Cytokine and Chemokine Profiles in Acute Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in South Korea.

In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1ß, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases.

Hypoalbuminemia and Albumin Replacement during Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with cardiorespiratory failure. The serum albumin level is an important prognostic marker in critically ill patients. We evaluated the efficacy of using pre-ECMO serum albumin levels to predict 30-day mortality in patients with cardiogenic shock (CS) who underwent venoarterial (VA) ECMO. Methods: We reviewed the medical records of 114 adult patients who underwent VA-ECMO between March 2021 and September 2022. The patients were divided into survivors and non-survivors. Clinical data before and during ECMO were compared. Results: Patients' mean age was 67.8±13.6 years, and 36 (31.6%) were female. The proportion of survival to discharge was 48.6% (n=56). Cox regression analysis showed that the pre-ECMO albumin level independently predicted 30-day mortality (hazard ratio, 0.25; 95% confidence interval [CI], 0.11-0.59; p=0.002). The area under the receiver operating characteristic curve of albumin levels (pre-ECMO) was 0.73 (standard error [SE], 0.05; 95% CI, 0.63-0.81; p<0.001; cut-off value=3.4 g/dL). Kaplan-Meier survival analysis showed that the cumulative 30-day mortality was significantly higher in patients with a pre-ECMO albumin level ≤3.4 g/dL than in those with a level >3.4 g/dL (68.9% vs. 23.8%, p<0.001). As the adjusted amount of albumin infused increased, the possibility of 30-day mortality also increased (coefficient=0.140; SE, 0.037; p<0.001). Conclusion: Hypoalbuminemia during ECMO was associated with higher mortality, even with higher amounts of albumin replacement, in patients with CS who underwent VA-ECMO. Further studies are needed to predict the timing of albumin replacement during ECMO.

Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

Association between baseline smoking status and clinical outcomes following myocardial infarction.

Background: Whether the effect of smoking on clinical outcomes following an acute myocardial infarction (AMI) is beneficial or detrimental remains inconclusive. We invesetigated the effect of smoking on the clinical outcomes in patients following an AMI. Methods: Among 13,104 patients between November 2011 and June 2015 from a nationwide Korean AMI registry, a total of 10,193 participants were extracted then classified into two groups according to their smoking habit: (1) smoking group (n = 6,261) and (2) non-smoking group (n = 3,932). The participants who smoked were further subclassified according to their smoking intensity quantified by pack years (PYs): (1) <20 PYs (n = 1,695); (2) 20-40 PYs (n = 3,018); and (3) ≥40 PYs (n = 2,048). Each group was compared to each other according to treatment outcomes. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCEs), which is a composite of all-cause mortality, non-fatal MI (NFMI), any revascularization, cerebrovascular accident, rehospitalization, and stent thrombosis. Secondary outcomes included the individual components of MACCEs. The Cox proportional hazard regression method was used to evaluate associations between baseline smoking and clinical outcomes following an AMI. Two propensity score weighting methods were performed to adjust for confounders, including propensity score matching and inverse probability of treatment weighting. Results: While the incidence of all clinical outcomes, except for stent thrombosis, was lower in the smoking group than in the non-smoking group in the unadjusted data, the covariates-adjusted data showed statistical attenuation of these differences but a higher all-cause mortality in the smoking group. For smokers, the incidence of MACCEs, all-cause mortality, cardiac and non-cardiac death, and rehospitalization was significantly different between the groups, with the highest rates of MACCE, all-cause mortality, non-cardiac death, and rehospitalization in the group with the highest smoking intensity. These differences were statistically attenuated in the covariates-adjusted data, except for MACCEs, all-cause mortality, and non-cardiac death, which had the highest incidence in the group with ≥40 PYs. Conclusion: Smoking had no beneficial effect on the clinical outcomes following an AMI. Moreover, for those who smoked, clinical outcomes tended to deteriorate as smoking intensity increased.

Prediction of 6-Month Mortality Using Pre-Extracorporeal Membrane Oxygenation Lactate in Patients with Acute Coronary Syndrome Undergoing Veno-Arterial-Extracorporeal Membrane Oxygenation.

