UVC-Protective Activity of Lemongrass Among 12 Fat-soluble Herbal Extracts: Rapid Decay Due to Cytotoxicity.

BACKGROUND/AIM: The COVID-19 pandemic led to the rapid spread of the use of ultraviolet C (UVC) sterilizers in many public facilities. Considering the harmful effects of prolonged exposure to UVC, manufacturing of safe skin care products is an important countermeasure. In continuation of our recent study of water-soluble herbal extracts, the present study aimed at searching for anti-UVC components from fat-soluble herbal extracts. MATERIALS AND METHODS: Human dermal fibroblast and melanoma cells were exposed to UVC (1.193 W/m2) for 3 min. Viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell-cycle analysis was performed using a cell sorter. UVC-protective activity was quantified by the selective index (SI), i.e., the ratio of the 50% cytotoxic concentration for unirradiated cells to the concentration that restored viability of UVC-treated cells by 50%. RESULTS: Only lemongrass extract, among 12 fat-soluble herbal extracts, showed significant anti-UVC activity, comparable to that of lignified materials and tannins, but exceeding that of N-acetyl-L-cysteine and resveratrol. Lemongrass extract was highly cytotoxic, producing a subG1 cell population. During prolonged incubation in culture medium, the anti-UVC activity of lemongrass extract, sodium ascorbate and vanillic acid declined with an approximate half-life of <0.7, 5.4-21.6, and 27.8-87.0 h, respectively. CONCLUSION: Removal of cytotoxic principle(s) from lemongrass extract is crucial to producing long-lasting UVC-protective effects.

Association between Carotid Bifurcation Angle and Vulnerable Plaque Volume Using Black Blood Magnetic Resonance Imaging.

The morphology of the internal carotid artery (ICA) bifurcation is increasingly being recognized as the cause of atherosclerosis and vulnerable plaque leading to cerebral infarction. In this study, we investigated the relationship between carotid bifurcation angle and carotid plaque volume evaluated using black blood magnetic resonance imaging (BB-MRI). Among the 90 patients who underwent revascularization for atherosclerotic symptomatic carotid stenosis between April 2016 and October 2022 using BB-MRI, carotid plaque was evaluated in 57 patients. Relative overall signal intensity (roSI) was defined as the signal intensity of the plaque on T1-weighted images relative to the signal intensity of the sternocleidomastoid muscle in the same slice as the common carotid bifurcation. Regions showing roSI ≥ 1.0 were defined as plaque, and the plaque volume and relative plaque volume were measured from roSI ≥1.0 to ≥2.0 in 0.1 increments. We calculated the angles between the common carotid artery (CCA) and the ICA and between the CCA and the external carotid artery (ECA) on magnetic resonance angiography. We classified two groups according to carotid bifurcation angles based on the ICA angle: Group A = <35° and Group B = ≥35°. Compared with Group A (n = 42), Group B (n = 15) showed a greater relative plaque volume between roSI ≥ 1.3 and roSI ≥ 1.5. A significant correlation was identified between relative plaque volume with roSI ≥ 1.4 and ICA angle (p = 0.049). Vulnerable plaque was significantly more frequent in the group with an ICA angle of ≥35. Moreover, the ICA angle was significantly greater in patients with a roSI of ≥1.4.

Comprehensive Study of Anti-UVC Activity and Cytotoxicity of Hot-water Soluble Herb Extracts.

BACKGROUND/AIM: COVID-19 pandemic caused the rapid dissemination of ultraviolet C (UVC) sterilization apparatuses. Prolonged exposure to UVC, however, may exert harmful effects on the human body. The aim of the present study was to comprehensively investigate the anti-UVC activity of a total of 108 hot-water soluble herb extracts, using human dermal fibroblast and melanoma cell lines, for the future development of skin care products. MATERIALS AND METHODS: Exposure time to UVC was set to 3 min, and cell viability was determined using the MTT assay. Anti-UVC activity was determined using the selective index (SI), a ratio of 50% cytotoxic concentration for unirradiated cells to 50% effective concentration that restored half of the UVC-induced decrease of viability. RESULTS: Dermal fibroblasts at any population doubling level were more resistant to UVC irradiation than melanoma cells. Both 49 herb extracts recommended by Japan Medical Herb Association (JAMHA) and 59 additional herb extracts showed comparable anti-UVC activity. SI values of selected herbs (Butterbur, Cloves, Curry Tree, Evening Primrose, Rooibos, Stevia, Willow) were several-fold lower than those of vitamin C and vanillin. Their potent anti-UVC activity was maintained for at least 6 h post irradiation, but declined thereafter to the basal level, possibly due to cytotoxic ingredients. CONCLUSION: UVC sensitivity may be related to the growth potential of target cells. Removal of cytotoxic ingredients of herb extracts may further potentiate and prolong their anti-UVC activity.

