Publication date: Available online 24 February 2018
Source:Injury
Author(s): Hyung-Joo Lee, Youn-Jung Kim, Dong-Woo Seo, Chang Hwan Sohn, Seung Mok Ryoo, Shin Ahn, Yoon-Seon Lee, Won Young Kim, Kyoung Soo Lim
ObjectiveThe detection of intracranial injury in patients with facial injury rather than traumatic brain injury (TBI) remains a challenge for emergency physicians. This study aimed to evaluate the incidence and risk factors of intracranial injury in patients with orbital wall fracture (OWF), who were classified with a chief complaint of facial injury rather than TBI.MethodsThis retrospective case-control study enrolled adult OWF patients (age ≥ 18 years) who presented at the hospital between January 2004 and March 2016. Patients with definite TBI were excluded because non-contrast head computed tomography (CT) is recommended for such patients.ResultsA total of 1220 patients with OWF were finally enrolled. CT of the head was performed on 677 patients, and the incidence of concomitant intracranial injury was found to be 9% (62/677). Patients with definite TBI were excluded. Symptoms raising a suspicion of TBI, such as loss of consciousness, alcohol intoxication, or vomiting, were present in 347 of the patients, with 44 of these patients (13%) showing a concomitant intracranial injury. Of the 330 patients without such symptoms, 18 (6%) demonstrated a concomitant intracranial injury. In OWF patients, superior wall fracture (odds ratio [OR], 4.15; 95% confidence interval [CI], 2.06–8.34; P < 0.001), associated frontal bone fracture (OR, 4.38; 95% CI, 2.08–9.23; P < 0.001), and older age (decades) (OR, 1.03; 95% CI, 1.01–1.04; P = 0.002) were independent risk factors for concomitant intracranial injury.ConclusionsEmergency physicians should maintain a high degree of suspicion of TBI, even when their primary concern is facial trauma with OWF. Head CT is recommended for OWF patients with a superior OWF, frontal bone fracture, or increased age.
http://ift.tt/2F01zux
Σάββατο 24 Φεβρουαρίου 2018
Incidence of intracranial injury in orbital wall fracture patients not classified as traumatic brain injury
Blood vessel occlusion with erythrocyte aggregates causes burn injury progression: microvasculature dilation as a possible therapy
Abstract
Other than radiation, caustic strong alkali insults, and massive over-reactive inflammation (pyoderma gangrenosum), injury progression after trauma is usually secondary to ischemia from decreased blood vessel perfusion. Impeded blood flow contributes to injury progression in a variety of disorders including venous stasis ulcers, arterial ulcers, diabetic ulcers, flap and graft necrosis, sickle cell disease, cryoglobulinemia and other vasculopathies, vasculitis, post-myocardial infarction, and post stroke. The cause of impeded blood flow in these disorders/diseases is well known.
This article is protected by copyright. All rights reserved.
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Comparison of cyclic fatigue resistance and bending properties of two reciprocating nickel-titanium glide path files
Abstract
Aim
To compare the cyclic fatigue resistance and bending properties of R-Pilot and WaveOne Gold (WOG) Glider files, at intracanal temperature (35°C).
Methodology
Forty R-Pilot and 40 WOG Glider files were subjected to a cyclic fatigue resistance test (n = 20), calculating the time to fracture (TTF) in an artificial stainless-steel canal. The length of the fractured file tips (FL) was also measured. The fracture surface of fragments was examined with a scanning electron microscope and the cross-sectional area of the fractured surfaces were measured. Flexibility of the tested files (n = 20) was determined by 45° bending test. Data were analyzed statistically using the Mann-Whitney U test at 5% significance level.
Results
Time to fracture value was found to be significantly higher in the R-Pilot group compared to the WOG Glider (P < 0.05). There was no significant difference between groups according to the fracture length. The bending resistance of R-Pilot files was significantly higher than WOG Glider files (P < 0.05).
Conclusions
A significant greater cyclic fatigue resistance was observed for R-Pilot files compared to WOG Glider instruments, although the bending resistance of WOG Glider files was lower.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ouqqfy
Prevalence of vertical root fractures in teeth planned for apical surgery. A retrospective cohort study
Abstract
Aim
To evaluate retrospectively the prevalence of vertical root fractures (VRF) in a cohort of patients during apical surgery and the factors possibly associated with VRF.
Methodology
The sample consisted of 944 root filled teeth belonging to 768 patients (49.3% males and 50.7% females; mean age 43.5±11.2 years, range 22-68 years), consecutively referred for endodontic surgery over a six-year period. All patients underwent a clinical assessment of their signs and symptoms. Periapical radiographs of teeth that were candidates for endodontic surgery were taken. Sixty-eight teeth with VRF were identified. Vertical root fractures were identified in pre-surgical screenings in 32 cases (47.1%) and these did not undergo surgery. Another 36 cases of VRF were noted during the intervention for root-end resection. The influence of posts, post type, tooth type, periodontal probing defects, spontaneous pain, sinus tract, and follow-up duration was assessed using a logistic regression analysis.
Results
Vertical root fractures occurred significantly more frequently (P<0.001) when a post was present (61 VRF out of 377 teeth with post, prevalence 16.2%) than in teeth without a post (1.2%). Threaded posts and cast posts were significantly more involved in VRF than fibre, silica or carbide posts (P<0.001). Most fractures (80.9%) occurred 1 to 5 years after root canal treatment. Sinus tracts, probing defects and spontaneous pain were significantly more associated with VRF cases than with non-fractured teeth.
Conclusions
In the present group of teeth, the major risk for VRF was represented by posts retained by actively engaging the canal via mechanical design (thread), or by frictional fit (cast).
This article is protected by copyright. All rights reserved.
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Higher than reported adolescent and young adult clinical trial enrollment during the “Golden Age” of melanoma clinical trials
Abstract
Clinical trial enrollments in adolescents and young adults (AYA) with cancer have historically been lower than those in pediatric and older adult populations. We sought to examine therapeutic trial enrollment rates at our cancer center. We performed a retrospective evaluation of AYA patients treated before and after the first checkpoint inhibitor trial opened at our cancer center in 2007. We examined gender, stage at presentation and insurance status in terms of trial enrollment. We compared the trial participation rate of AYA patients with that of older adults. In this adult facility, 12.7% (1,831) of total patients were between age 15 and 39. Overall therapeutic clinical trial rate was 17.6% which increased to 19.8% since 2007. Both nodal disease or metastatic disease at presentation was associated with increasing odds of trial enrollment (OR = 5.36 and P < 0.001 for nodal disease and OR = 7.96 and P < 0.001 for metastatic disease). There was a nonstatistically significant trend toward improved 3-year overall survival in the AYA patients with advanced presentation that enrolled on clinical trials compared with those not enrolled on trials since 2007. AYA clinical trial enrollment at a comprehensive care center melanoma program was higher than reported in the literature overall for AYA patients. This 1,831 patient cohort may provide a foundation for more detailed investigation toward quantifying the effects of clinical trial enrollment in terms of age-specific benefits and toxicities for AYA patients with malignancies that have their peak incidence in older adults.
