Epidemiological study using IgM and IgG antibody titers against SARS-CoV-2 in The University of Tokyo,Japan (UT-CATS)

IntroductionThe worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to date. Given that some of the patients with coronavirus disease 2019 (COVID-19) are asymptomatic, antibody tests are useful to determine whether there is a previous infection with SARS-CoV-2. In this study, we measured IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects in The University of Tokyo, Japan.MethodsFrom June 2020, we recruited participants, who were students, staff, and faculty members of The University of Tokyo in the project named The University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS). Following blood sample collection, participants were required to answer an online questionnaire about their social and health information. We measured IgG and IgM titers against SARS-CoV-2 using iFlash-SARS-CoV-2 IgM and IgG detection kit which applies a chemiluminescent immunoassay (CLIA) for the qualitative detection.ResultsThere were 6609 volunteers in this study. After setting the cutoff value at 10 AU/mL, 32 (0.48%) were positive for IgG and 16 (0.24%) for IgM. Of six participants with a history of COVID-19, five were positive for IgG, whereas all were negative for IgM. The median titer of IgG was 0.40 AU/mL and 0.39 AU/mL for IgM. Both IgG and IgM titers were affected by gender, age, smoking status, and comorbidities.ConclusionsPositive rates of IgG and IgM titers were relatively low in our university. Serum levels of these antibodies were affected by several factors, which might affect the clinical course of COVID-19.     

Epidemiological impact of universal varicella vaccination on consecutive emergency department visits for varicella and its economic impact among children in Kobe City,Japan

IntroductionPrevious studies reported a dramatic decline in the incidence of varicella and varicella-related deaths after implementing universal varicella vaccination (VarV). Although previous studies reported the effectiveness and economic impact of VarV, they were unknown in the emergency department (ED) setting.MethodsTo determine the effectiveness and economic impact of VarV in the ED, Kobe, Japan, we retrospectively reviewed the clinical database of consecutive patients younger than 16 years presenting to our primary ED from 2011 to 2019.ResultsOf the 265,191 children presenting to our ED, 3,092 patients were clinically diagnosed with varicella. The number of patients with varicella was approximately 500 annually, before introducing the universal two-dose VarV for children aged 1 to <3 years in October 2014, in the Japanese national immunization program, and decreased to approximately 200 in 2019. The number of patients with varicella younger than 1 year (ineligible for the vaccination) also decreased. Regarding the economic impact, the medical cost in our ED reduced after the introduction of VarV was JPY 4.1 million (US$ 40,049) annually. From the central data, approximately 95% of children were vaccinated after October 2014; however, a relatively large percentage of infected unvaccinated children (59.0%) presented to ED in this study. After the implementation of the universal VarV, infection was mainly observed in older children (i.e., the unvaccinated generation).ConclusionsOur data showed the effectiveness and economic impact of VarV in the ED setting. Additionally, our data suggested that the public vaccination program should include older unvaccinated children and other unvaccinated individuals.     

Safety of and antibody response to the BNT162b2 COVID-19 vaccine in adolescents and young adults with underlying disease

BackgroundData are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease.MethodsThis prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose.ResultsStudy participants were 429 patients (241 [56.2%] age 12–15 years; 188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL).ConclusionsVaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease.     

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan,Korea

BackgroundLong-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce.Material and MethodsThis retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period.ResultsOf the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990–1997 to 124.8 per 100,000 PYs in 2014–2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998–2005 to 49% in 2014–2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs.ConclusionThe incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.     