Protonation states of Asp residues in the human Nudix hydrolase MTH1 contribute to its broad substrate recognition.

Human MutT homolog 1 (MTH1), also known as Nudix-type motif 1 (NUDT1), hydrolyzes 8-oxo-dGTP and 2-oxo-dATP with broad substrate recognition and has attracted attention in anticancer therapeutics. Previous studies on MTH1 have proposed that the exchange of the protonation state between Asp119 and Asp120 is essential for the broad substrate recognition of MTH1. To understand the relationship between protonation states and substrate binding, we determined the crystal structures of MTH1 at pH 7.7-9.7. With increasing pH, MTH1 gradually loses its substrate-binding ability, indicating that Asp119 is deprotonated at pH 8.0-9.1 in 8-oxo-dGTP recognition and Asp120 is deprotonated at pH 8.6-9.7 in 2-oxo-dATP recognition. These results confirm that MTH1 recognizes 8-oxo-dGTP and 2-oxo-dATP by exchanging the protonation state between Asp119 and Asp120 with higher pKa .

Clinical Presentation, Treatment, and Outcome of Nontraumatic Subarachnoid Hemorrhage in Patients with Preceding Antithrombotic Therapy.

With the aging of the population, the number of people taking antithrombotic drugs is increasing. Few reports have described the clinical presentation, treatment, and outcomes of nontraumatic subarachnoid hemorrhage (SAH) in patients with preceding antithrombotic therapy. This study included 459 patients with nontraumatic SAH who had been treated between April 2009 and May 2021. Overall, 39 of the 459 patients with aneurysmal SAH were on antithrombotic therapy before ictus (8.5%). Therefore, we classified patients into two groups: Group A (n = 39), patients with preceding antithrombotic therapy and Group B (n = 420), patients without preceding antithrombotic therapy. Hunt and Kosnik (H&K) grade on admission was significantly higher in Group A than in Group B (p = 0.02). Patients in Group A more frequently received endovascular treatment. The rate of endovascular therapy for symptomatic vasospasm after SAH was significantly lower in Group A (2.6%) than in Group B (15.5%; p = 0.03). The outcomes at 3 months after onset were significantly poorer in Group A patients than in Group B patients (p = 0.03). Patients with preceding antithrombotic drugs tended to be at greater risk of unfavorable outcomes, but this difference was not significant in the univariate analysis. In the multivariate analysis, patient age, H&K grade ≥4, and subdural hematoma remained as risk factors for poor outcomes; however, preceding use of antithrombotic drugs was not a significant risk factor.

Characteristics of risk factors for acute kidney injury among inpatients administered sulfamethoxazole/trimethoprim: a retrospective observational study.

BACKGROUND: Sulfamethoxazole/trimethoprim (SMX/TMP) potentially increases the serum creatinine levels, resulting in acute kidney injury (AKI). However, the clinical characteristics of the AKI associated with SMX/TMP and the risk factors for its development have not been fully characterized. METHODS: A retrospective cohort observational analysis was conducted on adult inpatients who started SMX/TMP treatment at the Tokyo Women's Medical University, Yachiyo Medical Center, from April 2018 to March 2020. The primary outcome was AKI, defined as an increase in serum creatinine level of ≥ 50% from baseline. Multivariate logistic regression analysis was used to determine the risk factors for the AKI associated with SMX/TMP. RESULTS: Of the 281 patients, 32 (11.4%) developed AKI. The multivariate logistic regression analysis identified that body mass index (BMI) (odds ratio [OR] = 0.86, 95% confidence interval [95% CI] 0.76-0.97, p < 0.01), presence of hypertension (OR = 2.69, 95% CI 1.11-6.49, p = 0.02), SMX/TMP daily dose (OR = 1.16, 95% CI 1.03-1.30, p = 0.02), and concomitant loop diuretic use (OR = 2.91, 95% CI 1.08-7.78, p = 0.04) were the associated risk factors for AKI in patients who were administered SMX/TMP. CONCLUSIONS: This study showed that low BMI, hypertension, high-dose SMX/TMP, and concomitant loop diuretic use increased the risk of AKI in patients administered SMX/TMP. Clinicians should consider monitoring the renal function in patients at a high risk of AKI.

