Usefulness of the modified hemophagocytic syndrome diagnostic score as a prognostic factor in lung transplantation patients

Background: Lung transplantation (LTX) is an established treatment for end-stage lung disease; however, the post-LTX mortality rate remains high. This study aimed to evaluate the prognostic value of the modified reactive hemophagocytic syndrome diagnostic score (mHScore) and its individual components on mortality after LTX.Methods: We retrospectively analyzed 294 patients who underwent LTX at Severance Hospital, Yonsei University, Korea, from January 2012 and December 2020, and classified them into high (n=114, mHScore > 104.0) and low mHScore (n=180, mHScore ≤ 104.0) groups. Triglyceride, ferritin, serum glutamic oxaloacetic transaminase, fibrinogen, and cytopenia were used to calculate the mHScore. We compared baseline characteristics and mortality rates as LTX prognostic factors.Results: The high mHScore group had significantly more cytopenia and higher ferritin, triglyceride, lactate dehydrogenase, and C-reactive protein levels than the low mHScore group. The mortality rate was significantly higher in the high than in the low mHScore group (hazard ratio, 4.429, p < 0.001). Multivariate regression analysis revealed that a high mHScore was significantly associated with postoperative mortality, even after adjusting for other confounding factors. A high mHScore was also associated with postoperative complications.Conclusions: The mHScore can be used to estimate post-LTX prognosis and predict postoperative mortality.

The Relationship Between Delirium and Statin Use According To Disease Severity in Patients in the Intensive Care Unit

Background There have been few earlier studies on the efficacy of statins in the prevention of delirium. However, the results were controversial. The aim of this study was to investigate the association between the use of statins and the occurrence of delirium in a large cohort of patients in the intensive care unit (ICU), considering disease severity and statin properties, which were not sufficiently considered in the previous works. Methods We obtained clinical and demographical information from 3604 patients admitted to the ICU of Gangnam Severance Hospital from January 2013 to April 2020. This included information on daily statin use and delirium state, as assessed by the Confusion Assessment Method for ICU. We used inverse probability of treatment weighting and categorized the ICU patients into four groups based on the Acute Physiology and Chronic Health Evaluation II score (group 1: 0-10 - mild; group 2: 11-20 – mild to moderate; group 3: 21-30 – moderate to severe; group 4: > 30 - severe). We analyzed the association between the use of statin and the occurrence of delirium in each group, while taking into account the properties of statins. Results Comparisons between statin and non-statin patient groups revealed that only in group 2, patients who were administered statin showed significantly higher occurrence of delirium (p=0.004, odds ratio [OR]=1.58) compared to the patients who did not receive statin. Regardless of whether statins were lipophilic (p=0.036, OR=1.47) or hydrophilic (p=0.032, OR=1.84), the occurrence of delirium was higher only in patients from group 2. Although both lipophilic and hydrophilic statins in group 2 were associated with delirium, neither showed a greater association than the other. Conclusions The use of statins may be associated with the increases in the risk of delirium occurrence in patients with mild to moderate disease severity, irrespective of statin properties, as revealed by results from a large cohort study.

Comparing Treatment Outcomes of Ampicillin-Sulbactam, Other β-Lactams, and Vancomycin in Blood Culture-Negative Infective Endocarditis

Selection of proper antibiotics for blood culture-negative infective endocarditis (BCNIE) is difficult due to limited data on antibiotic regimens for BCNIE in existing literature. The aim of this study was to compare ampicillin-sulbactam, other β-lactams antibiotics, and vancomycin among patients with BCNIE to determine the proper antibiotic regimens. This retrospective study included adult patients with BCNIE admitted to Severance Hospital from November 2005 to August 2017. Patients were classified into three groups as, treated with ampicillin-sulbactam, other β-lactams, and vancomycin. The primary outcome was 1-year all-cause mortality. A total of 74 cases with BCNIE were enrolled in this study. There were no statistically significant differences in clinical characteristics between the three groups. One-year mortality did not significantly differ between the study groups either. Further, in-hospital mortality, 28-day mortality and overall mortality showed no difference. However, Cox-regression analysis showed nosocomial infective endocarditis as an independent risk factor and a protective effect of surgery on 1-year mortality. This study showed no clear difference in the outcomes of BCNIE as per the antibiotic therapy but suggested the beneficial effect of surgical treatment. With increasing global concern of antimicrobial resistance, it might be reasonable to select ampicillin-sulbactam-based antibiotic therapy while actively considering surgical treatment in BCNIE.

