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Abstract Background The COVID-19 pandemic has widespread consequences for health facilities, social contacts, and health-seeking behaviour, affecting the incidence, diagnosis and reporting of other infectious diseases. We examined trends in reported chronic hepatitis C virus (HCV) infections and associated transmission routes in the Netherlands to identify the potential impact of COVID-19 on access to healthcare (testing) services. Methods We analysed notification data of patients with chronic HCV reported to the National Notifiable Disease Surveillance System from January 2019 until December 2021 in the Netherlands. Rates of newly reported chronic cases per 100,000 population with 95% confidence intervals (CI) were calculated, and we compared proportional changes in transmission routes for chronic HCV between 2019, 2020 and 2021. Results During the study period, a total of 1,521 chronic HCV infections were reported, 72% males, median age 52 years, and an overall rate of 8.8 (95%CI 8.4–9.2) per 100,000 population. We observed an overall decline (-41.9%) in the number of reported chronic HCV in 2020 compared to 2019, with the sharpest decline in men who have sex with men (MSM)-related transmission (-57.9% in 2020, p = 0.005). Conclusions Reported cases of chronic HCV strongly declined during the COVID-19 pandemic when healthcare services were scaled down. Between February and June 2021, reported chronic HCV cases increased again, indicating a recovery of healthcare services. MSM showed the largest decline compared to other groups. Further research is needed to fully understand the impact of access to healthcare, health seeking behaviour, and (sexual) transmission risks of HCV during the COVID-19 pandemic.

Objectives The Modern Innovative Solutions to Improve Outcomes in Asthma, Breathlessness and Chronic Obstructive Pulmonary Disease (COPD) (MABC) service aimed to enhance disease management for chronic respiratory conditions through specialist multidisciplinary clinics, predominantly in the community. This study assesses the outcomes of these clinics.Design This study used a prospective, longitudinal, participatory action research approach.Setting The study was conducted in primary care practices across Hampshire, UK.Participants Adults aged 16 years and above with poorly controlled asthma or COPD, as well as those with undifferentiated breathlessness not under specialist care, were included.Interventions Participants received care through the multidisciplinary, specialist-led MABC clinics.Primary and secondary outcome measures Primary outcomes included disease activity, quality of life and healthcare utilisation. Secondary outcomes encompassed clinic attendance, diagnostic changes, patient activation, participant and healthcare professional experiences and cost-effectiveness.Results A total of 441 participants from 11 general practitioner practices were recruited. Ninety-six per cent of participants would recommend MABC clinics. MABC assessments led to diagnosis changes for 64 (17%) participants with asthma and COPD and treatment adjustments for 252 participants (57%). Exacerbations decreased significantly from 236 to 30 after attending the clinics (p

Early detection of liver transplantation (LT) vascular complications enables timely management. Our aim was to assess if routine Doppler ultrasound (rDUS) improves the detection of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT) and hepatic venous outflow obstruction (HVOO). We retrospectively analysed timing and outcomes, number needed to diagnose one complication (NND) and positive predictive value (PPV) of rDUS on post-operative day (POD) 0,1 and 7 in 708 adult patients who underwent primary LT between 2010–2022. We showed that HAT developed in 7.1%, PVT in 8.2% and HVOO in 3.1% of patients. Most early complications were diagnosed on POD 0 (26.9%), 1 (17.3%) and 5 (17.3%). rDUS correctly detected 21 out of 26 vascular events during the protocol days. PPV of rDUS was 53.8%, detection rate 1.1% and NND was 90.5. Median time to diagnosis was 4 days for HAT and 47 days for PVT and 21 days for HVOO. After intervention, liver grafts were preserved in 57.1%. In conclusion, rDUS protocol helps to detect first week’s vascular events, but with low PPV and a high number of ultrasounds needed.

