PURPOSE OF REVIEW: To discuss recent changes in the multiple sclerosis (MS) treatment algorithm and to present therapies currently in MS clinical trials. RECENT FINDINGS: High efficacy disease modifying therapies are optimally beneficial when used in the early, inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of MS. Multiple therapies targeting remyelination failed to provide conclusive evidence of broad therapeutic benefit; however, more targeted approaches offer hope that myelin repair might be achieved resulting in specific clinical improvements. Strategies targeting chronic Epstein-Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions. SUMMARY: A striking number of diverse treatments under investigation bodes well for development of better and more effective therapies in MS.
- MeSH
- Algorithms MeSH
- Epstein-Barr Virus Infections * MeSH
- Humans MeSH
- Remyelination * MeSH
- Multiple Sclerosis * drug therapy MeSH
- Herpesvirus 4, Human MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Pulmonary fibrosis is one of the most severe long-term consequences of COVID-19. Corticosteroid treatment increases the chances of recovery; unfortunately, it can also have side effects. Therefore, we aimed to develop prediction models for a personalized selection of patients benefiting from corticotherapy. The experiment utilized various algorithms, including Logistic Regression, k-NN, Decision Tree, XGBoost, Random Forest, SVM, MLP, AdaBoost, and LGBM. In addition easily human-interpretable model is presented. All algorithms were trained on a dataset consisting of a total of 281 patients. Every patient conducted an examination at the start and three months after the post-COVID treatment. The examination comprised a physical examination, blood tests, functional lung tests, and an assessment of health state based on X-ray and HRCT. The Decision tree algorithm achieved balanced accuracy (BA) of 73.52%, ROC-AUC of 74.69%, and 71.70% F1 score. Other algorithms achieving high accuracy included Random Forest (BA 70.00%, ROC-AUC 70.62%, 67.92% F1 score) and AdaBoost (BA 70.37%, ROC-AUC 63.58%, 70.18% F1 score). The experiments prove that information obtained during the initiation of the post-COVID-19 treatment can be used to predict whether the patient will benefit from corticotherapy. The presented predictive models can be used by clinicians to make personalized treatment decisions.
BACKGROUND: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application. OBJECTIVE: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs). METHODS: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios. sNfL levels were defined as "high" (>90th percentile) vs "normal" (<80th percentile), based on normative values of control persons. In three rounds, 10 international and 18 Swiss MS experts, and 3 patient consultants rated their agreement on treatment algorithms. Consensus thresholds were defined as moderate (50%-79%), broad (80%-94%), strong (≥95%), and full (100%). RESULTS: The Delphi provided 9 escalation algorithms (e.g. initiating treatment based on high sNfL), 11 horizontal switch (e.g. switching natalizumab to another high-efficacy DMT based on high sNfL), and 3 de-escalation (e.g. stopping DMT or extending intervals in B-cell depleting therapies). CONCLUSION: The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice.
- Keywords
- Delphi study, de-escalation, escalation, personalized treatment strategies, serum neurofilament light chain,
- MeSH
- Algorithms * MeSH
- Delphi Technique MeSH
- Adult MeSH
- Immunologic Factors * therapeutic use MeSH
- Precision Medicine * methods MeSH
- Clinical Decision-Making * methods MeSH
- Consensus MeSH
- Middle Aged MeSH
- Humans MeSH
- Neurofilament Proteins * blood MeSH
- Multiple Sclerosis * blood drug therapy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Immunologic Factors * MeSH
- neurofilament protein L MeSH Browser
- Neurofilament Proteins * MeSH
Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.
