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1.
An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.  相似文献   
2.

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Methods

A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.

Results

The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.

Conclusions

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.  相似文献   
3.
Background::Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS.Objectives:To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk.Methods:We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models.Results:The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff’s classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff’s groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04).Discussion:Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.Key words: Soft tissue sarcoma, polychlorinated biphenyls, epidemiology, environmental risk factors, chemical contaminants, case-control study  相似文献   
4.

BACKGROUND CONTEXT

Lumbar spinal stenosis (LSS) can impair blood flow to the spinal nerves giving rise to neurogenic claudication and limited walking ability. Reducing lumbar lordosis can increases the volume of the spinal canal and reduce neuroischemia. We developed a prototype LSS belt aimed at reducing lumbar lordosis while walking.

PURPOSE

The aim of this study was to assess the short-term effectiveness of a prototype LSS belt compared to a lumbar support in improving walking ability in patients with degenerative LSS.

STUDY DESIGN

This was a two-arm, double-blinded (participant and assessor) randomized controlled trial.

PATIENT SAMPLE

We recruited 104 participants aged 50 years or older with neurogenic claudication, imaging confirmed degenerative LSS, and limited walking ability.

OUTCOME MEASURES

The primary measure was walking distance measured by the self-paced walking test (SPWT) and the primary outcome was the difference in proportions among participants in both groups who achieved at least a 30% improvement in walking distance from baseline using relative risk with 95% confidence intervals.

METHODS

Within 1 week of a baseline SPWT, participants randomized to the prototype LSS belt group (n=52) and those randomized to the lumbar support group (n=52) performed a SPWT that was conducted by a blinded assessor. The Arthritis Society funded this study ($365,000 CAN) with salary support for principal investigator funded by the Canadian Chiropractic Research Foundation ($500,000 CAN for 5 years).

RESULTS

Both groups showed significant improvement in walking distance, but there was no significant difference between groups. The mean group difference in walking distance was ?74 m (95% CI: ?282.8 to 134.8, p=.49). In total, 62% of participants wearing the prototype LSS belt and 82% of participants wearing the lumbar support achieved at least 30% improvement in walking distance (relative risk, 0.7; 95% CI: 0.5–1.3, p=.43).

CONCLUSIONS

A prototype LSS belt demonstrated significant improvement in walking ability in degenerative LSS but was no better than a lumbar support.  相似文献   
5.
6.
7.

Background and objective

Erector spinae plane block is a valid technique to provide simultaneously analgesia for combined thoracic and abdominal surgery.

Case report

A patient underwent open esophagectomy followed by reconstructive esophagogastroplasty but refused thoracic epidural analgesia; a multi‐modal analgesia with a multiple erector spinae plane block was then planned. Three erector spinae plane catheters (T5 and T10 on the right side and T9 on the left side) for continuous analgesia were placed before surgery. During the first 48 h pain was never reported in the thoracic area but the patient reported multiple times to feel a pain well localized in epigastrium, but never localized in any other abdominal quadrant.

Discussion

Erector spinae plane block is a valid technique to provide analgesia simultaneously for combined thoracic and abdominal surgery and could be a valid alternative strategy if the use of epidural analgesia is contraindicated.  相似文献   
8.
Ibrutinib is an oral inhibitor of Bruton tyrosine kinase approved for the treatment of chronic lymphocytic leukaemia, mantle cell lymphoma and refractory Waldenstrom's disease. It increases progression‐free survival, overall survival, response rate. The most frequent adverse reactions, are increased risk in of bleeding and atrial fibrillation, but several reports of more dangerous rhythm disturbances have been recently reported in literature. A case of a patient with refractory Waldenstrom's disease, who developed ventricular fibrillation while taking ibrutinib, is reported, along with a concise literature review.  相似文献   
9.

Objectives

This study applied advanced 4-dimensional flow magnetic resonance imaging processing to assess differences in aortic flow dynamics after valve sparing root replacement, with and without reconstruction of the Valsalva sinuses.

Methods

We enrolled patients after valve sparing root replacement with a straight tubular prosthesis (n = 10) or with a prosthesis with Valsalva neosinuses (n = 10); age-matched subjects without cardiovascular diseases served as controls (n = 10). 4-Dimensional flow magnetic resonance imaging acquisitions were performed on a 3.0T magnetic resonance imaging unit. In-house processing was used to segment the aortic lumen and extract the volumetric 4-dimensional flow velocity field. Velocity flow streamlines were computed to compare the amount of rotational flow and wall shear stress. Occurrence of abnormal wall shear stress (WSS) was estimated within the descending aorta of each surgical group.

Results

Physiologic-like sinus vortices were visible in the aortic root when using the prosthesis with neosinuses, whereas straight tubular graft revealed localized intrados malrotations (P = .003 for organized vortical structures vs neosinuses graft and P < .001 vs control). In the ascending aorta, recreation of the sinuses resulted in significantly lower velocity and WSS than in the straight tubular graft (P < .001) and controls (P < .001), these alterations were attenuated in the mid-descending aorta. Incidence of abnormal WSS was markedly higher in the straight tube grafts than neosinus of Valsalva grafts.

Conclusions

Re-creation of the sinuses of Valsalva during valve-sparing root replacement is associated with more physiologic flow and significantly lower WSS in the aortic root. Lower WSSs in the distal thoracic aorta is a novel finding with potential implications on distal aortic remodeling.  相似文献   
10.
The succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.  相似文献   
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