Background/Purpose(s): Since ALT flares after therapy withdrawal are associated with adverse outcomes, risk stratification is of major importance. We aimed to study whether off-treatment flares are related with virological outcomes, and if serum levels of novel biomarkers at end-of-treatment (EOT) can predict flares. Methods: Chronic hepatitis B patients who participated in three global randomised trials of peginterferon-based therapy were studied (99–01, PARC, ARES). HBV RNA, HBsAg and HBcrAg were quantified at EOT. Associations between EOT biomarker levels and flares were assessed as continuous data and after categorisation. Flares were defined as ALT ≥5xULN during six months after therapy cessation. Results: We included 344 patients; 230 HBeAg-positive and 114 HBeAg-negative. Patients were predominantly Caucasian (77.0%) and had genotype A/B/C/D in 23.3/7.3/13.4/52.3%. Flares were observed in 122 patients (35.5%). Flares were associated with lower rates of sustained response (3.5% vs 26.8% among patients with and without a flare; p

Background & Aims: Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation. Methods: Patients with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal. Results: We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels 20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p

Introduction/purpose: This paper reports on a pilot comparative analysis of the Cuckoo and Drakvuf sandboxes. These sandboxes are selected as the subjects of the analysis because of their popularity in the professional community and their complementary approaches to analyzing malware behavior. Methods: Both sandboxes were set up with basic configurations and confronted with the same set of malware samples. The evaluation was primarily conducted with respect to the question of to what extent a sandbox is helpful to the human analyst in malware analysis. Thus, only the information available in Web console reports was considered. Results: Drakvuf is expected to perform better when confronted with evasive malware and so-called “file-less” malware. Although still not mature in terms of integration, customization and tools, this sandbox is considered a second generation sandbox because of its agentless design. On the other hand, the Cuckoo sandbox creates a better overall experience: it is supported through good documentation and strong professional community, better integrated with various tools, support more virtualization, operating system and sample types, and generates more informative reports. Even with a smaller capacity to prevent evasive malware, its Python 2 agent script makes it more powerful than Drakvuf. Conclusion: To achieve the optimal open-source sandbox-based protection, it is recommended to apply both the Cuckoo and Drakvuf sandboxes. In circumstances of limited resources, applying the Cuckoo sandbox is preferable, especially if exposure to malware deploying evading techniques is not frequently expected.

Portable air purifiers have been extensively used to improve indoor air quality and mitigate the transmission of airborne diseases. However, the efficacy of mitigation is strongly affected by the interactions between jet flows of processed air from the air purifiers and the background airflows driven by the ventilation system. Critical factors in this context include the position and capacity of air purifiers and the ventilation rate of the heating ventilation and air-conditioning (HVAC) system. These factors are investigated in this study via computational fluid dynamics (CFD) simulations and the infection probability for different scenarios is quantified using the latest airborne infection predictive model incorporating recent pathological and clinical data for SARS-CoV-2. The results show that the use of air purifiers can significantly reduce the concentration of particulate matter, thus contributing to a generally lower risk of airborne transmission. However, the position of air purifiers affects their overall efficacy remarkably. Comparatively, a central HVAC system is more efficient at removing airborne particles under an equivalent ventilation rate assuming it uses a mixing ventilation scheme.

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used with other cancer treatment modalities. The most common AE associated with TTFields therapy is mild-to-moderate skin events, which can be treated with topical agents and may be managed without significant treatment interruptions. Currently, there are no guidelines for oncologists regarding the management of TTFields therapy-related skin AEs in the thoracic region, applicable for patients with pleural mesothelioma or NSCLC. This publication aims to provide guidance on preventing, minimizing, and managing dermatologic AEs in the thoracic region to help improve patient quality of life and reduce treatment interruptions that may impact outcomes with TTFields therapy.

The quality of life as a complex phenomenon may be observed and interpreted in different ways. This paper emphasize that term the quality of life should be studied as an interaction of human needs and subjective perception. This paper also attempt to explore how to build and create the basics for creating an innovative culture, or innovative environment, to improve measurement of objective and subjective perceptions and collect data for indicators of quality of life. The overview is presented as a possible working model that allows researchers and other interested parties to group individual factors into different categories of quality of life that may be considered as an additional value of systems and processes. The paper also tried to explain the relationship between public and organizational culture, the influence of cultural differences, known published standards in this field and the quality of life. Culture is structurally viewed as a traditional, civic, organizational, culture of quality, improvement culture and innovative culture. However, the emphasis is placed on ISO standards for innovation management systems, which are in the process of publishing, which relate to the creation of an innovative culture, or standardized management solutions to innovation systems. There is a well-founded and mutual relationship in the triangle of public and organizational culture, innovation culture and quality of life, based on international standards.

