Tile Type C Pelvic Fractures: Initial Management, Surgery and Rehabilitation Results of 12 Cases with Literature Review

We report the results of 12 patients followed for Tile type C pelvic fractures treated with percutaneous sacroiliac screwing combined to anterior ring reduction and fixation provided by plate or external fixator during the last 4 years. this study was carried out in the light of literature review to focus on the therapeutic principles of the initial management, the different surgical techniques described for the definitive treatment of bone lesions, the current attitude regarding the rehabilitation of patients and the perspectives under development.

Autophagy in Cancer Therapy—Molecular Mechanisms and Current Clinical Advances

Autophagy is a crucial general survival tactic of mammalian cells. It describes the capability of cells to disassemble and partially recycle cellular components (e.g., mitochondria) in case they are damaged and pose a risk to cell survival or simply if their resources are urgently needed elsewhere at the time. Autophagy-associated pathomechanisms have been increasingly recognized as important disease mechanisms in non-malignant (neurodegeneration, diffuse parenchymal lung disease) and malignant conditions alike. However, the overall consequences of autophagy for the organism depend particularly on the greater context in which autophagy occurs, such as the cell type or whether the cell is proliferating. In cancer, autophagy sustains cancer cell survival under challenging, i.e., resource-depleted, conditions. However, this leads to situations in which cancer cells are completely dependent on autophagy. Accordingly, autophagy represents a promising yet complex target in cancer treatment with therapeutically induced increase and decrease of autophagic flux as important therapeutic principles.

Dissociative Visual Loss in Children and Adolescents

Psychogenic vision disorders in children and adolescents are a common disorder primarily encountered by ophthalmologists at the onset because, as with other disorders of dissociation, the presentation suggests a neurologic or other somatic condition. Loss of visual acuity, blurred vision and visual field restriction–often described as tunnel vision–appears to be typical. The onset may be sudden, frequently related to a wide range of stressful life events (school failure, family conflicts, accidents). While the majority of these children quickly recover from their symptoms, a substantial percentage experience persistent symptoms or a fluctuating course. Due to the lack of efficacy studies of specific treatment protocols, diagnostic work-up and treatment suffer from a high degree of uncertainty. Differentiating dissociative visual loss from physical illness requires special expertise. The uncertainty of ophthalmologists and the other specialists involved in dealing with this clinical condition often delays the specialised treatment and may also trigger inadequate therapy with the iatrogenic risk of harming the patient. This article primarily describes the disorder-specific psychiatric diagnostic as well as the somatic differential diagnostic work-up and outlines the therapeutic principles of dissociative visual loss.

Therapeutic principles in upper limb trauma

Upper limb trauma cases vary from simple to high energy impactful injuries, with different etiologies; situations which frequently require unique, demanding and challenging endeavors in order to obtain the most favorable outcome. Experience, good decision-making and knowledge of functional goals are mandatory in order to elaborate a therapeutic plan and execute it accordingly. Although cases differ in nature and prognosis, respecting a set of therapeutic principles whilst dealing with either simple or complex cases, will enhance patient outcome and give the surgeon the confidence to tackle any kind of upper limb trauma. After clearing out vital threat, the emergency surgery represents the first threshold in achieving and restoring normal function and biomechanics, mostly in young and labor active patients, with the mindset to salvage as much tissue as possible, with a thorough debridement and step-by-step approach to different types of tissues. Secondary surgery and reconstructive surgery can be planned timely, with prior discussion with both the therapist and the patient in order to enhance patient’s upper limb function and aesthetic and ensure social reintegration.

Efficacy of rituximab in thymoma associated minimal change disease: case report

Background Thymomas have been associated with a broad spectrum of autoimmune diseases. Minimal change disease (MCD) is the most frequent pathological lesion reported. Pathophysiological mechanisms involved in secondary MCD, and linking MCD to thymoma are not yet fully explained, although the hypothesis of T cell dysfunction has been suggested. The fundamental therapeutic principles are steroids and surgical treatment of thymoma, but failures and relapses often require immunosuppressant combinations. Case presentation A 62-year-old female was admitted in our unit for a nephrotic syndrome associated with a thymoma. The diagnosis of thymoma associated MCD was confirmed by kidney biopsy. After surgical resection of the thymoma and steroid therapy, no remission was observed. Immunosuppressive therapy was then intensified with introduction of rituximab. Here, we report a steroid-resistant nephrotic syndrome secondary to MCD associated thymoma, which achieved complete remission after rituximab therapy. To the best of our knowledge, this is the first report of the use and efficacy of rituximab therapy in this pathology. Conclusions Our case report suggests that primary and secondary MCD may share similar pathophysiological mechanisms. It does not allow us to draw any conclusions about the mechanism of action of rituximab, but we believe this report argues for the safety and efficacy of rituximab use in thymoma-associated MCD, and therefore constitutes a rationale for future studies.

