Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

Clinical utilization of artificial intelligence-based COVID-19 pneumonia quantification using chest computed tomography - a multicenter retrospective cohort study in Japan.

BACKGROUND: Computed tomography (CT) imaging and artificial intelligence (AI)-based analyses have aided in the diagnosis and prediction of the severity of COVID-19. However, the potential of AI-based CT quantification of pneumonia in assessing patients with COVID-19 has not yet been fully explored. This study aimed to investigate the potential of AI-based CT quantification of COVID-19 pneumonia to predict the critical outcomes and clinical characteristics of patients with residual lung lesions. METHODS: This retrospective cohort study included 1,200 hospitalized patients with COVID-19 from four hospitals. The incidence of critical outcomes (requiring the support of high-flow oxygen or invasive mechanical ventilation or death) and complications during hospitalization (bacterial infection, renal failure, heart failure, thromboembolism, and liver dysfunction) was compared between the groups of pneumonia with high/low-percentage lung lesions, based on AI-based CT quantification. Additionally, 198 patients underwent CT scans 3 months after admission to analyze prognostic factors for residual lung lesions. RESULTS: The pneumonia group with a high percentage of lung lesions (N = 400) had a higher incidence of critical outcomes and complications during hospitalization than the low percentage group (N = 800). Multivariable analysis demonstrated that AI-based CT quantification of pneumonia was independently associated with critical outcomes (adjusted odds ratio [aOR] 10.5, 95% confidence interval [CI] 5.59-19.7), as well as with oxygen requirement (aOR 6.35, 95% CI 4.60-8.76), IMV requirement (aOR 7.73, 95% CI 2.52-23.7), and mortality rate (aOR 6.46, 95% CI 1.87-22.3). Among patients with follow-up CT scans (N = 198), the multivariable analysis revealed that the pneumonia group with a high percentage of lung lesions on admission (aOR 4.74, 95% CI 2.36-9.52), older age (aOR 2.53, 95% CI 1.16-5.51), female sex (aOR 2.41, 95% CI 1.13-5.11), and medical history of hypertension (aOR 2.22, 95% CI 1.09-4.50) independently predicted persistent residual lung lesions. CONCLUSIONS: AI-based CT quantification of pneumonia provides valuable information beyond qualitative evaluation by physicians, enabling the prediction of critical outcomes and residual lung lesions in patients with COVID-19.

Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study.

BACKGROUND: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD. METHODS: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed. RESULTS: The median age [interquartile range] of the patients was 67 [63-74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361-470] m and 1 [0-2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS. CONCLUSIONS: The decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient's condition and tailor their healthcare environment.

The Impact of Single-Stranded DNA-Binding Protein SSB and Putative SSB-Interacting Proteins on Genome Integrity in the Thermophilic Crenarchaeon Sulfolobus acidocaldarius.

The study of DNA repair in hyperthermophiles has the potential to elucidate the mechanisms of genome integrity maintenance systems under extreme conditions. Previous biochemical studies have suggested that the single-stranded DNA-binding protein (SSB) from the hyperthermophilic crenarchaeon Sulfolobus is involved in the maintenance of genome integrity, namely, in mutation avoidance, homologous recombination (HR), and the repair of helix-distorting DNA lesions. However, no genetic study has been reported that elucidates whether SSB actually maintains genome integrity in Sulfolobus in vivo. Here, we characterized mutant phenotypes of the ssb-deleted strain Δssb in the thermophilic crenarchaeon S. acidocaldarius. Notably, an increase (29-fold) in mutation rate and a defect in HR frequency was observed in Δssb, indicating that SSB was involved in mutation avoidance and HR in vivo. We characterized the sensitivities of Δssb, in parallel with putative SSB-interacting protein-encoding gene-deleted strains, to DNA-damaging agents. The results showed that not only Δssb but also Δalhr1 and ΔSaci_0790 were markedly sensitive to a wide variety of helix-distorting DNA-damaging agents, indicating that SSB, a novel helicase SacaLhr1, and a hypothetical protein Saci_0790, were involved in the repair of helix-distorting DNA lesions. This study expands our knowledge of the impact of SSB on genome integrity and identifies novel and key proteins for genome integrity in hyperthermophilic archaea in vivo.

