Opportunistic Infections In Patients Research Articles

Cryptococcal Cerebellitis in the Setting of Fingolimod Use for Multiple Sclerosis: Atypical Presentation of Dystonia and Imaging Finding Misinterpreted as Subacute Ischemic Stroke

Objective: Describe a case of cryptococcal cerebellitis in a patient on Fingolimod with atypical findings of generalized dystonia and imaging findings mistaken for bilateral subacute cerebellar strokes. Background: Fingolimod is used for multiple sclerosis (MS) and is often associated with lymphopenia with prolonged use. Cryptococcal opportunistic infections in patients on Fingolimod, have been rarely described. Design/Methods: Case report and review of literature. Results: 44-year-old man with MS in remission treated with Fingolimod for the last 8 years, and poorly controlled type-II diabetes mellitus (A1c 10.4), transferred to our facility for stroke work-up with brain MRI findings reportedly showing subacute bicerebellar ischemic strokes. On exam, he was somnolent and intermittently followed commands. He had nuchal rigidity and positive Kernig and Brudzinski signs. Meningitis was suspected and empiric treatment was initiated. MRI findings on DWI/ADC/FLAIR sequences were inconsistent with any vascular territory. Leptomeningeal enhancement was noted in the cerebellar folia, basal cisterns, suprasellar cistern, and brainstem surface. Labs were remarkable for lymphopenia (250), cerebrospinal fluid (CSF) and blood culture grew cryptococcus neoformans, so treatment with liposomal amphotericin B and flucytosine was started. On day 4, patient developed generalized dystonia that resolved with diphenhydramine. Unfortunately, patient did not respond to therapy as evident on repeat LP on day 6. His physical exam worsened, and he was intubated 2 days after. Repeat MRI showed with tonsillar herniation and patient expired. Conclusion: Cryptococcal cerebellitis is a rare opportunistic infection occurring in MS patients on Fingolimod. Early recognition is crucial to avoid rapidly worsening neurological outcomes.

Vitamin D deficiency and oral candidiasis in patients with HIV infection: A case‒control study.

Oral candidiasis is a common opportunistic infection in patients with human immunodeficiency virus (HIV). In addition, most of these patients suffer from vitamin D deficiency. This study aimed to investigate the association between vitamin D levels and oral candidiasis in patients with HIV infection. This case‒control study was conducted on HIV-infected patients. Cases were patients with oral candidiasis diagnosed based on physical examinations. Controls were age- and sex-matched individuals without oral candidiasis. The levels of 25-OH vitamin D and other laboratory markers (CD4 count and viral load) were compared between the case and control groups. A total of 104 cases and 102 controls were included in the study. The cases had significantly lower 25-OH vitamin D3 levels (MD = 33.86 ng/mL, 95% CI= (31.85, 35.87), P < 0.001) and CD4 counts (MD = 267.48 cells/mm3, 95% CI= (189.55, 345.41), P < 0.001) than the controls. In addition, viral load was significantly higher in cases than in controls (MD = 7.03 × 105 copies/mL, 95% CI= (4.46 × 105, 9.61 × 105), P < 0.001). The multivariate logistic regression analysis revealed that educational status (OR = 0.032, 95% CI= (0.002, 0.100), P < 0.001), current HAART (OR = 0.005, 95% CI= (0.001, 0.014), P < 0.001), history of oral candidiasis (OR = 20.114, 95% CI= (18.135, 21.957), P < 0.001), CD4 count (OR = 0.004, 95% CI= (0.001, 0.006), P < 0.001), viral load (OR = 12.181, 95% CI= (1.108, 133.392), P < 0.001), and vitamin D level (OR = 0.011, 95% CI= (0.008, 0.015), P < 0.001) were significantly associated with the risk of developing oral candidiasis. Based on the findings, most patients with HIV infection suffer from vitamin D deficiency, especially those with oral candidiasis. Hypovitaminosis D was significantly associated with an increased risk of oral candidiasis. Thus, vitamin D supplementation may assist HIV-positive patients in improving their oral health and preventing oral candidiasis.

