Machine learning prediction of the case-fatality of COVID-19 and risk factors for adverse outcomes in patients with non-small cell lung cancer.

Background: Since the emergence of coronavirus disease 2019 (COVID-19) across the globe, patients with cancer have been found to have an increased risk of infection with COVID-19 and are highly likely to experience a severe disease course. This study analyzed the clinical outcomes of COVID-19 in patients with non-small cell lung cancer (NSCLC) and identified the risk factors for adverse outcomes. Methods: The study included patients diagnosed with COVID-19 between January 2020 and April 2022 at the Samsung Medical Center in Seoul, Republic of Korea, who have a history of NSCLC. The case-fatality rate and risk factors for COVID-19 were analyzed using a machine-learning prediction method. Additionally, the study investigated the effect of COVID-19 on the systemic treatment of patients with advanced-stage NSCLC. Results: Overall, 1,127 patients were included in this study, with 10.3% of the patients being older than 75 years; of these patients, 51.8% were ex- or current smokers. Among the 584 patients cured after surgery, 91 had stable disease after concurrent chemo-radiotherapy, and 452 had recurrent or metastatic NSCLC. Among 452 patients with recurrent or metastatic NSCLC, 387 received systemic treatment in a palliative setting during COVID-19. Of these, 188 received targeted therapy, 111 received cytotoxic chemotherapy, 63 received immunotherapy +/- chemotherapy, and 26 received other agents. Among them, 94.6% of patients continued systemic treatment after the COVID-19 infection. Only one patient discontinued treatment because of complications of the COVID-19 infection, and 18 patients changed their systemic treatment because of disease progression. The case fatality rates were 0.86% for patients with early-stage NSCLC, 4.4% for patients with locally advanced NSCLC, and 9.96% for patients with advanced NSCLC. The factors associated with fatalities included palliative chemotherapy, type of palliative chemotherapy, age (≥75 years), diabetes, smoking history, history of lung radiotherapy, hypertension, sex, and chronic obstructive pulmonary disease (COPD). The predictive model using logistic regression and eXtreme Gradient Boosting (XGB) performed well [area under the curve (AUC) for logistic regression =0.84 and AUC for XGB =0.84]. Conclusions: The case fatality rate in patients with NSCLC was 4.8%, while most patients with advanced NSCLC continued to receive systemic treatment. However, patients with risk factors require careful management of COVID-19 complications.

Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation.

PURPOSE: This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation (HSCT). METHODS: We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease. RESULTS: Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p<0.001). Steroid administration (aOR=5.78; 95% confidence interval: 1.25-26.68, p=0.024), red blood cell transfusion within one month (aOR=14.63; 2.75-77.76, p=0.002), low BMI (aOR=13.46, 2.07-87.45, p=0.006), and hypoalbuminemia (aOR=26.48, 5.93-118.17, p<0.001) were independent risk factors associated with CMV disease. The 30-day mortality was higher in the case group and CMV disease was significantly associated with all-cause mortality (aOR=14.41, 3.23-64.31, p<0.001). CONCLUSION: In hematologic malignancy patients without HSCT, risk factors for CMV organ disease included high-dose steroid administration and RBC transfusion within one month, low BMI, and hypoalbuminemia. Overall mortality was significantly higher with CMV disease, and CMV disease occurrence was a significant risk factor for mortality.

Breakthrough invasive fungal infection in patients with myeloid malignancy receiving posaconazole tablet prophylaxis: Clinical features, risk factors, and posaconazole profiles.

