Calcineurin inhibitors (CNIs) have been a cornerstone in solid organ transplantation for many years; however, their prolonged use is linked to significant adverse effects, most notably nephrotoxicity. Belatacept, a modified version of cytotoxic T lymphocyte antigen-4 immunoglobulin with increased binding affinity for its ligand, has emerged as a viable alternative to traditional CNIs due to its lower toxicity profile. Despite these benefits, belatacept is associated with a higher rate of acute rejection, which presents a challenge for long-term graft survival. This review reevaluates the limitations of belatacept in achieving long-term acceptance of transplants and highlights the importance of regulatory T (Treg) cells in maintaining immune tolerance and preventing graft rejection. Additionally, it discusses the potential benefits of combining therapies that boost Treg cells with belatacept to increase the effectiveness of immunosuppression and improve graft outcomes.

Calcineurin inhibitors (CNIs) have been a cornerstone in solid organ transplantation for many years; however, their prolonged use is linked to significant adverse effects, most notably nephrotoxicity. Belatacept, a modified version of cytotoxic T lymphocyte antigen-4 immunoglobulin with increased binding affinity for its ligand, has emerged as a viable alternative to traditional CNIs due to its lower toxicity profile. Despite these benefits, belatacept is associated with a higher rate of acute rejection, which presents a challenge for long-term graft survival. This review reevaluates the limitations of belatacept in achieving long-term acceptance of transplants and highlights the importance of regulatory T (Treg) cells in maintaining immune tolerance and preventing graft rejection. Additionally, it discusses the potential benefits of combining therapies that boost Treg cells with belatacept to increase the effectiveness of immunosuppression and improve graft outcomes.

Calcineurin inhibitors (CNIs) have been a cornerstone in solid organ transplantation for many years; however, their prolonged use is linked to significant adverse effects, most notably nephrotoxicity. Belatacept, a modified version of cytotoxic T lymphocyte antigen-4 immunoglobulin with increased binding affinity for its ligand, has emerged as a viable alternative to traditional CNIs due to its lower toxicity profile. Despite these benefits, belatacept is associated with a higher rate of acute rejection, which presents a challenge for long-term graft survival. This review reevaluates the limitations of belatacept in achieving long-term acceptance of transplants and highlights the importance of regulatory T (Treg) cells in maintaining immune tolerance and preventing graft rejection. Additionally, it discusses the potential benefits of combining therapies that boost Treg cells with belatacept to increase the effectiveness of immunosuppression and improve graft outcomes.

