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Zeel Vishnubhai Patel,1 Priyadarshi Prajjwal,2 Lakshmi Deepak Bethineedi,3 Divyakshi J Patel,4 Kaarvi Khullar,5 Hinal Patel,6 Kanishka Khatri,2 Mohammed Dheyaa Marsool Marsool,7 Srikanth Gadam,8 Soumya Aleti,9 Omniat Amir10 1Internal Medicine, Medical College Baroda, Baroda, Gujarat, India; 2Internal Medicine, Bharati Vidyapeeth University Medical College, Pune, India; 3Internal Medicine, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India; 4Internal Medicine, Smt. NHL Municipal Medical College, Ahmedabad, India; 5Internal Medicine, Maharashtra University of Health Sciences, Government Medical College, Gondia, India; 6Internal Medicine, GMERS Medical College and Hospital Sola, Ahmedabad, India; 7Internal Medicine, University of Baghdad, Al-Kindy College of Medicine, Baghdad, Iraq; 8Internal Medicine, NYC Health+ Hospitals, New York, NYC, USA; 9Internal Medicine, Berkshire Medical Center, Pittsfield, MA, USA; 10Internal Medicine, Al Manhal Academy of Science, SudanCorrespondence: Omniat Amir, Internal Medicine, Al Manhal Academy of Science, Khartoum, 1442, Sudan, Email omniatamir123@gmail.comAbstract: Sickle cell disease (SCD), the most common autosomal recessive genetic disorder, affects the hemoglobin (Hb) chains in human red blood cells. It is caused by mutations in the β-globin genes, leading to the production of hemoglobin S, which results in the formation of sickle-shaped red blood cells (RBCs). These abnormal cells cause hemolysis, endothelial damage, and small vessel occlusion, leading to both acute and long-term complications. According to the World Health Organization’s 2008 estimates, SCD affects approximately 2.28 per 1000 individuals globally. Despite this high prevalence, therapeutic advancements have been slow. For many years, the only FDA-approved medications for managing SCD complications were hydroxyurea and deferiprone. However, recent years have seen the approval of several new therapies, including L-glutamine (2017), voxelotor and crizanlizumab (2019), as well as exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) (2023). These treatments have proven effective in managing both the acute and chronic effects of SCD, including hemolytic anemia, chronic pain, stroke, vaso-occlusive crises, and multiple organ damage syndromes. This review explores the mechanisms of action, practical considerations, and side effects of these emerging therapies, drawing from a comprehensive search of databases such as PubMed, Medline, and Cochrane.Keywords: sickle cell disease, L-Glutamine, Voxelotor, Crizanlizumab, Casgevy, Lyfgenia

Abstract Introduction Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects all age groups including children. AD is characterized by elevated inflammatory marker levels. Aim To assess the safety and effectiveness of topical tacrolimus ointment versus topical hydrocortisone cream in the treatment of pediatric AD by comparing the two treatments' ability to reduce serum cytokines. Patients and Methods One hundred AD patients who fulfilled the eligibility criteria completed this clinical study. Two groups of 50 AD patients each were selected from Tanta University's Dermatology Department., Group 1 (the hydrocortisone group) was administered topical hydrocortisone cream for a duration of 4 months. For 4 months, Group 2 was administered tacrolimus topically. Serum levels of thymus and activation regulated chemokine (TARC), cutaneous T cell attractant chemokine (CTAC), interleukin‐10 (IL‐10), interleukin‐6 (IL‐6), E selectin (E‐selectin), and thymic stromal lymphopoietin (TSLP) were measured during an evaluation of the patients by a dermatologist at the beginning and 4 months after the treatment had been started. Children's Dermatology Life Quality Index was used to assess quality of life in these patients. Results With the exception of E‐selectin, IL‐6, and IL‐10 (p > .05), the tacrolimus group had a significant reduction in TARC, CTACK, TSLP (p

IntroductionAtopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children.AimTo investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children.Patients and methodsThis clinical randomized investigation included 100 children with AD who met the eligibility criteria. AD patients were recruited from Tanta University’s Dermatology Department and divided into two groups (n = 50)., For four months, group 1 (the hydrocortisone group) received topical hydrocortisone cream. Group 2 received topical tacrolimus for four months. A dermatologist evaluated the patients at the start and four months after the treatment had been initiated to measure serum concentrations of neutrophil chemoattractant growth-related oncogene-α (GRO-α), interferon gamma induced protein 10 (IP-10), tumor necrosis factor alpha (TNF-α), vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1). All patients were examined using the modified Eczema Area and Severity Index (mEASI) score.ResultsTacrolimus group showed a significant reduction in serum levels of all measured biomarkers (p < 0.05) when compared to its baseline and when compared to the hydrocortisone group. Both groups displayed a significant decline in mEASI score in comparison with their baseline values (p < 0.05).ConclusionIn children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone, suggesting its potential as a more effective treatment option.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT05607901.

BackgroundNeuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression.AimTo investigate the mechanistic pathways of high dose atorvastatin in MDD.Patients and methodsThis trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured.ResultsThe atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively.ConclusionThese results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3.Clinical Trial Registrationclinicaltrials.gov, identifier NCT05792540.

Alexandra Kasim,1,&ast; Gabby Elbaz-Greener,2,3,&ast; Amjad Shalabi,4– 6 Erez Kachel,4– 6 Liza Grosman-Rimon,4,5 Michael Jerdev,4 offer amir,2– 5 Shemy Carasso2– 5 1Department of Radiology, B Padeh Medical Center, Poriya, Israel; 2Department of Cardiology, Hadassah Medical Center, Jerusalem, Israel; 3Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 4Cardiovascular Institute, B Padeh Medical Center, Poriya, Israel; 5The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel; 6Department of Cardiac Surgery, B Padeh Medical Center, Poriya, Israel&ast;These authors contributed equally to this workCorrespondence: Gabby Elbaz-GreenerDepartment of Cardiology, Hadassah Medical Center, Room Number 114, Jerusalem, IsraelTel +97226776564Fax +97226411028Email Gabby@hadassah.org.ilBackground: Severe mitral annulus calcification (MAC) is believed to bear high operative and post-operative risk during mitral valve replacement (MVR) surgery, including longer surgery time, post-surgical valvular leaks and increased rate of embolic phenomena. We hypothesized that quantification of mitral calcium in pre-operative chest computerized tomography (CCT), performed to assess aortic root before cross-clamping may help in risk assessment of adverse intraoperative and postoperative outcomes in patients undergoing MVR.Methods: We included patients who underwent MVR between the years 2015 and 2018 at Poriya medical center. Preoperative CCT was performed using Philips iCT 256 and Agatston mitral annulus calcium score (MACS) was retrospectively calculated using Philips Intellispace portal version 8.0. Patients were divided into MACS quintiles; 1– 3 quintiles were grouped (Low MACS) and compared to the 4– 5 quintiles (High MACS) group for demographic, clinical operative and post-operative parameters.Results: A total of 66 patients had MVR, out of which 61% were males, with mean age of 64± 9. Concomitant coronary or valvular procedures were done in 60% of patients. The median MACS was 43. High MACS (≥ 854) was not associated with longer bypass or cross clamp times. No differences in the MVR results were found between the groups. There were 6 post-operative embolic events; 1 mesenteric and 5 cerebral, which were not associated with MACS.Conclusion: MACS did not seem to be related to adverse outcomes in MVR. Due to a low event rate and probable pre-selection of patients without extreme mitral annulus calcifications our results should be confirmed in larger prospective study.Keywords: mitral annulus calcification, MACS, mitral valve replacement, MVR