Life-threatening Pneumocystis jiroveci Pneumonia with Cytomegalovirus Coinfection in a Follicular Lymphoma Patient During Rituximab-based Chemotherapy

Abstract In the era of target therapy, we face the challenge of the risk of opportunistic infection in patients with B-cell lymphoma who receiving rituximab-based chemotherapy. Opportunistic infections such as Pneumocystis jiroveci pneumonia (PJP) and Cytomegalovirus (CMV) pneumonia are life-threatening diseases. However, PJP with CMV coinfection is rare. Here, we report a follicular lymphoma patient who suffered from PJP with CMV coinfection after receiving three cycles of rituximab, cyclophosphamide, vincristine, and prednisone regimen and was successfully rescured after timely identification and treatment. We emphasize that physicians should be alert for the coinfection of PJP and CMV in lymphoma patients receiving rituximab-based chemotherapy and the timely recognition, and treatment that may avoid a deadly outcome.

Cytomegalovirus Transverse Myelitis Secondary to Influenza Infection and Early Recovery: A Case Report

Abstract Immunosuppression can lead to opportunistic infections in a host. The evidence of viral infections causing immunosuppression in a host for a transient period is gaining attention. In order to prolong their stay in the human body, viruses affect the human immune system in various ways. Common viral infections such as influenza can lead to transient lymphocytopenia, which lays the groundwork for more dangerous opportunistic infections. Cytomegalovirus (CMV) infection is a rare cause of inflammatory myelopathy. We present the case of a patient with an influenza infection who progressed to severe acute respiratory distress syndrome, methicillin-resistant Staphylococcus aureus necrotizing pneumonia, and idiopathic lymphocytopenia with a CD4 count of 61 per μL on arrival. After 2 weeks, the patient developed complete flaccid paralysis with sensory and autonomic dysfunction. Because his polymerase chain reaction results of cerebrospinal fluid and blood test were positive for CMV infection, he was treated with high doses of steroids and ganciclovir intravenously. Due to early diagnosis and intervention, the patient was able to recover in 2 months with only minimal residual weakness. Thus, this case stresses on the importance of looking out for opportunistic infections in patients affected by severe viral infections for their early recovery.

Opportunistic Infections in Patients Receiving Post-Transplantation Cyclophosphamide: Impact of Haploidentical versus Unrelated Donor Allograft

Post-transplant cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs) including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD) were assessed from day 0 through day +365. The one-year cumulative incidence function of OIs and non-relapse mortality were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% haploidentical vs. 25% MUD/MMUD; HR 1.70; 95% CI 1.16 - 2.49; p=0.006). On multivariable analysis, haploidentical donor (HR 1.50; 95% CI 1.01 - 2.23; p=0.046), prior HCT (HR 1.99; 95% CI 1.29 - 3.09; p=0.002), and diagnosis of acute GVHD (HR 1.47; 95% CI 1.02 - 2.14; p=0.041) were associated with an increased risk of OIs. Non-relapse mortality within the first year was not significantly different between the two groups (HR 1.11; 95% CI 0.64 - 1.93; p=0.70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although one-year NRM was not different between haploidentical and MUD/MMUD HCT recipients. CMV and adenovirus infections were significantly increased amongst haploidentical HCT recipients, while the incidence of EBV infection and IFD was similar between the groups. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.

Analysis of cluster of differentiation 4 cell counts with clinical stages and opportunistic infection in patients with human immunodeficiency virus-acquired immunodeficiency syndrome

Analysis of cluster of differentiation 4 cell counts with clinical stages and opportunistic infection in patients with human immunodeficiency virus-acquired immunodeficiency syndrome

Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature.

