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1.

Background

Invasive candidiasis by Candida albicans is associated with high morbidity and mortality, due in part to the late implementation of an appropriate antifungal therapy hindered by the lack of an early diagnosis.

Aims

We aimed to evaluate the in vitro antifungal activity of the antibodies against C. albicans germ tubes (CAGTA) raised in a rabbit model of candidemia.

Methods

We measured the effect of CAGTA activity by colorimetric XTT and crystal violet assays, and colony forming units count, both on C. albicans planktonic cells and during the course of biofilm formation and maturation. Viability and cell morphology were assessed by optical, fluorescent or scanning electron microscopy.

Results

CAGTA ≥50 μg/ml caused a strong inhibition of C. albicans blastospores growth, and DiBAC fluorescent staining evidenced a fungicidal activity. Moreover, electron microscopy images revealed that CAGTA induced morphological alterations of the surface of C. albicans germ tubes grown free as well as in biofilm. Interestingly, CAGTA ≥80 μg/ml reduced the amount of C. albicans biofilm, and this effect started at the initial adhesion stage of the biofilm formation, during the first 90 min.

Conclusions

This is the first report showing that CAGTA reduce C. albicans growth, and impair its metabolic activity and ability to form biofilm in vitro. The antigens recognized by CAGTA could be the basis for the development of immunization protocols that might protect against Candida infections.  相似文献   

2.

Background

Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries.

Aims

The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil.

Methods

A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data.

Results

A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference.

Conclusions

In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy.  相似文献   

3.

Background

Matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF-MS) represents a revolution in the identification of microorganisms of clinical interest. Many studies have confirmed the accuracy and fastness of this tool with routine strains.

Aims

To identify clinical isolates of Candida from patients diagnosed with candidemia.

Methods

Vitek-MS? system was used with a collection of 298 blood isolates of the genus Candida represented by 9 different species. Sequencing of the internal transcribed spacer (ITS) region of ribosomal DNA cluster was used as the reference method.

Results

The results of Vitek-MS? were concordant with those obtained with the reference method for 279 (93.62%) isolates (Kappa coefficient (κ) = 0.91). Vitek-MS? misidentified 10 (3.36%) isolates and did not identify 9 (3.02%) isolates.

Conclusions

This study determines the potential of Vitek-MS? in yeast identification, being a reliable and fast alternative in the clinical laboratory, with an acceptable sensitivity of 82% (IC 95%: 70–90.6%), in comparison with a 100% (IC 95%: 92.9–100%) sensitivity of the conventional methods.  相似文献   

4.

Introduction

The incidence of breast carcinoma (BC) has increased in the last years. Between 2 and 12% of patients diagnosed with BC will develop bilateral breast carcinoma (BBC). The treatment of these carcinomas is more aggressive than unilateral BC.

Purpose

To perform a retrospective qualitative analysis of BBC patients whose treatment has included brachytherapy (BT) and to present a revised literature on this issue.

Material and methods

The cases of BBC whose treatment included brachytherapy were revised. The literature on this issue was refreshed.

Results

Five women, aged between 54 and 78 at the time of the diagnosis, submitted to conservative surgery followed by external radiotherapy (RT) with boost of BT or exclusive BT (APBI), in the IPO-P BT Service between 2003 and 2016.

Discussion

The patients with BBC have slightly higher rates of local recurrences, mostly in the tumor bed, where there is a higher risk of local recurrence. Patients treated with BT had lower rates of recurrences than those treated with photons and electrons.

Conclusions

BBC represents a complex challenge for doctors, because in some cases there is a tendency to use more aggressive treatments and, at the same time, it is not easy to achieve the timing for the correct treatment.  相似文献   

5.

Background

Transforming growth factor beta (TGF-β) is a multipurpose cytokine, which plays a role in many cellular functions such as proliferation, differentiation, migration, apoptosis, cell adhesion and regulation of epithelial to mesenchymal transition. Despite many studies having observed the effect that TGF-β plays in colorectal cancer, its role in the colorectal stem cell population has not been widely observed.

Method

This systematic review will analyse the role of TGF-β in the stem cell population of colorectal cancer.

