Use Of Immunosuppressive Drugs Research Articles

#1960 Incidence of cancer in ANCA associated vasculitis (AAV)

Abstract Background and Aims We investigated the incidence rate and type of cancer in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in our Institute. Method We retrospectively included 210 patients with AAV [106 patients with microscopic polyangiitis (MPA), 93 with granulomatosis with polyangiitis (GPA) and 11 patients with eosinophilic GPA (EGPA)], and reviewed their medical records. We collected demographic, clinical and laboratory data. We selected patients with history of cancer, patients diagnosed with paraneoplastic AAV and patients who developed malignant disease after AAV. We reviewed the use of glucocorticoid and immunosuppressive drugs. Results Between 1993-2024 there were 16 patients with AAV who had cancer during their life in our Department. There were eight patients with malignancy-associated AAV. Two patients were simultaneously diagnosed with kidney carcinoma and vasculitis. One patient's serum was positive for cytoplasmatic ANCA, the other patient's for pANCA. Complete resection of cancer and renal biopsy was performed, they got steroid monotherapy. Five patients were diagnosed with pANCA vasculitis a few months (1-5) after the diagnosis of malignancies (two pts with breast carcinoma, two pts with ovarium carcinoma, one patient with ventricular carcinoma). In one case the pAAV was established after 5 months of oropharyngeal tumor's resection. Two patients had history of malignancy (one pts had colon carcinoma 4 ys before the appearance of AAV, the other patient had breast carcinoma 10 ys before the AAV). In both cases there were examinations for malignancy with negative results. In these cases the vasculitis was not associated with carcinoma. The therapeutic approach included the use of corticosteroids, plasmapheresis, and cyclophosphamide or rituximab. Six patients were observed malignancy 0.5-10 years after the diagnosis of AAV. There was one pancreas, one ventricular, two lung and two bladder carcinoma. Conclusion In our study we focused on the relationship of malignancy and AAV. Between the 210 patients with AAV eight cases (3.8%) were malignancy-associated, in one case cANCA associated, the other cases pANCA was presented. Treating paraneoplastic vasculitis can be challenging. Individualized treatment strategy tailored to patients' needs is crucial. Six patients were diagnosed with solid tumor during the follow-up. The cumulative overall cancer incidence rates were 1.4% and 2.8% at 5 and 10 years, respectively. Only in one patient with bladder cancer was treated with the cumulative CYC doses ≥ 36 g. No leukemia or non melanotic skin cancer (NMSC) was represented contrary to other studies.

#1312 Warfarin-related nephropathy in two patients with mechanical valves

Abstract Background and Aims Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical valves required long-term anticoagulant therapy, and warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical valves constitute a special group among the entire anticoagulant population. Method The present study recorded two patients receiving warfarin therapy for mechanical valve presented to the hospital with gross hematuria and progressive creatinine levels. Results The first patient was a 56-year-old female, who had previously undergone mechanical aortic valve replacement surgery nine months ago and was prescribed warfarin, was admitted to the hospital due to the occurrence of gross hematuria six days before hospitalization. Additionally, her creatinine levels exhibited a rapid increase from 120.5umol/L to 207.5 μmol/L within three days. Laboratory analysis revealed a creatinine level of 167.8 μmol/L, albumin level of 39.6 g/L, and an INR value of 2.08. The urinary test results indicated the presence of urinary protein (+) and urinary occult blood (3+). The quantification of urinary protein over a 24-hour period was measured at 0.69 g. The immunoglobulin, complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. The second patient was a 63-year-old male, who has been diagnosed with hypertension for the twenty years, underwent Bentall+Sun's surgery for type A aortic dissection five years ago. Following the surgery, the patient was prescribed warfarin. The patient was admitted to the hospital due to persistent gross hematuria for a duration of twenty days and an increase in creatinine levels. Upon admission, laboratory analysis revealed a creatinine level of 169.9μmol/L (which was within the normal range one year ago), and an INR of 2.69. The urinary test indicated the presence of urinary protein (2+) and urinary occult blood (3+). Urinary protein quantification was 3.06 g/24 hours. The serum IgA level was measured at 4.55 g/L (normal range: 1.0-4.2 g/L). The complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. Pathology of two patients all showed red blood casts and tubular injury consistent with ARN and underlying IgA nephropathy (Fig. 1). The two patients was administered a daily dosage of 20 mg of prednisolone and an oral dosage of 50 mg of cyclophosphamide every other day. During a subsequent follow-up after a two-month period, the first patient's creatinine had decreased to 109.2μmol/L, and the urine protein quantification was recorded as 119.7 mg/24 hours. The second patient's creatinine had decreased to 159.2 μmol/L, and the quantification of urine protein was recorded at 310 mg/24 hours. Conclusion Clinicians should maintain a state of increased alertness with regards to the potential occurrence of WRN who exhibit hematuria and elevated creatinine levels while on warfarin therapy, even if their INR remains within the normal range. Considering most patents of WRN have an underlying glomerular disease (mostly IgA nephropathy), the use of steroids and immunosuppressive drugs may appear to be an attractive option, particularly in patients who are unable to replace warfarin with direct oral anticoagulants (NOACs).

