Clinical characteristics and cytokine profiles of adult obese asthma with type2 inflammation.

Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4-5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma.

First Report of Klebsiella subsp. Ozaenae Meningitis in Japan.

Although the frequency of community-acquired infections caused by Klebsiella pneumoniae subsp. ozaenae (K. ozaenae) is low, they are often detected in sputum specimens. In addition, lung abscesses, necrotizing pneumonia, and urinary tract infections caused by K. ozaenae have also been reported. We herein report the first detection of K. ozaenae as an etiological agent of bacterial meningitis in Japan. Cases of K. ozaenae meningitis complicated by diabetes mellitus and sinusitis have been reported elsewhere. When Klebsiella pneumoniae is detected in such cases, it is important to use other detection methods in addition to mass spectrometry for correct identification.

Infrequent Thrombotic Complications in Japanese Patients with Warm Autoimmune Hemolytic Anemia.

Objective Patients with autoimmune hemolytic anemia (AIHA) are considered to be at an increased risk of thrombosis, and prophylaxis for venous thromboembolism (VTE) is often recommended. However, the occurrence of thrombosis in Asian patients has not been specifically studied. Thrombotic complications and features of Japanese warm AIHA (WAIHA) patients were studied to see if Japanese patients were at an increased risk of thrombosis and should receive prophylaxis for VTE. Patients and Methods Forty-seven consecutive patients with warm WAIHA were retrospectively studied. Twenty-nine patients were diagnosed as primary cases and 18 as secondary cases, and 10 patients were diagnosed with Evans syndrome. Results No patient presented with thrombosis, and over a median observation period of 15 months, 3 patients had ischemic cerebral vascular accidents. However, all three of those patients had other known risks for thrombosis, with only one taking thrombotic prophylaxis. No venous thrombosis occurred in any patients during the follow-up period. There was no mortality associated with thrombosis. D-dimer levels were often elevated in patients with WAIHA, indicating that the coagulation was activated in a considerable number of patients, but not to such a level as to be associated with clinically overt thrombosis. Conclusion Thrombotic complications occur infrequently in Japanese WAIHA patients, and these individuals do not appear to be at a particularly increased risk of thrombosis because of WAIHA. The indication of VTE prophylaxis should be determined individually, considering other risks.

Transient Pseudothrombocytopenia Detected 8 Months After COVID-19 Vaccination.

Pseudothrombocytopenia is an in vitro phenomenon of platelet aggregation due to conformational changes and exposure of cryptic antigens on the platelet surface caused by anticoagulants, leading to the aggregation of platelets and falsely lower automated platelet counts. Although it has no clinical relevance, it can lead to unnecessary fear, diagnostic errors, or unnecessary tests and interventions when unrecognized. Pseudothrombocytopenia was detected in a 25-year-old woman 8 months after the second dose of mRNA COVID-19 vaccine, BNT162b2. The pseudothrombocytopenia was transient and the duration was shorter than 3 months. As pseudothromobocytopenia is not detected unless blood is drawn for other objectives, it is difficult to determine its true occurrence among recipients of vaccines. This case shows that pseudothrombocytopenia may develop transiently even months after COVID-19 vaccination and should be considered when thrombocytopenia is found in recipients of the vaccine to avoid unnecessary fear, diagnostic errors, or unnecessary tests and interventions.

Reticulocyte Hemoglobin Equivalent in Patients with Idiopathic Warm Autoimmune Hemolytic Anemia: Implication in the Development of Macrocytosis.

