Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine ligand-receptor pairs that drive disease.

Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, including AIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.

Development and validation of a simple method for the determination of triamcinolone acetonide in nasal spray.

A rapid, convenient, and sensitive analytical technique for quantitative analysis of triamcinolone acetonide (TAC) in pharmaceutical nasal spray dosage form using the blue tetrazolium colorimetric reaction and UV spectrophotometric method was developed and validated. Beer's law of the developed method was proven in the concentration range of 10-40 µg/mL and showed a specific linear relationship with coefficient value R2 = 0.998. The LOQ level was 9.99 µg/mL, with (RSD = 0.26%). From precision assay, RSD values have been obtained for the repeatability and intermediate precision, which were found to be (RSD = 1.65%) and (RSD = 2.01%), respectively, indicating that the method is reproducible. Recovery studies showed mean recoveries in the range of (100.08-103.65 %), meeting the acceptance criteria for accuracy. In addition, we compared the results of the developed method UV-Vis spectrophotometric procedure with those of a well-established official USP analytical procedure (HPLC), and the results showed good agreement. The proposed UV method represents a potential alternative to the official USP analytical assay procedure (HPLC) for estimating TAC in nasal spray forms. Furthermore, it has the potential to be implemented in routine use for rapid qualitative and quantitative determinations for TAC.

Understanding the burden of mental and physical health disorders on families: findings from the Saudi National Mental Health Survey.

OBJECTIVE: To assess prevalence and correlation of factors of family burden associated with mental and physical disorders in the general population of Saudi Arabia. SETTING AND PARTICIPANTS: A secondary analysis of data from the Saudi National Mental Health Survey (SNMHS). OUTCOME MEASURES: Mental and physical health disorders of first-degree relatives and objective (time, financial) and subjective (distress, embarrassment) family burden. RESULTS: We found significant caregiver burden for family members with mental health disorders. Around one-third of the sample was providing care for a family member with a health issue. Within this group, 40% had a mental health diagnosis. 73% of the study population reported experiencing some form of burden as a result of the care they are obligated to provide for their family members. We found the highest burden on male caregivers, in providing care for family members with serious memory disorders, mental retardation, schizophrenia or psychosis, followed by, alcohol and drug disorders, anxiety, depression or manic depression. CONCLUSION: Our findings for family burden were statistically significant, indicating potential negative impact on caregiver coping ability with the demands of caring for family members with health issues. A comprehensive review of national mental health policies is required to integrate aspects of community mental health promotion, scale-up prevention, screening interventions and social support to protect against the difficulties of mental illness and reduce the burden on caregivers, the family, society, health system and the economy.

Risk of Postpartum Depression: The Considerable Role of Maternal Health Status and Lifestyle.

Women's health issues are complex and require collaborative efforts to unravel some of these complexities. This study aims to identify the incidence risk of Postpartum Depression (PPD) in a national sample of women in Saudi Arabia and the relationship with several health status, lifestyle, and sociodemographic factors. A cross-sectional study with an online questionnaire format assessed the risk of postpartum depression using the Edinburgh Postnatal Depression Scale (EPDS) and included several questions on postpartum health status and lifestyle factors. Of the 550 women who responded to the survey 75% scored within range of risk for PPD (≥12). We found significant associations between family income, younger baby age, birth difficulty, having family support, level of physical activity, and the risk for PPD (p < 0.05). Urgent attention and resources should be directed towards screening and treatment for PPD in the healthcare system. The development of programs for awareness, education, and support of postpartum mothers in the Kingdom of Saudi Arabia is also required.

Dairy products intake and the risk of postpartum depression among mothers: A pilot study.

Introduction: Postpartum depression is a prevalent consequence of childbirth experienced by many women. There has been evidence linking dairy intake during pregnancy with a reduction in postpartum depression symptoms. However, there is still a lack of understanding regarding the effects of postpartum dairy consumption on postpartum depression. Objectives: To examine whether dairy products intake and calcium in dairy is associated with postpartum depression. Methods: A pilot study was conducted (n = 49 postpartum women). A food frequency questionnaire was used to evaluate the participants' consumption of calcium and dairy products during pregnancy, and the Edinburgh Postnatal Depression Scale was used to screen for postpartum depression symptoms. Results: Of 49 participants, 26 (53%) were at risk for postpartum depression (Edinburgh Postnatal Depression Scale ⩾ 12). Consuming >1 serving of Laban per day is significantly associated with reduced risk of postpartum depression (odds ratio = 0.01, 95% confidence interval [0, 0.3]). Total dairy intake >1 serving per day is significantly associated with reduced risk of postpartum depression (odds ratio = 0.17, 95% confidence interval [0.03, 0.83]). No significant association was found between the postpartum intake of milk, cheese, yogurt, or calcium and postpartum depression. Conclusion: Our findings indicate that higher total dairy intake was associated with a lower likelihood of postpartum depression. Further assessment with a larger sample size of participants could provide additional insight into the potential of dietary dairy to mitigate postpartum depression.

