Πέμπτη 4 Μαρτίου 2021

Improving motor function after chronic stroke by interactive gaming with a redesigned MR-compatible hand training device

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Exp Ther Med. 2021 Mar;21(3):245. doi: 10.3892/etm.2021.9676. Epub 2021 Jan 22.

ABSTRACT

New rehabilitation strategies enabled by technological developments are challenging the prevailing concept of there being a limited window for functional recovery after stroke. In this study, we examined the utility of a robot-assisted therapy used in combination with a serious game as a rehabilitation and motor assessment tool in patients with chronic stroke. We evaluated 928 game rounds from 386 training sessions of 8 patients who had suffered an ischemic stroke affecting middle cerebral artery territory that incurred at least 6 months prior. Motor function was assessed with clinical motor scales, including the Fugl-Meyer upper extremity (FM UE) scale, Action Research Arm Test, Modified Ashworth scale and the Box and Blocks test. Robotic device output measures (mean force, force-position correlation) and serious game score elements (collisions, r ewards and total score) were calculated. A total of 2 patients exhibited a marginal improvement after a 10-week training protocol according to the FM UE scale and an additional patient exhibited a significant improvement according to Box and Blocks test. Motor scales showed strong associations of robotic device parameters and game metrics with clinical motor scale scores, with the strongest correlations observed for the mean force (0.677<Ρ<0.869), followed by the number of collisions (-0.670<Ρ<-0.585). Linear regression analysis showed that these indices were independent predictors of motor scale scores. In conclusion, a robotic device linked to a serious game can be used by patients with chronic stroke and induce at least some clinical improvements in motor performance. Robotic device output parameters and game score elements associate strongly with clinical motor scales and have the potential to be used as predictors in models of rehabilitation progress.

PMID:< a href="https://pubmed.ncbi.nlm.nih.gov/33603853/?utm_source=Inoreader&utm_medium=rss&utm_content=1ba2t84FK1dz-fAY5g7-lbp7yzA9oSsgU2XptRGyGkyx-wIkEA&ff=20210224025424&v=2.14.2" target="_blank" rel="noopener" class="underlink bluelink" tabindex="-1">33603853 | PMC:PMC7851602 | DOI:10.3892/etm.2021.9676

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The efficacy of immunotherapy for in-transit metastases of melanoma: an analysis of randomized controlled trials

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Nearly 10% of patients with high-risk early-stage melanoma will develop satellite or in-transit metastases (ITM), classified as stage III disease similar to lymph node metastases. The pivotal registration trials of the CTLA-4 antibody ipilimumab, and the PD-1 antibodies nivolumab and pembrolizumab, also included patients with unresectable stage III disease. However, there has been no analysis of patients with ITM, and anecdotal retrospective small series have indicated a potential lesser effect. This study aimed to identify patients with unresectable ITM within the randomized trials, and to determine response, progression-free survival and overall survival. The pivotal phase III randomized intervention trials that included melanoma patients with ITM, with or without nodal metastasis, and were treated with ipilimumab, nivolumab or pembrolizumab was identified. The datasets from each trial were then searched to identify the specific details of the investigated patient population for a pooled analysis. The primary endpoint was complete response rate. Seven trials that included stage III patients, and with accessible datasets, were identified. There was a total of 4711 patients, however, no patients with ITM could be identified, as this data was not captured by the case report forms. Evidence from prospective clinical trials on the use of immunotherapy in patients with ITM is lacking. We recommend pooling data from multiple institutions to examine efficacy of available drug therapies in this patient population, but more importantly, prospective clinical trials of locoregional treatments with or without systemic drug therapies are required. Received 30 November 2020 Accepted 12 January 2021 Correspondence to Roger Olofsson Bagge, MD, PhD, Department of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden, Tel: +46 31 3428207; e-mail: roger.olofsson@surgery.gu.se Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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A case of sudden brain metastases progression after temporary targeted therapy discontinuation: when to regret a drug holiday

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Targeted therapy improves outcomes in BRAF V600-mutant metastatic melanoma with active brain metastases. We present the case of a patient with rapid brain disease progression upon temporary targeted therapy discontinuation and unusual rapid disease response upon treatment resumption. This report presents a 78-year-old woman with metastatic BRAF V600E positive melanoma (bladder and brain localizations). The patient started first-line dabrafenib and trametinib with good tolerability and evidence of complete response (CR). After 8 months of maintained CR, the patient took a drug holiday for 14 days. Brain MRI performed after treatment pause showed extensive disease progression, whereas extracranial staging was negative. The patient was asymptomatic: she restarted targeted therapy a nd underwent evaluation for whole-brain radiotherapy. Brain computed tomography scan and subsequent MRI performed to plan radiotherapy showed brain CR after only 10 days of targeted therapy resumption. The patient continued treatment, and radiotherapy indication was withheld. Repeated brain MRI confirmed maintained CR. Treatment with dabrafenib and trametinib is ongoing with excellent tolerability. Rapid intracranial progression is a well-known finding after discontinuation of combined targeted therapy in the case of extracranial progressive disease. This is the first report of documented disease progression upon temporary treatment discontinuation for reasons other than toxicity, with an unusual response after retreatment. Caution should be used in tailoring treatment during targeted therapy, allowing pauses for reasons other than toxicity. Strict adherence to treatment is paramount to guarantee disease control. Received 9 November 2020 Accepted 16 January 2021 Correspondence to Alice Indini, MD, Department of Internal Medicine, Medical Oncology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milano, Italy, Tel: +39 0255032660; fax: +39 0255032659; e-mail: alice.indini@gmail.com. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment

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Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immunity by downregulating arginase 1 and inducible nitric oxide synthase production in MDSCs. Accordingly, decreased T cell anergy and helper to regulatory T cell conversion have been observed in the presence of NLGP, which ultimately augments T cell functions. Mechanistically, NLGP-mediated rectification of T cell suppressive functions of MDSCs was primarily associated with downregulation of the interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling axis within the tumor microenvironment, as confirmed by knockdown of STAT3 (by STAT3-siRNA) and using IL-10−/− mice. Thus, NLGP-mediated suppression of MDSC functions in tumor hosts is appeared to be another associated effective mechanism for the eradication of murine melanoma by NLGP. * Dr. Anamika Bose and Dr. Rathindranath Baral contributed equally to the writing of this article. Received 7 November 2020 Accepted 12 January 2021 Correspondence to Rathindranath Baral, PhD, Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Kolkata 700026, India, Tel: +91 033 2476 5101 ext. 334; fax: +91 033 2475 7606; e-mail: baralrathin@hotmail.com; rathindranath.baral@cnci.org.in Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model

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Melanoma-bearing Libechov minipig (MeLiM) represents a large animal model for melanoma research. This model shows a high incidence of complete spontaneous regression of melanoma – a phenomenon uncommon in humans. Here, we present the first metabolomic characterisation of the MeLiM model comparing animals with progressing and spontaneously regressing melanomas. Plasma samples of 19 minipigs with progression and 27 minipigs with evidence of regression were analysed by a targeted metabolomic assay based on mass spectrometry detection. Differences in plasma metabolomics patterns were investigated by univariate and multivariate statistical analyses. Overall, 185 metabolites were quantified in each plasma sample. Significantly altered metabolomic profile was found, and 42 features wer e differentially regulated in plasma. Besides, the machine learning approach was used to create a predictive model utilising Arg/Orn and Arg/ADMA ratios to discriminate minipigs with progressive disease development from minipigs with regression evidence. Our results suggest that progression of melanoma in the MeLiM model is associated with alteration of arginine, glycerophospholipid and acylcarnitines metabolism. Moreover, this study provides targeted metabolomics characterisation of an animal model of melanoma with progression and spontaneous regression of tumours. * Martin Kertys, Marian Grendar and Vratislav Horak contributed equally to the writing of this article. Received 18 September 2020 Accepted 12 January 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Jan Strnadel, Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin Comenius University in Bratislava, Mala Hora 4D 036 01, Martin, Slovak Republic, Tel: +421 43 2633652; e-mail: jan.strnadel@uniba.sk Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Immunohistochemistry analysis reveals lysyl oxidase-like 3 as a novel prognostic marker for primary melanoma

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Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan–Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stag es (P 
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Unexpected pure red series aplastic anemia secondary to pembrolizumab treatment: a case report and literature review

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Pembrolizumab is a treatment that has shown a survival benefit in patients with metastatic melanoma. Programmed death receptor 1 inhibitors are new therapeutic agents that produce clinical responses with a more manageable profile of adverse effects compared to chemotherapy. The most frequent adverse effects include fatigue, rash, myalgia, pyrexia and cough, with less frequent occurrence of immune-mediated adverse reactions such as colitis, pneumonitis, hepatitis and encephalitis. Immune-related hematological toxicities have been poorly described. Here we present the case of a patient with metastatic melanoma who develops pure red series aplasia after almost 3 years of treatment with pembrolizumab. To our knowledge, this is the first case of aplastic anemia during treatment with pembrol izumab, with some peculiarities compared to the published cases in the literature. Received 2 May 2020 Accepted 14 January 2021 Correspondence to Marina Merí Abad, MD, Consorci Hospital General Universitari de Valencia, Av/Tres Cruces, 14, 46009 Valencia, Spain, Tel: +619842788; e-mail: Marinameri@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Outcomes of Patients Undergoing Emergency Tracheostomy During COVID 19 Pandemic: Our Experience from a Tertiary Care Centre in North-East India