Background & Aims: A recent consensus document has defined metabolic dysfunction-associated fatty liver disease (MAFLD) as hepatic steatosis together with overweight, diabetes, and/or a combination of other metabolic risk factors. The clinical relevance of this novel diagnosis is unknown among patients with chronic hepatitis B (CHB). We studied the association between MAFLD (with or without steatohepatitis) and adverse clinical outcomes in patients with CHB. Methods: We performed a retrospective long-term follow-up cohort study at 2 tertiary hospitals in patients with CHB who underwent liver biopsy. Biopsies were reassessed for steatosis, degree of fibrosis, and presence of steatohepatitis. Associations with event-free hepatocellular carcinoma (HCC)-free and transplant-free survival were explored. Results: In our cohort, 1076 patients were included, median follow-up was 9.8 years (25th–75th percentile: 6.6−14.0), and 107 events occurred in 78 patients, comprising death (n = 43), HCC (n = 36), liver decompensation (n = 21), and/or liver transplantation (n = 7). MAFLD was present in 296 (27.5%) patients and was associated with reduced event-free (adjusted hazard ratio [aHR] 2.00, 95% CI 1.26–3.19), HCC-free (aHR 1.93, 95% CI 1.17–3.21), and transplant-free survival (aHR 1.80, 95% CI 0.98–3.29) in multivariable analysis. Among patients with MAFLD, the presence of steatohepatitis (p = 0.95, log-rank test) was not associated with adverse outcomes. Conclusions: The presence of MAFLD in patients with CHB was associated with an increased risk for liver-related clinical events and death. Among patients with MAFLD, steatohepatitis did not increase the risk of adverse outcomes. Our findings highlight the importance of metabolic dysfunction in patients with CHB. Lay summary: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been defined as fatty liver disease with signs of metabolic dysfunction. Among patients with chronic hepatitis B, MAFLD was associated with liver-related events and death. Metabolic health assessment should be encouraged among patients with chronic hepatitis B, especially in those with fatty liver disease.

BackgroundA limited number of targeted therapy options exist for papillary thyroid cancer (PTC) to date. Based on genetic alterations reported by the “The Cancer Genome Atlas (TCGA)”, we explored whether PTC shows alterations that may be targetable by drugs approved by the FDA for other solid cancers.MethodsDatabases of the National Cancer Institute and MyCancerGenome were screened to identify FDA-approved drugs for targeted therapy. Target genes were identified using Drugbank. Genetic alterations were classified into conferring drug sensitivity or resistance using MyCancerGenome, CiViC, TARGET, and OncoKB. Genomic data for PTC were extracted from TCGA and mined for alterations predicting drug response.ResultsA total of 129 FDA-approved drugs with 128 targetable genes were identified. One hundred ninety-six (70%) of 282 classic, 21 (25%) of 84 follicular, and all 30 tall-cell variant PTCs harbored druggable alterations: 259 occurred in 29, 39 in 19, and 31 in 2 targetable genes, respectively. The BRAF V600 mutation was seen in 68% of classic, 16% of follicular variant, and 93% of tall-cell variant PTCs. The RET gene fusion was seen in 8% of classic PTCs, NTRK1 and 3 gene fusions in 3%, and other alterations in

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the medical records of all CHB patients who visited our outpatient clinic in 2020. Adherence to guidelines was assessed based on predefined criteria based on the EASL guidance, and included the initiation of antiviral therapy when indicated, the optimal choice of antiviral therapy based on comorbidities, an assessment of HAV/HCV/HDV/HIV serostatus, renal function monitoring and enrolment in a HCC surveillance program if indicated. The adherence rates were compared across types of outpatient clinic (dedicated viral hepatitis clinic versus general hepatology clinic). Results: We enrolled 482 patients. Among the 276 patients with an indication for antiviral therapy, 268 (97.1%) received treatment. Among the patients with renal and/or bone disease, 26/29 (89.7%) received the optimal choice of antiviral agent. The assessment of HAV/HCV/HDV/HIV serostatus was performed in 86.1/91.7/94.4/78.4%. Among the 91 patients treated with tenofovir disoproxil, 57 (62.6%) underwent monitoring of renal function. Of the 241 patients with an indication for HCC surveillance, 212 (88.3%) were enrolled in a surveillance program. Clinics dedicated to viral hepatitis had superior adherence rates compared to general hepatology clinics (complete adherence rates 63.6% versus 37.2%, p < 0.001). Conclusions: Follow-up at a dedicated viral hepatitis clinic was associated with superior adherence to management guidelines.