Pulmonary Involvement in Microscopic Polyangiitis: Computed Tomography Findings in 55 Patients With Analysis of Risk Factors for Recurrence.

Background and objective Pulmonary involvement is seen in up to 30% of microscopic polyangiitis (MPA) patients. Pulmonary radiological findings for MPA have been scarcely reported to date. This study was conducted to evaluate computed tomography (CT) and clinical findings at the time of MPA diagnosis as predictors for systemic or lung recurrence. Methods We retrospectively reviewed the medical records and radiological data of 55 MPA patients with pulmonary involvement who were admitted to our hospital between April 2008 and December 2016. Results Aside from pulmonary lesions, lesions were found in the kidneys (52.7%), skin (7.3 %), and peripheral nerves (3.6%). Biopsies were performed for 29.1% of the patients, with an overall diagnostic accuracy of 78.9%. Parenchymal opacities (74.5%, mainly ground-glass opacities and reticular shadowing) were more commonly seen than airway abnormalities were (40.0%, mainly bronchiectasis). Systemic recurrence in the first year after diagnosis was found in 10.9% of the patients, and it mainly involved the kidneys or lungs. A serum WBC count ≥ 10,900/µL was a risk factor for predicting systemic recurrence within the first year after diagnosis according to the Cox regression analysis (HR 11.1, 95%CI: 1.3-95.9, p=0.028). Lung recurrence within five years after the diagnosis was observed in 9.1% of the patients. The incidences of reticular shadowing and honeycombing in thoracic CT at diagnosis were significantly higher in recurrence-positive patients than in recurrence-negative patients, but these differences could not be used to predict lung recurrence. Conclusions Ground glass opacities, reticular shadowing, and bronchiectasis are prominent thoracic CT findings for MPA. There are no radiological patterns capable of predicting recurrence. However, a serum WBC count ≥ 10,900/µL at diagnosis might be a predictive factor for systemic recurrence within the year.

Clinical predictors of nephrotoxicity associated with teicoplanin: Meta-analysis and meta-regression.

Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0-13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0-15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0-12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = -17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.

A meta-analysis of observational studies on anticholinergic burden and fracture risk: evaluation of conventional burden scales.

BACKGROUND: Anticholinergic burden potentially increases the risk of fracture. Although there are various anticholinergic burden scales, little is known about the inter-scale compatibility regarding the relationship of anticholinergic burden with fracture risk. We performed meta-analysis to examine the association of fracture risk with anticholinergic burden measured using various scales. METHODS: Primary literature was retrieved from PubMed (1966 to March, 2021), the Cochrane Library (1974 to March, 2021), Scopus (1970 to March, 2021), and Ichushi-web (1983 to March, 2021). Cohort and case-control studies that evaluated the association between any fracture and anticholinergic drugs were included. Additionally, we included studies in which patients were administered anticholinergic drugs included on the anticholinergic risk scale (ARS), anticholinergic cognitive burden (ACB), anticholinergic drug scale, or drug burden index-anticholinergic component. Random effects models were used to calculate pooled relative risk (RR) and 95% confidence interval (CI) due to heterogeneity among the studies. Publication bias was examined by funnel plots and the Begg's test. RESULTS: A total of 49 datasets from 10 studies were included in the meta-analysis. Six of the 10 studies included only patients aged over 65 years, who accounted for 93% of the total study population (453,186/487,247). Meta-analysis indicated a positive relationship between use of anticholinergic drugs and fracture risk, regardless of the anticholinergic burden scale used. However, the relationship between anticholinergic burden and fracture risk varied depending on the scale used. Fracture risk increased linearly with increasing anticholinergic burden measured using ARS. ARS 1 point was associated with 28% increase in fracture risk, ARS 1-2 point(s) with 39%, ARS 2 points with 54%, ARS 3 points with 66%, and ARS ≥ 4 points with 77%. On the other hand, ACB 1 point and ACB 2 points were associated with similar fracture risk (pooled RR [95% CI]: overall; 1.28 [1.18-1.39], 1 point; 1.12 [1.06-1.18], 2 points; 1.15 [1.08-1.23]). CONCLUSIONS: This result suggests that the relationship between anticholinergic drug burden and fracture risk may differ depending on the anticholinergic burden scale used.