Long-term transition of antibody titers in healthcare workers following the first to fourth doses of mRNA COVID-19 vaccine: Comparison of two automated SARS-CoV-2 immunoassays

Anti-spike receptor binding domain (S-RBD) antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which best correlates with virus-neutralizing antibody is useful for estimating the period of protection and identifying the timing of additional booster doses. Long-term transition of the S-RBD antibody titer and the antibody responses among healthy individuals remain unclear. In the present study, therefore, we monitored the S-RBD antibody titers of 16 healthcare workers every 4 weeks for 76 weeks after vaccination with a fourth dose of mRNA-1273 (Moderna) following three doses of BNT162b2 (Pfizer/BioNTech) using two commercial automated immunoassays (Roche and Abbott). Two antibody responses to the vaccine were similar with an up-down change before and after the second (weeks 3), third (weeks 40) and fourth (week 72) vaccinations, but the titer did not fall below the assay's positivity threshold in any individual. The peak level of the geometric mean titer (GMT) in the Roche assay was highest after the third vaccination, and that in Abbott assay was highest after the fourth vaccination but almost equal to that after the third vaccination. Both the geometric mean fold rise (GMFR) demonstrated by the Roche and Abbott assays were highest after the third vaccination. Antibody titers determined by the Roche and Abbott assays showed a positive strong correlation (correlation coefficient: 0.70 to 0.99), but the ratio (Roche/Abbott) of antibodies demonstrated by both assays increased 0.46- to 8.26-fold between weeks 3 and 76. These findings will be helpful for clinicians when interpreting results for SARS-CoV-2 antibody levels and considering future vaccination strategies.     

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model

BackgroundTo mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine.MethodsThis prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3–13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance.ResultsA trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models).ConclusionThe findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.     

Non-pharmacological interventions for spasticity in adults: An overview of systematic reviews

ObjectivesSpasticity causes significant long-term disability-burden, requiring comprehensive management. This review evaluates evidence from published systematic reviews of clinical trials for effectiveness of non-pharmacological interventions for improved spasticity outcomes.MethodsData sources: a literature search was conducted using medical and health science electronic (MEDLINE, EMBASE, CINAHL, PubMed, and the Cochrane Library) databases for published systematic reviews up to 15th June 2017. Data extraction and synthesis: two reviewers applied inclusion criteria to select potential systematic reviews, independently extracted data for methodological quality using Assessment of Multiple Systematic Reviews (AMSTAR). Quality of evidence was critically appraised with Grades of Recommendation, Assessment, Development and Evaluation (GRADE).ResultsOverall 18 systematic reviews were evaluated for evidence for a range of non-pharmacological interventions currently used in managing spasticity in various neurological conditions. There is “moderate” evidence for electro-neuromuscular stimulation and acupuncture as an adjunct therapy to conventional routine care (pharmacological and rehabilitation) in persons following stroke. “Low” quality evidence for rehabilitation programs targeting spasticity (such as induced movement therapy, stretching, dynamic elbow-splinting, occupational therapy) in stroke and other neurological conditions; extracorporeal shock-wave therapy in brain injury; transcranial direct current stimulation in stroke; transcranial magnetic stimulation and transcutaneous electrical nerve stimulation for other neurological conditions; physical activity programs and repetitive magnetic stimulation in persons with MS, vibration therapy for SCI and stretching for other neurological condition. For other interventions, evidence was inconclusive.ConclusionsDespite the available range of non-pharmacological interventions for spasticity, there is lack of high-quality evidence for many modalities. Further research is needed to judge the effect with appropriate study designs, timing and intensity of modalities, and associate costs of these interventions.     

Rotavirus vaccination in Japan: Efficacy and safety of vaccines,changes in genotype,and surveillance efforts

