Prevalence of depression and anxiety among adult patients with multiple sclerosis at Riyadh City,Saudi Arabia

Objectives:To determine the prevalence of depression and anxiety in adult multiple sclerosis patients attending tertiary facilities in Riyadh, Saudi Arabia.Methods:This is a cross-sectional study conducted among MS patients in Riyadh City, Saudi Arabia. A self-administered questionnaire was distributed among MS patients at Prince Sultan Military Medical City in Riyadh, Saudi Arabia between April 2020 and January 2021. The questionnaire consisted of socio-demographic characteristics and the Hospital Anxiety and Depression Scale (HADS). Univariate using Chi-square test and multivariate regression analysis had been performed to determine the factors associated with anxiety and depression among MS patients.Results:A total of 328 MS patients took part in the study. The most prevalent age group was 36–45 years old (38.4%), with over 70% of the participants being females. Anxiety and depression were shown to be prevalent in MS patients at 42.9 percent and 58.8 percent, respectively. According to statistical tests, being less educated and having partial to severe disability was linked to an increased rate of anxiety and depression, whereas being female was more prone to anxiety symptoms but not depression.Conclusion:Depression was more frequent than anxiety. As a result, while assessing psychiatric diseases in the study group, depression/anxiety may be expected to be more frequent amongst those of greater disability.

Multiple sclerosis (MS) is a central nervous system demyelinating disease caused by an immunological response. Depression and anxiety are more common in patients with multiple sclerosis (PWMS) than in the general population, ^1-4 which is a well-known phenomenon. However, we believe that these illnesses are under-recognized in PWMS because several MS symptoms overlap with depression and anxiety, making detection more difficult. Fatigue, sleeplessness, anorexia, memory loss, and concentration problems are all common symptoms of depression, MS, or both. ^5,6 Furthermore, the symptoms of MS might mislead self-report rating scales designed to detect depression and anxiety, resulting in false positives or negatives. ^5,6 Moreover, depression in PWMS can impair their quality of life (QOL), medication adherence, and compliance, worsening their prognosis. ^7-9 Suicidal thoughts and attempts are also common. ^10-13 The hospital Anxiety and Depression Scale is a one-of-a-kind measure for detecting anxiety and depression while taking into account both disorders’ possible confounders, and it has been validated for use in PWMS. ⁶ Depression is a significant mood illness that affects many people. It creates severe symptoms that impact how you feel, think, and handle day-to-day tasks like working, sleeping, and eating. ¹⁴ In PWMS, the lifetime prevalence of depression in up to 50%, ³ compared to 10.8% in the general population. ¹⁵ The cause of depressive disorders in people with MS is unknown. However, it is assumed to be complex, with psychological, social, and neurological aspects - as well as immunologic and genetic factors - all having a part. ¹⁶ Furthermore, depression can have a severe impact on these patients’ health by raising the severity of their symptoms and reducing their compliance with therapy and follow-up, both of which have an impact on their medical costs. ⁹ In addition to a decreased quality of life (QOL), cognitive impairment, and an increased risk of suicide, especially when anxiety is present. ^7,10,11 Furthermore, PWMS have a 10-year lower life expectancy than the general population of the same age. ² Patients, caregivers, and care providers should not underestimate the impact of sadness and anxiety on PWMS. Improved identification, diagnosis, and treatment in medical offices, where people with mood disorders are frequently seen for the first time, can assist to improve these negative outcomes. ¹⁷ Unfortunately, despite convincing evidence of its high incidence, greater influence on prognosis, and quality of life, depression and anxiety are still underdiagnosed and undertreated. ¹³ The goal of this study is to find out how common depression and anxiety are among adult patients with multiple sclerosis in Riyadh, Saudi Arabia. We’ll also see if there’s a link between Hospital Anxiety and Depression Scale (HADS) score and patients’ demographical, socio-educational, and MS-related characteristics, as well as MS duration, Immunomodulatory type, and EDSS scores.     

