Rejected

Breakthrough cancer pain (BTcP) is a transient exacerbation of pain that occurs over persistent, stable, and adequately controlled cancer background pain. It is prevalent and bears severe consequences to patients' quality-of-life. The effective management of BTcP depends on fast and reliable (re)assessment. The Breakthrough pain Assessment Tool (BAT) is one of the most concise and reliable self-report instruments adapted to clinical contexts so far, showing good psychometric qualities in the United Kingdom, the Netherlands, and South Korea. As to promote the effective management of BTcP in Portuguese-speaking communities this study, first aimed to culturally adapt and validate the Portuguese version of the BAT (BAT-Pt). Second, and most importantly, it sought to provide novel evidence on its criterion validity by investigating its association with measures of psychological distress, which has not been yet investigated.

The two major etiologies of shoulder superior labral tears anterior to posterior (SLAP) are traumatic and degenerative processes. Bucket handle tears of the superior labrum represent one-third of labral lesions. However, in this article, we present a double bucket handle tear which has been reported once in the literature.

Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease, are devastating diseases in the elderly world, which are closely associated with progressive neuronal loss induced by a variety of genetic and environmental factors. Unfortunately, currently available treatments for neurodegenerative disorders can only relieve the symptoms, but not modify the pathological processes. Over the past decades, our group by collaborating with Yuan-Ping Pang and Paul R. Carlier, has developed three series of homo/hetero dimeric acetylcholinesterase (AChE) inhibitors derived from tacrine and/or huperzine A. The representative dimers bis(3)-Cognitin (B3C), bis(12)-hupyridone (B12H), and tacrine(10)-hupyridone (A10E) might possess disease-modifying effects through the modulation of N-methyl-D-aspartic acid (NMDA) receptors, the activation of myocyte enhancer factor 2D (MEF2D) gene transcription, and the promotion of neurotrophic factor secretion. In this review, we summarize that the representative dimers, such as B3C, provide neuroprotection against a variety of neurotoxins via multiple targets, including the inhibitions of NMDA receptor with pathological-activated potential, neuronal nitric oxide synthase (nNOS), and β-amyloid cascades synergistically. More importantly, B3C might offer disease-modifying potentials by activating MEF2D transcription, inducing neuritogenesis, and promoting the expressions of neurotrophic factors in vitro and in vivo. Taken together, the novel dimers might provide synergistic disease-modifying effects, proving that dimerization might serve as one of the strategies to develop new generation of therapeutics for neurodegenerative disorders.

Cerebellar liponeurocytoma is a rare tumor of the central nervous system occurring mainly in the posterior fossa, which shows neuronal and variable astrocytic differentiation, along with foci of lipomatous differentiation.

Although the inactivated SARS-CoV-2 vaccine (CoronaVac) has undergone preclinical tests and clinical trials evaluating its efficacy and safety before being approved for authorization, few data have been reported in the post-licensure real-world setting. We aimed to assess the safety of the vaccine among healthcare workers.

Hashimoto's encephalopathy, also known as steroid responsive encephalopathy, is associated with thyroid antibodies (SREAT) and is a rare but serious form of encephalopathy. In this paper, we describe the signs, symptoms, outcome, and treatments as noted in the case reports reviewed.

Glenohumeral joint arthrodesis has become a rare entity due to the introduction of shoulder arthroplasty. It is an excellent salvage procedure for patients with severe shoulder dysfunction, with limited treatment options, indicated for brachial plexus injury, tumour resection, chronic infection, failed prosthetic arthroplasty, or pseudoparalysis of the shoulder due to combined rotator cuff and deltoid deficiency. Shoulder arthrodesis relieves the patient of pain and gives a decent amount of function. The aim of this study was to examine the mid-term outcomes of glenohumeral arthrodesis with 2 pelvic recon plates.

Parental cognitive-affective and behavioural responses impact on the chronification of the child's pain. Whether mothers and fathers differ in their responses and whether top-down variables (parental somatization, anxiety symptoms) and bottom-up variables (child's pain-related disability, anxiety symptoms) impact on parental responses remains unresolved.

On 21 January 2021, the European Commission amended the marketing authorisation granted for pembrolizumab to include the first-line treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) in adults. The recommended dose of pembrolizumab was either 200 mg every 3 weeks or 400 mg every 6 weeks by intravenous infusion. Pembrolizumab was evaluated in a phase III, open-label, multicentre, randomised trial versus standard of care (SOC: FOLFOX6/FOLFIRI alone or in combination with bevacizumab/cetuximab) as first-line treatment of locally confirmed mismatch repair-deficient or microsatellite instability-high stage IV CRC. Subjects randomised to the SOC arm had the option to crossover and receive pembrolizumab once disease progressed. Both progression-free survival (PFS) and overall survival were primary endpoints. Pembrolizumab showed a statistically significant improvement in PFS compared with SOC, with a hazard ratio of 0.60 [95% confidence interval (CI): 0.45-0.80], P = 0.0002. Median PFS was 16.5 (95% CI: 5.4-32.4) versus 8.2 (95% CI: 6.1-10.2) months for the pembrolizumab versus SOC arms, respectively. The most frequent adverse events in patients receiving pembrolizumab were diarrhoea, fatigue, pruritus, nausea, increased aspartate aminotransferase, rash, arthralgia, and hypothyroidism. Having reviewed the data submitted, the European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) considered that the benefit-risk balance was positive. This is the first time the CHMP has issued an opinion for a target population defined by DNA repair deficiency biomarkers. The aim of this manuscript is to summarise the scientific review of the application leading to regulatory approval in the European Union.