 symptoms may be an integral part of disease management, but it is crucial to understand that symptoms can vary over time in both frequency or severity.

A new scientific statement from the American Heart Association (AHA) presented the relevance of symptoms associated with CVD and the current state of the science, reviewing the genesis, manifestations, and similarities or differences between diagnoses.

Due to commonalities in symptoms across disorders, it is crucial to use established measures or develop reliable and responsive measures of CVD symptoms to track over a period of time, according to the investigators.

“Monitoring symptoms with reliable and valid measures in research and clinical practice may enhance clinical care by identifying those who may be at risk for poor outcomes more quickly (eg, lower quality of life, hospitalization, death),” wrote lead author Corrine Y. Jurgens, PhD, RN, AHA Council on Cardiovascular and Stroke Nursing.

Current research in CVD is focused on major adverse cardiovascular events, such as hospitalization or death, and less focus on symptoms, despite their noted significance. Investigators added that several caveats should be taken into consideration into the interpretation of symptoms in CVD.

These patients may experience symptoms in the absence of important changes in underlying pathogenesis, while the absence of symptoms does not necessarily confer the absecne of change in unlderying CVD, the authors added.

However, they noted that there are symptoms that have relevance in CVD, including acute coronary syndrome (ACS), heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease.

The statement reports the most frequently reported symptoms of ACS is chest pain, with the most common co-occurring symptoms being dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness.

Challenges in interpreting symptoms in ACS include the lack of consensus on the duration of the prodromal phase, with literature defining the range as between 1 month to 48 hours before an ACS event. Additionally, more similarities in symptom presentation in ACS have been reported among women compared with men, but there are salient differences.

Women with ACS on average are significantly older than men, but the contributions of chronological and biological aging to symptoms experienced by patients with ACS remain unknown.

Due to a lack of standard measures, bias in favor of certain symptom assessments and an inability to compare symptoms across cohorts may exist. The lack of agreement of ACS symptom measurement in research makes it difficult to synthesize findings about symptoms across research and to incorporate evidence-based information about symptoms into treatment guidelines, investigators added.

Dyspnea is a hallmark of heart failure and is often characterized in terms of provocation, including dyspnea at rest, dyspnea on exertion, otheropena, paroxysmal nocturnal dyspnea, and bendopnea. Early and subtle symptoms, such as gastrointestinal-related symptoms or fatigue, may be a sign of worsening heart failure and impending hospitalization or death.

The statement reported women experienced higher physical symptom burden, higher depression and anxiety, and lower quality of life compared with men. Moreover, older age is associated with issues in recognition and interpretation of dyspnea.

Quality of life and health status measures are most commonly used in heart failure, but the number of symptoms indirectly covered by these measures is limited. The current and future work in heart failure symptoms is now focused on symptom patterns and clustering over time.

Investigators noted valvular heart disease is a frequent cause of heart failure, with symptoms indistinguishable from other heart failure causes. The staging of valvular heart disease is based on a combination of valve findings, symptoms, and ventricular function.

Symptoms differ between sexes for aortic valve disease, while aortic stenosis is generally asymptomatic. Women often report dyspnea and exercise intolerance more often than men as stenosis progresses. Symptom presence and severity remain key to determining stage of disease and timing of surgical or transcather intervention, investigators added.

Acute symptoms after stroke help predict disability and quality of life. Thus, responding to stroke signs and symptoms quickly is essential for proper treatment. Investigators added stroke severity, physical disability, and cognitive impairments after stroke are associated with common symptoms of anxiety, depression, fatigue, and pain.

In order to better enhance public education about stroke, more research is needed to understand the presentation of stroke symptoms by other select demographic characteristics. Additionally, the statement added all individuals who experience a stroke should be screened for post stroke anxiety and depression, as well as other physical and psychological issues

Cardiac arrhythmias present with common symptoms, with palpitations being a characteristic symptom of many cardiac arrhythmias.

Patients with new-onset atrial fibrillation (AF) present either asymptomatically or with nonspecific symptoms, with palpatations 27%–70%), fatigue (26%–75%), and dyspnea (28%–76%) the most common symptoms reported.