- Keywords
- Botulinum toxin, Consensus guidelines, Dose limits, Dose variability, Dosing tables, Dystonia, Spasticity, Target muscles, Therapy, Total dose, Treatment algorithms, Typical dose,
- MeSH
- Algorithms MeSH
- Botulinum Toxins, Type A * MeSH
- Botulinum Toxins * MeSH
- Dystonic Disorders * drug therapy MeSH
- Dystonia * drug therapy MeSH
- Humans MeSH
- Muscle Spasticity drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Botulinum Toxins, Type A * MeSH
- Botulinum Toxins * MeSH
BACKGROUND: The optimal energy protocol for direct current cardioversion of atrial fibrillation remains uncertain. The Rational vs Maximum Fixed Energy (PROTOCOLENERGY) randomized trial compared a stepwise escalating energy algorithm (RaA, 150 J, 360 J, and 360 J) with a maximum fixed energy algorithm (MfA, 3 x 360 J). METHODS: In a 1:1 randomized trial, 300 patients with atrial fibrillation received biphasic discharges via hand-held paddles in the anterolateral position. Primary endpoints were sinus rhythm at 1 minute and neurologic complications at 2 hours; secondary endpoints included sinus rhythm at 2 hours, skin changes and chest discomfort at 24 hours. RESULTS: Sinus rhythm at 1 minute was achieved in 92.7% of RaA and 94.0% of MfA patients (P = 0.643) and maintained at 2 hours in 91.3% of both groups. There were no neurologic complications. The protocols differed significantly after the first shock (72.7% in RaA vs 83.3% in MfA; P = 0.026) but equalized after subsequent maximum energy shocks. Fewer RaA patients experienced skin redness compared with MfA patients (19.3% vs 36.0%, P = 0.001), which was attributed to the lower initial 150-J shock and total energy delivered (r = 0.243, P < 0.0001). Chest discomfort at 24 hours was not different between groups (P = 0.378). In multivariate analysis, lower body mass index (P < 0.001, cutoff 29 to 34 kg/m2) was associated with cardioversion success after the initial 150-J shock. CONCLUSIONS: Both protocols showed similar high cumulative efficacy, but RaA with the initial 150-J shock proved to be beneficial in patients with body mass index less than 29 to 34 kg/m2 because of fewer skin complications. CLINICAL TRIAL REGISTRATION NO: NCT05148923.
- MeSH
- Algorithms * MeSH
- Electric Countershock * methods MeSH
- Atrial Fibrillation * therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
OBJECTIVE: To develop a follow-up algorithm for urinary stone patients after definitive treatment. MATERIALS AND METHODS: The panel performed a systematic review on follow-up of urinary stone patients after treatment (PROSPERO: CRD42020205739). Given the lack of comparative studies we critically evaluated the literature and reached a consensus on the follow-up scheme. RESULTS: A total of 76 studies were included in the analysis, including 17 RCTs. In the stone-free general population group, 71-100% of patients are stone-free at 12 months while 29-94% remain stone-free at 36 months. We propose counselling these patients on imaging versus discharge after the first year. The stone-free rate in high-risk patients not receiving targeted medical therapy is < 40% at 36 months, a fact that supports imaging, metabolic, and treatment monitoring follow-up once a year. Patients with residual fragments ≤ 4 mm have a spontaneous expulsion rate of 18-47% and a growth rate of 10-41% at 12 months, supporting annual imaging follow-up. Patients with residual fragments > 4 mm should be considered for surgical re-intervention based on the low spontaneous expulsion rate (13% at 1 year) and high risk of recurrence. Plain film KUB and/or kidney ultrasonography based on clinicians' preference and stone characteristics is the preferred imaging follow-up. Computed tomography should be considered if patient is symptomatic or intervention is planned. CONCLUSIONS: Based on evidence from the systematic review we propose, for the first time, a follow-up algorithm for patients after surgical stone treatment balancing the risks of stone recurrence against the burden of radiation from imaging studies.
- Keywords
- Algorithm, Follow-up, Imaging, Metabolic, Urinary stone treatment,
- MeSH
- Algorithms * MeSH
- Humans MeSH
- Aftercare methods MeSH
- Follow-Up Studies MeSH
- Urolithiasis * therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
PURPOSE OF THE STUDY The aim of the present study was to evaluate the postoperative outcome of patients with pilon tibial fractures with a minimum follow-up of 24 months, treated according to a staged treatment algorithm. MATERIAL AND METHODS In total, 27 patients (mean age 43.6 ± 13 years, range 18-69) with a pilon tibial fracture and a minimum follow-up of 24 months were included in the study. Medical recordings (discharge documents and surgical reports) and radiographic examinations were analyzed. All enrolled patients were invited for a clinical and radiological follow-up examination (ROM, AOFAS hindfoot score, Kellgren score). The mean follow-up time was 44.5 ± 16 months (range 24-82). RESULTS In 21 cases a two-stage operative strategy with initial closed reduction and external fixation was necessary prior to definitive osteosynthesis. Overall, the patients scored 82.1 ± 20 points (range 30-100) in AOFAS hindfoot score, which represents a good clinical outcome. Patients with B-type fractures scored significantly better than those with C-type fractures. Patients with closed pilon tibial fractures reached significantly higher values in the AOFAS hindfoot score than those with open ones. Age and gender did not affect the functional outcome. Total ankle range of motion was 41° ± 10° for B-type fractures (range 20°-55°) and 35° ± 17° (range 0°-60°) for C-type fractures respectively (p > 0.05). Only five patients reached higher scores (Grade III) in Kellgren classification system. DISCUSSION Within the last decades, the therapeutic algorithm of pilon fractures underwent a paradigm shift; a two-stage protocol has prevailed today. However, the initial severity of the fracture in terms of initial absorbed energy, bony comminution and softtissue trauma still affects the outcome. Moreover, the necessity for bone grafting, as an indirect measurement of bone comminution and bone defects, resulted in higher degrees of osteoarthritis in the final follow-up. Higher initial soft-tissue injury also had an impact on the functional outcome of the patients, as patients with closed fractures scored better in AOFAS at the final follow-up. In order to counteract these risk factors and to reduce complications that define the outcome of these severe injuries, clearly defined surgical principles and standardized treatment protocols are needed. CONCLUSIONS The present study confirms the fact that meticulous planning, respect of the soft-tissues and choice of the optimal timepoint for the definitive osteosynthesis and overall treatment according to standardized protocols can optimize the outcome of this severe injury. Key words:pilon, distal tibia fracture, outcome, algorithm.