BACKGROUND: The effectiveness of extracorporeal membrane oxygenation (ECMO) for patients with refractory cardiogenic shock or cardiac arrest is being established, and serum lactate is well known as a biomarker of end-organ perfusion. We evaluated the efficacy of pre-ECMO lactate for predicting 6-month survival in patients with acute coronary syndrome (ACS) undergoing ECMO. METHODS: We reviewed the medical records of 148 patients who underwent veno-arterial (VA) ECMO for ACS between January 2015 and June 2020. These patients were divided into survivors and non-survivors based on 6-month survival. All clinical data before and during ECMO were compared between the 2 groups. RESULTS: Patients' mean age was 66.0±10.5 years, and 116 (78.4%) were men. The total survival rate was 45.9% (n=68). Cox regression analysis showed that the pre-ECMO lactate level was an independent predictor of 6-month mortality (hazard ratio, 1.210; 95% confidence interval [CI], 1.064-1.376; p=0.004). The area under the receiver operating characteristic curve of pre-ECMO lactate was 0.64 (95% CI, 0.56-0.72; p=0.002; cut-off value=9.8 mmol/L). Kaplan-Meier survival analysis showed that the cumulative survival rate at 6 months was significantly higher among patients with a pre-ECMO lactate level of 9.8 mmol/L or less than among those with a level exceeding 9.8 mmol/L (57.3% vs. 31.8%, p=0.0008). CONCLUSION: A pre-ECMO lactate of 9.8 mmol/L or less may predict a favorable outcome at 6 months in ACS patients undergoing VA-ECMO. Further research aiming to improve the accuracy of predictions of reversibility in patients with high pre-ECMO lactate levels is essential.

Case Report: Intravascular Ultrasound-guided Intervention for Anastomosis Stenosis of the Left Main Coronary Artery Post-Cabrol Technique.

Introduction: Some cases of percutaneous coronary intervention (PCI) for the anastomotic site between the Cabrol-type conduit and the left main coronary artery (LMCA) have been reported. Nevertheless, the combination of PCI with a detailed description of lesion appearance using virtual histology-intravascular ultrasound (VH-IVUS) has never been reported. In this study, we present a case of acute myocardial infarction that was successfully treated with intravascular ultrasound (IVUS)-guided PCI for focal stenosis at the anastomotic site, and the plaque composition was studied in detail. Case Presentation: A 35-year-old Korean male with Behçet's disease was diagnosed with acute myocardial infarction. He had previously undergone three cardiothoracic surgeries including two aortic replacements, followed by modified Bentall operation with a Cabrol-type aortocoronary anastomosis. Coronary angiogram (CAG) showed focal critical stenosis at the anastomosis site between the conduit and the LMCA, and VH-IVUS showed fibrotic plaque with mainly fibrous tissue but without a confluent necrotic core. PCI was performed using a drug-eluting stent (4.5 × 12 mm, SynergyTM, Boston Scientific, Marlborough, MA, USA). Since a repeat CAG and IVUS post-surgery showed an under-expanded stent strut, post-dilation ballooning was additionally performed. Subsequently, the repeat IVUS revealed wellapposed and optimized deployment of the drug-eluting stent with full lesion coverage. Final CAG showed optimal angiographic results. After successful PCI, the patient's anginal symptoms improved dramatically, and he was successfully discharged from our hospital. Conclusion: This study presents an IVUS-guided PCI case for an anastomotic site between the conduit and the LMCA. It is the first to investigate the characteristics of this lesion through VH-IVUS, which demonstrated the presence of fibrous plaques at the anastomotic site. IVUS radiofrequency data allow for a detailed assessment of plaque composition and provide new insights into the histopathological nature of stenotic lesions at the anastomotic site, especially in patients with chronic inflammatory diseases like Behçet's disease.

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP. METHODS: We identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP. RESULTS: Fifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1-82) months. The median age was 55 (range, 33-75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement. CONCLUSIONS: The clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.

Rhinovirus Incidence Rates Indicate We Are Tired of Non-pharmacological Interventions Against Coronavirus Disease 2019.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of rhinovirus (RV) is inversely related to the intensity of non-pharmacological interventions (NPIs), such as universal mask wearing and physical distancing. METHODS: Using RV surveillance data, changes in the effect of NPIs were investigated in South Korea during the pandemic. The time to the first visible effect of NPIs after the onset of NPIs (T1), time to the maximum effect (T2), and duration of the maximum effect (T3) were measured for each surge. For each week, the RVdiff [(RV incidence during the pandemic) - (RV incidence within 5 years before the pandemic)] was calculated, and number of weeks for RVdiff to be below zero after NPIs (time to RVdiff ≤ 0) and number of weeks RVdiff remains below zero after NPIs (duration of RVdiff ≤ 0) were measured for each surge. RESULTS: During the study period, four surges of COVID-19 were reported. As the pandemic progressed, T1 and T2 increased, but T3 decreased. Additionally, the "time to RVdiff of ≤ 0" increased and "duration of RVdiff of ≤ 0" decreased. These changes became more pronounced during the third surge (mid-November 2020), before the introduction of the COVID-19 vaccine, and from the emergence of the delta variant. CONCLUSION: The effect of NPIs appears slower, the duration of the effect becomes shorter, and the intensity also decreases less than a year after the onset of the pandemic owing to people's exhaustion in implementing NPIs. These findings suggest that the COVID-19 response strategy must be completely overhauled.