Peculiarities of clabsi in oncologic hospitals

Currently, healthcare-associated infections (HAIs) are one of the most dangerous complications for hospitalized patients. The economic damage caused by HCAI in the Russian Federation annually is about 15 billion rubles; in addition, HCAI occupy the tenth place among the causes of mortality of the population. Catheter-associated bloodstream infection holds the leading place in the structure of ISMP morbidity. The concept of CVC-AIC (catheter-associated bloodstream infections or CLABSI), in turn, is included in CAIC. Purpose of the study. To analyze the current literature data of domestic and foreign authors for the years 2012-2022 concerning CAIC in patients of oncologic hospitals with CVCs, including subcutaneous central venous port catheters. Material and Methods. A review of 38 literature sources for the last 10 years was performed, including current information on catheter-associated bloodstream infections, measures to prevent them, and modern treatment approaches. Results. The studies have shown that the combination of drug resistance in microorganisms and immunity reduction in cancer patients, which occurs against the background of chemotherapy, makes them a risk group for the development of CAICs and episodes of their recurrence. Ensuring epidemiological safety of bloodstream catheterization in such patients is an important step in the prevention of CAIC. This is one of the priority tasks of oncoepidemiology today. Conclusion. The leading role in the occurrence of catheter-associated bleeding plays the term of catheterization and the condition of the patient, his age, stage of cancer development and concomitant chronic diseases. One of the most vulnerable risk groups are cancer patients from hemoblastosis chemotherapy and bone marrow and hematopoietic stem cell transplantation units. This may be due to the use of immunosuppressant drugs to suppress graft rejection, which significantly reduce patients' immunity. According to the results of studies, infection with drug-resistant Gram-negative microorganisms, including multidrug-resistant ones, is prevalent in cancer patients with CAIC. When using povidone iodine, there is a tendency to decrease the incidence of CAIC, but the use of chlorhexidine alcohol solution showed better results. A direct correlation was observed between the use of surgically implanted intravascular devices for long-term function and a lower incidence of CAIC, particularly in pediatric oncology.

Visual outcome of cataract surgery in paediatric uveitis

1. To analyse the visual outcome in patients of paediatric uveitis who underwent cataract surgery; 2. To analyse the post-operative complications of cataract surgery in paediatric uveitis.Retrospective observational study was done on patients of uveitis who underwent cataract surgery. Patients who were under 18 years and co-operative for examination were included.They underwent Phacoaspiration with posterior chamber IOL implantation by a single surgeon after 3 months of activity free interval, BCVA(in Log MAR) in every follow up, anterior segment examination using slit lamp and posterior segment examination using IDO, post-operative complications and Intra ocular pressure was recorded using Noncontact tonometer.Uveitis was classified using the SUN classification of uveitis. Use of corticosteroids, biologics and immunosuppressive drug were collected at each visit. Total of 18 subjects diagnosed with cataract as a complication of uveitis & undergone cataract surgery were studied (6 were females, 12 were males) 9 had anterior uveitis, 1had intermediate uveitis and 5 had pan uveitis. JRA (66.7%) was the most common cause identified. Improvement in vision from baseline was observed post-surgery at the end of first, third and 6th month which was statistically significant (P- Value <0.05). Average duration of disease before they underwent surgery was 18 months. Most common post op complication was posterior capsular opacification (50 %), others include secondary glaucoma (38.9), exudative retinal detachment (5.6%) and Vitritis (22.2%)Unlike adult uveitic patients, the surgical management of paediatric uveitic cataract is both challenging and controversial, and the surgery itself has been associated with poor visual outcomes. However, our study had shown that with implantation of IOL, good immunosuppressants and control of the disease can give these children a good visual outcome.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Macrophagic Activation Syndrome Revealing Tuberculosis: A Case Report