OBJECTIVE: Patients with warm autoimmune hemolytic anemia (WAIHA) present with anemia that is highly heterogeneous, and often have macrocytic anemia with inappropriately elevated mean corpuscular volume (MCV). The goal of this retrospectivecase study is to elucidate the characteristics of anemia in patients with idiopathic WAIHA. PROCEDURES: The hematological parameters were analyzed by automated hematology analyzers in 19 consecutive patients with idiopathic WAIHA. Thecontent of hemoglobin (Hb) in the reticulocytes was assessed as reticulocyte Hb equivalent (RET-He). Relevant laboratory data and medical records were retrospectively studied. RESULTS: The median MCV was 102.7 fL and ten patients had macrocytic anemia with MCV above 100 fL. There was a significant correlation between the percentage of reticulocytes and MCV. The median RET-He value was 35.9 pg, and the reticulocytes of patients with higher MCV had higher RET-He. There was a significant correlation between red cell volume distribution width (RDW) andMCV, while the association between RDW and RET-He was not significant. Red blood cell agglutination was not seen in any of the patients. Relative folate deficiency was implied to contribute to the increased Hb content in the reticulocytes of WAIHA patients. CONCLUSION: Reticulocytes in WAIHA patients often contain more Hb than normal reticulocytes and become inappropriately large, possibly due to relative folate deficiency. Elevated MCV in WAIHA patients is due to the increase in both the number and the Hb content of reticulocytes.

Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation.

Cigarette smoke impairs autophagy, an intracellular protein degradation system, but the consequences of this defect have not been fully elucidated, especially in macrophages. Dysfunctional alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD). Here we show that galectin-8, a danger receptor that identifies damaged intracellular host vesicles and initiates autophagosome engulfment, is elevated due to activation of autophagy by cigarette smoke extract (CSE) in macrophages. CSE impaired autophagic flux in PMA-differentiated U937 macrophage-like cells, resulting in intracellular accumulation of galectin-8 and the autophagic adaptor protein NDP52. COPD patients showed elevated levels of galectin-8 and NDP52 in the lung homogenates with significant increase in the serum galectin-8 levels in patients with frequent acute exacerbations. Soluble galectin-8 induced interleukin (IL)-6 release in bronchial epithelial cells via PI3Kα signalling. Thus, increased galectin-8 due to CSE-induced impaired autophagy may be involved in the pathogenesis of COPD and may be a biomarker of this disease.

Persistent Asthma from Childhood to Adulthood Presents a Distinct Phenotype of Adult Asthma.

BACKGROUND: In approximately 30% of children with asthma, the condition persists into adulthood. The longer duration of asthma in these patients is a risk factor for poor asthma control. However, the characteristics of adult patients with asthma that has persisted since childhood are not well documented. OBJECTIVE: We sought to compare the clinical characteristics among patients with adult-onset asthma, patients who outgrew childhood asthma but relapsed, and patients with persistent asthma since childhood. METHODS: We conducted a cross-sectional study of adult patients with asthma who visited our hospital. We classified them into 3 groups: those with adult-onset asthma (adult-onset), those who had remitted childhood asthma that relapsed (relapsed), and those who had asthma that had persisted since childhood (persistent). The clinical characteristics of these groups were compared. RESULTS: A total of 1443 patients were enrolled. The persistent group was younger and included fewer patients with a smoking history. There were statistically significant differences among the 3 groups in the percentages of patients with a family history of asthma and comorbidities of allergic rhinitis and atopic dermatitis. The proportion of patients with severe asthma differed among the 3 groups (31% in the adult-onset group, 34% in the relapsed group, and 40% in the persistent group; P = .015). The values of forced expiratory flow at 75% of vital capacity were lower in the persistent group than the relapsed or adult-onset group. A multivariable logistic regression analysis (dependent variable: severe asthma) in each group revealed that the factors associated with severe asthma differed among the adult-onset, relapsed, and persistent groups. When we established an overall model that included interaction terms of cohort-by-other factors, there was a trend that comorbidity of allergic rhinitis affected the severity of asthma differently in the relapsed group compared with the other groups. CONCLUSION: The clinical phenotype of asthma that persists from childhood to adulthood seems to be a distinct phenotype of adult asthma.

Isolation of three distinct carbapenemase-producing Gram-negative bacteria from a Vietnamese medical tourist.