Gabby Elbaz-Greener,1,&ast; Guy Rozen,2– 4,&ast; Shemy Carasso,5,6 Fabio Kusniec,5,6 Ibrahim Marai,5,6 Maneesh Sud,7 Bradley Strauss,7 Frank W Smart,8 David Planer,1 Offer Amir1,5,6 1Department of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 2Cardiology Division, Hillel Yaffe Medical Center, Hadera, Israel; 3The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; 4Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 5Division of Cardiovascular Medicine, Baruch Padeh Medical Center, Poriya, Israel; 6The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel; 7Schulich Heart Centre, Division of Cardiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 8LSU School of Medicine, New Orleans, LA, USA&ast;These authors contributed equally to this workCorrespondence: Gabby Elbaz-GreenerDepartment of Cardiology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Room Number 114, Jerusalem, IsraelTel +972(2)6776564Fax +972(2)6411028Email Gabbyelbaz@yahoo.comBackground: The association between body mass index (BMI) and clinical outcomes following an acute myocardial infarction (AMI) remains controversial. Our objective was to investigate the relationship between BMI and AMI presentation, in-hospital clinical course and mortality in the contemporary era of AMI management.Methods: Patients, hospitalized for an AMI between October 2015 and December 2016, were identified in the National Inpatient Sample (NIS) database. Socio-demographic and clinical data, including BMI, were collected and outcomes, including length of stay and mortality, were analyzed. Patients were divided into 6 BMI (kg/m2) subgroups; under-weight (≤ 19), normal-weight (20– 25), over-weight (26– 30), obese I (31– 35), obese II (36– 39) and extremely obese (≥ 40). Multivariable logistic regression model was used to identify predictors of in-hospital mortality. Linear regression model was used to identify predictors of length of stay (LOS).Results: An estimated total of 125,405 hospitalizations for an AMI across the US were analyzed. Compared to the other BMI subgroups, the under-weight, normal-weight and extremely obese groups presented with a non-ST segment elevation AMI (NSTEMI) more frequently and were less likely to undergo coronary revascularization. The data show a J-shaped relationship between BMI and study outcomes with lower mortality in patients with BMI over 25 compared to normal- and low-weight patients. In the multivariate regression model, BMI group was found to be an independent predictor of mortality.Conclusion: J-shaped relationship between BMI and mortality was documented in patients hospitalized for an AMI in the recent years. These findings confirm that the “obesity paradox” persists during the contemporary era of an AMI management.Keywords: body mass index, BMI, acute myocardial infarction, obesity paradox

Introduction: Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects all age groups including children. AD is characterized by elevated inflammatory marker levels. Aim: To assess the safety and effectiveness of topical tacrolimus ointment versus topical hydrocortisone cream in the treatment of pediatric AD by comparing the two treatments' ability to reduce serum cytokines. Patients and Methods: One hundred AD patients who fulfilled the eligibility criteria completed this clinical study. Two groups of 50 AD patients each were selected from Tanta University's Dermatology Department., Group 1 (the hydrocortisone group) was administered topical hydrocortisone cream for a duration of 4 months. For 4 months, Group 2 was administered tacrolimus topically. Serum levels of thymus and activation regulated chemokine (TARC), cutaneous T cell attractant chemokine (CTAC), interleukin‐10 (IL‐10), interleukin‐6 (IL‐6), E selectin (E‐selectin), and thymic stromal lymphopoietin (TSLP) were measured during an evaluation of the patients by a dermatologist at the beginning and 4 months after the treatment had been started. Children's Dermatology Life Quality Index was used to assess quality of life in these patients. Results: With the exception of E‐selectin, IL‐6, and IL‐10 (p >.05), the tacrolimus group had a significant reduction in TARC, CTACK, TSLP (p <.05) when compared to its baseline and when compared to the hydrocortisone group. Both groups showed a significant improvement in quality of life but no significant changes between groups were observed. Conclusion: In children with AD, tacrolimus reduces inflammatory biomarkers better than hydrocortisone. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris (AV) is an inflammatory skin disorder leading to scars and discomfort, its intensity has major psychological consequences such as depression. Aim: To investigate the effect of isotretinoin (ISO) on NF‐κB/NLRP3, biotinidase, and HMGB and correlation with depression. Patients and Methods: This was a case–control study that involved two groups. Group 1 is 20 healthy control, and group 2 is 20 patients diagnosed with AV according to Global Acne Grading System (GAGS) and received 20 mg ISO for 2 months. Before and after therapy, the Hamilton Depression Rating Scale (HDRS) was applied to assess each participant's level of depression. Nuclear factor kappa B (NF‐ĸB), biotinidase, high mobility group box protein (HMGB1), nucleotide‐binding domain, leucine‐rich–containing family, and pyrin domain–containing‐3 (NLRP–3) were measured in serum samples. Results: There was no significant difference in all measured markers of healthy group before and after 2 months. Regarding group 2, there was a statistically significant decrease in all measured markers after 2 months of treatment and significant correlations between GAGS, NF‐ĸB, HMGB1, NLRP3, biotinidase, and depression score. Conclusion: Increased GAGS, HMGB1, NLRP3, and biotinidase were associated with depression severity in AV patients and ISO treatment significantly reduced these parameters and reduced depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/ NLRP3 and IL-6/STAT-3. [ABSTRACT FROM AUTHOR]

