Risk factors that limit use of oral JAK inhibitors in chronic hand eczema: Findings from the Danish Skin Cohort.

Background: Oral Janus kinase inhibitors (JAKis) have black-box warnings of infections, cancer risk, and cardiovascular and venous thromboembolic events. They may be used off-label for chronic hand eczema (CHE). Objectives: Assess the prevalence of risk factors potentially impacting oral JAKi safety in CHE patients. Methods: In the Danish Skin Cohort, CHE patients were examined for risk factors affecting oral JAKi use at baseline and followed for 12 months. Data were collected through register linkage (eg, cancer history) and through patient interviews (eg, smoking habits). Results: Of 941 adults with CHE (66.2% women; mean age 55.5 [SD 13.3] years), 768 (81.6%) patients had at least one risk factor potentially impacting oral JAKi use, of which 682 (72.5%) had nonmodifiable risk factors. Most common risk factors were current or former heavy smoking (62.8%, n = 591), obesity (28.1%, n = 264), hypercholesterolemia (21.5%, n = 202), and hypertension (18.8%, n = 177). Among patients without any risk factors at baseline (n = 173), 20.2% (n = 35) developed ≥1 risk factor during the following 12 months. Limitations: Certain risk factors may be underreported. Conclusion: Most CHE patients have risk factors limiting appropriateness of oral JAKi use. Health care providers should assess risk factors in their patients when choosing treatment for CHE.

Risk factors for oral frailty among community-dwelling pre-frail older adults in Japan: A cross-sectional analysis.

OBJECTIVES: Oral frailty is a well-established risk factor for frailty and plays a significant role in progression to frailty. However, the association between oral frailty and pre-frailty in elderly individuals remains unclear. This cross-sectional study aimed to clarify the characteristics and risk factors of pre-frailty in elderly individuals with oral frailty. METHODS: A total of 377 elderly individuals participated. Oral examinations comprised simple and non-invasive measures of chewing function, self-reported swallowing function, and oral moisture. The frailty screening index was used to assess frailty phenotypes. RESULTS: The overall prevalence of pre-frailty was 63.1%, after excluding 40 frail and 99 robust individuals. The mean age of the pre-frail participants was 76.6 ± 5.8 years; 70.6% were women. 10.5% of the pre-frail elderly participants had oral frailty. In multivariate analysis diabetes mellitus, history of cancer, denture wearing, and malnutrition were independently associated with oral frailty among pre-frail elderly individuals (adjusted odds ratio (OR) 3.8, 95% confidence interval (CI) 1.06-13.54; OR 4.5, CI 1.32-15.36; OR 8.8, CI 1.76-43.78; and OR 3.6, CI 1.30-9.67; respectively). CONCLUSIONS: The prevalence of oral frailty was low among community-dwelling pre-frail elderly individuals. Early interventions involving oral, nutritional, and disease management may prevent or improve oral frailty in pre-frail elderly individuals and may prevent progression to frailty. Further studies are required to elucidate the underlying mechanisms.

Patient characteristics and disease burden of alopecia areata in the Danish Skin Cohort.

PURPOSE: Alopecia areata (AA) is a common disorder of patchy hair loss which carries a substantial psychological burden for patients. The current understanding of AA prevalence, disease course and burden is limited, and further research is needed to improve patient care. This prospective cohort of AA patients within the Danish Skin Cohort was established to provide data that can serve as a tool in future studies of for example, AA epidemiology and disease burden. PARTICIPANTS: A total of 1494 patients with dermatologist-verified AA were included in the cohort. Patients were invited and included through electronic or phone-based questionnaires. Information regarding demographics, biometrics, lifestyle factors, skin type, AA onset and development, health-related quality of life and self-reported severity assessment was collected. FINDINGS TO DATE: The mean (SD) age of AA onset was 32.7 (17.6) years. The mean body mass index and history of cigarette smoking was comparable with the general population. The majority (92.5%) of participants were Caucasian. In total, 72.4% of patients received their diagnosis by a physician within a year after onset of symptoms, and 66.9% reported to still have symptoms of AA within the past year. A total of 12% reported to have a first-degree family member with AA. In total, 31.4% of patients were missing all or nearly all hairs on their scalp, 32.2% had no or barely no eyelashes and 36.2% had no or barely no eyebrow hairs. Overall, most patients (55.7%) did not experience irritated eyes, but 30% reported slight eye irritation and 47.2% reported no damage to finger nails or toenails. FUTURE PLANS: Observational studies regarding comorbidities, psychosocial burden of AA and efficacy of pharmacological interventions will be carried out and additional data will be linked from nationwide registries of routinely collected data. Furthermore, follow-up survey data will be added for longitudinal analyses.

Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma.

