Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Evaluation of cognitive deficits in patients infected with COVID-19.

OBJECTIVE: COVID-19 infection can cause impairments in many cognitive areas. The aim of the present study was to evaluate the cognitive functions of patients who had been infected with COVID-19. PATIENTS AND METHODS: The demographic and infection-related characteristics of patients who had been infected with COVID-19 were determined. Their cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) findings were recorded. The Mini-Mental State Evaluation (MMSE), clock drawing test, forward and backward digit span tests, visual memory test, and Frontal Assessment Battery were applied to the patients. Finger agnosia and ideomotor apraxia were also determined. RESULTS: The study included 176 patients [100 female (56.8%), 76 male (43.2%), mean age 66.09±13.96 years]. About half of the patients were hospitalized for symptoms of COVID-19 infection (n=82, 46.6%). One third of these patients required intensive care (n=26, 14.8%). While 50 (45.9%) of the 109 patients diagnosed with dementia before infection were hospitalized, 32 (47.8%) of the 67 patients without a diagnosis of dementia required hospitalization (p=0.46). The most common neurological finding during COVID-19 infection was insomnia (n=36, 20.5%). The MMSE and visual memory test scores of the patients who were hospitalized for severe respiratory distress were lower than those whose treatment at home was completed (respectively 17.92±7.69/20.59±7.01, p=0.02; 2.53 ±1.73/3.69±2.80, p=0.01). The patients with moderate to severe cognitive impairment had significantly higher CRP levels at admission than the others (37.52±43.09/20.93±31.74, p=0.01, respectively). CONCLUSIONS: Cognitive damage in COVID-19 infection may be caused by ACE receptor density in the pial, hippocampal, and amygdala areas. In addition, the reason why people with severe dementia have a milder infection might be explained by the atrophy in these areas.

Factors influencing the functional outcomes of tibia plateau fractures after surgical fixation.

AIMS: The aim of this study is to assess the functional and radiological outcomes of 52 surgically treated tibial plateau fractures and to determine the factors affecting functional outcomes. SUBJECTS AND METHODS: A total of 52 patients who were operated between 2007 and 2014 due to tibial plateau fractures were retrospectively reviewed. The Knee Society Score (KSS) was used for the functional outcome assessment. The Kellgren-Lawrence radiological evaluation score was used for the relationship between postoperative trauma and osteoarthritis in the last follow-up. RESULTS: Patients' mean age was 47.7 years (range, 14-84 years). The immobilization period was 4.2 weeks (range, 0-8 weeks), the full weightbearing time was 3.3 months (range, 1.5-5 months), and the follow-up time was 47 months (range, 17-102 months). Patients' mean KSS was 84.3 (range, 40-100). According to the Kellgren-Lawrence classification, 26 patients had grade 0, 11 patients had grade 1, 8 patients had grade 2, 5 patients had grade 3, and 2 patients had grade 4 postoperative osteoarthritis. CONCLUSION: Use of graft if there is collapse on joint surface, early knee motion, and early started full weightbearing after surgical fixation of tibial plateau fracture is essential for successful outcome. Findings of osteoarthritis on X-rays are not related to poor functional outcome at the mid- to long-term follow-up of surgical treated tibial plateau fractured patients.

Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats.

Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g/kg of P, (3) 2 g/kg of P + 5 mg/kg of AML, (4) 2 g/kg of P + 10 mg/kg of AML, and (5) 10 mg/kg of AML. Some liver enzymes, oxidative parameters, cytokine mRNA expressions, histopathology, and immunohistochemical studies were performed in liver and blood samples. The serum levels of alanine aminotransferase and aspartate aminotransferase and the mRNA expression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta in the liver tissues were significantly increased in the group treated with P. The superoxide dismutase and glutathione parameters decreased and malondialdehyde levels increased in the livers of the rats treated with P. All these parameters were increased with both doses of the AML similar to the control group. A histopathological examination of the liver showed that AML administration ameliorated the P-induced inflammatory liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the P group but not in other treatment groups when compared to the control. In conclusion, AML treatment showed significant protective effects against P-induced hepatotoxicity by increasing the activity of antioxidants and reducing inflammatory cytokines.