In Japan, a monovalent rotavirus vaccine (RV1) and a pentavalent rotavirus vaccine (RV5) were launched as voluntary vaccinations in November 2011 and July 2012, respectively. Rotavirus (RV) vaccine coverage in Japan increased from 30.0% in 2012 to 78.4% in 2019. The number of RV gastroenteritis hospitalizations decreased after 2014 in Japan, and is expected to decrease further following the introduction of RV vaccines into the national immunization program in October 2020. The incidence rates of intussusception (IS) among children aged <1 year were 102.8 and 94.0 per 100,000 person-years in the pre-vaccine (2007–2011) and post-vaccine (2012–September 2014) eras, respectively. IS incidence did not increase following RV vaccine introduction in Japan. The efficacy and safety of RV vaccination were both documented in Japan. To reduce the risk of IS following RV vaccination, it is important that children receive a first dose of RV vaccine at age <15 weeks, preferably at age 2 months. Some strains that have emerged since RV vaccine introduction, such as DS-1-like G1P[8], eG3, and G8P[8], have spread nationwide. These three emerging genotypes did not affect the severity of the RV infection. Continuous city-level surveillance, using analysis of all 11 RV genome segments, is necessary to elucidate the genetic characteristics of prevalent RV strains. These efforts would also clarify the influence of vaccination on genetic changes of RV strains and the emergence of new genotypes.     

The prevalence and antimicrobial susceptibility of Streptococcus pneumoniae isolated from patients at Jikei University Hospitals after the implementation of the pneumococcal vaccination program in Japan

Studies have shown that pneumococcal vaccination reduces the incidence of Streptococcus pneumoniae infections but does not change the prevalence of S. pneumoniae nasopharyngeal colonization. To comprehensively and longitudinally assess the epidemiology of S. pneumoniae after the introduction of pneumococcal vaccination, we monitored the prevalence and antimicrobial susceptibility of S. pneumoniae, irrespective of its serotypes or pathogenicity, by analyzing specimens collected from a large number of patients at Jikei University Hospitals from 2009 to 2017. A total of 5763 S. pneumoniae isolates were identified out of 375,435 specimens from various sources of patients in different age groups. The prevalence of S. pneumoniae isolated only from patients <5 years old was significantly reduced with the widespread use of pneumococcal vaccines, although this reduction differed by areas where patients resided. The incidence of pneumococcal infections, including bacteremia and otitis media, clearly decreased among patients <5 years old after the introduction of pneumococcal vaccination, while the prevalence of S. pneumoniae isolated from blood specimens of patients 15–64 years old increased, suggesting the involvement of non-vaccine serotypes in the incidence of invasive pneumococcal infections. The antimicrobial susceptibility of S. pneumoniae improved after the introduction of pneumococcal vaccination. Our results show that pneumococcal vaccination has a suppressive effect on the prevalence of S. pneumoniae and the incidence of pneumococcal infections, at least for children <5 years old, in association with an improvement in the antimicrobial susceptibility of S. pneumoniae. However, further measures will be needed to control invasive pneumococcal infections caused by non-vaccine serotypes.     

Haemophilus influenzae type b capsular polysaccharide antibody levels in Japanese young patients with hematological malignancies and asplenia

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 μg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 μg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.     

Management of the Patient With Patent Foramen Ovale in 2021: A Spectrum of Cases

Patients with patent foramen ovale can manifest in a variety of ways. These presentations and their resolution are discussed in this article.     

Critically ill patients with COVID-19 in Tokyo,Japan: A single-center case series

IntroductionWe reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan.MethodsThis is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected.ResultsBetween February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure.ConclusionsAs in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.     

Trends in Metabolic Phenotypes According to Body Mass Index Among US Adults, 1999-2018