Purpose: To report a case of ocular toxoplasmosis following long-term treatment with adalimumab and review the literature on ocular toxoplasmosis following anti-Tumour necrosis factor-α therapy. Method: A retrospective chart review of A 21-year-old male who developed retinochoroiditis in his left eye following adalimumab therapy combined with oral methotrexate. Result: A known patient of juvenile idiopathic arthritis (JIA) on adalimumab and oral methotrexate for the last four years presented to us with a blurring of vision for the last 15 days. Fundus examination of the left eye revealed severe vitritis and two patches of retinochoroiditis in the inferior part of the fundus. Subsequent investigations confirmed it to be a case of toxoplasma retinochoroiditis, and he responded to anti-toxoplasma treatment. A review of literature on a similar topic revealed five such cases, and the index case was the first such report in patients with JIA. Conclusion: The index case highlights the importance of early recognition and management of opportunistic infections in patients receiving biologicals.

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Changes in the balance of Th17/Treg cells and oxidative stress markers in patients with HIV‑associated pulmonary tuberculosis who develop IRIS.

Tuberculosis (TB) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and is one of the primary causes of death from AIDS. The increased accessibility to highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of patients with HIV infection. However, following ART, rapid restoration of the immune system leads to immune reconstitution inflammatory syndrome (IRIS). Oxidative stress and innate immunity play a role in TB-associated IRIS (TB-IRIS). The present study investigated the changes that occur in oxidative stress markers and T helper (Th)17/regulatory T (Treg) cell balance and their significance in IRIS patients with HIV-associated pulmonary TB. A total of 316 patients with HIV-associated pulmonary TB were treated with HAART and followed up regularly for 12 weeks. Those who developed IRIS were included in the IRIS group (n=60), while the remaining patients were included in the non-IRIS group (n=256). The changes in plasma oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA) were detected with the ELISA, and the ratio of Th17 to Treg cells in whole blood were analyzed before and after treatment through the flow cytometric assay. Following treatment, MDA and Th17 cells levels were significantly increased while SOD and Treg cells levels were decreased in the IRIS group (P<0.05) compared with before treatment. In the non-IRIS group, a non-significant decrease was observed in SOD levels (P>0.05), while the MDA levels significantly decreased compared with before treatment (P<0.05) and the Th17 and Treg cells levels were both significantly increased (P<0.05). After treatment, compared with the non-IRIS group, the IRIS group showed a significant increase in MDA and Th17 cells and decrease in SOD and Treg cells levels (P<0.05). In addition, Th17 cells levels were positively correlated with MDA but negatively correlated with SOD levels. Treg levels were negatively correlated with MDA and positively correlated with SOD levels (P<0.05). The area under the curve values of serum MDA and SOD, Th17 and Treg levels predicting the occurrence of IRIS were 0.738, 0.883, 0.722 and 0.719, respectively (P<0.05). These results indicated that the above parameters have certain diagnostic value for the occurrence of IRIS. The occurrence of IRIS in patients with HIV-associated pulmonary TB may be associated with oxidative stress and Th17/Treg cell imbalance.

Recuento de linfocitos CD4 e infecciones oportunistas en pacientes con VIH en un hospital de Chiclayo, Perú, 2020

Objective. To determine the relationship between CD4 lymphocytes with opportunistic infections in patients with HIV infection in a hospital in Chiclayo, Peru, 2020. Material and methods: The study was observational, retrospective and analytical cross-sectional, the study population was 135 medical records. of patients with a confirmed diagnosis of HIV-AIDS who were treated in the infectious disease service. Results: The male sex predominated (81.5%), 97.8% were between 18 and 59 years old and were mostly single (69.6%). The most frequent infections were gastroenteritis (29.6%), tuberculosis (9.6%) and toxoplasmosis (8.1%), the majority presented a CD4+ lymphocyte count less than 200 cells/uL, in addition the most frequent clinical stages were B3 and B2 (42.2%). An association was found between the frequency of opportunistic infections and the CD4+ count (p=0.001), these were more frequent in patients with a CD4+ lower than 200 cells/uL (71.4%). Conclusions: The study population had a high frequency of opportunistic infections, which were associated with a CD4+ lymphocyte count of less than 200 cells/uL.