Evaluation of receiver-stimulator migration in cochlear implantation using the subperiosteal pocket technique: a prospective clinical study.

OBJECTIVE: This study aimed to evaluate migration of the receiver-stimulator after cochlear implantation using the subperiosteal pocket technique. METHODS: A prospective clinical study was performed of 32 paediatric patients (aged between 12 months and 8 years; mean ± standard deviation, 28 ± 19 months) who underwent cochlear implantation in tertiary referral centres. The degree of migration was evaluated using measurements between the receiver-stimulator and selected reference points: the lateral canthus, tragus and mastoid tip. All distances were measured during and six months after surgery. RESULTS: No receiver-stimulator migration was observed when using the subperiosteal pocket technique. CONCLUSION: Concerns about implant migration in the subperiosteal pocket technique are unwarranted: this is a safe technique to use for cochlear implantation.

Designing Self-Standing Three Dimensional Composite SiCu Thin Films as Anodes for Lithium Ion Battery.

Three dimensional nanostructured silicon based electrodes are promising for high capacity anodes in lithium ion battery. Though the specific capacity of silicon is very high compared to the conventional graphite anode, its large volume changes in cycling results in poor cycle life, which eventually restricts Si use in commercial applications. This problem could be overcomed by producing selfstanding nanostructures that can provide facile relaxation to prevent electrode pulverization. Plus, nanostructured electrodes maintain effective electrical contacts in cycling and provide short Li diffusion distances improving their electrochemical performances. In this paper, by using electron beam evaporation glancing angle deposition method three dimensional Si based composite (10%at. Cu) self-standing nanostructures with different porosities are produced. After the morphological and structural characterizations, their potential uses as anodes in lithium ion batteries are evaluated by means of electrochemical tests.

The effects of different suture materials in the nasal cavity.

OBJECTIVE: To investigate the effects of different suture materials in the nasal cavity on encrustation and micro-organism colonisation. METHODS: Four different suture materials were used to suture the nasal septum. The effects of suture materials on intranasal encrustation were evaluated with anterior rhinoscopy. The sutures were removed and evaluated in terms of micro-organism colonisation on the 7th and 21st post-operative days. RESULTS: Monofilament sutures were found to cause less encrustation and micro-organism colonisation. There was increased late-stage encrustation if an absorbable monofilament suture remained in place for a long time. The removal of a non-absorbable monofilament suture in the early or late post-operative period made no difference in terms of micro-organism growth on the suture. CONCLUSION: The material and physical characteristics of sutures placed inside the nose may indirectly affect the healing process. It may be more appropriate to use different materials depending on the length of time the suture is to remain in place.

The Effects of Film Thickness and Evaporation Rate on Si-Cu Thin Films for Lithium Ion Batteries.

The reversible cyclability of Si based composite anodes is greatly improved by optimizing the atomic ratio of Si/Cu, the thickness and the evaporation rates of films fabricated by electron beam deposition method. The galvanostatic test results show that 500 nm thick flim, having 10%at. Cu-90%at. Si, deposited with a moderate evaporation rate (10 and 0.9 Å/s for Si and Cu respectively) delivers 2642.37 mAh g(-1) as the first discharge capacity with 76% Coulombic efficiency. 99% of its initial capacity is retained after 20 cycles. The electron conductive pathway and high mechanical tolerance induced by Cu atoms, the low electrical resistivity of the film due to Cu3Si particles, and the homogeneously distributed nano-sized/amorphous particles in the composite thin film could explain this outstanding electrochemical performance of the anode.

Silicon-Copper Helical Arrays for New Generation Lithium Ion Batteries.

The helical array (with 10 atom % Cu) exhibits 3130 mAh g(-1) with 83% columbic efficiency and retains 83% of its initial discharge capacity after 100th cycle. Homogeneously distributed interspaces between the helical arrays accommodate high volumetric changes upon cycling and copper atoms form a conductive network to buffer the mechanical stress generated in the electrode while minimizing electrochemical agglomeration of Si. Also, ion assistance is believed to enhance the density of the helices at the bottom thus increasing the adhesion.

