Objective
There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to ...verify the reliability and validity of the developed scale.
Methods
The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
Results
A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient ICC = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92).
Interpretation
CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352–358.
Flexible hybrid electronics (FHE), designed in wearable and implantable configurations, have enormous applications in advanced healthcare, rapid disease diagnostics, and persistent human-machine ...interfaces. Soft, contoured geometries and time-dynamic deformation of the targeted tissues require high flexibility and stretchability of the integrated bioelectronics. Recent progress in developing and engineering soft materials has provided a unique opportunity to design various types of mechanically compliant and deformable systems. Here, we summarize the required properties of soft materials and their characteristics for configuring sensing and substrate components in wearable and implantable devices and systems. Details of functionality and sensitivity of the recently developed FHE are discussed with the application areas in medicine, healthcare, and machine interactions. This review concludes with a discussion on limitations of current materials, key requirements for next generation materials, and new application areas.
Aim
To report our initial experience with robotic single‐port myomectomy (RSPM) using the da Vinci SP surgical system and to evaluate the feasibility of the procedure.
Material and Methods
This ...prospective observational study was performed at a university teaching hospital from January 2019 to December 2019. Sixty‐one women with symptomatic fibroids received RSPM.
Results
Based on seven resected fibroids and a maximal diameter of resected fibroids <10 cm, the women were arbitrarily divided into two groups. The mean number and maximal diameter of the removed fibroids were 3.7 ± 3.8 (2.3 ± 1.8 in Group 1 vs. 7.2 ± 5.3 in Group 2) and 7.6 ± 2.9 cm (6.8 ± 1.6 in Group 1 vs. 9.5 ± 4.3 in Group 2), respectively. The mean operation time, hemoglobin change, and hospital stay were 149.9 ± 72.9 min (123.8 ± 43.8 in Group 1 vs. 217.6 ± 89.4 in Group 2), 2.3 ± 1.0 g/dL (2.1 ± 0.9 in Group 1 vs. 2.7 ± 1.2 in Group 2), and 4.5 ± 0.8 days (4.4 ± 0.8 in Group 1 vs. 4.7 ± 0.9 in Group 2). There was no conversion to multi‐port laparoscopy or laparotomy nor were there any major complications.
Conclusions
RSPM using the da Vinci SP surgical system is feasible surgical modality for women with symptomatic fibroid and is expected to increase indications of single‐port myomectomy by solving many of the ergonomics problems inevitably accompanying single‐port laparoscopic myomectomy.
A highly stretchable, low-cost strain sensor was successfully prepared using an extremely cost-effective ionic liquid of ethylene glycol/sodium chloride. The hysteresis performance of the ...ionic-liquid-based sensor was able to be improved by introducing a wavy-shaped fluidic channel diminishing the hysteresis by the viscoelastic relaxation of elastomers. From the simulations on visco-hyperelastic behavior of the elastomeric channel, we demonstrated that the wavy structure can offer lower energy dissipation compared to a flat structure under a given deformation. The resistance response of the ionic-liquid-based wavy (ILBW) sensor was fairly deterministic with no hysteresis, and it was well-matched to the theoretically estimated curves. The ILBW sensors exhibited a low degree of hysteresis (0.15% at 250%), low overshoot (1.7% at 150% strain), and outstanding durability (3000 cycles at 300% strain). The ILBW sensor has excellent potential for use in precise and quantitative strain detections in various areas, such as human motion monitoring, healthcare, virtual reality, and smart clothes.
Background and Aims
Metabolic dysfunction‐associated fatty liver disease (MAFLD) encompasses heterogeneous fatty liver diseases associated with metabolic disorders. We aimed to evaluate the ...association between MAFLD and extrahepatic malignancies based on MAFLD subtypes.
Methods
This nationwide cohort study included 9 298 497 patients who participated in a health‐screening programme of the National Health Insurance Service of Korea in 2009. Patients were further classified into four subgroups: non‐MAFLD, diabetes mellitus (DM)‐MAFLD, overweight/obese‐MAFLD and lean‐MAFLD. The primary outcome was the development of any primary extrahepatic malignancy, while death, decompensated liver cirrhosis and liver transplantation were considered competing events. The secondary outcomes included all‐cause and extrahepatic malignancy‐related mortality.
