Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4+CD25+FOXP3+ regulatory T cells (Tregs). Previous phase 1 studies identified a low daily dose ...of interleukin-2 (IL-2) that was well tolerated, did not exacerbate alloimmunity, augmented Treg in vivo, and was associated with improvement of active cGVHD. In the current phase 2 study, 35 adults with steroid-refractory cGVHD received daily IL-2 (1 × 106 IU/m2) for 12 weeks. Median time from transplantation and cGVHD onset was 616 days (range, 270-2145 days) and 317 days (range, 28-1880 days), respectively. Two patients withdrew and 5 required IL-2 dose reductions due to side effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites (liver, skin, gastrointestinal tract, lung, joint/muscle/fascia). Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and natural killer cell counts rose >fivefold (P < .001) and >fourfold (P < .001), respectively, without significant change in conventional CD4 T cells (Tcons) or CD8 T cells. The Treg:Tcon ratio rose >fivefold (P < .001). Clinical responders initiated IL-2 earlier (508 vs 917 days after transplantation, P = .005; 249 vs 461 days after cGVHD onset; P = .03). Treg:Tcon ratios ≥0.07 at baseline and ≥0.2 at week 1 also predicted clinical response (P = .003; P = .0003, respectively). After a 4-week treatment hiatus, clinical responders were eligible to continue IL-2 therapy indefinitely. During 2 years of extended IL-2 therapy, clinical and Treg immune responses persisted, while Tcon count and Treg:Tcon ratio gradually normalized. Low-dose IL-2 provides durable clinical improvement in active cGVHD and extended therapy is well-tolerated.
•Low-dose IL-2 is efficacious in steroid-refractory cGVHD, with objective responses in >50% of patients, and durable disease control.•IL-2 initiation earlier after cGVHD onset, prior to severe impairment of Treg:Tcon ratios, improves likelihood of clinical response.
Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a ...monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab.
Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection.
Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter.
Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.
Screen time, social media, and weight-related bullying are ubiquitous among adolescents. However, little research has been conducted among international samples. Therefore, the aim of this study was ...to determine the association between screen time, social media use, and weight-related bullying victimization among an international sample of adolescents from six countries. Data from the 2020 International Food Policy Study Youth Survey were analyzed (N = 12,031). Multiple modified Poisson regression models were estimated to determine the associations between weekday hours of five forms of screen time, and total screen time, and use of six contemporary social media platforms and weight-related bullying victimization. Analyses were conducted among the overall sample, and stratified by country (Australia, Canada, Chile, Mexico, United Kingdom, United States). Greater hours of weekday screen time and use of each of the six social media platforms were associated with weight-related bullying victimization among the sample. Each additional hour of social media use was equivalent to a 13% (confidence interval CI 1.10-1.16) increase in the prevalence of weight-related bullying victimization. The use of Twitter was associated with a 69% (CI 1.53-1.84) increase in the prevalence of weight-related bullying victimization. Associations between hours of weekday screen time, use of six social media, and weight-related bullying victimization differed by country. Findings underscore the associations between screen time, social media, and weight-related bullying among a sample of adolescents from six medium- and high-income countries. Country-specific and global public health and technology efforts are needed to address this burgeoning social problem.
Autoimmune blistering disease management can be challenging as treatment modalities vary greatly and no single standard of care exists. We consolidated the recommendations of international management ...guidelines in order to provide optimal management suggestions to physicians. A comprehensive literature search in PubMed/MEDLINE for published blistering disease management guidelines and consensus statements was conducted in November 2019. Search terms included "guideline or guidelines" or "consensus" and "pemphigoid" or "autoimmune blistering disease" or "epidermolysis bullosa acquisita". We included guidelines from established dermatologic societies and expert consensus groups. We excluded literature reviews, guidelines established by an association without dermatologists, or those specific to a single treatment. Guidelines in all languages were considered. Eleven guidelines from dermatologic associations and consensus groups meeting our inclusion criteria were selected. Several differences between recommendations, most notably when to introduce adjuvants for refractory disease, were found in bullous pemphigoid. In mucous membrane pemphigoid, treatment was directed to the sites involved and managed with systemic corticosteroids and immunosuppressants/biologics. There was no universal consensus on the first-line treatment for epidermolysis bullosa acquisita, but a combination of immunosuppressive, anti-inflammatory, and anti-neutrophil therapy was utilized. Comparison of the management guidelines revealed underrepresentation of guidelines from developing nations and key differences between the management styles among dermatologists from Europe and Asia. We attribute these discrepancies to the time elapsed between guidelines, regional differences, and demands of the local healthcare systems.