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Abstract

Airway management in the form of tracheostomy may be done as an emergency or elective procedure depending on when the patient presents and it usually involves a multi-disciplinary team including the anesthesiologist and emergency physician. The purpose of this study is to present our experience with emergency tracheostomies carried out for patients presenting with tumors in the aerodigestive tract during this period of covid 19 pandemic and their outcomes. This is a cross sectional observational study. All the patients who underwent emergency tracheostomy at Dr. B. Borooah Cancer Institute, Guwahati, India, during the period 24th March, 2020 to 23rd September, 2020(6 months) are included in this study. A total of 115 patients underwent 117 emergency tracheostomies (two underwent redo tracheostomies). Median age of patients was 55 years. More than 85% of patients were male. The most common initial presenting complaint was dysphagia (40%) followed by dyspnea (25%). Most common site of tumor was pyriform sinus cancer (45.2%). Almost 45% of patients presented with stage IVA. Complications were seen in 10 patients (8.7%). These included stomal stenosis in 4(3.5%), primary hemorrhage in 3(2.6%), subcutaneous emphysema, infection and wound break down each in one patient (0.9% each). Among the eight residents who performed these procedures, five developed covid 19 symptoms subsequently, and were tested covid positive. Emergency tracheostomy is a safe procedure for patients; however it carries a higher risk of covid transmission despite using proper precautions.

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A cause‐specific Cox model for second primary tumors in patients with head and neck cancer: A RONCDOC study

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Abstract

Background

The aim of this study was to identify risk factors for the development of second primary tumors (SPTs) in the head and neck region, lungs, and esophagus in patients with head and neck cancer.

Methods

We collected data from 1581 patients. A cause‐specific Cox model for the development of an SPT was fitted, accounting for the competing risks residual/recurrent tumor and mortality.

Results

Of all patients, 246 (15.6%) developed SPTs. Analysis showed that tobacco and alcohol use, comorbidity, and the oral cavity subsite were risk factors for SPTs. The C‐index, the discriminative accuracy, of the model for SPT was 0.65 (95% confidence interval, 0.61–0.68).

Conclusions

Our results show that there is potential to identify patients who have an increased risk to develop an SPT. This might increase their survival chances and quality of life. More research is needed to provide head and neck clinicians with definitive recommendations.

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Does nutritional treatment in patients with dysphagia affect malnutrition and anxiety?

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Nutr Hosp. 2021 Mar 4. doi: 10.20960/nh.03430. Online ahead of print.

ABSTRACT

INTRODUCTION: dysphagia is common in patients with cerebrovascular disease (CVD), with an incidence reported to be 35 %-50 %. Dysphagia can result in malnutrition, dehydration, and death, and negatively affects anxiety levels.

OBJECTIVES: this study aimed to evaluate the effects of recommended nutritional treatment (NT) on nutritional status and anxiety levels in patients with dysphagia based on cl inical and fiber-optic endoscopic evaluation of swallowing (FEES) tests.

METHODS: seventy-five patients over the age of 50 who were diagnosed with CVD, hospitalized at the Mersin City Research and Training Hospital, Neurology Clinic, from October 2019 to January 2020 were followed up for the study. The FEES test was performed to diagnose dysphagia in CVD patients. Anthropometric measurements of the patients were taken to calculate their body mass index (BMI) values. To determine a patient's daily energy and food intake, 24-h food recalls were taken, and the Nutritional Risk Screening 2002 (NRS 2002) test was used to identify patients at risk of malnutrition. State (SAI)-Trait Anxiety Inventories (TAI) were used to determine instant and general anxiety levels. After patient evaluations NT was provided. All evaluations were repeated 8 weeks after NT. Our study was carried out based on a longitudinal design since we worked with the same units at two different time points.

R ESULTS: post-NT SAI scores were significantly lower than pre-NT scores (p < 0.05). A moderate correlation was found between pre- and post-NT SAI scores and daily energy and fluid intake status, and between TAI scores and daily energy, fat, and fluid intake amounts (p < 0.05). Post-NT SAI scores significantly decreased with both NRS 2002 and BMI values (p < 0.05).

CONCLUSIONS: this study highlights the importance of NT in improving rehabilitation outcomes of patients with dysphagia. Since exercises such as postural techniques or maneuvers, and muscle strengthening to reduce swallowing difficulties are an important part of NT for dysphagia, a multidisciplinary study is required for the management of dysphagia, and further studies are needed on this subject.

PMID:33657826 | DOI:10.20960/nh.03430

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Temporomandibular Joint Arthrocentesis: A Case Series

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Abstract

Arthrocentesis is a simple minimally invasive procedure with less risk of complications and significant benefits in patients with internal derangement of temporomandibular joint. Here we report a study on four patients to evaluate the efficacy of arthrocentesis in the treatment of internal derangement of temporomandibular joint.

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