We present a case involving an immunocompetent infant diagnosed with miliary tuberculosis complicated by macrophage activation syndrome. Macrophage activation syndrome (MAS), also known as bone marrow hemophagocytosis, presents as a non-specific clinical condition characterized by fever and hepatosplenomegaly. A 22-month-old infant from a non- consanguineous marriage, the only child in the family, was admitted to a regional hospital due to prolonged fever lasting 15 days. The syndrome can manifest as a primary disorder (familial HLH) due to various genetic mutations or as a sporadic secondary disorder triggered by infections, autoimmune diseases, or malignant conditions. The early initiation of antibacillary treatment in AMS complicating tuberculosis without the use of immunosuppressive drugs provides better management and improves the vital prognosis.

"Getting the Dose Right"-Revisiting the Topic With Focus on Biologic Agents.

Nearly two decades after the Peck and Cross article '"Getting the dose right: facts, a blueprint, and encouragements" was published, a review of dose recommendations for biologics shows that the success in getting the dose right appears to have improved given the relatively low incidence of drug withdrawals and dosing/label changes. However, the clinical experience with monoclonal antibodies (MAbs) following approval has been less than perfect. In inflammatory diseases, the disease burden changes with time and high treatment failure rates have been reported. In addition, the use of concomitant steroids and immunosuppressant drugs with MAbs is common. These concomitant agents have their own safety issues and many immunosuppressant agents are not well-tolerated although they have been shown to reduce the incidence of anti-drug antibodies (ADA). This same complexity is seen in MAbs used in oncology as well, although with these agents the doses appear to be higher than needed, which results in high treatment costs and incidence of adverse events. Given the complexity of MAb pharmacokinetics, which makes providing a detailed description of dose options difficult, product labeling should include the options for alternative dose strategies and potentially include the use of therapeutic drug monitoring with dose individualization which have been shown to improve clinical response and reduce the incidence of ADA. So, while the recommended dosing for biologics seems improved over the issues noted 17 years ago, we still have some work to do.

Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children.

Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, evidence of immune abnormalities provides the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, and antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant percentage of affected patients and are burdened by significant toxicities. Recent developments of new biologics, including anti-BAFF/APRIL inhibitors and molecules targeting complement components, offered the opportunity to selectively target immune cell subsets or activation pathways, leading to more effective and safer hypothesis-driven treatments. However, studies testing new biologic agents in IgAN should also consider paediatric populations to address the unique needs of children and close the therapeutic gap between adult and paediatric care.

The Effects of Chronic Immunosuppressive Treatment on Morphological Changes in Cardiac Tissue and the Balance between Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitors in the Rat Heart.

Using different three-drug immunosuppressive treatment regimens in a rat model, we aimed to determine the effects of long-term therapy on metalloproteinase-2 and metalloproteinase-9 activity and the expression of their inhibitors, as well as to assess the morphology of the animals' cardiac tissue. Our results suggest that chronic use of immunosuppressive drugs disrupts the balance between the activity of MMPs and TIMPs. Depending on the type of drug regimen used, this leads to abnormalities in the cardiac structure, collagen fiber accumulation, or cardiomyocyte hypertrophy. The information obtained in the present study allows us to conclude that the chronic treatment of rats with the most common clinical immunosuppressive regimens may contribute to abnormalities in the myocardial structure and function. The results presented in this study may serve as a prelude to more in-depth analyses and additional research into the optimal selection of an immunosuppressive treatment with the lowest possible risk of cardiovascular complications for patients receiving organ transplants.

A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan.

Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.

Reactivation of Varicella-Zoster Virus in Patients with Lung Cancer Receiving Immune Checkpoint Inhibitors: Retrospective Nationwide Population-Based Cohort Study from South Korea.