Importance: Tumor Treating Fields (TTFields) are an anti-mitotic treatment approved for treating newly diagnosed and recurrent glioblastoma, and mesothelioma. TTFields in glioblastoma comprise alternating electric fields (200 kHz) delivered continuously, ideally for ≥18 h/day, to the tumor bed via transducer arrays placed on the shaved scalp. When applied locoregionally to the tumor bed and combined with systemic temozolomide chemotherapy, TTFields improved overall survival vs. temozolomide alone in patients with newly diagnosed glioblastoma. Improved efficacy outcomes with TTFields were demonstrated, while maintaining a well-tolerated and manageable safety profile. The most commonly-reported TTFields–associated adverse events (AEs) are beneath-array dermatologic events. Since survival benefit from TTFields increases with duration-of-use, prevention and management of skin AEs are critical to maximize adherence. This paper describes TTFields-associated dermatological AEs and recommends prevention and management strategies based on clinical trial evidence and real-world clinical experience.Observations: TTFields–associated skin reactions include contact dermatitis (irritant/allergic), hyperhidrosis, xerosis or pruritus, and more rarely, skin erosions/ulcers and infections. Skin AEs may be prevented through skin-care and shifting (~2 cm) of array position during changes. TTFields–related skin AE management should be based on clinical phenotype and severity. Depending on diagnosis, recommended treatments include antibiotics, skin barrier films, moisturizers, topical corticosteroids, and antiperspirants. Water-based lotions, soaps, foams, and solutions with minimal impact on electrical impedance are preferred with TTFields use over petroleum-based ointments, which increase impedance.Conclusions: Early identification, prophylactic measures, and symptomatic skin AE management help patients maximize TTFields usage, while maintaining quality-of-life and optimizing therapeutic benefit.Implications for practice: TTFields confer a survival benefit in patients with glioblastoma that correlates positively with duration of daily use. Skin events (rash) are the primary treatment-related AE that can limit duration of use. The recommendations described here will help healthcare professionals to recognize, prevent, and manage dermatologic AEs associated with TTFields treatment. These recommendations may improve cutaneous health and support adherence to therapy, both of which would maximize treatment outcomes.

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p

Several open issues remain concerning the quantitative understanding of irradiation hardening in high-Cr steels. One of these issues is addressed here by correlating yield points that are observed in stress-strain curves with dislocation decoration observed by TEM for neutron-irradiated Fe-Cr alloys. It is found that both higher neutron exposure and higher Cr content promote irradiation-induced loops to arrange preferentially along dislocation lines. Consequently, the activation of dislocation sources requires unlocking from the decorating loops, thus resulting in a yield drop. This process is considered within the source hardening model as opposed to the dispersed barrier hardening model, the latter aimed to describe dislocation slip through a random array of obstacles. Microstructure-informed estimates of the unlocking stress are compared with measured values of the upper yield stress. As functions of neutron exposure, a cross-over from the dominance of dispersed-barrier hardening accompanied by smooth elastic-plastic transitions to the dominance of source hardening accompanied by yield drops is observed for Fe-9% Cr and Fe-12% Cr.

