FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA.

Unlabelled: Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed and validated FUME-TCRseq, a robust and sensitive RNA-based TCR sequencing methodology that is suitable for formalin-fixed paraffin-embedded samples and low amounts of input material.

Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19-A retrospective cohort study.

COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor monoclonal antibodies are associated with heterogenous treatment effects between male and female patients.

Effective prolonged suppression of HIV-1 viral load using tenofovir alafenamide, emtricitabine and efavirenz in an adult with BMI >59 kg/m.

Limited information is available regarding the efficacy of antiretrovirals in people with HIV-1 and high or very high Body Mass Index (BMI). This is especially the case for the alafenamide salt of tenofovir as clinical trials have only enrolled patients with BMI ≤30 kg/m. Lower concentrations of some antiretrovirals are expected in patients with BMI >30 kg/m due to potential changes in clearance and distribution of medication.

CAR-T cells, the first pharmaceutical cell therapy.

The success of genetically engineered adoptive cell therapies in haematological malignancy in the second decade of the 21st century has surprised both immunologists and oncologists. It challenges much of our understanding of the role of personalised medicine, the divide between cell products and pharmaceutical drugs and the limitations of the immune system to clear cancer. Furthermore, many challenges remain, the therapy is both expensive, hazardous and largely restricted to lymphoproliferative disease.

[RADIONUCLIDE THERAPY OF NEUROENDOCRINE TUMORS - IMPROVEMENTS IN THE PROTOCOL FOR MEASUREMENT OF PATIENT RADIATION EXPOSURE].

Aims: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment.

Background: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy.

Efficacy and Safety of Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study.

The purpose of this study was to assess the efficacy and safety of Lu-DOTATATE in patients with somatostatin receptor (SSR)-positive lung neuroendocrine tumors (NETs). This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with Lu-DOTATATE at 2 ENETS Centers of Excellence. Morphologic imaging (RECIST 1.

Can a penalized-likelihood estimation algorithm be used to reduce the injected dose or the acquisition time in Ga-DOTATATE PET/CT studies?

Background: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality.

The diagnostic role of diffusional kurtosis imaging in glioma grading and differentiation of gliomas from other intra-axial brain tumours: a systematic review with critical appraisal and meta-analysis.

Purpose: We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas.

Methods: A review protocol was developed according to the (PRISMA-P) checklist, registered in the international prospective register of systematic reviews (PROSPERO) and published. A literature search in 4 databases was performed using the keywords 'glioma' and 'diffusional kurtosis'.

Role of diffusional kurtosis imaging in grading of brain gliomas: a protocol for systematic review and meta-analysis.

Introduction: Central nervous system (CNS) gliomas are the most common primary intra-axial brain tumours and pose variable treatment response according to their grade, therefore, precise staging is mandatory. Histopathological analysis of surgical tumour samples is still deemed as the state-of-the-art staging technique for gliomas due to the moderate specificity of the available non-invasive imaging modalities. A recently evolved analysis of the tissue water diffusion properties, known as diffusional kurtosis imaging (DKI), is a dimensionless metric, which quantifies water molecules' degree of non-Gaussian diffusion, hence reflects tissue microenvironment's complexity by means of non-invasive diffusion-weighted MRI acquisitions.

A practical approach to Events Medicine provision.

In the past three decades, mass casualty incidents have occurred worldwide at multiple sporting events and other mass gatherings. Organisational safety and healthcare provision can consequently be scrutinised post-event. Within the UK, such incidents in the 1980s provided incentives to improve medical services and subsequent high profile UK-based international sporting events (London Olympics and Paralympics 2012, Glasgow Commonwealth Games 2014, Rugby World Cup 2015) added a further catalyst for developing services.

Ascertainment bias causes false signal of anticipation in genetic prion disease.

Anticipation is the phenomenon whereby age of onset in genetic disease decreases in successive generations. Three independent reports have claimed anticipation in Creutzfeldt-Jakob disease (CJD) caused by the c.598G > A mutation in PRNP encoding a p.