Chronic and opportunistic infections in patients with immuno-inflammatory rheumatic diseases: screening and prevention issues (based on the materials of the EULAR recommendations)

At the present stage of development of rheumatology, much attention is paid to the problem of comorbid infections, which have a significant impact on mortality and mortality, especially in immuno-inflammatory rheumatic diseases (IIRD). The active introduction into clinical practice of innovative drugs, the action of which is aimed at specific components of the pathogenesis of IIRD, has led to an increase in the risk of developing infections of various nature and localization, including chronic and opportunistic (COI). This article analyzes the recommendations for screening and prevention of COI in adult patients with acute respiratory infections, proposed in November 2022 by experts of the European Alliance of Rheumatology Associations (EULAR). It is noted that these recommendations should be considered through the prism of national guidelines that take into account regional risk factors, features of the course, diagnosis, therapy and prevention of СOI. At the same time, it seems absolutely justified to periodically review screening and preventive procedures as new scientific data accumulate. Despite the importance of a multidisciplinary approach and the need for close cooperation with doctors of other specialties, the EULAR working group emphasizes the central role of a rheumatologist in the management of patients with HOI that occur against the background of IIRD and are associated with the received anti-rheumatic therapy.

P816 The efficacy of an over the counter multivitamin and mineral supplement to prevent opportunistic infections in patients with inflammatory bowel disease in remission

Abstract Background Patients with inflammatory bowel disease (IBD) treated with immunomodulators or biological therapy are at increased risk of infections. Malnutrition and vitamin or mineral deficiencies are common among patients with IBD. The results of various studies have indicate that vitamin deficiencies might increase the risk of infections. Methods Single-centre, randomized, double-blinded, placebo-controlled clinical trial to compare a multivitamin and mineral supplement (vitamin group) versus identical in appearance placebo (placebo group). Patients with Crohn’s disease or ulcerative colitis using immunomodulators and/or biological therapy without vitamin deficiency were considered for participation in our study. Participants were asked to take a daily multivitamin and mineral supplement or placebo and report the occurrence of infections during a 24 weeks period of follow up. The primary endpoint of this study was the difference in incidence of infection between the two groups measured by a validated questionnaire, the revised version of the ID screen to assess infection13. Randomization was conducted by using computer generated random numbers with an allocation ratio of 1:1 to vitamin supplement or placebo in blocks of 8 and stratified according to type of IBD.Results Between July 2020 and February 2021, 320 patients were randomized. Treatment arms consisted out of 162 and 158 for vitamin and placebo, respectively. Both groups showed similarity in patient characteristics. All patients were included in the intention-to -Treat (ITT), 265 patients in the per protocol (PP) (compliance &amp;gt;80%) analyses. For both groups, 107 patients reported an infection during the 24 weeks follow up period (Unadjusted Odds Ratio: 0.93 (95% confidence interval: 0.56-1.48). In the vitamin group, 32 patients received antibiotics for an infection compared with 21 patients in the placebo group (Unadjusted Odds Ratio: 1.61 (95% confidence interval: 0.88-2.93). 166 patients in the PP analysis reported an infection (Unadjusted Odds Ratio: 0.91 (95% confidence interval: 0.55-1.50), 23 reported a serious infection (Unadjusted Odds Ratio: 2.57 (95% confidence interval: 1.02 -6.46). None of the patients was hospitalized due to serious infection. Conclusion An over the counter multivitamin and mineral supplement did not reduce the risk of infection for patients with IBD in remission with immunomodulators and/or biological therapy.

A Simian Immunodeficiency Virus-Infected Macaque Model of Enterocytozoon bieneusi Infection.