Women and younger patients with AF were reported to typically present with palpitations, while men are more commonly asymptomatic. Increasing age additionally increases likelihood of a nonclassic or asymptomatic presentation of AF.

Thus, symptom monitoring and the association between symptoms and heart rate are essential components of medication titration for rate control and selection of a rate versus rhythm control management strategy. Clinicians often underrepresented AF symptom severity, thus clinical-reported measures should be avoided unless necessary, according to investigators.

Peripheral vascular disease and associated symptoms can occur from either arterial or venous pathology. Symptoms of peripheral arterial disease (PAD) vary with a range from none, despite disease progression, to leg pain at rest.

Symptomatic PAD has been associated with increased risk of major adverse cardiovascular events, with men at higher risk. However, women with PAD are more likely to have non-classic or absence of symptoms, as well as a more rapid decline and lower quality of life.

Similarly, peripheral venous disease (PVD) can be symptomatic or asymptomatic. The clinical classification of the disease includes symptoms such as leg pain, aching, and fatigue.

The existing measures of PVD are quality-of-life measures including symptoms, limitations of activities of daily living, and psychological impact. Limitations of PVD measures are similar to other CVD regarding minimally important differences. The existing legacy measures of PVD are centered on clinician appraisal and not patient-reported symptoms.

Overall, investigators require more information on the relationship between symptoms and clinical events and underlying CVD pathogenesis, particularly among individuals living with multiple chronic conditions.

“Despite limitations in measurement and complexities in how they are experienced, symptoms have clear relevance to the diagnosis, monitoring, and treatment of CVD,” Jurgens and colleagues concluded.

State of the Science: The Relevance of Symptoms in Cardiovascular Disease and Research: A Scientific Statement From the American Heart Association

Articles

The scientific statement reviews symptoms associated with ACS, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease. 

New AHA Statement Highlights Symptom Relevance in Cardiovascular Disease 

New data shows various clinical presenting features for pediatric patients in the UK with 

A team, led by Chayarani Kelgeri, MD, the Liver Unit, Birmingham Women’s and Children’s NHS Foundation Trust, attempted to identify the causative agent or agents of acute hepatitis of unknown causes in pediatric patients in the UK.

There has been increases in cases of acute hepatitis of unknown causes in pediatric patients since January 2022, the majority of which occurring in the UK.

In the retrospective study, the investigators examined pediatric patients 10 years of age or younger referred to a single pediatric liver-transplantation center in the UK between January 1 and April 11, 2022. Each of the 44 participants had hepatitis that met the case definition of the U.K. Health Security Agency for confirmed acute hepatitis that was not hepatitis A through E.

The patients also did not have a metabolic, inherited or genetic, congenital, or mechanical cause in the context of a serum aminotransferase level greater than 500 IU per liter.

The investigators reviewed medical records and documented demographic characteristics, clinical features, and results of liver biochemical, serologic, and molecular tests for hepatotropic and other viruses. They also documented radiologic and clinical outcomes that were classified as an improving condition, liver transplantation or death.

All of the participants met the confirmed case definition and the majority were previously healthy. The median age was 4 years.

Some noticeable presenting features included jaundice, which occurred in 93% of patients, vomiting, which occurred in 54%, and diarrhea, which occurred in 32%. There were also 30 patients who underwent molecular testing for human adenovirus, 90% (n = 27) of which were positive. An additional 14% (n = 6) developed fulminant liver failure, all of whom received a liver transplant.

No patient died and each participant was discharged home, including the 6 who received liver transplants.

“In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established,” the authors wrote.

A June US Centers for Disease Control and Prevention (CDC) report does not show an increase in pediatric acute 

 cases during the COVID-19 pandemic in comparison with pre-pandemic levels.

A team led by Anita K. Kambhampati, MPH, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC, assessed trends in hepatitis-associated emergency department visits and hospitalizations, liver transplantations, and adenovirus stool testing results in pediatric patients in the US.

The CDC first identified a cluster of previously healthy pediatric patients with hepatitis of unknown etiology at a single US hospital in November 2021.

In April 2022, the CDC requested additional data on pediatric hepatitis cases of unknown etiology, which resulted in test results positive for adenovirus, which is not known to cause hepatitis in immunocompetent pediatric patients.

