Double Primary Cancers of Earlobe Merkel Cell Carcinoma and Lung Adenocarcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma with a high rate of metastasis. MCC is rarely suspected during clinical examination, thus requiring biopsy to establish a pathologic diagnosis. In addition, MCC sometimes occurs in double primary cancers. Although there have been reviews on double primary cancers, only a few cases involving MCC have been described. Herein, we report a case of a 54-year-old female patient who presented to our clinic with a diagnosis of earlobe MCC following an excisional biopsy performed by another clinic. Further evaluation, including chest imaging, revealed a mass in the lung. The patient underwent a wide excision of the right earlobe, and video-assisted thoracic surgery on the lung. Pathology confirmed MCC in the right earlobe and adenocarcinoma in the lung. The patient underwent postoperative adjuvant chemotherapy followed by radiotherapy. Up to this point, 3 years after the surgery, there has been no evidence of recurrence.

Virological characteristics and the rapid antigen test as deisolation criteria in immunocompromised patients with COVID-19: A prospective cohort study.

There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19). Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Clinical scoring system to predict viable viral shedding in patients with COVID-19.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends 5-10 days of isolation for patients with COVID-19, depending on symptom duration and severity. However, in clinical practice, an individualized approach is required. We thus developed a clinical scoring system to predict viable viral shedding. METHODS: We prospectively enrolled adult patients with SARS-CoV-2 infection admitted to a hospital or community isolation facility between February 2020 and January 2022. Daily dense respiratory samples were obtained, and genomic RNA viral load assessment and viral culture were performed. Clinical predictors of negative viral culture results were identified using survival analysis and multivariable analysis. RESULTS: Among 612 samples from 121 patients including 11 immunocompromised patients (5 organ transplant recipients, 5 with hematologic malignancy, and 1 receiving immunosuppressive agents) with varying severity, 154 (25%) revealed positive viral culture results. Multivariable analysis identified symptom onset day, viral copy number, disease severity, organ transplant recipient, and vaccination status as independent predictors of culture-negative rate. We developed a 4-factor predictive model based on viral copy number (-3 to 3 points), disease severity (1 point for moderate to critical disease), organ transplant recipient (2 points), and vaccination status (-2 points for fully vaccinated). Predicted culture-negative rates were calculated through the symptom onset day and the score of the day the sample was collected. CONCLUSIONS: Our clinical scoring system can provide the objective probability of a culture-negative state in a patient with COVID-19 and is potentially useful for implementing personalized de-isolation policies beyond the simple symptom-based isolation strategy.

Antibody Response Induced by Two Doses of ChAdOx1 nCoV-19, mRNA-1273, or BNT162b2 in Liver Transplant Recipients.

Coronavirus disease 2019 (COVID-19) vaccination in immunocompromised, especially transplant recipients, may induce a weaker immune response. But there are limited data on the immune response after COVID-19 vaccination in liver transplant (LT) recipients, especially on the comparison of Ab responses after different vaccine platforms between mRNA and adenoviral vector vaccines. Thus, we conducted a prospective study on LT recipients who received two doses of the ChAdOx1 nCoV-19 (ChAdOx1), mRNA-1273, or BNT162b2 vaccines compared with healthy healthcare workers (HCWs). SARS-CoV-2 S1-specific IgG Ab titers were measured using ELISA. Overall, 89 LT recipients (ChAdOx1, n=16 [18%]) or mRNA vaccines (mRNA-1273 vaccine, n=23 [26%]; BNT162b2 vaccine, n=50 [56%]) received 3 different vaccines. Of them, 16 (18%) had a positive Ab response after one dose of COVID-19 vaccine and 62 (73%) after 2 doses. However, the median Ab titer after two doses of mRNA vaccines was significantly higher (44.6 IU/ml) than after two doses of ChAdOx1 (19.2 IU/ml, p=0.04). The longer time interval from transplantation was significantly associated with high Ab titers after two doses of vaccine (p=0.003). However, mycophenolic acid use was not associated with Ab titers (p=0.53). In conclusion, about 3-quarters of LT recipients had a positive Ab response after 2 doses of vaccine, and the mRNA vaccines induced higher Ab responses than the ChAdOx1 vaccine.

Enterococcus raffinosus bacteremia: clinical experience with 49 adult patients.

This study is to evaluate the clinical characteristics and outcomes of Enterococcus raffinosus bacteremia in adults. We analyzed the medical records of adult patients with E. raffinosus bacteremia who were diagnosed and treated between 1997 and 2020 at a tertiary care teaching hospital in Seoul, Republic of Korea. The demographic, clinical, and laboratory data were collected and assessed. A total of 49 cases of E. raffinosus bacteremia were identified. E. raffinosus accounted for 0.6% of all enterococcal bacteremia events, and the incidence was 0.02 cases per 1,000 admissions. Of the 49 cases of E. raffinosus bacteremia, 35 (71.4%) had underlying malignancy. The biliary tract was the most common source of infection (81.6%, 40/49) and polymicrobial bacteremia was found in 25 cases (51.0%). The resistance rates of E. raffinosus bacteremia cases to penicillin, ampicillin, vancomycin, and linezolid were 61.2%, 49.0%, 2.0%, and 0%, respectively. In our case series, there was one case of vanA-type vancomycin-resistant E. raffinosus. The all-cause 60-day mortality rate was 22.4% (11/49), and the E. raffinosus bacteremia-related mortality rate was 4.1% (2/49). Cases of E. raffinosus bacteremia mainly originated from biliary tract infection and had a low rate of bacteremia-related mortality.