Paraneoplastic syndromes associated with classic Hodgkin lymphoma, a systematic literature review.

PNS are uncommon manifestations of cancer. The current literature about these syndromes in the setting of cHL is disintegrated. A systematic literature review of all published literature was conducted. One hundred twenty-eight patients from 115 publications met the inclusion/exclusion criteria. Eight-five patients were of the NS subtype (66.4%). The most frequent clinical presentation of the PNS was CNS manifestation (25.8%). The majority of patients were diagnosed with the cHL and PNS simultaneously (42.2%). In 33.6% of patients, the lymphoma diagnosis preceded the PNS diagnosis. In 16.4% of patients, the PNS diagnosis preceded the lymphoma diagnosis. The presence of PNS antibodies was reported in 35 patients (27.3%). Age older than 18 was associated with higher prevalence of PNS. The CR rate of the lymphoma was 77.3%. The complete resolution rate of the PNS was 54.7%. Relapse of lymphoma was reported in 13 patients, and recurrence of the PNS upon relapse was reported in 10/13 patients.

Efficacy and Safety of Bedside Removal of Tunnelled Hemodialysis Catheter by Noninterventional Nephrologists among Adult Patients in the King Abdulaziz University Hospital Hemodialysis Centre in Jeddah: A Retrospective Cohort Study.

This study aimed to assess the efficacy and safety of bedside removal of tunnelled hemodialysis catheter (TDC) by noninterventional nephrologists among adult patients. It is a retrospective study that involved 53 patients from March 2020 to February 2022 at the King Abdulaziz University Hospital (KAUH) Hemodialysis Centre in Jeddah, Saudi Arabia. Of the 53 participants, 60.4% were male and 40.6% female, and their mean age was 50.94 ± 18.89 years. The most common comorbidities were hypertension (HTN) in 47 (88.7%), diabetes mellitus (DM) in 24 (45.3%), and DM and HTN together in 23 (43.4%) patients. The most common site of TDC removal was the right internal jugular vein (77.4%). In 84.9% of the cases, the TDC was removed as an inpatient procedure, and in the majority of the cases (64.2%), the TDC was removed by a noninterventional nephrologist. The most common reasons for TDC removal were sepsis or clinical concerns for infection (64.2%) and TDC not needed (20.8%) due to recovery of the renal function or access maturation. Most patients (96.2%) suffered no complications; only one of 34 (%) patients with catheter removal by a noninterventional nephrologist had bleeding, which required more observation and monitoring before discharge on the same day. Our study revealed that the bedside TDC removal was well tolerated with a minimal complication rate.

Light-Related Cutaneous Symptoms of Erythropoietic Protoporphyria and Associations With Light Sensitivity Measurements.

Importance: Erythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients. Objectives: To describe the cutaneous symptoms of erythropoietic protoporphyria (EPP) and to determine if these symptoms are associated with the degree of light sensitivity. Design, Setting, and Participants: This was a cross-sectional study of adolescent and adult (≥15 years) patients with EPP across the US conducted by a single academic hospital via a remotely administered survey, measurements of light sensitivity by light dosimetry and by text message symptom assessments. Data analyses were conducted from November 2020 to April 2022. Exposures: Sunlight exposure. Main Outcomes and Measures: Self-reported symptoms and association with measured light sensitivity. Results: The study sample consisted of 35 patients with EPP (mean [SD] age, 39.1 (15.5) years; 21 [60%] female; 14 [40%] male; 35 [100%] White individuals). The patients' median [range] skin tone was 3.0 (1.0-8.0), based on self-reporting from 1 (lightest) to 12 (darkest). A total of 24 participants completed the light dosimeter measurements. Phototoxic reactions were characterized by pain (97%; 34 patients), burning (97%; 34), tingling (97%; 34), pruritus (83%; 29), allodynia (89%; 31), improvement of symptoms with cold (89%; 31), achiness (24%; 12), fatigue (46%; 16), mild swelling (83%; 29), severe swelling (63%; 22), erythema (51%; 18), petechiae (40%; 14), skin cracking (43%; 15), scabbing (46%; 16), scarring (66%; 23), and other chronic skin changes (40%; 14). Patients with EPP reported that their hands, feet, and face were most sensitive to light and that their shoulders and legs were least sensitive; 25.7% (9 patient) reported no chronic skin changes, and 5.7% (2 patients) reported never having had any visible symptoms. None of these findings varied with the degree of light sensitivity except that lower overall light sensitivity was associated with lower ranked sensitivity of the neck and arms. Conclusions and Relevance: The findings of this cross-sectional study suggest that patients with EPP have distinctive cutaneous symptoms that may aid in identification of this underdiagnosed disease. Characteristic EPP symptoms include light-induced cutaneous burning pain and occasional swelling, particularly over the hands, with a prodrome of pruritus and paresthesias. Minimal skin changes or the absence of visible skin changes during reactions to light, including lack of erythema, do not exclude an EPP diagnosis nor suggest low EPP disease burden.