Utility of B-Mode, Color Doppler and Elastography in the Diagnosis of Breast Cancer: Results of the CD-CONFIRM Multicenter Study of 1351 Breast Solid Masses.

The usefulness of color Doppler ultrasound (CD) in distinguishing between benign and malignant breast lesions remains controversial. Our prior study, the Japan Association of Breast and Thyroid Sonology (JABTS) BC-04 study (malignant: 839, benign: 569), found CD was useful in breast cancer diagnosis, and we developed CD diagnostic criteria. The first aim of the current study (the CD-CONFIRM study) was to evaluate the usefulness of the CD diagnostic criteria. The second aim was to evaluate the relationship between CD and elastography. We evaluated ultrasound images of breast masses from 13 institutions (malignant: 639, benign: 712). While the sensitivity of B-mode alone was very high and was not significantly improved with CD, the specificity was significantly improved with CD (61.2%-69.2%, p < 0.0001). Furthermore, the specificity of the combination of B-mode and CD improved significantly with the addition of elastography (72.8%-79.0%, p < 0.0001). This study found that the CD criteria are useful, and CD and elastography are independent.

Effects of walking with a "draw-in maneuver" on the knee adduction moment and hip muscle activity.

[Purpose] To investigate the effect of performing a draw-in maneuver (DI) on knee adduction moment (KAM) and hip and trunk muscle activities while walking. [Participants and Methods] We included 30 healthy young adults (21.5 ± 0.6 years, 16 males and 14 females) in this study. We measured the KAM and lever arm while participants walked with either a normal gait or a DI gait. We also performed surface electromyography (EMG) of the hip and trunk muscles (i.e., internal oblique abdominal muscle [IO], external oblique abdominal muscle [EO], multifidus muscle [MF], and gluteus medius muscle [GM]). [Results] The 1st peak of the KAM was significantly lower when walking with a DI gait compared to when walking with a normal gait. The integrated EMG activity of the IO, EO, and GM during the 1st half of the stance phase, and of the IO and EO during the 2nd half of the stance phase was significantly higher during the DI than during normal gait. [Conclusion] Compared with a normal gait, a DI gait leads to a decrease in the 1st peak of the KAM as a result of the shorter lever arm, and an increase in the muscular activity of the GM, IO, and EO.

A simple method for discrimination of carcinomatous meningitis using CEA, total protein, and total cell count in the cerebrospinal fluid of primary lung cancer patients.

ABSTRACT: Carcinomatous meningitis (CM) is a critical issue for physicians. However, no study has reported a simple and useful diagnostic or predictive marker for CM.This study aimed to elucidate the potential markers for diagnosing CM derived from cerebrospinal fluid (CSF).We retrospectively enrolled 78 lung cancer patients with suspected CM during the clinical course, including 42 CM and 36 non-CM patients. We compared the clinical and CSF findings, including carcinoembryonic antigen (CEA), between CM and non-CM patients, and explored the diagnostic markers for early identification of CM as well as the contributing factors for mortality.On CSF analysis, with cutoff values of CEA ≥5 ng/ml, total protein (TP) in CSF ≥45 g/dl, and total cell count (TCC) ≥7 cells/µL, the sensitivity, specificity, and area under the curve (AUC) for CM were 85.7%, 84.6%, and 0.887 (95% CI: 0.758-1.0, P < .001); 80.5%, 69.4%, and 0.755 (95% CI: 0.646-0.865, P < .001); and 56.1%, 100%, and 0.817 (95% CI: 0.722-0.912, P < .001), respectively. TP levels in CSF ≥the patients' age had a sensitivity, specificity, and an AUC of 48.8%, 77.8%, and 0.633 (95% CI: 0.722-0.912, P = .045) for CM, respectively. Among CM patients, patients with 'TP in CSF (>patients' age)" (n = 19, P = .008) showed significantly shorter 90-day survival probability than the residual patients (n = 20). None of the CSF parameters could predict the risk of mortality on Cox regression analysis.The cutoff value of CEA ≥5 ng/ml in CSF is a simple and useful method with a high diagnostic value for CM diagnosis, but not a suitable predicting factor for mortality. 'TP in CSF >patients' age" might be a novel factor for assessing short-term mortality.

Effectiveness of Transvenous Aspiration Thrombectomy for Cerebral Venous Sinus Thrombosis: A Report of Three Cases.