Laparoscopic extended right hemicolectomy with superior-to-inferior dissection: a mentee's initial experience.

Laparoscopic right hemicolectomy is a widely accepted procedure for right colon cancer. Among the various approaches, the superior approach has potential benefits in that it exposes the gastrocolic trunk early and consistently allows for D3 lymph node dissection along superior mesenteric vessels. In this video, we present a beginner performing a laparoscopic extended right hemicolectomy using a superior approach without an assistant.

Lateral Pelvic Lymph Node Dissection After Neoadjuvant Chemoradiotherapy in Patients With Rectal Cancer: A Single-Center Experience and Literature Review.

PURPOSE: We aimed to evaluate the surgicopathological outcomes of lateral pelvic lymph node dissection (LPLD) and long-term oncological outcomes of selective LPLD after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer and compare them to those of total mesorectal excision (TME) alone based on pretreatment magnetic resonance imaging (MRI). METHODS: We compared the TME-alone group (2001-2009, n=102) with the TME with LPLD group (2011-2016, n=69), both groups having lateral lymph nodes (LLNs) of ≥5 mm in short axis diameter. The surgicopathological outcomes were analyzed retrospectively. Oncological outcomes were analyzed using the Kaplan-Meier method. RESULTS: The rates of overall postoperative 30-day morbidity (42.0% vs. 26.5%, P=0.095) and urinary retention (13.7% vs. 10.1%, P=0.484) were not significantly different between the LPLD and TME-alone groups, respectively. Pathologically proven LLN metastasis was identified in 24 (34.8%) LPLD cases after nCRT. The LPLD group showed a lower 5-year local recurrence (LR) rate (27.9% vs. 4.6%, P<0.001) and better recurrence-free survival (RFS) (59.6% vs. 78.2%, P=0.008) than those of the TME-alone group, while the 5-year overall survival was not significantly different between the 2 groups (76.2% vs. 86.5%, P=0.094). CONCLUSION: This study suggests that LPLD is a safe and feasible procedure. The oncological outcomes suggest that selective LPLD improves LR and RFS in patients with clinically suspicious LLNs on pretreatment MRI. Considering that lateral nodal disease is not common, a multicenter large-scale study is necessary.

Effects of Smoking on Long-Term Clinical Outcomes and Lung Cancer in Patients with Acute Myocardial Infarction.

BACKGROUND AND OBJECTIVES: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the "smoker's paradox". This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. RESULTS: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594-0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443-0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009-1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026-1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensity-score matched HR, 2.749; 95% CI, 1.416-5.338; p=0.003). CONCLUSIONS: In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. MATERIAL AND METHODS: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. RESULTS: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). CONCLUSION: The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Case Report: Fulminant Myocarditis Successfully Treated With Extracorporeal Membrane Oxygenation in Ikeda Strain Orientia tsutsugamushi Infection.

Scrub typhus is an acute zoonotic febrile illness caused by Orientia tsutsugamushi having a specific geographic endemic area. This infection could be complicated with multi-organ involvement including myocarditis with variable severity. Here, we report a rare case of scrub typhus with biopsy-proven acute fulminant myocarditis which progressed very rapidly to cardiac arrest and was treated successfully with extracorporeal cardiopulmonary resuscitation. Clinicians should be alert to possible rapid progression of scrub typhus myocarditis to fulminant form and be prepared for close monitoring and temporary mechanical support if indicated.

Clinical impact of echocardiography-defined pulmonary hypertension on the clinical outcome in patients with multiple myeloma.

Pulmonary hypertension (PH) is a complication of multiple myeloma (MM); however, the clinical outcomes and prognosis are relatively not well known. We aimed to investigate the risk factors of transthoracic echocardiography-defined PH and its impact on the clinical outcome in patients with MM.A retrospective study was performed using data from the Chonnam National University Hwasun Hospital database for patients who underwent transthoracic echocardiography (TTE) within 1 month of the MM diagnosis between January 2007 and December 2017. PH was defined as an estimated right ventricular systolic pressure (RVSP) > 40 mmHg. A total of 390 patients were included. TTE-defined PH was observed in 107 patients (27%). During the follow-up period (median, 688 days), all-cause death was noted for 134 patients (34.4%). In the Kaplan-Meier survival analysis, the cumulative overall survival and cardiovascular death-free survival rates were significantly lower in the PH group than in the non-PH group (P < .001). In the propensity score-matched population, RVSP > 40 mmHg on TTE and history of congestive heart failure (CHF) were identified as the significant independent predictors of all-cause and cardiovascular death.This study reports that the prevalence of TTE-defined PH is higher in patients with MM than in the general population. Moreover, TTE-defined PH and a history of CHF are the independent prognostic factors for all-cause and cardiovascular death in patients with MM. These results highlight the risk of associated cardiovascular disease in patients with MM and emphasize the importance of management strategies that prevent the deterioration of cardiac function.

