Short stature is an inflammatory disadvantage among middle-aged Japanese men.

OBJECTIVES: A positive association between white blood cell count and carotid atherosclerosis has been reported. Our previous study also found an inverse association between height and carotid atherosclerosis in overweight but not non-overweight men. However, no studies have reported on the association between high white blood cell (WBC) count and height accounting for body mass index (BMI) status. METHODS: We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30-59 years undergoing general health check-ups between April 2013 and March 2014. High WBC count was defined as the highest tertiles of WBC count among total subjects. RESULTS: Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for subjects with a BMI ≥ 23 kg/m2. The classical cardiovascular risk factors adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) of high WBC count for an increment of one standard deviation (SD) in height (5.7 cm) were 0.91 (0.83-0.99) for total subjects, 1.00 (0.86-1.15) for subjects with a BMI < 23 kg/m2 and 0.86 (0.77-0.96) for subjects with a BMI ≥ 23 kg/m2. CONCLUSION: Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for those with a BMI ≥ 23 kg/m2. Compared to high stature, short stature appears to convey an inflammatory disadvantage among Japanese men, especially those with a BMI ≥ 23 kg/m2.

Serum triglyceride levels in relation to high-density lipoprotein cholesterol (TG-HDL) ratios as an efficient tool to estimate the risk of sleep apnea syndrome in non-overweight Japanese men.

OBJECTIVES: Several studies have reported the association between sleep apnea syndrome and insulin resistance. Being overweight is known risk factor both for sleep apnea syndrome and insulin resistance. However, no studies have reported on the association between serum triglyceride levels in relation to high-density lipoprotein cholesterol (TG-HDL) ratios (a marker of insulin resistance) and sleep apnea syndrome accounting for body mass index (BMI) status. METHODS: Subjects for the present cross-sectional study consisted of 1,528 men aged 30-69 years undergoing pulse oximetry at a sleep disorders clinic for sleep apnea syndrome. Sleep apnea syndrome was diagnosed as a 3 % oxygen desaturation index (ODI) of ≥15 events/h. RESULTS: Among study participants, 241 men were diagnosed with sleep apnea syndrome. Independent of classical cardiovascular risk factors, TG-HDL was significantly positively associated with sleep apnea syndrome in participants with a BMI <25 kg/m2, but not in participants with a BMI ≥25 kg/m2. The multivariable adjusted odds ratio (OR) and 95 % confidence interval (95 % CI) of sleep apnea syndrome per Log TG-HDL was 2.03 (95 % CI: 1.36-3.03) for a BMI <25 kg/m2 and 1.23 (95 % CI: 0.89-1.70) for a BMI ≥25 kg/m2. CONCLUSIONS: An independent positive association between TG-HDL levels and risk of sleep apnea syndrome was observed in participants with a BMI of <25 kg/m2, but not in participants with a BMI ≥25 kg/m2. TG-HDL levels could be an efficient tool to estimate the risk of sleep apnea syndrome in non-overweight Japanese men.

Validation of sleep-staging accuracy for an in-home sleep electroencephalography device compared with simultaneous polysomnography in patients with obstructive sleep apnea.

Efforts to simplify standard polysomnography (PSG) in laboratories, especially for obstructive sleep apnea (OSA), and assess its agreement with portable electroencephalogram (EEG) devices are limited. We aimed to evaluate the agreement between a portable EEG device and type I PSG in patients with OSA and examine the EEG-based arousal index's ability to estimate apnea severity. We enrolled 77 Japanese patients with OSA who underwent simultaneous type I PSG and portable EEG monitoring. Combining pulse rate, oxygen saturation (SpO2), and EEG improved sleep staging accuracy. Bland-Altman plots, paired t-tests, and receiver operating characteristics curves were used to assess agreement and screening accuracy. Significant small biases were observed for total sleep time, sleep latency, awakening after falling asleep, sleep efficiency, N1, N2, and N3 rates, arousal index, and apnea indexes. All variables showed > 95% agreement in the Bland-Altman analysis, with interclass correlation coefficients of 0.761-0.982, indicating high inter-instrument validity. The EEG-based arousal index demonstrated sufficient power for screening AHI ≥ 15 and ≥ 30 and yielded promising results in predicting apnea severity. Portable EEG device showed strong agreement with type I PSG in patients with OSA. These suggest that patients with OSA may assess their condition at home.