Tailed Palva flap in the subperiosteal pocket technique for cochlear implantation.

BACKGROUND: In recent years, the subperiosteal pocket technique has become popular for minimal access cochlear implantation. Many incision techniques have been described in cochlear implantation. OBJECTIVE: This study aimed to demonstrate the safety and reliability of a new periosteal incision, called tailed Palva incision, in cochlear implantation. METHODS: A total of 280 patients who underwent cochlear implantation with the subperiosteal pocket technique between June 2008 and January 2013 were included in the study. RESULTS: The patients were followed up for between 11 and 74 months (mean ± standard deviation = 34 ± 19 months). No intracranial complications were seen during or after the operations. Additionally, there was no migration of the receiver-stimulator. Revision surgery was performed in eight patients (3 per cent), one of whom (0.4 per cent) had local flap failure and infection. CONCLUSION: This study shows that the tailed Palva incision facilitates easy insertion of the implant and, by creating a one-way obscured pocket, this technique also enhances stabilisation of the receiver-stimulator, thereby avoiding anterior migration.

[Ouabain induces Rho-dependent rock activation and membrane blebbing incultured endothelial cells].

Small G protein Rho and its most studied effectors, ROCK I and ROCK II, are involved in several cellular fuctions including smooth muscle and non-muscle cell contractions, cell migration and apoptosis. Activation of ROCK I by caspase-3 and activation of ROCK II by granzyme B are essential for membrane blebbing in the execution phase of apoptosis. In contrast, it has been demonstrated that Rho signaling is critical for blebbing developed after serum removal. As it was shown by us previously, ouabain induces membrane blebbing and proteolitic cleavage of ROCK I and ROCK II via caspases in human umbilical endothelial cells. However, caspase inhibitors do not prevent ouabain-induced blebs. Ouabain induces concentration-dependent cell death and membrane blebbing in endothelial cells. The aim of this study was to identify the possible role of Rho in ouabain-induced membrane blebbing. Pretreatment of endothelial cells with a Rho inhibitor CT04 did not inhibit the ouabain-induced cell death but prevented the development ofbleb formation. These results indicate that bleb formation is dependent on Rho activity in ouabain-induced cell death in HUVECs. Taken together, these results suggest that the mechanism of membrane bleb formation might be different depending on cell type and cell death-stimuli.

Endometrial echotexture variables in postpartum cows with subclinical endometritis.

The aim of this study was to evaluate endometrial echotexture changes on ultrasonographic digital images during subclinical endometritis using a computer-assisted image analysis program. Endometrial samples were collected from 140 Brown Swiss cows (days in milk = 35 ± 3) using a cytobrush method and classified as having a non-inflamed uterus (n = 66) and uterus with acute (n = 42), subacute (n = 21), and chronic (n = 11) inflammations. The mean cellular infiltration density was 0%, 31 ± 5%, 37 ± 6%, and 16 ± 8% for cows with non-inflamed uterus and cows with acute, subacute, and chronic uterine inflammations (P < 0.0001). As the cell infiltration density increased, both cervical diameter and mean gray level did not change. There were a liner decrease in homogeneity and a linear increase in contrast in response to increased cellular infiltration density. The sensitivity and specificity were 79.73% and 46.97% for the homogeneity value and 59.46% and 69.70% for the contrast value, respectively. In conclusion, monitoring endometrial echotexture alterations, especially homogeneity and contrast, changed depending on the cellular density and inflammation status and may be potential diagnostic markers for subclinical endometritis in cows.

Interleukin-6 and C-reactive protein levels in the amniotic fluid as indicators of preterm delivery in Turkish women.