Objective: We report three patients successfully treated by emergent transvenous thrombectomy for cerebral venous sinus thrombosis (CVST). Case Presentation: (Case 1) A 77-year-old man presented with vomiting, dizziness, and headache. CT revealed local subarachnoid hemorrhage (l-SAH), and angiography confirmed occlusion of the right transverse sigmoid sinus and superior sagittal sinus (SSS). Emergent transvenous aspiration thrombectomy using a Penumbra catheter (PC) resulted in effective reperfusion. (Case 2) A 60-year-old man developed disorientation, sensory aphasia, and right hemiparesis. MRI demonstrated extensive cerebral edema caused by venous congestion in both thalami, and angiography revealed poor opacification of the SSS, straight sinus, and bilateral transverse sinuses. Venous sinus flow was restored by catheter aspiration using a PC and topical infusion of urokinase (UK). (Case 3) A 19-year-old man developed a headache, numbness of the right upper limb, motor paralysis, and convulsions. CT revealed l-SAH and dense clot sign in the SSS. The SSS was poorly delineated on angiography. Thrombus aspiration using a PC and topical UK administration achieved partial recanalization. Conclusion: Transvenous aspiration thrombectomy using large lumen catheters for patients with CVST is effective and safe. In particular, this method may be a better option than anti-coagulation therapy alone for patients presenting with a severe neurological condition or intracranial hemorrhage.

Anticholinergic and Sedative Drug Burden and Functional Recovery after Cerebrovascular Accident: A Retrospective Descriptive Study.

OBJECTIVES: Medications with anticholinergic or sedative effects induce impaired cognitive and physical performances. The aim of this study was to evaluate the associations of anticholinergic and sedative drug burden with recovery of physical function and activities of daily living in patients admitted to a Japanese rehabilitation hospital after cerebrovascular accidents. METHODS: We retrospectively reviewed the medical records of patients aged 18 years or older who had undergone the inpatient rehabilitation program for cerebrovascular disease in Nerima Ken-ikukai Hospital. Patients who did not complete the rehabilitation program because of acute unexpected changes of physical or psychological condition or the need for surgical procedures were excluded. The primary outcome was recovery of activities of daily living as measured by the motor and cognitive subscores of the Functional Independence Measure. The secondary outcome was recovery of physical function as assessed by the 10-m walk test and the Berg balance scale. Multiple Cox proportional hazard regression analyses were conducted to calculate hazard ratios with 95% confidence intervals for the outcome measures. RESULTS: Of 122 patients included in the study, 81 (66%) were exposed to anticholinergics and sedatives. Patients' age, body mass index, and average daily drug burden during hospitalization were independently associated with achieving the cutoff Functional Independence Measure-motor subscore. Patients' age and average daily drug burden during hospitalization were independently associated with achieving the Berg balance scale cut-off score. CONCLUSIONS: Our study of Japanese patients who were transferred from acute stroke care hospitals to a rehabilitation facility identified the drug burden of anticholinergics and sedatives as an independent factor associated with the time to recovery of activities of daily living and postural balance.

Biological Properties of the Aggregated Form of Chitosan Magnetic Nanoparticle.

BACKGROUND/AIM: Chitosan-coated iron oxide nanoparticles (Chi-NP) have gained attention because of their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. In this study, we investigated various biological properties of Chi-NP. MATERIALS AND METHODS: Chi-NP was prepared by mixing magnetic NP with chitosan FL-80. Particle size was determined by scanning and transmission electron microscopes, cell viability by MTT assay, cell cycle distribution by cell sorter, synergism with anticancer drugs by combination index, PGE2 production in human gingival fibroblast was assayed by ELISA. RESULTS: The synthetic process of Chi-NP from FL-80 and magnetic NP increased the affinity to cells, up to the level attained by nanofibers. Upon contact with the culture medium, Chi-NP instantly formed aggregates and interfered with intracellular uptake. Aggregated Chi-NP did not show cytotoxicity, synergism with anticancer drugs, induce apoptosis (accumulation of subG1 cell population), protect the cells from X-ray-induced damage, nor affected both basal and IL-1ß-induced PGE2 production. CONCLUSION: Chi-NP is biologically inert and shows high affinity to cells, further confirming its superiority as a scaffold for drug delivery.

Augmentation of Neurotoxicity of Anticancer Drugs by X-Ray Irradiation.