In the era of micro-dissection sperm retrieval (m-TESE) is an isolated testicular biopsy necessary in the management of men with non-obstructive azoospermia?

Objectives: To assess the outcome of sperm retrieval using micro-dissection-TESE (m-TESE) and simultaneous diagnostic biopsy in NOA to determine if the final definitive histology correlated with the outcome of sperm retrieval by m-TESE in men with NOA. To determine if there was a correlation between FSH levels and positive sperm retrieval rates and assessed the success rate of m-TESE as either a primary or a salvage procedure after previous negative sperm retrieval. The EAU guidelines (2010) recommend that in men with non obstructive azoospermia 'a testicular biopsy is the best procedure to define the histological diagnosis and the possibility of finding sperm'.

Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy.

Background: Idiopathic dilated cardiomyopathy is a familial disorder in 25% to 50% of patients, but the genetic basis in the majority of cases remains unknown. Genes encoding desmosomal proteins, currently regarded as synonymous with another disorder, arrhythmogenic right ventricular cardiomyopathy, are known to cause left ventricular dysfunction, but their importance in unselected patients with unequivocal dilated cardiomyopathy is unknown. The objective of this study was to determine the prevalence of mutations in 5 desmosomal protein genes in patients with dilated cardiomyopathy.

A Phase II Study of Docetaxel for the Treatment of Recurrent Osteosarcoma.

Purpose: To determine the response and toxicity of docetaxel in recurrent osteosarcoma and related spindle cell tumours of bone.

Patients And Methods: Fourteen patients, 10 males and four females, were enrolled, median age 30.5 years (range, 17-46).

Doubling the resolution of echo-planar brain imaging by acquisition of two k-space lines per gradient reversal using TRAIL.

Single-shot echo-planar imaging (EPI) is an important method for MRI of the brain. A method has been developed to double the resolution of EPI in the phase-encode direction, without requiring increases in the maximum gradient amplitude or slew rate. The new approach is based on an EPI implementation of the TRAIL (two reduced acquisitions interleaved) method, in which two images, acquired in rapid succession, are spatially interleaved.

Plaque incision and fascia lata grafting in the surgical management of Peyronie's disease.

Objective: To assess the outcome of using modified human fascia lata (Tutoplast, Mentor Corp, Santa Barbara, CA, USA) in the surgical management of Peyronie's disease (PD), as the penile deformity associated with PD can be corrected by plaque incision and saphenous vein grafting (Lue procedure).

Patients And Methods: In all, 14 patients (mean age 51 years, range 34-59) with PD had their penile deformity corrected by plaque incision and Tutoplast grafting. Three patients had a previous unsuccessful Nesbit operation.

EPI distortion correction from a simultaneously acquired distortion map using TRAIL.

Purpose: To develop a method for shot-by-shot distortion correction of single-shot echo-planar imaging (EPI) that is capable of correcting each image individually using a distortion measurement performed during acquisition of the image itself.

Materials And Methods: The recently-introduced method known as two reduced acquisitions interleaved (TRAIL) was extended to measure the distribution of the main magnetic field B0 with each shot. This corresponded to a map of distortion, and allowed distortion to be corrected in the acquired images.

A phase I/II study of doxorubicin, ifosfamide, etoposide and interval methotrexate in patients with poor prognosis osteosarcoma.

Background: The prognosis for patients with metastatic or axial-skeletal osteosarcoma is poor. A phase I/II study was conducted of intensive chemotherapy with interval methotrexate, to assess the feasibility, response rate and toxicity in this group of patients.

Patients And Methods: Thirteen patients, median age 18 (range: 8-34), with metastatic or axial-skeletal osteosarcoma were treated with ifosfamide 2.

Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy and radiotherapy for Ewing's sarcoma: a review of the literature and implications for practice.

Radiation myelopathy is a rare, devastating, late effect of radiotherapy to the spinal cord. Spinal cord tolerance is currently accepted as about 50 Gy in 1.8-2 Gy fractions.