IgA pemphigus: A systematic review Kridin, Khalaf; Patel, Payal M.; Jones, Virginia A. ...
Journal of the American Academy of Dermatology,
June 2020, 2020-Jun, 2020-06-00, 20200601, Volume:
82, Issue:
6
Journal Article
Peer reviewed
The clinical, histologic, and immunopathologic features of IgA pemphigus have not been studied on a large scale.
To synthesize existing data on the epidemiologic, clinical, histologic, and ...immunologic features of IgA pemphigus.
We performed a systematic review using MEDLINE, Embase, and Web of Science databases. Case reports and series of patients with IgA pemphigus were included.
A total of 119 eligible studies, comprising 137 patients with IgA pemphigus with a mean age of 51.5 ± 21.0 years, were included. Most patients presented with vesicles (80.8%), pustules (75.0%), and circinate plaques (63.6%). Pruritus was present in 65.6% of reported patients. Intercellular deposition of IgA was noted in almost all patients (97.0%), and the remaining 3.0% of patients had IgA positivity on indirect immunofluorescence or enzyme-linked immunosorbent assay confirming the diagnosis. IgA circulating intercellular antibodies were detected in only 66.7% patients. IgA gammopathy and ulcerative colitis were associated with IgA pemphigus in 9.5% and 6.6% patients, respectively. Oral dapsone and corticosteroids were the mostly commonly used treatments.
Results are mainly based on case reports and small case series.
The diagnosis of IgA pemphigus may be considered in patients presenting with vesiculopustular eruption and circinate plaques with truncal and extremity involvement.
Alterations in the extracellular matrix (ECM) likely facilitate the first steps of cancer cell metastasis and supports tumor progression. Recent data has demonstrated that alterations in collagen ...XVII (BP180), a transmembrane protein and structural component of the ECM, can have profound effects on cancer invasiveness. Collagen XVII is a homotrimer of three α1 (XVII) chains. Its intracellular domain contains binding sites for plectin, integrin β4, and BP230, while the extracellular domain facilitates interactions between the cell and the ECM. Collagen XVII and its shed ectodomain have been implicated in cell motility and adhesion and are believed to promote tumor development and invasion. A strong association of collagen XVII ectodomain shedding and tumor invasiveness occurs in squamous cell carcinoma (SCC). Aberrant expression of collagen XVII has been reported in many epithelial cancers, ranging from squamous cell carcinoma to colon, pancreatic, mammary, and ovarian carcinoma. Thus, in this review, we focus on collagen XVII's role in neoplasia and tumorigenesis. Lastly, we discuss the importance of targeting collagen XVII and its ectodomain shedding as a novel strategy to curb tumor growth and reduce metastatic potential.
Dipeptidyl peptidase‐4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and ...soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T‐cell biology, the induction of skin‐specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin‐1, CXCR4 receptor, M6P/insulin‐like growth factor II‐receptor and fibroblast activation protein‐α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1‐like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.