BACKGROUND: In order to investigate the combination effect of anticancer drugs and X-ray irradiation on neurotoxic side-effects (neurotoxicity), a method that provides homogeneously X-ray-irradiated cells was newly established. MATERIALS AND METHODS: PC12 cell suspension was irradiated by X-ray (0.5 Gy) in serum-supplemented medium, immediately inoculated into 96-microwell plates and incubated overnight. The medium was replaced with fresh serum-depleted medium containing 50 ng/ml nerve growth factor to induce differentiation toward nerve-like cells with characteristic neurites according to the overlay method without changing the medium. The differentiated cells were treated by anticancer drugs as well as antioxidants, oxaliplatin or bortezomib, and the viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS: Antioxidants and anticancer drugs were cytotoxic to differentiating PC12 cells. Combination of anticancer drugs and X-ray irradiation slightly reduced cell viability. CONCLUSION: The present 'population irradiation method' may be useful for the investigation of the combination effect of X-ray irradiation and any pharmaceutical drug.

Relationship between Recurrent Falls and Medication Use during Acute-Care Hospitalization: A Retrospective Descriptive Study.

Although recurrent falls during hospitalization lead to discharge to nursing homes, their association with medications has not been comprehensively assessed. We aimed to assess risk factors for recurrent falls focusing on medications during hospitalization in an acute-care setting. This retrospective descriptive study was conducted in Tokyo Women's Medical University, Medical Center East. Patients who experienced a fall during hospitalization were included and the incidence of recurrent falls was assessed during hospitalization. Multivariate logistic regression analysis was performed to assess the relationship between recurrent falls and medications and to calculate odds ratio and 95% confidence interval. Sensitivity analysis was performed on data stratified by sex or age. This study included 124 patients with an incidence of 20 (16%) recurrent falls. Multivariate logistic regression analysis revealed that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with recurrent falls (odds ratio = 5.98, 95% confidence interval: 1.38-25.9, p = 0.02). Additionally, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were significant risk factors for recurrent falls in women and those aged > 80 years. Selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants were associated with an increased risk of recurrent falls during hospitalization in an acute-care setting. Clinicians should pay attention to patients receiving selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants, especially women and aged > 80 years old.

[Association between Elimination Half-life of Benzodiazepines and Falls in the Elderly: A Meta-analysis of Observational Studies].

Benzodiazepine receptor agonists (BZDRAs) have been associated with an increased risk of falls in the elderly. However, the association between the elimination half-life (t1/2) of BZDRAs and the difference between benzodiazepines (BZDs) and non-benzodiazepines (Z-drugs) has not been clarified. By conducting a meta-analysis of observational studies, we compared the risk of falls with respect to 1) short-acting BZDRAs (t1/2<12 h) vs. long-acting BZDRAs (t1/2≥12 h) and 2) BZDs vs. Z-drugs in elderly patients. Data were retrieved from MEDLINE, the Cochrane Library, and Igaku Chuo Zasshi. In total, 13 observational studies from 12 articles were included in our study (short-acting BZDRAs, n=12; long-acting BZDRAs, n=9; BZDs, n=13; Z-drugs, n=7). The risk of falls was significantly increased by the use of short-acting BZDRAs [Odds ratio (OR) (95% Confidence interval (CI)): 2.00 (1.46-2.73)], long-acting BZDRAs [OR (95%CI): 2.16 (1.61-2.89)], BZDs [OR (95%CI): 1.67 (1.31-2.13)], and Z-drugs [OR (95%CI): 2.42 (1.35-4.34)] compared to the risk in BZDRAs non-users. The increased risk of falls in elderly patients was similar in each group and unrelated to t1/2. This study suggested that all BZDRAs including Z-drugs should be avoided in elderly patients.

Amelanotic Malignant Melanoma with Dense Pleural Thickening Mimicking Malignant Mesothelioma.

A 51-year-old man was diagnosed with stage IIC nodular malignant melanoma (T4bN0M0) of the right upper arm. The tumor was treatment-refractory, and left-sided pleural effusion emerged 1.5 years later. Aspiration of pleural fluid revealed abundant amelanotic, atypical cells that resembled epithelial malignant mesothelioma or lung adenocarcinoma cells; these cells were positive for melanoma-associated antigen recognized by T cells (MART-1)/Melan-A, HMB-45, and S-100 on immunocytochemistry. Thoracic computed tomography (CT) revealed marked diffuse pleural thickening in the left hemithorax that mimicked malignant mesothelioma; thus, the present report describes the unique cytological and radiological findings of this case.

Serum sST2 levels predict severe exacerbation of asthma.

BACKGROUND: Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. METHODS: This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. RESULTS: High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H2O2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /µl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. CONCLUSIONS: High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.