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

Background All healthcare workers (HCWs) in Yongin Severance Hospital were allocated to receive the ChAdOx1 nCov-19 vaccine according to national policy. A report of thrombosis and thrombocytopenia syndrome (TTS) associated with ChAdOx1 nCoV-19 led to hesitancy about receiving the second dose among HCWs who had received the first dose. Methods From 7 to 14 May, 2021, we performed a survey to identify the factors associated with hesitancy about receiving the second vaccine dose among HCWs at the hospital who had received the first dose of the vaccine. Based on survey results, a hospital-wide campaign was implemented on 18 May 2021 to improve vaccine coverage. HCWs who completed the second dose completed a self-administered questionnaire to evaluate the effect of the campaign. Findings Of 1,171 HCWs who had received the first dose of the vaccine, 71.5% completed the online survey, of whom 3.7% refused to take the second dose and 22.3% showed hesitancy. Hesitancy to receive a second dose was significantly associated with age under 30 years and concerns about TTS, and was less common among those who trusted effectiveness and safety of the vaccine. Among HCWs who received the first dose, 96.2% completed vaccination with the second dose between 27 May and 4 June, 2021. Of those who answered the questionnaire asked about the timing of their decision to receive the second dose, 57.1% reported that they were motivated by the hospital-wide campaign. Conclusion A tailored intervention strategy based on a survey can improve COVID-19 vaccination uptake among HCWs.

Risk factors and mortality of acute kidney injury within 1 month after lung transplantation

After lung transplantation (LT), some patients are at risk of acute kidney injury (AKI), which is associated with worse outcomes and increased mortality. Previous studies focused on AKI development from 72 h to 1 week within LT, and reported main risk factors for AKI such as intraoperative hypotension, need of ECMO support, ischemia time or longer time on waiting list. However, this period interval rarely reflects medical risk factors probably happen in longer post-operative period. So, in this study we aimed to describe the incidence and risk factor of AKI within post-operative 1 month, which is longer follow up duration. Among 161 patients who underwent LT at Severance hospital in Seoul, Korea from October 2012 to September 2017, 148 patients were retrospectively enrolled. Multivariable logistic regression and Cox proportional hazard models were utilized. Among 148 patients, 59 (39.8%) developed AKI within 1-month after LT. Stage I or II, and stage III AKI were recorded in 26 (17.5%) and 33 (22.2%), respectively. We also classified AKI according to occurrence time, within 1 week as early AKI, from 1 week within 1 month was defined as late AKI. AKI III usually occurred within 7 days after transplantation (early vs. late AKI III, 72.5% vs 21.1%). Risk factor for AKI development was pre-operative anemia, higher units of red blood cells transfused during surgery, colistin intravenous infusion for treating multi drug resistant pathogens were independent risk factors for AKI development. Post-operative bleeding, grade 3 PGD within 72 h, and sepsis were more common complication in the AKI group. Patients with AKI III ([24/33] 72.7%) had significantly higher 1-year mortality than the no-AKI ([18/89] 20.2%), and AKI I or II group ([9/26] 34.6%), log-rank test, P < 0.001). AKI was associated with worse post-operative outcome, 3-month, and 1-year mortality after LT. Severity of AKI was usually determined in early post op period (ex. within 7 days) after LT, so optimal post-operative management as well as recipients selection should be considered.

Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

Prediction accuracy of conventional and total keratometry for intraocular lens power calculation in femtosecond laser-assisted cataract surgery

This study evaluated the accuracy of total keratometry (TK) and standard keratometry (K) for intraocular lens (IOL) power calculation in eyes treated with femtosecond laser-assisted cataract surgery. The retrospective study included a retrospective analysis of data from 62 patients (91 eyes) who underwent uneventful femtosecond laser-assisted cataract surgery with Artis PL E (Cristalens Industrie, Lannion, France) IOL implantation by a single surgeon between May 2020 and December 2020 in Severance Hospital, Seoul, South Korea. The new IOLMaster 700 biometry device (Carl Zeiss Meditec, Jena, Germany) was used to calculate TK and K. The mean absolute error (MAE), median absolute error (MedAE), and the percentages of eyes within prediction errors of ± 0.25 D, ± 0.50 D, and ± 1.00 D were calculated for all IOL formulas (SRK/T, Hoffer-Q, Haigis, Holladay 1, Holladay 2, and Barrett Universal II). There was strong agreement between K and TK (intraclass correlation coefficient = 0.99), with a mean difference of 0.04 D. For all formulas, MAE tended to be lower for TK than for K, and relatively lower MAE and MedAE values were observed for SRK/T and Holladay 1. Furthermore, for all formulas, a greater proportion of eyes fell within ± 0.25 D of the predicted postoperative spherical equivalent range in the TK group than in the K group. However, differences in MAEs, MedAEs, and percentages of eyes within the above prediction errors were not statistically significant. In conclusion, TK and K exhibit comparable performance for refractive prediction in eyes undergoing femtosecond laser-assisted cataract surgery.

