Cases Of Opportunistic Infections Research Articles

Abstract 4998: Pralsetinib induces opportunistic infection in RET fusion-positive NSCLC patients via inhibition of IL-2 production by blocking Jak3-Stat5 activation

Abstract Background: Oncogenic alteration in RET, representing 1-2% of non-small cell lung cancer (NSCLC), is one of the important targets. Pralsetinib is a selective RET inhibitor that targets RET fusions. We present a case series on opportunistic infections and the mechanism of immunosuppression. Methods: From October 2021 to March 2022, we administered pralsetinib to a total of 15 patients with NSCLC harboring RET fusion. We retrospectively analyzed the clinical efficacy and adverse event related to pralsetinib. To investigate the potential impact of pralsetinib on T-cells, we examined cytokine release from Jurkat T (JT) cells after pralsetinib treatment. To test if Stat5 bind to IL-2 promotor, we conducted Chromatin Immunoprecipitation (ChIP). Results: Out of a total of 18 patients with measurable disease, 14 patients (93%) achieved a partial response. With the median follow-up duration of 8.7 months, four cases of opportunistic infections were occurred. Notably, three patients (16.6%) experienced invasive pulmonary aspergillosis, and one patient (5.5%) experienced cytomegalovirus pneumonia. To mimic conditions akin to activated T cells, we treated JT cells with PMA and ionomycin, inducing IL-2 release through the binding of NFAT, AP-1, and NF-κB to the IL-2 promoter. Following approximately two weeks of pralsetinib treatment, a decrease of IL-2 releases, the inhibition of Jak3 and the reduced-expression of JunB and c-Jun was observed. Additionally, to investigate the direct correlation between Jak3 and IL-2 release, JT cells were treated with ritlecitinib, the Jak3-selective inhibitor, for approximately two weeks. Like pralsetinib, a reduction in IL-2 release was observed. Furthermore, based on the evidence that Stat5 inhibition leads to reduced IL-2 release, we also showed that the transcription factor Stat5, a direct downstream signaling component of Jak3, binds to the IL-2 promoter during the activation of Jurkat T cells. Conclusion: Pralsetinib inhibits additional IL-2 production by blocking Jak3/Stat5 activation triggered by IL-2 released during early T cell activation. As a result, the Jak3 inhibition induced by pralsetinib leads to a decrease in JunB/c-Jun expression and blocking Stat5 activation by reducing IL-2 release. Consequently, Pralsetinib-related opportunistic infections may be caused by inhibition of the JAK3 pathway and IL-2 release. Citation Format: Shinkyo Yoon, Hyun-Min Ryu, Sang-We Kim, Kang-Seo Park, Dae Ho Lee. Pralsetinib induces opportunistic infection in RET fusion-positive NSCLC patients via inhibition of IL-2 production by blocking Jak3-Stat5 activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4998.

#6402 IMPACT OF DARATUMUMAB AND BELATACEPT ON HLA ANTIBODIES IN KIDNEY TRANSPLANT CANDIDATES WITH 100% CPRA: EARLY RESULTS OF ATTAIN (ITN090ST)

Abstract Background and Aims Despite high allocation priority, <10% of kidney transplant candidates with cPRA 100% can find a compatible donor. Current desensitization strategies are ineffective due to antibody rebound. Adding costimulation blockade to plasma cell (PC) depletion prevents antibody rebound in nonhuman primates by countering nodal B cell and Tfh expansion. Method ATTAIN is a pilot, phase I/II trial of daratumumab, a CD38 mAb used in multiple myeloma, plus belatacept, a high affinity CTLA4-Ig, to desensitize kidney transplant candidates with cPRA ≥99.9%. Enrolled subjects receive daratumumab (6 doses: 8 mg/kg) and belatacept (4 doses: 10 mg/kg) over 10 weeks with bone marrow and blood assessments pre-and post-treatment. The primary efficacy endpoint (PE) is a composite of (1) elimination of ≥1 HLA antibody specificity, (2) ≥50% reduction in the MFI of ≥3 HLA antibody specificities, or (3) kidney transplant from a previously incompatible donor. Target accrual is 15, enrolled in 2 cohorts (5+10). Results Cohort 1 (n = 5, mean age 44, 60% with previous transplant) has been enrolled and treated, with 5-31 weeks follow-up to date. The treatment was tolerated well in all 5 patients who showed a significant reduction in most HLA antibodies after treatment without manifestation of rebound. 3 of 5 participants reached the PE and 5 of 5 had >50% bone marrow (BM) PC depletion. One patient received a kidney transplant from a previously incompatible deceased donor and is doing well at 7 months post-transplant without rejection or rebound of HLA antibody. Treatment was temporarily paused in 3 subjects due to AEs (acute cholecystitis and COVID, upper GI bleed, fevers); no cases of opportunistic infection or malignancy occurred. Conclusion A novel HLA desensitization regimen consisting of PC depletion with Daratumumab and costimulatory blockade with Belatacept appears safe and successful in the ongoing ATTAIN clinical trial. In the initial subject, this regimen led to transplant without HLA antibody rebound or acute rejection. Longer follow-up and additional subjects are needed to confirm these promising results. ATTAIN (NCT04827979) is a trial conducted by the Immune Tolerance Network and sponsored by NIAID (award UM1AI109565).

