Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan–Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.

Iniencephaly

Iniencephaly is an uncommon form of neural tube defects which is characterized by retroflexion of the head and absence of neck as a consequence of defective closure of the vertebral body and arch. Multiple identified risk factors for its causation include environmental, genetic and drugs. We report a case of 38-year-old woman with prior history of still birth and abortions who presented at 35 weeks of gestation with lower abdominal pain and high blood pressure. Mother had consanguineous marriage. Her hypothyroidism was untreated in the first and second trimester. She delivered an iniencephalic baby girl via emergency c-section with multiple malformations at 38 weeks gestation secondary to fetal cardiac deceleration. Baby survived for less than 18 hours. In this case, proper antenatal care and follow up visits were needed along with postnatal genetic and pathological evaluation including assessment of risk factors. Appropriate management is important to prevent complications and recurrence in subsequent pregnancies.

Présentation atypique de la trichotillomanie : un cas clinique avec revue de la littérature

Trichotillomania is a chronic mental illness with an elevated rate of psychiatric comorbidities. Patients with Trichotillomania often have a low insight putting them at risk for serious health problems such as depression, social dysfunction, body damage, malnutrition, even death in severe cases if untreated. Not all patients have access to health care, most of them live in difficult environments with different cultural variations and attitudes toward mental illness making them more vulnerable. The literature suggests that there is a variety of psychotherapies and medications that may help in managing Trichotillomania. The present case is of a woman with no prior history of mental illness, who was brought by her father for behavioral issues. During her evaluation we observed various symptoms associated with different pathologies, exemplifying the difficulties to diagnose individuals with Trichotillomania and to prepare a treatment plan for them

Metastatic Breast Signet-Ring Cell Carcinoma from a Colonic Primary: Review of a Rare Case Report

Introduction: Colonic signet-ring cell carcinoma is a distinctive rare subtype of adenocarcinoma with a predilection for early metastasis. Among the rare extramammary metastatic adenocarcinomas to the breast, colonic signet-ring cell carcinomas constitute a small percentage. The distinction of a primary from a secondary breast signet ring cell carcinoma is indispensable since it may result in different therapeutic approaches. Here we presented a rare case of metastatic breast signet-ring cell carcinoma from a rectal origin and review its distinctive histopathologic features. Case Presentation: A 37-year-old woman presented with a breast mass 3 months after undergoing low anterior resection surgery to remove a rectal mass, diagnosed as signet ring cell carcinoma. Histopathologic examination of the core needle breast mass biopsy revealed tumor cells with signet-ring cell cytomorphology. The performed immunohistochemistry confirmed carcinoma of colonic origin. Conclusions: Colorectal signet-ring cell carcinoma is a rare and aggressive tumor. Its metastatic spread is most seen in the intra-abdominal area, with seldom reported cases of breast metastasis. Histologically, it can mimic a primary breast carcinoma, especially if no prior history of colonic origin exists. Accurate diagnosis is important since these 2 entities carry different therapeutic management. Proper immunophenotyping, obtaining a thorough clinical history and imaging studies facilitate a correct diagnosis.

Prevalence and Duration of Post-Concussive Headaches in a Pediatric Sports Clinic: A Cross-sectional Study

ObjectiveWe aim to identify the potential risk factors associated with increased susceptibility for persistent post-concussive headaches.BackgroundConcussions are common, but complex, traumatic brain injuries seen in pediatric athletes of all ages & skill levels & occur in a wide variety of athletic settings. These mild traumatic brain injuries often have neurologic sequelae, including headaches. Although athletes are advised to rest, duration of post-concussive symptoms is often unpredictable.Design/MethodsWe conducted a cross sectional study on patients with head injury aged 5–18 years presented to pediatric concussion clinic (N = 603) from September 2013 to Dec 2018. We excluded patients with skull fractures and intracranial hemorrhage. The data was compiled & analyzed using frequency, Pearson correlation test, chi square & ANOVA test using IBM SPSS- 26.ResultsPatient cohort consisted of 364 males & 239 females. The age range for males was 5–18 years (Mean age ± SD: 13.45 ± 2.86) & for females was 6–18 years (Mean age ± SD: 13.97 ± 2.84). There was statically significant association between various age groups & presence of headache at 3 & 6 months (p < 0.05). Out of all ages, age group 5–8 years had highest risk of persistent headache while the age group 14–18 years reported headaches at 3 months but then resolution of symptoms by one year (p < 0.05). Females were more likely than males (of all ages) to have persistent headaches despite treatment (p = 0.00). There was also a statistically significant difference between loss of consciousness, prior history of headaches & prior history of concussions towards the development of persistent headaches (p < 0.05). Furthermore, football, soccer and basketball had significantly more headaches compared to other sports related injuries (p = 0.001).ConclusionsThere was a statistically higher risk of developing persistent headaches for females and those with a history of prior headache, prior concussion, younger age, and those playing football, soccer or basketball.

