Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice.

Prelamin A is a farnesylated precursor of lamin A, a nuclear lamina protein. Accumulation of the farnesylated prelamin A variant progerin, with an internal deletion including its processing site, causes Hutchinson-Gilford progeria syndrome. Loss-of-function mutations in ZMPSTE24, which encodes the prelamin A processing enzyme, lead to accumulation of full-length farnesylated prelamin A and cause related progeroid disorders. Some data suggest that prelamin A also accumulates with physiological aging. Zmpste24-/- mice die young, at ∼20 wk. Because ZMPSTE24 has functions in addition to prelamin A processing, we generated a mouse model to examine effects solely due to the presence of permanently farnesylated prelamin A. These mice have an L648R amino acid substitution in prelamin A that blocks ZMPSTE24-catalyzed processing to lamin A. The LmnaL648R/L648R mice express only prelamin and no mature protein. Notably, nearly all survive to 65 to 70 wk, with ∼40% of male and 75% of female LmnaL648R/L648R mice having near-normal lifespans of 90 wk (almost 2 y). Starting at ∼10 wk of age, LmnaL648R/L648R mice of both sexes have lower body masses than controls. By ∼20 to 30 wk of age, they exhibit detectable cranial, mandibular, and dental defects similar to those observed in Zmpste24-/- mice and have decreased vertebral bone density compared to age- and sex-matched controls. Cultured embryonic fibroblasts from LmnaL648R/L648R mice have aberrant nuclear morphology that is reversible by treatment with a protein farnesyltransferase inhibitor. These novel mice provide a model to study the effects of farnesylated prelamin A during physiological aging.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

A lamin A/C variant causing striated muscle disease provides insights into filament organization.

The LMNA gene encodes the A-type lamins, which polymerize into ∼3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in LMNA cause a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts from LmnaH222P/H222P mice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filaments in situ and using a nuclear extraction protocol. Averaging of individual segments of filaments in LmnaH222P/H222P mouse fibroblasts resolved two polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure.

Diagnostic performance of synthetic relaxometry for predicting neurodevelopmental outcomes in premature infants: a feasibility study.

OBJECTIVES: To investigate the predictability of synthetic relaxometry for neurodevelopmental outcomes in premature infants and to evaluate whether a combination of relaxation times with clinical variables or qualitative MRI abnormalities improves the predictive performance. METHODS: This retrospective study included 33 premature infants scanned with synthetic MRI near or at term equivalent age. Based on neurodevelopmental assessments at 18-24 months of corrected age, infants were classified into two groups (no/mild disability [n = 23] vs. moderate/severe disability [n = 10]). Clinical and MRI characteristics associated with moderate/severe disability were explored, and combined models incorporating independent predictors were established. Ultimately, the predictability of relaxation times, clinical variables, MRI findings, and a combination of the two were evaluated and compared. The models were internally validated using bootstrap resampling. RESULTS: Prolonged T1-frontal/parietal and T2-parietal periventricular white matter (PVWM), moderate-to-severe white matter abnormality, and bronchopulmonary dysplasia were significantly associated with moderate/severe disability. The overall predictive performance of each T1-frontal/-parietal PVWM model was comparable to that of individual MRI finding and clinical models (AUC = 0.71 and 0.76 vs. 0.73 vs. 0.83, respectively; p > 0.27). The combination of clinical variables and T1-parietal PVWM achieved an AUC of 0.94, sensitivity of 90%, and specificity of 91.3%, outperforming the clinical model alone (p = 0.049). The combination of MRI finding and T1-frontal PVWM yielded AUC of 0.86, marginally outperforming the MRI finding model (p = 0.09). Bootstrap resampling showed that the models were valid. CONCLUSIONS: It is feasible to predict adverse outcomes in premature infants by using early synthetic relaxometry. Combining relaxation time with clinical variables or MRI finding improved prediction. CLINICAL RELEVANCE STATEMENT: Synthetic relaxometry performed during the neonatal period may serve as a biomarker for predicting adverse neurodevelopmental outcomes in premature infants. KEY POINTS: • Synthetic relaxometry based on T1 relaxation time of parietal periventricular white matter showed acceptable performance in predicting adverse outcome with an AUC of 0.76 and an accuracy of 78.8%. • The combination of relaxation time with clinical variables and/or structural MRI abnormalities improved predictive performance of adverse outcomes. • Synthetic relaxometry performed during the neonatal period helps predict adverse neurodevelopmental outcome in premature infants.

Hepatocytes Deficient in Nuclear Envelope Protein Lamina-associated Polypeptide 1 are an Ideal Mammalian System to Study Intranuclear Lipid Droplets.