Impact of arsenic releaching from excavated rock after once-arsenic leaching on potential arsenic leaching.

Massive quantities of naturally arsenic-containing rocks are excavated from urbanized and mountainous areas for construction. Treatments such as chemical immobilization are applied to such excavated rocks for reuse. To design such treatments, determining the potentially leachable arsenic amounts in excavated rocks is imperative. This study aims to understand whether the arsenic releached amount from the excavated rock after once-arsenic leaching should be included in the potentially leachable arsenic amount or estimated using the sequential extraction procedure (SEP). Arsenic was releached at exceeding 0.01 mg L-1, even from the excavated rock that leached arsenic to less than 0.01 mg L-1, and this amount corresponded to approximately 12% of that of arsenic leached from the arsenic non-leached rock. The arsenic (re)leached amount corresponded to 84-116% (102 ± 7%) of that of arsenic in the readily soluble fraction using SEP, regardless of whether the arsenic was leached or not. These results indicate that the source of arsenic (re)leached from the excavated rock is arsenic extracted as the readily soluble fraction through SEP, regardless of whether the rock was arsenic-leached or not. This study's findings suggest that the arsenic releached amount from the excavated rock should be considered in the potentially leachable arsenic amount. In addition, the potentially leachable arsenic amount can be relatively and readily estimated by performing SEP.

Successfully treated bronchopulmonary oxalosis caused by Aspergillus tubingensis in a non-neutropenic patient: A case report and review of the literature.

Pulmonary oxalosis can be fatal, and Aspergillus tubingensis is commonly resistant to azoles in Japan. We report a case of bronchopulmonary oxalosis caused by A. tubingensis in a non-neutropenic patient who was successfully treated with voriconazole monotherapy. The susceptibility of the isolates to voriconazole and the effective elimination of contagious necrotic tissue by expectoration seemed to be two major factors contributing to the patient's survival. According to the literature review, pulmonary oxalosis is associated with a high mortality rate over a short term. An exploration of detailed information about the genomic characteristics and drug susceptibility of Aspergillus isolates is important for the development of treatment strategies for this life-threatening disease.

Osteoporosis in nontuberculous mycobacterial pulmonary disease: a cross-sectional study.

BACKGROUND: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E2) and 25-hydroxyvitamin D (25OHD) levels. METHODS: We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017-September 2019. The E2 and 25OHD levels were measured in 165 patients with available stored serum samples. We performed multivariable logistic regression analyses for osteopenia and osteoporosis. RESULTS: Osteoporosis (T-score ≤ - 2.5) and osteopenia (T-score - 1 to - 2.5) were diagnosed in 35.1% and 36.8% of patients with NTM-PD, respectively. Compared with the general population, the proportion of osteoporosis was significantly higher in 50-59-, 60-69-, and 70-79-year-old women with NTM-PD. Multivariable analysis revealed that older age (adjusted odds ratio [aOR] for 1-year increase = 1.12; 95% confidence interval [CI] = 1.07-1.18), female sex (aOR = 36.3; 95% CI = 7.57-174), lower BMI (aOR for 1 kg/m2 decrease = 1.37; 95% CI = 1.14-1.65), and chronic Pseudomonas aeruginosa (PA) infection (aOR = 6.70; 95% CI = 1.07-41.8) were independently associated with osteoporosis. Additionally, multivariable analysis in 165 patients whose serum E2 and 25OHD levels were measured showed that both low E2 levels (< 10 pg/mL) and lower 25OHD levels were independently associated with osteoporosis. CONCLUSIONS: Middle-aged/elderly women with NTM-PD have a higher prevalence of osteoporosis than the general population. BMD screening should be considered in NTM-PD, especially in older females with severe diseases such as chronic PA infection and lower BMI, and low serum E2 and 25OHD levels.