E088 Safety of guselkumab in patients with psoriatic disease: an integrated analysis of 11 Phase 2 and 3 clinical studies in psoriasis and psoriatic arthritis

Abstract Background/Aims Guselkumab is a monoclonal antibody approved to treat moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). In this analysis, safety data from 11 Phase 2/3 studies of guselkumab were pooled to evaluate guselkumab safety in a large population of patients with psoriatic disease. Methods Guselkumab was generally administered as 100-mg injections at Week (W)0, W4, then Q8W in 7 psoriasis studies and at W0, W4, then Q4W or Q8W in 4 PsA studies. Patients randomized to placebo crossed over to guselkumab Q8W at W16 in 5 PsO studies and to guselkumab Q4W or Q8W at W24 in all PsA studies. Safety data were summarized for the placebo-controlled period (W0-W16 in PsO; W0-W24 in PsA) and through the end of the reporting period (up to 5 years in PsO; up to 2 years in PsA). Incidence rates of key safety events were integrated post-hoc, adjusted for duration of follow-up, and reported per 100 patient-years (PY). Results During the placebo-controlled periods, 1061 patients received placebo (395 PY) and 2257 received guselkumab (856 PY). Through the long-term reporting periods, 4399 guselkumab-treated patients (PsO: 2891; PsA: 1508) contributed 10787 PY of follow-up (PsO: 8662 PY; PsA: 2125 PY). In PsO and PsA studies, pooled incidence rates of overall adverse events (AEs) were similar between guselkumab- and placebo-treated patients. Rates of serious AEs, AEs leading to discontinuation, serious infections, malignancy, and major adverse cardiovascular events were low and generally similar between guselkumab- and placebo-treated patients. Rates of safety events remained consistent through the long-term reporting period for guselkumab-treated patients (Table). No cases of Crohn’s disease or ulcerative colitis were reported in guselkumab-treated patients. No serum sickness-like or anaphylactic reactions related to guselkumab were reported. No opportunistic infections were reported in any guselkumab-treated PsO patient. Three cases of opportunistic infection were reported in pooled PsA studies (0.14/100 PY; all post-W52 in DISCOVER-2). No cases of active tuberculosis were reported across all studies. Conclusion In the most comprehensive analysis of guselkumab safety to date, AE rates in guselkumab-treated patients were similar to those observed with placebo and were stable throughout long-term follow-up. Disclosure B. Strober: Grants/research support; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Eli Lilly, Meiji Seika Pharma, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Dermira, Leo Pharma, Inc, Arcutis, Are. L. Coates: Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB; grant/research support from AbbVie, Amgen, Celgene, Eli Lilly, Jan. J. Yu: Shareholder/stock ownership; Janssen Research & Development, LLC, Johnson & Johnson. K. Rowland: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. E. Leibowitz: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. M. Miller: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. A. Kollmeier: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Li: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. Y. Wang: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Leibowitz, Janssen Scientific Affairs, LLC, Johnson & Johnson. D. Chan: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson. S. Chakravarty: Shareholder/stock ownership; Janssen Scientific Affairs, LLC, Johnson & Johnson; Y. Yang, Janssen Pharmaceutical Companies, Johnson & Johnson. Y. Yang: Shareholder/stock ownership; Janssen Pharmaceutical Companies, Johnson & Johnson. M. Shawi: Shareholder/stock ownership; Janssen Pharmaceutical Companies of Johnson and Johnson. M. Lebwohl: Grants/research support; Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy's Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Cor. P. Rahman: Shareholder/stock ownership; Janssen, Novartis, AbbVie, Eli Lilly and Company, Pfizer.