Lipid droplets (LDs) are generally considered to be synthesized in the ER and utilized in the cytoplasm. However, LDs have been observed inside nuclei in some cells, although recent research on nuclear LDs has focused on cultured cell lines. To better understand nuclear LDs that occur in vivo, here we examined LDs in primary hepatocytes from mice following depletion of the nuclear envelope protein lamina-associated polypeptide 1 (LAP1). Microscopic image analysis showed that LAP1-depleted hepatocytes contain frequent nuclear LDs, which differ from cytoplasmic LDs in their associated proteins. We found type 1 nucleoplasmic reticula, which are invaginations of the inner nuclear membrane, are often associated with nuclear LDs in these hepatocytes. Furthermore, in vivo depletion of the nuclear envelope proteins lamin A and C from mouse hepatocytes led to severely abnormal nuclear morphology, but significantly fewer nuclear LDs than were observed upon depletion of LAP1. In addition, we show both high-fat diet feeding and fasting of mice increased cytoplasmic lipids in LAP1-depleted hepatocytes but reduced nuclear LDs, demonstrating a relationship of LD formation with nutritional state. Finally, depletion of microsomal triglyceride transfer protein did not change the frequency of nuclear LDs in LAP1-depleted hepatocytes, suggesting that it is not required for the biogenesis of nuclear LDs in these cells. Together, these data show that LAP1-depleted hepatocytes represent an ideal mammalian system to investigate the biogenesis of nuclear LDs and their partitioning between the nucleus and cytoplasm in response to changes in nutritional state and cellular metabolism in vivo.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

A consensus document on definition and diagnostic criteria for orthorexia nervosa.

PURPOSE: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with "correct" eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. METHODS: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A-Definition, Clinical Aspects, Duration; B-Consequences; C-Onset; D-Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. RESULTS: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. CONCLUSIONS: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. LEVEL OF EVIDENCE: Level V: opinions of expert committees.

Postnatal development of mice with combined genetic depletions of lamin A/C, emerin and lamina-associated polypeptide 1.

Mutations in LMNA encoding lamin A/C and EMD encoding emerin cause cardiomyopathy and muscular dystrophy. Lmna null mice develop these disorders and have a lifespan of 7-8 weeks. Emd null mice show no overt pathology and have normal skeletal muscle but with regeneration defects. We generated mice with germline deletions of both Lmna and Emd to determine the effects of combined loss of the encoded proteins. Mice without lamin A/C and emerin are born at the expected Mendelian ratio, are grossly normal at birth but have shorter lifespans than those lacking only lamin A/C. However, there are no major differences between these mice with regards to left ventricular function, heart ultrastructure or electrocardiographic parameters except for slower heart rates in the mice lacking both lamin A/C and emerin. Skeletal muscle is similarly affected in both of these mice. Lmna+/- mice also lacking emerin live to at least 1 year and have no significant differences in growth, heart or skeletal muscle compared to Lmna+/- mice. Deletion of the mouse gene encoding lamina-associated protein 1 leads to prenatal death; however, mice with heterozygous deletion of this gene lacking both lamin A/C and emerin are born at the expected Mendelian ratio but had a shorter lifespan than those only lacking lamin A/C and emerin. These results show that mice with combined deficiencies of three interacting nuclear envelope proteins have normal embryonic development and that early postnatal defects are primarily driven by loss of lamin A/C or lamina-associated polypeptide 1 rather than emerin.

Lamina-associated polypeptide 1 is dispensable for embryonic myogenesis but required for postnatal skeletal muscle growth.

Lamina-associated polypeptide 1 (LAP1) is an integral protein of the inner nuclear membrane that has been implicated in striated muscle maintenance. Mutations in its gene have been linked to muscular dystrophy and cardiomyopathy. As germline deletion of the gene encoding LAP1 is perinatal lethal, we explored its potential role in myogenic differentiation and development by generating a conditional knockout mouse in which the protein is depleted from muscle progenitors at embryonic day 8.5 (Myf5-Lap1CKO mice). Although cultured myoblasts lacking LAP1 demonstrated defective terminal differentiation and altered expression of muscle regulatory factors, embryonic myogenesis and formation of skeletal muscle occurred in both mice with a Lap1 germline deletion and Myf5-Lap1CKO mice. However, skeletal muscle fibres were hypotrophic and their nuclei were morphologically abnormal with a wider perinuclear space than normal myonuclei. Myf5-Lap1CKO mouse skeletal muscle contained fewer satellite cells than normal and these cells had evidence of reduced myogenic potential. Abnormalities in signalling pathways required for postnatal hypertrophic growth were also observed in skeletal muscles of these mice. Our results demonstrate that early embryonic depletion of LAP1 does not impair myogenesis but that it is necessary for postnatal skeletal muscle growth.

Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation.

