The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans.

The therapeutic potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC-EVs accelerated Achilles tendon healing compared with P12 MSC-EVs. Fucose-specific lectin TJA-II was indicated as a glycan marker for therapeutic MSC-EVs. The present study demonstrated that early passaged MSC-EVs promote Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC-EVs in regenerative medicine.

Arthroscopic mobilization for metacarpophalangeal joint extension contracture.

BACKGROUND: As a first-line surgical treatment for treating metacarpophalangeal (MCP) joint extension contractures, mobilization surgery with open dorsal approach has been indicated. However, this procedure has the possibility to result in postoperative recurrence over the course of time because its invasive open dorsal approach has a negative impact on the postoperative gliding of the extensor mechanism. We report the preliminarily outcomes of patients who underwent a minimally invasive arthroscopic mobilization to alter and enhance their existing surgical strategy in place of MCP joint extension contractures. METHODS: This retrospective study included seven patients with 13 MCP joint extension contractures who had received an arthroscopic release of the bilateral collateral ligament and/or dorsal capsule of affected MCP joint. The extension contractures were caused by long-time immobilization with inadequate extended position of the MCP joint after either hand and wrist fractures, extensor tendon injury, or peripheral nerve palsy. All patients received sufficient exercise under the supervision of a physical therapist for more than 3 months before surgery. However, physical therapy did not improve the MCP joint extension contractures. We measured the active and passive flexion angles preoperatively at 1 and 6 months after surgery. The passive flexion angle was also measured after arthroscopic mobilization on the operation table. Surgery-related complications regarding nerve, vessel, skin, and tendon were also assessed. RESULTS: In all patients, significant improvements were observed in both the active and passive flexion angles 1 month after surgery, and continued to improve 6 months after surgery. Two out of 13 metacarpophalangeal joints developed blisters on the dorsal side of the joint, but conservatively recovered. CONCLUSIONS: Based on the positive improvements observed in our patients, we conclude that this minimally invasive arthroscopic technique has the potential to alter and enhance the surgical treatment strategy for MCP joint extension contractures.

Extensive Lung Resection for Nontuberculous Mycobacterial Lung Disease With Multilobar Lesions.

BACKGROUND: Nontuberculous mycobacterial lung disease often spreads to multiple lobes, and extensive lung resection (ELR) is sometimes required to control the disease. The safety and feasibility of ELR for nontuberculous mycobacterial lung disease remain unclear, however. METHODS: This retrospective study included patients with nontuberculous mycobacterial lung disease who underwent adjuvant lung resection. Characteristics were compared between patients who underwent ELR and those who underwent simple anatomic lung resection (SALR). The outcome data were analyzed by a Cox regression analysis. RESULTS: A total of 146 patients underwent ELR (n = 54) or SALR (n = 92). ELR was associated with a longer operative time (306 vs 237 minutes; P < .001) and higher incidence of prolonged air leak (17% vs 3.3%; P = .016) than SALR. Rates of mortality, sputum culture conversion (positive to negative), and microbiological recurrence did not differ markedly between the groups. In the multivariate analysis, ELR was not a significant risk factor for an unfavorable outcome after nontuberculous mycobacterial lung disease surgery (hazard ratio, 2.23; 95% confidence interval, 0.82-6.03; P= .11). CONCLUSIONS: ELR for nontuberculous mycobacterial lung disease has some drawbacks compared with SALR but seems as safe and feasible as SALR. ELR may provide improved disease control in some cases of nontuberculous mycobacterial lung disease with multilobar lesions.

How was cognitive behavioural therapy for mood disorder implemented in Japan? A retrospective observational study using the nationwide claims database from FY2010 to FY2015.

OBJECTIVES: To clarify the dissemination status of cognitive behavioural therapy (CBT) in Japan under the national health insurance scheme. DESIGN: Retrospective observational study. SETTING: National Database of Health Insurance Claims and Specific Health Checkups of Japan. PARTICIPANTS: Patients who received CBT under the national health insurance scheme from fiscal years (FY) 2010 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the change rate and the standardised claim ratio (SCR) for the number of patients receiving CBT and analysed the association between the CBT status and several regional factors. RESULTS: We found that (a) a total of 60 304 patients received CBT during the study period; (b) the number of patients receiving CBT was highest in the first year (-1.8% from FY2010 to FY2015); (c) the number of patients who received CBT per 100 000 population decreased (or remained at zero) in most prefectures (32 out of 47); (d) there was a maximum 424.7-fold difference between prefectures in the standardised claim ratio for CBT and (e) the number of registered CBT institutions was significantly associated with the number of patients who received CBT. CONCLUSIONS: The provision of CBT did not increase in the first 6 years (FY2010-2015) after its coverage in Japan's national health insurance scheme. Further studies including a questionnaire survey of registered CBT institutions are required to get more detailed information on the dissemination of CBT in Japan.