Serological response to a third dose of SARS-CoV-2 vaccine according to previous infection history.

The IgG antibody titer against SARS-CoV-2 receptor binding protein (RBD) after mRNA vaccine were compared between those with and without previous infection (PI) for up to 48 weeks. Though sustained higher IgG-RBD were observed in the PI group after two doses of vaccines, both groups benefited from the booster shots of the third vaccine. This data supports the necessity of the booster shots to those with PI.

Multimodal Telemonitoring for Weight Reduction in Patients With Sleep Apnea: A Randomized Controlled Trial.

BACKGROUND: Telemonitoring the use of CPAP devices and remote feedback on device data effectively optimizes CPAP adherence in patients with OSA. RESEARCH QUESTION: Can expanding the scope of telemonitoring and remote feedback to body weight (BW), BP, and physical activity enhance efforts for BW reduction in Patients with OSA receiving CPAP? STUDY DESIGN AND METHODS: Participants were recruited from patients at 16 sleep centers in Japan with OSA and obesity who were receiving CPAP therapy. Obesity was defined as a BMI of ≥ 25 kg/m2, based on Japanese obesity guidelines. Implementation of CPAP telemonitoring was enhanced with electronic scales, BP monitors, and pedometers that could transmit data from devices wirelessly. Participants were randomized to the multimodal telemonitoring group or the usual CPAP telemonitoring group and were followed up for 6 months. Attending physicians provided monthly telephone feedback calls to the usual CPAP telemonitoring group on CPAP data obtained remotely. In the multimodal telemonitoring group, physicians additionally encouraged participants to reduce their BW, after sharing the remotely obtained data on BW, BP, and step count. The primary outcome was set as ≥ 3% BW reduction from baseline. RESULTS: One hundred sixty-eight participants (BMI, 31.7 ± 4.9 kg/m2) completed the study, and ≥ 3% BW reduction occurred in 33 of 84 participants (39.3%) and 21 of 84 participants (25.0%) in the multimodal telemonitoring and usual CPAP telemonitoring groups, respectively (P = .047). Whereas no significant differences were found between the two groups in the change in office and home BP, daily step counts during the study period were significantly higher in the multimodal telemonitoring group than in the usual CPAP telemonitoring group (4,767 steps/d [interquartile range (IQR), 2,864-6,617 steps/d] vs 3,592 steps/d [IQR, 2,117-5,383 steps/d]; P = .02) INTERPRETATION: Multimodal telemonitoring may enhance BW reduction efforts in patients with OSA and obesity. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000033607; URL: www.umin.ac.jp/ctr/index.htm.

A Randomized Controlled Trial of Telemedicine for Long-Term Sleep Apnea Continuous Positive Airway Pressure Management.

