Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.

CAR T cell therapy has revolutionized the treatment of a spectrum of blood-related malignancies. However, treatment responses vary among cancer types and patients. Accurate monitoring of CAR T cell dynamics is crucial for understanding and evaluating treatment efficacy. Positron emission tomography (PET) offers a comprehensive view of CAR T cell homing, especially in critical organs such as lymphoid structures and bone marrow. This information will help assess treatment response and predict relapse risk. Current PET imaging methods for CAR T require genetic modifications, limiting clinical use. To overcome this, we developed an antigen-based imaging approach enabling whole-body CAR T cell imaging. The probe detects CAR T cells in vivo without affecting their function. In an immunocompetent B cell leukemia model, CAR-PET signal in the spleen predicted early mortality risk. The antigen-based CAR-PET approach allows assessment of CAR T therapy responses without altering established clinical protocols. It seamlessly integrates with FDA-approved and future CAR T cell generations, facilitating broader clinical application.

A CAR enhancer increases the activity and persistence of CAR T cells.

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2). This selectively induces IL-2 signaling in CAR T cells upon antigen-CAR binding, enhancing T cell activation and antitumor activity while reducing IL-2-associated toxicities. We show that the BCMA CAR-E selectively binds CAR T cells and increases CAR T cell proliferation, clearance of tumor cells and development of memory CAR T cells. The memory cells retain the ability to re-expand upon restimulation, effectively controlling tumor growth upon rechallenge. Mechanistic studies reveal the involvement of both CAR and IL-2 receptor endodomains in the CAR-E mechanism of action. The CAR-E approach avoids the need for specific engineering and enables CAR T cell therapy with lower cell doses.

Pemphigus Disease and Area Index: Unmet needs in the real-world management of pemphigus.

Over the past few decades, a number of scoring instruments have been developed to assess the severity and activity of autoimmune bullous diseases (AIBDs) (Daneshpazhooh et al., 2019; Nili et al., 2020; Nili et al., 2021; Nili et al., 2022). The Pemphigus Disease Area Index (PDAI), developed by the International Pemphigus Definitions Group, is an easy-to-use, quick, and reliable method for determining pemphigus severity. As a reliable and effective tool in clinical trials, PDAI may also have some limitations and might require some revisions to be used on a daily basis. Here, we propose some recommendations to improve the use of PDAI in the clinical setting.

Prediction of Foot Ulcers Using Artificial Intelligence for Diabetic Patients at Cairo University Hospital, Egypt.

Introduction: In Egypt, diabetic foot ulcers markedly contribute to the morbidity and mortality of diabetic patients. Accurately predicting the risk of diabetic foot ulcers could dramatically reduce the enormous burden of amputation. Objective: The aim of this study is to design an artificial intelligence-based artificial neural network and decision tree algorithms for the prediction of diabetic foot ulcers. Methods: A case-control study design was utilized to fulfill the aim of this study. The study was conducted at the National Institute of Diabetes and Endocrine Glands, Cairo University Hospital, Egypt. A purposive sample of 200 patients was included. The tool developed and used by the researchers was a structured interview questionnaire including three parts: Part I: demographic characteristics; Part II: medical data; and Part III: in vivo measurements. Artificial intelligence methods were used to achieve the aim of this study. Results: The researchers used 19 significant attributes based on medical history and foot images that affect diabetic foot ulcers and then proposed two classifiers to predict the foot ulcer: a feedforward neural network and a decision tree. Finally, the researchers compared the results between the two classifiers, and the experimental results showed that the proposed artificial neural network outperformed a decision tree, achieving an accuracy of 97% in the automated prediction of diabetic foot ulcers. Conclusion: Artificial intelligence methods can be used to predict diabetic foot ulcers with high accuracy. The proposed technique utilizes two methods to predict the foot ulcer; after evaluating the two methods, the artificial neural network showed a higher improvement in performance than the decision tree algorithm. It is recommended that diabetic outpatient clinics develop health education and follow-up programs to prevent complications from diabetes.

Cord Herniation through the Site of Undiagnosed Thoracic Dermoid Tumour during Spinal Anaesthesia; Report of a Case and Describing Ways to Avoid.