Monitoring Vascular Compromise Using Ultrasound After Free Tissue Transfer.

OBJECTIVES: To report the clinical utility of high-resolution ultrasound (US) for monitoring vascular compromise after free tissue transfer. METHODS: Fifty-two tissue transfers in the extremities were included in this study. Blood flow around the anastomotic pedicle and subcutaneous tissue of the grafted flap was monitored with pulsed color and power Doppler US whenever the conventional monitoring method, comprising the bedside assessment of the temperature, capillary refill, and flap color, showed abnormalities until 1 week after reconstruction. RESULTS: All flaps were indicated for US monitoring, with 44 flaps showing Doppler signals in each position, even though conventional flap monitoring showed an abnormality. Forty of the 44 flaps showed no flap failure, whereas the remaining 4 flaps developed partial necrosis. Abnormal US findings were noted in 8 of the 52 flaps. Ultrasound revealed interruption of venous blood flow around the anastomotic pedicle in 6 of 8 flaps. Emergent exploration revealed venous occlusion at the anastomotic pedicle, similar to the US finding. In 2 of the 8 flaps, US showed no blood flow to either the anastomotic pedicle or subcutaneous tissue. Emergent exploration revealed arterial occlusion at the anastomotic pedicle. Seven of the 8 reexplored flaps were salvaged after revision surgery with complete flap survival. Partial flap survival was noted in 1 case, but complete flap failure was avoided. CONCLUSIONS: Ultrasound is a useful adjunct that enables a direct assessment of perfusion in grafted tissues, which may reduce unnecessary exploration when conventional flap monitoring shows an abnormality.

Outcomes and risk factors after adjuvant surgical treatments for Mycobacterium avium complex lung disease.

BACKGROUND: Limited information is currently available on the postoperative outcomes of Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVE: To show the outcomes of pulmonary resection and identify risk factors after adjuvant surgical treatments for MAC-LD. METHODS: One hundred and eight patients underwent adjuvant lung resection for MAC-LD at two hospitals between January 2008 and July 2016. We retrospectively evaluated outcomes and risk factors. RESULTS: Postoperative complications occurred in 14 patients (13%). After lung resection, 98 out of 108 patients (91%) achieved sputum culture conversion, eight (8.2%) of whom developed microbiological recurrence during the follow-up period. As a result, the success rate of adjuvant surgical treatments for MAC-LD with drug resistance was 83%. A multivariable analysis showed that a longer period from the initial medical treatment to surgery (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p = 0.008) was independently associated with an increased risk of unfavorable outcomes after adjuvant surgery. CONCLUSIONS: Adjuvant surgical treatments for MAC-LD have acceptable outcomes. Better control of the disease may be achieved in some patients with drug resistance and indications for surgery through surgical treatments, and pulmonary resection needs to be performed earlier rather than continuing chemotherapy in these patients because it reduces unfavorable outcomes.

Joint distraction and early mobilization using a new dynamic external finger fixator for the treatment of fracture-dislocations of the proximal interphalangeal joint.

BACKGROUND: Dynamic external fixation is a useful treatment option for unstable fracture-dislocations of the proximal interphalangeal (PIP) joint, because it simultaneously reduces axial pressure load on the joint surface, maintains congruent joint reduction, and permits early joint motion. However, most current devices are large, hindering finger movement, and unstable. To address these problems, we developed a dynamic external finger fixator, named the Micro Ortho Fixator®. The purpose of this study was to review the results of using the new external finger fixator to treat unstable fracture-dislocations of the PIP joint. MATERIALS AND METHODS: Nine patients who sustained unstable fracture-dislocation injuries of the PIP joint were treated with the Micro Ortho Fixator®. Seven fractures were accompanied by depressed bony fragments at the base of the middle phalanx. All patients were evaluated for pain and range of PIP motion at the final follow-up. Radiographs of the affected fingers were evaluated for PIP congruity and reduction. The mean follow-up duration was 11.1 months (range: 6-33 months). RESULTS: At the final follow-up, pain averaged 0.3 (range: 0-2) on the Numeric Pain Rating Scale, and the total arc of motion at the PIP joint averaged 91.2° (range: 50-110°). All fractures had healed, and the intra-articular step-off improved from 1.9 mm (SD: 1.0) before surgery to 0.2 mm (SD: 0.4) at the final follow-up. The patients who sustained sports injuries returned to competition after an average of 3.5 months (range: 2.5-4 months). CONCLUSION: The external fixator is compact and facilitates range-of-motion (ROM) exercises, has high stability, and achieves good joint congruity and an ROM equivalent to the healthy joint of the patient. STUDY DESIGN/LEVEL OF EVIDENCE: Therapeutic/IV.