Detection data from a regional, reptile-monitoring program conducted by the U.S. Geological Survey were analyzed to understand the effects of urbanization and habitat composition on site occupancy of the coachwhip (Masticophis flagellum) and striped racer (M. lateralis) in coastal southern California. Likelihood-based occupancy models indicated striped racers responded to habitat composition, favoring scrub-dominated sites. Coachwhips also responded to habitat composition, favoring open habitats. However, unlike racers, coachwhip spatial population dynamics were strongly associated with the fragmentation and isolation of natural areas caused by urbanization. The odds of coachwhips occupying a site were 64 times greater in large connected areas than the most urbanized and fragmented sites. For coachwhips within urbanized and fragmented sites, the odds of extinction were 10 times greater and odds of colonization were five times lower than in large connected sites. Observed differences between the species in habitat use and specificity are supported by telemetry studies and corroborate existing knowledge of historical patterns of occurrence within the region. Movement data on the coachwhip and striped racer indicate the coachwhip is a wider-ranging species with a greater propensity to encounter roads and other edge environments. Collectively, the results suggest there is widespread loss of the coachwhip from the region, and that long-term persistence of remaining populations is dependent on metapopulation dynamics. The substantially different response of the two species to land-use change serves as a caution against the casual use of closely related species as surrogates in the development of species-specific conservation plans. Keywords: Connectivity, Extinction, Habitat fragmentation, Isolation, Masticophis flagellum, Masticophis fuliginosus, Masticophis lateralis, Occupancy

This paper explores the experience of the Zavodi “Crvena Zastava” (Red Flag factory) of building the Yugoslav automobile industry between 1950s and 1980s. In 1954 Zastava began to manufacture automobiles based on the FIAT license and became the engine that drove the transformation of Yugoslavia from an agrarian into industrialized, urban and motorized country. However, its own development was hampered by the lack of stability in the Yugoslav socialist system under continual process of change and decentralization. This paper will examine crucial stages in Zastava’s development in the context of the Yugoslav evolving self-management system in order to discuss some theoretical issues and problems of practical applications. The aim is to show that while the concept of self-management was reasonable in the light of Yugoslavia’s break from the Soviet bloc, the net effect of its practices proved problematic for the automobile industry.

Ethics in the social life of the people there since ancient times. Not so long ago, jobs were assembled so that, after the deal, people shake hands. Such a ritual was enough to formalize the act of entering into a business deal. Over time, he grew up living standards, it appears that the mistrust between the people grew, the business is not the same as before, and corruption is all over. Countries in transition, going through a period when food is fixed in a sensitive stage and when corruption is playing a very important role in the progress of the economy of a country.

BACKGROUND/OBJECTIVE:Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. PATIENTS AND METHODS:This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. RESULTS:In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p

Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have been maintained in eukaryotic chaperone evolution.

Treatment of cancer with EGFR inhibitors is limited by on-target skin toxicities induced by inhibition of the MAPK pathway. BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. We then conducted a phase I clinical trial testing the hypothesis that topical therapy with the BRAF inhibitor LUT014 could improve skin toxicities induced by EGFR inhibitors. Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. LUT014 was well tolerated, and there were no dose-limiting toxicities. The acneiform rash improved in the 6 patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation. SIGNIFICANCE: BRAF inhibitor topical therapy could avoid dose reductions of EGFR inhibitors, locally treating the main dose-limiting skin toxicity of this class of agents.This article is highlighted in the In This Issue feature, p. 2113.

Pemphigus is an autoimmune bullous disease with a number of described associations, including medications, which have been grouped into three structural categories - thiol drugs, phenol drugs, and drugs with neither functional group [1]. Discontinuation of the offending medication is considered a mainstay of therapy. We report a patient in whom the onset of pemphigus foliaceus was associated with initiation of imatinib mesylate adjuvant therapy in a patient with resected gastrointestinal stromal tumor (GIST). Imatinib was continued because of the survival benefit to the patient with a resected, high risk GIST. Treatment with rituximab resulted in near resolution of his blistering rash and follow up enzyme-linked immunosorbent assay (ELISA) demonstrated reference range immunoreactivity for both desmoglein 1 and desmoglein 3. After dose increase of imatinib therapy owing to tumor growth, the patient subsequently again developed a similar eruption. Re-biopsy and ELISA were consistent with recurrence of pemphigus. In conclusion, although the patient's pemphigus was cleared with a single cycle of rituximab infusions while continuing imatinib therapy, the disease returned after imatinib dose was increased a year later, suggesting a dose-response relationship.