Rationale: The effects of telemedicine on adherence in patients with obstructive sleep apnea with long-term continuous positive airway pressure (CPAP) use have never been investigated.Objectives: To examine effects of a telemedicine intervention on adherence in long-term CPAP users.Methods: In a prospective, randomized, multicenter noninferiority trial conducted in 17 sleep centers across Japan, patients who had used CPAP for >3 months and were receiving face-to-face follow-up by physicians every 1 or 2 months were randomized by a coordinating center in a blind manner to the following three groups: 1) follow-up every 3 months accompanied by a monthly telemedicine intervention (telemedicine group: TM-group), 2) follow-up every 3 months (3-month group: 3M-group), or 3) monthly follow-up (1-month group: 1M-group). Each group was followed up for 6 months. The change in percentage of days with ≥4 h/night of CPAP use from baseline to the end of the study period was evaluated. A decline of ≥5% from baseline was considered deterioration of adherence. Noninferiority of TM- and 3M-groups compared with the 1M-group according to the number of patients with deterioration of adherence was evaluated with the Farrington and Manning test (noninferiority margin 15%).Results: A total of 483 patients were analyzed (median duration of CPAP use, 29 [interquartile range, 12-71] mo), and deterioration of adherence was found in 41 of 161 (25.5%), 55 of 166 (33.1%), and 35 of 156 (22.4%) patients in the TM-, 3M-, and 1M-groups, respectively. The noninferiority of the TM-group compared with the 1M-group was verified (difference in percentage of patients with adherence deterioration, 3.0%; 95% confidence interval [CI], -4.8% to 10.9%; P < 0.01). Conversely, the 3M-group did not show noninferiority to the 1M-group (percentage difference, 10.7%; 95% CI, 2.6% to 18.8%; P = 0.19). In the stratified analysis, adherence in TM- and 1M-group patients with poor adherence at baseline improved (TM: 45.8% ± 18.2% to 57.3% ± 24.4%; P < 0.01; 1M: 43.1% ± 18.5% to 53.6% ± 24.3%; P < 0.01), whereas that of the 3M-group did not (39.3% ± 20.8% to 39.8% ± 24.8%; P = 0.84).Conclusions: Intensive telemedicine support could help to optimize CPAP adherence even after long-term CPAP use.Clinical trial registered with www.umin.ac.jp/ctr/index.htm (trial number: UMIN000023118).

Adult community-acquired pneumonia caused by macrolide resistant Mycoplasma pneumoniae.

A 28-year-old woman with community-acquired pneumonia was treated with sulbactam/ampicillin and clarithromycin, but failed to show any improvement after 4 days. The antibiotic regimen was changed to pazufloxacin and rapid clinical improvement was seen. Mycoplasma pneumoniae was identified as the causative agent, and adenine (A) to guanine (G) mutation at position 2063 in domain V of the 23S rRNA was noted in the isolate. The minimum inhibitory concentration of macrolide antibiotics, including clarithromycin, of this isolate was greatly elevated.

Tacrolimus as a reinforcement therapy for a patient with MPO-ANCA-associated diffuse alveolar hemorrhage.

A 67-year-old woman, suffering from continuous hemoptysis, was admitted to our hospital where she was managed with mechanical ventilation. Computed tomography of the chest demonstrated bilateral massive alveolar hemorrhage without evidence of infectious disease. She was diagnosed with anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated diffuse alveolar hemorrhage because a high titer of MPO-ANCA was found in the serum. Plasmapheresis as well as methylprednisolone pulse therapy were initiated, followed by intravenous administration of cyclophosphamide. Tacrolimus was employed for the maintenance therapy, and the oral prednisolone dosage could successfully be tapered without recurrence, along with the decrement of the titer of MPO-ANCA.

Height correlates with dyslipidemia in non-overweight middle-aged Japanese men.

BACKGROUND: Our previous study showed that height is inversely associated with the risk of stroke in middle-aged Japanese men, particularly in those with a low body mass index (BMI). Since height is regarded as a surrogate maker of childhood social and physical condition, while BMI may reflect primarily on the current physical condition, a detailed analysis of those with a lower BMI may elucidate the effects of childhood conditions. On the other hand, dyslipidemia is recognized as a prominent risk factor for cardiovascular disease. However, no studies have reported on the association between height and dyslipidemia accounting for BMI status. METHODS: We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30-59 years. Dyslipidemia is defined by the Japan Atherosclerosis Society (JAS) Guidelines as follows: triglycerides (TG) ≥ 150 mg/dL and/or low-density lipoprotein-cholesterol (LDL) ≥ 140 mg/dL, and/or high-density lipoprotein-cholesterol (HDL) < 40 mg/dL, and/or lipid lowering medication use. RESULTS: Independent of classical cardiovascular risk factors, height was found to be inversely associated with dyslipidemia in subjects with a BMI <25 kg/m2 but not in subjects with a BMI ≥25 kg/m2. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of dyslipidemia for an increment of one standard deviation (SD) in height (5.7 cm) were 0.90 (0.82-0.99) for subjects with a BMI < 25 kg/m2 and 1.02 (0.89-1.17) for subjects with a BMI ≥ 25 kg/m2. CONCLUSION: Height is inversely associated with dyslipidemia in those with a BMI < 25 kg/m2 but not with a BMI ≥ 25 kg/m2.