Adolescents and young adult (AYA) patients have had lower clinical trial accruals over the past few decades and this has led to fewer survival benefits when comparing these patients to children and older adults with cancer. Here we report nearly 1 out of 5 AYA melanoma patients enrolled on trials during the past decade when these trials improved survival substantially.
http://ift.tt/2FuPjQt
Humoral immune responses to infection: common mechanisms and unique strategies to combat pathogen immune evasion tactics
Ismail Sebina | Marion Pepper
http://ift.tt/2F0GCiT
“The pen is mightier than the sword” – suicidal trans-orbital intracranial penetrating injury from a pencil
Abstract
A 40-year-old drug addict, who was being treated with methadone and occupational therapy, committed suicide by striking a wooden pencil into his right eye socket. While still conscious, he hit his head hard against a table, jamming the pencil even deeper into his head. The autopsy showed that the pencil missed the globe and lodged in the inner part of the right eye socket. It pierced the orbital part of the right ethmoid bone, the right ethmoid cells, and the right superior nasal concha, then passed through the body of the sphenoid bone and the clivus of the occipital bone before stopping in the brain tissue. The basilar artery was transected at the pontomedullary junction, where the tip of the pencil had lodged. Also, at the pontomedullary junction, an approximately 3 mm deep laceration of the brainstem was evident together with flecks of green paint. Histological examination revealed that laceration at the pontomedullary junction was even deeper than the macroscopic appearance had suggested, with several small lateral cracks, focal deep hemorrhage, and disruption of both gray and white matter of the brainstem. Fragments of cellulose originating from the wooden pencil could also be clearly distinguished. Toxicological analysis was performed using liquid chromatography with mass spectrometry, and it showed traces of methadone in the blood and humor vitreous samples. The cause of death was damage to the vital structures in the brainstem, resulting from a penetrating injury to the head by a pencil. Herein, we present a self-inflicted trans-orbital penetrating injury by a non-missile, low-velocity object – a pencil, with a rather unusual, immediately incapacitating outcome.
http://ift.tt/2HJ6Y7N
The utility of plastinates in court: a case of firearm homicide
Abstract
Plastination is a technique renowned for its use in the preservation of human tissues or organs, and is mainly employed in anatomical training and in research regarding various scientific fields. The advantages of this method are related to the natural appearance, absence of odor, and easy-handling of the plastinated products. The use of plastinates in forensic sciences, their potential role in personal identification, and their usefulness in interpretation of post-mortem findings has been described, although literature on this topic is poor. The present paper is the first report of a firearm homicide where the brain of the victim was plastinated and presented in court as documentary evidence. Three dimensional examination of the brain during the trial allowed the judge to directly evaluate the pathway of the projectile and to compare it with the information that was presented based on depositions, post mortem data and police investigations, in a more straightforward manner. The important role played by plastination in the reported case in assisting with the final verdict could be a catalyst to extend the use of this technique to other criminal cases.
http://ift.tt/2GH9gmt
Impact of time-related factors on biologically accurate radiotherapy treatment planning
Abstract
Background
The incomplete repair (IR) model expresses the cell repair effect from radiation-induced damage over time, which is given little consideration in actual treatment planning. By incorporating the IR model into the normal tissue complication probability (NTCP), the accuracy and safety of treatment plan evaluations concerning the effect of repair can be improved. This study aims to evaluate the impact of incorporating the IR model into the NTCP by varying time-related factors such as the repair half-time (T1/2) and the junction-shift sc3hedule in craniospinal irradiation (CSI).
Methods
CSI was planned retrospectively, and the NTCP of the spinal cord was calculated with the IR model for values of T1/2 from 1 to 10 h. The NTCP in the case of changing the junction-shift schedule was also examined in the same manner.
Results
The NTCP with the IR model increased with increasing T1/2, which is prominent for the larger T1/2. By changing the junction-shift schedule, the NTCP with the IR model decreased when adjacent fields overlapped.
Conclusions
The IR model is a valuable addition to treatment planning because it enables the NTCP to be evaluated including the effect of repair and differences in scheduling to be reflected in the NTCP. However, these are largely dependent on the value of the T1/2.
http://ift.tt/2F2El6U
Dosimetric impact of tumor treating field (TTField) transducer arrays onto treatment plans for glioblastomas – a planning study
Abstract
Background
Tumor-Treating Fields (TTFields) are a novel treatment strategy for glioblastoma (GBM) that is approved for the use concomitantly to adjuvant chemotherapy. Preclinical data suggest a synergistic interaction of TTFields and radiotherapy (RT). However, the dosimetric uncertainties caused by the highly dense arrays have led to caution of applying the TTF setup during RT.
Methods
In a RW3 slab phantom we compared the MV- and kV-CT based planned dose with the measured dose. VMAT-plans were optimized on MV-CTs of an Alderson head phantom without TTF arrays and then re-calculated on the same phantom equipped with TTF arrays. Dose at organs at risk (OAR) and target volumes (PTVs) were compared.
Results
Measurements at a depth of 2, 3 and 4 cm of a RW 3 slab phantom show an attenuation due to TTField arrays of 3.4, 3.7 and 2.7% respectively. This was in-line with calculated attenuations based on MV-CT (1.2, 2.5 and 2.5%) but not with the attenuation expected from kV-CT based calculations (7.1, 8.2 and 8.6%). Consecutive MV-CT based VMAT planning and re-calculation reveals, that the conformity and homogeneity are not affected by the presence of TTField arrays. The dose at organs at risk (OAR) can show increases or decreases by < 0.5 Gy, which should be considered especially in cases next to the scull base.
Conclusion
MV-CT based dose calculation results in reliable dose distributions also in the presence of TTField arrays. There is a small but clinically not relevant interaction between the TTField arrays and VMAT dose application. Thus, daily replacement of TTField arrays is not necessary in regard to deeply located OARs. RT is feasible, when a VMAT treatment plan is optimized to an array free planning CT. As the biologic effect of a concomitant treatment especially on OARs is currently unknown, a concomitant treatment should be performed only within clinical trials.
http://ift.tt/2CHfYGH
Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment
Abstract
Background
We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy.
Methods
We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (Dmax) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy.
Results
A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26–77 years), and 14 (53.8%) had grade III/IV tumors. The median Dmax to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD2/2), was 7.4 Gy2 (0.7–13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were − 7.7% (95% confidence interval [CI], − 19.6% to 4.2%), − 9.2% (95% CI, − 25.4% to 7.0%), and − 3.4% (− 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration.
Conclusions
The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.
http://ift.tt/2EZ1GXh
Unresectable hepatic PEComa: a rare malignancy treated with stereotactic body radiation therapy (SBRT) followed by complete resection
Abstract
Background
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors occurring in various anatomic regions. Although diagnostic criteria and treatment management are not established, current treatment options consist of surgery and chemotherapy including mTOR inhibitors.
Stereotactic body radiation therapy (SBRT) is a non-invasive ablative treatment which has shown excellent control rates for more common types of unresectable liver tumors and metastases. In this report we present a rare case of PEComa of the liver that was treated by stereotactic radiotherapy followed by resection. Staging and evaluation of treatment response was done by FDG-PET/CT. This case highlights the potential of SBRT as a neoadjuvant treatment even for rare liver malignancies. It is the first case of liver PEComa treated by SBRT and resection.
Case presentation
A 52-year-old woman presented at an external hospital with abdominal pressure and pain in the right upper abdominal quadrant. A CT scan showed a 700 cm3 liver lesion in segment IV. In repeated biopsy in July 2015 histopathological workup showed a pleomorphic epitheloid tumor with small to medium sized cells expressing vimentin and melan-A while being negative for cytokeratin establishing the diagnosis of PEComa of the liver.
To achieve high, ablative doses a stereotactic body radiotherapy (SBRT) technique was chosen consisting of 60Gy (biologically effective dose 105Gy) in 8 fractions of 7.5Gy. Radiotherapy planning was based on MRI resulting in a planning target volume (PTV) of 1944 cm3. Treatment toxicity was limited to a slight elevation of transaminases (grade 1 and 3). A complete resection was performed 21 weeks after radiotherapy confirmed by negative surgical margins.
At last follow-up 21 months after therapy, MRI showed neither local nor distant tumor recurrence. The patient was in stable condition (ECOG 1) and without late radiation toxicity.
Conclusions
This is the first documented case of liver PEComa treated by SBRT and resection. A favorable post-treatment course demonstrates that SBRT is a potential neoadjuvant treatment that is capable of reducing an inoperable rare liver tumor to a resectable lesion.
http://ift.tt/2CH7LlZ
Monitoring of mechanical errors and their dosimetric impact throughout the course of non-coplanar continuous volumetric-modulated arc therapy
Abstract
Background
Volumetric-modulated Dynamic WaveArc therapy (VMDWAT) is a non-coplanar continuous volumetric modulated radiation therapy (VMAT) delivery technique. Here, we monitored mechanical errors and their impact on dose distributions in VMDWAT using logfiles throughout the course of treatment.
