Use Of Immunosuppressive Drugs Research Articles

P-1021. Comparative Clinical profile, Anti-Fungal resistance rates and in-hospital mortality in hospitalized patients with Candidaemia caused by Candida Auris versus Non-Auris Candida in a tertiary-care centre

Abstract Background Candidemia, a severest manifestation of invasive candidiasis, often encountered in intensive care units (ICUs) is predisposed by prolonged ICU-stay, immunosuppression or mechanical ventilation. In India, while various species of Candida (C. tropicalis, C. albicans, C. auris and others) are involved in candidemia, C. auris is particularly known for displaying higher anti-fungal resistance. We investigated, whether there was a difference in the clinical pattern of candidemia caused by C. auris vs non-auris Candida in our tertiary-care centre.Figure 1.Comorbidities among patients with candidaemia: C. auris group versus non-auris candida group CANDIDA AURIS VS NON-AURIS CLINICAL RISK FACTORS Methods The analysis involved 65 unique episodes (one patient per episode) of documented candidemia in our tertiary-care centre during January 2022 to April 2024. The clinical data was retrieved from the blinded hospital records. The day of admission of patients in to ICU was considered as hospital day-1. Results Among 65 episodes, 17 (26.2%) and 48 (73.8%) were that of C. auris and non-auris candida, respectively. The time to blood culture positivity was longer with C. auris cohort compared to non-auris candida cohort (median hospital days 27 vs 19). Total hospitalization days (median) were 49 and 15.5, P value 0.002 respectively. In-hospital mortality was 58% in C. auris group and 62.5% in non-auris candida group. There was more proportion of cancer patients in non-auris candida cohort while use of immunosuppressive drugs was more frequent in C. auris cohort (Figure 1). Resistance rates to fluconazole, amphotericin, and echinocandins were higher in C. auris group (94.5% vs 25%; 70.5% vs 6.3%; 11% vs 2.1%, respectively)..Total Parenteral Nutrition > 5 days (26.2% vs 73.9%) P value 0.38, Transplant Patients (47.05% vs 14.58%) , immunosuppressive drugs (64.7% vs 39.6% ) P value 0.07 and Mechanical Ventilation (88.2% vs 52.1%) P value 0.008 respectively. Conclusion C. Auris has emerged as a notorious Non Albicans Candida species with substantial morbidity and mortality suggesting change in the epidemiology of candidaemia. Patients with Candida auris had longer hospital stay and blood to positivity than others. Fluconazole resistance remains highest in candida auris than other species of candida and majority of isolates of C.auris had high MICs for amphotericin B. Disclosures All Authors: No reported disclosures

Risk and protective factors of disease flare during pregnancy in systemic lupus erythematosus: a systematic review and meta-analysis.

To synthesize available evidence on predictive factors associated with systemic lupus erythematosus (SLE) flares during pregnancy, we systematically searched MEDLINE, Embase, and the Cochrane Library through January 2024 for observational studies on risk and protective factors of SLE flares during pregnancy. Odds ratios (OR) and mean differences (MD), as well as their 95% confidence intervals (CI) were used to quantify effect sizes. We employed fixed-effect or random-effect models based on heterogeneity assessments (I2 statistics). Sensitivity analyses were performed using the leave-one-out method, and publication bias was assessed through Egger's test. Thirty-two studies were included in the meta-analysis. Significant baseline SLE characteristics associated with higher risks for flares during pregnancy were identified: thrombocytopenia (with OR [95%CI], 2.29 [1.14-4.58]), hypocomplementemia (1.70 [1.28-2.27]), anti-dsDNA positivity (1.43 [1.16-1.77]), and a history of lupus nephritis (2.34 [1.70-3.21]). Protective factors included achieving remission before pregnancy (0.32 [0.20-0.49]) and antimalarial use at baseline (0.71 [0.55-0.92]) and during pregnancy (0.44 [0.33-0.58]). Additional risk factors included baseline glucocorticoid usage (1.51 [1.17-1.94]), glucocorticoid administration during pregnancy (3.39 [1.90-6.06]), use of other immunosuppressive drugs at baseline (1.46 [1.00-2.12]), and hypertension (2.16 [1.45-3.23]). Furthermore, individuals in the flare group were younger, had higher baseline disease activity, and lower C3/C4 levels compared to the non-flare group. This study highlighted the critical role of managing SLE disease activity prior to pregnancy to minimize flare risks, and identified significant risk and protective factors associated with flares. These evidences facilitate better clinical management strategies for pregnant women with SLE. Key Points • Synthesizes existing evidence on the risk and protective factors associated with SLE flares during pregnancy. • Highlights the critical importance of effectively managing disease activity prior to conception. • Provides insights to enhance risk stratification and management strategies for pregnancies in patients with SLE.

