perioperative glucose levels <200 mg/dL in DM rTKA patients decreases infectious complications is warranted. Future work analyzing the role of tranexamic acid administration and 24-h postoperative antibiotics in rTKA IDDM patients may be warranted given the elevated risk of pneumonia, septic shock, and blood transfusions.

Surgical complications associated with congestive heart failure in elderly patients following primary hip hemiarthroplasty for femoral neck fractures.

INTRODUCTION: Although there are reports of the impact of congestive heart failure (CHF) on total knee arthroplasty and total hip arthroplasty, there is a lack of literature analyzing CHF in hip hemiarthroplasty (HHA) procedures. The main objective of this study was to evaluate the effect of CHF on risks for complications following HHA for the treatment of FNF. METHODS: The ACS-NSQIP database was queried for all patients who had undergone HHA from 2005 to 2016. Patients were propensity-matched without replacement in a 1:1 manner based on age and gender. Pearson's Chi squared tests and Fischer's exact tests were utilized to compare differences in demographics, comorbidities, and complication rates. Multivariate logistic regression analyses were used to assess the impact of CHF as an independent risk factor for postoperative complications. RESULTS: A propensity-matched cohort of 537 (4.24%) non-CHF patients was generated in order to analyze differences between the two cohorts. CHF was found to be a significant independent risk factor for pneumonia (p = 0.003), progressive renal insufficiency (p = 0.040), myocardial infarctions (p = 0.050), extended length of stay (≥ 5 days) (p < 0.001), and mortality (p < 0.001). CONCLUSION: This study has established CHF as an independent risk factor for various postoperative complications following HHA for the treatment of FNF. Although orthopedic surgeons may decline to perform elective procedures on CHF patients, FNFs require urgent surgical intervention. Therefore, it is important to be aware of various increased risks of certain complications in this subset patient population.

Evaluation of Xpert®Mycobacterium tuberculosis/rifampin in sputum-smear negative and sputum-scarce patients with pulmonary tuberculosis using bronchoalveolar lavage fluid.

CONTEXT: Sputum smear-negative and sputum-scarce pulmonary tuberculosis (PTB) is a diagnostic challenge. Xpert® Mycobacterium tuberculosis/rifampin (MTB/RIF) provides a rapid diagnosis on high-quality biological specimen obtained by bronchoscopy. AIMS: The aim of this study is to evaluate Xpert® MTB/RIF on bronchoalveolar lavage (BAL) fluid in sputum smear-negative and sputum-scarce PTB patients. SETTINGS: Tertiary care hospital in India. DESIGN: This was prospective observational study. MATERIALS AND METHODS: Between January 2015 and November 2016, we prospectively recruited sputum-smear negative and sputum-scarce patients under evaluation for PTB and performed BAL. Sensitivity, specificity, positive, and negative predictive values were calculated for the diagnosis of PTB on BAL fluid for acid-fast bacilli smear and Xpert® MTB/RIF using liquid culture as the reference standard and compared to the final diagnosis based on composite reference standard. Sensitivity, specificity, and predictive values were calculated with 95% class intervals. McNemar's test was used for comparison of sensitivities. RESULTS: Of the 60 patients included, 52 (88.3%) had a final diagnosis of PTB and 16 (26.7%) were culture confirmed. Xpert® MTB/RIF had a sensitivity and specificity of 81% (54%-96%) and 73% (56%-85%) in culture confirmed cases; 46% (32%-60%) and 100% (63%-100%) for the final diagnosis; 32% (17%-51%) and 100% (54%-100%) in culture negative cases, respectively. Culture had a sensitivity of 32% (20%-47%) for the final diagnosis. CONCLUSIONS: In sputum smear-negative and sputum-scarce patients with clinico-radiological features of PTB Xpert® MTB/RIF has good sensitivity for diagnosis on BAL fluid. It is useful even when cultures are negative.

Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a suppressor of innate immunity in Arabidopsis thaliana.

BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45-1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. RESULTS: Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45-1 plants do indeed show enhanced immunity. CONCLUSION: We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.