Results

The effects on the stem cell phenotype are through the downstream proteins involved in activation of the TGF-β pathway. Its involvement in the initiation of the epithelial to mesenchymal transition (EMT), the effect of colorectal invasion and metastasis regulated through the Smad protein involvement in the EMT, initiation of angiogenesis, promotion of metastasis of colorectal cancer to the liver and its ability to cross-talk with other pathways.

Conclusion

TGF-β is a key player in angiogenesis, tumour growth and metastasis in colon cancer.  相似文献   

6.

Aim

To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology.

Background

The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy.

Materials and methods

Clinical information of patients who received PBT and VDC-IE between April 2009 and May 2016 was collected retrospectively. The intervals between each course of VDC-IE and adverse events were assessed.

Results

Fifteen patients were evaluated. No delays in the intervals of chemotherapy due to transfer were observed. There were no adverse events caused during/just after transfer and no increases in adverse events. The estimated 4-year overall and event-free survival rates were 94.6% and 84.8%, respectively.

Discussion

Although the results of efficacy are preliminary, survival rates were comparable with past studies. More experience and follow-up are required to further assess the efficacy of PBT for patients with ESFT.

Conclusion

Multidisciplinary therapy for children with ESFT involving transfer to our hospital for PBT during VDC-IE was feasible without treatment delay or an increase in adverse events.  相似文献   

7.

Background

Fungal rhinosinusitis has become an increasingly recognized disease, being Aspergillus species responsible for most of the cases. Its diagnosis is quite difficult because of the non-specific symptoms and low sensitivity of the current diagnostic methods.

Aims

An Aspergillus-specific nested polymerase chain reaction (PCR) assay using biopsy specimens taken from the maxillary sinuses was performed in order to assess its usefulness. Conventional diagnostic methods (histology and culture) were also carried out.

Methods

A case–control study was performed in the Institute of Stomatology, Jagiellonian University in Kraków, between 2011 and 2014. The case group consisted of 21 patients with suspected rhinosinusal mycetoma while the control group included 46 patients with no suspicion of fungal rhinosinusitis. The two-step PCR assay amplified an Aspergillus specific portion of the 18S rRNA gene. Interval estimation of sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated to assess the diagnostic test performance. The agreement between the PCR and the other tests was evaluated using the Kappa coefficient (k).

Results

Ninety percent of the samples obtained from patients diagnosed with mycetoma yielded positive PCR results. The PCR showed almost perfect concordance with histology (k = 0.88). Sensitivity, specificity, PPV and NPV estimates were 90%; 95% CI: (55.5–99.7%), 98.3%; 95% CI: (90.9–100%), 90%; 95% CI: (55.5–99.7%) and 98.3%; 95% CI: (90.9–100%), respectively. One clinical sample showed growth of Aspergillus fumigatus and positive PCR despite the negative histological examination.

Conclusions

Nested PCR assay is a promising diagnostic tool to evaluate the presence of Aspergillus in the tissue of maxillary sinus from patients with suspicion of sinus aspergillosis.  相似文献   

8.

Purpose of Review

This review summarizes the fungal diagnostic measures currently available for use in paediatric patients at high risk for developing invasive fungal disease (IFD) and those suspected of having an IFD. The clinical utility of each test is described based on reported performances of individual tests in specific paediatric populations.

Recent Findings

Available studies in the paediatric population are scarce and are characterized by a huge heterogeneity in underlying diseases (e.g. different risk for IFD), different study objectives and management strategies (screening versus diagnostic) used.

Summary

A final valuation of paediatric studies on fungal diagnostic tools is limited. While the galactomannan and fungal PCR assays are useful to exclude the presence of IFD, it is unclear if mannan, mannan antibodies and β-D-glucan are of benefit due to a lack of studies or validation of the cut-off, respectively. Well-designed multicentre paediatric studies are urgently needed to improve the outcome of IFD.
  相似文献   

9.
10.

Aim

To develop a tool in order to guide pre-irradiation dental care (PIDC) for patients with oropharyngeal cancers.