Microsporidiosis caused by Enterocytozoon bieneusi is a common opportunistic infection in patients with HIV/AIDS and those on immunosuppressive therapy. A significant loss of mucosal or peripheral CD4+ T cells and subsequent dysfunction of the intestinal immune system may be responsible for the development of chronic microsporidiosis in these patients. We have used the Simian immunodeficiency virus (SIV)-infected macaque model to investigate this relationship. To establish the course of E. bieneusi infection in SIV-infected animals, four SIV-infected animals were experimentally challenged with E. bieneusi when their CD4+ counts dropped to less than 300 cells/μL of blood. Analysis of fecal samples by nested polymerase chain reaction revealed that three out of four E. bieneusi-infected macaques continued to shed spores for 7-24 months after infection, an indication of chronic microsporidiosis. Four other SIV-infected macaques, after having an initial negative phase, spontaneously acquired E. bieneusi infection when their CD4+ counts dropped to less than 600 cells/μL of blood and shed spores for 8-19 months. The shedding of E. bieneusi spores in the feces increased relative to decrease in peripheral blood CD4+ T cell numbers. Gut biopsies were obtained before and after challenge to phenotype the mucosal lymphocyte subsets using flow cytometry. The immunophenotypic analysis showed no restoration of CD4+ T cells after E. bieneusi infection in the intestinal cells. A slight increase in the percentage population of CD4+ T cells in peripheral blood did not have any effect on the control of E. bieneusi infection in the SIV-infected macaques. These preliminary studies demonstrate that SIV-infected macaques develop chronic E. bieneusi infections as their CD4+ counts dropped to below 300 cells/μL of blood.

High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease.

Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production. Serum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA. Among 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, p < 0.05). Depleted serum IgG from anti-IFN-γ autoAbs-positive AOSD patients with OIs restored phosphorylated STAT-1 upon IFN-γ treatment. Sera from autoantibody-positive AOSD patients more effectively inhibited IFN-γ-mediated production of MCP-1 (45.65 pg/ml) and IP-10 (22.44 pg/ml) than sera from HC (263.1 pg/ml and 104.0 pg/ml, both p < 0.05). Serum samples showing the strongest inhibition of IFN-γ-signaling were from two patients with high-titer autoantibodies and OIs. AOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs.

Incidence, Description, and Timing of Serious or Opportunistic Infections in Patients with Hairy Cell Leukemia Treated with Purine Nucleoside Analogues

Background: Hairy cell leukemia (HCL) is an uncommon B-cell malignancy characterized by pancytopenia on presentation. While the purine nucleoside analogues (PNAs) cladribine and pentostatin have resulted in long overall survival, infections remain a major cause of mortality. PNAs are known to be immunosuppressive, and in combination with the inherent infection risk of HCL, patients are vulnerable to serious and/or opportunistic infections throughout the disease course. Furthermore, there is prolonged CD4+ lymphopenia post-PNA treatment for 1-3 years. We thus conducted a comprehensive retrospective review at an academic center to (1) describe the incidence and types of infections seen in HCL and (2) determine how treatment with pentostatin versus cladribine may affect infection risk. Methods: We reviewed charts of all HCL patients that were seen at The Ohio State University between January 1 2012 and June 30 2020. Patients with less than 1 year of follow up were excluded. We defined our infections of interest as (1) serious i.e. requiring hospitalization or (2) opportunistic i.e. organisms commonly seen in immunosuppression. These patients’ baseline demographics, disease characteristics, bone marrow biopsies, and treatment histories were abstracted from medical records. Time to infection was calculated from the start of HCL treatment to the onset of infections, treating death without infection as a competing risk. The cumulative incidence of infection was estimated, and the associations with patient characteristics were evaluated using Fine and Gray sub-distribution hazard models accounting for competing risks. Overall survival was calculated from diagnosis to date of death or last contact. Kaplan-Meier method was used to estimate the survival functions and corresponding 95% confidence intervals. Results: Our study included 149 patients with a median follow up time of 6.9 years (range 1.3 - 48.8) and a 10-year estimated overall survival of 99% (95% CI: 93 - 100%). Median age at diagnosis was 51 years (range 22 - 80) and most patients (n = 117, 78.5%) were male. A total of 138 (92.6%) had classical HCL and 11 (7.4%) had variant HCL. There was a total of 70 incidents of infection, with 52 patients (35%) experiencing at least one infection and 18 (12%) with a second infection. Forty-six infections (66%) were serious and 24 (34%) were opportunistic. Most infections were likely to be seen 2 months prior to (n = 10, 14%) or 2 months after (n=14, 20%) initial treatment. The cumulative incidence of infection increased during the 50 days after starting treatment (Figure 1). Based on infection site, clinical presentation, and/or laboratory findings, 36 infections (51%) were classified as bacterial, 14 (20%) were viral, 8 (11%) were fungal, and 1 was concurrent viral and bacterial. Eleven (16%) infections did not have a confirmed organism. Sixty-seven (96%) infection cases had resolved; the outcomes in 2 cases were unknown, and 1 case resulted in death. Organisms were confirmed in 38 cases and are listed in Table 1. We examined baseline factors that could be associated with increased risk of infection, including sex, age at diagnosis, variant histology, total number of HCL treatment courses, prior infection, and a palpable spleen at diagnosis: none of these were associated with increased risk. Using cladribine as a reference, no treatment agents (including newer, non-PNA therapies) were associated with lower or higher infection risk. Examining the PNAs specifically, treatment with pentostatin versus cladribine was not associated with a significant difference in infection incidence (HR 1.12, 95% CI: 0.48 - 2.63). Conclusions: In our large institutional cohort of patients with HCL, a considerable fraction (35%) of patients experienced serious or opportunistic infections. The majority of these were in the 2 months before or after initial treatment. We did not identify any demographic or disease factors associated with infection, although this is limited by the small sample size. Notably, treatment with either cladribine or pentostatin was not associated with a significant difference in infection incidence. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study.