The results did not show an increase in weekly emergency department visits with hepatitis-associated discharge codes during the pandemic among patients aged 0-4 years or 5-11 years compared to the pre-COVIID-19 figures.

Between January 2019 and March 2022 there was a median of 22 and 10 hepatitis-associated hospitalizations in those age groups, respectively, recorded each month.

There was also no significant changes observed in hepatitis-associated hospitalizations during the pandemic study period, compared to the same months prior to COVID-19 among pediatric patients aged 0–4 years (22 and 19.5, respectively, 

 = 0.26) or 5–11 years (12 and 10.5, respectively, 

Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause

Some noticeable presenting features included jaundice, vomiting, and diarrhea.

Human Adenovirus Prominently Found in Children With Acute Hepatitis

This week, Viridian Therapeutics, Inc reported positive initial clinical data from the ongoing Phase 1/2 clinical trial of the anti-IGF-1R antibody VRDN-001 in patients with 

The double-blind, placebo-controlled Phase 1/2 trial is evaluating two infusions of VRDN-001 administered intravenously, with efficacy measurements including proptosis, Clinical Activity Score (CAS), and diplopia.

Data suggest significant and rapid improvements in both signs and symptoms of TED at week 6 after two infusions of 10 mg/kg VRDN-001. The findings report proptosis response (≥2mm reduction) was achieved by 83% of patients, with a 2.3 mm mean reduction from baseline.

Moreover, the Clinical Activity Score of 0 or 1 was achieved by 83% of patients with a mean reduction of 4.3 points from baseline and complete resolution of diplopia was achieved by 75% of patients with diplopia at baseline.

“TED is a severe, debilitating eye disease that threatens patients’ vision and overall quality of life,” said Raymond Douglas, MD, PhD, Director of Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center and investigators of VRDN-001 trial. “In this trial, rapid and significant improvements in a broad set of efficacy measures suggests that VRDN-001 may have a differentiated profile that could offer meaningful benefits to patients.”

The ongoing trial is evaluating two infusions of VRDN-001 3 weeks apart with efficacy measured 6 weeks following the first dose. Each dose is evaluated in a cohort of 8 patients, randomized so that 6 patients receive VRDN-001 and 2 patients receive placebo.

A second cohort is evaluating a dose of 20 mg/kg with results expected in the fourth quarter of 2022. A third cohort will evaluate a dose of 3 mg/kg with data expected in the fourth quarter of 2022.

The agent was well-tolerated by all patients treated at the 10mg/kg dose, with no reported serious adverse events (SAEs), no patient discontinuations, and no hyperglycemia or infusion reactions of August 2022. They reported two cases of mild muscle spasm which did not require intervention, as well as a single report of “ringing in the ears” which was later resolved.

In addition, the ongoing second cohort at 20 mg/kg has reported no adverse events of hyperglycemia, muscle spasm, hearing impairment, infusion reactions, or any serious adverse events as of August 9, 2022.

“These data exceeded our expectations and compare very favorably to Tepezza, the only approved therapy in TED,” said Barrett Katz, MD, MBA, Chief Medical Officer at Viridan in a statement. “We plan to accelerate the start of our Phase 3 THRIVE program, now starting later this year, in a broad TED population of both active and chronic disease. We believe VRDN-001 could show a more rapid onset of action and afford a shorter course of treatment with the potential for a differentiated profile versus other TED therapies, due to its full antagonism of IGF-1R.” 

Significant rapid improvement were observed in both signs and symptoms of thyroid eye disease at week 6 after 2 infusions of 10mg/kg VRDN-001. 

Phase 1/2 Trial Reports Positive Initial Clinical Data of VRDN-001 in Thyroid Eye Disease 

The presence of ultra wide-field fluorescein angiography (UWF-FA) detected predominantly peripheral lesions (PPLs) was associated with greater risk of worsening disease in eyes with 

nonproliferative diabetic retinopathy (NPDR)

The greater risk was determined to be independent of the baseline Diabetic Retinopathy Severity Scale (DRSS) score, suggesting peripheral findings on UWF-FA allow more accurate risk identification in eyes with NPDR.

