Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

BACKGROUNDS: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. METHODS: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. RESULTS: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. CONCLUSION: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

Case Report: Cryptococcal Meningitis in a Previously Immunocompetent Patient with Coronavirus Disease 2019.

Cryptococcus neoformans infections occur most frequently in immunocompromised patients. Here, we report a case of cryptococcal meningitis in a previously immunocompetent 78-year-old female patient after treatment of COVID-19. Underlying diseases included hypertension, hyperlipidemia, and diabetes. The patient was critically ill and was treated with remdesivir, baricitinib, and dexamethasone. During hospitalization, her mental state changed, and C. neoformans was detected in the cerebrospinal fluid. She died despite receiving antifungal treatment. Treatment of COVID-19 may be a predisposing factor for C. neoformans infection. There is a need for concern and countermeasures for opportunistic fungal infections that may accompany COVID-19.

Increased incidence of teicoplanin-non-susceptible Staphylococcus epidermidis strains: a 6-year retrospective study.

Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis.

Loss of thyroid gland circadian PER2 rhythmicity in aged mice and its potential association with thyroid cancer development.

Molecular clocks operate in peripheral tissues, including endocrine glands, and play important regulatory roles in this context. However, potential age-related changes in the expression rhythmicity of clock genes and the effects of these changes on the thyroid gland remain unknown. In the present study, we evaluated the expression rhythmicity of peripheral thyroid clock genes in aged mice using RNA-seq transcriptomic analysis in young (3.5-month) versus aged (20-month) mice. In addition, we determined the cellular effects of silencing of PER2, a major clock gene regulator, in human thyroid cell lines. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) in the thyroid glands of aged mice were involved in mitogen-activated protein kinase (MAPK) signaling, chemokine signaling, circadian entrainment, PI3K/AKT signaling, and Apelin signaling. The expression of circadian clock genes Arntl/Bmal1 was significantly downregulated in thyroid glands of aged mice, whereas the expression of genes involved in regulation of cell proliferation, migration, and tumorigenesis was upregulated. Peripheral thyroid clock genes, particularly Per mRNA and PER2 protein, were downregulated in the thyroid glands of aged mice, and circadian oscillation of these genes was declined. Knockdown of the circadian clock gene PER2 in human thyroid follicular cells induced AP-1 activity via JNK MAPK signaling activation, which increased cell proliferation. Furthermore, the aging-related loss of PER2 circadian oscillation activated the AP-1 transcription factor via the JNK MAPK pathway, which could contribute to thyroid hyperplasia, a common age-related condition.

Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections.

PURPOSE: This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). MATERIALS AND METHODS: We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. RESULTS: A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. CONCLUSION: Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

Ruptured pseudoaneurysm of the internal maxillary artery in zygomaticomaxillary fracture: a case report.

Post-traumatic pseudoaneurysms of internal maxillary artery are rare, but may be life-threatening. When arterial damage leads to pseudoaneurysm formation, delayed intractable epistaxis can occur. We report our experience with the diagnosis and management of a ruptured internal maxillary arterial pseudoaneurysm that was discovered preoperatively in a patient with a zygomaticomaxillary complex (ZMC) fracture. He presented to the emergency room with epistaxis, which ceased shortly, and sinus hemorrhage was observed with a fracture of the posterior maxillary wall. The patient was scheduled for open reduction and internal fixation (ORIF) of the ZMC fracture. However, immediately before surgery, uncontrolled epistaxis of unknown origin was observed. Angiography indicated a pseudoaneurysm of the posterior superior alveolar artery. Selective endovascular embolization was performed, and hemostasis was achieved. After radiologic intervention, ORIF was successfully implemented without complications. Our case shows that in patients with a posterior maxillary wall fracture, there is a risk of uncontrolled bleeding in the perioperative period that could be caused by pseudoaneurysms, which should be considered even in the absence of typical symptoms.

Concordance rate of radiologists and a commercialized deep-learning solution for chest X-ray: Real-world experience with a multicenter health screening cohort.