ObjectiveTo examine the prevalence, distribution, and temporal trends of metabolic phenotypes that are jointly determined by obesity and metabolic health status among US adults, overall and in key population subgroups.Participants and MethodsA nationally representative sample of civilian, noninstitutionalized US adults aged 20 years and older from the National Health and Nutrition Examination Survey between 1999-2000 and 2017-2018 were included. Metabolic phenotypes were characterized jointly by body mass index and metabolic health: metabolically healthy underweight, normal weight, overweight, and obese (MH-OB); and metabolically unhealthy underweight, normal weight, overweight, and obese (MU-OB). Metabolic health was defined using the 2009 joint scientific statement for metabolic syndrome from the International Diabetes Federation Task Force on Epidemiology and Prevention, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity as having 2 or less components (primary analysis) or no components (secondary analysis) of the following: waist circumference of 102 cm or greater in men and 88 cm or greater in women, fasting plasma glucose level of 100 mg/dL or greater, blood pressure of 130/85 mm Hg or greater, triglyceride level of 150 mg/dL or greater, and high-density lipoprotein cholesterol level of less than 40 mg/dL in men and less than 50 mg/dL in women.ResultsOf 19,941 adults, the mean age was 46.9 years; 10,005 (50.6%) were female. From 1999 to 2018, the prevalence in primary analysis declined from 33.2% (465465 of 1646) to 25.1% (454454 of 2058) (difference, ?8.09%; 95% CI, ?12.5% to ?3.70%) for metabolically healthy normal weight, whereas it increased from 9.92% (178178 of 1646) to 14.1% (277277 of 2058) (difference, 4.17%; 95% CI, 1.13% to 7.21%) for MH-OB (both P<.001 for trend). The prevalence of metabolically healthy underweight and overweight remained stable at about 1.62% (298298 of 19,94119,941) (95% CI, 1.38% to 1.89%; P=.34 for trend) and 22.2% (4,275 of 19,941) (95% CI, 21.4% to 23.0%; P=.14 for trend), respectively. The prevalence declined from 3.77% (72 of 1646) to 2.10% (68 of 2058) (difference, ?1.67%; 95% CI, ?3.22% to ?0.12%; P=.006 for trend) for metabolically unhealthy normal weight, whereas it increased from 19.0% (343 of 1646) to 26.4% (574 of 2058) (difference, 7.41%; 95% CI, 2.67% to 12.2%; P<.001 for trend) for MU-OB. The prevalence of metabolically unhealthy underweight and overweight remained stable at 0.06% (11 of 19,941) (95% CI, 0.03% to 0.15%; P=.84 for trend) and 11.2% (2528 of 19,941) (95% CI, 10.6% to 11.8%; P=.29 for trend), respectively. Persistent differences in the prevalence of metabolic phenotypes were identified across multiple sociodemographic subgroups. For example, the prevalence of MH-OB increased from 7.58% (53 of 754) to 12.0% (79 of 694) (P<.001 for trend) for non-Hispanic Whites and 12.2% (60 of 567) to 18.4% (76 of 493) for Hispanics (P=.01 for trend) and remained stable at 22.6% (756 of 3,825) for non-Hispanic Blacks (P=.62 for trend and P=.05 for interaction). Results in secondary analyses revealed similar patterns.ConclusionFrom 1999 to 2018, US adults experienced major increases in the prevalence of both MH-OB and MU-OB, largely due to decreases in MH-N. The prevalence of MU-OB increased across all subgroups, with higher values observed in older adults and those with lower education and income levels.     

The effects of an 8-week knitting program on osteoarthritis symptoms in elderly women: A pilot randomized controlled trial

BackgroundExercise therapy is effective in reducing symptoms and disability associated with hand osteoarthritis (HOA) but often has low adherence. An intervention consisting in a meaningful occupation, such as knitting, may improve adherence to treatment. This pilot randomized controlled trial (RCT) studied the adherence and clinical effectiveness of a knitting program in older females suffering from HOA to evaluate the acceptability of this intervention and assess the feasibility of a larger-scale RCT.MethodsSingle-blind, two-arm pilot RCT with a parallel group design with 37 participants (18 control, 19 intervention). Control participants were given an educational pamphlet and assigned to a waiting list. The knitting program (8-week duration) had two components: bi-weekly 20-min group knitting sessions and daily 20-min home knitting session on the 5 remaining weekdays. Measures included knitting adherence (implementation outcomes) as well as stiffness, pain, functional status, hand physical activity level, patient's global impression of change, health-related quality of life, self-efficacy, and grip strength (clinical outcomes measured throughout the 8-week program and 4 weeks after the intervention).ResultsOur protocol is feasible and the intervention was acceptable and enjoyable for participants, who showed high adherence. No difference was observed between the two groups for any of the clinical outcome measures (all p > .05).ConclusionKnitting is a safe and accessible activity for older women with HOA. However, our 8-week knitting program did not result in improvements in any of our outcome measures. Knitting for a longer period and/or with higher frequency may yield better outcomes.     

