Promises and challenges of adoptive T-cell therapies for solid tumours

Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas—cancer genomics, cancer immunology and cell-therapy manufacturing—that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.Subject terms: Immunotherapy, Cancer genomics, Cancer immunotherapy, Tumour immunology     

A biomechanical assessment of the relation between the oral implant stability at insertion and subjective bone quality assessment

AIM: The study was set to evaluate the validity of subjective jaw bone quality assessment. MATERIALS AND METHODS: A total of 298 patients (198 females, mean age 56.4) were treated with oral implants at the Periodontology Department at the University Hospital of KUL. A total of 761 TiUnite implants have been installed. Subjective bone quality assessment was performed on radiographs and by the surgeon's tactile sensation and was compared with torque measurements. In a subset of patients, implant stability was also assessed by implant stability quotient and/or periotest values. RESULTS: Subjective assessment of bone quality was related to the PTV, ISQ and placement torque [in the crestal, the second and the apical third (N cm)], respectively; in grade 1: -5.3, 73.3 (4.2, 9.6, 15.2), and grade 3 or 4: -1.6, 55 (3.3, 5.5, 8.4). For the surgeon's tactile sensation, a good correlation was noted for the presence of a thick cortex: -4.6, 70.3 (4.2, 9.7, 15.1), or a thin one: -0.3, 65.9 (3.6, 6.9, 10.1). For dense trabecular bone, the values were -2.8, 69.4 (4.4, 9.7,14.8), while for poor trabecular bone, the values were-1.7, 66.4 (3.6, 6.4, 9.8). CONCLUSIONS: Subjective assessment of bone quality is related to PTV, ISQ and placement torque measurements at implant insertion.     

A Novel Switching Delayed PSO Algorithm for Estimating Unknown Parameters of Lateral Flow Immunoassay

In this paper, the parameter identification problem of the lateral flow immunoassay (LFIA) devices is investigated via a new switching delayed particle swarm optimization (SDPSO) algorithm. By evaluating an evolutionary factor in each generation, the velocity of the particle can adaptively adjust the model according to a Markov chain in the proposed SDPSO method. During the iteration process, the SDPSO can adaptively select the inertia weight, acceleration coefficients, locally best particle pbest and globally best particle gbest in the swarm. It is worth highlighting that the pbest and the gbest can be randomly selected from the corresponding values in the previous iteration. That is, the delayed information of the pbest and the gbest can be exploited to update the particle’s velocity in current iteration according to the evolutionary states. The strategy can not only improve the global search but also enhance the possibility of eventually reaching the gbest. The superiority of the proposed SDPSO is evaluated on a series of unimodal and multimodal benchmark functions. Results demonstrate that the novel SDPSO algorithm outperforms some well-known PSO algorithms in aspects of global search and efficiency of convergence. Finally, the novel SDPSO is successfully exploited to estimate the unknown time-delay parameters of a class of nonlinear state-space LFIA model.     

Erratum to: Prevalence of sleep disturbance in patients with low back pain

European Spine Journal -     

Potentially misleading extratemporal lobe lesions in patients with temporal lobe epilepsy

From a series of 217 consecutive temporal resections for intractable epilepsy between 1993 and 2000, we identified all patients with large non-neoplastic extratemporal lesions. Only patients with known postsurgical outcomes with follow up for more than two years were included. Fifteen patients were identified. All patients had a history of medically refractory epilepsy with clinical and ictal evidence of mesial temporal seizure onset. Eleven patients had extratemporal lesions ipsilateral to the seizure focus, whereas four patients had the lesions contralateral to the seizure focus. Nine of the 15 patients had evidence of hippocampal atrophy on magnetic resonance imaging (MRI). Following temporal resection, nine of these patients (60%) became seizure free (Engel class 1A), two patients were free of disabling seizures only (Engel class 1B), and two patients had a few early seizures but then became seizure free for at least two years (Engel class 1C). Two patients had significant improvement (Engel class 2). Thus, the finding of large extratemporal lesions on MRI was potentially misleading. When clinical semiology and ictal EEG recordings provide evidence of temporal onset seizures, anterior temporal resection should be considered in patients with extratemporal lesions.     