Decreased serum opsonic activity against Streptococcus pneumoniae in human immunodeficiency virus-infected Ugandan adults.

Type-specific immunoglobulin G (IgG) to pneumococcal capsular polysaccharide (CPS) and opsonic activity against Streptococcus pneumoniae were evaluated in serum samples from 36 Ugandan adults with community-acquired pneumonia and 58 asymptomatic Ugandan adults with or without human immunodeficiency virus type 1 (HIV-1) infection. The levels of serum IgG to CPS were significantly higher in HIV-1-infected subjects than in HIV-uninfected subjects. Serum samples from HIV-1-infected subjects that had lower IgG titers demonstrated higher opsonic activity against type 3 (titers of 7) and type 9 (titers of 7-11) pneumococcal strains. Plasma HIV-1 load also correlated inversely with serum opsonic activity against these strains, and peripheral blood CD4+ lymphocyte numbers also tended to correlate with serum opsonic activity in asymptomatic HIV-1-infected adults. Our findings suggest that the opsonic activity of type-specific IgG is impaired in the serum of HIV-1-infected African adults, which may expose them to a serious risk of invasive pneumococcal infections.

Vaccine effectiveness against medically attended laboratory-confirmed influenza in Japan, 2011-2012 Season.

The objective of this study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza during the 2011-2012 season in Japan using a test-negative case-control study design. The effect of co-circulating non-influenza respiratory viruses (NIRVs) on VE estimates was also explored. Nasopharyngeal swab samples were collected from outpatients with influenza-like illnesses (ILIs) in a community hospital in Nagasaki, Japan. Thirteen respiratory viruses (RVs), including influenza A and B, were identified from the samples using a multiplex polymerase chain reaction. The difference in VE point estimates was assessed using three different controls: ILI patients that tested negative for influenza, those that tested negative for all RVs, and those that tested positive for NIRVs. The adjusted VE against medically attended, laboratory-confirmed influenza using all influenza-negative controls was 5.3% (95% confidence interval [CI], -60.5 to 44.1). The adjusted VEs using RV-negative and NIRV-positive controls were -1.5% (95% CI, -74.7 to 41) and 50% (95% CI, -43.2 to 82.5), respectively. Influenza VE was limited in Japan during the 2011-2012 season. Although the evidence is not conclusive, co-circulating NIRVs may affect influenza VE estimates in test-negative case-control studies.

Estimating the influenza vaccine effectiveness against medically attended influenza in clinical settings: a hospital-based case-control study with a rapid diagnostic test in Japan.

BACKGROUND: Influenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting. METHODS: A prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records. RESULTS: Between December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures. CONCLUSION: The test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.

Feasibility trial of adjuvant chemotherapy with paclitaxel and carboplatin after surgical resection in Japanese patients with non-small cell lung cancer: report of the Lung Oncology Group in Kyushu (LOGIK) protocol 0501.

OBJECTIVES: The present study was designed to determine whether adjuvant chemotherapy with paclitaxel (TXL) and carboplatin (CBDCA) after surgical resection is feasible in Japanese patients with non-small cell lung cancer (NSCLC) in a multiinstitutional trial. METHODS: From August 2005 to March 2006, 34 patients received the following regimen: TXL (175 mg/m2) and CBDCA (AUC = 5) on day 1, every 3 weeks. The primary endpoint of this trial was the completion rate of four cycles. RESULTS: The completion rate of four cycles was 79.4% [90% confidence interval (CI), 67.5%-91.3%]. Perfect completion rate of four cycles on schedule and full doses without delay was 50% (90% CI, 34.9%-65.1%). The reasons for incomplete cycles were hypersensitivity to TXL infusion during the first cycle in 3 patients, patients refusal in 2, and anemia and cerebral infarction in 1 patient each. As a consequence of delay and/or dose reductions, the relative dose intensity of TXL and CBDCA was 86.2% and 85.8%, respectively. CONCLUSION: Doublet chemotherapy with TXL and CBDCA in the planned doses and schedule was found to be a feasible treatment for Japanese patients following surgical resection for NSCLC:

Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults.