Quality of Work Life of Magnetic Resonance Imaging Technologists: A Cross-Sectional Study.

Quality of Work Life is a multi-dimensional discipline that is concerned with the quality of life in the workplace. This study aimed to assess quality of work-life level and identify the correlation between its dimensions and Job and Career Satisfaction. The study used the 32-item WRQoL-2 tool, a questionnaire consisting of 6 subscales: Job and Career Satisfaction, Control at Work, Home-Work Interface, General Wellbeing, Stress at Work, and Work Conditions, to assess for these correlations. 57 Magnetic Resonance Imaging Technologists (MRITs) (100%) responded to the questionnaire. The study found a high level of QWL among MRITs (66.2%, 3.31/5). The level of the JCS was high (71.6%, 3.59/5), with significant correlations between JCS and WCS, CAW, HWI, and GWB. An inverse relationship was noted between SAW and JCS. Further research on QWL is advised to diagnose and provide recommendation to resolve issues that may adversely affect the quality of healthcare service provision.

The Effect of Dairy Products and Nutrient Intake after Childbirth on the Risk of Postpartum Depression.

Previous studies have shown an association between the intake of dairy products during pregnancy and reduced symptoms of postpartum depression (PPD). However, the effect of postpartum intake of dairy products on PPD is not fully understood. This study evaluates the effects of dairy products and nutrient intake after childbirth on the risk of PPD. A cross-sectional survey-based study was conducted asking participants to fill out a food frequency questionnaire (FFQ) to assess intake of dairy products and other nutrients. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for PPD symptoms. Out of 530 participants, almost three-quarters subjectively reported PPD (N = 395, 74.11%). The risk of PPD was relatively high for a Q1 level of consumption of all four dairy products and other nutrients, and from Q2 to Q4 there appeared to be an increase in the risk of PPD as consumption increased. However, after adjustment for confounding factors, there was no significant association between postpartum intake of dairy products and other nutrients and PPD. The results indicate that the potential of dairy products and nutrient intake to reduce PPD are minimal. Further longitudinal and intervention studies of dairy products and other (particularly anti-depressants) nutrients are required to draw firm conclusions about their associations with the risk of PPD.

The Demographic Data and Prevalence of Thromboembolic Events Among Inflammatory Bowel Disease Patients in Buraydah, Al-Qassim Region.