We compared the incidences of four opportunistic infections (OI) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. We identified 205 906 patients with RA who were prescribed molecular-targeted drugs 2010-2017 from the National Database of Japan, and calculated the incidence of four OIs (Pneumocystis pneumonia [PCP], tuberculosis [TB], nontuberculous mycobacterial infection [NTM], and herpes zoster [HZ]). The total number of PCP, TB, NTM, and HZ patients with biological disease-modifying antirheumatic drugs (bDMARDs) or tofacitinib treatment history in RA were 765, 1158, 834, and 18 336, respectively. The incidence rates (IRs) of each OI for all bDMARDs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively; while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among bDMARDs. All OIs showed higher incidence in those older than 65 years; but PCP, NTM and HZ showed no difference between those 65-74 years old and those over 75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. We counted real IRs of OIs for the whole nation from big claims data.

Dysphagia in Alzheimer's disease

The article highlights the problem of dysphagia, which is often present in patients with Alzheimer's disease (AD), as a rule, at advanced stages of the disease and significantly complicates the management of this group of patients. Issues of age-related physiologic swallowing changes are considered. Mechanisms of dysphagia development in the elderly and in AD patients are discussed. It is noted that in AD areas of the cerebral cortex, involved in the act of normal swallowing are affected. The most dangerous complication of dysphagia is aspiration, which increases the risk of pneumonia and death. It is noted that dysphagia in patients with AD leads to weight loss and increased dependence on nutrition. Weight loss increases the risk of opportunistic infections in patients with AD. In the case of dysphagia symptoms development, pill administration causes great problems. In this scenario, the solution is the use of dispersible or liquid forms of drugs. We describe a clinical case of severe AD in which a dispersible form of memantine, Memoritab, was used. The complications associated with dysphagia in patients with AD highlight the importance of early detection and treatment of this symptom. Understanding the specific pathological processes of the underlying disease that contribute to the development of dysphagia is necessary in order to adapt the treatment of patients in a timely fashion.

Pneumocystis jirovecii Pneumonia in Patients with Solid Malignancies: A Retrospective Study in Two Hospitals.