INTRODUCTION: Risk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long-term follow-up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT. METHODS AND RESULTS: We enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed-up. During a follow-up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2 DS2 -VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri-atrial EAT volume. Multivariate regression analysis demonstrated larger peri-atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005-1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut-off value of peri-atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri-atrial EAT volume showed significantly higher ES-free survival. CONCLUSION: Larger peri-atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2 DS2 -VASc score. (ClinicalTrials.gov number, NCT03479073).

Employment conditions and use of gastric cancer screening services in Korea: a nationwide survey.

BACKGROUND: Although it is well known that employment conditions exert considerable effects on health and health equity, the association between employment conditions and the use of preventative health services has rarely been studied. We explored whether inequities in the use of preventative services were associated with employment conditions. We used gastric cancer screening as a surrogate for the use of preventative health services. METHODS: The study population was derived from the Korea National Health and Nutrition Survey IV (2007-2009), which included data on 5626 individuals over 40 years of age. Employment conditions were grouped by employment status, work hours, employment contract term, and salary source. Participants who had undergone gastroscopy or an upper gastrointestinal series within the past 2 years were considered to have used cancer screening services according to the National Cancer Screening Program guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression analysis. As the survey procedure incorporated sample weights, we adjusted our calculations to consider the complex sample design. RESULTS: Self-employed workers were less likely to participate in regular cancer screening than were wage workers (OR = 0.79, 95% CI = 0.68-0.92), and part-time workers were less likely to participate than were full-time workers (OR = 0.81, 95% CI = 0.67-0.99). Among wage workers, temporary workers and daily workers exhibited lower participation rates than did regular workers (OR = 0.81, 95% CI = 0.63-1.05 and OR = 0.58, 95% CI = 0.44-0.76, respectively). Dispatched workers also exhibited lower participation rates (OR = 0.45, 95% CI = 0.25-0.80). CONCLUSIONS: We found obvious inequities in the use of preventative health services associated with various employment conditions. Self-employed, irregular, and dispatched workers were significantly less likely to participate in cancer screening than were other workers. Political efforts should be made to reduce employment insecurity and to improve participation in preventative screening services by vulnerable employees so as to resolve the evident health inequities.

Chasms in Achievement of Recommended Diabetes Care among Geographic Regions in Korea.

BACKGROUND: Although effective care for type 2 diabetes (T2DM) is well known, considerable inadequate care has been still existed. Variations in achievement of the recommended quality indicators inT2DM care among small areas are not well known in Korea. This study examined the quality of care T2DM care and its geographical variations. METHODS: We used the national health insurance database and national health screening database. Seven quality indicators were used to evaluate continuity of care (medication possession ratio), process of care (hemoglobin A1c test, lipid profile, microalbuminuria test, and eye examination), and intermediate outcome (blood pressure control, and low-density lipoprotein control). Crude and age-standardized proportions were calculated for each 252 districts in Korea. RESULTS: All quality indicators failed to achieve the recommended level. Only about 3% and 15% of the patients underwent eye examination and microalbuminuria test, respectively. Other indicators ranged from 48% to 68%. Wide variation in the quality existed among districts and indicators. Eye examination and microalbuminuria test varied the most showing tenfold (0.9%-9.2%) and fourfold (6.3%-28.9%) variation by districts, respectively. There were 32.4 and 42.7 percentage point gap between the best and the worst districts in hemoglobin A1c test and blood pressure control, respectively. CONCLUSION: Considerable proportion of T2DM patients were not adequately managed and quality of care varied substantially district to district. To improve the quality of diabetes care, it is necessary to identify the poor performance areas and establish a well-coordinated care system tailored to the need of the district.

A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder.

In 1994 in the Journal of Cell Science, Hennekes and Nigg reported that changing valine to arginine at the endoproteolytic cleavage site in chicken prelamin A abolishes its conversion to lamin A. The consequences of this mutation in an organism have remained unknown. We now report that the corresponding mutation in a human subject leads to accumulation of prelamin A and causes a progeroid disorder. Next generation sequencing of the subject and her parents' exomes identified a de novo mutation in the lamin A/C gene (LMNA) that resulted in a leucine to arginine amino acid substitution at residue 647 in prelamin A. The subject's fibroblasts accumulated prelamin A, a farnesylated protein, which led to an increased percentage of cultured cells with morphologically abnormal nuclei. Treatment with a protein farnesyltransferase inhibitor improved abnormal nuclear morphology. This case demonstrates that accumulation of prelamin A, independent of the loss of function of ZMPSTE24 metallopeptidase that catalyzes processing of prelamin A, can cause a progeroid disorder and that a cell biology assay could be used in precision medicine to identify a potential therapy.

Comparison of cervical cancer screening among women with and without hysterectomies: a nationwide population-based study in Korea.