Surgical site infection prevention: best practices and new approaches

Surgical site infections (SSIs) remain a significant challenge in surgical care, posing a substantial threat to postoperative morbidity and mortality. There are many risk factors that can cause SSIs, encompassing patient-related factors and healthcare team practices. The risk factors for SSIs include advanced age, diabetes, smoking, obesity, distant site infections, elevated biomarkers, low HDL levels, opioid addiction, immunosuppressive drug use, higher ASA grade, comorbidities, prolonged preoperative hospitalization, and antibiotic resistance. Preoperative, intraoperative, and postoperative precautions have all been used as part of comprehensive preventative efforts to reduce the incidence of SSIs. Furthermore, emerging technologies, such as artificial intelligence and machine learning, have demonstrated potential in enhancing SSI detection and prevention, offering promising advancements to further optimize surgical outcomes. This review aims to explore the current evidence, risk factors, and emerging strategies in SSI prevention. By understanding the multifactorial nature of SSIs and implementing comprehensive preventive measures, healthcare providers can significantly mitigate the burden of these infections, ultimately improving patient outcomes and the overall quality of surgical care.

About two French cases of disseminated Cryptococcus neoformans infection associated with COVID-19.

SARS-CoV-2 infection is an acute respiratory distress syndrome associated with immune dysfunction, causing COVID-19 disease. The use of immunosuppressive drugs in its treatment increases the risk of opportunistic infections. In particular, opportunistic fungal infections have been described in initially non-immunocompromised patients with severe COVID-19 disease. Among them, rare cases of cryptococcosis have been described. Here we present the first two French cases of non-HIV non-transplant patients who developed disseminated Cryptococcus neoformans fungal infection in the setting of severe COVID-19 disease. Blood cultures appear to be an interesting diagnostic tool for post-COVID-19 cryptococcosis, which is an often fatal complication.

Clinical presentation and outcome of patients with endogenous endophthalmitis.

The study aims to evaluate the clinical characteristics, risk factors, microbiological findings, and visual outcomes, as well as patient and eye survival, of patients diagnosed with endogenous endophthalmitis (EE). A retrospective study was conducted on 29 eyes from 21 patients diagnosed with EE. The mean age of presentation was 56.8 years, with a male predominance. The most common predisposing factors were diabetes mellitus and recurrent urinary tract infections. 42.9% of patients exhibited positive blood cultures, whereas positive vitreous cultures were detected in 38.1% of patients. The majority of cases were caused by bacterial infections. The median final visual acuity was 2 (0.1-2.9) LogMAR, with no significant difference between the bacterial and fungal groups. According to the Kaplan-Meier analysis, first-year survival rate was 90.5%, and the rate of eye preservation (at least one eye) was significantly lower in the presence of immunosuppresant drug usage (p = 0.004, Log Rank = 8.348). Endogenous endophthalmitis typically has a poor visual prognosis, with the loss of anatomical integrity or mortality not being uncommon. The findings of the study provide insights into the clinical and microbiological characteristics of patients with EE in Turkey. Initial visual acuity and severe intraocular inflammation at presentation have been identified as predictors of poor visual outcomes. The negative impact of immunosuppressive drug use on globe survival has been noted. In patients using immunosuppressive drugs, healthcare providers being vigilant towards infectious pathologies and prompt intervention may increase the chances of success in EE treatment.

Myeloid-derived Suppressor Cells and Multiple Sclerosis.