Risk of hepatocellular carcinoma after spontaneous and nucleos(t)ide analogue induced hepatitis B surface antigen seroclearance.

e16162 Background: Despite a favorable clinical course, the risk of hepatocellular carcinoma (HCC) still exists in patients achieving HBsAg seroclearance. Therefore, we investigated the incidence of HCC after spontaneous and nucleos(t)ide analogue (NA) induced HBsAg seroclearance in real-life clinical practice. Methods: A cohort study was conducted using data from Gangnam Severance Hospital. We identified all subjects with positive HBsAg between January 1, 2001 and March 21, 2018. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was the incidence of HCC after naturally and NA induced HBsAg seroclearance. Results: Among the 5,609 HBsAg-positive patients, 83 chronic hepatitis B (CHB) patients achieved HBsAg seroclearance during 19 years. The cumulative incidence of HBsAg seroclearance was 0.024% at 2 years to 32.4% at 19 years. Of the 83 patients with HBsAg seroclearance, 52 patients achieved spontaneous HBsAg seroclearance and 31 patients achieved NA-induced HBsAg seroclearance. Of 52 patients with spontaneous HBsAg seroclearance, only one patient (2%) developed HCC 6 months after HBsAg seroclearance. On the other hands, there was no development of HCC in patients with NA-induced HBsAg seroclearance. No significant difference was observed in the cumulative incidence of HCC between two groups ( P=0.443). All patients had sustained HBsAg seroclearance and there was no HBsAg seroreversion. Conclusions: The incidence of HCC was extremely rare after spontaneous and NA induced HBsAg seroclearance in real-life clinical practice. NA-induced HBsAg seroclearance is also as durable as spontaenous HBsAg seroclearance.

Fall Patterns Are Independent Risk Factors for Mortality After Hip Fracture in Older Adults

Hip fracture is becoming a major health problem with high mortality and morbidity in older adults. However, whether specific fall patterns could act as independent risk factors for predicting mortality after hip fracture remains unknown. We aimed to investigate whether fall patterns can serve as an independent risk factor for mortality after hip fracture. Electronic medical records (EMR) of individuals who visited emergency room or admitted to the Severance hospital, Seoul, Korea, between January 2005 to December 2019 were reviewed to categorize fall patterns. Fall patterns were categorized upon review of explanatory description in EMR, using modified classification based on motion analysis of video-captured falls in a prior study. Among 1,991 study subjects (mean age 77 years, 71% women), 211 patients died (10.6%; median survival 296 days). Fall location was divided into home (67.4%) and outdoor (32.6%) with mortality rate of 11.9% and 8.0% (p=0.009), respectively. Fall patterns were specified by “cause of fall” (6 categories; slip [29.6%], trip or stumble [17.5%], etc.) and by “activity at time of fall” (6 categories; walking [54.8%], getting up or rising [14.1%], etc). Among the combinations of both causes and activities, individuals who sustained hip fracture during “incorrect weight shift while sitting down or lowering”(hazard ratio [HR] 3.35, p=0.003), “collapsed during unclassified activity”(HR 2.37, p=0.006), “incorrect weight shift while getting up or rising”(HR 2.13, p=0.003), and “slipped while walking”(HR 1.83, p=0.004) had increased mortality after hip fracture compared to those with outdoor falls, after adjustment for age, sex, and Charlson comorbidity index. Specific fall patterns in individuals who sustained hip fracture predicted excess mortality in older adults, independent of age, sex, and comorbidities. Acknowledgement: We thank Doori Cho of the the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team (4-2018-1215) for the data acquisition process. Conflict of Interest: SB, NH, and YR have nothing to declare.