A History of Mild Traumatic Brain Injury Is Associated With a a More Severe Long-term Migraine Phenotype

ObjectiveThis study aimed to investigate the effect of prior mTBI on the clinical features and disability in patients presenting with migraine.BackgroundHead injury is a risk factor for chronic migraine (CM) and migraine is a risk factor for persistent headache after mild traumatic brain injury (mTBI).Design/MethodsOf 2,161 migraine patients without a diagnosis of post-traumatic headache (PTH) who participated in the American Registry for Migraine Research (ARMR) between February 2016 and March 2020, 1,120 answered questions about a history of mTBI. After controlling for age, gender, and having CM, demographics, headache characteristics, Patient Health Questionnaire-2 (PHQ-2) score, General Anxiety Disorder-7 (GAD-7) grade, and Migraine Disability Assessment Scale (MIDAS) scores were compared between those with a history of mTBI to those without.ResultsAmong 1,098 migraine patients, 37.6% (n = 413) had a history of mTBI. The patients with mTBI were more likely to have CM (p = 0.004), dizziness (p = 0.003), vertigo (p = 0.009), and difficulty finding words (p < 0.001). Patients with mTBI had significantly greater scores on the MIDAS (58.6 ± 52.6 vs 50.0 ± 47.8, p = 0.034) and PHQ-2 (1.6 ± 1.8 vs 1.3 ± 1.6, p = 0.012), and had significantly higher proportion of moderate to severe GAD-7 grade (21.7% vs 17.1%, p = 0.017) compared to those without mTBI.ConclusionsIn patients presenting with migraine, a prior history of mTBI was associated with a diagnosis of chronic migraine, disability, anxiety and depression severity, as well as dizziness, vertigo, and word finding difficulty. A history of mTBI should be assessed in patients presenting with migraine, and people with migraine who have a high exposure risk to mTBI, should be aware of the potential for migraine progression and psychiatric symptoms after mTBI.

Impact of Playing Surface on Concussion Symptoms in Young American Football Players

ObjectiveTo identify differences in symptoms following sports-related concussion (SRC) on natural grass vs artificial turf in youth and adolescent football players.BackgroundThere is continued interest in reducing risk of SRC in football, with playing surface being one potentially modifiable factor. It is estimated that 15–30% of concussions result from helmet-to-ground contact, and some studies have suggested a higher incidence of SRC on grass in competitive contact sports compared to turf. To our knowledge, our study is the first to investigate reported post-concussive symptoms after SRC as they relate to playing surface.Design/MethodsData were prospectively collected from the North Texas Concussion Registry (ConTex), a longitudinal multi-institutional concussion database. We selected male football players between the ages of 10 and 24 who sustained a helmet-to-ground SRC (GCS 13–15) on either grass or turf. Pre-injury information and post-concussive symptoms (Graded Symptom Checklist from the SCAT-5) were collected at an initial in-person visit within 2 weeks of injury and via electronic follow up at 3 months.ResultsFifty-eight participants were included (grass = 32, turf = 26), and groups were similar in age (p = 0.089), time since injury (p = 0.500), history of headache (χ2 = 0.167), and prior history of concussion (χ2 = 0.868). Athletes who sustained SRC on grass reported significantly higher scores on the Graded Symptom Checklist (p = 0.018, mean 26.0 vs 11.4) and higher numbers of distinct symptoms (p = 0.013, mean 10.2 vs 5.5) compared to those who sustained SRC on turf. Symptoms that were rated significantly higher after SRC on grass included headache (p = 0.010), phonophobia (p = 0.014), dizziness (p = 0.001), fatigue (p = 0.021), blurred vision (p = 0.001), feeling “in a fog” (p = 0.014), difficulty remembering (p = 0.004), and feeling emotional (p = 0.041).ConclusionsYouth and adolescent football players who sustain SRC on grass report higher post-concussive symptom severity and burden. Elucidating differential effects of SRC on grass vs turf is important, as competitive playing surface is a modifiable risk factor.