Genetic Study of Four Candidate Holliday Junction Processing Proteins in the Thermophilic Crenarchaeon Sulfolobus acidocaldarius.

Homologous recombination (HR) is thought to be important for the repair of stalled replication forks in hyperthermophilic archaea. Previous biochemical studies identified two branch migration helicases (Hjm and PINA) and two Holliday junction (HJ) resolvases (Hjc and Hje) as HJ-processing proteins; however, due to the lack of genetic evidence, it is still unclear whether these proteins are actually involved in HR in vivo and how their functional relation is associated with the process. To address the above questions, we constructed hjc-, hje-, hjm-, and pina single-knockout strains and double-knockout strains of the thermophilic crenarchaeon Sulfolobus acidocaldarius and characterized the mutant phenotypes. Notably, we succeeded in isolating the hjm- and/or pina-deleted strains, suggesting that the functions of Hjm and PINA are not essential for cellular growth in this archaeon, as they were previously thought to be essential. Growth retardation in Δpina was observed at low temperatures (cold sensitivity). When deletion of the HJ resolvase genes was combined, Δpina Δhjc and Δpina Δhje exhibited severe cold sensitivity. Δhjm exhibited severe sensitivity to interstrand crosslinkers, suggesting that Hjm is involved in repairing stalled replication forks, as previously demonstrated in euryarchaea. Our findings suggest that the function of PINA and HJ resolvases is functionally related at lower temperatures to support robust cellular growth, and Hjm is important for the repair of stalled replication forks in vivo.

ADAM10 partially protects mice against influenza pneumonia by suppressing specific myeloid cell population.

The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene (Adam10)flox/flox/Lyz2-Cre (Adam10ΔLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10ΔLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-α, IL-1ß, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10ΔLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocyte/macrophage-like phenotype, were significantly increased in the lungs of Adam10ΔLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10ΔLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10ΔLyz2 mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10ΔLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.

Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease.

RATIONALE: Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear. OBJECTIVES: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen. METHODS: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping. RESULTS: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry. CONCLUSIONS: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.

Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. METHODS: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). RESULTS: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. CONCLUSION: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

Hyperammonemic encephalopathy associated with post-radiotherapy vesicointestinal fistula following cervical cancer.

The majority of hyperammonemic encephalopathy is due to liver cirrhosis. However, urinary tract infection caused by urease-producing bacteria increases ammonia in urine and can lead to hyperammonemic encephalopathy, especially in cases with obstructive uropathy and vesicointestinal fistula. This is the first case report of hyperammonemic encephalopathy in a cervical cancer patient associated with postradiotherapy vesicointestinal fistula. A 52-year-old woman developed diarrhea due to vesicosigmoidal fistula 14 years after radical hysterectomy and radiotherapy to treat cervical cancer. She refused urinary and/or fecal diversion. Twelve months after the diagnosis of fistula, she was admitted due to somnolence. Blood examination showed hyperammonemia without liver dysfunction. Urine culture showed Proteus rettgeri and Klebsiella pneumoniae. She recovered after intravenous antibiotics. Eight months after recovery, she was readmitted due to somnolence reoccurring with failed intravenous, but successful oral antibiotic treatment. She finally agreed to undergo percutaneous nephrostomy and hyperammonemia never recurred during 7 years of follow-up.

Mesh exposure after transvaginal mesh prolapse surgery: Out of permissible range?