“Thus, among eyes with NPDR, the presence of PPL identified using UWF-FA imaging appears to be a marker for increased risk of disease worsening that is not detectable using standard ETDRS 7-field photography or UWF-color imaging alone,” wrote study author Adam R. Glassman, MS, Jaeb Center for Health Research.

The DRCR Retina Network Protocol AA evaluated whether the detection of PPL on UWF-color or UWF-FA improves the ability to predict the rate of worsening retinopathy beyond baseline risk.

The prospective observational longitudinal study was conducted at 37 clinical sites in the United States and Canada. Individuals were 18 years or older, had type 1 or type 2 diabetes, and had at least 1 eye with NPDR confirmed on ETDRS modified 7-field grading.

Investigators noted the procedure for the UWF-color imaging included two 200° central images and two 200° steered images obtained and graded for DRSS at a reading center. The score on the DRSS was evaluated on ETDRS 7-field and UWF-color images and PPL presence was determined independently from UWF-color and UWF-FA images.

Primary outcomes as disease worsening as a time-to-event outcome was defined as either worsening by 2 or more steps on the DRSS assessed within the ETDRS fields from the UWF-color images or receipt of DR treatment over 4-years of follow-up.

From February 2015 - December 2015, the study enrolled a total of 388 participants with data analyzed from May 2020 - June 2022. The analysis cohort consisted of 544 study eyes from 367 participants (182 [50%] female participants; median age, 62 years; 68% White) who had ≥1 eye with NPDR on UWF-color that was gradable for PPL.

Among the 544 eyes, PPLs were present in 221 eyes (41%) on UWF-color and 247 (46%) on UWF-FA. The median baseline visual acuity letter score was 86 letters. Over 4 years, treatment for DR or DME was initiated in 18% of eyes with 11% receiving treatment for DR and 14% receiving treatment for DME.

Data suggest the cumulative proportion of disease worsening through 4 years was 40% (95% confidence interval [CI], 36% - 45%) overall.

Then, the worsening rates were 45% (95% CI, 37% - 54%) in eyes with baseline mild NPDR, 40% (95% CI, 32% - 49%) with moderate NPDR, 26% (95% CI, 17% - 38%) with moderately severe NPDR, and 43% (95% CI, 34% - 53%) with severe or very severe NPDR on UWF-color masked images.

When stratified by baseline PPL status, 38% (95% CI, 31% - 45%) of eyes with color PPL and 43% (95% CI, 37% - 49%) without color PPL met the primary outcome of disease worsening (HR, 0.78; 95% CI, 0.57 - 1.08; 

Moreover, investigators noted the primary outcome rate was 50% (95% CI, 44% - 57%) in eyes with FA-PPL and 31% (95% CI, 25% - 38%) in eyes without FA PPL (HR, 1.72; 95% CI, 1.25 - 2.36; 

“These findings support use of UWF-FA for future DR staging systems and clinical care to more accurately determine prognosis in NPDR eyes,” Glassman added.

Association of Predominantly Peripheral Lesions on Ultra-Widefield Imaging and the Risk of Diabetic Retinopathy Worsening Over Time

Ultra-widefield fluorescein angiography allow more accurate risk identification of eyes with non proliferative diabetic retinopathy than baseline severity level alone in new findings. 

Usage of UWF-FA May Improve Ability to Predict Disease Worsening in Eyes with NPDR 

While the systemic treatment of psoriasis has improved significantly over the last two decades, there remains no consensus on or validated criteria for defining remission and cure. Notably, some researchers have abandoned the PASI50 criterion for stricter and narrower treatment goals, such as, PASI90, PASI ≤ 2, and body surface area (BSA) ≤ 1%.

A new systematic literature review, led by Deepak Balak of LangeLand Hospital in the Netherlands, has further identified and assessed various definitions of remission and cure of psoriasis as a means to inform and aid the development of consensus-based definitions. The review authors note that this “concept of psoriasis remission and cure as endpoint in clinical trials is becoming more relevant,” and thus stress the importance of their study in addressing such knowledge gaps.

At the outset of their review, Balak and team used Medline/PubMed (National Library of Medicine), EMBASE (Embase.com/Elsevier), and The Cochrane Central Register of Controlled Trials (cochranelibrary.com) to identify studies discussing remission or cure of psoriasis.