Oren Yagel,* Naseem Shadafny,* Ran Eliaz, Gil Dagan, David Leibowitz, Ilgar Tahiroglu, David Planer, Offer Amir, Gabby Elbaz Greener,* Ronny Alcalai* Department of Cardiology, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Gabby Elbaz GreenerHadassah Medical Center, Cardiology Division, Room Number 114, Jerusalem, IsraelTel +972(2)6776564Fax +972(2)6411028Email Gabby@hadassah.org.ilBackground: Acute coronary syndrome (ACS) at a young age is uncommon. Limited data regarding the long-term follow-up and prognosis in this population are available. Our objectives were to evaluate the long-term clinical outcomes of patients presenting with ACS at a young age and to assess factors that predict long-term prognosis.Methods: A retrospective analysis of consecutive young patients (male below 40 and female below 50 years old) that were admitted with ACS and underwent percutaneous coronary intervention (PCI) between the years 1997 and 2009. Demographics, clinical characteristics, and clinical outcomes including major cardiovascular (CV) events and mortality were analyzed. Multivariable cox proportional hazard model was performed to identify predictors of long-term prognosis.Results: One-hundred sixty-five patients were included with a mean follow-up of 9.1± 4.6 years. Most patients were men (88%), and mean age (years) was 36.8± 4.2. During follow-up, 15 (9.1%) died, 98 (59.4%) patients had at least one major CV event, 22 (13.3%) patients had more than two CV events, and the mean number of recurrent CV events was 1.4± 1.48 events per patient. In multivariate analysis, the strongest predictors of major CV events and/or mortality were coronary intervention without stent insertion (HR1.77; 95% CI 1.09– 2.9), LAD artery involvement (HR 1.59; 95% CI 1.04– 2.44) and hypertension (HR 1.6; 95% CI 1.0– 2.6).Conclusion: Patients with ACS in young age are at high risk for major CV and/or mortality in long-term follow-up with a high rate of recurrent CV events. Close follow-up and risk factor management for secondary prevention have a major role, particularly in this population.Keywords: acute coronary syndrome, ACS, NSTEMI, STEMI, young population, outcomes

Consumers' lives are filled with myriad behaviors that can be successfully executed with minimal attention. Many such low-attention behaviors benefit from persistence but are often not performed long enough (e.g. hygiene, exercise). The current work examines consumer persistence-failures through an attentional lens. Specifically, drawing on boredom and resource-matching frameworks, we suggest one key driver of poor consumer persistence is that many behaviors demand less attention than consumers have available, leaving excess attention that leads to boredom and premature abandonment. The current research thus proposes an attention-matching framework for persistence and suggests that concurrently performing a task that engages excess attention will improve the match between attentional demands and available resources, thereby increasing persistence. Five experiments across a range of low-attention behaviors (e.g. toothbrushing, coordination exercise) demonstrate that concurrently performing a task that occupies excess attention (e.g. reading, listening), delays boredom and increases persistence. Moreover, two important boundary conditions arise. First, the focal behavior must require minimal attention, leaving excess attention available to attend to the tangential task. Second, the tangential task must engage excess attention without exceeding attentional capacity. This research provides important theoretical and practical contributions, offering the potential to improve consumer well-being by increasing persistence in low-attention behaviors. [ABSTRACT FROM AUTHOR]

Economics has typically been the social science of choice to inform public policy and policymakers. In the current paper we contemplate the role behavioral science can play in enlightening policymakers. In particular, we provide some examples of research that has and can be used to inform policy, reflect on the kind of behavioral science that is important for policy, and approaches for convincing policy-makers to listen to behavioral scientists. We suggest that policymakers are unlikely to invest the time translating behavioral research into its policy implications, and researchers interested in influencing public policy must therefore invest substantial effort, and direct that effort differently than in standard research practices.