PURPOSE OF REVIEW: In this review article, we summarize the current evidence about atopic dermatitis (AD)-associated comorbidities, beyond the traditional atopic and allergic conditions. RECENT FINDINGS: Patients with AD may have an increased risk of cardiovascular diseases, certain malignancies, autoimmune diseases, and neuropsychiatric diseases. The causes of these associations are likely multifactorial and may include genetic predispositions, systemic low-grade inflammation, environmental exposures, medication, and lifestyle and behavioral risk factors. There appears to be geographical variations in prevalence of comorbidities in patients with AD, indicating that differences in ethnicity and lifestyle factors may significantly influence the risk of certain comorbidities. SUMMARY: The reported comorbidities in recent literature emphasize the burden of disease in patients with AD. Early appropriate AD therapy, in combination with reduction of risk factors, may help prevention of certain comorbidities. The reported observations may generate hypotheses for future investigations in underlying risk factors for AD-associated comorbidities.

Prevalence of Cancer in Adult Patients with Atopic Dermatitis: A Nationwide Study.

is missing (Short communication).

Ten-year mortality is increased after hospitalization for atopic dermatitis compared with the general population, but reduced compared with psoriasis.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin disorders. Mortality is increased in psoriasis, yet no studies on mortality in AD are currently available. OBJECTIVE: We investigated 10-year mortality after hospitalization for AD compared with psoriasis and the general population. METHODS: Between 1996 and 2002 all Danes aged 18 years or older with a first-time hospitalization as a result of AD or psoriasis and AD-matched healthy control subjects were examined in nationwide registers. Multivariable (adjusted for age, sex, socioeconomic status, Charlson Comorbidity Index score, smoking, and medication) hazard ratios were estimated by Cox regression. RESULTS: The study comprised 576 and 951 hospitalized patients with AD and psoriasis, respectively, with a maximum follow-up time of 10 years. During the study period, there were 65 and 286 deaths among patients with AD and psoriasis. Risk of death was decreased in patients with AD versus psoriasis (hazard ratio 0.75; 95% confidence interval 0.57-1.00), but higher than in general population control subjects (n = 5760) (hazard ratio 1.71; 95% confidence interval 1.20-2.44). Patients hospitalized with AD died on average 8.3 years younger than control subjects. LIMITATIONS: Lifestyle may have affected the risk. CONCLUSIONS: The 10-year mortality was significantly lower after hospitalization for AD compared with psoriasis, but increased when compared with the general population.

Autoimmune diseases in adults with atopic dermatitis.

BACKGROUND: An increased susceptibility to autoimmune disease has been shown in patients with atopic dermatitis (AD), but data remain scarce and inconsistent. OBJECTIVE: We examined the co-occurrence of selected autoimmune diseases in adult patients with AD. METHODS: Nationwide health registers were used. Adult patients with a hospital diagnosis of AD in Denmark between 1997 and 2012 were included as cases (n = 8112) and matched with controls (n = 40,560). The occurrence of autoimmune diseases was compared in the 2 groups. Logistic regression was used to estimate odds ratios. RESULTS: AD was significantly associated with 11 of 22 examined autoimmune diseases. In addition, AD was associated with having multiple autoimmune comorbidities. Patients with a history of smoking had a significantly higher occurrence of autoimmune comorbidities compared to nonsmokers. LIMITATIONS: This study was limited to adult patients with AD. No information about AD severity or degree of tobacco consumption was available. Results from a hospital population of AD patients cannot be generalized to the general population. CONCLUSIONS: Our results suggest a susceptibility of autoimmune diseases in adult patients with AD, especially in smokers. While we cannot conclude on causality based on these data, an increased awareness of autoimmune comorbidities in patients with AD may be warranted.

Synthesis of Paclitaxel. 1. Synthesis of the ABC Ring of Paclitaxel by SmI2-Mediated Cyclization.

A convergent synthesis of the ABC ring of antitumor natural product paclitaxel (Taxol) is described. SmI2-mediated reductive cyclization of an allylic benzoate possessing an aldehyde function, synthesized from tri-O-acetyl-d-glucal and 1,3-cyclohexanedione, smoothly afforded the highly strained 6-8-6 tricarbocyclic structure in 66% yield.

Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia.

The purpose of this study was to explore the role of the organic anion-transporting polypeptide (OATP) 1A2, which is encoded by SLCO1A2, in the cellular uptake of the Bcr-Abl tyrosine kinase inhibitor imatinib, and the relationship between SLCO1A2 polymorphisms and the pharmacokinetics of imatinib in patients with chronic myeloid leukemia (CML). Imatinib uptake was significantly enhanced in OATP1A2-transfected human embryonic kidney (HEK) 293 cells (P = 0.002). Naringin, an OATP1A2 inhibitor, decreased the transport of imatinib in OATP1A2-transfected HEK293 cells, the human intestinal cell line Caco-2, and K562 CML cells. Linkage disequilibrium was found between the SLCO1A2 -1105G>A and -1032G>A genotypes in 34 CML patients and 100 healthy subjects. Imatinib clearance in CML patients was influenced by the SLCO1A2 -1105G>A/-1032G>A genotype (P = 0.075) and the SLCO1A2 -361GG genotype (P = 0.005). These findings suggest that imatinib is transported into cells by OATP1A2, and that SLCO1A2 polymorphisms significantly affect imatinib pharmacokinetics.