They included observational and interventional studies that used consensus-based and non-consensus-based definitions of remission and/or cure in adults >18 years with plaque psoriasis.

“Additionally, we explored studies reporting consensus-derived psoriasis treatment goals and studies evaluating cut-off values of treatment goals for psoriasis remission and cure definitions,” they wrote.

Following screening and the application of inclusion/exclusion criteria (absence of definition, language restrictions, etc.), Balak’s team proceeded to evaluate a total of 136 articles. Of this total, 78% included a definition for psoriasis remission, and 5% provided a cure definition. The remaining 17% utilized consensus-derived psoriasis treatment goals or cut-off values for treatment goals.

They found that, of the studies reporting a definition for psoriasis remission, PASI75 was the most commonly used criterion (n = 16), followed by PASI90 (n = 10), and PASI100 (n = 10). Endpoints based on absolute PASI values were much less common.

Some studies (n = 7) used descriptive remission definitions, including “clearance” or related terms such as “clear” or “clearing” (n = 17). Other descriptions included “free of disease” and “no active skin lesions.

Body surface area (BSA) was used in 6 definitions, with the most commonly reported endpoints being BSA improvement > 90% (n = 3) and BSA improvement > 75% (n = 3).A small consensus-initiative defined drug-free remission as BSA of 0 with no therapy for ≥12 months.

The investigators noted few studies and definitions that specified time-frame, on/off treatment or other psoriasis-related disease domains.

“Most studies (n = 14) defined relapse by a PASI-increase >50% of baseline PASI. Other frequently reported definitions were BSA-increase >50% of baseline BSA (n = 7), need for treatment (n = 6), new lesions or exacerbation of existing lesions (n = 3), and increase in BSA ≥10% (n = 3),” the investigators wrote.

Partial remission was found in 12 studies and based on PASI (i.e. PASI improvements between PASI50 and PASI75 [n = 4] and > PASI75 [n = 3]).

Only 7 studies had defined psoriasis cure using same or similar endpoints to those commonly used to define remission – i.e. PASI100 (n = 1), PASI of 0 (n = 1), or 100% improvement on a 4-point physician overall assessment scale (n = 1).

“Our results indicate that a wide range of instruments and thresholds were used to define a state of psoriasis remission,” the investigators wrote. They indicated that 41 unique definitions were found among all evaluated studies.

“Due to the broad search strategy, this [systematic literature review] will inform potential future applications of a remission definitions across the breadth of both clinical research, interventional trials and clinical practice,” they concluded. “The benefit of a potential harmonized definition for psoriasis remission across clinical trials and clinical practice is that it would allow for seamless comparison of trial results vs. real-world evidence sources of data.”

Definitions of Remission in Psoriasis: A Systematic Literature Review from the National Psoriasis Foundation

The Journal of the European Academy of Dermatology and Venereology

A systematic literature review identifies 41 unique definitions for psoriasis remission among 106 studies.

Psoriasis Remission, Cure Definitions Vary Widely Across Studies

New findings from a 4-year longitudinal study suggest that both greater baseline retinal nonperfusion and the presence of predominantly peripheral lesions (FA-PPL) on ultra-widefield fluorescein angiography (UWF-FA) were associated with higher risk of 

These findings remained even following adjustments for baseline DR Severity Scale (DRSS) score, as well as individual-level risk factors including diabetes duration and glycemic control.

“These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research,” wrote study author Adam R. Glassman, MS, Jaeb Center for Health Research.

Previous research observed the presence of predominantly peripheral DR lesions on UWF-FA was linked to greater risk of DR worsening, but there is uncertainty regarding the predictive nature of baseline retinal nonperfusion assessment on disease worsening.

Glassman and colleagues reported the 4-year longitudinal data from the Protocol AA UWF-FA in detail to determine the extent of UWF-FA retinal nonperfusion on disease worsening and if the association is independent of known risk factors for DRSS worsening.