Infection Risk in Patients with Dermatomyositis Associated with Anti-MDA5 Antibodies: A Historical Cohort Study.

Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population. A retrospective cohort study comparing the number and type of infections during the follow-up of 19 patients with DM-MDA5+ and 37 patients with another type of inflammatory myopathy was analyzed. Patients in both groups were matched on initial immunosuppressive therapy. We described and compared significant infectious complications (SIC) in each group. Patients DM-MDA5+ had more SIC: 27 events in the DM-MDA5+ group versus 6 in the controls (HR 7.08, 95% CI 2.50-20.04, p < 0.0001). The number of SIC per patient was higher in DM-MDA5+ (1.4 ± 1.57 vs. 0.16 ± 0.44, p < 0.001). These were mainly lung (n = 13, 48%) and skin infections (n = 6, 22%), more often infections of an undetermined infectious agent (n = 11, 41%) or of bacterial origin (n = 9, 33%). A few cases of opportunistic infections were reported. The median duration of follow-up without SIC event in the DM-MDA5+ cohort was 3.5 months. Patients with DM-MDA5+ have an increased infection risk compared to others inflammatory myopathies irrespective of immunosuppressive therapy exposure. These results highlight the importance of monitoring for infection during patient follow-up.

Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFα therapy: a placebo-controlled phase II study

ObjectiveThis phase 2a randomised, double blind, placebo controlled, parallel group study evaluated the safety and efficacy of a first-in-class drug candidate ABX464 (obefazimod, 50 mg and 100 mg per day),...

Alemtuzumab as Second-Line Treatment for Late Antibody-Mediated Rejection of Transplanted Kidneys

Whether the anti-CD52 monoclonal antibody alemtuzumab can be an effective treatment option for late antibody-mediated rejection (ABMR) is not known. In a single-center pilot study, 12 patients with late ABMR were given 30 mg subcutaneous alemtuzumab.Median time from transplantation to biopsy was 22 months with 10 of 12 recipients fulfilling criteria for the histologic diagnosis chronic-active ABMR. The estimated glomerular filtration rate (eGFR) loss before diagnosis was 1.2 mL/min/mo with graft loss (eGFR <15 mL/min) expected to occur within 2 years in 11 of 12 cases. All recipients showed no or an inadequate response to initial treatment with steroids and intravenous immunoglobulin. eGFR at time of alemtuzumab administration was 35 mL/min/1.73 m2 (IQR, 30-42) and stabilized or improved in 10 of 12 recipients within 12 months. Proteinuria was stable in the year after alemtuzumab. At 3-year follow-up, the death-censored graft survival was 68% (uncensored graft survival was 58%). Five cases of 10 cases that could be evaluated at 3-year follow-up had stable eGFR (on average 44 mL/min at 12 months and 42 mL/min at 36 months). Alemtuzumab was generally well tolerated and only 2 cases of opportunistic infections were noted. One case of symptomatic parvovirus B infection and 1 case of BK viral infection occurred, which both cleared at follow-up. In conclusion, alemtuzumab may be of value as a second-line treatment for late ABMR with rapid loss of eGFR.

First case of &lt;em&gt;Arthrographis kalrae&lt;/em&gt; pulmonary infection in a patient with AIDS

Arthrographis kalrae is a hyaline fungus. It is a saprophyte of the environment, mainly found in soil and compost. It is a rare isolate in clinical specimen. In recent years this pathogen has been attributed to various cases of opportunistic infections. Our patient was a 51-year-old Indian woman, farmer by occupation, who had HIV infection and was under HAART treatment. She presented with complaints of cough with scanty expectoration for 2 months. Her CD4 count was 75 cells/μl. Induced sputum was collected and sent for detailed microbiological examination. Bacteriological and mycological profile was checked. The causal agent was identified as Arthrographis kalrae based on morphological characteristics (culture). Unfortunately, samples could not be preserved and sent for ITS region sequencing due to COVID-19 outbreak. The case is of interest because, to the best of our knowledge, Arthrographis kalrae has not been reported so far from our country, India.