Myeloid-Derived Suppressor Cells (MDSCs) are a heterogeneous population of immature myeloid cells that play important roles in maintaining immune homeostasis and regulating immune responses. MDSCs can be divided into two main subsets based on their surface markers and functional properties: granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). Recently greatest attention has been paid to innate immunity in Multiple Sclerosis (MS), so the aim of our review is to provide an overview of the main characteristics of MDSCs in MS and its preclinical model by discussing the most recent data available. The immunosuppressive functions of MDSCs can be dysregulated in MS, leading to an exacerbation of the autoimmune response and disease progression. Antigen-specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non-specific immunosuppressive drugs, is a promising approach for autoimmune diseases, but the cellular mechanisms behind successful therapy remain poorly understood. Therefore, targeting MDSCs could be a promising therapeutic approach for MS. Various strategies for modulating MDSCs have been investigated, including the use of pharmacological agents, biological agents, and adoptive transfer of exogenous MDSCs. However, it remained unclear whether MDSCs display any therapeutic potential in MS and how this therapy could modulate different aspects of the disease. Collectively, all the described studies revealed a pivotal role for MDSCs in the regulation of MS.

Rheumatoid arthritis and viral hepatitis. Tactics of a rheumatologist. Literature review

Rheumatoid arthritis (RA) is an autoimmune disease that can be accompanied by complex liver involvement. The diagnosis and differentiation of these conditions are often complicated by the rarity of liver biopsies and the similarity of symptoms to other liver diseases. Viral hepatitis B and C in the context of rheumatoid arthritis can mimic rheumatological manifestations, further complicating timely diagnosis and worsening the prognosis for patients with rheumatoid arthritis. This literature review aims to systematize knowledge and assess the risks associated with the treatment of rheumatoid arthritis in patients with viral hepatitis B and C. Additionally, the article aims to provide recommendations for screening and treatment of viral hepatitis in these patients. The review is based on the analysis of available literature for the last ten years, including clinical trials, meta‑analyses, systematic reviews, and recommendations for the treatment of viral hepatitis in patients with rheumatoid arthritis. According to the literature, liver involvement in patients with rheumatoid arthritis can be caused by the disease itself, its treatment, or viral infections. Research results emphasize the importance of regular monitoring of liver function and screening for viral hepatitis B and C before starting rheumatoid arthritis treatment and during the use of immunosuppressive drugs. The integration of screening for viral hepatitis B and C into standard medical protocols for patients with rheumatoid arthritis before starting immunosuppressive therapy is essential. The timely detection of these infections is crucial because the treatment of hepatitis and immunosuppressive therapy for rheumatoid arthritis are interconnected and require a comprehensive approach. Adaptation of treatment depending on the status of viral infection is necessary to minimize liver risks and optimize the outcomes of rheumatoid arthritis treatment.

Optimizing growth in pediatric renal transplant recipients: An update.

Growth retardation is a significant complication observed in pediatric renal transplant recipients, originating from a multifactorial etiology. Factors contributing to growth impairment encompass pre-transplant conditions such as primary kidney disease, malnutrition, quality of care, growth deficits at the time of transplantation, dialysis adequacy, and the use of recombinant human growth hormone. Additionally, elements related to the renal transplant itself, such as living donors, corticosteroid usage, and graft functioning, further compound the challenge. Although renal transplantation is the preferred renal replacement therapy, its impact on achieving final height and normal growth in children remains uncertain. The consequences of growth delay extend beyond the physiological realm, negatively influencing the quality of life and social conditions of pediatric renal transplant recipients, and ultimately affecting their educational and employment outcomes. Despite advancements in graft survival rates, growth retardation remains a formidable clinical concern among children undergoing renal transplantation. Major risk factors for delayed final adult height include young age at transplantation, pre-existing short stature, and the use of specific immunosuppressive drugs, particularly steroids. Effective management of growth retardation necessitates early intervention, commencing even before transplantation. Strategies involving the administration of recombinant growth hormone both pre- and post-transplant, along with protocols aimed at minimizing steroid usage, are important for achieving catch-up growth. This review provides a comprehensive outline of the multifaceted nature of growth retardation in pediatric renal transplant recipients, emphasizing the importance of early and targeted interventions to mitigate its impact on the long-term well-being of these children from birth to adolescence.

Patients with Darier disease have an increased risk of keratinocyte carcinoma: a Swedish registry-based nationwide cohort study.