Neural representation of the parent–child attachment from infancy to adulthood

Attachment theory is built on the assumption of consistency; the mother–infant bond is thought to underpin the life-long representations individuals construct of attachment relationships. Still, consistency in the individual’s neural response to attachment-related stimuli representing his or her entire relational history has not been investigated. Mothers and children were followed across two decades and videotaped in infancy (3–6 months), childhood (9–12 years) and young adulthood (18–24 years). In adulthood, participants underwent functional magnetic resonance imaging while exposed to videos of own mother–child interactions (Self) vs unfamiliar interactions (Other). Self-stimuli elicited greater activations across preregistered nodes of the human attachment network, including thalamus-to-brainstem, amygdala, hippocampus, anterior cingulate cortex (ACC), insula and temporal cortex. Critically, self-stimuli were age-invariant in most regions of interest despite large variability in social behavior, and Bayesian analysis showed strong evidence for lack of age-related differences. Psycho–physiological interaction analysis indicated that self-stimuli elicited tighter connectivity between ACC and anterior insula, consolidating an interface associating information from exteroceptive and interceptive sources to sustain attachment representations. Child social engagement behavior was individually stable from infancy to adulthood and linked with greater ACC and insula response to self-stimuli. Findings demonstrate overlap in circuits sustaining parental and child attachment and accord with perspectives on the continuity of attachment across human development.     

Sleep Apnea and Atrial Fibrillation: Role of the Cardiac Autonomic Nervous System

Sleep apnea is highly associated with atrial fibrillation (AF), and both diseases are highly prevalent in the United States. The mechanistic underpinnings that contribute to their association remain uncertain, but numerous possible mechanisms have been proposed, including dysfunction of the cardiac autonomic nervous system (ANS). Studies have reported that apnea induces hyperactivity of the ANS, leading to increases in AF susceptibility. This review compiles the latest evidence on the role of the ANS in sleep-apnea-induced AF.     

Optimizing T-cell receptor avidity with somatic hypermutation

Adoptive transfer of T cells that have been genetically modified to express an antitumor T-cell receptor (TCR) is a potent immunotherapy, but only if TCR avidity is sufficiently high. Endogenous TCRs specific to shared (self) tumor-associated antigens (TAAs) have low affinity due to central tolerance. Therefore, for effective therapy, anti-TAA TCRs with higher and optimal avidity must be generated. Here, we describe a new in vitro system for directed evolution of TCR avidity using somatic hypermutation (SHM), a mechanism used in nature by B cells for antibody optimization. We identified 44 point mutations to the Pmel-1 TCR, specific for the H-2D^b-gp100_25-33 melanoma antigen. Primary T cells transduced with TCRs containing two or three of these mutations had enhanced activity in vitro. Furthermore, the triple-mutant TCR improved in vivo therapy of tumor-bearing mice, which exhibited improved survival, smaller tumors and delayed or no relapse. TCR avidity maturation by SHM may be an effective strategy to improve cancer immunotherapy.     

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model

Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.     

The TopClosure? 3S System, for skin stretching and a secure wound closure

The principle of stretching wound margins for primary wound closure is commonly practiced and used for various skin defects, leading at times to excessive tension and complications during wound closure. Different surgical techniques, skin stretching devices and tissue expanders have been utilized to address this issue. Previously designed skin stretching devices resulted in considerable morbidity. They were invasive by nature and associated with relatively high localized tissue pressure, frequently leading to necrosis, damage and tearing of skin at the wound margins. To assess the clinical effectiveness and performance and, to determine the safety of TopClosure? for gradual, controlled, temporary, noninvasive and invasive applications for skin stretching and secure wound closing, the TopClosure? device was applied to 20 patients for preoperative skin lesion removal and to secure closure of a variety of wound sizes. TopClosure? was reinforced with adhesives, staples and/or surgical sutures, depending on the circumstances of the wound and the surgeon's judgment. TopClosure? was used prior to, during and/or after surgery to reduce tension across wound edges. No significant complications or adverse events were associated with its use. TopClosure? was effectively used for preoperative skin expansion in preparation for dermal resection (e.g., congenital nevi). It aided closure of large wounds involving significant loss of skin and soft tissue by mobilizing skin and subcutaneous tissue, thus avoiding the need for skin grafts or flaps. Following surgery, it was used to secure closure of wounds under tension, thus improving wound aesthetics. A sample case study will be presented. We designed TopClosure?, an innovative device, to modify the currently practiced concept of wound closure by applying minimal stress to the skin, away from damaged wound edges, with flexible force vectors and versatile methods of attachment to the skin, in a noninvasive or invasive manner.     

A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93 ± 0.06 and specificity of 0.91 ± 0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.