Adult T-Cell Leukemia/Lymphoma-Related Ocular Manifestations: Analysis of the First Large-Scale Nationwide Survey.

Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive T-cell malignancy with a high mortality rate, resulting in a lack of information among ophthalmologists. Here, we investigated the state of ophthalmic medical care for ATL and ATL-related ocular manifestations by conducting the first large-scale nationwide survey in Japan. A total of 115 facilities were surveyed, including all university hospitals in Japan that were members of the Japanese Ophthalmological Society and regional core facilities that were members of the Japanese Ocular Inflammation Society. The collected nationwide data on the state of medical care for ATL-related ocular manifestations and ATL-associated ocular findings were categorized, tallied, and analyzed. Of the 115 facilities, 69 (60%) responded. Overall, 28 facilities (43.0%) had experience in providing ophthalmic care to ATL patients. ATL-related ocular manifestations were most commonly diagnosed “based on blood tests and characteristic ophthalmic findings.” By analyzing the 48 reported cases of ATL-related ocular manifestations, common ATL-related ocular lesions were intraocular infiltration (22 cases, 45.8%) and opportunistic infections (19 cases, 39.6%). All cases of opportunistic infection were cytomegalovirus retinitis. Dry eye (3 cases, 6.3%), scleritis (2 cases, 4.2%), uveitis (1 case, 2.1%), and anemic retinopathy (1 case, 2.1%) were also seen. In conclusion, intraocular infiltration and cytomegalovirus retinitis are common among ATL patients, and ophthalmologists should keep these findings in mind in their practice.

Epidemiology of Opportunistic Infections in HIV Infected Patients on Treatment in Accredited HIV Treatment Centers in Cameroon.

Background:The African continent accounts for over 70% of people infected with Human Immunodeficiency Virus (HIV). The HIV sero-prevalence rate in Africa is estimated at 4.3%. In developed countries, such as France, pneumocystis is indicative of AIDS in 30% of patients; however, in Africa, pulmonary tuberculosis (TB) is the most-documented opportunistic infection (OI) and the leading cause of death in HIV-infected patients. In 2016, Cameroon had 32,000 new cases of OI and 29,000 deaths as a result of these infections. However, there is little existing data on the epidemiological profile of OIs in Cameroon, which is why we conducted this study in accredited HIV treatment centers and care/treatment units in the two cities of Douala and Yaounde, Cameroon.Methods:This was a retrospective descriptive and analytical study carried out in 12 accredited HIV treatment centers in the cities of Yaoundé and Douala, Cameroon, over a period of seven months from October 2017 to April 2018. A stratified sampling method was used with three sampling levels: the city, type of health facility and size of active files. Ethical clearance and administrative authorization were obtained from the appropriate authorities and data were collected using a pre-tested survey form. The data collected was entered and analyzed using Epi Info version 3.5.4.Results:Out of a total of 1,617 HIV-infected patients sampled, 419 (25.9%) had at least one OI. Of these patients with an OI, 246 or 65% had a baseline CD4 count of <200/mm3. There was a significant relationship between the male gender and the onset of OI (OR = 1.47; p = 0.01). Age ≥ 50 years was associated with the occurrence of OI (OR = 2.57; p = 0.01). A CD4 count of <200/mm3 was also associated with the risk of developing an OI (OR = 3.12; p = <0.01).Conclusion and Global Health Implications:The prevalence of OI is high among people living with HIV (25.9%). Shingles was the most common OI found followed by pulmonary tuberculosis. Male gender, age ≥ 50 years, and CD4 <200/mm3 were the most common factors associated with the occurrence of these OI. These findings suggest that public health interventions for reducing HIV related co-morbidities (and implicitly mortality) should especially target the male gender for greater impact in addition to other measures.

Burden of Fungal Infections in Colombia

Data with respect to the epidemiological situation of fungal diseases in Colombia is scarce. Thus, the aim of this study is to estimate the burden of fungal infections. A population projection for 2017 from the Colombian Department for National Statistics was used, as well as official information from the Ministry of Health and National Institute of Health. A bibliographical search for Colombian data on mycotic diseases and population at risk (chronic obstructive pulmonary disease, HIV infection/AIDS, cancer, and transplant patients) was done. The Colombian population for 2017 was estimated at 49,291,609 inhabitants, and the estimated number of fungal infections for Colombia in 2017 was between 753,523 and 757,928, with nearly 600,000 cases of candidiasis, 130,000 cases of aspergillosis, and 16,000 cases of opportunistic infection in HIV, affecting around 1.5% of the population. In conclusion, fungal infections represent an important burden of disease for the Colombian population. Different clinical, epidemiological, and developmental scenarios can be observed in which fungal infections occur in Colombia.