Calcineurin inhibitors (CNIs) have been a cornerstone in solid organ transplantation for many years; however, their prolonged use is linked to significant adverse effects, most notably nephrotoxicity. Belatacept, a modified version of cytotoxic T lymphocyte antigen-4 immunoglobulin with increased binding affinity for its ligand, has emerged as a viable alternative to traditional CNIs due to its lower toxicity profile. Despite these benefits, belatacept is associated with a higher rate of acute rejection, which presents a challenge for long-term graft survival. This review reevaluates the limitations of belatacept in achieving long-term acceptance of transplants and highlights the importance of regulatory T (Treg) cells in maintaining immune tolerance and preventing graft rejection. Additionally, it discusses the potential benefits of combining therapies that boost Treg cells with belatacept to increase the effectiveness of immunosuppression and improve graft outcomes.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Purpose: To assess and compare the diagnostic efficacies of magnetic resonance arthrography (MRA) and computed tomography arthrography (CTA) in identifying labral and chondral lesions within the hip joints. To analyze the diagnostic confidence levels of radiologists when interpreting images obtained from MRA and CTA. Materials and Methods: Labral and chondral lesions in 100 hips of 95 patients on 3.0 tesla MRA, CTA (128- and 160-slice multi-detector computed tomography), and arthroscopic findings were retrospectively reviewed by three radiologists. We analyzed the sensitivity, specificity, accuracy, positive predictive value, and area under the curve (AUC) using receiver operating characteristic curves. The diagnostic confidence of the radiologists was also assessed during image interpretation. Results: Both MRA and CTA showed good diagnostic performances in the assessment of labral and chondral lesions. MRA showed higher sensitivity and accuracy, with a higher AUC for labral lesions than CTA (MRA/CTA: 97.3%/84.8% [p < 0.001], 93.8%/89.8%, and 0.945/0.896 [p = 0.003], respectively). CTA outperformed MRA in diagnostic performance in terms of sensitivity, specificity, accuracy, and AUC in acetabular cartilage lesions (MRA/ CTA: 75.8%/93.9% [p = 0.020], 67.6%/88.2% [p < 0.001], 73.0%/92.0% and 0.717/0.911 [p < 0.001], respectively) and sensitivity, accuracy and AUC in femoral cartilage lesions (60.5%/78.9% [p = 0.020], 80.0%/87.0%, and 0.762/0.854 [p = 0.018], respectively). The diagnostic confidence was higher with MRA for labral lesions (p = 0.002) and with CTA for chondral lesions (p < 0.001). Conclusion Both MRA and CTA showed strong diagnostic abilities for hip joint lesions, with MRA being better for labral lesions and CTA for chondral lesions. Radiologists showed greater confidence in diagnosing labral lesions using MRA and chondral lesions using CTA.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background: Gastrointestinal (GI) drugs are often co-prescribed with other medications to prevent GI complications. This study aimed to evaluate the prescribing pattern of potentially unnecessary GI drugs in patients with acute cystitis who were prescribed oral antibiotics and investigate the influencing factors affecting this. Methods: We identified female patients ≥20 years with acute cystitis who visited the outpatient clinic and were prescribed oral antibiotics between July and December by analyzing Health Insurance Review and Assessment Service (HIRA)-National Patients Sample (NPS)-2019 data. Patients with no prior history of GI disorders within 180 days prior to acute cystitis, excluding or including the date of diagnosis of acute cystitis, were selected (Group A and B). Multiple logistic regression analysis was performed to estimate the factors affecting the prescription of potentially unnecessary GI drugs. Results: A total of 1,544 in Group A and 552 patients in Group B were included for the final analysis. Potentially unnecessary GI drugs were presc ribed in 1,176 patients in Group A (76.2%) and 231 patients in Group B (41.8%). Third generation cephalosporines and sulfonamides showed the lower odds ratio for prescribing GI drugs than penicillins. Prescribers from Urology clinics showed more than twice odds ratio for the prescription of GI drugs compared to prescribers from internal medicine clinics. Conclusion The results of this study showed that potentially unnecessary GI drug prescriptions for patients with acute cystitis were high in South Korea. The positive risk factors affecting the prescription of unnecessary GIs were not patient-related factor but healthcare facility and prescriber-related factors.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Background: Acute rhinosinusitis (ARS) is a common condition encountered in ambulatory practice and is one of the most common reasons for antibiotic prescriptions. This study aimed to evaluate the potentially inappropriate antibiotic prescribing for ARS in South Korea and identify influencing factors. Methods: We analyzed Health Insurance Review and Assessment Service-National Patient Samples data. We selected outpatients aged 20 to 64 with ARS, prescribed antibiotics between February and November 2020. Potentially inappropriate antibiotic prescribing was categorized as: 1) inappropriate antibiotic selection and 2) inappropriate antibiotic dosage or duration. Multiple logistic regression was conducted to estimate the impact of various factors on inappropriate antibiotic prescribing. Results: Of 1,210 patients, 80.83% received potentially inappropriate ARS antibiotic prescriptions.Inappropriate antibiotic selection accounted for 43.55%, and inappropriate antibiotic dosage and duration contributed to 37.28%.Otolaryngologists had higher odds ratio (OR) of potentially inappropriate antibiotic prescribing compared to internal medicine practitioners, while dentists had lower OR. Patients aged 20 to 29 years had a higher OR than other age groups, and those who visited primary care clinics had a higher OR than those who visited hospitals. Conclusion Potentially inappropriate antibiotic prescribing for ARS is prevalent in South Korea. This study identified physician specialty, patient age group, and the level of healthcare facility as factors influencing potentially inappropriate antibiotic prescriptions. Addressing this issue through targeted interventions, such as improved guidelines adherence and patient education, is imperative to mitigate the risks associated with antibiotic misuse and antibiotic resistance.