Darier disease is a genodermatosis which manifests as hyperkeratotic papules and superficial erosions mainly in seborrheic skin areas. This retrospective registry-based cohort study aimed to estimate the association between Darier disease and skin cancer. Patients diagnosed with Darier disease were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) in 2016-2020. The local cohort included 13 patients. Verification of Darier disease diagnosis in the National Patient Registry showed positive predictive value of more than 90%. National Patient Registry was searched for Darier disease in 2001-2020, Swedish Cancer Registry for cancers and Prescribed Drug Register for medications. The national cohort included 770 patients and tenfold matched control cohort. Patients with Darier disease had an increased relative risk of keratinocyte carcinoma (basal cell carcinoma and cutaneous squamous cell carcinoma combined) (hazard ratio [HR], 1.6, 95% confidence interval [CI], 1.0-2.5, P = 0.036). The risk increase was significant for basal cell carcinoma (HR, 1.8, 95% CI, 1.1-2.9, P = 0.012), whereas there was a trend for cutaneous squamous cell carcinoma, (HR, 1.9, 95% CI, 0.9-4.1, P = 0.086) and cutaneous melanoma (HR, 2.4, 95% CI, 0.9-6.2, P = 0.083). Standardized incidence ratio for keratinocyte cancers was 2.9 (95% CI, 2.4-3.3. The results were consistent in two subgroup analyses adjusting for use of retinoid and/or immunosuppressive drugs. Patients with Darier disease have an increased risk of skin cancer, particularly keratinocyte carcinoma. This risk was consistent even when known risk modifiers for keratinocyte carcinoma were excluded in sensitivity analyses. The results support previously proposed molecular links between Darier disease and skin cancer, but further investigations are needed. Additional studies are also required to develop clinical management recommendations for Darier disease. In the meantime, dermatologists should be aware of the cancer risk in these patients and remain vigilant, as detecting cancer can be challenging in hyperkeratotic and/or eroded skin.

A complex case of severe thrombocytopenia in systemic lupus erythematosus complicated by Corynebacterium spp. infection

BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disease the course of which is still indefinite. Thrombocytopenia concurrent with Corynebacterium spp.—an infrequent complication in SLE patients—is seldom reported. CASE A 34-year-old female was admitted for continuous bleeding from the gums that had been ongoing for three days. The patient had been suffering from SLE since 2018 and took immunosuppressive medication regularly. The anemia, lymphocytopenia, and severe thrombocytopenia were shown in her laboratory tests. Besides, the infection of Corynebacterium spp. was detected in the patient. In fact, hematologic abnormalities and infections in SLE patients usually mutually overlap for the reason that these conditions possess the potential to influence each other. Infection can be both the cause and result of hematologic abnormalities in SLE. Thus, the pathophysiology of hematologic abnormalities in SLE patients can often be related to the use of immunosuppressive drugs. However, some theories suppose that increased SLE activity correlates with infection occurrence in SLE—even without the use of immunosuppressive drugs. CONCLUSION Thrombocytopenia and Corynebacterium spp. infection in SLE patients is a case rarely reported, and establishing the diagnosis requires detailed examination.

Exploring lymphocyte subsets in COVID-19 patients: insights from a tertiary academic medical center with a high proportion of patients on immunosuppression.

Severe COVID-19 is associated with reduced absolute lymphocyte counts, suggesting that lymphocyte subsets may serve as predictors of clinical outcomes in affected patients. Early identification of patients at risk for severe disease is crucial for optimizing care, accurately informing patients and their families, guiding therapeutic interventions, and improving patient flow in the ED. Given that immunosuppressive drugs significantly impact lymphocyte profiles, we aimed to determine the association between prior use of immunosuppressive drugs, lymphocyte subsets, and COVID-19 severity in our population with a high prevalence of immunosuppression. In 2021, suspected COVID-19 patients were included in the ED. Lymphocyte subsets were determined in peripheral blood within 24 hours after presentation and comparative analyses was performed between SARS-CoV-2 negative and positive patients, mild versus severe disease and patients with and without prior immunosuppressive drug use. Mild cases were patients discharged home or admitted to a general ward, severe cases were patients with COVID-19-related mortality or necessitating ICU admission. Logistic regression analysis was performed to assess the association between lymphocyte subsets and COVID-19 severity, and between prior immunosuppressive drug use and COVID-19 severity. Twenty-five SARS-CoV-2 negative and 77 SARS-CoV-2 positive patients were included, whereof 57 (74%) had mild and 20 (26%) severe COVID-19. No significant differences were observed in the absolute counts of CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes, and NK-cells between SARS-CoV-2 negative and positive patients or between mild and severe cases. The 36 patients with prior use of immunosuppressive drugs had significantly lower CD4+ T-lymphocytes (p<0.01). Prior use of immunosuppressive drugs was not associated with COVID-19 severity (adjusted OR 1.074, 0.355-3.194). Lymphocyte subsets were not significantly different between SARS-CoV-2 negative and positive patients and between mild versus severe cases. Neither lymphocyte subsets nor prior immunosuppressive drug use were associated with COVID-19 severity.