Methods
Fifteen patients were enrolled (2 skull base tumor patients and 13 prostate cancer patients). VMDWAT plans were created for the enrolled patients. The prescribed dose for the skull base tumor was set as 54 Gy at 1.8 Gy per fraction, and that for the prostate cancer was set as 72 to 78 Gy at 2 Gy per fraction. We acquired logfiles to monitor mechanical errors and their impact on dose distribution in each fraction. The root mean square error (RMSE) in the multi-leaf collimator (MLC), gantry angle, O-ring angle and monitor unit (MU) were calculated using logfiles throughout the course of VMDWAT for each patient. The dosimetric impact of mechanical errors throughout the course of VMDWAT was verified using a logfile-based dose reconstruction method. Dosimetric errors between the reconstructed plans and the original plans were assessed.
Results
A total of 517 datasets, including 55 datasets for the 2 skull base tumor patients and 462 datasets for the 13 prostate cancer patients, were acquired. The RMSE values were less than 0.1 mm, 0.2°, 0.1°, and 0.4 MU for MLC position, gantry angle, O-ring angle, and MU, respectively. For the skull base tumors, the absolute mean dosimetric errors and two standard deviations throughout the course of treatment were less than 1.4% and 1.1%, respectively. For prostate cancer, these absolute values were less than 0.3% and 0.5%, respectively. The largest dosimetric error of 2.5% was observed in a skull base tumor patient. The resultant dosimetric error in the accumulated daily delivered dose distribution, in the patient with the largest error, was up to 1.6% for all dose-volumetric parameters relative to the planned dose distribution.
Conclusions
MLC position, gantry rotation, O-ring rotation and MU were highly accurate and stable throughout the course of treatment. The daily dosimetric errors due to mechanical errors were small. VMDWAT provided high delivery accuracy and stability throughout the course of treatment.
Trial registration
UMIN000023870. Registered: 1 October 2016.
http://ift.tt/2EQt6PC
Stereotactic Body Radiotherapy (SBRT) for liver metastasis – clinical outcomes from the international multi-institutional RSSearch® Patient Registry
Abstract
Background
Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry.
Methods
Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED10. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test.
Results
The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31–91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm3 (1.6–877 cm3), median SBRT dose was 45 Gy (12–60 Gy) delivered in a median of 3 fractions [1–5]. At a median follow-up of 14 months (1–91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm3) correlated with improved OS (25 months vs 15 months p = 0.0014). BED10 ≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED10 ≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm3 (52 vs 39 months). There was no difference in LC based on histology of the primary tumor.
Conclusions
In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted.
Trial registration
Clinicaltrials.gov: NCT01885299.
http://ift.tt/2CFyyPv
Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation
Abstract
Background
To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de–escalation in stereotactic body radiotherapy for non–small cell lung carcinomas (NSCLC).
Methods
For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re–normalized to the median gross tumor volume dose (GTV–based prescription) to assess the impacts of PTV and normal tissue dose reduction.
Results
With PTV–based prescription, GTV mean dose was much higher with the optimized PIL at 60% with significant reduction of normal lung receiving 30 to 10 Gy (V30–10Gy ), and observable but insignificant dose reduction to spinal cord, esophagus, ribs, and others compared with 85% PIL. Mean doses to the normal lung between PTV and GTV was higher with 60–70% PIL than 85%. The dose gradient index was 5.0 ± 1.1 and 6.1 ± 1.4 for 60 and 85% PIL (p < 0.05), respectively. Compared with the reference 85% PIL plan using PTV–base prescription, significant decreases of all normal tissue doses were observed with 60% and 70% PIL by GTV–based prescription. Yet, the resulting biological effective (BED) mean doses of PTV remain sufficiently high, ranging 104.2 to 116.9 Gy α/β = 10.
Conclusions
Optimizing the PIL with VMAT has notable advantage of improving the dosimetric quality of lung SBRT and offers the potential of dose de–escalation for surrounding tissues while increasing the GTV dose simultaneously. The clinical implication of re–normalizing plans from PTV–prescription at 60–70% to the GTV median dose requires further investigations.
http://ift.tt/2EQDqHx
Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma
Abstract
Background
The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy.
Methods
A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue.
Results
Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart.
Conclusions
When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.
http://ift.tt/2CHHjs8
Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases
Abstract
Background
The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice.
Methods
Data were provided by the population-based Munich Cancer Registry. Between 1998 and 2014, 1048 female patients with diagnosis of DCIS and treated at two Breast Care Centres were included in this observational study. The effectiveness of postoperative radiotherapy and variables predicting the use of radiotherapy were retrospectively analysed.
Results
After adjusting for age, tumour characteristics and therapies, Cox regression analysis for local recurrence-free survival identified RT as an independent predictor for improved local control (HR: 0.579; 95%CI: 0.384–0.872, p = 0.008). Ten-year cumulative incidence of in-breast recurrences was 20.0% following BCS, compared to 13.6% in patients receiving postoperative radiotherapy (p = 0.012). As an estimate for disease-specific survival, 10-year relative survival was 105.4% for patients receiving postoperative radiotherapy and 101.6% without radiotherapy. On multivariate analysis, postoperative radiotherapy was not associated with improved overall survival (HR 0.526; 95%CI: 0.263–1.052, p = 0.069). Over time, a significant increase of RT was registered: while 1998 only 42.9% of patients received postoperative radiotherapy, the proportion rose to 91.2% in 2014. Women aged < 50 years (OR: 2.559, 95%CI: 1.416–4.625, p < 0.001) or with negative hormone receptor status (OR: 2.625, 95%CI: 1.458–4.728, p = 0.001) or receiving endocrine therapy (OR: 1.762, 95%CI: 1.060–2.927, p = 0.029) were more likely to receive postoperative radiotherapy after BCS.
Conclusions
In conclusion, this study provides insights regarding the adoption and treatment pattern of postoperative RT following BCS for DCIS in a large cohort reflecting "real-life" clinical practice in this setting. Postoperative RT was found to be associated with a reduced risk of ipsilateral recurrence and no survival benefit compared to observation alone.
http://ift.tt/2F29irP
Early evaluation of radiation-induced parotid damage in patients with nasopharyngeal carcinoma by T2 mapping and mDIXON Quant imaging: initial findings
Abstract
Background
Radiation-induced parotid damage is a common complication in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy to head and neck region, which severely reduce the life quality of those patients. The aim of this study was to early evaluate the changes of irradiated parotid glands with T2 mapping and mDIXON Quant imaging.
Methods
Forty-one patients with NPC underwent conventional magnetic resonance imaging for nasopharynx and neck, and T2 mapping and mDIXON Quant imaging for bilateral parotid glands within 2 weeks before radiotherapy (pre-RT), 5 weeks after the beginning of radiotherapy (mid-RT), and 4 weeks after radiotherapy (post-RT). Parotid volume, T2 values, fat fraction (FF) values, and mean radiation dose were recorded and analyzed.
Results
From pre-RT to mid-RT, parotid volume decreased (atrophy rate, 27.0 ± 11.5%), while parotid T2 and FF values increased (change rate, 6.0 ± 6.2% for T2 value and 9.1 ± 9.9% for FF value) significantly. From mid-RT to post-RT, parotid T2 value continuously increased (change rate, 4.6 ± 7.7%), but parotid FF value decreased (change rate, − 9.9 ± 18.2%) significantly. Change rate of parotid T2 value significantly correlated with parotid atrophy rate from pre-RT to post-RT (r = 0.313, P = 0.027). Multiple linear regression analysis showed that parotid T2 value (standardized coefficient [SC] = − 0.259, P = 0.001) and FF value (SC = − 0.320, P = 0.014) negatively correlated with parotid volume, while parotid T2 value positively correlated with MR scan time point (SC = 0.476, P = 0.001) significantly. Parotid T2 and FF values showed excellent reproducibility (intraclass correlation coefficient, 0.935–0.992).