This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICI and non-ICI groups based on the prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs and 2262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients receiving ICIs were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICI group was significantly lower than that in the non-ICIs group. The Kaplan-Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower incidence of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48-1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19-0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34-0.99). In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

A case of leprosy in an immunocompromised traveller.

We describe a case of leprosy in an immunocompromised Dutch male whose parents were born in a leprosy-endemic country. The use of immunosuppressive drugs in Mycobacterium leprae infected individuals therefore increases the risk of development of leprosy. Exposure and infection at a young age through his parents is another possible risk factor.

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

BackgroundImmune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs. ObjectiveTo investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE. MethodsWe prospectively collected data from the medical records of patients with solid tumors or lymphoma in the French REISAMIC cohort and who had been treated with ICBs between June 2014 and June 2020. Results184 ICB-treated patients experienced at least one Common Terminology Criteria for Adverse Events grade ≥ 2 irAE. 107 (58.2%) were treated with steroids alone, 20 (10.9%) with steroids plus IS, 57 (31.0%) not received steroids or IS. The median OS was significantly shorter for patients treated with steroids alone (25.2 months [95% confidence interval (CI): 22.3–32.4] than for patients treated without steroids or IS (63 months [95%CI: 40.4-NA]) and those receiving an IS with steroids (53.4 months [95%CI: 47.3-NA]) (p < 0.001). The median PFS was significantly shorter for patients treated with steroids alone (17.0 months [95%CI: 11.7–22.9]) than for patients treated without steroids or IS (33.9 months [95%CI: 18.0-NA]) and those receiving an IS with steroids (41.1 months [95%CI: 26.2-NA]) (p = 0.006). There were no significant intergroup differences in the hospital admission and infection rates. ConclusionIn a prospective cohort of ICB-treated patients, the use of IS was not associated with worse OS or PFS, contrasting with the use of steroids for the management of irAEs.

Mucormycosis: a rare forgotten but fatal disease—a case report and literature review

Mucormycosis is a perilous fungal infection that primarily affects individuals with compromised immune systems. The escalating incidence of conditions such as diabetes, cancer and the use of immunosuppressive drugs renders more individuals susceptible to contracting this disease. This report delves into the case of a 45-year-old woman from Tanzania with diabetes who succumbed to rhino-cerebral mucormycosis. Despite aggressive treatment, which often involves disfiguring surgical debridement and administration of antifungal drugs, the mortality rate remains high. Additionally, we present a comprehensive literature review of the various clinical aspects of Mucormycosis, an uncommon yet fatal condition.

Treatment with lysophosphatidic acid improves glomerulonephritis through the suppression of macrophage activation in a murine model of systemic lupus erythematosus.

Several therapeutic agents have been developed and used for the clinical treatment of systemic lupus erythematosus (SLE). In cases where SLE is accompanied by severe organ failures, such as neuropsychiatric lupus erythematosus (NPSLE) and acute onset of lupus nephritis, the use of potent immunosuppressive drugs, such as cyclophosphamide, is necessary. However, potent immunosuppressive drugs are known to increase infection risks. Thus, the development of therapeutic agents with novel mechanisms is urgently required. Previously, we reported that treatment with lysophosphatidic acid (LPA) prevents depression-like behaviours by suppressing microglial activation in MRL/lpr mice. In this study, we examined whether the treatment with LPA improves glomerulonephritis by affecting systemic immunity in MRL/lpr mice. Eighteen-week-old MRL/lpr mice were treated with a vehicle or LPA for 3 weeks. After treatment, the glomerular inflammation and damage parameters were compared between the 2 groups. Moreover, we examined the effects of LPA on immune cells by flow cytometry using isolated splenocytes. LPA treatment in MRL/lpr mice significantly reduced the daily urinary albumin content and suppressed the CD68-positive cells and Periodic acid-Schiff (PAS)-positive areas in the glomeruli. The treatment also suppressed plasma anti-dsDNA antibodies and inflammatory cytokines in MRL/lpr mice. Although LPA did not significantly affect the total number of splenocytes, the treatment significantly reduced CD11b+Ly6G-Ly6C- cells (mature macrophages), as well as CD11b+Ly6G-Ly6C-CD68+ cells (activated mature macrophages). These results suggest that LPA may improve glomerulonephritis by suppressing macrophage activation in MRL/lpr mice.