Retrospective evaluation of the clinical characteristics associated with Corynebacterium species bacteremia

ABSTRACT Objectives: Corynebacterium spp. are becoming recognized as pathogens that potentially cause various infections. We aimed to evaluate the clinical characteristics associated with Corynebacterium spp. bacteremia. Patients and methods: We retrospectively reviewed the medical records of all adult patients who had positive blood cultures for Corynebacterium spp. in a single university hospital between January 2014 and December 2016. Patients were divided into a bacteremia group and a contamination group based on microbiological test results and clinical characteristics. Patients' characteristics, antimicrobial susceptibility of isolated species, antimicrobials administered, and patient outcomes were evaluated. Results: Corynebacterium spp. were isolated from blood samples of 63 patients; Corynebacterium striatum was the predominant isolate. Twenty-eight patients were determined to have bacteremia. Younger age (p = 0.023), shorter time to positivity (p = 0.006), longer hospital stay (p = 0.009), and presence of an indwelling vascular catheter (p = 0.002) were observed more often in the bacteremia group compared to the contamination group. The source of infection in most patients with bacteremia was an intravenous catheter. All tested strains were susceptible to vancomycin. Four of the 27 patients with bacteremia died, despite administration of appropriate antimicrobial therapy. Conclusions: We found that younger age, shorter time to positivity, and presence of an indwelling catheter were related to bacteremia caused by Corynebacterium spp. Appropriate antimicrobials should be administered once Corynebacterium spp. are isolated from the blood and bacteremia is suspected.

Edwardsiella tarda Bacteremia with Psoas and Epidural Abscess as a Food-borne Infection: A Case Report and Literature Review.

Edwardsiella tarda is commonly isolated from aquatic environments and a variety of animals. We present the first case of E. tarda bacteremia with psoas and epidural abscess. The patient was a 65-year-old woman with recurrent gastric cancer who had frequently consumed raw fish and grilled eel. She was successfully treated with antimicrobials and surgery. We also review reports published in English regarding E. tarda bacteremia in Japan and the experience at our hospital. On the basis of this review, we conclude that the major underlying disease leading to E. tarda bacteremia is malignancy and that the gastrointestinal tract is the most commonly affected organ. The overall mortality rate due to E. tarda bacteremia in our review was 38.1% (8/21). Although E. tarda bacteremia is rare, clinicians should be aware of this fatal food-borne infection.

Rituximab Restores IFN-γ-STAT1 Function and Ameliorates Disseminated Mycobacterium avium Infection in a Patient with Anti-Interferon-γ Autoantibody.

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m2, every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102 Consecutive Cases.

RATIONALE: The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVES: This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB. METHODS: The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital. MEASUREMENTS AND MAIN RESULTS: Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC. CONCLUSIONS: Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

Bronchial occlusion with Endobronchial Watanabe Spigots for massive hemoptysis in a patient with pulmonary Mycobacterium avium complex infection.

The safety of occlusion with Endobronchial Watanabe Spigots (EWS) for the management of hemoptysis associated with chronic respiratory tract infection has not yet been established. A 57-year-old woman diagnosed as having pulmonary Mycobacterium avium complex (MAC) infection presented to our hospital with hemoptysis. She underwent bronchoscopy for bronchial occlusion with EWS, which resulted in the resolution of hemoptysis. Subsequently, she underwent bronchial artery embolization and then EWS were removed. During placement of EWS, no worsening of infection was observed. After removal of EWS, there was no recurrence of hemoptysis. Bronchial occlusion with EWS for hemoptysis associated with pulmonary MAC infection can be performed safely.

[Invasive pneumococcal disease of serotype 6C with skin and soft tissue infections in an immunocompetent adult].

We report herein on a rare case of deep-soft tissue infection due to invasive pneumococcal disease (IPD). A 77-year-old woman was admitted to our hospital with progressive pain in the right upper arm and the distal leg associated with swelling. We diagnosed the condition as multiple instances of cellulitis that were initially treated with ceftriaxone and clindamycin. Penicillin-susceptible Streptococcus pneumoniae (PSSP) was isolated from blood cultures on admission. Although inflammatory marker levels improved following susceptive antibiotic therapy (ampicillin), multiple abscesses, septic arthritis and osteomyelitis were detected with image testing. The antibiotic was then changed to meropenem and arthroscopic surgery was performed for the right shoulder; the patient's clinical symptoms improved. Since pneumococcal infection including skin and soft tissue infection (SSTI) often causes blood stream invasion or metastatic suppurative complications, metastatic lesions or multiple abscesses should be taken care of.

Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells.

The lung is a primary target for oxygen toxicity because of its constant exposure to high oxygen levels and environmental oxidants. Quercetin is one of the most commonly found dietary flavonoids, and it provides cytoprotective actions via activation of specific transcriptional factors and upregulation of endogenous defensive pathways. In the present study, we showed that quercetin increased the levels of heme oxygenase (HO)-1 expression and protected against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in lung epithelial cell lines. Quercetin suppressed H(2)O(2)-induced apoptotic events, including hypodiploid cells, activation of caspase 3 enzyme activity and lactate dehydrogenase release. This cytoprotective effect was attenuated by the addition of the HO inhibitor, tin protoporphyrin IX. In addition, the end products of heme metabolites catalyzed by HO-1, carbon monoxide and bilirubin, protect against H(2)O(2)-induced cytotoxicity in LA-4 cells. Quercetin may well be one of the promising substances to attenuate oxidative epithelial cell injury in lung inflammation.

Involvement of heme oxygenase-1 in kaempferol-induced anti-allergic actions in RBL-2H3 cells.

Kaempferol is one of the most commonly found dietary flavonoids. The exposure to kaempferol is known to inhibit degranulation from mast cells, but the inhibitory mechanism of degranulation has not been clarified yet. In this study, we investigated the involvement of heme oxygenase (HO)-1 in the anti-allergic action of kaempferol against degranulation in rat basophilic leukemia (RBL-2H3) cells. Our results demonstrate upregulation of HO enzymatic activity after short (15 min) exposure to kaempferol, followed by the induction of HO-1 expression in protein. The involvement of HO-1 in the kaempferol-induced inhibition of degranulation was confirmed using tin protoporphyrin IX (SnPP), a HO-1 inhibitor. These findings strongly suggest that kaempferol exerts anti-allergic actions via activation of the HO-1.

Up-regulation of surfactant protein production in a mouse model of secondary pulmonary alveolar proteinosis.

Although Pneumocystis infection might be one of the causes of secondary pulmonary alveolar proteinosis (PAP), the mechanism of its pathogenesis is uncertain. We analyzed a mouse model of secondary PAP resulting from Pneumocystis infection using mice deficient in CD40 (CD40KO), and evaluated the mechanism of the pathogenesis of secondary PAP from the viewpoint of surfactant-associated protein (SP) homeostasis, the overproduction of SP by type II alveolar epithelial cells, and the phagocytic function of alveolar macrophages (AMs). The effect of CD40 on SP production was also investigated in vitro using the H441 cell line, which has a phenotype similar to type II alveolar epithelial cells and primary alveolar epithelial cells. After long-term exposure to ovalbumin, CD40KO mice showed Pneumocystis infection and accumulation of surfactants in the alveoli (ApCD40KO). The amounts of SP production were up-regulated in ApCD40KO mice compared with wild-type mice treated using the same procedure. On the other hand, AMs from ApCD40KO mice did not show either phagocytic dysfunction or down-regulation of PU.1 expression. Furthermore, the stimulation of CD40-CD40 ligand (CD154) pathway regulated the production of SPs in H441 cells or primary alveolar epithelial cells. These results suggested that CD40KO mice could be one of the models useful for developing secondary PAP resulting from Pneumocystis infection. Surfactant accumulation was due to the overproduction in our model of secondary PAP. The CD40-CD154 interaction plays an important role in the regulation of surfactant-associated protein production.

[Moderately differentiated adenocarcinoma of the lung presenting as multiple pulmonary metastases with thin-walled cavities].

A 63-year-old woman was admitted because of diabetes mellitus and abnormal chest radiographic findings. Computed tomographic scan showed a large mass in the S1 region of the right lung and many pulmonary nodules with thin-walled cavities in both lung fields. A transbronchial biopsy specimen revealed moderately differentiated adenocarcinoma of bronchial gland origin. The patient could not receive systemic chemotherapy because of her poor physical status, and died of respiratory failure due to advanced pulmonary metastases. Histopathological examination of an autopsy specimen confirmed the diagnosis of primary bronchial adenocarcinoma with multiple cavitary metastases. The cavity wall consisted of moderately differentiated adenocarcinoma cells, and central necrosis with neutrophil infiltration and fibrin precipitation were recognized. These findings suggest that the mechanism of cavity formation in this case may depend on the ischemic tumor necrosis or colliquative tumor necrosis associated with neutrophil infiltration into the central portion of metastatic lesion.