Evaluation of Demographic and Clinical Characteristics of Patients Diagnosed with Herpes Zoster

Objective: Varicella-zoster virus (VZV) infections result in two distinct clinical entities: varicella (chickenpox) and herpes zoster (HZ). VZV, the causative agent of chickenpox, remains latent in the dorsal root or cranial nerve ganglia and reactivates due to suppression of the cellular immune system, leading to HZ. Risk factors for HZ include advanced age, stress, concomitant infections, use of immunosuppressive drugs, and comorbid conditions. This study retrospectively evaluates patients diagnosed with HZ who presented to our hospital. The aim is to determine the frequency of herpes zoster based on age, gender, season, and months, as well as the accompanying diseases, complications, and treatments provided. Materials and Methods: Patients diagnosed with HZ (ICD10 code B02) who presented to our hospital’s dermatology outpatient clinic between December 1, 2022, and November 30, 2023, were included in this study using our hospital's automation system. Results: A total of 211 patients were included in the study, consisting of 115 women (54.50%) and 96 men (45.50%), with a female/male ratio of 1.19. The average age of the patients diagnosed with HZ was found to be 53.38 years. It was observed that HZ occurred more frequently in march (12.32%), august (11.37%), and april (9.95%), and seasonally, it was more common in the spring (29.86%). The most commonly affected body region was the trunk (54.5%), and the most frequently involved dermatome was thoracic (46.4%). The most common comorbidities in patients diagnosed with HZ were hypertension (32.05%) and diabetes mellitus (12.82%). The most frequently administered treatment was valacyclovir (47.87%). Postherpetic neuralgia (PHN) was observed in 37 patients (17.53%) with HZ. Conclusion: As the frequency of HZ increases with age, early recognition and treatment are crucial for reducing pain, viral spread, and complications. There is a need for large-scale studies on the clinical and demographic data of HZ.

Epidemiology and pathogen characteristics of infections following solid organ transplantation.

Solid organ transplantation (SOT) recipients have a heightened risk for infection due to prolonged immunosuppressive drug use following transplant procedures. The occurrence of post-transplant infections is influenced not only by the transplanted organ type but also by varied factors. The kidney is the most common organ in SOT, followed by the liver, heart, and lung. This review aims to provide a comprehensive overview of the current epidemiological characteristics of infections after kidney, liver, heart, and lung transplantation, focusing on bacterial, fungal, and viral infections. The incidence and infection types demonstrated significant variability across different SOTs. Furthermore, this review attempts to elucidate the clinical characteristics of infections across patients following different SOTs and contribute to the development of individualized prevention strategies according to infection incidence, ultimately enhancing the quality of life of transplant recipients.

The real-world impact of biologics for NMOSD: A retrospective single-center study compared with natural course and conventional treatments in Japanese