Factors of Severity in Patients with COVID-19: Cytokine/Chemokine Concentrations, Viral Load, and Antibody Responses.

The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription-PCR. Anti-SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ-induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5-10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.

Efficacy and Safety of Cystatin C-Guided Renal Dose Adjustment of Cefepime Treatment in Hospitalized Patients with Pneumonia.

Cystatin C (CysC) may estimate renal function more accurately than serum creatinine (SCr). The clinical impact of renal dose adjustment of cefepime according to CysC rather than SCr has remained uncertain. We investigated the efficacy and safety of CysC-guided cefepime dosing compared with SCr-guided dosing in hospitalized patients with pneumonia. All adults hospitalized with pneumonia between July 2016 and December 2018 who used cefepime for at least 3 days were enrolled. Mortality, acute kidney injury (AKI), cefepime-induced encephalopathy (CIE), and Clostridium difficile infection were compared between the CysC-guided and SCr-guided groups. One hundred and ninety patients were divided into two groups: 129 and 61 received cefepime based on CysC and SCr, respectively. In-hospital mortality did not significantly differ between the groups (12% versus 31%; hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.31-1.77; p = 0.50). CysC-guided cefepime dosing decreased the risk of AKI (13% versus 61%; HR 0.18; 95% CI, 0.07-0.44; p < 0.001) and CIE (2% versus 11%; HR 0.11; 95% CI, 0.03-0.47; p = 0.003) compared with SCr-guided dosing. There was no significant difference in the risk of Clostridium difficile infection. CysC-guided dosing of cefepime was associated with decreased risk of the cefepime-associated morbidities including AKI and CIE without increasing mortality among the hospitalized patients with pneumonia.

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study.

BACKGROUND: This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. METHODS: This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1-3 (Q1-3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. CONCLUSION: This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677.

Synergistic Interactions Are Prevalent in Catalytic Amyloids.

Interactions between multiple functional groups are key to catalysis. Previously, we reported synergistic interactions in catalytic amyloids formed by mixtures of heptameric peptides that lead to significant improvements in esterase activity. Herein, we describe the in-depth investigation of synergistic interactions within a family of amyloid fibrils, exploring the results of functional group interactions, the effects of chirality and the use of mixed enantiomers within fibrils. Remarkably, we find that synergistic interactions (either positive or negative) are found in the vast majority of binary mixtures of catalytic amyloid-forming peptides. The productive arrangements of functionalities rapidly identified by mixing different peptides will undoubtedly lead to the development of more active catalysts for a variety of different transformations.

Clinical Outcome of Novel Reconstruction of Double Shouldering Technique after Proximal Gastrectomy.

Purpose: Various reconstruction methods have been proposed to reduce reflux after proximal gastrectomy, and we report here a double shouldering technique. The purpose of this study is to compare the novel double shouldering technique with conventional esophagogastrostomy in terms of short term and 3-year clinical outcome. Methods: A retrospective observational case control study was performed on 63 patients for cT1N0 upper third gastric cancer who underwent proximal gastrectomy from January 2012 to November 2016 at the National Cancer Center, Korea. There were 26 patients with conventional esophagogastrostomy, and 37 patients with novel double shouldering technique. The primary outcome was endoscopic reflux esophagitis findings one and three year after surgery according to Los Angeles classification. Secondary outcomes were short term surgical outcome and reflux symptom. Results: There was no significant difference in reflux esophagitis on endoscopic findings at 1 and 3 years after surgery between the two group. The double shouldering (DS) technique group showed significantly better postoperative outcomes with bile reflux at one and three years via endoscopic findings versus conventional esophagogastrostomy (CEG). Operative time and hospital stay were significantly shorter in the CEG group than the DS group. There was no significant difference in terms of reflux symptoms and complications. Conclusion: This novel DS technique is a reconstruction method for use after proximal gastrectomy. It did not show a significant clinical benefit. Development of surgical techniques and further study is needed to identify the optimal reconstruction method after proximal gastrectomy.