Spinal anaesthesia (SA) is one of the most prevalent types of anaesthetic procedures. There are very few reports of cord herniation through the site of spinal canal stenosis due to tumour. A 33-year-old female presented with acute paraparesis after spinal anaesthesia for caesarean section. Magnetic resonance imaging (MRI) revealed an intradural mass from posterior of T6 to T8-T9 interface. We operated the patient and after laminectomy of T6 to T9, dermoid tumour containing hairs was totally resected and cord was completely decompressed. After 6 months, the patient is without any neurological deficit. Puncturing the dura with cerebrospinal fluid (CSF) in the presence of an extramedullary mass could cause cord herniation through the blockade. In these cases, awareness about related signs even in absence of symptoms or complaints could help us to prevent post-SA neurological deficit.

Infections in Hospitalized Patients with Psoriasis in a Skin Referral Hospital.

INTRODUCTION: Psoriasis and its treatments may predispose patients to various infections. This is considered one of the most significant complications in patients with psoriasis. OBJECTIVES: In the present study, we aimed to determine the prevalence of infection in hospitalized psoriasis patients and its relationship with systemic and biologic treatments. METHODS: All hospitalized patients with psoriasis from 2018 to 2020 in Razi Hospital in Tehran, Iran, were studied and cases of infection were recorded. RESULTS: Overall, 516 patients were studied and 25 types of infection in 111 patients were found. The most common types of infection were pharyngitis and cellulitis, followed by oral candida, urinary tract infections, common cold, fever of unknown origin, and pneumonia. Female sex and pustular psoriasis were significantly associated with infection in psoriatic patients. Those patients who received prednisolone had a higher risk of infection, and those under treatment with methotrexate or infliximab had a lower risk of infection. CONCLUSION: Overall, 21.5% of psoriasis patients in our study had at least one episode of infection. This demonstrates that the prevalence of infection in these patients is not low. Using systemic steroids was associated with a higher risk of infection, while using methotrexate or infliximab was concomitant with a lower risk of infection.

Nail abnormalities in subepidermal blistering diseases: a cross-sectional study.

BACKGROUND: Nail involvement in subepidermal autoimmune blistering diseases (SEABD) is not common. Although these changes can be transient, permanent changes can also occur. This study addresses nail involvement manifestations and their associated factors in patients with SEABD. METHODS: From March 2020 to March 2021, we enrolled 56 patients with SEABD who were being examined at a tertiary skin hospital and checked their nail changes. We investigated the association between the SEABD subtypes and treatments that patients were receiving and the nail abnormalities. Additional factors including age, gender, duration since diagnosis, presence of mucosal involvement, and anti-bp230 and anti-bp180 IgG antibody quantitative levels (in those patients with bullous pemphigoid) were analyzed. RESULTS: The most common nail abnormalities were ridging, onycholysis, and onychoschizia. We observed a lower prevalence of onycholysis in EBA, a lower prevalence of periungual bullae in MMP, and a higher prevalence of scarring loss in EBA. Rituximab and dapsone were effective in preventing onycholysis as well as prednisolone in preventing subungual hematoma. Multiple lesions were found to be more common in the foot digits including great toes, probably because of higher exposure to trauma. CONCLUSIONS: In summary, in patients with SEABD and concomitant nail involvement, the underlying disease control, proper treatment, and avoidance of trauma may be helpful.

Factors associated with the healing time of pemphigus vulgaris oral lesions: A prospective study.

OBJECTIVES: This study determines the healing time of lesions on different locations and the contributing factors to the healing time in patients with pemphigus. METHODS: In this prospective study, newly diagnosed patients with mucosal lesions were included. A dermatologist evaluated the lesions, disease status, side effects and assigned the PDAI. Follow-up visits were conducted monthly until the patient reached complete remission and every three months thereafter. A Tzanck smear was performed on lesions clinically suspected to be herpetic in origin. RESULTS: Sixty patients enrolled in the study with a mean age of 45.9 ± 11.7 years. The buccal lesions took the longest to resolve (73[33.5-105.5] days). However, the posterior pharynx lesions showed the shortest healing time (20[13.0-25.5] days). The likelihood of improvement in buccal and soft palate lesions decreased by 5% and 3% with each additional year of age, respectively. Also, the resolution duration of soft palate lesions was significantly shorter in female patients than males (median of 24.0 days vs. 38.5 days). In contrast, lower gingival lesions resolve significantly faster in male patients by a median of 9 days. Herpes simplex virus infection increases the healing time of lesions by 26 days (median of 55 days vs. 29 days, hazard ratio 2.62, 95% CI: 1.04-5.92). CONCLUSIONS: Buccal and lower gingival lesions are more recalcitrant to treatment, while posterior pharynx lesions heal most rapidly. Furthermore, older age was also associated with a lower rate of lesion improvement.