Incidence and Type of Opportunistic Infections during Ibrutinib Treatment at a Single Academic Center

BACKGROUNDIbrutinib is an irreversible inhibitor of Burton's tyrosine kinase (BTK) in the B-cell receptor (BCR) signaling cascade and is a practice changing treatment for chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Ibrutinib also inhibits Interleukin-2 Inducible Kinase (ITK) in T-cells and has demonstrated immunomodulatory effects. Recently, cases of opportunistic infections (OI) have been reported during ibrutinib treatment including pneumocystis jirovecii pneumonia (PJP), cryptococcus, and fusarium. To date there are no reports on OI in large unselected cohorts of patients taking ibrutinib. We conducted a single-institution retrospective study to determine the incidence and type of OI during ibrutinib treatment as well as outcomes and characteristics associated with risk. METHODSWe reviewed medical records of all patients treated with ibrutinib at the Ohio State University between June 1st 2010 and March 31st 2016. Patients who received ibrutinib for graft versus host disease were excluded. All charts were initially reviewed by one of the investigators and patients with OI were independently reviewed by a second investigator. Baseline patient and disease characteristics were captured at time of starting ibrutinib. All OI occurring after the first dose of ibrutinib were recorded. Onset of OI was considered as the time of first presentation for a complaint related to OI. Time to OI was calculated from the date of starting ibrutinib until the onset of OI or censored at the last assessment date, discontinuation of ibrutinib, or death prior to OI as competing risks. The cumulative incidence of OI was estimated and the Fine and Gray regression models were used to examine the association between patient characteristics and risk of OI. Covariates with significance level of p<0.20 from univariable analyses were further evaluated in a multivariable analysis using a stepwise selection procedure, retaining those with p<0.05 in the final model. RESULTSThe cohort included 566 patients. Median age was 65 (range 23-89) and 70.1% (397/566) were men. The majority of patients had CLL (73.7%, 417/566). Other diagnoses included mantle cell lymphoma (9.9%, 56/566), indolent B-cell malignancies (8.1%, 46/566; 11 Waldenström's Macroglobulinemia, 13 Hairy Cell Leukemia, 15 Follicular Lymphoma, 6 Marginal Zone Lymphoma, and 1 Prolymphocytic Leukemia), and aggressive lymphoma (8.3%, 47/566; 35 diffuse large B-cell or transformed lymphoma and 12 Richter's syndrome). Median number of prior treatments was 3 (range 0-18) and 6.5% (37/566) of patients were treatment naïve. Ibrutinib was prescribed on clinical trial for 80.9% (458/566) of patients with the rest receiving it as standard of care. A second agent was given with ibrutinib in 30.9% (175/566) of cases and was most often a monoclonal antibody (81.7%, 143/175). Use of antiviral prophylaxis was common (78.6%, 445/566) with fewer patients receiving PJP (44.9%, 254/566) or fungal (11.5%, 65/566) prophylaxis. The most utilized prophylactic antifungal agent was fluconazole (70.8%, 46/65). Total ibrutinib exposure for the cohort was 1,225 person-years with a median exposure of 1.98 (range 0.008-6.40) years. Median duration of follow-up was 2.69 (range 0.03-6.40) years. Twenty-three of 566 (4.1%) patients developed an OI at a median of 0.39 (range 0.03-4.33) years after starting ibrutinib. The cumulative incidence of OI was 2.3% (95% CI: 1.3-3.8%) at 0.5 years and increased to 4.7% (95% CI: 3.0-7.0-%) at 5 years. Types of OI and outcomes are detailed in Table 1. Median survival of the entire cohort was not reached. Among 23 OI patients, the median survival after infection was 1.39 years. Univariable analysis revealed ≥3 prior treatments (HR 2.61), diabetes (HR 3.03), pulmonary disease (HR 2.81), chronic kidney disease (HR 2.56), and liver disease (HR 6.42) were associated with an increased risk for OI (p<0.05). In a multivariable analysis ≥3 prior treatments (HR 2.87, 95% CI: 1.12-7.35; p=0.028), diabetes (HR 3.63, 95% CI: 1.50-8.77; p=0.004), and liver disease (HR 7.53, 95% CI: 2.14-26.49; p=0.002) retained independent association with OI development. CONCLUSIONSThe cumulative incidence of OI during ibrutinib treatment was low (4.7% at 5 years) and the most common type was invasive fungal (61%) with no PJP cases. Three or greater prior treatments, diabetes, and liver disease were independently associated with risk for OI. [Display omitted] DisclosuresByrd:Janssen: Research Funding; The Ohio State University: Patents & Royalties: OSU-2S; Genentech: Research Funding; Acerta Pharma: Research Funding; Pharmacyclics: Research Funding.