Conclusions
T2 mapping and mDIXON Quant imaging is useful for noninvasive evaluation of radiation-induced parotid damage.
http://ift.tt/2CIphGh
1x8 Gy versus 5x4 Gy for metastatic epidural spinal cord compression: a matched-pair study of three prognostic patient subgroups
Abstract
Background
This study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses.
Methods
Patients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included.
Results
In poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function.
Conclusions
Since in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.
http://ift.tt/2F29hUN
Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning
Abstract
Background
To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients.
Methods
Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing.
Results
Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 – 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 – 8%).
Conclusions
We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing.
http://ift.tt/2CHfzUR
Clinical results of proton beam therapy for elderly patients with non-small cell lung cancer
Abstract
Background
The purpose of the present study was to evaluate retrospectively the efficacy and safety of proton beam therapy for elderly patients (≥80 years of age) with non-small cell lung cancer.
Methods
Patients diagnosed with T1–4 N0 M0 non-small cell lung cancer and treated with proton beam therapy between January 2009 and 2015 were recruited from our database retrospectively. Toxicity was evaluated using The Common Terminology Criteria for Adverse Events version 4.0.
Results
Thirty-five patients, including 25 (71%) with clinically inoperable lung cancer, were administered proton beam therapy. The median age was 82 years (range: 80–87 years), and the median follow-up time was 34 months (range: 10–72 months). The median dose of proton beam therapy was 80.0 Gy relative biological effectiveness (RBE) (range: 60.0–80.0 Gy [RBE]), and all patients completed the treatments. All patients were followed for at least 23 months or until their death. The 3-year overall survival rate was 67.2% (90.0% in patients with operable lung cancer, and 58.2% in those with inoperable lung cancer). The 3-year local control rate was 86.5%. Two patients presented with grade 2 pneumonitis. The occurrence rate of grade 2 pneumonitis was significantly correlated with a high lung V20 (p = 0.030), and a high mean lung dose (p = 0.030), and a low ratio of lung volume spared from 0.05 Gy (RBE) dose (total lung volume minus lung volume irradiated at least 0.05 Gy [RBE]) (p = 0.030). However, there were no cases of grade 3 or higher radiation pneumonitis.
Conclusions
This study suggests that the proton beam therapy was feasible for elderly patients with non-small cell lung cancer and can be considered as one of the treatment choices for elderly patients with lung cancer.
http://ift.tt/2EQBvmf
Side effects of CT-guided implantation of 125 I seeds for recurrent malignant tumors of the head and neck assisted by 3D printing non co-planar template
Abstract
Background
For the recurrence of head and neck cancer after operation and radiotherapy, the local control of radioactive seed implantation is good, and it has a certain palliative effect. This study aims to investigate the acute and late side effects of a three-dimentional printing non co-planar template (3D–PNCT) for computed tomography (CT)-guided radioactive 125I seed (RIS) implantation in recurrent cancer of the head and neck.
Methods
Between January 2016 and December 2016, forty-two patients with local recurrent malignant tumors of the head and neck received 3D–PNCT-assisted RIS implantation. The prescribed dose was 110–160 Gy. Preoperative planning design, production of individual guide plates, RIS implantation, postoperative dose evaluation, and follow-up were completed for all patients. Side effects in the skin, mucous membranes, blood and spinal cord were evaluated.
Results
All patients underwent surgery successfully. Duration of follow-up was 4–14 (median, of 8.5) months. The activity of a single RIS was 0.34–0.7 (median, 0.6) mCi. The number of RIS was 10–126 (median, 34). The number of implantation needles was 4–31 (median, 11). The mean D2cc (dose to the most exposed 2-cc volume) and D0.1cc (dose to the most exposed 0.1-cc volume) of the skin were 24.9 (7.1–85.5) and 47.5 (9.4–167.2), respectively, whereas those of the spinal cord were 8.4 (4.5–33.3) and 14.2 (13.6–63.0), mucosa were 35.1 (4.2–82.8) and 87.0 (6.6–214.1), parotid glands were 16.2 (12.8–19.7) and 29.8 (26.1–33.4) and those of the trachea were 17.9 (2.5–45.9) and 32.7 (3.9–83.9), respectively. No case had an acute reaction of grade ≥ 3. Three cases had a grade-1 skin reaction. Blood toxicity did not occur, nor spinal-cord injury. Xerostomia was not aggravated than that of before brachytherapy. One case had a grade-3 nerve response.
Conclusions
3D–PNCT-assisted RIS implantation can provide good accuracy for positioning. For local recurrent malignant tumor of head and neck, there were no obvious adverse reactions.
http://ift.tt/2CGIwA5
From IB2 to IIIB locally advanced cervical cancers: report of a ten-year experience
Abstract
Background
Despite screening campaigns, cervical cancers remain among the most prevalent malignancies and carry significant mortality, especially in developing countries. Most studies report outcomes of patients receiving the usual standard of care. It is possible that these selected patients may not correctly represent patients in a real-world setting, which may be a limitation in interpreting outcomes. This study was undertaken to identify prognostic factors, management strategies and outcomes of locally advanced cervical cancers (LACC) treated in daily clinical practice.
Methods
Medical files of all consecutive patients treated with curative intent for LACC in a French Cancer Care Center between 2004 and 2014 were reviewed retrospectively.
Results
Ninety-four patients were identified. Performance status was ≥ 2 in 10.6%. Median age at diagnosis was 63.0. Based on the International Federation of Gynecology and Obstetrics classification, tumours were classified as follows: 10.6% IB2, 22.3% IIA, 51.0% IIB, 4.3% IIIA and 11.7% IIIB. Pelvic lymph nodes were involved in 34.0% of cases. Radiotherapy was delivered for all patients. Radiotherapy technique was intensity modulated radiation therapy or volumetric modulated arc therapy in 39.4% of cases. A concurrent cisplatin chemotherapy was delivered in 68.1% of patients. Brachytherapy was performed in 77.7% of cases. The recommended standard care (concurrent chemoradiotherapy with at least five chemotherapy cycles during radiotherapy, followed by brachytherapy) was delivered in 43.6%. The median overall treatment time was 56 days. Complete tumour sterilisation was achieved in 55.2% of cases. Mean follow-up was 54.3 months. Local recurrence rate was 18.1%. Five-year overall survival was 61.9% (95% Confident Interval (CI) = 52.3–73.2) and five-year disease-specific survival was 68.5% (95% CI = 59.2–79.2). Poor performance status, lymph nodes metastasis and absence of concurrent chemotherapy were identified as poor prognostic factors in multivariate analysis.
Conclusions
Less than 50% of patients received the standard care. Because LACC patients and disease are heterogeneous, treatment tailoring appears to be common in current clinical practice. However, guidelines for tailoring management are not currently available. More data about real-world settings are required in order to to optimise clinical trials' aims and designs, and make them translatable in daily clinical practice.
Trial registration
retrospectively registered.
http://ift.tt/2EPsqKn
Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy
Abstract
Background
To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.
Methods
Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.
Results
For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.
Conclusions
Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.
http://ift.tt/2CGVQ7A
Evaluation of the tumor movement and the reproducibility of two different immobilization setups for image-guided stereotactic body radiotherapy of liver tumors
Abstract
Background
The purpose of this study is to evaluate the tumor movement and accuracy of patient immobilization in stereotactic body radiotherapy of liver tumors with low pressure foil or abdominal compression.
Methods
Fifty-four liver tumors treated with stereotactic body radiotherapy were included in this study. Forty patients were immobilized by a vacuum couch with low pressure foil, 14 patients by abdominal compression. We evaluated the ratio of gross tumor volume/internal target volume, the tumor movement in 4D-computed tomography scans and daily online adjustments after cone beam computed tomography scans.