BackgroundNeuromyelitis optica spectrum disorder (NMOSD), a central nervous system inflammatory disease associated with aquaporin-4 immunoglobulin G (AQP4-IgG), is conventionally treated with oral steroids and immunosuppressants (IS) in Japan. Several biologics which show great efficacy in the clinical trials have been developed recently. However, studies on their efficacy, especially those comparing them with conventional treatments in real-world situations are lacking. ObjectiveHere, we conducted a single-center retrospective cohort study in Japan comparing the efficacy of biologics, over conventional drugs, in treating AQP4-IgG-positive NMOSD. MethodsWe extracted the medical history of patients with AQP4-IgG-positive NMOSD who visited the Tohoku University Hospital between 2000 and 2023, from the hospital patient database. All patients were diagnosed according to the international consensus diagnostic criteria for NMOSD 2015. We then classified the disease duration of each patient into four periods based on their prescription history as: no-treatment, prednisolone monotherapy (PSL-mono), immunosuppressants (IS) treatment, and biologics (Bio) treatment. Subsequently, the efficacy of Bio treatment, over the conventional treatment, in alleviating AQP4-IgG-positive NMOSD was estimated. We used univariate Poisson regression analysis to compare the annualized relapse rate (ARR), log-rank test for the first attack, and the hazard ratios (HR)—calculated using multivariate Andersen-Gill model for recurrent attacks—of the Bio and conventional treatment period groups. The safety of each treatment period group was assessed by comparing infection and mortality rates. ResultsA total of 109 patients (92 % females) met the eligibility criteria of the study. We could extract a total of 1,283 patient years with 289 NMOSD attacks from their medical history data. The mean ARR of no-treatment group was 0.60. Most of the Bio group initially received combined treatments with PSL or IS. The mean ARR of the Bio group was 0.01 [95 % confidence interval (CI): 0.002 to 0.08], which was significantly lower than the PSL-mono group (0.16, 95 % CI: 0.13 to 0.19, p = 0.03) and the IS group (0.17, 95 % CI: 0.13 to 0.22, p = 0.02). In the survival analysis, the Bio group showed a significantly prolonged attack-free period than the other groups, suggesting its potential in reducing 79 % of relapses in the no-treatment group, 33 % in the PSL-mono group, and 31 % in the IS group during the two years. The multivariate analysis using Andersen-Gill model showed that the Bio group had significantly lower HR (log HR −2.75, 95 % CI: −4.71 to −0.8, p = 0.006), relative to the PSL-mono group. Importantly, the patients needed significantly lower PSL (median 5 mg/day) during the Bio group treatment period than in the PSL-mono group treatment period (median 10 mg/day). Further, the concomitant use of IS could be stopped safely in all patients who were on Bio treatment. All treatment period groups showed similar safety profiles. ConclusionIn patients with AQP4-IgG-positive NMOSD, biologics demonstrated more efficacy than conventional PSL and/or IS treatment, without increasing infection and mortality rates.

Abstract 4138738: Clinical Evidence of Immune Response to Transplanted Allogeneic iPS Cell-Derived Cardiomyocytes

Background&amp;Purpose: The clinical application of cell transplantation therapy utilizing induced pluripotent stem cells (iPS cells) for heart failure is progressing, with the primary strategy being the use of pre-prepared allogeneic iPS cells. The immune response to these transplanted cells is crucial and may affect therapeutic efficacy, necessitating the use of immunosuppressive drugs. However, detailed clinical reports on immune responses are sparse. This study aims to analyze the immune response to transplanted cells in clinical iPS cell-derived cardiomyocyte (iPSC-CM) transplants and examine the correlation between immune response and therapeutic efficacy. Methods: In the "Phase 1 multicenter clinical trial of transplantation of iPSC-CMs for ischemic cardiomyopathy" (https://jrct.niph.go.jp/en-latest-detail/jRCT2053190081), conducted as the First-in-Human trial, the immune response to transplanted cells was analyzed in four cases at our hospital. Comprehensive analysis of anti-human leukocyte antigen (HLA) antibodies in serum and single-cell RNA sequencing in peripheral blood mononuclear cells was performed to investigate their relationship with therapeutic effects on cardiac function. Results: Patients received immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and steroids) for 3 months post-transplantation, followed by a 1-year follow-up. In all cases, an increase in transplant cell HLA-specific antibodies was observed after discontinuing immunosuppressive drugs (Figure 1 and 2). Single-cell analysis revealed a decrease in immunocompetent cells in peripheral blood during immunosuppressive therapy. Cardiac function analysis showed improvements in all cases except Case 2 (Figure 3), where pre-existing anti-HLA-DQ antibodies were present before transplantation. Conclusions: No immune response to the transplanted cells was observed during immunosuppressive therapy. In a case with limited therapeutic response, pre-existing antibodies to transplanted cells were detected, potentially impacting the therapeutic outcome.