Background

Osteoradionecrosis of the jaws is a potential complication of radiotherapy (RT) for head and neck cancers. To prevent this complication, PIDC can involve multiple dental extractions as a preventative measure to avoid post-RT complications. However, there is no standardized tool to guide PIDC.

Materials and methods

From January 2005 to October 2015, 120 head and neck cancer patients were prospectively included in a study investigating dysgeusia after RT. From this cohort, patients were enrolled according to the following inclusion criteria: histopathological confirmation of oropharyngeal squamous cell carcinoma; stage T1-4 N1-3 M0; ≤10 missing teeth. Individual teeth were retrospectively delineated on planning computed tomography and doses to dentition were assessed to generate templates.

Results

Thirty-three patients were included. Molars received highest doses with a mean dose of 50?Gy (range; 19–75?Gy). Ipsi-lateral and contralateral wisdom teeth received RT dose superior to 50?Gy in 92% and 56% of cases, respectively. Patients with advanced disease (T4 or N2c-3) received higher mean doses on inferior and ipsi-lateral dental arches compared to other patients (T1-3 N0-2b): 42?Gy vs. 39?Gy and 44?Gy vs. 39?Gy (p?<?0.05), respectively.

Conclusion

Pre-RT dose distribution templates are an objective way to prepare PIDC. Further studies with a larger cohort are needed to validate these templates.  相似文献   

11.

Aim

This study evaluated the frequency and long-term dynamics of early and late post irradiation damage after proton–photon or photon therapy for locally advanced prostate cancer.

Background

The results of a randomized study of proton–photon or photon therapy using several fractionation regimes were analyzed in 272 patients with high and intermediate risk of progression.

Materials and methods

Three variants of proton boost fractionation were studied sequentially: 3.0 (8 daily fractions), 4.0 (5 fractions, 3 or 5 fractions/week), and 5.5 (3 fractions, 3 fractions/week) Gy(RBE).

Results

A significant decrease in the severity of both acute and late gastrointestinal injuries is achievable with a proton beam. The dynamics of late gastrointestinal and genitourinary toxicity over a 10-year period were generally characterized by a decrease in severity of morbidity by 30% and 15%, respectively.

Conclusions

Local irradiation with a fractional dose of 3.0–5.5 Gy(RBE) and a cumulative dose of 28.0–28.8 Gy(RBE) for protons significantly reduces the early and late rectitis severity, but does not reduce the risk of lower urinary tract injuries. Fractionation regimens do not significantly differ in toxicity levels.  相似文献   

12.

Aim

The present retrospective study was to compare toxicity and survival outcomes in a group of low-risk PCa patients treated with either the preoperative planning technique (145?Gy) or the real-time IoP technique (160?Gy).

Background

The two most common permanent seed implantation techniques are preoperative planning (PP) with 145?Gy and real-time intraoperative planning (IoP) with 160?Gy. Although IoP has largely replaced PP at many centres in recent years, few studies have directly compared these two techniques.

Materials and methods

Retrospective study of 408 patients with low-risk PCa treated with permanent seed implant brachytherapy at our institution between October 2003 and December 2014. Of these, 187 patients were treated with PP at a dose of 145?Gy while 221 received real-time IoP with 160?Gy.

Results

At a median follow up of 90 months, 5- and 8-year rates of biochemical relapse-free survival (BRFS) were 94.8% and 86% with the IoP technique versus 90.8% and 83.9%, respectively, with PP. The maximum dose to the urethra was <217?Gy with both techniques. Despite the higher dose, IoP did not cause any significant increase in toxicity (p?=?0.11).

Conclusions

The present study shows that real-time intraoperative brachytherapy at a dose of 160?Gy yield better biochemical control than preoperative planning at 145?Gy. In addition, urinary toxicity did not increase, despite the dose escalation, probably because the dose constraints to the urethra were met despite the increased dose escalation. These findings support the use of real-time IoP.  相似文献   

13.

Aim

To evaluate whether hypofractionation with integrated boost to the tumour bed using intensity-modulated radiation therapy is an acceptable option and to determine whether this treatment compromises local control, toxicity and cosmesis.