PURPOSE: Lunit INSIGHT CXR (Lunit) is a commercially available deep-learning algorithm-based decision support system for chest radiography (CXR). This retrospective study aimed to evaluate the concordance rate of radiologists and Lunit for thoracic abnormalities in a multicenter health screening cohort. METHODS AND MATERIALS: We retrospectively evaluated the radiology reports and Lunit results for CXR at several health screening centers in August 2020. Lunit was adopted as a clinical decision support system (CDSS) in routine clinical practice. Subsequently, radiologists completed their reports after reviewing the Lunit results. The DLA result was provided as a color map with an abnormality score (%) for thoracic lesions when the score was greater than the predefined cutoff value of 15%. Concordance was achieved when (a) the radiology reports were consistent with the DLA results ("accept"), (b) the radiology reports were partially consistent with the DLA results ("edit") or had additional lesions compared with the DLA results ("add"). There was discordance when the DLA results were rejected in the radiology report. In addition, we compared the reading times before and after Lunit was introduced. Finally, we evaluated systemic usability scale questionnaire for radiologists and physicians who had experienced Lunit. RESULTS: Among 3,113 participants (1,157 men; mean age, 49 years), thoracic abnormalities were found in 343 (11.0%) based on the CXR radiology reports and 621 (20.1%) based on the Lunit results. The concordance rate was 86.8% (accept: 85.3%, edit: 0.9%, and add: 0.6%), and the discordance rate was 13.2%. Except for 479 cases (7.5%) for whom reading time data were unavailable (n = 5) or unreliable (n = 474), the median reading time increased after the clinical integration of Lunit (median, 19s vs. 14s, P < 0.001). CONCLUSION: The real-world multicenter health screening cohort showed a high concordance of the chest X-ray report and the Lunit result under the clinical integration of the deep-learning solution. The reading time slight increased with the Lunit assistance.

Pneumonia-targeted lopinavir/ritonavir-based treatment for patients with COVID-19: an early-period retrospective single center observational study.

BACKGROUND: Robust evidenced treatment strategy for Coronavirus disease 2019 (COVID-19) has not been established yet. Early, targeted, comprehensive management approach can be essential. METHODS: A lopinavir/ritonavir (LPV/r)-based antiviral treatment was administered to the patients with computed tomography (CT)-documented pneumonia. Medical records of patients with COVID-19, previously discharged or hospitalized for ≥ 21 days at the Seoul Medical Center from January 29 to April 15, 2020 were reviewed to analyze clinical and virological outcomes. Patients were divided into two groups (PCR-Negative conversion group vs. Non-negative conversion group and requiring oxygen group vs. Non-requiring oxygen group). RESULTS: In total, 136 patients with a mean age of 41.8 ± 18.2 years were included with median 3-day delay of hospitalization after illness. Thirteen (9.56%) were initially asymptomatic, and 5 (3.67%) were persistently asymptomatic. Eighty-five (62.5%) had CT-documented pneumonia, 94% of whom received LPV/r treatments. A total of 53 patients (38.97%) had negative polymerase chain reaction (PCR) results within 28 days. Eight (9.4%) out of 85 pneumonic patients received oxygen supplementation. Patients with initial lower respiratory symptoms showed significant delay in PCR negative conversion (> 28 days) (odds ratio [OR] 0.166; 95% confidence interval [CI] 0.067-0.477; P < 0.001). However, antiviral treatment for pneumonic patients was significantly related with early conversion within 28 days (OR 3.049; 95% CI 1.128-8.243; P = 0.028). Increasing age increased the likelihood of oxygen supplementation requirement in the pneumonic patient group (OR 1.108; 95% CI 1.021-1.202; P = 0.014). CONCLUSIONS: Early, pneumonia targeted LPV/r-based antiviral therapy resulted in a significantly higher probability of negative conversion of PCR within 28 days compared to symptomatic treatment.

Factors Associated with Worsening Oxygenation in Patients with Non-severe COVID-19 Pneumonia.