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4(+) cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and 26.7-42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy.

Norepinephrine inhibits human immunodeficiency virus type-1 infection through the NF-kappaB inactivation.

Exercise or acute stress can exert significant effects on immune system as well as cardiovascular and respiratory systems through catecholamines. In this study, we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays, NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF-kappaB-binding sites or cotreatment with H89 (a protein kinase A inhibitor) abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF-kappaB activity in NE-treated cells. NE increased cytoplasmic levels of IkappaB-alpha, a natural inhibitor of NF-kappaB. Thus, NE apparently inhibits HIV-1 infection, at least in part through NF-kappaB inactivation.

Significant reduction of nosocomial pneumonia after introduction of disinfection of upper airways using povidone-iodine in geriatric wards.

We investigated the efficacy of disinfection of the upper airway using povidone-iodine against nosocomial pneumonia in geriatric wards. Cases of nosocomial pneumonia were retrospectively analyzed between January 1991 and March 1995 in geriatric wards (190 beds). Moreover, the relationship concerning methicillin-resistant Staphylococcus aureus (MRSA) isolates between patient and environment was investigated using pulsed-field gel electrophoresis (PFGE) with the SmaI restriction enzyme. The incidence of nosocomial pneumonia decreased significantly (p < 0.05). Major causative organisms of nosocomial pneumonia were MRSA and Pseudomonas aeruginosa, which significantly decreased. PFGE studies showed that the patterns of MRSA isolates show a strong association between patient and environment. Our study indicates that disinfection of the upper airways by povidone-iodine is very important in the prevention of nosocomial pneumonia in geriatric wards.

Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan.

BACKGROUND: A high frequency of drug-resistant pneumococci has been reported in Asian countries. Few data on the drug-resistance or serotype of pneumococcal strains responsible for community-acquired pneumonia (CAP), however, are available for the past two decades in Japan. METHODOLOGY: Susceptibility to antibiotics and the genotype of antibiotic-resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003. RESULTS: Most of the cases were non-bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide-resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23-valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted. CONCLUSION: A high frequency of altered pbp gene mutations or of macrolide-related genes and a high serotype coverage by the 23-valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23-valent PPV in adults older than 65 years in Japan.

Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages.

An inflammation of the airway of patients with diffuse panbronchiolitis (DPB), is characterized by dense neutrophil infiltration. Resolution of the inflammation can be achieved by the removal of apoptotic neutrophils by human alveolar macrophages (AM) without liberating neutrophil proteases in the airway. To understand clinical efficacy for the treatment of DPB by 14- or 15-member macrolides, their effects on the phagocytosis of apoptotic neutrophils by AM were examined. Treatment of AM with erythromycin (ERY) or clarithromycin at clinically achievable levels significantly increased the levels of phagocytosis of apoptotic neutrophils. A serum factor was not essential for the enhancement by these 14-member macrolides. Of the antibiotics tested, these effects were specific for the 14-member macrolides and a 15-member macrolide, azithromycin, but not for the 16-member macrolides, clindamycin or beta-lactam antibiotics. The enhanced phagocytosis of apoptotic neutrophils by ERY had no effect on the levels of interleukin-8 or tumor necrosis factor alpha production by lipopolysaccharide-stimulated AM after phagocytosis of the apoptotic neutrophils. The increased phagocytosis of apoptotic neutrophils by ERY was also found to be phosphatidylserine receptor-dependent for AM. These data indicate a novel anti-inflammatory action of 14-member and 15-member macrolides, and suggest that such antibiotics achieve clinical efficacy for patients with DPB, in part, through enhancing the nonphlogistic phagocytosis of apoptotic neutrophils by AM.