They performed an analysis of a prospective observational longitudinal study conducted by the DRCR Retina Network at 37 clinical sites in the United States and Canada from February 2015 to March 2020. Adult participants with type 1 or 2 diabetes and ≥1 eye with nonproliferative DR (NPDR) on modified 7-field standard Early Treatment Diabetic Retinopathy Study (ETDRS) color photographic grading (ETDRS levels 35 - 53) were enrolled in the study.

The primary outcome of disease worsening was a time-to-event outcome, defined as worsening by 2 or more steps on the DRSS or receiving treatment for DR during the 4 years of follow-up. The DRSS score at baseline and follow-up visits were assessed within the ETDRS fields from the UWF-color images.

A total of 508 eyes were graded as having NPDR and gradable UWF-FA nonperfusion at baseline, among which 47 eyes (9%) did not have any nonperfusion identified. Baseline characteristics were identified as similar among the 4 subgroups, although eyes with greater nonperfusion had a larger proportion of patients with type 1 diabetes (T1D), longer duration of diabetes, more severe baseline DRSS score, and higher prevalence of FA PPL.

Data show the 4-year cumulative proportion of eyes meeting the primary disease-worsening outcome was 26% (95% CI, 15% - 43%) in the no-nonperfusion group and 43% (95% CI, 34% - 52%), 38% (95% CI, 30-47%), and 46% (95% CI, 38% - 55%) in the low-, medium-, and high-nonperfusion subgroups, respectively (HR, 1.11; 95% CI, 1.02 - 1.21; 

Multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02 - 1.22; 

 = .02) and presence of FA-PPL (HR, 1.89; 95% CI, 1.35 - 2.65; 

 <.001) remained associated with disease worsening.

“These results suggest that retinal nonperfusion and FA PPL should be included in staging systems to predict risk of disease worsening over time,” Glassman added.

The study, “Association of Ultra-Widefield Fluorescein Angiography–Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time,” was published in 

An increasing retinal nonperfusion index was associated with a significantly higher risk of Diabetic Retinopathy Severity Scale worsening. 

Greater Baseline Retinal Nonperfusion Linked to Worsening  Diabetic Retinopathy 

The armamentarium of medications for psychiatric disorders is growing rapidly.

What started with the US Food and Drug Administration’s (FDA) approval of esketamine (Spravato) in 2019 for major depressive disorder (MDD), has spawned the studies of other compounds and options such as LSD and psilocybin.

And then there is cannabis, a somewhat vague term that describes a treatment that contains tetrahydrocannabinol (THC) and cannabidiol (CBD).

“One of the biggest issues currently is that cannabis is a very vague and general term,” Miller said. “Back in the early 60s when it was being used recreationally it was from the original plant. Those strains of cannabis had about 2% THC and 2% CBD.”

2022 Annual Psychiatric Times™ World CME Conference

 to talk about misunderstandings regarding the use of cannabis in psychiatry and the promising future of using psilocybin and psychedelics in the field.

Podcasts

The FDA approved esketamine in 2019 for major depressive disorder.

John J. Miller, MD: A New Era For Psychiatric Medications

New research indicates aluminum exposure induces cytokine secretion in the colons of patients with 

, but does not do so in a healthy control group.

A team, led by Madjid Djouina, Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, examined the role aluminum transport and subcellular localization on human colon susceptibility to aluminum-induced inflammation.

Environmental factors are known to play a role in the pathogenesis of IBD. However, while aluminum exposure is suspected to be an IBD risk factor, the mechanisms linking aluminum exposure to disease development are not known.

“We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeostasis and to the expression of IBD,” the authors wrote.

In the study, the investigators isolated human colon biopsies from patients with Crohn’s disease and control patients. They also induced Caco-2 cells with aluminum and evaluated the effects of aluminum on cytokine secretion and transporter expression.

The investigators also studied the role of aluminum kinetics parameters in Caco-2 using transport inhibitors and in human colon biopsies by assessing genetic polymorphisms of transporters.

The results show aluminum exposure induces cytokine secretion in the colons of patients with Crohn’s disease. However, this was not found in the healthy control group.

They also found aluminum internalization was correlated with inflammatory status in Caco-2 cells.

In the human colon, the analysis of genetic polymorphisms and the expression of decreased activity of 

 transporters was involved in aluminum induced inflammation.