Actinomycose révélée par une ulcération du palais et de la gencive

Actinomycosis is a chronic and extensive granulomatous, bacterial infection. Revelation by oral ulceration is rare. A 76-year-old patient with diabetes was treated with dabrafenib for stage IV melanoma. A follow-up visit revealed two ulcerated, infiltrated and hyperalgesic lesions of the palate and gingiva. There were no associated signs. The laboratory findings were normal. The possibility of squamous cell carcinoma occurring with BRAF inhibitors was discussed, despite the rarity of such cases in the literature. Histological examination showed an actinomycotic grain. A scan of the facial mass showed no osteitis. Antimicrobial therapy was initiated with amoxicillin for four months, with a favorable outcome. Actinomycetes are Gram-positive filamentous saprophytic bacteria of the oral cavity and the gastrointestinal tract. They can become pathogenic under the influence of several factors. Cervicofacial involvement in the form of a peri-mandibular inflammatory nodule with secondary fistulation on the skin or in the mouth is the classic presentation. To our knowledge, no cases of opportunistic infection under BRAF inhibitors have been described. Only two cases of tuberculosis have been reported with sorafenib. The initial presentation led to suspicion of squamous cell carcinoma. In our patient, poor oral hygiene and diabetes were the two key factors considered. Moreover, this is the first case reported under dabrafenib, which does not appear to be a favoring factor. We would stress the importance of mucosal examination in patients treated with BRAF inhibitors.

Opportunistic Infections in Renal Transplantation &amp;lt;br/&amp;gt;—A Case Series

Background: Porto’s Hospital Centre is one of the most active Portuguese hospitals in renal transplantation (performed since 1983). Although increasingly rare, opportunistic infections in transplanted patients are associated with high mortality rate in kidney transplantation and remain a major diagnostic challenge. Methods: We investigated 2041 cases of hospital admissions (from 2004 to 2012), any time after kidney transplantation. We described the infection location, the diagnostic techniques used and the mortality after the infection. Results: We found 82 cases of opportunistic infection caused by Herpes virus (Zoster and simplex), Cytomegalovirus, Polyomavirus, Aspergilus, Alternaria, Mucorales, Candida, Mycobacterium tuberculosis, Cryptococcus and Pneumocystis. Conclusions: In this article we highlight the important role of histology/cytology in the diagnostic process of these infections. In many cases prompt diagnosis and treatment are necessary to avoid life-threatening complications and may greatly improve prognosis.

Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis

There are no systemic therapies approved in the United States to treat pediatric psoriasis. We sought to evaluate long-term safety and efficacy of etanercept in children and adolescents with moderate to severe plaque psoriasis. This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (∼ 60%-70%) and 90% improvement in Psoriasis Area and Severity Index score (∼ 30%-40%) and static physician global assessment status clear/almost clear (∼ 40%-50%) were maintained through week 264. The number of patients remaining on study at week 264 was small. Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.