Results
The ratio of gross tumor volume/internal target volume was smaller with low pressure foil. The tumor movement in 4D-computed tomography scans was smaller with abdominal compression, the cranial movement even significantly different (p = 0.02). The mean online adjustments and their mean absolute values in the vertical, lateral and longitudinal axis were smaller with abdominal compression. The online adjustments were significantly different (p < 0.013), their absolute values in case of the longitudinal axis (p = 0.043). There was no significant difference of the adjustments' 3D vectors.
Conclusions
In comparison to low pressure foil, abdominal compression leads to a reduction of the tumor movement. Online adjustments decreased significantly, thus leading to higher accuracy in patient positioning.
http://ift.tt/2EQt4qY
HyperArc VMAT planning for single and multiple brain metastases stereotactic radiosurgery: a new treatment planning approach
Abstract
Purpose
The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT).
Material and methods
For 23 patients (1–4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20–24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy-V16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared.
Results
HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p < 0.01), CI (0.93 ± 0.02 vs. 0.90 ± 0.05, p = 0.01) and lower GI (3.06 ± 0.42 vs. 3.91 ± 0.55, p < 0.01) values. Moderate-to-low dose spreads (V4Gy-V16Gy) were significantly reduced (p < 0.01) in the HA-VMAT plan over that of C-VMAT. HA-VMAT plans resulted in more complex MLC patterns (lower MCSV, p < 0.01) and higher MU (p < 0.01).
Conclusions
HA-VMAT plans provided significantly higher conformity and rapid dose falloff with respect to the C-VMAT plans.
http://ift.tt/2CHVw8G
Evaluation of Mediators Associated with the Inflammatory Response in Prostate Cancer Patients Undergoing Radiotherapy
A recent "hot topic" in prostate cancer radiotherapy is the observed association between acute/late rectal toxicity and the presence of abdominal surgery before radiotherapy. The exact mechanism is unclear. Our working hypothesis was that a previous surgery may influence plasma level of inflammatory molecules and this might result in enhanced radiosensitivity. We here present results on the feasibility of monitoring the expression of inflammatory molecules during radiotherapy. Plasma levels of a panel of soluble mediators associated with the inflammatory response were measured in prostate cancer patients undergoing radical radiotherapy. We measured 3 cytokines (IL-1b, IL-6, and TNF alpha), 2 chemokines (CCL2 and CXCL8), and the long pentraxin PTX3. 20 patients were enrolled in this feasibility evaluation. All patients were treated with IMRT at 78 Gy. 3/20 patients reported grade 2 acute rectal toxicity, while 4/20 were scored as grade 2 late toxicity. CCL2 was the most interesting marker showing significant increase during and after radiotherapy. CCL2 levels at radiotherapy end could be modelled using linear regression including basal CCL2, age, surgery, hypertension, and use of anticoagulants. The 4 patients with late toxicity had CCL2 values at radiotherapy end above the median value. This trial is registered with ISRCTN64979094.
http://ift.tt/2EPrOV5
Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer
Purpose. The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. Methods. Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers. mRNA levels of these markers in publicly available data from the Cancer Genome Atlas project and Kaplan-Meier plotters were analyzed. Results. Expression of G6PDH and 6PGL was higher in HER-2 type ( and , resp.) and lower in luminal A type. 6PGDH expression was detected only in TNBC subtype (). G6PDH positivity was associated with ER negativity (), PR negativity (), and HER-2 positivity (), whereas 6PGL positivity was associated with higher T stage (). The 562 expression profile from the TCGA database revealed increased expression of G6PDH and 6PG in the tumor compared with normal adjacent breast tissue. The expression of G6PDH was highest in HER-2 type. HER-2 and basal-like subtypes showed higher expression of 6PGDH than luminal types. Conclusion. PPP-related proteins are differentially expressed in breast cancer according to molecular subtype, and higher expression of G6PDH and 6PGL was noted in HER-2 subtype.
http://ift.tt/2CI0iCS
A critical appraisal of gabapentinoids for pain in cancer patients
http://ift.tt/2CHi9tC
Central and peripheral processes in headache
http://ift.tt/2F2zwdF
Opioid addiction, diversion, and abuse in chronic and cancer pain
http://ift.tt/2CFRcqs
Toxins in pain
http://ift.tt/2F0ZUEN
Osteoarthritis pain. Recent advances and controversies
http://ift.tt/2CEjDVz
Nonsteroidal anti-inflammatory drugs and cancer pain
http://ift.tt/2EN9wUx
Prognostic Factors in the Era of Targeted Therapies in CLL
Abstract
Purpose of Review
Chronic lymphocytic leukemia is heterogeneous disease characterized by a variable clinical course that is greatly influenced by various patient and disease characteristics. Over the last two decades, advent of new diagnostic methodologies has led to the identification of several factors of prognostic and predictive relevance. Furthermore, recent advances in next-generation sequencing techniques has identified recurrent novel mutations in NOTCH1, SF3B1, BIRC3, and ATM genes whose role as prognostic and predictive markers is currently being investigated. These biologic markers carry new prognostic information and their incorporation into prognostic scoring systems will likely lead to refined multi-parameter risk models.
Recent Findings
While the prognostic impact of many of the most commonly used markers on clinical outcomes in patients treated with chemo-immunotherapy is well documented, it is important to review their predictive and prognostic role in the era of novel targeted therapies.
Summary
This article will discuss the currently available information on the clinical relevance of prognostic markers in patients treated with novel targeted therapies.
http://ift.tt/2EOqWQx
Common Adverse Effects of Novel Therapies for Multiple Myeloma (MM) and Their Management Strategies
Abstract
Purpose of Review
The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor.
Recent Findings
There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class. Additionally, several agents have critically important drug-drug interactions or dose-modification implications in hepatic or renal insufficiency that can be easily overlooked, and exacerbate adverse effects.
Summary
As treatment of MM moves from fixed-duration traditional chemotherapy to novel agent-based regimens, commonly administered continuously until disease progression or intolerable toxicities, providers must adopt their management strategies for both acute and long-term adverse effects. Early and frequent monitoring for therapy-related complications, dose adjustments when needed, and timely treatment for toxicities are all important steps toward ensuring longevity of treatment from a limited array of therapeutic options that currently exist for a disease with a relapsing and remitting course.
http://ift.tt/2BNs5oQ
Recent Developments in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia
Abstract
Purpose of review
Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years.
Recent findings
The preponderance of data favors the treatment of AYA ALL patients with pediatric-inspired treatment regimens due to better relapse-free and overall survival. Minimal residual disease (MRD) measurement is emerging as an important prognostic factor and can serve as a new measure of efficacy of the addition of novel therapies to the treatment of patients with new diagnoses. There have been several treatment advances ranging from new cytotoxic agents for ALL to new antibody-based therapy to novel immune therapies such as CAR-T cells.
Summary
The care of AYA ALL patients is improving as the unique issues for this patient population are addressed.
http://ift.tt/2ouhkR1
Updates of Peripheral T Cell Lymphomas Based on the 2017 WHO Classification
Abstract
Purpose of Review
This review will describe and update the readers on the recent changes of the 2017 WHO classification in regard to peripheral T cell lymphomas.
Recent Findings
Significant advances in molecular studies have resulted in revisions of the classification as well as introduction of provisional entities (such as breast implant-associated ALCL, nodal PTCL with TFH phenotype).
Summary
Major advances in molecular and gene expression profiling have expanded our knowledge of T cell lymphomas, including updates in the diagnostic criteria and sub-classification which will facilitate in improving patient care and research.
http://ift.tt/2BMdaLD
Autonomic function test in progressive lacunar infarction
Objective
Neurological progression is a major problem in managing the patients with acute lacunar infarction. The purpose of this was to investigate whether autonomic dysfunction is associated with neurological progression in patients with acute lacunar infarction.