Comparison of the effectiveness of online supportive parenting intervention (SPACE) and timid to tiger program (FTTT) on childhood anxiety disorders and family accommodation with samples of Iranian parents.

Studies have supported the effectiveness of the From Timid to a Tiger (FTTT) and Supportive Parenting for Anxious Childhood Emotions (SPACE) program in reducing childhood anxiety. This study is the first to compare the effectiveness of the two programs in the treatment of childhood anxiety disorder and reducing family accommodations levels. Parents of children aged 6 to 9 (n = 49, 49% boys) were randomly allocated to either FTTT (n 26) or SPACE (n = 23) groups, and each attended ten online sessions following the manuals of the interventions. Throughout the study, 9 participants dropped out, resulting in a total of 49 participants, and we performed statistical analyses based on data from these 49 participants. The assessment took place pre- and post-treatment and at a ten-week follow-up on parent-rated child anxiety and family accommodation measures. Analyses of variance (repeated measures) and gain scores were conducted to examine the data. The results indicated that both treatments approaches produced significant reductions in outcome measures, and the post-treatment gains of both treatments were maintained at a ten-week follow-up, though when considering the mean differences and effect sizes across the assessment scores and between groups, overall, the FTTT was significantly more effective in reducing child anxiety scores and family accommodation levels. Our results demonstrated that FTTT significantly outperformed the SPACE program in reducing childhood anxiety problems and family accommodation levels.

Coping with weight stigma: Validation of the Persian brief coping responses inventory with Iranian adolescents sample.

Individuals who are overweight or obese encounter frequent weight-related stigma experiences, which are associated with negative health outcomes. In this regard, the Brief Coping Responses Inventory (BCRI) was developed as a measure of core coping responses to weight stigma, with 10 items loading on two subscales of reappraisal and Disengagement coping. The current study aimed to examine the psychometric properties of the Persian BCRI with 253 Iranian school-attending youth (Mage = 15.38, SD ± 0.50; 53% female) who had BMI score over 30. The results of the confirmatory factor analysis supported the originally proposed two-factor model (RMSEA = 0.028; CFI = 0.996; TLI = 0.994), which yielded acceptable internal consistency based on various reliability measures such as Cronbach's alpha coefficients (0.79 and 0.88 for reappraisal and disengagement factors, respectively) and demonstrated the expected convergent and divergent associations with external correlates of interest (e.g., anxiety, depression, and body dissatisfaction scores). This study was also the first one worldwide to examine and report that the originally proposed two-factor model of the BCRI is invariant across gender groups, which allows for examining mean differences in BCRI scores across gender groups. Overall, our results indicated that the BCRI is a valid and reliable measure with a solid factor structure, which could be used to examine the coping reactions to weigh related stigma experiences among youth samples in Iran. Our results may encourage future studies on the psychometrics of the BCRI with other Iranian samples (e.g., university students, community, and clinical samples).

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

Background and Aim: There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods: In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results: Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion: Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.

Adverse outcome and severity of COVID-19 in patients with autoimmune bullous diseases: A historical cohort study.

The ongoing COVID-19 pandemic has raised concerns regarding the outcome of this infection in patients with autoimmune bullous dermatoses (AIBDs) due to effect of drugs used to treat these disorders. This investigation was performed from the onset of the pandemic to June 1, 2021. Patients with AIBDs who contracted COVID-19 were evaluated. A generalized linear model was employed to find the predictors of severe COVID-19 among patients with AIBDs. Ninety-three patients with AIBDs with a mean age of 50.3 years were evaluated. The most COVID-19 related symptoms were tiredness (76.3%) myalgia (69%), and cough (63.4%). During follow-up, the rate of hospitalization and death were 45.2% and 4.3%, respectively. Previous comorbidities (ß = 0.61) and mean prednisolone dosage above 10 mg/day in the last 3 months (ß = 1.10) significantly increased COVID-19 severity. Also, vaccination against SARS-CoV-2 (ß = -1.50) and each passing month from the last rituximab dose decreased severity (ß = -0.02). Notably, 19.3% of the patients developed AIBD flare-ups following COVID-19 infection. Higher prednisone dose and the shorter interval from the last rituximab infusion were determinants of severe COVID-19. Physicians should assess the risk versus the benefits when prescribing the medications. Moreover, vaccination could successfully attenuate COVID-19 severity.

