Lifetime Of Patient Research Articles

Cost-Utility Analysis of Multigene Assays to Guide Treatment Decisions for Node-Negative Early Breast Cancer.

Clinicopathologic and patient factors, such as tumor grade, size, age, and menopausal status, provide limited prognostic and predictive information in hormone receptor positive (HR +), human epidermal growth receptor 2 negative (HER2-), node-negative early-stage breast cancer, leading to potential over- or under-treatment. Multigene expression profile tests used in clinical practice in the USA, including the 21-gene assay, 70-gene assay, 12-gene assay, and 50-gene assay, offer prognostic information beyond traditional clinicopathologic features to improve treatment decisions. This study aimed to estimate the cost-effectiveness of these four multigene assays compared with clinicopathologic risk assessment alone. A decision tree categorized hypothetical patients with HR + /HER2- early-stage invasive breast cancer according to clinical and genomic risk, and integrated clinical expert insights for chemotherapy allocation with literature inputs. A Markov model simulated lifetime costs and outcomes of chemotherapy decisions over a patient's lifetime. The probability of distant breast cancer recurrence was derived from TAILORx (21-gene assay), MINDACT (70-gene assay), and TransATAC (12-gene assay, 50-gene assay) studies. Costs were calculated from a US societal perspective in 2021 US dollars, considering healthcare costs, lost productivity, and patient out-of-pocket expenses. The 21-gene assay and 50-gene assay were less costly ( -$12,189 and -$2410, respectively) and more effective [0.23 and 0.07 quality-adjusted life years (QALYs), respectively] compared with clinicopathologic risk alone. Similarly, the 70-gene assay and 12-gene assay are also cost-effective alternatives [incremental cost-effectiveness ratio (ICER): 27,760 and 7942, respectively]. All four multigene assays were cost-effective from a societal perspective, offering low net lifetime costs or savings with improved outcomes compared with clinicopathologic risk assessment alone. These assays can help refine treatment decisions by providing prognostic risk estimates. In the case of the 21-gene assay, it can also predict chemotherapy benefit leading to the highest lifetime cost savings and greatest QALY gain.

Surgical Management of Early Metacarpophalangeal Joint Silicone Implant Fracture in Patient With Rheumatoid Arthritis

Introduction: Metacarpophalangeal (MCP) joint arthroplasty is a common treatment modality to correct ulnar drift, pain, and functional deficits in patients with rheumatoid arthritis, an autoimmune condition targeting the synovium of joints. While silicone MCP joint implants are susceptible to revision in the long term, there is a lack of literature discussing their early breakage. The present case illustrates silicone implant fracture only 10 weeks after MCP arthroplasty—the first instance in the literature to the authors’ knowledge. Materials and Methods: The patient is a 64-year-old female with stage 4 rheumatoid arthritis who underwent right index and middle finger MCP joint arthroplasties using 0-degree silicone implants, radial sagittal band imbrication on these digits, and right ring and small finger extensor tendon centralization at the MCP joint. Results: During the 10th postoperative week, the patient presented with atraumatic middle finger pain and ulnar deviation. Imaging revealed a right middle finger MCP implant fracture at the distal stem, which underwent successful revision using a 30-degree flexed implant and index and middle extensor tendon centralization. Discussion: Nineteen months after revision surgery, the patient continues to have no pain and an improved range of motion. Ultimately, we are hopeful that the flexed silicone implant will last the patient's lifetime.

Building Digital Twins for Cardiovascular Health: From Principles to Clinical Impact.

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual-physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.

Case Report: Delorme Technique for the Treatment of Giant Non-Reducible Rectal Prolapse at the Second Level of Care

Rectal prolapse is an invagination of the rectum that causes it to protrude through the anus. Irreducible rectal prolapse is an unusual condition; in most cases, the prolapse reduces spontaneously. Non-surgical treatment alternatives have been noted, such as the use of sugar, which reduces rectal prolapse. The results have not yet been compared against surgical treatment, so they cannot yet be considered the preferred option. Given the many techniques and procedures, it should be considered that the best procedure must be chosen not only to correct the prolapse but also to restore defecatory function and to improve fecal incontinence throughout the patient's lifetime. The Delorme procedure is a transanal technique that addresses complete rectal prolapse with a low surgical risk and minimal morbidity (less damage to pelvic and hypogastric nerves compared to abdominal procedures). It is associated with a significant improvement in anal continence, low recurrence rates, short hospital stays, and patient comfort.

Introduction and interpretation of The European Society of Endodontology S3-level clinical practice guideline for treatment of pulpal and apical disease

The European Society of Endodontology published the S3-level clinical practice guideline for the treatment of pulpal and apical disease in October 2023, which provides best current therapeutic strategies supported by scientific evidences. The guideline was divided into four parts: the diagnosis and treatment of pulpitis, diagnosis and nonsurgical treatment of apical periodontitis, surgical treatment of apical periodontitis, and regenerative treatment. This article aims to introduce and interpret the guideline, and to better manage patients with pulpitis and apical periodontitis for preserving teeth over a patient's lifetime in China.

Melanoma overdiagnosis: What do we know and what do we do?

Melanoma overdiagnosis occurs when melanomas, not destined to cause morbidity or death in a patient's lifetime, are identified and treated. This study considers the causes and magnitude of melanoma overdiagnosis in Australia. We also speculate about a possible benefit of overdiagnosis in Australia; namely, a reduction in excess deaths in the geographical areas where melanoma is diagnosed most frequently. Overdiagnosis can arguably be mitigated by factors that reduce the number of lesions treated for each melanoma identified. Data from the Australian Cancer Atlas show that there is a reduction in excess deaths from melanoma in geographical areas where diagnostic rates are higher (Pearson correlation coefficient r=-0.5978, 95% CI: -0.6243 to -0.5699, P<0.0001); this being the strongest inverse correlation observed among the 20 cancer types in the Atlas. Is early diagnosis of actual life-threatening melanomas in these geographical regions impacting survival? Further research is planned.

