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stration for patients who can use their paretic arms. This could benefit patients without access to health care centres or in situations requiring physical distancing. This home-based tDCS combined with exercise has the potential to be incorporated into telemedicine in stroke rehabilitation.IMPLICATIONS FOR REHABILITATIONTwelve sessions of home-based dual-tDCS combined with exercises (3 days/week for 4 weeks) facilitated upper and lower limb motor recovery in patients with chronic stroke compared with exercise alone, with a post-effect for at least 1 month.Home-based tDCS could be safe and easily self-administrable by patients who can use their paretic arms.This intervention could be beneficial for patients living in the community without easy access to a health care centre or in situations where physical distancing is required.Introduction The prognosis of patients with advanced biliary tract cancer (BTC) remains dismal, with a 5-year overall survival rate of less than 10%. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of several hematological and solid tumors, controversial results have been reported in BTC. In this setting, the anti-PD-L1 inhibitor durvalumab is currently under investigation in several clinical trials as monotherapy, or in combination with other pharmacological agents.Areas covered We offer an overview of immunotherapies for BTC, discuss recently published or presented data on durvalumab pharmacology, safety, and efficacy in the treatment of BTC and consider future research directions for the agent in this setting.Expert opinion The promising antitumor activity shown by durvalumab in early trials warrants further investigation because it may provide more effective, much needed treatment options. The results of clinical trials of this PD-L1 inhibitor, as a monotherapy or in combination, are eagerly awaited. Sapitinib chemical structure Future efforts should focus on the identification and development of reliable biomarkers of response to durvalumab in BTC, clarifying the role of PD-L1 expression, microsatellite instability (MSI), mismatch repair (MMR), tumor mutational burden (TMB) and other emerging predictors.Background Patients with renal cancer are at increased risk of comorbid congestive heart failure (CHF) due to several shared risk factors and the cardiotoxicity of some medications used for renal cancer treatment. We aimed to examine the relationship between CHF and hospital outcomes among renal cancer patients in the U.S.Methods In this cross-sectional study, we identified hospitalizations of renal cancer patients using the 2015-2017 National Inpatient Sample. We assessed the relationship between CHF and hospital outcomes in this patient population, including in-hospital mortality, length-of-stay (LoS), and hospital costs.Results Among the 20,321 hospitalizations of renal cancer patients identified, 6.1% involved patients with comorbid CHF (n = 1,231). The odds of in-hospital mortality did not differ based on CHF presence (odds ratio = 1.21; p = 0.354). Hospitalizations of renal cancer patients with CHF were associated with a greater LoS (incidence rate ratio = 1.44; p less then 0.001) and higher hospital costs (cost ratio = 1.27; p less then 0.001) than those without CHF.Conclusions CHF in renal cancer patients is associated with increased LoS and higher hospital costs. These findings suggest that optimal management of comorbid CHF may improve hospital outcomes in patients with renal cancer and provides evidence to support the emerging field of cardio-oncology.

Fibrosis is a serious disease that occurs in many organs, such as kidney, liver and lung. The deterioration of these organs ultimately leads to death. Due to the complex mechanisms of fibrosis, research and development of antifibrotic drugs is difficult. One solution is to focus on core pathways, one of which is the TGF-β signaling pathway. In virtually every type of fibrosis, TGF-β signaling is recognized as a critical pathway.

This review discusses patents on active molecules related to the TGF-β signaling. Molecules targeting components related to the activation of TGF-β are introduced. Several strategies preventing signal propagation from active TGF-β to downstream targets are also introduced, including TGF-β antibodies, TGF-β ligand traps, and inhibitors of TGF-β receptor kinases. Finally, molecules affecting downstream targets in both canonical and noncanonical TGF-β signaling pathways are described.

Since the approval of pirfenidone, targeting TGF-β signaling has been anticipated as an effective therapy for fibrosis. The potential of this therapy has been further supported by emerging patents on the TGF-β signaling. This pathway can be entirely inhibited, from the activation of TGF-β to downstream signaling. Inhibiting TGF-β signaling is expected to provide more effective treatments for fibrosis.

Since the approval of pirfenidone, targeting TGF-β signaling has been anticipated as an effective therapy for fibrosis. The potential of this therapy has been further supported by emerging patents on the TGF-β signaling. This pathway can be entirely inhibited, from the activation of TGF-β to downstream signaling. Inhibiting TGF-β signaling is expected to provide more effective treatments for fibrosis.

Intraorbital encephalocele (OMEC) is a rare entity in adults, usually secondary to an orbital pathology or prior trauma, in particular orbital roof fractures. Treatment of the OMEC is warranted to alleviate the pulsating exophthalmos and prevent potential visual decline. OMEC and orbital roof fractures have been predominantly treated via a craniotomy with a reconstruction of the orbital roof using various implants. With the advances in the endoscopic techniques, neuroendoscopy found its application in the treatment of orbital pathologies. We report a minimally invasive alternative endoscopic transorbital repair of OMEC.