Study of the effects of cognitive behavioral therapy versus dialectical behavior therapy on executive function and reduction of symptoms in generalized anxiety disorder.

INTRODUCTION: The effects of dialectical behavior therapy on generalized anxiety disorder have not been examined to date, whereas cognitive behavioral therapy is a well-known psychotherapy for generalized anxiety disorder. OBJECTIVES: This study investigated the effects of cognitive behavioral therapy versus dialectical behavior therapy on executive function and reduction of symptoms in generalized anxiety disorder. METHOD: In the present study, 72 generalized anxiety disorder patients were randomly assigned to one of two groups: dialectical behavior therapy or cognitive behavioral therapy. Evaluations were performed at baseline, post-test, and three months after interventions as a follow-up. Measures included the Structured Clinical Interview for DSM-IV Axis I disorders, the Generalized Anxiety Disorder scale, the Beck Anxiety Inventory, the Beck Depression Inventory, the Tower of London Task, and the Wisconsin Card Sorting Task.Results: The results of the present study showed that both groups had reduced scores for depression and anxiety and increased scores for executive function after the psychotherapies. These changes were maintained at follow-up. CONCLUSION: Although depression and anxiety symptoms were significantly reduced by cognitive behavioral therapy, dialectical behavior therapy was more effective for improving executive function.

Serum and cervico-vaginal glycodelin concentrations as predictors of successful implantation after embryo transfer.

OBJECTIVE: Evaluation of glycodelin (Gd) concentrations in serum and cervico-vaginal secretions as a predictor for implantation after ICSI. MATERIALS AND METHODS: Prospective study on 50 women undergoing ICSI where long protocol ovarian stimulation was used. Serum and cervico-vaginal lavage Gd concentrations were measured then rates of biochemical and clinical pregnancy were detected and predictive value was evaluated using logistic regression analysis. RESULTS: Using cut-off values of 2.2 ng/ml and 1.9 ng/ml for serum and cervico-vaginal Gd concentrations respectively for biochemical pregnancy and values of 2.7 ng/ml and 1.3 ng/ml respectively for clinical pregnancy, there was no significant difference regarding sensitivity (72% & 56%, and 72% & 89%, respectively and respectively). Specificity was statistically similar for biochemical pregnancy (72% and 89%, respectively) while specificity was significantly higher for clinical pregnancy using cervico-vaginal Gd concentration of 1.3 ng/ml (88%) compared to serum Gd concentration of 1.9 ng/ml (53%). CONCLUSION: Glycodelin appears to be a promising marker for implantation after IVF/ICSI.

Oral isotretinoin combined with topical clobetasol 0.05% and tacrolimus 0.1% for the treatment of frontal fibrosing alopecia: a randomized controlled trial.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia with no promising treatment. OBJECTIVE: To evaluate the additive efficacy of oral isotretinoin to topical treatments. METHODS: Between November 2017 and August 2018, FFA patients were randomly assigned to receive either isotretinoin (20 mg/d) plus topical treatments (clobetasol 0.05% and tacrolimus 0.1%) or monotherapy with topical treatments. Treatments' efficacy was evaluated through Frontal Fibrosing Alopecia Severity Index (FFASI) after two and 6 months. RESULTS: From 38 participants, 28 patients completed the study. Facial papules improved after 6 months (p value < .001) in the isotretinoin group. Moreover, frontotemporal hairline (p values for frontal < .001; R lateral: 0.03; L Lateral: 0.02), total scalp margins, total additional features' scores, and total combined (p value < .001 for all) improved more in the isotretinoin group than in the control group. Frontal band improved in the treatment group (p value: .02). Frontal margin (p value: .01), R lateral (p value: .01), total scalp (p value < .01), and combined total scores (p value: .01) worsened in the control group. Isotretinoin-related side-effects included lip dryness, telogen effluvium, and malaise. LIMITATIONS: Small sample size and lost to follow-up. CONCLUSION: Isotretinoin combined with topical treatments is more effective than monotherapy with clobetasol and tacrolimus for FFA. CLINICAL TRIAL CODE: (IRCT.ir) IRCT2017091736173N1.