Introduction Inflammatory bowel diseases (IBD) (Crohn's disease (CD) and ulcerative colitis (UC)) are considered among the commonest gastrointestinal (GI) tract diseases manifesting with chronic, recurring episodes of gut inflammation, especially in the colon. Each disease has its pattern, symptoms, severity of pain, extension, management, and prognosis. However, these diseases share most of the various complications, including the GI tract and extending it to other systems such as musculoskeletal, skin, liver, and pulmonary systems. Objectives We aim to identify the demographic data, prevalence, risk factors, clinical presentation, and management (medications given and investigations ordered) of thromboembolic events (TEE) among inflammatory bowel disease patients at King Fahad Specialist Hospital (KFSH) in Buraydah, Al-Qassim, Saudi Arabia. Materials and methods This is a retrospective, cross-sectional study. All included patients with IBD who meet the inclusion criteria between January 2020 and January 2022 in KFSH were reviewed, and data were analyzed using the Statistical Package for the Social Sciences (SPSS) Statistics version 23.0 (IBM Corp., Armonk, NY, USA). Results A total of 187 participants were included in the current study. The mean age of the participants ± standard deviation (SD) was 28.7 ± 10.8 years old. Of the participants, 107 (57.2%) were males. A total of 121 (64.7%) participants were diagnosed with Crohn's disease (CD), 56 (29.9%) with ulcerative colitis (UC), and 10 (5.3%) with both CD and UC. In 156 (83%) participants, the duration of the disease was 1-5 years. Among the IBD patients, two (1.1%) had TEE in the interval resolution middle and left portal vein, as well as the inferior mesenteric vein. The majority of the participants (73.3%) were with no history of comorbid conditions. The most reported clinical symptoms were chest pain as reported by 3.2% of the participants. Abdominal computed tomography (CT) was the most reported method of diagnosis as reported by 35.8% of the participants. Of the participants, 8.6% used heparin prophylactically, 0.5% used heparin as a treatment, and 0.5% used enoxaparin as a treatment. Moreover, 20.3% of the participants used prophylactic treatment, whereas about 79.7% did not use prophylactic treatment. Old age, extensive disease, colorectal surgery, and pregnancy were not found to be associated with thromboembolic events (p = 1.000, 0.400, 0.164, and 0.053, respectively). Age, gender, and nationality were not significantly associated with thromboembolic events (p = 0.915, 1.000, and 1.000, respectively). Conclusion Despite IBD being one of the emerging health concerns in the Kingdom of Saudi Arabia, records showed that the prevalence of thromboembolic events was found to be lower when compared to the prevalence reported in the relevant multinational studies. The was no difference in factors affecting the development of thromboembolic events between IBD patients and the general population. Recommendations We should stress raising awareness of IBD patients about their condition, the increased risks of developing thromboembolic events, and the proper prevention methods.

Physical activity patterns among women during the postpartum period: an insight into the potential impact of perceived fatigue.

BACKGROUND: Regular participation in physical activity (PA) improves physical well-being and reduces the risk of contracting noncommunicable diseases. However, fatigue could negatively impact the PA participation of women in their postpartum period. This study delineated the levels of perceived fatigue and characterized the association between fatigue and the PA patterns of postpartum women. METHODS: A cross-sectional study was conducted using an online questionnaire distributed to postpartum women living in Saudi Arabia. Their perceived postpartum fatigue (PPF) was assessed using the fatigue severity scale; their PA, using the short form of the International Physical Activity Questionnaires; and their postpartum depression, using the Edinburgh Postnatal Depression Scale. Descriptive statistics were expressed as the mean ± standard deviation for normally distributed variables and as the median (interquartile range) for non-normally distributed variables. Between-group differences were tested using the Mann-Whitney U test for independent samples. To determine the relationship between the study variables, Spearman's rho correlation coefficient was calculated. Multiple linear regression analysis was performed to explain the role of fatigue severity as an independent predictor of the variance of the PA level. RESULTS: A total of 499 postpartum women were divided into the PPF group (43%), who self-reported fatigue, and the non-PPF group (57%), who self-reported no fatigue. There was a significant difference in the median of vigorous PA, and moderate PA which were significantly higher in the non-PPF group than in the PPF group. The women with PPF reported less engagement in walking and a longer sitting duration than the women without PPF. High fatigue severity was associated with lower moderate PA (ß = -10.90; p = .005; R2 = .21) and vigorous PA (ß = -04; p < .001; R2 = .13). These associations remained significant in the regression model after adjustment for the mother's depression score; age; number of children; body mass index (kg/m2); employment status; intake of vitamins B1 (thiamin), C, and D and of Omega-3; and walking metabolic equivalent. CONCLUSION: PPF may reduce the PA of postpartum women. Strategies targeting PPF may buffer its harmful impacts, and thus, improve postpartum women's health.

Topical treatments for erythromelalgia.

Erythromelalgia is a rare neurovascular disease that causes episodes of pain, redness, and warmth in the extremities, and can be debilitating. Currently, there is no universally effective treatment for erythromelalgia. As the precise etiology of erythromelalgia remains obscure, presently available treatments are aimed at alleviating erythromelalgia's wide-ranging symptoms. In general, topical therapies for erythromelalgia are preferred for their more limited side effects and for those with contraindications to systemic therapies. This review will summarize the current topical therapies available to treat erythromelalgia and discuss emerging therapies based on our growing understanding of erythromelalgia pathophysiology.

Successful Treatment of Brunsting-Perry Cicatricial Pemphigoid With Dupilumab.