BACKGROUND: This study aimed to determine the parameters for worsening oxygenation in non-severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This retrospective cohort study included cases of confirmed COVID-19 pneumonia in a public hospital in South Korea. The worsening oxygenation group was defined as that with SpO2 ≤94% or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the non-worsening oxygenation group that did not experience any respiratory event. Parameters were compared, and the extent of viral pneumonia from an initial chest computed tomography (CT) was calculated using artificial intelligence (AI) and measured visually by a radiologist. RESULTS: We included 136 patients, with 32 (23.5%) patients in the worsening oxygenation group; of whom, two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups; however, univariate logistic regression analysis revealed that a variety of parameters on admission were associated with an increased risk of a desaturation event. A subset of patients was studied to eliminate potential bias, that ferritin ≥280 µg/L (p=0.029), lactate dehydrogenase ≥240 U/L (p=0.029), pneumonia volume (p=0.021), and extent (p=0.030) by AI, and visual severity scores (p=0.042) were the predictive parameters for worsening oxygenation in a sex-, age-, and comorbid illness-matched case-control study using propensity score (n=52). CONCLUSION: Our study suggests that initial CT evaluated by AI or visual severity scoring as well as serum markers of inflammation on admission are significantly associated with worsening oxygenation in this COVID-19 pneumonia cohort.

Chest CT Findings of COVID-19 Patients with Mild Clinical Symptoms at a Single Hospital in Korea.

Purpose: To retrospectively evaluate the chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) in patients with mild clinical symptoms at a single hospital in South Korea. Materials and Methods: CT scans of 87 COVID-19 patients [43 men and 44 women; median age: 41 years (interquartile range: 26.1-51.0 years)] with mild clinical symptoms (fever < 38℃ and no dyspnea) were evaluated. Results: CT findings were normal in 39 (44.8%) and abnormal in 48 (55.2%) patients. Among the 48 patients with lung opacities, 17 (35.4%) had unilateral disease and 31 (64.6%) had bilateral disease. One (2.1%) patient showed subpleural distribution, 9 (18.8%) showed peribronchovascular distribution, and 38 (79.2%) showed subpleural and peribronchovascular distributions. Twenty-two (45.8%) patients had pure ground-glass opacities (GGOs) with no consolidation, 17 (35.4%) had mixed opacities dominated by GGOs, and 9 (18.8%) had mixed opacities dominated by consolidation. No patients demonstrated consolidation without GGOs. Conclusion: The most common CT finding of COVID-19 in patients with mild clinical symptoms was bilateral multiple GGO-dominant lesions with subpleural and peribronchovascular distribution and lower lung predilection. The initial chest CT of almost half of COVID-19 patients with mild clinical symptoms showed no lung parenchymal lesions. Compared to relatively severe cases, mild cases were more likely to manifest as unilateral disease with pure GGOs or GGO-dominant mixed opacities and less likely to show air bronchogram.

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Clinical Course and Outcomes of 3,060 Patients with Coronavirus Disease 2019 in Korea, January-May 2020.

BACKGROUND: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. METHODS: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. RESULTS: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3-4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5-7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50-59, 60-69, 70-79, and ≥ 80 years of age, respectively. CONCLUSION: In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

Clinical Experience with Use of Remdesivir in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2: a Case Series.

BACKGROUND: A novel antiviral agent, remdesivir (RDV), is a promising candidate treatment for coronavirus disease 2019 (COVID-19) in the absence of any proven therapy. MATERIALS AND METHODS: This retrospective case series included 10 patients with a clinically and laboratory confirmed diagnosis of severe COVID-19 pneumonia who had received RDV for 5 days (n = 5) or 10 days (n = 5) in the Phase III clinical trial of RDV (GS-US-540-5773) conducted by Gilead Sciences. The clinical and laboratory data for these patients were extracted. RESULTS: One patient in the 10-day group received RDV for only 5 days because of nausea and elevated liver transaminases. No patient had respiratory comorbidity. Seven patients had bilateral lesions and three had unilateral lesions on imaging. All patients had received other medications for COVID-19, including lopinavir/ritonavir and hydroxychloroquine, before administration of RDV. Five patients required supplemental oxygen and one required mechanical ventilation. All patients showed clinical and laboratory evidence of improvement. Half of the patients developed elevated liver transaminases and three had nausea. There were no adverse events exceeding grade 2. CONCLUSION: Our experience indicates that RDV could be a therapeutic option for COVID-19. A well-designed randomized controlled clinical trial is now needed to confirm the efficacy of RDV in patients with COVID-19.