Tranquility: An evaluation and co-design of an internet-based cognitive-behavioural therapy (iCBT) program for anxiety and depression (Preprint)

BACKGROUND Internet-based cognitive-behavioural therapy (iCBT) is a necessary step towards increasing the accessibility of mental health services. Yet, few iCBT programs have been evaluated for their fidelity to therapeutic principles of CBT or usability standards. Additionally, many existing iCBT programs do not include treatments targeting both anxiety and depression – commonly co-occurring conditions. OBJECTIVE Evaluate the usability and fidelity of Tranquility, a novel iCBT program for anxiety, to CBT principles, and engage in a co-design process to adapt Tranquility to include treatment elements for depression. METHODS CBT experts (n = 6) and mental health informed peers (n = 6) reviewed the iCBT program Tranquility. CBT experts assessed Tranquility’s fidelity to CBT principles and were asked to identify necessary interventions for depression using two simulated client case examples. Mental health informed peers engaged in two co-design focus groups to discuss adaptations to the existing anxiety program and the integration of interventions for depression. Both groups completed online surveys assessing Tranquility’s usability and the likelihood that they would recommend the program. RESULTS CBT experts’ mean rating of Tranquility’s fidelity to CBT was 91%, indicating a high fidelity to CBT. Five out of six CBT experts and all mental health informed peers (88% of participants) rated Tranquility as satisfactory, indicating that they may recommend Tranquility to others, and they rated its usability highly (M = 76.56, SD = 14.07). Mental health informed peers provided suggestions about how to leverage engagement with Tranquility (e.g., add incentives, notification control). CONCLUSIONS This preliminary study demonstrated Tranquility’s strong fidelity to CBT and usability standards. Results highlight the importance of involving stakeholders in the co-design process and future opportunities to increase engagement.

The Pathophysiology and Treatment of Graft-Versus-Host Disease: Lessons Learnt From Animal Models

Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for hematologic malignancies, bone marrow failure syndromes, and inherited immunodeficiencies and metabolic diseases. Graft-versus-host disease (GVHD) is the major life-threatening complication after allogeneic HCT. New insights into the pathophysiology of GVHD garnered from our understanding of the immunological pathways within animal models have been pivotal in driving new therapeutic paradigms in the clinic. Successful clinical translations include histocompatibility matching, GVHD prophylaxis using cyclosporine and methotrexate, posttransplant cyclophosphamide, and the use of broad kinase inhibitors that inhibit cytokine signaling (e.g. ruxolitinib). New approaches focus on naïve T cell depletion, targeted cytokine modulation and the inhibition of co-stimulation. This review highlights the use of animal transplantation models to guide new therapeutic principles.

Mouse Models of Germinal Center Derived B-Cell Lymphomas

Over the last decades, the revolution in DNA sequencing has changed the way we understand the genetics and biology of B-cell lymphomas by uncovering a large number of recurrently mutated genes, whose aberrant function is likely to play an important role in the initiation and/or maintenance of these cancers. Dissecting how the involved genes contribute to the physiology and pathology of germinal center (GC) B cells –the origin of most B-cell lymphomas– will be key to advance our ability to diagnose and treat these patients. Genetically engineered mouse models (GEMM) that faithfully recapitulate lymphoma-associated genetic alterations offer a valuable platform to investigate the pathogenic roles of candidate oncogenes and tumor suppressors in vivo, and to pre-clinically develop new therapeutic principles in the context of an intact tumor immune microenvironment. In this review, we provide a summary of state-of-the art GEMMs obtained by accurately modelling the most common genetic alterations found in human GC B cell malignancies, with a focus on Burkitt lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma, and we discuss how lessons learned from these models can help guide the design of novel therapeutic approaches for this disease.

Takotsubo Cardiomyopathy: Current Treatment

Management of takotsubo syndrome (TTS) is currently empirical and supportive, via extrapolation of therapeutic principles worked out for other cardiovascular pathologies. Although it has been emphasized that such non-specific therapies for TTS are consequent to its still elusive pathophysiology, one wonders whether it does not necessarily follow that the absence of knowledge of TTS’ pathophysiological underpinnings should prevent us for searching, designing, or even finding, therapies efficacious for its management. Additionally, it is conceivable that therapy for TTS may be in response to pathophysiological/pathoanatomic/pathohistological consequences (e.g., “myocardial stunning/reperfusion injury”), common to both TTS and coronary artery disease, or other cardiovascular disorders). The present review outlines the whole range of management principles of TTS during its acute phase and at follow-up, including considerations pertaining to the recurrence of TTS, and commences with the idea that occasionally management of TTS should consist of mere observation along the “first do no harm” principle, while self-healing is under way. Finally, some new therapeutic hypotheses (i.e., large doses of insulin infusions in association with the employment of intravenous short- and ultrashort-acting β-blockers) are being entertained, based on previous extensive animal work and limited application in patients with neurogenic cardiomyopathy and TTS.

Fixed-Dose Combination of NSAIDs and Spasmolytic Agents in the Treatment of Different Types of Pain—A Practical Review

This review presents the most common disease entities in which combinations of NSAIDs and spasmolytic drugs are used to reduce pain. The benefits of fixed-dose combination products (FDCs) are that they improve the response in people with insufficient monotherapy. Using the synergy or additive effect of drugs, it is possible to obtain a significant therapeutic effect and faster action with the use of smaller doses of individual drugs. In addition, one active ingredient may counteract adverse reactions from the other. Another essential aspect of the use of FDCs is the improvement of medical adherence due to the reduction in the pill burden on patients. It is also possible to develop a fixed-dosed combination product de novo to address a new therapeutic claim and be protected by patents so that the manufacturer can obtain exclusive rights to sell a particular FDC or a formulation thereof. The proposed fixed-dose combinations should always be based on valid therapeutic principles and consider the combined safety profile of all active substances included in the medicinal product. This review aims to identify which combinations of NSAIDs and spasmolytics have been developed and tested and which combinations are still under development.