Posaconazole (PSC) delayed-release tablet prophylaxis is the standard of care for preventing invasive fungal infection (IFI) in patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. The clinical features, risk factors, and PSC profiles of breakthrough IFI (bIFI) in patients receiving PSC tablet prophylaxis were investigated. A single-center retrospective cohort study was conducted, including adult patients with myeloid malignancy who received prophylactic PSC tablets while undergoing chemotherapy from June 2016 to June 2021. Logistic regression analysis was used to identify risk factors for bIFI. A receiver operating characteristic curve was used to predict the relationship between PSC trough level at steady state and bIFI. A total of 434 patients with myeloid malignancy who received PSC tablets were screened. A total of 10 patients with bIFI were compared with 208 non-IFI patients. There were four proven and six probable IFI cases, nine due to Aspergillus, and one due to Fusarium species. The bIFI patients had higher in-hospital mortality (30.0%) than the non-IFI patients (1.9%; P < 0.001). History of allogeneic hematopoietic stem cell transplantation (odds ratio [OR] 6.27; 95% confidence interval [CI] 1.63-24.09), prolonged neutropenia ≥28 days (OR 4.33; 95% CI 1.20-15.70), and low plasma PSC concentration <0.7 µg/ml (OR 16.33; 95% CI 4.15-64.26) were risk factors for bIFI. The optimal cutoff value of plasma PSC concentration predicting bIFI was 0.765 µg/ml (sensitivity, 60.0%; specificity, 91.3%; area under the curve, 0.746). bIFI was not uncommon in patients with myeloid malignancy receiving PSC tablet prophylaxis and associated with poor outcomes. Therapeutic drug monitoring may still be necessary, even in patients receiving PSC tablets.

Invasive fungal infections increase mortality in acute myeloid leukemia patients. This study investigated breakthrough invasive fungal infection cases in patients receiving posaconazole tablet prophylaxis. Our results will contribute to improving the outcome of patients with myeloid malignancy.

Clinical Features and Outcomes of Invasive Fusariosis: A Case Series in a Single Center with Literature Review.

Fusarium species, which are commonly found in soil, water, and organic substrates, can cause serious infections especially in immunocompromised patients. Fusarium infection is notoriously difficult to treat, because of their inherently high minimum inhibitory concentrations (MICs) to most antifungal agents. There have been limited data on invasive fusariosis in Korea. We identified 57 patients with culture-proven fusariosis at Samsung Medical Center, Seoul, Korea, from September 2003 through January 2017. Invasive fusariosis was defined as any case with at least one positive blood culture or with concurrent involvement of 2 or more non-contiguous sites. Superficial infections such as keratitis and onychomycosis were excluded. We reported 14 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, of which 6 cases were fusarium fungemia. Hematologic malignancies (7/14, 50%), solid organ transplantation (2/14, 14.2%), or immunosuppressive therapy (2/14, 14.2%), were the predominant underlying conditions. The overall mortality rate was 37%, however, that of disseminated fusariosis was up to 83%. Antifungal treatment with voriconazole or liposomal amphotericin B was commonly administered. In this report, we described the clinical characteristics and treatment outcomes of invasive fusariosis in Korea. Given the high mortality in disseminated cases, invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients.

Predictive and prognostic factors associated with unliquefied pyogenic liver abscesses.

INTRODUCTION: Poor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown. METHODS: We conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis. RESULTS: A total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73-0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14-6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13-2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23-5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization. CONCLUSION: Several clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.

Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia.

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

Impact of vancomycin use trend change due to the availability of alternative antibiotics on the prevalence of Staphylococcus aureus with reduced vancomycin susceptibility: a 14-year retrospective study.

BACKGROUND: We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available. METHODS: Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005-2018 was analyzed. RESULTS: Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531-0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981-1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend. CONCLUSIONS: During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems.

Clinical application of an algorithm to screen for malignant cells in body fluids using an automated hematology analyzer.