The repair technique is described with illustrations and clinical images. Narrated operative video demonstrating the procedure is provided.

Illustrative case 50-year-old female presented with progressive right eye proptosis over 6 months. Computed tomography (CT) demonstrated bony erosion in the lateral orbital roof, and magnetic resonance imaging (MRI) showed a small hyperintense T2-weighted and T1-weighted contrast enhancing lesion in the orbit, in the area of the bony erosion. Intraoperatively, the lesion was found to be an orbital encephalocele. The orbital defect was successfully repaired by employing the 'sandwich' technique, in which a dural substitute reinforced with tissue glue were deployed without repair of the osseous orbital roof. The patient tolerated the procedure well with ultimate resolution of proptosis. The cosmetic outcome was excellent.

The transorbital neuroendoscopic approach (TONES) presents a feasible, minimally invasive alternative treatment option for circumscribed intraorbital encephaloceles with minimal side effects, well tolerated by patients.

The transorbital neuroendoscopic approach (TONES) presents a feasible, minimally invasive alternative treatment option for circumscribed intraorbital encephaloceles with minimal side effects, well tolerated by patients.Objectives To do a systematic review covering assessments and interventions for central facial palsy (CFP) in patients with acquired brain injury.Methods PubMed, Embase, Cinahl, PsycInfo, and Web of Science were screened until April 2019. Assessments were defined as clinical- and instrumental tools and rating scales. Interventions were defined as rehabilitation interventions alleviating CFP.Results 690 articles were screened based on the title and abstract. Interrater agreement was 98.12%. Sixteen articles were included six clinical trials and 10 observational studies. Assessment Commonest scale for assessing CFP was the House-Brackmann facial nerve Grading System. Strain gauges for measuring lip and cheek strength were applied in five studies and neurophysiological methods of assessing motor neuron pathways were applied in three studies. Interventions An oral screen for improving lip strength was reported in three studies. Other interventions reported were neuromuscular electrical stimulation, Castillo Morales therapy, mirror therapy, exercises with electromyography feedback, and acupuncture.Conclusions Scales for assessing peripheral facial palsy were applied for assessing CFP. Based on neurophysiological differences in the manifestation of peripheral facial palsy and CFP, these scales should be validated in patients with CFP. More studies on interventions for CFP are required before conclusions may be drawn about their effectiveness.

Results from studies investigating life satisfaction, positive affect and happiness of near-centenarians (95+) and centenarians are inconsistent. This is the first systematic review to summarise the extant literature on the subjective well-being of this unique age group.

Seven electronic databases (PubMed, MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science and the Cochrane database for systematic reviews) were systematically searched. Subjective well-being was defined as life satisfaction, positive affect and happiness. A narrative synthesis of relevant articles was undertaken.

Of 28 studies eligible for inclusion in this review, 20 predominantly examined life satisfaction, 11 positive affect and 4 happiness. Sex and other demographic variables were not significant predictors of subjective well-being. In contrast, greater perceived health was significantly associated with higher levels of life satisfaction and positive affect. Fatigue and visual impairment were significantly correlated with lower levels ns on subjective well-being. Future research should be directed towards interventions that promote subjective well-being in the oldest-old.Purpose To evaluate changes in oral health-related quality of life (OHRQoL) and associated factors in individuals with acquired brain injury (ABI) during hospitalization.Methods Forty-six individuals with ABI were examined at week 1 and 5 of hospitalization. OHRQoL was recorded through Oral Health Impact Profile-14 (OHIP-14), clinical oral examinations were conducted, while orofacial health-related 'motor' and 'cognitive' scores were retrieved from patients' e-journal. Association between variables were investigated using factor analysis and multilevel regression modeling.Results There were no significant differences in the OHIP-14 scores between week 1 and 5. Factors analysis revealed two OHIP-14 domains, 'psychosocial' and 'physica'. Individuals who improved their cognitive skills over study period and those with 'severe' periodontitis at baseline had increased scores of OHIP-14 'psychosocial' domain. Individuals who improved orofacial health-related 'motor' skills over study period had decreased 'physical' domain scores. Increased cognition over study period, current smoking and dental calculus were associated with increased 'physical' domain.Conclusions The OHRQoL was poor both at week 1 and 5. Individual's cognitive and motor skills as well as their oral health status influenced their OHRQoL. Thus, individual's awareness and involvement in addition to oral care seem to be imperative in improving the OHRQoL in neurorehabilitation setting.

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