Microsaccadic Fixational Eye Movements as an Oculomotor Marker for Concussion

ObjectiveTo identify whether concussion causes abnormalities in fixational eye movements, specifically the generation of microsaccades.BackgroundMicrosaccades are microscopic rapid eye movements that occur normally with attempted fixation. However, changes in microsaccade rate, magnitude, etc have been linked with neurologic and ophthalmic pathologies.Design/MethodsWe collected baseline data for college athletes (n = 116) at Sterling College (Sterling, KS) as they reported for the physical examination before the beginning of the athletic season. None of the athletes had a prior history of concussion. Concussion patients (n = 86) were selected from patients who had an initial visit for concussion at a private concussion clinic. Patients were included if they presented within 50 days of injury. All participants were between 18 and 23 years of age. For each participant we measured the number of saccades generated, the size and speed of the micro saccades, the area covered and the ratio of vertical-to-horizontal direction component of the fixational eye movements, using a 250 Hz video-eye tracker mounted inside a HTC Vive VR headset. Participants were instructed to fixate on a central dot for 140 seconds, in 20-second intervals. We performed a logistic regression with the log-transformed oculomotor characteristics as independent variables and concussion yes/no as dependent variables. Errors are presented as standard error from the mean.ResultsThe average microsaccade magnitude was higher in concussed than in non-concussed participants (1.85 ± 0.12° vs 1.32 ± 0.06°, p < 0.001). Similarly, the fixational eye movements (microsaccades + drifts) of concussed patients tended to cover a more vertical area during fixation periods (vertical-to-horizontal ratio of 3.49 ± 0.94 vs 1.12 ± 0.04, p < 0.005).ConclusionsOculomotor testing, specifically microsaccades is a potential marker for concussion. Concussion patients present larger and more vertical eye movements during fixation.

Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients

Toll-like receptors (TLR) are crucial components in the initiation of innate immune responses to a variety of pathogens, triggering the production of pro-inflammatory cytokines and type I and II interferons, which are responsible for innate antiviral responses. Among the different TLRs, TLR7 recognizes several single-stranded RNA viruses including SARS-CoV-2. We and others identified rare loss-of-function variants in X-chromosomal TLR7 in young men with severe COVID-19 and with no prior history of major chronic diseases, that were associated with impaired TLR7 signaling as well as type I and II IFN responses. Here, we performed RNA sequencing to investigate transcriptome variations following imiquimod stimulation of peripheral blood mononuclear cells isolated from patients carrying previously identified hypomorphic, hypofunctional, and loss-of-function TLR7 variants. Our investigation revealed a profound impairment of the TLR7 pathway in patients carrying loss-of-function variants. Of note, a failure in IFNγ upregulation following stimulation was also observed in cells harboring the hypofunctional and hypomorphic variants. We also identified new TLR7 variants in severely affected male patients for which a functional characterization of the TLR7 pathway was performed demonstrating a decrease in mRNA levels in the IFNα, IFNγ, RSAD2, ACOD1, IFIT2, and CXCL10 genes.

Separate Roles for State and Trait Anxiety in the Formation of SHU Syndrome: Testing a Moderated Mediation Hypothesis

It has been proposed that state anxiety, aroused when an inmate is initially placed in restrictive housing, interacts with the sequestering Special Housing Unit (SHU) environment to overtax the individual's already limited coping resources, and promotes later emotional problems and psychological deterioration. This study tested a SHU syndrome hypothesis with a moderated mediation path analysis of 69 male inmates. Results revealed that group status (general population vs. restrictive housing) interacted with state anxiety to increase trait anxiety and ineffective coping, which then gave rise to higher staff ratings of psychological disturbance in inmates with no prior history of mental illness.