Four cases of coronavirus disease 2019 in the early stage of pandemic of South Korea: a single public hospital experience.

In view of this pandemic, as of February 2020, South Korea has the second highest number of confirmed cases in the world. Herein, we report four confirmed coronavirus disease 2019 (COVID-19) cases in the early stage of the pandemic in South Korea and describe the identification, diagnosis, clinical course, and management, including one patient's initial mild symptoms at presentation and their progression to pneumonia on day 21 of illness. Within 48 hours of hospitalization, all four patients underwent evaluation for initial laboratory parameters, COVID-19 polymerase chain reaction (PCR), and chest computed tomography (CT) findings. All four mild COVID-19 patients were discharged, and they were re-examined 14 days after discharge. Despite all four of them being asymptomatic, one patient was re-admitted after confirmation of COVID-19 through PCR viral nucleic acid detection. She could be discharged after 7 days with two subsequent negative COVID-19 PCR at 24-hour intervals. Patients with mild COVID-19 generally have normal follow-up chest CT scans after discharge, even if the early chest CT definitely indicates pneumonia. Re-hospitalized patients with COVID-19 PCR positive results after discharge were not related to her initial chest CT, lab, symptoms compared other three patients.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Multidrug-resistant Acinetobacter baumannii infection in lung transplant recipients: risk factors and prognosis.

Backgrounds: Infectious complication is an important cause of poor outcome of lung transplantation (LT). Infections with Acinetobacter baumannii (A. baumannii) are problematic, because of limited therapeutic option due to increasing resistance to antibiotics. However, there are few studies on A. baumannii infection in lung transplant recipients. Thus, we aimed to investigate epidemiology and risk factors for infection with A. baumannii in lung transplant recipients. Methods: Lung transplant recipients ≥18 years of age in a university hospital were enrolled in this retrospective cohort study. Risk factors for infection with multidrug resistant A. baumannii and 90-day mortality were analysed. Results: Fifty-one of 96 lung transplant recipients experienced A. baumannii infection. Infected patients had a significantly higher 90-day mortality rate than uninfected (19.6% vs. 2.2%, p = .009). High blood urea nitrogen (BUN) before transplantation (odds ratio [OR] 1.16; p = .008), long duration of surgery (OR 1.16; p = .029) and hypoalbuminemia before transplantation (OR 4.01; p = .037) were independent risk factors for infection with multidrug resistant A. baumannii. On multivariate analysis, severe thrombocytopenia (OR 28.69; p = .005), high serum creatinine (OR 1.48; p = .042) and infection with multidrug resistant A. baumannii (OR 22.58; p = .031) were independent risk factors for 90-day mortality. Conclusions: Prolonged surgery, high BUN and hypoalbuminemia before LT were significant risk factors for infection with multidrug resistant A. baumannii. Severe thrombocytopenia, high serum creatinine and infection with multidrug resistant A. baumannii infection were independent risk factors for 90-day mortality.

Risk factors for mortality in patients with low lactate level and septic shock.