Carbapenem-resistant Klebsiella pneumoniae and Escherichia coli, multidrug-resistant Pseudomonas aeruginosa and vancomycin-resistant Enterococcus faecium were isolated from a single patient. The patient came to Japan for advanced medical treatment after having undergone laparoscopic cholecystectomy and hospitalization in Vietnam. Whole-genome sequence analysis revealed that K. pneumoniae harbored blaOXA-48 that was found on a Col156 -type small plasmid, E. coli harbored blaNDM-5 and P. aeruginosa harbored both blaNDM-1 and 16S rRNA methyltransferase (rmtB). To the best of our knowledge, this is the first report of detection of K. pneumoniae harboring blaOXA-48 on a Col156-type small plasmid in the world and P. aeruginosa coharboring genes encoding NDM-1 and RmtB in Japan.

Obesity-associated severe asthma in an adult Japanese population.

BACKGROUND: Severe asthma is increasingly being recognized as an important public health issue. Obesity has been identified as a risk factor for poor asthma control and for worsening of asthma severity. However, most studies investigating obese patients with asthma have been performed in Western countries. Reports on the characteristics of obese Japanese individuals with severe asthma are lacking. Herein, we investigated the clinical characteristics of patients with obesity-associated severe asthma in a Japanese population and the association between obesity and poor asthma control. METHODS: We conducted a retrospective observational study of adult patients with severe asthma. Patients were classified into two groups based on the definition of obesity recommended by the Japan Society for the Study of Obesity: obese (OB) group (body mass index [BMI] ≥25 kg/m2) and non-obese (NOB) group (BMI <25 kg/m2). The two groups were compared. The characteristics of obesity and the metabolic functions are known to differ between males and females; therefore, we analyzed male-only and female-only cohorts separately. RESULTS: A total of 492 patients were enrolled. Age, smoking history in terms of number of pack-years, daily controller medications use, and spirometric data were not significantly different between the OB and NOB groups in either cohort. In the female cohort, the annual exacerbation ratio and the percentage of frequent exacerbators were significantly higher in the OB group compared to the NOB group. A multivariate logistic regression analysis showed that obesity was independently associated with frequent asthma exacerbations in the female cohort. CONCLUSIONS: Our study revealed that obesity, defined as a BMI ≥25 kg/m2, was independently associated with poor asthma control (including acute exacerbations) in adult Japanese females with severe asthma.

Long-Term Favorable Course of Aspergillus Endo-, Myo-, and Pericarditis.

Here, we report on a healthy 30-year-old man with no significant medical history, who tested negative for human immunodeficiency virus antigenemia but developed Aspergillus pancarditis. A case of this kind is extremely rare, and to the best of our knowledge, this is the first report of a patient with Aspergillus pancarditis, which generally leads to a very poor outcome, who had a long-term favorable clinical course. A biopsy from the right atrium of hypertrophied atrial septum was essential for obtaining the definitive diagnosis. Long-term administration of an effective antifungal oral agent might account for the patient's favorable outcome.

Reduced HDAC2 in skeletal muscle of COPD patients.

BACKGROUND: Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. METHODS AND RESULTS: Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/ß-actin: 0.59 ± 0.34) was significantly lower than that in SM (1.9 ± 1.1, p = 0.0007) and NS (1.2 ± 0.7, p = 0.029). HDAC2 protein in skeletal muscle was significantly correlated with forced expiratory volume in 1 s % predicted (FEV1 % pred) (rs = 0.53, p = 0.008) and quadriceps maximum voluntary contraction force (MVC) (rs = 0.42, p = 0.029). HDAC5 protein in muscle biopsies of COPD patients (HDAC5/ß-actin: 0.44 ± 0.26) was also significantly lower than that in SM (1.29 ± 0.39, p = 0.0001) and NS (0.98 ± 0.43, p = 0.020). HDAC5 protein in muscle was significantly correlated with FEV1 % pred (rs = 0.64, p = 0.0007) but not with MVC (rs = 0.30, p = 0.180). Nuclear factor-kappa B (NF-κB) DNA binding activity in muscle biopsies of COPD patients (10.1 ± 7.4) was significantly higher than that in SM (3.9 ± 7.3, p = 0.020) and NS (1.0 ± 1.2, p = 0.004and significantly correlated with HDAC2 decrease (rs = -0.59, p = 0.003) and HDAC5 (rs = 0.050, p = 0.012). HDAC2 knockdown by RNA interference in primary skeletal muscle cells caused an increase in NF-κB activity, NF-κB acetylation and basal tumour necrosis factor (TNF)-α production, as well as progressive cell death through apoptosis. CONCLUSION: Skeletal muscle weakness in COPD may result from HDAC2 down-regulation in skeletal muscle via acetylation and activation of NF-κB. The restoration of HDAC2 levels might be a therapeutic target for improving skeletal muscle weakness in COPD.