Results
In total, 2 500 080 patients were diagnosed with MAFLD. During a median follow‐up of 10.3 years, 447 880 patients (6.0%) with extrahepatic malignancies were identified. The DM‐MAFLD (adjusted subdistribution hazard ratio aSHR = 1.13; 95% confidence interval CI = 1.11–1.14; p < .001) and the lean‐MAFLD (aSHR = 1.12; 95% CI = 1.10–1.14; p < .001) groups were associated with higher risks of extrahepatic malignancy than the non‐MAFLD group. However, the overweight/obese‐MAFLD group exhibited a similar risk of extrahepatic malignancy compared to the non‐MAFLD group (aSHR = 1.00; 95% CI = .99–1.00; p = .42). These findings were reproduced in several sensitivity analyses. The DM‐MAFLD was an independent risk factor for all‐cause mortality (adjusted hazard ratio aHR = 1.41; 95% CI = 1.40–1.43; p < .001) and extrahepatic malignancy‐related mortality (aHR = 1.20; 95% CI = 1.17–1.23; p < .001).
Conclusion
The diabetic or lean subtype of MAFLD was associated with a higher risk of extrahepatic malignancy than non‐MAFLD. As MAFLD comprises a heterogeneous population, appropriate risk stratification and management based on the MAFLD subtypes are required.
Abstract
Background
This study aimed to compare clinical and surgical outcomes of robotic single‐port hysterectomy (RSPH) using the da Vinci® SP surgical system and robotic multisite hysterectomy ...(RMSH) with the da Vinci Xi system in benign gynecologic disease.
Methods
The retrospective study included 134 patients who underwent RSPH or RMSH between November 2019 and December 2020. Total operation time, amount of blood loss, and the change in hemoglobin (Hb) after surgery and the weight of the removed uteri were also measured. Data on complications such as post‐operative fever and length of hospitalization were also compared and analyzed.
Results
There was no significant difference in the total operation time between the two groups, although the operation time was slightly longer in the RSPH group. Results in the RSPH group were superior to the RMSH group in docking time and wound incision time (1.67 ± 0.79 vs. 5.46 ± 2.25 min,
p
‐value <0.01; 6.48 ± 4.29 vs. 9.10 ± 4.64 min,
p
‐value <0.01, respectively). On the other hand, wound suture time took longer in the RSPH group (18.12 ± 5.66 vs. 10.69 ± 3.18 min,
p
‐value <0.01). The weights of the removed specimens were higher in the RMSH group (302.64 ± 190.56 vs. 369.24 ± 181.70 g,
p
‐value <0.04). The amount of blood loss during surgery and the difference in hemoglobin (Hb) before and after surgery were less in the RSPH group (97.39 ± 113.79 vs. 224.93 ± 152.29 mL,
p
‐value <0.01, 1.51 ± 1.08 vs. 2.54 ± 1.08 g/dL,
p
‐value <0.01). When considering the weight difference as a correction between the two surgical groups (because there were many heavier samples in the RMSH group), the blood loss of the RSPH group was also less than that of the RMSH group by 115.95 ± 23.78 mL (
p
‐value <0.01).
Conclusions
On the basis of our data, the robotic hysterectomy using the da Vinci SP surgical system might be feasible and safe, even if the hysterectomy is complex, and comparable to robotic multisite surgery by the da Vinci Xi system.
•Yuzu, wasabi, and rosemary were selected to inhibit the growth of microorganisms.•In optimal mixing conditions using RSM, yuzu juice was 3.92% (v/w).•Wasabi and rosemary extracts were 23.41% (v/w) ...and 3.93% (v/w), respectively.•The application of mixing antimicrobial agents was more effective than alone.
This study aimed to determine the antimicrobial effectiveness of natural antimicrobial agents (NAAs) (yuzu juice, wasabi extract, and rosemary extract) against three target microorganisms (TMs) (Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium) and to determine the optimal concentration of these agents using response surface methodology (RSM) to ensure the safety of meal kits manufactured using marinade sauce. The three NAAs added to marinade sauce effectively inactivated TMs (P<0.05), in particular, yuzu juice had the greatest antimicrobial effect against TMs, followed by wasabi and rosemary extracts. To determine the optimal concentration of NAAs using RSM, 17 concentrations were tested with three TMs as dependent variables and three NAAs as independent variables. The results showed that E. coli was not present under any of the conditions tested, whereas S. aureus and S. Typhimurium exhibited different characteristics depending on the conditions. Through response surface analysis of the TMs except for E. coli, which was not detected, it was determined that S. aureus had a coefficient of determination (R2) of 0.928 and a lack of fit of 0.074, and the linear regression of yuzu juice (X1) and quadratic regression of yuzu juice2 (X12) were both significant (P<0.05). S. Typhimurium had an R2 of 0.8955 and a lack of fit of 0.051, and only the quadratic regression of yuzu juice2 (X12) was significant (P<0.05). Based on RSM and ridge analysis, the optimal mixed conditions were determined to be 3.92% (v/w) yuzu juice, 23.41% (v/w) wasabi extract, and 3.93% (v/w) rosemary extract. After investigating the antimicrobial effect under the optimal conditions, E. coli and S. Typhimurium were absent, and S. aureus was reduced to 2.50 ± 0.09 log colony-forming units/g after 24 h. The results indicated that mixed treatment with the three NAAs had a more significant antimicrobial effect due to their synergistic properties compared to when used in isolation.