“Our study emphasizes the complexity of gene/environment interaction for aluminum adverse health effect, highlighting at risk populations or subtypes of patients,” the authors wrote. “A better understanding of correlations between gene expression or SNP and xenobiotic kinetics parameters would shift the medical paradigm to more personalized disease management and treatment.”

Diet is another risk factor for developing IBD.

Recently, a team, led by Farnaz Farsi, PhD, Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, evaluated whether any relationship between nutrients and IBD exists.

In the case-control study, the investigators examined 145 participants newly diagnosed with IBD between 2017-2019. They also matched these patients with 145 health control participants by body mass index (BMI), sex, and age.

Each participant completed a 168-item food frequency questionnaire and the investigators conducted anthropometric measurements and physical activity levels. The participants also gave information on age, past drug history, socioeconomic and education status, alcohol consumption, smoking history, and IBD subtypes through a general information questionnaire.

Overall, higher amounts of seafood consumed and cholesterol were related to an increased risk of IBD, specifically ulcerative colitis.

On the other hand, individuals with a higher intake of calcium were less likely to have Crohn’s disease compared to the healthy group.

The investigators also found a positive relation between honey and jam, seafood, organ meats, salt, fruits on trees, fruit juice, olives, and nuts and the probability of IBD. However, there was a negative association between refined grains, potatoes, salty snacks, legumes, dairy, and cruciferous and the probability of IBD.

Gene/environment interaction in the susceptibility of Crohn's disease patients to aluminum

Aluminum internalization was correlated with inflammatory status in Caco-2 cells. 

Aluminum Exposure Induces Cytokine Secretion in Crohn’s Disease Colons

Stevens-Johnson syndrome toxic epidermal necrolysis (SJS/TEN), 

, is characterized by impaired wound healing, severe disease, and sometimes mortality. It can present before or secondary to SJS/TEN, though the clinical characteristics and outcomes of those affected by it are not well understood due to limited data. 

A team of investigators, led by Leo Wang MD, PhD, Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, decided to examine this population in the setting of hospital admission. They looked at factors associated with leukopenia and the subsequent patients outcomes.

In the multi-institutional cohort analysis, baseline characteristics of patients admitted with luekopenia, defined by having a white blood cell count of less than 4000/μL, were compared to those without the condition. Logistic regression was used to evaluate the risk of in-hospital complications. 

A higher median body surface area percentage involvement was observed in patients with SJS/TEN on admission (30%) compared with those without leukopenia (15%). These patients also displayed higher rates of active malignant neoplasm (22.5% vs 9.5%), and connective tissue disease (22.5% vs 8.5%).

The study included 377 patients with a mean age of 50 years and 198 women (52.5%). Of the patient population, 49 (13%) patients had leukopenia at the time of admission. There was no difference in age or sex between the groups.

The use of leukopenia-inducing medication was present in 179 (47.5%) patients, but investigators found that those patients did not have develop the disease at higher rates compared to patients who were not taking drugs associated with SJS/TEN. Because of this finding, results suggest that in this cohort, leukopenia was not dependent on medication use.

Identifying Factors Associated with Leukopenia

Results identified from the multivariable logistic regression analysis, included body surface area involvement on admission, malignant neoplasm, and connective tissue disease as the independent factors associated with leukopenia in SJS/TEN.

Additional associations observed after a univariable logistic regression comprised of in-hospital complications of bacteremia and pnemonia. However, there was no correspondence between leukopenia and hospital complications like acute kidney failure, major thrombotic events, intubation, sepsis, cellulitis, urinary tract infection, or in-hospital mortality. 

Without factoring in patients with fatal outcomes, those with leukopenia had a significantly longer length of stay in the hospital (15 days) compared with those without the disease (9 days).

"Additional prospective studies and clinical trials are necessary to confirm these observations and delineate the association between leukopenia and SJS/TEN," investigators wrote. "However, because leukopenia is common, these observations are important for current clinical practice. Dermatologists should be aware of this association to mitigate its effects. Therapeutic medications that may exacerbate leukopenia may be less desirable in such patients, whereas granulocyte colony-stimulating factor may warrant further study to assess the effect of leukopenia-directed therapies for SJS/TEN outcomes."