A case of falciparum malaria: Acute hearing loss as the initial symptom.

A 49-year-old healthy woman, who returned from Burkina Faso, visited an ear, nose, and throat clinic with complaints of left hearing loss, tinnitus, and dizziness. Pure tone audiometry demonstrated bilateral mild sensorineural hearing loss. Three days later, she was transported in an ambulance to a general hospital due to high fever and disturbance of consciousness. Plasmodium falciparum was found in the peripheral blood smear. After diagnosing severe falciparum malaria with cerebral involvement, quinine hydrochloride, clindamycin, and artemether/lumefantrine were administered. After recovery of consciousness, she was followed up at our department with bilateral hearing loss. After taking prednisolone for 10 days, there was improvement to normal hearing level. Furthermore, no neurologic sequelae were observed. In this case, acute sensorineural hearing loss occurred before administration of the antimalarial drug. Therefore, hearing loss was not drug-induced, but was caused by the malaria itself. In patients with acute hearing loss and who have history of travel to tropical regions, physicians should include malaria and other causes of acute deafness in the differential diagnoses.

[A Case of Dengue Fever and Subsequent Long-lasting Depression Accompanied by Alopecia in a Japanese Traveler Returning from Bali, Indonesia].

Recovery from dengue fever is generally rapid and uneventful. However, recuperation is often prolonged and may be accompanied by noticeable depression. We present herein on a traveler to Indonesia who developed long-lasting depression after the classic symptoms of dengue fever such as fever, arthralgia, and macropapular rash had resolved. A previously healthy 42-year old japanese woman presented to the Travel Clinic of Seirei Yokohama Hospital with complaints of 4 days of fever, joint aches, bone pain, and a macropapular rash on her torso. She had returned from Bali 5 days previously. During her 1-week stay, one day was spent in rural, mountainous areas where she was exposed to several mosquito bites. The 1st serum sample collected 4 days after the disease onset gave positive result in the rapid dengue IgM antibody test and the rapid dengue NS1 antigen immunechromatographic test. The DENV-1 genome was detected with RT-PCR. Her 13-year old son, who had accompanied her, was also diagnosed as having dengue fever and he recovered without event. The Above-mentioned symptoms resolved within one week. However, the patient suffered from prolonged depression. She also noticed loss of hair 3 months after the disease onset Administration of a Serotonin-Noradrenalin Reuptake Inhibitor and a minor tranquillizer required to allow her requied to lead a normal life. Although she gradually felt better, it took approximately 2 years until she had recovered completely without taking any antidepressant and minor tranquillizer. It is a well-known fact in endemic countries that dengue fever could have an significant impact on the patients' mental well-being. However, it appears that physicians in non-endemic countries are not fully aware of the prolonged depression, which can occur subsequent to the acute illness. Follow-up consultations of returing travelers who have recoverd from dengu fever should be arranged to monitor their mental and emotional states closely.

Detection of active schistosome infection by cell-free circulating DNA of Schistosoma japonicum in highly endemic areas in Sorsogon Province, the Philippines.

The current status of schistosomiasis in highly endemic areas is difficult to determine by ovum detection because of the superficially low parasite load after mass drug administration, whereas the parasite transmission rates are still high. Cell-free parasite DNA is fragments of parasite-derived DNA existing in the host's body fluids. We conducted population-based studies to test the presence of cell-free schistosome DNA in endemic areas of Sorsogon Province, the Philippines. Schistosome DNA in the serum and urine of Kato-Katz (KK)-positive subjects was detected by PCR (100% sensitivity). Schistosome DNA was also detected from KK-negative subjects (9/22 serum and 10/41 urine samples). Schistosome DNA was found to be network echogenic pattern (NW)-positive (serum 53.3%, urine 42.9%) or NW-negative (serum 25.5%, urine 20.8%) and enzyme-linked immunosorbent assay (ELISA)-positive (serum 47.1%, urine 40%) or ELISA-negative (serum 33.3%, urine 13.3%). These results indicate that cell-free schistosome DNA is a promising diagnostic marker for active schistosome infection in the case of light infection.