The outcome of status epilepticus (SE) largely varies depending on clinical characteristics. Risk stratification is necessary for tailoring the aggressiveness of treatment and predicting outcomes of ...individual patients with SE. In this study, we assessed differences in mortality, neurologic disability, and prognostic factors associated with SE across sociodemographic and clinical characteristics.
We conducted a nationwide population-based retrospective cohort study using the National Health Insurance Service (NHIS) database linked with the national death and disability registries. SE was identified from admission or emergency department visits using a diagnostic code of G41 from the
. Individuals with new-onset SE that occurred from January 1, 2010, to December 31, 2018, were included. Active epilepsy, refractoriness of SE, potential etiology, and comorbidities were ascertained by diagnostic codes and/or prescription records from the NHIS database as potential prognostic factors. Outcomes included 30-day and 1-year mortality and neurologic disabilities after SE. Prognostic factors for mortality were assessed by the Cox regression hazard model. We performed a subgroup analysis according to age: pediatric SE (age <20 years) and adult SE (age ≥20 years).
A total of 33,814 patients with new-onset SE were included (6,818 children/adolescents and 26,996 adults). The 30-day mortality was 8.5% (1.8% in pediatric SE and 10.2% in adult SE), and the 1-year mortality was 25.1% (4.6% in pediatric SE and 30.3% in adult SE). Overall, 10.7% of patients newly acquired neurologic disabilities after SE, with the highest incidence in children aged 5-9 years (21.3%). Intractable epilepsy developed in 0.8% of entire SE. Old age, presence of acute etiology, and refractoriness were poor prognostic factors for mortality in both pediatric and adult SE. Male sex, low economic status, no active epilepsy, and comorbidities were additional factors for a poor prognosis in adults.
New-onset SE was associated with substantial mortality and disability. Although SE-related mortality was higher in adults, disabilities developed more commonly in children and adolescents. The major determinants of mortality differed between pediatric and adult SE.
People with epilepsy (PWE) are at risk of premature death with considerable variability according to the study population. We aimed to estimate the risk and causes of death in PWE according to age, ...disease severity, disease course, comorbidities, and socioeconomic status in Korea.
We conducted a nationwide population-based retrospective cohort study using the National Health Insurance database linked with the national death register. Newly treated PWE from 2008 to 2016 who were identified by antiseizure medication (ASM) prescriptions and diagnostic codes for epilepsy/seizure were included and observed until 2017. We assessed all-cause and cause-specific crude mortality rates and standardized mortality ratios (SMRs).
Among 138,998 PWE, 20,095 deaths were identified, and the mean follow-up period was 4.79 years. The SMR was 2.25 in the overall group of PWE, with a higher value in the younger age group at diagnosis and a shorter time interval after diagnosis. The SMR in the monotherapy group was 1.56, while that in the group with 4 or more ASMs was 4.93. PWE without any comorbidities had an SMR of 1.61. PWE who were rural residents had a higher SMR than those who were urban residents (2.47 vs 2.03, respectively). The causes of death among PWE were cerebrovascular disease (18.9%, SMR 4.50), malignant neoplasms outside the CNS (15.7%, SMR 1.37), malignant neoplasms of the CNS (6.7%, SMR 46.95), pneumonia (6.0%, SMR 2.08), and external causes (7.2%, SMR 2.17), including suicide (2.6%, SMR 2.07). Epilepsy itself and status epilepticus accounted for 1.9% of the overall death. The excess mortality associated with pneumonia and external causes was persistently high, whereas the excess mortality associated with malignancy and cerebrovascular diseases tended to decrease with increasing time since diagnosis.
This study showed excess mortality in PWE, even in those without comorbidities and those receiving monotherapy. Regional disparities and sustained risks of deaths from external causes over 10 years imply potential points of intervention. In addition to active control of seizures, education about injury prevention, monitoring for suicidal ideation, and efforts to improve accessibility to epilepsy care are all required to reduce mortality.
As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ...ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).
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•A high-throughput screening of chemical libraries identifies several ANO6 inhibitors•SARS-CoV-2 Spike evokes ANO6-mediated phosphatidylserine scrambling in host cells•Phosphatidylserine scrambling promotes fusion of the viral and cell membranes•The identified ANO6 inhibitors inhibit SARS-CoV-2 viral replications
Sim et al. show that ANO6/TMEM16F-mediated phosphatidylserine scrambling participates in the SARS-CoV-2 entry into host cells and ANO6 inhibitors are effective against SARS-CoV-2 infection. These findings provide mechanistic insights into the viral entry process as well as a potential target for the development of drugs to treat COVID-19.
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