OBJECTIVES: To investigate the prevalence of postoperative complications after transvaginal mesh prolapse surgery, and whether modified transvaginal mesh prolapse surgery (without transobturator arms or posterior mesh) has less prevalence of mesh exposure compared with conventional transvaginal mesh prolapse surgery. METHODS: Medical charts were retrospectively examined for 2648 patients who underwent transvaginal mesh prolapse surgery in a general hospital (2006-2017). Conventional transvaginal mesh prolapse surgery (Prolift-type, n = 2258) was used, with a shift from 2015 to modified transvaginal mesh prolapse surgery (Uphold-type, n = 330). Patients were instructed to have >2 years of follow up and to report if they had problems regarding the operation. RESULTS: The prevalence of mesh exposure was 34 out of 2648 (1.28%); 18 vagina (0.68%), 10 bladder (0.38%), two ureter (0.08%) and four rectum (0.15%). The modified transvaginal mesh prolapse surgery group had only one case with vaginal exposure. Vaginal exposure was managed transvaginally or followed by observation. Rectal exposure was managed transvaginally without colostomy. Bladder exposure was managed by transurethral resection with saline. Open ureterocystostomy was carried out to treat ureteral exposure. In the conventional transvaginal mesh prolapse surgery group, three cases of ureteral stenosis and one case with vaginal evisceration of the small intestine were managed transvaginally. The prevalence of postoperative chronic pain was 13 out of 2648 (0.49%; with one patient in the modified transvaginal mesh prolapse surgery group). The patients underwent pharmacotherapy, and one patient underwent additional surgical treatment. CONCLUSIONS: The reoperation rate as a result of complications after transvaginal mesh prolapse surgery seems to be low. The reoperation rate as a result of prolapse recurrence is also low. A shift from conventional transvaginal mesh prolapse surgery to modified transvaginal mesh prolapse surgery might contribute to a further decrease in the risk of complications.

ADAM17 protects against elastase-induced emphysema by suppressing CD62L+ leukocyte infiltration in mice.

Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17flox/flox/Mx1-Cre (Adam17ΔMx1) mice (8-10 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17ΔMx1 mice. Furthermore, flow cytometry showed that CD62L+ neutrophil, CD62L+ macrophage, and CD62L+ B lymphocyte numbers were significantly increased in Adam17ΔMx1 mice. Moreover, the pharmacological depletion of CD62L+ cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17ΔMx1 mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema.

Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia.

Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage-HLA-DR-CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides.

Razor-type dermatomes enable quick and thin vaginal dissection with less bleeding in colpocleisis.

INTRODUCTION AND HYPOTHESIS: Although colpocleisis is a low-invasive surgical option to treat pelvic organ prolapse, it sometimes involves a long operative time with substantial bleeding. To streamline the vaginal dissection process in colpoclesis, we introduced the usage of dermatomes. METHODS: All patients were sexually inactive women with post-hysterectomy prolapse. Data of the dermatome group were retrospectively compared with those of the historical control group based on operative features, perioperative complications and pathology of dissected tissue. In the dermatome group, 34 women underwent total colpocleisis with vaginal dissection using dermatomes; 4 were done mainly with electric dermatomes, and 30 were done with razor-type dermatomes. In the control group, 20 women underwent total colpocleisis with vaginal dissection using Metzenbaum scissors. RESULTS: Using dermatomes in vaginal dissection was helpful to shorten total operative time (including perineoplasty) by one third from 76 to 51 min, to shorten the time of colpocleisis by half, from 62 to 32 min, and to reduce intraoperative bleeding by 76%, from 62 to 15 ml. In addition, none in the dermatome group and 2/20 patients in the control group had unintended peritoneal opening. Dissection with scissors removed not only the epithelium and submucosal layer but also the muscle layer. This was minimized with razor-type dermatomes and never occurred with electric dermatomes. Whereas electric dermatomes are difficult to get accustomed to and are expensive, razor-type dermatomes enable thinner dissection compared with scissors, are easy to handle and are inexpensive. CONCLUSIONS: Razor-type dermatomes enable quick and thin vaginal dissection with less bleeding. Therefore, they can be recommended as a practical tool for colpocleisis, a prolapse operation mainly for frail elderly patients.

Estimation of potential arsenic leaching from its phases in excavated sedimentary and metamorphic rocks.