Correlation between opportunistic infections in patients with HIV/AIDS in Dali of Yunnan Province and lymphocyte count

Objective To investigate the correlation between opportunistic infections in patients with HIV/AIDSin Dali of Yunnan Province and lymphocyte count,discover the incidence trend of opportunistic infections in patients with HIV/AIDSin Dali and instruct early diagnosis and treatment. Methods Choosing 454 cases of opportunistic infections in patients with HIV/AIDSin Infectious Disease Dali Prefectural Hospital were chosen,analyze various opportunistic infections,examining lymphocyte count and analyze the differences of opportunistic infections on lymphocyte count. Results 454 cases opportunistic infections with HIV/AIDS,48.24%were HCV infections,38.72%of various tuberculosis consumption phthisis,28.41%of bacterial pneumonia and 25.77%of oral condida monilia infections,high rate of opportunistic infections when lymphocyte count >350/μL of 5.56%(χ2=34.88, P P <0.01),comparing to 18.79%of those with the treatment Conclusion The common opportunistic infections in our area are HCV,various tuberculosis consumption phthisis,bacterial pneumonia and oral condida monilia infections;high rate of opportunistic infections happens when lymphocyte count are low and lower rate on those with the treatment of HAART,offering an effective method on controlling opportunistic infections. Key words: HIV/AIDS; lymphocyte count; Opportunistic infections

The characteristic analysis of nosocomial infections and opportunistic infections of death cases in HIV/AIDS patients

Objective To analyze the characteristics of nosocomial infections (NI) and opportunistic infections (OI) of death cases in HIV/AIDS patients in a hospital.Method A retrospective analysis on a group of 408 HIV/AIDS death cases from Jan 2001 to Dec 2012 was conducted.Results There were 4,434 hospitalized cases with HIV/AIDS in a hospital in total and 408 cases died,the fatality rate was 9.20％.Since the introduction of free anti-viral treatment,the fatality rate of HIV/AIDS declined.49 cases of NI were found among 408 death cases,and the NI rate was 12.01％.Bacteria were the most common pathogens in NI.The most frequent infection sites were respiratory system and digestive system.The risk factors for NI were opportunistic infection of at least two sites,hospital stay over 30 days,invasive operations,CD4+T lymphocyte count lower than 200 cells/μ l and combination antibiotics administration.There were 1041 cases of OI totally.81.13％ of OI was related to death directly.Fungal infection was the most common in OI.Most of the OI occurred in lung,mouth.The AIDS defining opportunistic infections accounted for 32.08％.Conclusions Opportunistic infections involving nosocomial infections are the most important cause of death.Early diagnosis and treatment for opportunistic infections,preventing and controlling nosocomial infection is the key to improve the life quality of HIV/AIDS patients. Key words: HIV/AIDS; Death; Risk factor; Nosocomial infection; Opportunistic infection

Safety and Efficacy Of Rituximab In adult's Immune Thrombocytopenia (ITP) : Results After One-Year Of Follow-Up In 252 Patients From The Prospective French ITP-Ritux Registry