Prevalence of Leukopenia and Associated Outcomes in Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Investigators found that body surface area involvement on admission, malignant neoplasm, and connective tissue disease were independent factors associated with leukopenia in SJS/TEN.

Investigation Identifies Factors Associated with Leukopenia in SJS/TEN

Patients with psoriasis who were younger, less obese and had less severe psoriasis were more likely to achieve complete skin clearance from treatment with guselkumab, a monoclonal antibody targeting interleukin 23, a recent study found.

The study was a post-hoc analysis of pooled data from VOYAGE-1 and VOYAGE-2 studies. Out of 664 participants included in the analysis, 271 achieved super-response, which is defined by a Psoriasis Area and Severity Index (PASI) 100 response at weeks 20 and 28.

“Although most patients with moderate-to-severe psoriasis receiving biologics will require continuous long-term treatment due to the chronic nature of their disease, data from this post hoc analysis suggest that guselkumab-treated patients with super-response have distinguishable baseline demographic and disease characteristics,” the authors, led by Kristian Reich, MD, PhD (equivalent), of University Medical Center Hamburg-Eppendorf in Germany, wrote.

“These results may allow clinicians to predict which patients at their baseline might achieve super-response, which may be beneficial in drug selection, managing patient expectations of treatment response, and improving patient-physician communication; however, the clinical relevance of these findings requires further study.”

The study used a stepwise logistic regression analysis to evaluate which factors were potentially predictive of super-response. Patients who achieved super-response compared with those with non-super-response were:

Lighter, with a median body weight of 187 pounds vs 198 pounds

Less obese, with a BMI of 30 or above among 35.4% vs 45.3%

Had lower baseline IGA scores of 4 among 16.2% vs. 26.5%

Less likely to have nail psoriasis, 49.1% vs 64.9%

Less previous use of systemic non-biologic treatments, 60.9% vs 69%

Less likely to have metabolic syndrome at baseline, 19.9% vs 25.4%

Factors that were similar between the two groups included diabetes mellitus and hypertension, cigarette use, and baseline blood pressure, fasting glucose, and lipid levels.

“Based on the stepwise logistic regression model, only patient age at study entry, baseline body weight (≤90 kg vs >90 kg), baseline PASI, and baseline IGA score were significant predictors of super-response status,” the authors wrote.

Patients who achieved super-response were more likely to demonstrate early clinical responses, with 5.5% demonstrating a PASI 75 response as early as Week 2 compared with 1.8% of those with non-super-response. PASI 90 was achieved as early as Week 4 among 10% of those who achieved super-response versus 3.6% of those who didn’t, and PASI 100 was achieved as early as Week 8 among 22.5% versus 3.3%.

Limitations of the study include that it is a post hoc analysis with a relative small number of patients, super-response was only evaluated through Week 28 and super-response status was not analyzed for the adalimumab comparator group.

Guselkumab is the first IL-23 inhibitor approved for adults with psoriasis.

 found that guselkumab was associated with longer adherence and greater proxy remission rates than other biologic therapies, including adalimumab, secukinumab and ixekizumab.

Another recent study found that guselkumab was 

 and efficacious in patients with moderate to severe psoriasis regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. The interleukin 23 biologic also was associated with sustained tolerability and consistent psoriasis clearance 

“The availability of new biologics approved for psoriasis now makes achievement of clear skin a pragmatic treatment goal,” the study authors wrote. “Guselkumab, a first-in-class novel IL-23 p19 inhibitor, is effective and safe in the treatment of patients with moderate-to-severe plaque psoriasis, and complete clearance can be obtained in a significant proportion of patients.”

Super-Response to Guselkumab Treatment in Patients With Moderate-to-Severe Psoriasis: Age, Body Weight, Baseline Psoriasis Area and Severity Index, and Baseline Investigator’s Global Assessment Scores Predict Complete Skin Clearance

Journal of the European Academy of Dermatology and Venerology

A post-hoc analysis of clinical trial data found that psoriasis patients who were younger, less obese and had less severe psoriasis were more likely to achieve super-response to biologic treatment with guselkumab.

Greater Guselkumab Response More Likely Among Younger, Less Obese Psoriasis Patients

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