Case report of Laurence-Moon-Bardet-Biedl syndrome

We report a case of Laurence-Moon-Bardet-Biedl Syndrome with all five recognised features: tapetoretinal dystrophy, polydactily, obesity, mental retardation and hypogonadism. Nevertheless the correct diagnosis was delayed due to the fact, that the patient has a macular dystrophy (instead of a pigmentary retinopathy). He had an operation of the polydactily during childhood. This was not revealed at first. The case underlines the importance of an exact anamnesis of the parents.     

An integrated neuropsychiatric approach to diagnosis and management of patients with epileptic seizures

Opinion statement In patients who present to neurology settings with history of epileptic seizures, psychiatric disorders may be the sole manifestation of apparent neurologic symptoms, or they may coexist. Current challenges for clinicians include distinguishing between two disorders and making the correct diagnoses, interpreting test results, and (co-) managing the disorder(s). Our goal is to provide the clinician with an integrated neuropsychiatric approach for the triage, assessment (history, screening tools, examination, diagnostic tests), and treatment (neurologic and/or psychiatric) of these challenging patients. In particular, use of schemata, tables, and algorithms will offer step-by-step approaches and guidelines for the clinician. Recommendations are made for the indications for psychiatric consultation, and co-management is recommended for patients with emergencies, those who fail routine psychiatric treatments, and those with complex presentations or multiple comorbid conditions.     

Predisposing conditions for retrograde peri-implantitis, and treatment suggestions

Background: Recent case reports introduced the term retrograde peri‐implantitis as a lesion (radiolucency) around the most apical part of an osseointegrated implant. It develops within the first months after insertion. This retrospective study aimed to find predisposing conditions for such peri‐apical lesions and to evaluate treatment strategies. Methods: All single implants (426 in the upper, 113 in the lower jaw, all Brånemark system^® type) placed at the department of Periodontology of the University Hospital (Catholic University Leuven) were included in this retrospective evaluation to check the incidence of retrograde peri‐implantitis. Eventual predisposing factors such as patient characteristics (age, medical history), recipient site (local bone quality and quantity, cause of tooth loss), periodontal and endodontic conditions of neighboring teeth, implant characteristics (length, surface characteristics), and surgical aspects (guided bone regeneration, osseous fenestration, or dehiscency) were considered. Moreover, implants with retrograde peri‐implantitis were followed longitudinally to verify their treatment outcome by means of different parameters (Periotest^® values (PTV), marginal bone level, radiological size of peri‐apical defect). Results: Seven implants in the upper (1.6%) and 3 in the lower jaw (2.7%) showed retrograde peri‐implantitis, before or at abutment connection. In comparison with successful implants, such peri‐apical lesions occurred preferably at sites with a history of an obvious endodontic pathology of the extracted tooth to be replaced. The incidence of retrograde peri‐implantitis was significantly higher (P<0.0001) for TiUnite^® implants when compared with the machined implants (8/80 vs. 2/459). The machined implant surface, however, showed a higher failure rate (6.8%) than the TiUnite^® implants (2.5%). Failures with machined surfaces preferably occurred at extraction sites of teeth with a history of endodontic pathology or sites adjacent to teeth with an obvious endodontic pathology. No other predisposing factors could be identified. A curettage of the peri‐apical lesions and the use of a bone substitute material prevented further progression of such lesions in the upper jaw (implants maintained their marginal bone and low PTV scores). A treatment in the lower jaw was less successful. Conclusions: Within the limitations of a retrospective study, these results seem to indicate that retrograde peri‐implantitis is provoked by remaining scar or granulomatous tissue at the recipient site: endodontic pathology of extracted tooth (scar tissue‐impacted tooth) or possible endodontic pathology from a neighboring tooth.     

Soft tissue augmentation of the cheeks detected on intra- and extraoral radiographs: a case report

Augmentation material used in plastic surgery such as facelift procedures can be radiopaque and thus become visible on extra- and intraoral radiographs. These objects may obscure anatomical structures and mask critical findings, therefore leading to potential misinterpretation of otherwise successful images. The present report describes a case in which the radiographic intra- and extraoral data are partly masked by a superimposed radiopaque mesh, which was suspected to originate from a facelift procedure. A gold thread lift was confirmed by the plastic surgeon.