Brunsting-Perry is a rare variant of cicatricial pemphigoid, characterized by subepidermal bullae localized to the head and neck. Currently, treatment relies on non-specific immunosuppression, which in many cases, does not lead to a remission of treatment or significant clinical improvement. Dupilumab, a human monoclonal antibody against IL-4 receptor alpha, has been shown to provide relief of allergic inflammatory lesions and is the first biologic agent approved for the treatment of moderate-to-severe atopic dermatitis. We present the case of a 63-year-old patient with history of Brunsting-Perry cicatricial pemphigoid who proved refractory to multiple conventional therapies but was successfully treated with a dupilumab regimen of 300 mg every two weeks. This case suggests the potential role of dupilumab in the management of Brunsting-Perry cicatricial pemphigoid. J Drugs Dermatol. 2021;20(10):1113-1115. doi:10.36849/JDD.6032.

Gene Expression Analysis in Four Dogs With Canine Pemphigus Clinical Subtypes Reveals B Cell Signatures and Immune Activation Pathways Similar to Human Disease.

Pemphigus is a group of autoimmune-mediated mucocutaneous blistering diseases characterized by acantholysis. Pemphigus has also been recognized in dogs and shares similar clinical characteristics and variants with human pemphigus. While relationships between human and canine pemphigus have been reported, gene expression patterns across species have not been described in the literature. We sought to perform gene expression analysis of lesional skin tissue from four dogs with various forms of pemphigus to examine gene expression during spontaneous disease in dogs. We found increased T and B cell signatures in canine pemphigus lesions compared to controls, as well as significant upregulation of CCL3, CCL4, CXCL10, and CXCL8 (IL8), among other genes. Similar chemokine/cytokine expression patterns and immune infiltrates have been reported in humans, suggesting that these genes play a role in spontaneous disease. Direct comparison of our dataset to previously published human pemphigus datasets revealed five conserved differentially expressed genes: CD19, WIF1, CXCL10, CD86, and S100A12. Our data expands our understanding of pemphigus and facilitates identification of biomarkers for prediction of disease prognosis and treatment response, which may be useful for future veterinary and human clinical trials.

Comparison of fluid resuscitation weight-based dosing strategies in obese patients with severe sepsis.

OBJECTIVE: This study aims to compare the composite outcome of progression to septic shock between 30 mL/kg/ideal body weight (IBW) versus 30 mL/kg/non-IBW fluid resuscitation dosing strategies in obese patients with severe sepsis. METHODS: We retrospectively evaluated obese patients admitted to an academic tertiary care center for the management of severe sepsis. Patients were included if they had a fluid bolus order placed using the sepsis order set between Oct 2018 and Sept 2019. The primary objective was the composite of progression to septic shock, defined as either persistent hypotension within 3 h after the conclusion of the 30 mL/kg fluid bolus administration or the initiation of vasopressor(s) within 6 h of the bolus administration. RESULTS: Of 72 included patients, 49 (68%) were resuscitated using an IBW-based and 23 (32%) using a non-IBW-based dosing strategy. There were similar rates of progression to septic shock in the IBW and non-IBW groups (18% vs. 26%; p = 0.54). Median ICU and hospital LOS in the IBW group versus non-IBW group were (0 [IQR 0] vs. 0 [IQR 0 to 4] days; p = 0.13) and (6 [IQR 3 to 10] vs. 8 [IQR 5 to 12] days; p = 0.07), respectively. In-hospital mortality rates were similar between the groups. CONCLUSIONS: Our study results suggest that in obese septic patients, fluid administration using an IBW-dosing strategy did not affect the progression to septic shock.

Correcting hypokalaemia in a paediatric patient with Bartter syndrome through oral dose of potassium chloride intravenous solution.

Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalaemia. Hypokalaemia is defined as low serum potassium concentration ˂3.5 mmol/L, which may lead to arrhythmia and death if left untreated. The aim of this case report was to normalize serum potassium concentration without the need for intravenous intervention. A 5-month-old male of 2.7 kg body weight diagnosed with Bartter syndrome was admitted to the general paediatric ward with acute severe hypokalaemia and urinary tract infection. The main challenge was the inability to administer drugs through intravenous route due to compromised body size. Therefore, we shifted the route of administration to the nasogastric tube/oral route. A total of 2 mL of concentrated intravenous potassium chloride (4 mEq potassium) were dissolved in distilled water and administered through nasogastric tube. Serum potassium concentration was rapidly normalized, which culminated in patient discharge. In conclusion, shifting drug administration from intravenous to oral route in a paediatric patient with Bartter syndrome includes numerous advantages such as patient convenience, minimized risk of cannula-induced infection, and reduced nurse workload.