Clinical utility of procalcitonin as a marker of sepsis: a potential predictor of causative pathogens.

OBJECTIVE: Sepsis is one of the leading causes of mortality in critically ill patients, and providing a timely diagnosis and early intervention is necessary for successful treatment. Procalcitonin (PCT) may be a better marker of sepsis than conventional inflammatory markers. The aim of this study was to evaluate the clinical utility of the PCT level as a marker of sepsis. METHODS: Forty-five patients with sepsis, 24 patients with pneumonia who did not meet the SIRS criteria (PN) and 56 controls were enrolled in this study. The levels of PCT and other serum markers were measured, and their utility as markers of sepsis was assessed. RESULTS: The serum PCT levels exhibited statistically significant differences between the three groups (p<0.0001). The PCT levels in the sepsis group (29.3 ± 85.3 ng/mL) were significantly higher (p<0.001) than those observed in the PN group (0.34 ± 8.6 ng/mL) and the control group (0.74 ± 2.1 ng/mL), according to a post hoc analysis. There were no differences in the white blood cell (WBC) counts or C-reactive protein (CRP) levels between the three groups. Fourteen of the 45 patients with sepsis had positive microbiological blood cultures (Gram-positive cocci [GPC] in seven patients, Gram-negative rods [GNR] in six patients, other types of bacteria in one patient). The 13 patients with GNR or GPC were categorized into the GNR group or GPC group according to the identified pathogens. The serum PCT levels were significantly higher in the GNR group (149.8 ± 199.7 ng/mL) than in the GPC group (19.1 ± 41.8 ng/mL) (p<0.05), although there were no differences in the WBC counts or CRP levels between these groups. When the cut-off value for the PCT level was set at 16.9 ng/mL, the sensitivity and specificity for the detection of GNR infection were 85.7% and 83.3%, respectively. CONCLUSION: The PCT level is a potentially useful marker of the type of causative pathogen in patients with sepsis whose measurement may facilitate the selection of appropriate empiric antibiotic treatment.

[Clinical and microbiological features of patients with pulmonary nontuberculous mycobacterial infection].

BACKGROUNDS: The prevalence of pulmonary nontuberculous mycobacterial infection (pNTM) is currently increasing. Furthermore, its clinical feature is reported to be gradually changing. However, few reports to clarify the current features of pNTM have been published. The aim of this study is to investigate microbiological and clinical features of pNTM. PATIENTS AND METHODS: This study was a retrospective observational study. Patients with pNTM visited to Dokkyo Medical University Koshigaya Hospital between January 2009 and December 2010 were enrolled. All patients fulfilled the diagnostic criteria in Japanese guidelines for nontuberculous mycobacterial pulmonary disease published in 2008. Medical records were reviewed to obtain information about the enrolled patients. RESULTS: Total 143 patients (49 males and 94 females, age 67 +/- 10 yrs) were enrolled in this study. Only 11.9% of patients had malignant diseases and 5.6% had diabetes mellitus whereas 79% had no comorbidity. Nearly 60% of patients showed normal BMI. At the time of diagnosis, 52.0% of patients had no symptom whereas 22.3% had cough and/or sputum, and 7.1% had hemoptysis. The results of smear examination with acid-fast staining were negative in 80.4%, +/- in 9.8%, 1 + in 7.7% and 2 + in 2.1%. Causative pathogens detected with acid-fast bacillus culture were Mycobacterium avium (M. avium) (74.8%), M. intracellulare (14.0%), M. fortuitum (3.5%), M. abscessus (2.8%), M. kansasii (2.8%) and others. CONCLUSION: This study showed that majority of patients had no symptoms and/or negative results of smear examination with acid-fast staining. It is crucial to consider these facts when a diagnostic test of pNTM is performed.