Comorbidities in Patients With End-Stage Knee OA: Prevalence and Effect on Physical Function

ObjectiveTo investigate the prevalence of comorbidities and their effect on physical function, quality of life (QOL), and pain, in patients with end-stage knee osteoarthritis (OA).DesignA cross-sectional study.SettingA rehabilitation facility at university hospital.ParticipantsPatients (N=577; 503 women and 74 men) diagnosed with end-stage knee OA between October 2013 and June 2018.InterventionNot applicable.Main Outcome MeasuresComorbidities were as follows: osteoporosis, presarcopenia, degenerative spine disease, diabetes, and hypertension. All patients completed the following performance-based physical function tests: stair-climbing test (SCT), 6-minute walk test (6MWT), timed Up and Go (TUG) test, and gait analysis. Self-reported physical function and pain were measured using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and a visual analog scale (VAS), respectively, and self-reported QOL was measured using EuroQoL 5 dimensions (EQ-5D) questionnaire.ResultsUnivariate analyses revealed that patients with osteoporosis had significantly higher scores in SCT ascent, SCT descent, TUG, WOMAC pain tests, and lower scores in 6MWT, gait speed, and cadence tests than those without osteoporosis. Patients with presarcopenia recorded higher scores in SCT ascent, TUG, EQ-5D, and lower scores in 6MWT and gait speed tests than those without presarcopenia. Patients with degenerative spine disease showed higher scores in WOMAC pain and lower scores in gait speeds than those without degenerative spine disease. Patients with diabetes showed higher scores in SCT ascent than those without diabetes, and patients with hypertension showed lower scores in 6MWT than those without hypertension. After adjusting age, sex, and body mass index, SCT descent retained significant association with osteoporosis, SCT ascent showed independent association with presarcopenia and diabetes, and WOMAC pain revealed significant association with degenerative spine disease.ConclusionThe results confirm associations between comorbidities, performance-based and self-reported physical functions, and QOL in patients with end-stage knee OA.     

Prevalence of antimicrobial resistant genes in Bacteroides spp. isolated in Oita Prefecture,Japan

IntroductionBacteroides spp. are the most common anaerobic bacteria isolated from the human gastrointestinal tract. Several resistant genes are present in Bacteroides spp. However, most studies have focused on the prevalence of the c?A gene in Bacteroides fragilis alone. We assessed the susceptibility to antimicrobial agents and the prevalence of cepA, cfiA, cfxA, ermF, nim, and tetQ genes in Bacteroides strains isolated from clinical specimens in our hospital.MethodsWe isolated 86 B. fragilis and 58 non-fragilis Bacteroides strains from human clinical specimens collected from January 2011 to November 2021. Resistance against piperacillin (PIPC), cefotaxime (CTX), cefepime (CFPM), meropenem (MEPM), clindamycin, and minocycline was determined.ResultsThe resistant rates of penicillins and cephalosporins in non-fragilis isolates were significantly higher than those in B. fragilis isolates. In B. fragilis isolates, the resistant rates of PIPC, CTX, and CFPM in cfxA-positive isolates were significantly higher than those in cfxA-negative isolates (71% vs. 16%, 77% vs. 19%, and 77% vs. 30%, respectively). Thirteen B. fragilis isolates harbored the cfiA gene, two of which were resistant to MEPM. Six of the 13 cfiA-positive B. fragilis isolates were heterogeneously resistant to MEPM.ConclusionIt is important to evaluate the use of MEPM as empirical therapy for Bacteroides spp. infections, considering the emergence of carbapenem resistance during treatment, existence of MEPM-resistant strains, and heterogeneous resistance.     