Materials and Methods
The study comprised 60 patients with acute lacunar infarction. All enrolled subjects underwent autonomic function tests including the 30° head-up tilt test, Valsalva test, heart rate response to deep breathing, and sympathetic skin response. The primary endpoint is the neurological progression, and the secondary endpoint is the 3-month outcome.
Results
Increased initial National Institute of Health stroke scale (NIHSS), decreased time to admission from onset, decreased rise of heart rate in the 30° head-up tilt test, abnormal blood pressure response in the Valsalva test, and decreased rise of systolic blood pressure in stage IV of the Valsalva test are associated with neurological progression of acute lacunar infarction; an abnormal blood pressure response in the Valsalva test is significant in logistic regression analysis of neurological progression. Advanced age, increased initial NIHSS and modified Rankin scale, decreased expiration/inspiration ratio of heart rate to deep breathing, decreased rise of systolic blood pressure in stage IV of the Valsalva test, and neurological progression were associated with an unfavorable 3-month outcome; neurological progression was significant in logistic regression analysis of 3-month outcome.
Conclusions
An abnormal blood pressure change in the Valsalva test is associated with neurological progression in patients with acute lacunar infarction, and neurological progression can induce an unfavorable 3-month outcome.
http://ift.tt/2ESD0MG
Development and validation of Spasticity Index—Amyotrophic Lateral Sclerosis
Objectives
Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS.
Methods
Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life.
Results
A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale—the Spasticity Index for ALS (SI-ALS)—which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life.
Conclusions
The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.
http://ift.tt/2FtJ0fX
Tuberculous Enteritis Presenting as Acute Appendicitis and Perirectal Abscess
Mycobacterium tuberculosis has a wide variety of presentations. A rare occurrence is gastrointestinal tuberculosis. It may occur anywhere along the alimentary canal but usually occurs in the ileocecum with rare involvement of the appendix.
http://ift.tt/2GK0ZOL
Improvement of l-ornithine production by attenuation of argF in engineered Corynebacterium glutamicum S9114
l-Ornithine, a non-essential amino acid, has enormous industrial applications in food, pharmaceutical, and chemical industries. Currently, l-ornithine production is focused on microorganism fermentation using Esc...
http://ift.tt/2F4L1RZ
Enhanced laccase-mediated transformation of diclofenac and flufenamic acid in the presence of bisphenol A and testing of an enzymatic membrane reactor
The inadequate removal of pharmaceuticals and other micropollutants in municipal wastewater treatment plants, as evidenced by their detection of these substances in the aquatic environment has led to the need ...
http://ift.tt/2CHCQFS
Biodegradation of decabromodiphenyl ether (BDE 209) by a newly isolated bacterium from an e-waste recycling area
Polybrominated diphenyl ethers (PBDEs) have become widespread environmental pollutants all over the world. A newly isolated bacterium from an e-waste recycling area, Stenotrophomonas sp. strain WZN-1, can degrade...
http://ift.tt/2F6cMd7
Biologics Delay Progression of Crohn’s Disease, but Not Early Surgery, in Children
Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course.
http://ift.tt/2CGIqIG
Primary low-grade fibromyxoid sarcoma of breast: A rare case report with immunohistochemical and fluorescence in situ hybridization detection
Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a bland histological appearance but malignant biological behavior. Primary LGFMS of breast has not been described in the English-language literature. Here, we report a 58-year-old Chinese female patient who presented with a painless mass in the right breast for more than 30 years. The tumor consists of spindle cells resembling fibroblasts and includes two kinds of morphological change, which are alternating collagenized hypocellular zone and cell-rich myxoid area.
http://ift.tt/2GH8K7V
Multimodal Imaging of Pathologic Response to Chemoradiation in Esophageal Cancer
To examine the value of early changes in quantitative diffusion-weighted imaging (DWI) and 18F-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for discriminating complete pathologic response (pCR) to chemoradiation (CRT) in esophageal cancer.
http://ift.tt/2FsVVP8
Using Big Data Analytics to Advance Precision Radiation Oncology
Big Clinical Data Analytics as a primary component of precision medicine is discussed, ] identifying where these emerging tools fit in the spectrum of genomic and radiomic research. A learning health system (LHS) is conceptualized that utilizes clinically acquired data with machine learning to advance the initiatives of precision medicine. The LHS is comprehensive and can be used for clinical decision support, discovery, and hypothesis derivation. These developing uses can positively impact the ultimate management and therapeutic course for patients.
http://ift.tt/2EPMcBj
Measurement of Tumor Hypoxia in Patients with Locally Advanced Cervical Cancer using Positron Emission Tomography (PET) with 18F-Fluoroazomyin Arabinoside (18F-FAZA)
Poor tumor oxygenation (hypoxia) is associated with inferior survival in cervical cancer and resistance to radiotherapy. Positron emission tomography (PET) imaging of tumor hypoxia is minimally invasive and allows evaluation of the entire tumor, but has not been widely studied in cervical cancer. This study assesses cervical tumor hypoxia using hypoxia tracer 18F-fluoroazomycin arabinoside (18F-FAZA), and compares different reference tissues and thresholds for quantifying tumor hypoxia.
http://ift.tt/2FsVTH0
In Patients With ST-Segment Elevation Myocardial Infarction, Which Fibrinolytic Agent Is the Safest and Most Effective?
Forty studies met inclusion criteria, involving 128,071 STEMI patients treated with 12 fibrinolytic regimens. Four fibrinolytic agents (streptokinase, reteplase, tenecteplase, and alteplase at 2 separate dosing regimens) were compared as reperfusion therapy alone or in combination with antithrombotic agents, including parenteral anticoagulants (ie, low-molecular-weight heparin, heparin, anti-Xa inhibitor, and direct thrombin inhibitor) or glycoprotein IIb or IIIa inhibitors (ie, abciximab, tirofiban, or eptifibatide) (Table).
http://ift.tt/2CHrjGC
Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity
Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the...
http://ift.tt/2sQuuvY
Flavanones from Sedum sarmentosum Bunge Alleviate CCl4-Induced Liver Fibrosis in Rats by Targeting TGF-β1/TβR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition
Objective. The aim of the study is to evaluate the therapeutic effects of flavanones from Sedum sarmentosum Bunge (FSSB) on CCl4-induced liver fibrosis in rats and the underlying mechanisms of action. Methods. An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl4 (40% v/v, 3 ml/kg) twice per week for six weeks. FSSB (100, 200, and 400 mg/kg) was intragastrically administered once per day consecutively for five weeks. Results. Our results showed that FSSB significantly attenuated CCl4-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), and laminin (LN) level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-β1, TGF-β1 receptors I and II (TβRI and TβRII), Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin. Conclusions. The results suggest that FSSB alleviated CCl4-induced liver fibrosis probably through inhibition of TGF-β/TβR/Smad pathway in turn inhibiting epithelial mesenchymal transition.
http://ift.tt/2BM2Wuy
Interview with Dr Philip McCarthy
International Journal of Hematologic Oncology, Ahead of Print.
http://ift.tt/2GHgK90
Antigout Effects of Plantago asiatica: Xanthine Oxidase Inhibitory Activities Assessed by Electrochemical Biosensing Method
The XOD inhibitory effects of Plantaginis Semen, that is, the seeds of P. asiatisca, and its representative four single compounds, acteoside, 1H-indolo-3-carbaldehyde, isoacteoside, and myristic acid, were evaluated by electron transfer signal blocking activities (ETSBA), which is based on the electron transfer signal of XOD enzymatic reaction. The blocking activities were detected using an electrochemical biosensing method. Compared with control, significant effects were observed after the addition of P. asiatica extract, acteoside, and 1H-indolo-3-carbaldehyde (all ). The IC50 values of the extract and acteoside are 89.14 and 7.55 μg·mL−1, respectively. The IC20 values of the extract, acteoside, and 1H-indolo-3-carbaldehyde are 24.28, 3.88, and 16.16 μg·mL−1, respectively. Due to the relatively lower inhibitory potential of 1H-indolo-3-carbaldehyde, its IC50 was not obtained. In addition, isoacteoside and myristic acid did not show any XOD inhibitory effects. Our data demonstrated that the XOD inhibitory effects of the extract, acteoside, and 1H-indolo-3-carbaldehyde can be accurately evaluated by the ETSBA method. The results from this study indicated that Plantaginis Semen significantly inhibited XOD activities to reduce hyperuricemia and treat gout. The study also proves that measuring the electron transfer signal blocking activities is a simple, sensitive, and accurate method to evaluate the XOD inhibitory effects.