It is important that hazardous excavated sedimentary and metamorphic rocks are treated appropriately and reused without posing an environmental risk. Up-flow column leaching tests were conducted to examine whether arsenic leaching behavior varied among five hazardous excavated sedimentary and metamorphic rocks (two mudstones, clay sediment of marine origin, slate, and black schist) and to determine whether the potential amount of arsenic leaching could be estimated based on the arsenic-bearing mineral phases in the rock. Changes in arsenic concentration with pore volume (PV) showed the same pattern across all rock types, except for one that contained an extremely low amount of water-soluble arsenic, exhibiting an initial increase to reach a peak, followed by a decrease. The arsenic amounts leached before and after the PV at which the arsenic concentration peaked, corresponded to 88% ± 20% of the amount of arsenic fraction 1 obtained by sequential extraction and 76% ± 10% of the amount of arsenic fraction 2, respectively, while the potential amount of arsenic leaching corresponded to 65-89% of the summed total of arsenic fractions 1 + 2. These findings indicate that arsenic exhibits the same leaching behavior among different types of hazardous excavated sedimentary and metamorphic rocks except where extremely low amounts of water-soluble arsenic are present and that the potential amount of arsenic leaching can be approximated by calculating the summed total of arsenic fractions 1 + 2, which allows us to estimate the minimum amount of material required for treatments such as immobilization conducted to prevent arsenic leaching.

[Two-debranching Thoracic Endovascular Aortic Repair for Thoracic Aortic Aneurysm Complicated by Idiopathic Thrombocytopenic Purpura;Report of a Case].

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which the number of platelets decreases due to auto-antibodies against platelets. We report that thoracic endovascular aortic repair (TEVAR) was successfully performed for a thoracic aortic aneurysm complicated by ITP. The patient was a man of 77 years of age. He had a history of splenectomy due to ITP. He was admitted to our hospital with an aneurysm of the aortic arch that enlarged to a maximum minor axis of 63 mm. An operation was planned. Because of ITP, it was judged that replacement of the aortic arch using a cardio-pulmonary pump would be associated with a high risk of bleeding. Thus, 2-debranching TEVAR was selected and performed with no hemorrhagic complications. He was discharged from the hospital on the 12th day after surgery. We believe that 2-debranching TEVAR is effective for reducing perioperative bleeding in patients with ITP.

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy.

BACKGROUND: Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition. METHODS: We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP). RESULTS: Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not. CONCLUSIONS: Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality. CLINICAL TRIALS REGISTRATION: JMA-IIA00146.

Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice.

Increasing evidence indicates that obesity is a risk factor for increased severity of influenza virus infection. However, its precise immunological mechanism is not fully understood. To investigate this, diet-induced obese (DIO) mice were established by feeding C57BL/6 male mice a high-fat diet for 16 weeks. DIO and lean control mice were infected intranasally with 3000 pfu of influenza A virus (IAV) (PR8/H1N1). Interestingly, we found adipose tissue located along the bronchus in naïve DIO mice. In addition, the Nos2 level was significantly higher and Arg1 level was significantly lower in lung macrophages of naïve DIO mice, consistent with an M1-skewed phenotype. The survival rate and body weight of DIO mice infected with IAV were significantly lower than those of lean control mice and associated with higher viral load in the lungs of DIO mice. Histopathological analysis demonstrated higher numbers of inflammatory cells in the lungs of DIO mice after IAV infection. Levels of cytokines, including TNF-α, IL-6, IL-10, and type I IFN (IFN-α and IFN-ß), in bronchoalveolar lavage fluid (BALF) were altered after IAV infection; in particular, IFN-α and IFN-ß levels were significantly suppressed in the BALF of DIO mice. In vitro, bone marrow-derived macrophages were stimulated with ligands of toll-like receptor (TLR) 7/8, a pattern recognition receptor for single-stranded RNA, and levels of TNF-α, IL-6, and IL-10 were similarly altered. In addition, levels of IFN-α and IFN-ß were significantly lower in culture supernatants of alveolar macrophages sorted from naïve DIO mice and infected with IAV, compared to those in macrophages sorted from lean control mice. Collectively, these results suggest that macrophages may be the main contributors to poor outcomes of influenza virus infection in obesity.