This study aimed to investigate whether screen time and social media use are associated with weight-change behaviors among an international sample of adolescents. Cross-sectional data from the 2020 ...International Food Policy Study Youth Survey (ages 10–17; Australia, Canada, Chile, Mexico, United Kingdom, United States; N = 12,031) were analyzed. Self-reported hours of use of five forms of screen time (e.g., social media use), and total screen time per weekday were assessed. Use of six contemporary social media platforms (e.g., Facebook, Instagram) were also assessed. Weight-change behaviors included current attempts to gain weight, lose weight, stay the same weight, and not do anything to change weight, as well as dieting to lose weight in the past 12 months. Greater total screen time per weekday was associated with attempts to gain weight and lose weight, and dieting to lose weight. Specific social media platform use was associated with weight-change behaviors. For example, use of Twitter was most strongly associated with attempts to gain weight, lose weight, and dieting to lose weight. Findings underscore the international pervasiveness of screen time and social media use correlating with weight-change behaviors among adolescents. Global efforts are needed to ensure the appropriate use of screens and social media among adolescents.
•We investigated associations between screen time, social media use, and weight-change behaviors.•Greater total recreational screen time was associated with both weight loss and weight gain attempts.•Use of Twitter was most strongly associated with both weight loss and weight gain attempts.
Introduction Non-fatal shooting rates vary tremendously within cities in the USA. Factors related to structural racism (both historical and contemporary) could help explain differences in non-fatal ...shooting rates at the neighbourhood level. Most research assessing the relationship between structural racism and firearm violence only includes one dimension of structural racism. Our study uses an intersectional approach to examine how the interaction of two forms of structural racism is associated with spatial non-fatal shooting disparities in Baltimore, Maryland.Methods We present three additive interaction measures to describe the relationship between historical redlining and contemporary racialized economic segregation on neighbourhood-level non-fatal shootings.Results Our findings revealed that sustained disadvantage census tracts (tracts that experience contemporary socioeconomic disadvantage and were historically redlined) have the highest burden of non-fatal shootings. Sustained disadvantage tracts had on average 24 more non-fatal shootings a year per 10 000 residents compared with similarly populated sustained advantage tracts (tracts that experience contemporary socioeconomic advantage and were not historically redlined). Moreover, we found that between 2015 and 2019, the interaction between redlining and racialized economic segregation explained over one-third of non-fatal shootings (approximately 650 shootings) in sustained disadvantage tracts.Conclusion These findings suggest that the intersection of historical and contemporary structural racism is a fundamental cause of firearm violence inequities in Baltimore. Intersectionality can advance injury prevention research and practice by (1) serving as an analytical tool to expose inequities in injury-related outcomes and (2) informing the development and implementation of injury prevention interventions and policies that prioritise health equity and racial justice.
Background:
There has been a renewed interest in ulnar collateral ligament (UCL) repair in overhead athletes because of a greater understanding of UCL injuries, an improvement in fixation technology, ...and the extensive rehabilitation time to return to play.
Purpose/Hypothesis:
To evaluate the clinical outcomes of a novel technique of UCL repair with internal brace augmentation in overhead throwers.
Study Design:
Case series; Level of evidence, 4.
Methods:
Patients undergoing a novel technique of UCL repair with internal brace augmentation were prospectively followed for a minimum of 1 year. Potential candidates for repair were selected after the failure of nonoperative treatment when imaging suggested a complete or partial avulsion of the UCL from either the sublime tubercle or medial epicondyle, without evidence of poor tissue quality of the ligament. The final decision on UCL repair or traditional reconstruction was determined intraoperatively. Demographic and operative data were collected at the time of surgery. Return to play, and Kerlan-Jobe Orthopaedic Clinic (KJOC) scores were collected at 1 year and then again at 2 years postoperatively.
Results:
Of the 111 overhead athletes eligible for the study, 92% (102/111) of those who desired to return to the same or higher level of competition were able to do so at a mean time of 6.7 months. These patients had a mean KJOC score of 88.2 at final follow-up.
Conclusion:
UCL repair with internal brace augmentation is a viable option for amateur overhead throwers with selected UCL injuries who wish to return to sport in a shorter time frame than allowed by traditional UCL reconstruction.
PDF