Pneumocystis jirovecii pneumonia (PJP) is a rare opportunistic infection in patients with solid malignancies. This study aimed to examine the characteristics of patients with solid cancers and PJP. We retrospectively reviewed the medical records of patients with solid tumors and PJP over an 11-year period, enrolling a total of 47 patients (30-day survival group: n = 20, 30-day mortality group: n = 27). Only 34% of patients received ≥20 mg of prednisolone for ≥2 weeks, and the 30-day mortality rate was 57.4%. The 30-day survival group included more women and patients with colon cancer than the mortality group. Furthermore, absolute lymphocyte counts (ALCs) were decreased at PJP symptom onset, as compared with the values observed 1–3 months earlier. Increased oxygen demand and low ALCs after 5–7 days of PJP treatment were also related to poor prognosis. Due to the limitations of this retrospective study, further studies that adhere to the PJP criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium will be needed to evaluate PJP in solid malignancies more clearly.

Factors Influencing Survival Status of HIV/AIDS after HAART in Huzhou City, Eastern China.

Background Highly active antiretroviral therapy (HAART) can effectively reduce the risk of death and opportunistic infections in patients with HIV/AIDS. The aim of this study was to analyse the survival status and its influencing factors in HIV/AIDS after HAART. Methods The data on patients' sociodemographic characteristics, treatment information, and follow-up results from the Information Management System of the Chinese Center for Disease Control and Prevention were obtained. Bivariate and stepwise multivariate Cox proportional hazards regression model analyses were performed. Results A total of 1812 participants were included in this study, of which 1716 were still alive (survival group) and 96 had died (death group). The results indicated that respondents who were elderly (HR = 1.053, 95% CI: 1.037–1.069, P < 0.01), who had heterosexual transmission (HR = 2.422, 95% CI: 1.314–4.465, P < 0.01) and whose current WHO clinical stage was stage III or IV (HR = 2.399, 95% CI: 1.215–4.735, P < 0.05) were more likely to have died; respondents whose baseline CD4+ T-lymphocyte count was equal to or more than 200 cells/μL (HR = 0.412, 95% CI: 0.275–0.616, P < 0.05) were unlikely to have died. Conclusions It is recommended that HAART be provided to HIV/AIDS patients at an early clinical stage and that the health services for HIV/AIDS patients after taking medicines be strengthened, which will help promote adherence to therapeutic regimens and improve quality of life.

S1003 Safety of Ustekinumab in Patients 65 Years or Older With Inflammatory Bowel Disease: A Propensity-Based Match Analysis

Introduction: Ustekinumab (UST) is a monoclonal antibody targeting both IL-12 and IL-23 receptors. Owing to its mechanism, there is always a concern for its adverse effects, including malignancy and opportunistic infections (OI). Our study aimed to study the risk of malignancy and OI in patients who were treated with UST and were 65 and older Methods: A retrospective cohort study was conducted using TriNetX, a multi-institutional database of more than 70 million patients from 49 healthcare organizations in the USA. We compared the 3-year risk of malignancy and opportunistic infections (OIs) in patients with inflammatory bowel disease (IBD) who were treated with UST who were 65 years and older compared with patients between the age of 18-65 years. Exclusion criteria included patients who were on the biologic agent for less than 3 months or had a prior history of any adverse event. 1:1 propensity-score matching was performed, gender, race, ethnicity, diabetes, nicotine dependence, obesity, PO and IV steroids, mean Hb, CRP, albumin, and calprotectin within 1 year before medication initiation. Adjusted odds ratios (aOR) with 95% confidence interval (CI) were calculated to express the risk of each adverse event Results: A total of 22,242 patients with IBD were identified who were 65 years or older. At the time of analysis, 147 patients received UST, 1,493 patients were on anti-TNF alpha (TNFi), 494 were on vedolizumab (VDZ), and 92 on tofacitinib, and 6040 patients were on a 5-ASA therapy. There was no difference in malignancy rates ( OR: 0.58, 95% CI; 0.29-1.15) and OI ( OR: 1.04, 95% CI; 0.50-2.1) in patients 65 years or older when treated with UST compared to 5-ASA therapy. There was also no difference seen in outcomes of malignancy and OI when UST was compared with other medications (TNFi, VDZ, tofacitinib) in the cohort Conclusion: In conclusion, Ustekinumab appears safe to be used in patients with IBD who are 65 years or older