Comparing efficacy and safety of potassium hydroxide 5% solution with 5-fluorouracil cream in patients with actinic keratoses: a randomized controlled trial.

BACKGROUND: Actinic keratosis (AK) is a pre-cancerous skin lesion, associated with development of squamous cell carcinoma. Current treatment options are limited. OBJECTIVES: To compare the efficacy and safety of topical 5-fluorouracil cream (5-FU) and potassium hydroxide 5% (KOH) in the treatment of AK. METHODS: Eighteen patients with AK applied KOH solution or 5-FU on each side of their scalp/face, randomly. The efficacy and safety of these treatments were compared. RESULTS: Thirteen (118 lesions) and ten (83 lesions) patients were successfully followed for one and three months, respectively. After one month, KOH showed a better clinical response (81% vs. 58%; p-value = 0.007) and dermoscopic response (KOH, 65% vs. 5-FU, 46%; p-value = 0.04); while no differences were noted after three months (clinical response, 83% vs.70%, p-value = 0.1; dermoscopic response, 76% vs. 59%, p-value = 0.1). No significant differences in the recurrence rate of the lesion between the two groups were noted at the end of the third month (p-value = 0.5). Regarding the safety of the treatments, the risk of developing erythema, scaling, sand swelling was higher in 5-FU group (p-value < 0.0001, for all), while more patients in KOH group had erosion and ulcer (p-value < 0.001 for both). KOH was up to 96% less expensive than 5-FU. LIMITATIONS: Low number of patients and short-term follow-up limited the analysis. CONCLUSION: KOH solution offers a faster and less expensive resolution of AK lesions than does 5-FU. CLINICAL TRIAL CODE (IRCT.IR): IRCT20180909040978N1.

Study of the effects of cognitive behavioral therapy versus dialectical behavior therapy on executive function and reduction of symptoms in generalized anxiety disorder

Abstract Introduction The effects of dialectical behavior therapy on generalized anxiety disorder have not been examined to date, whereas cognitive behavioral therapy is a well-known psychotherapy for generalized anxiety disorder. Objectives This study investigated the effects of cognitive behavioral therapy versus dialectical behavior therapy on executive function and reduction of symptoms in generalized anxiety disorder. Method In the present study, 72 generalized anxiety disorder patients were randomly assigned to one of two groups: dialectical behavior therapy or cognitive behavioral therapy. Evaluations were performed at baseline, post-test, and three months after interventions as a follow-up. Measures included the Structured Clinical Interview for DSM-IV Axis I disorders, the Generalized Anxiety Disorder scale, the Beck Anxiety Inventory, the Beck Depression Inventory, the Tower of London Task, and the Wisconsin Card Sorting Task.Results: The results of the present study showed that both groups had reduced scores for depression and anxiety and increased scores for executive function after the psychotherapies. These changes were maintained at follow-up. Conclusion Although depression and anxiety symptoms were significantly reduced by cognitive behavioral therapy, dialectical behavior therapy was more effective for improving executive function.

Oral simvastatin combined with narrowband UVB for the treatment of psoriasis: A randomized controlled trial.

Psoriasis is a common chronic skin condition, which is an immune-related hyperproliferative disorder. Among the different treatments for psoriasis, statins have been found to reduce the severity of the disease. Accordingly, fluvastatin and simvastatin are known to have anti-inflammatory effects by inhibiting inflammatory cytokines and lymphocyte function. Narrowband ultraviolet B (NB-UVB) is known as an effective and safe modality for psoriasis treatment. In this double blind, randomized controlled trial, we investigated the efficacy and safety of adding simvastatin to NB-UVB phototherapy in patients with psoriasis. Forty-eight patients with psoriasis undergoing NB-UVB phototherapy were randomly divided into placebo groups; one received oral simvastatin, and the other received a placebo for 12 weeks. Psoriasis severity was assessed with the Psoriasis Area and Severity Index (PASI) and Dermatology Life and Quality Index (DLQI). Both groups showed a significant decline in PASI score after 6 and 12 weeks compared to the baseline. The differences in reducing PASI score and DLQI between the two groups were not significant neither at week sixth nor 12th. In addition, DLQI decreased significantly in the placebo group at week 12th. In contrast with previous studies, we did not find any additional effects for oral simvastatin5 in treating psoriasis with NB-UVB. Also, an insignificant difference in the improvement of quality of life between both groups was ascertained.