INTRODUCTION: The detection of malignant cells in body fluids (BF) with an automated hematology analyzer has been proposed as an alternative to morphological examination owing to its various advantages; however, its limitations have also been highlighted. In this study, we devised a practical algorithm to screen for malignant cells in BFs using an automated hematology analyzer. METHODS: A total of 558 BF samples, including 232 cerebrospinal fluid (CSF) samples and 326 non-CSF samples, were consecutively collected. Thereafter, the results obtained using the BF mode of Sysmex XN-350 (Sysmex, Kobe, Japan) were compared with the cytological diagnosis. A cutoff was also established to screen for malignant cells using receiver operating characteristic (ROC) curve analysis based on the final clinical judgment. RESULTS: The automated hematology analyzer showed a moderate correlation or good agreement with the existing cytological diagnosis. Further, of the ROC curves for detecting malignant cells, the absolute value of highly fluorescent cells on BF (HF-BF) in total body fluids showed the highest area under the curve (0.85 [95% confidence interval 0.82-88], p < .0001, Youden index >7×106 /L, sensitivity 93%, and specificity 65%). CONCLUSION: An automated hematology analyzer could function as a complement to cytological examination. We propose a practical and comprehensive algorithm for cytological examination that requires low- and high-resolution microscopy based on the absolute value of HF-BF in BF samples suspected of malignancy. This algorithm can more usefully detect malignant cells while taking advantage of the automated analyzer and cytological examination.

The impact of vancomycin-resistant Enterococcus (VRE) screening policy change on the incidence of healthcare-associated VRE bacteremia.

OBJECTIVE: To evaluate the impact of a vancomycin-resistant Enterococcus (VRE) screening policy change on the incidence of healthcare-associated (HA)-VRE bacteremia in an endemic hospital setting. DESIGN: A quasi-experimental before-and-after study. SETTING: A 1,989-bed tertiary-care referral center in Seoul, Republic of Korea. METHODS: Since May 2010, our hospital has diminished VRE screening for admitted patients transferred from other healthcare facilities. We assessed the impact of this policy change on the incidence of HA-VRE bacteremia using segmented autoregression analysis of interrupted time series from January 2006 to December 2014 at the hospital and unit levels. In addition, we compared the molecular characteristics of VRE blood isolates collected before and after the screening policy change using multilocus sequence typing and pulsed-field gel electrophoresis. RESULTS: After the VRE screening policy change, the incidence of hospital-wide HA-VRE bacteremia increased, although no significant changes of level or slope were observed. In addition, a significant slope change in the incidence of HA-VRE bacteremia (change in slope, 0.007; 95% CI, 0.001-0.013; P = .02) was observed in the hemato-oncology department. Molecular analysis revealed that various VRE sequence types appeared after the policy change and that clonally related strains became more predominant (increasing from 26.1% to 59.3%). CONCLUSIONS: The incidence of HA-VRE bacteremia increased significantly after VRE screening policy change, and this increase was mainly driven by high-risk patient populations. When planning VRE control programs in hospitals, different approaches that consider risk for severe VRE infection in patients may be required.

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes.

BACKGROUND: Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. METHODS: A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. RESULTS: 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1-33.2%. CONCLUSION: Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

Sequence type 17 is a predictor of subsequent bacteremia in vancomycin-resistant Enterococcus faecium-colonized patients: a retrospective cohort study.

BACKGROUND: Sequence type (ST) 17 vancomycin-resistant Enterococcus faecium (VREF) is frequently isolated in nosocomial settings. The aim of this study was to identify whether ST17 contributes to subsequent bacteremia more often than other STs among hospitalized patients carrying VREF. METHODS: A retrospective cohort study was conducted in patients carrying ST17 VREF and those with non-ST17 VREF. Rectal screening according to hospital policy was used to identify patients with VREF. Subsequent VREF bacteremia events within a year of detection of colonization were recorded. Cox regression analysis was used to adjust the covariates involved in determining the association between ST17 and subsequent bacteremia events. RESULTS: The cohorts comprised 52 patients with ST17 and 169 patients with non-ST17 VREF. One-year VREF bacteremia-free rates were 85.9% and 90.2%, respectively. In multivariate analysis, ST17 was associated with subsequent bacteremia at an adjusted hazard risk (aHR) of 4.02 (95% confidence interval [CI], 1.32-12.29). Liver transplantation (aHR, 40.08; 95% CI, 4.87-329.76) and hematologic malignancy (aHR, 20.97; 95% CI, 4.87-87.82) were also significant. All cases of subsequent bacteremia in ST17 VREF carriers were caused by ST17; however, subsequent bacteremia in non-ST17 carriers was often caused by ST17 or another ST variant. CONCLUSIONS: A specific genotype, ST17 is a predictor of subsequent bacteremia in hospitalized patients carrying VREF. Patients with a hematologic malignancy and those receiving a liver transplant are also at high risk. More targeted strategies may be needed to prevent VREF infection in hospitals.