BACKGROUND: Cervical cancer screening is not recommended for women who underwent hysterectomy with no history of cervical intraepithelial neoplasia (CIN) of grade 2 or higher. We aimed to determine the cervical cancer screening rate in Korean women who underwent hysterectomies and compare it to that in women with intact uteri. METHODS: We used data from the 2014-2016 Korean National Cancer Screening Survey; 6807 women aged 30-74 years were included in the study. Participants were asked about their experiences with cervical cancer screening, hysterectomy status, and other variables associated with cancer screening. RESULTS: The screening rates among women who have undergone a hysterectomy vs. those who have not during the past 2 years were 61.8% (95% confidence interval [CI], 58.8-64.9) and 64.7% (95% CI, 64.1-65.3), respectively. Among younger women (30-44 years) and women with a family history of cancer, those with hysterectomies showed a higher cervical cancer screening rate than those without (77.8% vs. 57.1% and 75.0% vs. 67.1%, respectively). CONCLUSIONS: Despite available evidence and clinical recommendations, a considerable number of Korean women who no longer have a cervix continue to undergo unnecessary cervical cancer screening. It is necessary to identify the exact underlying causes for this phenomenon, and systematic efforts are required to prevent unnecessary screening for women who have undergone a hysterectomy.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review.

BACKGROUND: Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. CASE PRESENTATION: A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. CONCLUSION: Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study.

OBJECTIVES: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. METHODS: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. RESULTS: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31-41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7-21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27-37% were omalizumab-eligible and 18% were reslizumab-eligible. CONCLUSIONS: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Physical activity status by pain severity in patients with knee osteoarthritis: a nationwide study in Korea.

BACKGROUNDS: Few reports have explored the extent to which physical activity is affected by pain severity in knee osteoarthritis (KOA) patients. We used national representative data to investigate the physical activity of KOA patients compared to the general population to determine what proportion of patients met physical activity recommendations and to explore how the proportion changes with pain severity. METHODS: We used data from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V; 2010-2012). In total, 1279 participants aged ≥50 years who had radiographic KOA and who evaluated knee pain on a numerical rating scale were selected. KOA was assessed using the Kellgren-Lawrence system. The Korean short version of the International Physical Activity Questionnaire was used to measure physical activity status. We used the physical activity recommendations of the American College of Rheumatology Work Group Panel when evaluating the extent of activity in KOA patients. RESULTS: Only 18.6% of KOA patients met the osteoarthritis expert panel recommendations, lower than in the general population (23.2%; p = 0.003). The percentages that met the recommendations in the none to mild pain group, moderate pain group, and severe pain group were 23.4%, 17.6%, and 18.3%, respectively (p = 0.341). In terms of flexibility, a somewhat higher percentage of those with moderate pain engaged in physical activity compared to those with little or no pain (17.1% vs. 12.3%), but the difference was not significant (p = 0.585). CONCLUSIONS: Regardless of pain severity, overall physical activity was suboptimal in Korean KOA patients. It is important to emphasize to osteoarthritis patients in clinical settings the need for physical activity, and a policy-based effort is required to facilitate appropriate exercise.

More accurate correction can be obtained using a three-dimensional printed model in open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to compare the accuracy of the preoperative planning method using a three-dimensional (3D) printed model with that of a method using picture archiving and communication system (PACS) images in high tibial osteotomy (HTO). METHODS: Patients who underwent HTO using a 3D printed model (20 patients) and a method based on PACS images (20 patients) from 2012 to 2016 were compared. After obtaining the correction angle, in the 3D printed method, the wedge-shaped 3D printed model was designed. The PACS method used preoperative radiographs. The accuracy of HTO for each method was compared using radiographs obtained at the first postoperative year. The preoperative and postoperative posterior tibial slope angles were also compared. RESULTS: The weight-bearing line was corrected 21.2 ± 11.8% from preoperatively to 61.6 ± 3.3% postoperatively in the 3D group and from 19.4 ± 12.3% to 61.3 ± 8.1% in the PACS group. The mean absolute difference with the target point was lower in the 3D group (2.3 ± 2.5) than in the PACS group (6.2 ± 5.1; p = 0.005). The number of patients in an acceptable range was higher in the 3D group than in the PACS group. The posterior tibial slope angle was not significantly different in the 3D group (8.6°-8.9°), but was significantly different in the PACS group (9.9°-10.5°, p = 0.042). CONCLUSIONS: In open-wedge HTO, a more accurate correction for successful results could be obtained using the 3D printed model. LEVEL OF EVIDENCE: IV.

Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea, 2015.

From May through July 2015, a total of 26 cases of Middle East Respiratory Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1 index case and 25 new cases. We examined the epidemiologic features of these cases and found an estimated median incubation period of 6.1 days (8.8 days in hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in hospital A and 3.0% in hospital B), and the attack rates among inpatients and caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case-fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of cohort quarantine may have played a role in preventing community spread, but additional transmission occurred among members of the hospital cohort quarantined together. Caregivers may have contributed in part to the transmission.