Humoral and cellular immune responses to COVID-19 mRNA vaccines in immunosuppressed liver transplant recipients

BackgroundLiver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear.MethodsWe longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses.ResultsHere, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs.ConclusionsThe third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.

The Outcome of Total Hip Arthroplasty Without Subtrochanteric Shortening Osteotomy in Severe Developmental Dysplasia of the Hip

Background: Total hip arthroplasty (THA) is a surgical technique to correct developmental dysplasia of the hip (DDH). Various THA-based methods have been developed for managing end-stage osteoarthritis in patients with DDH Crowe type III or IV. Objectives: In this study, we evaluate the Harris hip score (HHS) before and after cementless THA without subtrochanteric shortening osteotomy (STO) in patients with DDH Crowe type III or IV who were candidates for THA, as well as complications and the need for revision surgery. Methods: This retrospective cohort study was conducted on patients with DDH Crowe type III and IV, who were candidates for cementless THA using the Watson Jones technique without shortening STO. The HHS was calculated and recorded in their medical files before surgery. Patients with missing or incomplete medical files, without written informed consent, with neurovascular diseases, immunosuppressive drug use, congenital bone and articular anomalies, low back pain radiating to the lower extremities, simultaneous fractures, a history of lower extremity fractures, or joint infections were excluded. The HHS was recalculated during outpatient follow-up. Neurovascular defects and the need for reoperation were also evaluated. All data were recorded and analyzed. Results: Thirty-two patients were enrolled with a mean ± SD age of 50.34 ± 15.45 years, most of whom were women (75%). The patients were followed for 2 to 7 years. Postoperative nerve defects were observed in only 1 (3.1%) patient. Hip reoperation was performed in 1 (3.1%) patient. The mean ± SD of HHS before surgery was 50.10 ± 12.48, which increased significantly to 77.99 ± 15.60 after surgery (P &lt; 0.001). Furthermore, the HHS was evaluated before and after the intervention for each gender, showing a significant increase in both. Conclusions: Cementless THA without shortening osteotomy can improve HHS in patients with DDH Crowe III and IV, providing satisfactory outcomes. Furthermore, complications, such as neurological defects and the need for reoperation, are minimal with this method.

A narrative review of the controversy on the risk of mycobacterial infections with immune checkpoint inhibitor use: does Goldilocks have the answer?

Immune checkpoint inhibitors (ICIs) have revolutionized oncologic treatment. Whether ICIs increase susceptibility to or provide protection against mycobacterial infections remains controversial. The objective of this narrative review is to summarize the literature on the link between ICI use and mycobacterial infections-tuberculosis and non-tuberculous mycobacterial (NTM) infections-and to critically discuss evidence linking ICIs with mycobacterial infections, the possible confounders, and, if indeed the ICIs predispose to such infections, the potential mechanisms of how this may occur. We conducted a literature search on PubMed for relevant articles published from 2011 to current time [2024] utilizing specific keywords of "immune checkpoint inhibitors", "programmed cell death protein-1", "PD-1", "programmed death-ligand 1", "PD-L1", "cytotoxic T-lymphocyte-associated protein-4", or "CTLA-4" with that of "non-tuberculous mycobacterial lung disease", "tuberculosis", or "mycobacteria". The bibliographies of identified papers were perused for additional relevant articles. Ex vivo studies using human cells indicate that ICIs would be salubrious for the host against mycobacteria. Yet, many case reports associate ICI use with mycobacterial infections, mostly tuberculosis. Potential confounders include immunosuppression from the cancer, concomitant use of immunosuppressive drugs, lung injury and distortion from chemotherapeutics or radiation, and reporting bias. Mice with genetic disruption of the programmed cell death protein-1 (PD-1) gene are paradoxically more susceptible to Mycobacterium tuberculosis (M. tuberculosis). In contrast, mice administered neutralizing antibody to T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) or knocked out for TIM3 gene have greater capacity to control an M. tuberculosis infection. We posit that hosts with greater baseline immunodeficiency are more likely to derive benefit from ICIs against mycobacterial infections than those with more intact immunity, where ICIs are more likely to be detrimental. Studies are needed to test the hypothesis that ICIs may either protect or predispose to mycobacterial infections, depending on the baseline host immune status. Prospective studies are required of patients on ICIs that control for potential confounders as anecdotal case reports are insufficient to provide a causal link. Murine studies with ICIs are also required to corroborate or refute studies of mice with genetic disruption of an immune checkpoint.