Introduction Adults with ITP usually respond to corticosteroids but typically relapse after discontinuation. Rituximab is thought to be an effective off-label second-line treatment but only few prospective data exist about its long-term efficacy and its long-term safety is a matter of concern. The tolerance and particularly the risk of severe infection is a crucial factor for assessing the risk/benefit ratio of this treatment in ITP. Three years ago, we opened a non-interventional prospective registry in France to investigate the safety (primary outcome) and the efficacy of rituximab in off-trials adults with ITP (ClinicalTrials.Gov: NC1101295). Two hundred and fifty two patients were included on a two-year period. A follow-up duration of five-year is planned. We report here the first results after one year of follow-up. Methods The ITP-Ritux registry was set up by the French reference center of adult’s immune cytopenias. Thirty one centers participated to the study. Consecutive patients diagnosed with primary ITP according to the international guidelines (Rodeghiero et al, Blood 2009) who were treated with rituximab were included. Patients with a secondary ITP and those who were previously treated with rituximab were excluded. Response to treatment was assessed according to international guidelines: complete response (CR) was defined by platelet count ³100x109/L and response (R) by a platelet count between 30 and 100x109/L with at least a doubling of the pre-treatment count. The prospective and sequential monitoring of rituximab efficacy and safety was made by using of a standardized electronic case report form. Study nurses visited each center regularly to update the clinical and biological data on the enrolled patients. Results Between July 2010 and July 2012, 252 patients (64% of females) with a mean age of 51±21 (16-97) years were enrolled. The median duration of ITP was 1.3 (0-56) years with 44 patients (17%) with a newly diagnosed ITP, 61 (24%) with persistent ITP and 147 (58%) with chronic ITP at time of rituximab treatment. The median platelet counts at time of ITP diagnosis and rituximab first infusion were respectively 18x109/L (1-100) and 17x109/L (1-186). Patients received a median of 2 treatment lines (range 0-7) before rituximab and 25 (10%) were splenectomized. The standard regimen of 375 mg/m2 weekly rituximab infusions for 4 weeks was administered to 179 patients whereas 73 patients (29%) received a fixed dose of 1000 mg on day 1 and day 15. At time of the present analysis, the median follow-up was 18 months and the one-year response was available in 209 patients. A one-year overall response was observed in 90/209 (43%) patients including a CR in 28% and a R in 15%. Nineteen patients who failed to respond to rituximab were splenectomized during the year following rituximab infusions. Sixty eight adverse events occurred in 47 patients (19%). Rituximab infusions have to be stopped in only 3 patients for severe hypotension, dyspnoea with laryngeal discomfort and reversible serum sickness respectively. Three other patients developed severe adverse event related to rituximab requiring admission in hospital including 1 episode of profound neutropenia while 6 episodes of infections occurred in 2 patients. Seven patients (2.7%) have died during follow-up, 52 to 385 days after rituximab infusions. All patients who died but one aged of 18 were 68 to 98-year old. Only one death could be potentially related to rituximab (enterococcus faecium pulmonary infection), 2 deaths were of unknown origin, other causes were: suicide (n=1), multiple myeloma (n=1) and fatal haemorrhage related to ITP (n=2). We did not observe any episode of progressive multifocal encephalopathy or any other case of opportunistic infection. Discussion and conclusion Our preliminary results based on the first large non-interventional prospective registry of ITP-adults treated with rituximab in the “real life” confirm that this treatment leads overall to 40% of response after one year of follow-up. Safety of rituximab at 1 year appears to be good since severe infections were uncommon and no opportunistic infections were observed. The ongoing monitoring and upcoming analysis with a planned follow-up up to 5-years will provide more data on long-term safety. Disclosures: No relevant conflicts of interest to declare.

SAT0459 Tocilizumab Therapy in Children with Systemic Juvenile Idiopathic Arthritis. Russian Experience

BackgroundSystemic Juvenile Idiopathic Arthritis (sJIA) is classified as an acquired autoinflammatory disease. The interleukin-1 and interleukin-6 play a pivotal role in pathogenesis of this disease. The systemic manifestations as well...

THU0302 Safety and efficacy of tocilizumab therapy in children with systemic onset of juvenile idiopathic arthritis

BackgroundThe treatment of systemic onset of juvenile idiopathic arthritis (JIA is one of the serious problem of paediatric rheumatology, therefore development and implementation of new high-tech methods of treatment is...

Analysis of death causes of 345 cases with HIV/AIDS in Guangdong area

To analyze the death causes of 345 cases with HIV/AIDS in Guangdong area. The situations of 345 hospitalized death cases with HIV/AIDS were conducted by retrospective analysis. (1)There were total 3406 hospitalized cases with HIV/AIDS in a hospital from January 2001 to December 2011 and 345 cases died, the fatality rate was 10. 13%. Since 2005 the introduction of free anti-viral treatment, the fatality rate of HIV/AIDS declined. The fatality rate of the patients whose CD4+ T lymphocyte counts <200 cells/microl was 14.61% (299/2046) and it was significantly higher than that of patients whose CD4 T lymphocyte counts >or=200 cells/microl (P <0.01). (2) 99.42% of the death cases had more than one kind of opportunistic infections (OI) and there were 924 cases of OI totally. 84. 64% of OI related to the death directly. Fungal infection was the most common in OI, followed by bacterial infection. Most OI occurred in the lungs, mouth, other systemic disseminated diseases, gastrointestine, central nerver system, septicemia, skin. The AIDS defining opportunistic infections such as several pneumonia, disseminated penicilliosis marneffei and CNS infections accounted for 29.65%. Other factors that caused HIV/AIDS death included opportunistic tumors, HIV related disease and non AIDS-related disease accounted for 15.36%. No accepted effective highly active antiretroviral therapy (HARRT) also constituted factors of death. Among cases which accepted HARRT treatment, only 6.96% had the period of treatment over three months. The fatality rate of end-stage AIDS patients was high and the opportunistic infections was the most important cause of death. Early diagnosis and treatment for opportunistic infections, timely effective HARRT were the key to improve the quality of life of AIDS patients.