http://ift.tt/2BNS67r
Effectiveness of Massage Therapy and Abdominal Hypopressive Gymnastics in Nonspecific Chronic Low Back Pain: A Randomized Controlled Pilot Study
Background. There are a great number of interventions in physiotherapy, but with little evidence of their effectiveness in chronic low back pain. Therefore, this study assesses effectiveness of Massage Therapy and Abdominal Hypopressive Gymnastics and the combination of both to decrease pain and lumbar disability while increasing joint mobility and quality of life in patients with chronic nonspecific low back pain. Methods. A randomized, single-blinded, controlled, clinical trial with sample () was comprised of patients between 20 and 65 years, diagnosed with pain of mechanical origin characterized by having a duration of at least 12 weeks and no serious complications. Each group received 8 interventions of 30 minutes. Results. Friedman ANOVA test obtained statistically significant differences of Oswestry, NRS, and Schober variables () in the three measurements (pretest, posttest 1, and posttest 2), in each individual group. ANOVA Kruskal-Wallis test was used for comparison between groups, and Oswestry Disability values were significantly higher () in the group receiving both treatments. Conclusion. Both individual groups reduce pain levels, improve disability, and increase the flexibility of the lumbar spine. The combination therapy provides greater benefits in terms of lumbar disability. This study is registered on March 8, 2016, with NCT02721914.
http://ift.tt/2EO35QZ
Nearest Neighbor Algorithm Coupled with Metabonomics to Study the Therapeutic Mechanism of Sendeng-4 in Adjuvant-Induced Rheumatoid Arthritis Rat
As a traditional Mongolian medicine, Sendeng-4 (SD) has been widely used to treat rheumatoid arthritis (RA) in Inner Mongolia and exhibits a good curative effect. Unfortunately, due to geographical factors, it is difficult to popularize this drug throughout the whole country, and the mechanism of action of SD has been unclear. In this study, a serum metabolite profile analysis was performed to identify potential biomarkers associated with adjuvant-induced RA and investigate the mechanism of action of SD. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed for the metabonomics analysis. nearest neighbor (KNN) models were established in both positive and negative spectra for classifying data from the control, model, and SD administration groups. Accuracy rate for classification was 95.8% in positive ion mode and 91.7% in negative ion mode. Orthogonal partial least squares discriminant analysis (OPLS-DA) enabled the identification of 12 metabolites as potential biomarkers of adjuvant-induced RA. After treatment with SD, the levels of uridine triphosphate, calcitroic acid, dynorphin B (6-9), and docosahexaenoic acid were restored to normal, indicating that SD likely ameliorated RA by regulating the levels of these biomarkers. This study identified early biomarkers of RA and elucidated the underlying mechanism of action of SD, which is worth further investigation for development as a clinical therapy.
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Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100)
Medications or dietary components can affect both the host and the host's gut microbiota. Changes in the microbiota may influence medication efficacy and interactions. Daikenchuto (TU-100), a herbal medication, comprised of ginger, ginseng, and Japanese pepper, is widely used in Japanese traditional Kampo medicine for intestinal motility and postoperative paralytic ileus. We previously showed in mice that consumption of TU-100 for 4 weeks changed the gut microbiota and increased bioavailability of bacterial ginsenoside metabolites. Since TU-100 is prescribed in humans for months to years, we examined the time- and sex-dependent effects of TU-100 on mouse gut microbiota. Oral administration of 1.5% TU-100 for 24 weeks caused more pronounced changes in gut microbiota in female than in male mice. Changes in both sexes largely reverted to baseline upon TU-100 withdrawal. Effects were time and dose dependent. The microbial profiles reverted to baseline within 4 weeks after withdrawal of 0.75% TU-100 but were sustained after withdrawal of 3% TU-100. In summary, dietary TU-100 changed mouse microbiota in a time-, sex-, and dose-dependent manner. These findings may be taken into consideration when determining optimizing dose for conditions of human health and disease with the consideration of differences in composition and response of the human intestinal microbiota.
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Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, on Arthritis Model Rats
Objectives. In China, Oldenlandia diffusa (OD) is a natural herb that is widely used and has been proven to be effective in the treatment of rheumatoid arthritis (RA). This study aimed to preliminarily reveal the mechanism by which OD exerts its beneficial effect. Methods. Ultra-performance liquid chromatography photodiode array was applied to identify the absorbable compounds in the plasma of collagen-induced arthritis (CIA) model rats. After 2 weeks, an OD decoction or the identified absorbable compound was administered to CIA rats. Morphology, X-ray images of the joints, pathological images, arthritis index, and cytokine (TNF-α and IL-6) levels were evaluated. Results. p-Coumaric acid (p-CA) was identified as the absorbed compound in plasma. After administration of p-CA solution or the OD decoction, symptoms in the treated rats were alleviated as compared to the untreated model rats, and inflammatory cell infiltration was suppressed. The arthritis index and serum levels of TNF-α and IL-6 were decreased as compared to the control group. Conclusions. OD may exert its anti-inflammatory effect on RA via its active ingredient, p-CA. This information sheds light on the mechanism by which OD exerts its anti-inflammatory effort in RA and forms the basis for further development of therapeutic agents for RA.
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The Potential Effect of Chinese Herbal Formula Hongqijiangzhi Fang in Improving NAFLD: Focusing on NLRP3 Inflammasome and Gut Microbiota
The present study investigates the potential therapeutic mechanism underlying the effects of the Chinese herbal formula Hongqijiangzhi Fang (HJF) on nonalcoholic fatty liver disease (NAFLD) in rats. Male Sprague Dawley (SD) rats were randomly divided into 4 groups (): control group was fed a normal diet, three other groups were fed high-fat diets (HFD), and the two treatment groups were intragastrically given a compound probiotic or HJF during the molding time. After 16 w, related indices were detected. The results showed that HJF significantly reduced abdominal aorta serum cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), IL-1β, and IL-18, portal venous serum lipopolysaccharide (LPS), and liver TC and TG levels in HFD-fed rats. HJF ameliorated hepatic steatosis in the liver and improved the intestinal barrier in HFD-fed rats. Activation of the NLRP3 inflammasome was reduced by HJF in HFD-fed rats. Additionally, the abundances of A. muciniphila (Verrucomicrobiaceae), F. rappini (Helicobacteraceae), and Enterobacteriaceae bacteria significantly decreased in HJF-treated HFD-fed rats. In conclusion, these result suggested that the Chinese herbal formula HJF reduced hepatic steatosis maybe through decreasing certain gut bacteria (such as Enterobacteriaceae bacteria and F. rappini), alleviating intestinal endotoxemia and reducing NLRP3 inflammasome activation.
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Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials
Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment.
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Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models
Background. Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method. The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and was considered significant. Results. The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (). Conclusion. The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models.
