SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells increased, peaking at approximately 120 DPSO. Development of TSCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.

ARB/ACEI use and severe COVID-19: a nationwide case-control study

BackgroundAngiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. MethodsA retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for [≥]30 days during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. FindingsOf 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8{middle dot}6%, 22{middle dot}2%, and 16{middle dot}7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0{middle dot}43, 95% confidence interval [CI] 0{middle dot}28 - 0{middle dot}65) and broad control group (aOR 0{middle dot}49, 95% CI 0{middle dot}33 - 0{middle dot}71). The association was smaller for newly diagnosed hypertension patients (aOR 0{middle dot}11, 95% CI 0{middle dot}03 - 0{middle dot}42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. InterpretationARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse. FundingNone Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAnimal studies reported that ACE2 attenuates lung injury and provides a protective effect against severe pneumonia. Additionally, retrospective studies found that ARBs/ACEIs may have beneficial effects on ARDS patient survival. Previous observational studies have reported no potential harmful association of either ARBs or ACEIs with COVID-19 outcomes. Added value of this studyBy analyzing nationwide claims data in South Korea, we found that previous use of ARB/ACEI was associated with improved outcomes in COVID-19 compared with either nonuse or use of a different class of antihypertensive drugs. The risk of severe infection or death was consistently about 55% lower in those treated with ARB/ACEIs than those who were not exposed to ARB/ACEIs. The protective effect of ARB/ACEI was remained significantly among the male subgroup and patients with diabetes. This association was also observed among COVID-19 patients with newly diagnosed hypertension. Implications of all the available evidenceThese results provide supporting evidence for the continued use of ARBs/ACEIs among patients with COVID-19. Moreover, for newly diagnosed hypertension patients, initiation of ARB/ACEI use may not adversely affect COVID-19 prognosis. Given the poor prognosis of COVID-19 patients with hypertension and lack of curable strategy, these findings may have considerable clinical implications in prevention of poor outcome in patients with hypertension.

Antimicrobial Therapy and Antimicrobial Stewardship in Sepsis / 감염과화학요법

Since sepsis was first defined, sepsis management has remained challenging. To improve mortality rates for sepsis and septic shock, an accurate diagnosis and prompt administration of appropriate antibiotics are essential. The goals of antimicrobial stewardship are to achieve optimal clinical outcomes and to ensure cost-effectiveness and minimal unintended consequences, such as toxic effects and development of resistant pathogens. A combination of inadequate diagnostic criteria for sepsis and time pressure to provide broad-spectrum antimicrobial therapy remains an obstacle for antimicrobial stewardship. Efforts such as selection of appropriate empirical antibiotics and de-escalation or determination of whether or not to stop antibiotics may help to improve a patient's clinical prognosis as well as the successful implementation of antimicrobial stewardship.

Trend of Olfactory and Gustatory Dysfunction in COVID-19 Patients in a Quarantine Facility

Background@#Olfactory and gustatory dysfunction has been reported as characteristic symptoms of coronavirus disease 2019 (COVID-19). This study evaluated olfactory and gustatory dysfunction in mild COVID-19 patients using validated assessment methods. @*Methods@#A prospective surveillance study was conducted for mild COVID-19 patients who were isolated at the Gyeonggi International Living and Treatment Support Center (LTSC), Korea.Olfactory function was assessed using the Korean version of the Questionnaire of Olfactory Disorders (QOD) and Cross-Cultural Smell Identification Test (CC-SIT). Gustatory function was assessed using an 11-point Likert scale and 6-n-propylthiouracil, phenylthiocarbamide, and control strips. All patients underwent nasal and oral cavity endoscopic examination. @*Results@#Of the 62 patients at the LTSC, 15 patients (24.2%) complained of olfactory or gustatory dysfunction on admission. Four of 10 patients who underwent functional evaluation did not have general symptoms and 2 were asymptomatic. The mean short version of QOD-negative statements and QOD-visual analogue scale scores were 13 ± 6 and 4.7 ± 3.6, respectively. The mean CC-SIT score was 8 ± 2. No patients showed anatomical abnormalities associated with olfactory dysfunction on endoscopic examination. The mean Likert scale score for function was 8 ± 2, and there were no abnormal lesions in the oral cavity of any patient. @*Conclusions@#The prevalence of olfactory and gustatory dysfunction was 24.2% in mild COVID-19 patients. All patients had hyposmia due to sensorineural olfactory dysfunction, which was confirmed using validated olfactory and gustatory evaluation methods and endoscopic examination. Olfactory and gustatory dysfunction may be characteristic indicators of mild COVID-19.

Temporary Haptic Externalization and Four-point Fixation of Intraocular Lens in Scleral Fixation to Enhance Stability

PURPOSE: To report the results of a new technique for intraocular lens scleral fixation of temporary haptic externalization and four-point fixation for enhanced stability. METHODS: Two 10–0 polypropylene strands were fixed at two points 2 mm apart on each haptic of a conventional three-piece intraocular lens, using our previously reported method of temporary haptic externalization after injector implantation. Postoperative refractive outcome and stability were evaluated. RESULTS: Although the intraocular lens was fixed at a total of four points, no intraoperative difficulties were observed during the process. Patients showed successful fixation of the intraocular lens postoperatively. The fixed intraocular lens showed good centering and minimal tilting. When compared to the two-point fixation technique, postoperative astigmatism was significantly smaller in the four-point fixation group (1.80 ± 0.84 vs. 1.00 ± 0.0.50, p = 0.033). Lens-induced astigmatism calculated from subtraction of corneal astigmatism from total astigmatism was also significantly smaller in the four-point fixation group (2.23 ± 0.98 vs.1.17 ± 0.0.70, p = 0.043). No postoperative complications were identified during a mean follow-up period of 14.8 months (range, 10 to 19 months). CONCLUSIONS: By fixing the intraocular lens at two points on each side of the haptics, this method minimizes the tilting of the intraocular lens and thus decreases postoperative lens-induced astigmatism. Also, the possibility of intraocular lens dislocation in the long term might be decreased by this two-point fixation technique.