OBJECTIVE: The aim of this study was to determine the value of amniotic fluid interleukin-6 (IL-6) and C-reactive protein (CRP) levels in the prediction of preterm delivery in singleton pregnancies without any known risk factors for preterm delivery in Turkish women. MATERIALS AND METHODS: Patients in the present perinatology department who underwent mid-trimester genetic amniocentesis due to evidence of increased risk of aneuploidy in their prenatal serum screening tests were included in the study. A sample of amniotic fluid from each patient was assessed for IL-6 and CRP. Concentrations of IL-6 and CRP in the amniotic fluid of preterm delivery and term delivery groups were compared. RESULTS: Of 151 singleton pregnancies, 142 participants were included in the study. The participants were assigned to either the preterm or term delivery group based on pregnancy outcome. IL-6 levels in the amniotic fluid were significantly higher in the preterm delivery group, and there was a statistically significant negative correlation between IL-6 concentrations in the amniotic fluid and gestational age at delivery (correlation coefficient (CC): -18.5%, p < 0.05). A negative correlation was also detected between CRP levels in the amniotic fluid and gestational age at delivery, but the correlation was not statistically significant (p = 0.068). CONCLUSION: Measuring IL-6 in the amniotic fluid can identify women at risk of preterm delivery. Because it is not acceptable to perform amniocentesis for this screening, it is more convenient for patients in whom genetic amniocentesis is performed.

Examination of the effects of thiamine and thiamine pyrophosphate on Doxorubicin-induced experimental cardiotoxicity.

BACKGROUND AND PURPOSE: To investigate the effect of thiamine and thiamine pyrophosphate on doxorubicin-induced cardiotoxicity biochemically and histopathologically and to examine whether doxorubicin cardiotoxicity is related to the conversion of thiamine into thiamine pyrophosphate and inhibition of thiamine pyrophosphokinase (TPK) enzyme. EXPERIMENTAL APPROACH: A total of 48 Albino Wistar male rats were used. Rats were divided into groups as thiamine + doxorubicin (TIA + DOX), thiamine pyrophosphate + doxorubicin (TPP + DOX), DOX, and healthy (HEA) groups. One hour after the administration of thiamine and TPP in 25 mg/kg doses, 5 mg/kg doxorubicin were injected to all groups except HEA group during 7 days. Then, the samples were collected for biochemical (glutathione [GSH], malondialdehyde [MDA], DNA damage, creatine kinase (CK), CK-MB, and troponine I [TP-I]), molecular (TPK), and histopathological examinations. KEY RESULTS: Oxidant parameters (MDA and DNA damage) decreased and antioxidant parameter (GSH) increased in TPP + DOX group. In addition, levels of CK, CK-MB, and TP-I were low in the TPP + DOX group and high in the TIA + DOX and DOX groups. Cardiac tissue was protected in TPP + DOX group, and no protective effect was observed in TIA + DOX and DOX groups. Messenger RNA expression of TPK was decreased in DOX and TIA + DOX groups. CONCLUSION AND IMPLICATIONS: The cardiotoxic effect of doxorubicin originated from the inhibition of TPK enzyme resulting in insufficient production of thiamine pyrophosphate.

The effect of thin film morphology on the electrochemical performance of Cu-Sn anode for lithium rechargeable batteries.

We investigate the anode performance of non ordered and ordered nanostructured Cu-Sn thin films deposited via electron beam deposition technique. The ordered nanostructured Cu-Sn thin film having nano-porosities was fabricated using an oblique (co)deposition technique. Our results showed that the nano structured Cu-Sn thin film containing Cu-Sn nanorods had higher initial anodic capacity (790 mA h g(-)) than that of the non ordered thin film (330 mA h g(-)). But the capacity of the ordered nanostructured Cu-Sn thin film diminished after the first cycle and a steady state capacity value around 300 mA h g(-) is sustainable in following up to 80th cycle, which is attributed to the composition and morphology of the thin film. The presence of copper containing Sn nanorods leading to form nano-porosities as interstitial spaces among them, enhanced lithium ions movement within thin film and increased the thin film tolerance against the stress generated because of the drastic volume change occurred during lithiation-delithiation processes; hence, homogenously distributed porosities increased the cycle life of the thin film.

