Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding

BackgroundInformation on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated.MethodsMild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days.ResultsA total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively.ConclusionsNirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.     

Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study

PurposeThe estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR_6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR_6m <60 mL/min/1.73 m² (eGFR_6m <60) and identify the risk factors that can predict the occurrence of eGFR_6m <60 in living kidney donors.Materials and MethodsLiving kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR_6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR_6m <60 occurrence were determined using the Youden index.ResultsThe eGFR_6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR_6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR_6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863–0.908] vs. 0.862 (95% CI, 0.838–0.887), p<0.001}.ConclusionThe incidence of eGFR_6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR_6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR_6m <60.     

Predictive accuracy of a health risk appraisal program using mortality risk age in 116,927 Korean men

Health risk appraisal (HRA) is a tool for determining health risk factors and motivating individuals to maintain a healthy lifestyle. We performed this study to describe the HRA algorithm and evaluate the accuracy of an HRA program for 10-yr mortality prediction in Korean men. We used data derived from periodic health examinations of 116,927 male public officials and school personnel aged 20 or older. Risk age and the difference between risk age and calendar age were calculated. We obtained the hazard ratio (HR) of 10-yr mortality according to the calculated age difference. Of the 116,927 subjects, 1,900 (1.6%) died during the 10 yr after the 1992 medical examinations. The HR of 10-yr mortality increased significantly with age difference. Compared with the HR in the reference group (age difference below 2 yr), the HR in the group with a 2- to 6-yr age difference was 1.20 (95% confidence interval [CI]: 1.05 to 1.38) and HR in the group with more than 7-yr age difference was 1.35 (95% CI: 1.14 to 1.75). Risk age is a relatively good predictor of 10-yr mortality in Korean men and may be useful in identifying high-risk middle-aged men for health interventions.     

An Optimized CFSE‐based T‐cell Suppression Assay to Evaluate the Suppressive Capacity of Regulatory T‐Cells Induced by Human Tolerogenic Dendritic Cells

In autoimmune diseases or transplant graft rejection, a therapy that will prevent or reduce the present immune activation is highly desired. Ex vivo generated tolerogenic dendritic cells (DC) are considered to have a strong potential as cellular therapy for these diseases. One of the mechanisms of immune suppression mediated by tolerogenic DC is the induction of regulatory T‐cells (Treg). Consequently, the efficacy of such DC to induce Treg will reflect their tolerogenic capacity. Because no specific markers have been described for human induced (i)Treg yet, the Treg can only be appreciated by functionality. Therefore, we have optimized an in vitro suppression assay to screen for human DC‐induced‐Treg activity. IL‐10‐generated tolerogenic DC were used to induce Treg that were previously shown to effectively suppress the proliferation of responder T‐cells stimulated with allogeneic mature DC (mDC). Our results show that the suppressive capacity of IL‐10 DC‐induced Treg measured in the suppression assay increases with the iTreg dose and decreases with higher numbers of antigen‐presenting cells (APC) as T‐cell stimulation. Lowering the ratio between responder T‐cells and stimulator mDC present in the coculture clearly improved the read‐out of the suppression assay. Furthermore, mDC‐primed T‐cells in the suppression assay were shown to be an essential control condition. In conclusion, we recommend titrations of both APC and iTreg in the suppression assay and to include a negative control condition with T‐cells primed by mDC, to distinguish specific and functional suppression by iTreg from possible generalized suppressive activity.     

Alleviation of capsular formations on silicone implants in rats using biomembrane-mimicking coatings

Despite their popular use in breast augmentation and reconstruction surgeries, the limited biocompatibility of silicone implants can induce severe side effects, including capsular contracture – an excessive foreign body reaction that forms a tight and hard fibrous capsule around the implant. This study examines the effects of using biomembrane-mimicking surface coatings to prevent capsular formations on silicone implants. The covalently attached biomembrane-mimicking polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), prevented nonspecific protein adsorption and fibroblast adhesion on the silicone surface. More importantly, in vivo capsule formations around PMPC-grafted silicone implants in rats were significantly thinner and exhibited lower collagen densities and more regular collagen alignments than bare silicone implants. The observed decrease in α-smooth muscle actin also supported the alleviation of capsular formations by the biomembrane-mimicking coating. Decreases in inflammation-related cells, myeloperoxidase and transforming growth factor-β resulted in reduced inflammation in the capsular tissue. The biomembrane-mimicking coatings used on these silicone implants demonstrate great potential for preventing capsular contracture and developing biocompatible materials for various biomedical applications.     

Evidence-Based,Pharmacological Treatment Guideline for Depression in Korea,Revised Edition

This paper aims to introduce, summarize, and emphasize the importance of the ''Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition''. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.