Background

Retrospective studies have demonstrated that patients who are treated with HF and integrated boost experience adequate local control, a dosimetric benefit, decreased toxicity and acceptable cosmesis compared with conventional fractionation.

Materials and methods

A retrospective, observational and longitudinal study was conducted from January 2008 to June 2015 and included 34 patients with breast cancer (stage 0–II) who were undergoing conservative surgery.The prescribed doses were 45?Gy in 20 fractions (2.25?Gy/fraction) to the breast and 56?Gy in 20 fractions (2.8?Gy/fraction) to the tumour bed.

Results

Thirty-four patients were included. The mean follow-up was 49.29 months, and the mean age was 52 years. The mean percentage of PTV from the mammary region that received 100% of the prescribed dose was 97.89% (range 95–100), and the mean PTV percentage of the tumour bed that received 100% of the dose was 98% (95–100).The local control and the overall survival were 100%, and the cosmesis was good in 82% of the patients. Grade 1 acute toxicity was present in 16 patients (47%), and grade 1 chronic toxicity occurred in 6 cases (18%).

Conclusion

The results of the present study demonstrate that hypofractionation with integrated boost using intensity-modulated radiation therapy is an acceptable option that provides excellent local control and low toxicity.  相似文献   

14.

Aim

This study aims at examining absolute dose verification of step-and-shoot intensity modulated radiation treatment (IMRT) of prostate and brain patients by use of ion chambers of two different volumes and thermoluminescent detectors (TLD).

Background

The volume of the ion chamber (IC) is very important for absolute dose verification of IMRT plans since the IC has a volume average effect. With TLD detectors absolute dose verification can be done measuring the dose of multiple points simultaneously.

Materials and methods

Ion chambers FC65-P of volume 0.65 cc and semiflex of volume 0.125 cc as well as TLDs were used to measure the central axis absolute dose of IMRT quality assurance (QA) plans. The results were compared with doses calculated by a treatment planning system (TPS). The absolute doses of off axis points located 2 cm and 4 cm away from the isocenter were measured with TLDs.

Results

The measurements of the 0.125 cc ion chamber were found to be closer to TPS calculations compared to the 0.65 cc ion chamber, for both patient groups. For both groups the root mean square (RMS) differences between doses of the TPS and the TLD detectors are within 3.0% for the central axis and points 2 cm away from the isocenter of each axis. Larger deviations were found at the field edges, which have steep dose gradient.

Conclusions

The 0.125 cc ion chamber measures the absolute dose of the isocenter more accurately compared to the 0.65 cc chamber. TLDs have good accuracy (within 3.0%) for absolute dose measurements of in-field points.  相似文献   

15.
16.

Objective

To determine the frequency of successful aging (SA) and its relationship with frailty in an elderly population.

Material and methods

An analytical cross-sectional study of subjects ≥60 years of age seen as outpatients in a general hospital. Successful aging was defined as scores of ≥ 90 in the Barthel index and ≤ 2 in the Pfeiffer test. Frailty was determined using the Fried criteria.

Results

The study included 400 subjects (272 women and 128 men), with a mean age of 71.6 ± 8.2 years. The SA frequency was 40.4%. frail status was statistically higher in non-successful aging subjects than in SA subjects (161.7 versus 7.9%; P<.001). Women were more frequently frail, while being a pensioner/retired and married were associated less frequently with frailty.

Conclusions

Successful aging is associated with a lower level of frailty.  相似文献   

17.

Objective

The current study proposes an automated machine learning approach for the quantification of cells in cell death pathways according to DNA fragmentation.

Methods

A total of 17 images of kidney histological slide samples from male Wistar rats were used. The slides were photographed using an Axio Zeiss Vert.A1 microscope with a 40x objective lens coupled with an Axio Cam MRC Zeiss camera and Zen 2012 software. The images were analyzed using CellProfiler (version 2.1.1) and CellProfiler Analyst open-source software.

Results

Out of the 10,378 objects, 4970 (47,9%) were identified as TUNEL positive, and 5408 (52,1%) were identified as TUNEL negative. On average, the sensitivity and specificity values of the machine learning approach were 0.80 and 0.77, respectively.