Generation of prostate IMAT plans adaptable to the inter-fractional changes of patient geometry.

We present the results of 2-Step generation of adaptable IMAT plans for prostate carcinoma cases. The 2-Step IMAT plans show clinical and dosimetric equivalence to the reference SmartArc™-generated VMAT plans. The 2-Step plans are adapted to inter-fractional changes of prostate-rectum geometry using 2-Step adaptation rules for a cohort of ten adaptation cases. The adapted 2-Step IMAT plans show statistically significant improvement (Wilcoxon 1-tail p < 0.05) of target coverage and of rectum sparing when compared to isocenter relocated plans.

Elastosonographic strain index in thyroid nodules with atypia of undetermined significance.

AIM: In this study, we aimed to evaluate the diagnostic accuracy of elastosonography (ESG) scoring and strain ratio in patients who had atypia of undetermined significance (AUS) cytology and underwent surgery for thyroid nodules. MATERIALS AND METHODS: 250 patients were included in this study. They had at least one nodule in thyroid USG, underwent USG-guided FNAC according to the current guidelines and had AUS cytology according to the Bethesda system. Both elastosonographic color scoring and strain index were evaluated. RESULTS: A total of 270 nodules in 250 patients were evaluated. Histopathologically, 81 (30 %) nodules were malignant and 189 (70 %) were benign. According to the ESG, 10 (3.7 %) nodules were assigned a score of 1, while 13 (4.8 %) nodules were assigned a score of 5. All of the nodules with an ESG score of 1 were histopathologically benign and 92.3 % of the patients with ESG score 5 were in the malignant group. Median SI in the benign histopathologic group was significantly lower compared to malignant group [(2.58 (IQR = 2.35) vs. 14.54 (IQR = 10.71)]. The optimal SI cut-off value to distinguish between the benign and malignant nodules was 6.66, with a sensitivity of 98.77 % and specificity of 96.30 %. CONCLUSION: Our study is one of the first studies evaluating the role of SI for discriminating malignant and benign nodules with AUS cytology. Malignant nodules had a significantly higher stiffness compared to benign ones and SI had high sensitivity, specificity, positive predictive value, negative predictive value and accuracy for these nodules. We think SI may be helpful for the presurgical selection of nodules with AUS cytology.

Parapharyngeal space tumours: the efficiency of a transcervical approach without mandibulotomy through review of 44 cases.

The aim of this study was to describe our experience with benign parapharyngeal space tumours resected via a transcervical route without mandibulotomy and to investigate associated postoperative sequelae and complications. The study investigated and analysed the retrospective charts of 44 patients who underwent surgery for benign parapharyngeal space tumours over a 10-year period. The diagnosis was reached in all patients with clinical and radiologic findings; preoperative fine-needle aspiration biopsy was not performed in any case. The preferred means of accessing the parapharyngeal space in all patients was a transcervical route. In 5 of these patients, transparotid extension was performed due to the position of the tumour. Tumours were classified radiologically as poststyloid in 27 cases and prestyloid in 17 cases. The final histopathologic diagnosis was vagal paraganglioma in 16 cases, pleomorphic adenoma in 13 cases, schwannoma in 10 cases and comparatively rarer tumours in the remaining 5 cases. In three patients, cranial nerve paralysis was observed during preoperative evaluation. Permanent cranial nerve paralysis occurred in 19 cases (43.2%) in the postoperative period, the majority of which were neurogenic tumours such as vagal paraganglioma (n = 16) and schwannoma (n = 2), and one case of non-neurogenic parapharyngeal tumour. The median duration of follow-up was 61 ± 33 months. There was no local recurrence in any patient during the follow-up period. A transcervical approach should be the first choice for excision of parapharyngeal space tumours, except for recurrent or malignant tumours, considering its advantages of providing direct access to the neoplasm, adequate control of neurovascular structures from the neck and optimal aesthetic outcomes due to preservation of mandibular continuity with minimal morbidity and hospitalisation time.