Controversies Regarding the New Definition of Sepsis / 대한내과학회지

The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) task force assessed the latest pathophysiological parameters associated with sepsis and septic shock and defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. This SEPSIS-3 definition may be applied using relevant clinical and biological criteria including changes in the Sequential Organ Failure Assessment score and serum lactate levels. The new definition does not include criteria for systemic inflammatory response syndrome or the concept of 'severe sepsis.' The SEPSIS-3 definition aims to devise more precise descriptions of sepsis and to improve clinical care. However, there are important questions relating to the clinical application of the new definition. We review the main characteristics and limitations of previous definitions and discuss some of the potential controversies raised by the new framework.

Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.

The Change of Multifocal Visual Evoked Potential in Unilateral Anisometropic Amblyopia before and after Occlusion Treatment

PURPOSE: To evaluate the change in multifocal visual evoked potential (mfVEP) in unilateral anisometropic amblyopia before and after occlusion treatment. METHODS: The mfVEP was performed using RETIscan(R) (Roland,Brandenburg, Germany) for patients with unilateral anisometropic amblyopia before and after occlusion treatment. Amplitude and latency values of mfVEP were analyzed according to the field divided by 6 rings or 4 sectors. RESULTS: The each amplitude of values of all 6 rings were not significantly different before treatment (p = 0.077) in amblyopic eyes. However, the value of ring 1 (p = 0.00) was significantly higher than the value of other rings after treatment. In fellow eyes, the values of ring 1 was consistently significantly higher than the value of other rings before (p = 0.014) and after (p = 0.049) occlusion treatment. Additionally, the amplitudes of ring 1 (p = 0.005) and ring 3 (p = 0.007) were significantly increased in amblyopic eyes after occlusion treatment. In fellow eyes, the values of all rings did not change significantly. The analysis of amplitudes with 4 sectors revealed no significant result. The analysis of latencies with 6 rings and 4 sectors revealed no significant result. CONCLUSIONS: The change in amplitude on the central field (ring 1) in amblyopic eyes can be a useful objective monitoring method observing the improvement progress in visual acuity.

The Change of Multifocal Visual Evoked Potential in Unilateral Anisometropic Amblyopia before and after Occlusion Treatment

PURPOSE: To evaluate the change in multifocal visual evoked potential (mfVEP) in unilateral anisometropic amblyopia before and after occlusion treatment. METHODS: The mfVEP was performed using RETIscan(R) (Roland,Brandenburg, Germany) for patients with unilateral anisometropic amblyopia before and after occlusion treatment. Amplitude and latency values of mfVEP were analyzed according to the field divided by 6 rings or 4 sectors. RESULTS: The each amplitude of values of all 6 rings were not significantly different before treatment (p = 0.077) in amblyopic eyes. However, the value of ring 1 (p = 0.00) was significantly higher than the value of other rings after treatment. In fellow eyes, the values of ring 1 was consistently significantly higher than the value of other rings before (p = 0.014) and after (p = 0.049) occlusion treatment. Additionally, the amplitudes of ring 1 (p = 0.005) and ring 3 (p = 0.007) were significantly increased in amblyopic eyes after occlusion treatment. In fellow eyes, the values of all rings did not change significantly. The analysis of amplitudes with 4 sectors revealed no significant result. The analysis of latencies with 6 rings and 4 sectors revealed no significant result. CONCLUSIONS: The change in amplitude on the central field (ring 1) in amblyopic eyes can be a useful objective monitoring method observing the improvement progress in visual acuity.

Neovascular Glaucoma with Ocular Ischemia in Superior Vena Cava Syndrome

PURPOSE: To report a case of neovascular glaucoma (NVG) with ocular ischemia in superior vena cava syndrome (SVCS). CASE SUMMARY: A 57-year old male who had been treated for small cell lung cancer (SCLC) visited our hospital because of SVCS-like symptoms and decreased visual acuity in the right eye. On the initial examination, best corrected visual acuity was 0.5, intraocular pressure (IOP) was 38 mm Hg and relative afferent papillary defect was positive in the right eye. Slit lamp examination showed mild dilatation and tortuosity of the episcleral vessels and ruobeosis iridis. Gonioscopic examination showed neovascularization of the opened angle. Fluorescein angiography showed delayed choroidal filling and nevascularization of the disc. The patient was diagnosed with NVG with ocular ischemia in SVCS and was treated with chemotherapy and steroid therapy. In addition, intravitreal bevacizumab and IOP lowering eyedrops were administered to the right eye. During follow-up, neovascularizations disappeared and IOP was well controlled. CONCLUSIONS: NVG with ocular ischemia in SVCS should be considered as a possible cause of high IOP in SCLC patients.

Magnetic resonance imaging evaluation of Yukatan minipig brains for neurotherapy applications / 한국실험동물학회지

Magnetic resonance imaging (MRI) of six Yukatan minipig brains was performed. The animals were placed in stereotaxic conditions currently used in experiments. To allow for correctpositioning of the animal in the MRI instrument, landmarks were previously traced on the snout of the pig. To avoid movements, animal were anesthetized. The animals were placed in a prone position in a Siemens Magnetom Avanto 1.5 System with a head coil. Axial T2-weighted and sagittal T1-weighted MRI images were obtained from each pig. Afterwards, the brains of the pigs were fixed and cut into axial sections. Histologic and MR images were compared. The usefulness of this technique is discussed.