Risk factors and pathogen characteristics associated with unfavorable outcomes among adults with pneumococcal meningitis in Japan, 2006 to 2016

PurposeIn this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM).MethodsSurveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1–4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups.ResultsOverall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney diseases were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with unfavorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormal pbp genes (pbp1a, 2x, and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20.ConclusionsIn the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered.     

Daily practice and prognostic factors for pneumonia caused by methicillin-resistant Staphylococcus aureus in Japan: A multicenter prospective observational cohort study

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia.This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed.In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31–14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35–7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26–9.92) were risk factors for mortality.In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.     

Establishment and application of an immunoassay for the simultaneous detection of IgG and its subtype IgG4 autoantibodies against M-type phospholipase A2 receptor

BackgroundThe renal biopsy is an accurate and reliable gold standard for membranous nephropathy (MN) diagnosis. However, it is an invasive procedure involving the risk of hemorrhage or infection. Thus, an alternative approach that can facilitate the effective diagnosis and treatment monitoring of idiopathic membranous nephropathy (IMN) is urgently needed.MethodsWe established a dual-labeled time-resolved fluoroimmunoassay (TRFIA) to simultaneously detect phospholipase A2 receptor (PLA2R)-IgG4 and PLA2R-IgG antibodies. Utilizing this assay, we determined the ratio of autoantibodies in the serum of patients with different kidney diseases and normal controls.ResultsThe sensitivity of TRFIA for detecting anti-PLA2R-IgG and anti-PLA2R-IgG4 was 0.12 µg/mL and 0.001 µg/mL, respectively. Human IgA did not interfere with the assay. Compared to anti-PLA2R-IgG alone, the positive rate of IMN could be increased from 86.5 % to 91.7 % through the combined use of anti-PLA2R-IgG4 and the PLA2R-IgG4/IgG ratio. In contrast, the false-positive rates for the detection of IgA nephropathy, lupus nephropathy, diabetic nephropathy, and minimal change nephropathy decreased from 25 to 50 % to 0 %.ConclusionsThe dual-labeled PLA2R-IgG4/IgG-TRFIA for simultaneous detection of anti-PLA2R-IgG4 and anti-PLA2R-IgG will contribute to improved accuracy of IMN diagnosis.     

Effect of Resistance Exercise on Body Structure and Function,Activity, and Participation in Individuals With Parkinson Disease: A Systematic Review

ObjectiveTo investigate the effects of resistance exercise (RE) on body structure and function, activity, and participation in individuals with Parkinson Disease (PD) in the mild to moderate stages.Data SourcesMedline, Embase, Web of Science, The Cochrane Library, Lilacs, and PEDro were searched from inception until June 2020 using the terms “Parkinson Disease,” “Exercise,” “Resistance Training,” “Muscle Strength,” “Cardiorespiratory Fitness,” “Postural Balance,” “Gait,” and “Quality of Life.”Study SelectionWe included studies conducted in individuals with PD involving RE compared with a control group. Two independent reviewers performed the selection process based on titles, abstracts, and full-text reading. In total, 270 individuals with PD were included from 10 selected studies.Data extractionTwo reviewers independently extracted characteristics related to participants, intervention and control types, and results. The PEDro scale was used to assess the methodological quality, and the level of evidence was analyzed and synthesized using the Grading of Recommendation, Assessment, Development, and Evaluations approach.Data SynthesisThe level of evidence for body structure and function was low and without effect for lower limb muscle strength; very low and with effect for upper limb muscle strength, cardiorespiratory fitness, and postural balance; and very low and without effect for flexibility after RE training. For activity, the evidence was very low and with effect for gait and very low and without effect for mobility. For participation (ie, quality of life) the evidence was very low and without effect.ConclusionsAlthough the level of evidence was low to very low, RE was shown to promote improvements in body structure and function (upper limb muscle strength, cardiovascular function, postural balance) and activity (gait). In contrast, RE did not significantly improve participation (quality of life). However, based on the present findings, the practice of RE can be recommended for individuals with PD in the mild to moderate stages.