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Seasonal Effect on the Biological Activities of Litsea glaucescens Kunth Extracts
This study shows the seasonal effect on the antioxidant, antiproliferative, and antimicrobial activities of L. glaucescens Kunth (LG) leaves extracts. Their antioxidant activity was evaluated through the DPPH, FRAP, and ORAC assays. Their phenolic content (PC) was determined by means of the Folin-Ciocalteu method, and the main phenolic compounds were identified through a HPLC-DAD analysis. Antiproliferative activity was determined by MTT assay against HeLa, LS 180, M12.C3.F6, and ARPE cell lines. Antimicrobial potential was evaluated against Staphylococcus aureus and Escherichia coli using a microdilution method. All the LG extracts presented high antioxidant activity and PC, with quercitrin and epicatechin being the most abundant. Antioxidant activity and PC were affected by the season; particularly autumn (ALGE) and summer (SULGE) extracts exhibited the highest values (). All extracts presented moderate antiproliferative activity against the cell lines evaluated, HeLa being the most susceptible of them. However, ALGE and SULGE were the most active too. About antimicrobial activity, SULGE ( μg/mL; MIC50
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The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway
Treating type 2 diabetes mellitus (T2DM) using thiazolidinediones and biguanides can present several challenges for patients. Sanggua Drink (SGD) is a commonly used agent in traditional Chinese medicine, and it consists of Folium Mori, Fructus Momordicae Charantiae, Radix Puerariae Lobatae, and Rhizoma Dioscorea. The hypoglycemic effects and mechanisms of SGD extracts on insulin resistance in diabetic rats were investigated. SGD (1.24 g/kg orally) was verified in T2DM rats induced by a high-fat diet and streptozotocin. The results showed that SGD treatment was observed to reduce fasting blood glucose, water and food intake, total cholesterol triglycerides, and LDL, OGTT, FINS, HOMA-IR, GHb, and MDA and increase hepatic glycogen, HDL, SOD, CAT, and GSH-Px in diabetic rats. Simultaneously, SGD treatment by T2DM showed significantly ameliorated pathological changes and reduced inflammation in the pancreas. Treatment was also observed to increase gene and protein expressions of InsR, IRS-2, PI3K, AKT, and Glut4 in the livers of diabetic treated rats. These results suggest that SGD extracts have hypoglycemic properties and may alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Therefore, SGD appears to be a promising insulin sensitizer.
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In Vitro Wound Healing Potential of Stem Extract of Alternanthera sessilis
Impaired wound healing is one of the serious problems among the diabetic patients. Currently, available treatments are limited due to side effects and cost effectiveness. In line with that, we attempted to use a natural source to study its potential towards the wound healing process. Therefore, Alternanthera sessilis (A. sessilis), an edible and medicinal plant, was chosen as the target sample for the study. During this investigation, the wound closure properties using stem extract of A. sessilis were analyzed. Accordingly, we analyzed the extract on free radical scavenging capacity and the cell migration of two most prominent cell types on the skin, human dermal fibroblast (NHDF), keratinocytes (HaCaT), and diabetic human dermal fibroblast (HDF-D) to mimic the wound healing in diabetic patients. The bioactive compounds were identified using gas chromatography-mass spectrometry (GC-MS). We discovered that the analysis exhibited a remarkable antioxidant, proliferative, and migratory rate in NHDF, HaCaT, and HDF-D in dose-dependent manner, which supports wound healing process, due to the presence of wound healing associated phytocompounds such as Hexadecanoic acid. This study suggested that the stem extract of A. sessilis might be a potential therapeutic agent for skin wound healing, supporting its traditional medicinal uses.
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Potential Hypoglycaemic and Antiobesity Effects of Senna italica Leaf Acetone Extract
Background. Type II diabetes is on the rise while obesity is one of the strongest risk factors of type II diabetes. The search for a drug for type II that can equally mitigate obesity related complication is desired. Methods. The acetone leaf extract of Senna italica was evaluated for its cytotoxic, antiglycation, and lipolytic effect, glucose uptake, and GLUT4 translocation and expression using published methods, while that for adipogenesis and protein expression levels of obesity related adipokines was assessed using adipogenesis assay and mouse adipokine proteome profiler kit, respectively. The possible mechanism of glucose uptake was assessed through the inhibition of PI3K pathway. Results. The extract had no adverse effect on 3T3-L1 cell viability (CC50 > 1000 g/ml). High antiglycation effect was attained at 10 mg/ml, while at 25–200 g/ml it showed no significant increase in adipogenesis and lipolysis. The extract at 100 g/ml was shown to decrease the expression levels of various adipokines and minimal glucose uptake at 50–100 g/ml with a nonsignificant antagonistic effect when used in combination with insulin. GLUT4 translocation and expression were attained at 50–100 g/ml with an increase in GLUT4 expression when in combination with insulin. Conclusion. The acetone leaf extract of S. italica stimulates glucose uptake through the PI3K-dependent pathway and can serve as a source of therapeutic agent for the downregulation of obesity-associated adipokines in obesity and antiglycation agents.
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Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice
From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.
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Evaluation of Analgesic and Anti-Inflammatory Activities of Water Extract of Galla Chinensis In Vivo Models
Aim. Pain and inflammation are associated with many diseases in humans and animals. Galla Chinensis, a traditional Chinese medicine, has a variety of pharmacological properties. The purpose of this study was to evaluate analgesic and anti-inflammatory activities of Galla Chinensis through different animal models. Method. The analgesic activities were evaluated by hot-plate and writhing tests. The anti-inflammatory effects were assessed by ear edema, capillary permeability, and paw edema tests. The contents of cytokines (NO, iNOS, PGE2, and IL-10) in serum of rats in paw edema test were inspected by ELISA assays. Results. In the hot-plate test, Galla Chinensis could significantly extend pain threshold when compared to control group. The inhibitory rates of writhes ranged from 36.62% to 68.57% in Galla Chinensis-treated mice. Treatment with Galla Chinensis (1 and 0.5 g/kg) could significantly inhibit ear edema (47.45 and 36.91%, resp.;
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Effect of Qingxin Kaiqiao Fang on Hippocampus mRNA Expression of the Inflammation-Related Genes IL-1β, GFAP, and Aβ in an Alzheimer’s Disease Rat Model
Objective. To investigate the effects of QKF on expression of amyloid-beta (Aβ), interleukin-1 beta (IL-1β), and glial fibrillary acidic protein (GFAP) using a rat model of AD. Materials and Methods. Fifty-six male Sprague-Dawley rats were randomly divided into seven groups (eight rats each): control group, sham-operated group, AD model group, groups of AD rats administered with low, medium, and high doses of QKF, and the donepezil group. AD was established by bilateral injection of β-amyloid (Aβ) 1–40 into the hippocampus. Two days after AD was established, drugs were administered by gavage. After 14 days of treatment, we used RT-PCR, Western blotting, and immunohistochemistry to measure the transcript expression and protein abundance of Aβ, IL-1β, and GFAP, and methenamine silver staining was used to detect amyloid protein particle deposition. Results. Compared to the control group, the rats from the AD model group showed significantly greater expression levels of Aβ, IL-1β, and GFAP. However, these differences in expression were abolished by treatment with QKF or donepezil. Conclusion. QKF possesses therapeutic potential against AD because it downregulated Aβ, IL-1β, and GFAP in the hippocampus of AD rats. Future studies should further examine the mechanisms through which QKF produces its effects and the consequences of long-term QKF administration.
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Total Flavonoids from Oroxylum indicum Induce Apoptosis via PI3K/Akt/PTEN Signaling Pathway in Liver Cancer
Total flavonoids (TF), derived from the seeds of Oroxylum indicum (L.) Vent., possess many pharmacological functions. In the present study, H22-bearing mice and SMMC-7721 models were employed to evaluate the antitumor activity of TF and to and investigate its possible mechanisms both in vitro and in vivo. Cell viability was evaluated by MTT assay; cell apoptosis rate was analyzed via Annexin V-FITC/PI double staining by flow cytometer. Meanwhile, the expressions of apoptosis-related mRNA and proteins were evaluated by RT-PCR and Western blot analysis. The results revealed that TF could significantly inhibit the tumor growth, and the possible mechanism was related to the effect of inducing tumor cells apoptosis through PI3K/Akt/PTEN signaling pathway. This study has provided a theoretical basis for the further development and application of TF as antitumor drugs.
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Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat
Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