- MeSH
- Algorithms * MeSH
- Adult MeSH
- Tibial Fractures * surgery MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Radiography MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Fracture Fixation, Internal MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
Objective.In the present hadrontherapy scenario, there is a growing interest in exploring the capabilities of different ion species other than protons and carbons. The possibility of using different ions paves the way for new radiotherapy approaches, such as the multi-ions treatment, where radiation could vary according to target volume, shape, depth and histologic characteristics of the tumor. For these reasons, in this paper, the study and understanding of biological-relevant quantities was extended for the case of4He ion.Approach.Geant4 Monte Carlo based algorithms for dose- and track-averaged LET (Linear Energy Transfer) calculations, were validated for4He ions and for the case of a mixed field characterised by the presence of secondary ions from both target and projectile fragmentation. The simulated dose and track averaged LETs were compared with the corresponding dose and frequency mean values of the lineal energy,yD¯andy¯F, derived from experimental microdosimetric spectra. Two microdosimetric experimental campaigns were carried out at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud of Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) using two different microdosimeters: the MicroPlus probe and the nano-TEPC (Tissue Equivalent Proportional Counter).Main results.A good agreement ofL¯dTotalandL¯tTotalwithy¯Dandy¯Texperimentally measured with both microdosimetric detectors MicroPlus and nano-TEPC in two configurations: full energy and modulated4He ion beam, was found.Significance.The results of this study certify the use of a very effective tool for the precise calculation of LET, given by a Monte Carlo approach which has the advantage of allowing detailed simulation and tracking of nuclear interactions, even in complex clinical scenarios.
- Keywords
- Geant4, Monte Carlo, linear energy transfer, microdosimetry, target fragmentation,
- MeSH
- Algorithms MeSH
- Ions MeSH
- Linear Energy Transfer * MeSH
- Monte Carlo Method MeSH
- Protons MeSH
- Radiometry * methods MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ions MeSH
- Protons MeSH
This review article summarizes the most recently available data covering the modern trends and methods in the diagnosis and treatment of mesenteric artery disease. Its aim is to point out the critical moments in the whole spectrum of matters such as early diagnosis and treatment of the chronic form of bowel ischemia, role of MDCT in prompt diagnosis, and urgent therapeutic modalities of treating its acute forms. To achieve the best possible results, we must minimize the time of diagnosis while the treatment has to be tailored individually to each patient according to occlusion type, age and co-morbidities (Fig. 2, Ref. 66).
- MeSH
- Algorithms MeSH
- Mesenteric Arteries MeSH
- Ischemia diagnosis surgery therapy MeSH
- Humans MeSH
- Mesenteric Vascular Occlusion diagnosis surgery therapy MeSH
- Vascular Surgical Procedures MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Treatment algorithms of proximal humerus fractures are still controversially discussed. The enthusiasm towards operative treatment after the introduction of locking implants, has not been justified by the functional results in the elderly population. The majority of those fractures in the geriatric patients can be successfully treated conservatively. Thorough clinical and radiological examination for fracture analysis, dynamic stability control with the use of an image intensifier, and meticulous reduction, in addition with the appropriate orthesis for its retention and rehabilitation, are the keys for the successful treatment of the proximal humerus fracture in the elderly patient. The present review reports on the main treatment aspects of proximal humerus fractures in the geriatric population and proposes a treatment algorithm.
- MeSH
- Algorithms MeSH
- Fracture Fixation methods MeSH
- Shoulder Fractures diagnostic imaging surgery MeSH
- Humans MeSH
- Orthotic Devices MeSH
- Aged MeSH
- Radiographic Image Enhancement methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