Inappropriate Prescribing of Nirmatrelvir/Ritonavir in Solid Organ Transplantation With COVID-19 Infection: A Multicenter Retrospective Study

BackgroundNirmatrelvir-ritonavir (NR) has demonstrated effectiveness in halting the progression to severe coronavirus disease 2019 (COVID-19) among solid organ transplant recipients (SOTRs) infected with Severe Acute Respiratory Syndrome Coronavirus 2. However, it has a wide range of interactions, especially with immunosuppressants. The study aimed to comprehensively evaluate the Inappropriate prescribing of NR and immunosuppressants in SOTRs with COVID-19, while also highlighting the essential aspects. MethodsWe included hospitalized SOTRs who received NR at five tertiary hospitals between December 2022 and June 2023, and evaluated their prescription. ResultsA total of 211 patients were enrolled, of which 205 did not meet all criteria for appropriate prescribing (97.16%). Inappropriateness primarily stemmed from starting treatment more than 5 days after symptom onset (87.68%), followed by application in severe-to-critical cases of COVID-19 (52.13%), the inappropriate dosages based on renal function (47.87%). Contraindications encompassed 17.06% of patients with severe renal impairment and 5.69% with contraindicated drug interactions. Inappropriate resumption of immunosuppressants accounted for a larger proportion than inappropriate discontinuation or dose adjustment (30.16% vs 8.99%). More than one-third of patients neglected to monitor concentrations. About 8% experienced abnormal high concentrations. ConclusionInappropriate prescribing of NR is widespread among hospitalized SOTRs. Adjusting doses based on patients’ renal function and paying attention to concurrent use of immunosuppressive drugs are crucial, and therapeutic drug monitoring is necessary. Clinical practitioners should enhance their vigilance and attention.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce. To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health. Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner. Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR>800, N>10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin. This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

Neglected Pulmonary Infection Caused by Exophiala dermatitidis Misidentified as Rhodotorula spp.

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

A capsule-based scaffold incorporating decellularized extracellular matrix and curcumin for islet beta cell therapy in type 1 diabetes mellitus

The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62% ± 1.09% and a tensile stress of 1.85 ± 0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96 ± 0.08 mIU ml-1, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1β, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.

Clinical characteristics of pyoderma gangrenosum: Case series and literature review.

Pyoderma gangrenosum (PG) is a neutrophilic skin disease characterized by recurrent painful cutaneous ulcers, often accompanied by inflammatory bowel disease, joint pain, and other systemic damage. This disease is relatively rare in clinical practice and its diagnosis and treatment are often delayed, leading to secondary infections in the skin lesions, prolonged disease course, and increased disease burden on patients. This study retrospectively analyzed the clinical characteristics and treatment strategies of patients with PG admitted to our hospital and conducted a literature review, in order to improve the understanding of the disease among clinical doctors, enable patients to receive better diagnosis and treatment, and ultimately improve patient prognosis. Clinical data of patients diagnosed with PG and hospitalized in Beijing Chaoyang Hospital, Capital Medical University from January 2014 to December 2022 were retrospectively collected. The clinical manifestations, treatment strategies, efficacy, and disease outcomes were analyzed. A total of 14 patients, including 8 males and 6 females, aged 14 to 66 years, were included. Skin lesion types: 13 cases were ulcer-type, 1 case was pustule combined with ulcer-type, and the lower limbs were the most commonly affected areas. All the 14 patients presented with comorbidities. All patients were treated with glucocorticoids, with a daily dose equivalent to 20 to 100 mg prednisone and a median dose of 40 mg. Among them, 3 patients were treated with minocycline in combination, 1 patient was treated with mycophenolate mofetil 0.5 twice daily in combination, 1 patient was treated with cyclophosphamide 0.1 once daily in combination, and 1 patient was treated with thalidomide 0.1 every night in combination. PG is a relatively rare immune-related skin disease. Our small sample data analysis found that male PG is not uncommon in the Chinese population. Systemic glucocorticoids can quickly control the symptoms of PG in most patients with PG. In patients with poor efficacy or limited use of glucocorticoids, immunosuppressive drugs or novel targeted drugs such as biologics or small-molecule drugs should be used in combination as early as possible. Skin lesion care focuses on preventing infection, avoiding surgical debridement, and emphasizing pain management and the symptomatic treatment of comorbidities.