Multidisciplinary and Multisociety Practice Guideline on Reprocessing Flexible Gastrointestinal Endoscopes and Endoscopic Accessories.

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

Severe Thrombocytopenia in a Patient with COVID-19.

Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm³ and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.

Characteristics and Clinical Outcomes of Extended-Spectrum beta-lactamase-producing Klebsiella pneumoniae Bacteremia in Cancer Patients.

BACKGROUND: Cancer patients can be at a higher risk of infection due to drug-resistant bacteria than the general population for various reasons. We performed a retrospective study to evaluate possible risk factors and outcomes of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteremia in cancer patients. MATERIALS AND METHODS: Cases were divided into two groups based on whether or not the isolated strain produced ESBL and multivariable regressions were done to identify possible risk factors of ESBL-KP bacteremia and mortality. For ESBL-producing strain, additional molecular analysis was done. RESULTS: 278 cases with KP bacteremia were identified between 2010 and 2012, of which ESBL-producers were 50 (18%). The presence of percutaneous drainage catheter [odds ratio (OR) 4.99, P <0.001] and prior exposure to certain classes of antibiotics including third-generation cephalosporin (OR 2.14, P = 0.03) had significant associations with ESBL-KP bacteremia. Individuals who died within 14 days after the onset of KP bacteremia were more likely to have higher mean Pitt bacteremia score (1.56 in survival group vs. 3.43 in mortality group, P <0.001), hemodialysis (OR 17.03, P = 0.01) and chronic liver disease (OR 5.57, P = 0.01). Although 14-day mortality was higher with ESBL production (OR 2.76, P = 0.04), no significant differences in 30-day mortality (OR 1.67, P = 0.20) and other morbidity indices were observed. 49 ESBL-KP isolates, 65.4% of them produced CTX-M-14 and CTX-M-15 enzymes, and ST711 was the most common. CONCLUSION: There were several differences in clinical characteristics between ESBL-KP and non-ESBL-KP bacteremia in cancer patients, similar to previous reports including non-cancer patients.

Antifungal prophylaxis with posaconazole tablet and oral suspension in patients with haematologic malignancy: Therapeutic drug monitoring, efficacy and risk factors for the suboptimal level.

BACKGROUND: Posaconazole is used to prevent invasive fungal infections (IFIs) in patients with haematologic malignancy. In this study, we compared plasma posaconazole concentrations (PPCs) and the incidence of breakthrough IFIs between patients with haematologic malignancy receiving posaconazole oral suspension vs tablet. METHODS: We retrospectively collected data on adult patients with haematologic malignancies who received posaconazole prophylaxis during chemotherapy from April 2014 through May 2018. A total of 242 cases with PPCs, 88 in the oral suspension group and 154 in the tablet group, were included in this study. RESULTS: Patients receiving tablets achieved a significantly higher mean PPC than did those on oral suspension (1.631 ± 0.878 µg/mL in the tablet group vs. 0.879 ± 0.585 µg/mL in the oral suspension group). One hundred and thirty-seven of 154 patients (89.0%) receiving tablets had PPCs of 0.7 µg/mL or more, while only 41 of 88 patients (46.6%) receiving oral suspension attained an optimal level (P < .001). The incidence of breakthrough IFIs was significantly higher in the oral suspension group compared with in the tablet group (14.8% of oral suspension vs. 4.5% of tablet; P = .005). In the analysis including patients receiving posaconazole tablets, hypoalbuminemia (< 3.5 g/dL) was found to be a risk factor associated with suboptimal levels (odds ratio: 8.872; 95% confidence interval: 3.011 - 26.141; P < .001). CONCLUSIONS: Suboptimal PPCs in the tablet group were less common than those in the oral suspension group. Therapeutic drug monitoring may be still necessary even in patients receiving posaconazole tablets, especially in those with hypoalbuminemia.