A case of non-regenerative immune-mediated anemia treated by combination therapy of human immune globulin and mycophenolate mofetil in a dog.

A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe non-regenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune-mediated anemia was diagnosed. The dog was initially treated using prednisolone and cyclosporine. However, this treatment regimen did not prove effective. Nevertheless, the patient achieved a good hematological response after the administration of a combination therapy of human immune globulin and mycophenolate mofetil. Such a combination therapy may prove effective against non-regenerative immune-mediated anemia.

A immunohistochemical study of the peripheral ameloblastoma.

AIM: Peripheral ameloblastoma (PA) is a rare variant of ameloblastoma occurring in the extraosseous region. With regard to the histogenesis of the tumor, two major sources of origin are considered: odontogenic epithelial remnants and the gingival epithelium. In this study, we examined the immunohistochemical profiles of cytokeratins (CKs) and Ki-67 labeling index (LI) of PAs, and discuss the histogenesis and the biologic behavior of the PA. MATERIALS AND METHODS: Eight cases of PA were retrieved from the pathology files of 212 cases of ameloblastoma that had been registered at our hospital. Immunohistochemical staining was performed in seven cases using monoclonal antibodies of six CKs (7, 8, 13, 14, 18, and 19) and Ki-67. RESULTS: All cases of PA expressed CK13, 14, and 19. CK18 was positive staining in six cases, and CK8 in five cases. This staining pattern was similar to that in intraosseous ameloblastomas (IAs). The mean of Ki-67 LI of PAs (1.91%) was significantly lower than that of IAs (4.82%) (P = 0.002). CONCLUSION: We consider that the PA originates from odontogenic epithelial remnants rather than from the gingival epithelium, and the Ki-67 LI of the tumor is a good prognostic indicator.

Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma.

BACKGROUND: Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS: A retrospective case-control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFbetaRII, and BAX). The authors also looked for K-ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K-ras, p53, etc.) were investigated. RESULTS: Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3-5 investigated site (MSI-H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K-ras mutations. CONCLUSIONS: Thirty percent of patients with recurrent disease showed MSI-H, whereas none of the patients with nonrecurrent disease did so.

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis.

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.

Influence of Helicobacter pylori infection on the prevalence of reflux esophagitis in Japanese patients.

BACKGROUND AND AIM: Reflux esophagitis is caused by esophageal motor dysfunction in patients with sufficient gastric acid secretion. Helicobacter pylori causes atrophic gastritis and influences gastric acid secretion. Hiatus hernia (HH) of the esophagus causes motor dysfunction in the lower esophagus. Therefore, this study aimed to test whether H. pylori infection, gastric mucosal atrophy and HH are predictive factors for reflux esophagitis. METHODS: Helicobacter pylori infection was examined in 781 patients by the measurement of serum immunoglobulin (Ig)G antibody, bacteriological culture and histological examination of biopsy specimens. The prevalence of HH, endoscopically identified gastric mucosal atrophy (closed- or open-type) and reflux esophagitis were investigated by reviewing endoscopic films. Investigated patients were divided into three age groups, under 49, 50-69, and over 70 years. The prevalence of esophagitis, H. pylori infection, gastric mucosal atrophy, and HH were compared to identify the possible predictive factors for reflux esophagitis by using logistic regression analysis. RESULTS: Sixty-nine patients with reflux esophagitis were found among the 781 investigated cases. The odds ratios of negative H. pylori infection, endoscopically identified closed-type gastric mucosal atrophy, and HH for the prevalence of reflux esophagitis were 1.342, 1.751 and 5.527, respectively. These results indicated that the presence of H. pylori infection was only a weak negative risk factor, and that HH was the most reliable endoscopic predictive factor for reflux esophagitis. CONCLUSION: Helicobacter pylori infection is a weak negative risk factor for the prevalence of reflux esophagitis, while HH is the most reliable predictive factor.

Multifocal primary lymphoma of bone: scintigraphy and MR findings before and after treatment.

A case of multifocal primary lymphoma of bone is reviewed. Ga-67 citrate, Tc-99m HMDP, and Tl-201 scintigraphs all showed multifocal radiotracer accumulation. CT showed subtle osteolytic and osteosclerotic changes with surrounding soft tissue density mass. MRI clearly showed abnormal signal intensity in the bone marrow. After systemic chemotherapy and infield radiotherapy, the patient showed clinically complete remission. MRI showed reduction of the extraosseous components, but there was little signal change in the bone marrow despite the clinical response to the therapy. Scintigrams were more useful than MRI and CT for both staging and assessing the early response to therapy. The soluble interleukin-2 receptor level was found to be related to tumor cell activity.