Adverse Reactions Following the First Dose of ChAdOx1 nCoV-19 Vaccine and BNT162b2 Vaccine for Healthcare Workers in South Korea.

BACKGROUND: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. METHODS: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. RESULTS: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%]; BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. CONCLUSION: In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

Histologic features suggesting connective tissue disease in idiopathic pulmonary fibrosis.

Some patients with idiopathic pulmonary fibrosis (IPF) have histopathologic features suggesting connective tissue disease (CTD); however, their clinical course and prognosis remain unclear. Thus, we aimed to investigate the clinical course and prognosis of these patients with histologic autoimmune features. Among 114 patients with biopsy-proven IPF, the histologic features were semi-quantitatively graded, and CTD scores (range: 0-9) were calculated as the sum of each score of plasma cell infiltration, lymphoid aggregates, and germinal centres. Patients with high CTD scores (≥ 4) were classified into the interstitial pneumonia with histologic autoimmune features (IP-hAF) group. The mean age of the patients was 60.0 years; 74.6% were men, 69.3% were ever-smokers, and 35.1% had IP-hAF. During follow-up, the IP-hAF group showed slower decline in lung function, and better prognosis (median survival, 48.7 vs. 40.4 months; p = 0.015) than the no-IP-hAF group. On multivariate Cox analysis, IP-hAF was an independent prognostic factor (hazard ratio, 0.522; p = 0.016), along with the lower diffusing capacity for carbon monoxide, higher scores of reticulation and honeycombing, and usual interstitial pneumonia pattern on high-resolution computed tomography. Patients with IPF having histologic autoimmune features show distinct clinical characteristics and better outcome than those without histologic autoimmune features.

Estimation of utility weights for major liver diseases according to disease severity in Korea.

BACKGROUND: The global burden of liver diseases, such as hepatocellular carcinoma and liver cirrhosis, is substantial. In this study, we estimated utility weights of liver disease-related health states in the general population using a visual analogue scale (VAS) and the standard gamble (SG) method. METHODS: Depictions of standardized health states related to major liver diseases were developed based on patient education materials and previous publications. To fully reflect disease progression from diagnosis to prognosis, each health state comprised four parts: diagnosis, symptoms, treatment, and progression and prognosis. A total of 407 participants from the Korean general population evaluated the health states using the VAS and SG methods in computer-assisted personal interviews. After excluding illogical responses, mean utility weights were calculated for each health state. RESULTS: The utility weights for health states were significantly different according to the existence of inconsistency in general. According to the VAS results, the health state with the highest utility was 'Chronic hepatitis B virus infection' (0.64), whereas the health state with the lowest utility was 'Hepatocellular carcinoma that requires palliative therapy' (0.17). Similarly, the SG results revealed that the health state with the highest utility was 'Chronic hepatitis B virus infection' (0.85), and the health state with the lowest utility was 'Hepatocellular carcinoma that requires palliative therapy' (0.40). CONCLUSIONS: The estimated utility weights in this study will be useful to measure the burden of liver diseases and evaluate cost-utility of programs for reducing the burden of liver diseases.

Frequency, Expected Effects, Obstacles, and Facilitators of Disclosure of Patient Safety Incidents: A Systematic Review.

OBJECTIVES: We performed a systematic review to assess and aggregate the available evidence on the frequency, expected effects, obstacles, and facilitators of disclosure of patient safety incidents (DPSI). METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for this systematic review and searched PubMed, Scopus, and the Cochrane Library for English articles published between 1990 and 2014. Two authors independently conducted the title screening and abstract review. Ninety-nine articles were selected for full-text reviews. One author extracted the data and another verified them. RESULTS: There was considerable variation in the reported frequency of DPSI among medical professionals. The main expected effects of DPSI were decreased intention of the general public to file medical lawsuits and punish medical professionals, increased credibility of medical professionals, increased intention of patients to revisit and recommend physicians or hospitals, higher ratings of quality of care, and alleviation of feelings of guilt among medical professionals. The obstacles to DPSI were fear of medical lawsuits and punishment, fear of a damaged professional reputation among colleagues and patients, diminished patient trust, the complexity of the situation, and the absence of a patient safety culture. However, the factors facilitating DPSI included the creation of a safe environment for reporting patient safety incidents, as well as guidelines and education for DPSI. CONCLUSIONS: The reported frequency of the experience of the general public with DPSI was somewhat lower than the reported frequency of DPSI among medical professionals. Although we identified various expected effects of DPSI, more empirical evidence from real cases is required.

Synthesis of isoquinolinone-based tetracycles as poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors.

The isoquinolinone-based tetracyclic compounds were designed and synthesized and their PARP-1 inhibitory activity was evaluated. Most of synthesized compounds showed fairly good activity. Also the most active compound 6 showed its activity on potentiation of anticancer agents, temozolamide and etoposide, by 1.7 times, respectively.