BACKGROUND: According to the new definition of septic shock, vasopressor therapy and hyperlactatemia are essential for diagnosis. However, there is controversy regarding the cutoff value for lactate, and prognostic factors in patients with septic shock and hypolactatemia. This study evaluated the prognostic significance of the cutoff value for lactate level in septic shock patients. METHODS: The retrospective observational cohort study enrolled 1043 patients aged ≥18 years who meet the revised definition of septic shock. Clinical outcomes of patients with hyperlactatemia were compared with hypolactatemia. RESULTS: Of the 1022 eligible patients, 369 had an arterial lactate level ≤2 mmol/L. More patients in the high lactate group had poor prognosis than in the low lactate group. A high Sequential Organ Failure Assessment score (SOFA) score group was significant (p < 0.001) in predicting lactate levels. On the subgroup analysis of risk factors affecting mortality in the low lactate group, high Acute Physiology And Chronic Health Evaluation Ⅱ (APACHEⅡ) score (p = 0.003), high C-reactive protein (p = 0.034), and chronic heart failure (p = 0.001) were independently associated with 28-day mortality. CONCLUSION: Arterial lactate is a very reliable diagnostic and prognostic predictor of septic shock. However, despite low arterial lactate, patients with a high APACHEⅡ score, high C-reactive protein levels, and chronic heart failure had a poorer prognosis.

Clinical Response of Rifaximin Treatment in Patients with Abdominal Bloating.

BACKGROUND/AIMS: Abdominal bloating is a troublesome complaint due to insufficient understanding of the pathophysiology. The aim of this study was to evaluate the efficacy of rifaximin in reducing bloating associated with functional gastrointestinal disorders (FGIDs). METHODS: A total of 63 patients were treated with rifaximin for FGIDs with bloating or gas-related symptoms between 2007 and 2013 at Seoul National University Bundang Hospital. Rifaximin was administered at a dose between 800 mg/day and 1,200 mg/day for 5 to 14 days. The proportion of patients who had adequate relief of global FGID symptoms and FGID-related bloating was retrospectively assessed. The response was recorded when the symptoms were reduced by at least 50% at the follow-up after treatment cessation. RESULTS: The mean age was 56.8±14.2 years; 49.2% were females. According to Rome III criteria, 20.6% (13/63) had irritable bowel syndrome (IBS) with constipation, 9.5% (6/63) had IBS with diarrhea, 4.8% (3/63) had mixed IBS, 23.8% (15/63) had functional dyspepsia, and 12.7% (8/63) had functional bloating. Of the 51 subjects who were followed-up, 30 (58.8%) had adequate relief of global FGID symptoms and 26 (51.0%) experienced improvement of abdominal bloating after rifaximin treatment. The proportion of female was slightly higher in non-response group than in the response group (60.0% vs. 34.6%, p=0.069). Otherwise, there was no difference between the two groups. CONCLUSIONS: Despite the limitations of this retrospective study, our data confirms that rifaximin may be beneficial for abdominal bloating. Further prospective clinical trial with a larger cohort is needed.

An Imported Case of Brucella melitensis Infection in South Korea.

Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.

Increased Primary Cilia in Idiopathic Pulmonary Fibrosis.

Primary cilia are solitary, non-motile, axonemal microtubule-based antenna-like organelles that project from the plasma membrane of most mammalian cells and are implicated in transducing hedgehog signals during development. It was recently proposed that aberrant SHH signaling may be implicated in the progression of idiopathic pulmonary fibrosis (IPF). However, the distribution and role of primary cilia in IPF remains unclear. Here, we clearly observed the primary cilia in alveolar epithelial cells, fibroblasts, and endothelial cells of human normal lung tissue. Then, we investigated the distribution of primary cilia in human IPF tissue samples using immunofluorescence. Tissues from six IPF cases showed an increase in the number of primary cilia in alveolar cells and fibroblasts. In addition, we observed an increase in ciliogenesis related genes such as IFT20 and IFT88 in IPF. Since major components of the SHH signaling pathway are known to be localized in primary cilia, we quantified the mRNA expression of the SHH signaling components using qRT-PCR in both IPF and control lung. mRNA levels of SHH, the coreceptor SMO, and the transcription factors GLI1 and GLI2 were upregulated in IPF compared with control. Furthermore, the nuclear localization of GLI1 was observed mainly in alveolar epithelia and fibroblasts. In addition, we showed that defective KIF3A-mediated ciliary loss in human type II alveolar epithelial cell lines leads to disruption of SHH signaling. These results indicate that a significant increase in the number of primary cilia in IPF contributes to the upregulation of SHH signals.