Clinical factors associated with viral shedding time of SARS-CoV-2 Omicron variant in Japan.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 exhibits increased infectivity compared with all prior variants, and the timing of quarantine release should be carefully considered. However, to date, only two Chinese studies have analyzed the association between the viral shedding time (VST) and risk factors among patients infected with the Omicron variant. These studies included only limited numbers of severe cases and no analysis of underlying diseases and immunosuppressive drug use. Therefore, the current study aimed to analyze them in Japan. This retrospective observational study was conducted at the University of Occupational and Environmental Health, Japan, from January 2022 to October 2022 and included 87 hospitalized patients and 305 healthcare workers (HCWs) with coronavirus 2019 (COVID-19). In comparison with HCWs, hospitalized patients were significantly older and had a higher proportion of severe COVID-19 cases and significantly longer VST. A simple regression analysis showed that severe, current, or ex-smoking status, cardiovascular diseases, chronic kidney disease, and use of corticosteroids for underlying diseases were significantly correlated with a longer VST. Moreover, multiple linear regression analysis revealed that cardiovascular diseases, chronic kidney disease, and corticosteroid use were significantly associated with a longer VST. Therefore, COVID-19 patients with these underlying diseases may require a longer isolation period and the timing of quarantine release should be carefully considered.

EFFICACY, SAFETY AND IMMUNOGENICITY OF SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) MONOTHERAPY VERSUS COMBINATION THERAPY WITH IMMUNOSUPPRESSANTS – POST HOC ANALYSIS OF LIBERTY-CD AND LIBERTY-UC STUDY

Abstract INTRODUCTION CT-P13 subcutaneous (SC) infliximab formulation demonstrated superiority over placebo in maintenance therapy in Crohn's disease (CD) and Ulcerative Colitis (UC) patients in two parallel 54 weeks studies (LIBERTY-CD and LIBERTY-UC). We performed a post-hoc subgroup analysis comparing patients treated with CT-P13 SC with and without combination immunosuppressants (IS) at baseline in CD and UC. AIMS &amp; METHODS Patients with moderately to severely active CD and UC who responded at W10 to CT-P13 intravenous infliximab 5mg/kg (Weeks 0, 2 and 6) were randomized (2:1) to receive CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks until W54 as maintenance therapy. IS (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) were allowed if patients maintained stable doses at least 8 weeks prior to W0, and stable doses were maintained up to W54. RESULTS 231 CD and 294 UC patients were randomized to receive CT-P13 SC maintenance therapy. Among them, 71 (30.7%) and 65 (22.1%) patients received CT-P13 SC with IS in CD and UC, respectively (In CD; 63, 4 and 4 patients of AZA, 6-MP, MTX, respectively, In UC; 63, 2 and 0 patients of AZA, 6-MP, MTX, respectively). There were no meaningful differences in efficacy outcomes at Week 54 by CT-P13 concentration tertiles at Week 54 between monotherapy and combination therapy groups in both studies (Table 1). In combined analysis of CD and UC patients, no statistically significant differences were seen in safety profile between monotherapy and combination therapy groups in the maintenance period except for infection rate (Table 2). In combined analysis of CD and UC patients, rate of anti-drug antibody [ADA] positive conversion up to W54 was statistically lower in combination therapy group (70.2% monotherapy vs 47.8% combination therapy [p&amp;lt;0.0001]). CONCLUSION No meaningful differences in efficacy outcomes at W54 were observed between monotherapy and combination therapy of CT-P13 SC in CD and UC patients. Concomitant IS use was associated with less ADA formation, whereas more infections are seen for combination therapy during maintenance period in CD and UC patients. The overall safety profile during maintenance period was otherwise comparable between monotherapy and combination therapy in CD and UC patients. This post-hoc analysis suggests limited benefit of concomitant IS with CT-P13 SC but a higher infection risk. Notably, patients were not randomized according to IS use nor were the studies ‘powered’ to demonstrate differences. Proportion of patients achieving efficacy outcomes at W54 by tertile of Serum concentrations of Infliximab (ng/mL) at W54 (Pharmacokinetic population) Safety results in maintenance period (Safety population)