Conclusion

Image cytometry provides a quantitative analytical alternative to the more traditional qualitative methods more commonly used in studies.  相似文献   

18.

Aim

Isokinetic assessment of biomechanical parameters of the shoulder joint at the operated side versus non-operated side in patients treated surgically for breast cancer according to the type of surgery performed.

Background

Despite significant progress in medicine, comprehensive cancer therapy may still cause a number of undesired structural and functional effects. The most frequent complications include long-term weakening of muscles within the shoulder and upper extremity at the operated side.

Materials and methods

The study enrolled 57 patient, divided into two groups: mastectomy and BCT. Diagnostic tests were carried out on the groups to assess biomechanical parameters (peak torque, power, total work) of the shoulder joint in internal and external rotation.

Results

The results of the isokinetic test revealed a considerable reduction of dynamic properties of the muscle groups responsible for the function of the shoulder joint at the operated side. The deficits observed, depending on the angular speed and plane of rotation, were from 22.3% to 32.7% and from 23.1% to 29.4% for muscle power and total work, respectively. The least noticeable loss was that of muscular torque, ranging from 6.5% to 18.3%.

Conclusion

None of the treatment methods applied ensured a full release of the restriction within the shoulder and upper limb. The deficits observed may constitute a serious disorder of the musculoskeletal system; therefore, a clinical study of biomechanical parameters of the shoulder joint may be an important control of patients’ functional status after breast cancer treatment.  相似文献   

19.

Aim

To evaluate the association between dose–volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes.

Background

Data on the association between DVHs and health-related quality of life (HRQoL) in prostate cancer (PCa) patients are limited.

Materials and methods

Five-year follow-up study of 154 patients with organ-confined (stage T1/T2) PCa treated with EBRT between January 2003 and November 2005. HRQoL was evaluated with the Expanded Prostate Cancer Index (EPIC). DVH for OARs (penile bulb, rectum and bladder) were created for all patients for whom data were available (119/154; 77%). The functional data analysis (FDA) statistical method was used. HRQoL data was collected prospectively and data analysis was performed retrospectively.

Results

Worsening of urinary incontinence and obstructive symptoms correlated with higher DVH dose distributions at 24 months. Increased rectal bleeding at months 24 and 60 correlated with higher DVH dose distributions in the 40–70?Gy range. Patients with deterioration in rectal incontinence presented a higher DVH distribution range than patients without rectal incontinence. Penile bulb DVH values and erectile dysfunction were not significantly associated.

Conclusions

DVH parameters and post-radiotherapy HRQoL appear to be closely correlated, underscoring the importance of assessing DVH values prior to initiating EBRT to determine the risk of developing HRQoL related adverse effects. Advanced treatment modalities may be appropriate in high risk cases to minimize treatment-related toxicity and to improve treatment outcomes and HRQoL. Future studies are needed to better elucidate the association between pre-treatment DVH parameters in organs at risk and subsequent HRQoL.  相似文献   

20.

Background

Although fortunately very rare in countries with a temperate climate, certain factors, such as clinical or pharmacological immunosuppression, may cause Fusarium-related fungal infections to become an emerging problem. Moreover, Fusarium is one of the most important etiological agents in exogenous endophthalmitis, which is often favored by the disruption of the epithelial barriers.

Aims

The aim of this series of clinical cases is to identify characteristic clinical findings that may allow an early diagnosis and more efficient management of this ophthalmologic emergency.

Methods

Three cases of endophthalmitis due to Fusarium solani and Fusarium oxysporum, diagnosed in 2009, 2010, and 2014 in patients from two different health regions belonging to the same health system and separated by around 43 miles, are presented. The Fusarium isolates were initially identified microscopically and the species subsequently confirmed by sequencing the elongation factor alpha (EFα) and internal transcribed spacers (ITS). Susceptibility to antifungal agents was determined using the EUCAST broth dilution method.

Results

Evolution was poor as two of the three patients progressed to phthisis bulbi despite surgical measures and broad-spectrum antifungal antibiotic therapy.

Conclusions

It is essential to rapidly instigate multidisciplinary measures to combat suspected endophthalmitis due to Fusarium given the poor prognosis of this type of infection.  相似文献   

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