Long-standing preservation of levodopa response in progressive supranuclear palsy

The clinical and neuropathological characteristics of progressive supranuclear palsy (PSP) with preservation of levodopa (L-dopa) response are described in this report. We present the case of a 73-year-old Japanese man with a 13-year history of dopa-responsive Parkinsonism and abnormalities observed in metaiodobenzylguanidine (MIBG) myocardial scintigraphy, suggesting Parkinson's disease. However, autopsy results revealed PSP pathology, including tuft-shaped astrocytes and globose-type neurofibrillary tangles, without Lewy body pathology. The degeneration was moderately to severely distributed in the globus pallidus, subthalamic nucleus, and substantia nigra, whereas striatal degeneration was mild. These findings suggest an intact response to L-dopa therapy throughout the patient's lifetime. Pathological examination of cardiac sympathetic nerves revealed intact nerves, suggesting functional involvement in the MIBG abnormality. This study provides further evidence of the clinical and pathological heterogeneity of PSP. Homozygosity for both the rs564309-C allele at TRIM11 and the rs2242367-G allele at SLC2A13 might have played a protective role. This case indicates a protracted course-PSP, which may hold promise for future treatments.

The Broader Effects of Delayed Progression to End-Stage Kidney Disease: Delaying the Inevitable or a Meaningful Change?

A global rise in the prevalence of patients with chronic kidney disease (CKD) with end-stage kidney disease (ESKD) has led to a considerable and increasing burden to health systems, patients, and society. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are proven to reduce incidence of cardio-renal outcomes, including onset of ESKD. Recent post hoc analyses of SGLT2 inhibitor trials extrapolate substantial delays in the average time to ESKD over a patient's lifetime. In this article, we explore the possible real-world effects of such a delay by considering the available evidence reporting outcomes following onset of ESKD. From the patient perspective, a delay in reaching ESKD could substantially improve health-related quality of life and result in additional life years without the need for kidney replacement therapies, a target relevant to all CKD subpopulations. Furthermore, should a patient initiate dialysis at an older age as a result of CKD progression, the time spent in receipt of dialysis, and therefore associated healthcare costs, may also be reduced. A delay in progression may also lead to changes in the management of ESKD, such as increased election of conservative care in preference to dialysis, particularly in elderly populations. For younger patients with CKD, those who reach ESKD while employed face considerable work impairment and productivity loss, as may families and care partners of working age. Therefore, a delay to the onset of ESKD will reduce the proportion of their working lives affected by productivity losses or unemployment due to medical reasons. In conclusion, optimised treatment of CKD may lead to a shift in treatment options, but proper and timely implementation is essential for the realisation of improved outcomes.

ASSESSING SCREENING EFFICACY IN THE PRESENCE OF CANCER OVERDIAGNOSIS.

Cancer screening facilitates the early detection of cancer, at a stage when treatment is often most effective. However, it also brings the risk of over-diagnosis, where a diagnosis made through screening would not have led to symptoms or death during the patient's lifetime. In this paper, we tackle a significant unresolved issue in the evaluation of screening efficacy: selecting primary endpoints and inferential procedures that efficiently consider potential overdiagnosis in screening trials. This is motivated by the necessity to design and analyze a phase IV Early Detection Initiative (EDI) trial for evaluating a pancreatic cancer screening strategy. We introduce two novel approaches for assessing screening efficacy, grounded on cancer stage-shift. These methods address potential overdiagnosis by: i) borrowing information about clinical diagnosis from the control arm that hasn't undergone screening (the BR approach), and ii) performing sensitivity analysis, contingent upon a conservative bound of the overdiagnosis magnitude (the SEN-T approach). Analytical methods and extensive simulation studies underscore the superiority of our proposed methods, demonstrating enhanced efficiency in estimating and testing screening efficacy compared to existing methods. The latter either overlook overdiagnosis or adhere to a valid, yet conservative, cumulative incidence endpoint. We illustrate the practical application of these approaches using ovarian cancer data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The results affirm that our methods bolster an efficient and robust study design for cancer screening trials.

Maintenance of peri-implant health in general dental practice

The long-term maintenance or restoration of peri-implant tissues‘ health depends on the strategic implementation of preventive measures and interventions. These measures should be initiated before implant placement and continued throughout a patient's lifetime, as part of a tailored and comprehensive supportive peri-implant care (SPIC) programme. Central to the clinical efforts of maintaining and rehabilitating peri-implant tissues are several key factors, including the ongoing assessment and frequent monitoring of tissue health and stability, proactive oral health promotion, the control of risk factors and indicators and the provision of professional plaque biofilm removal. It is of paramount importance to underline that SPIC should not limit its scope exclusively to patients already in a state of peri-implant health; in fact, it is imperative that it should extend its protective effect to individuals who have been previously diagnosed and treated for peri-implant diseases, focusing on preventing its recurrence and progression, thereby avoiding further complications, such as implant loss.This narrative review presents an overview of the current literature on the maintenance of peri-implant tissues‘ health and the steps of SPIC providing insights into the critical factors to be considered when managing dental implant patients in the general dental practice.

Hysterectomy versus chemotherapy for low-risk non-metastatic gestational trophoblastic neoplasia (GTN): A cost-effectiveness analysis

ObjectiveDetermine the cost-effectiveness for hysterectomy versus standard of care single agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). MethodsA cost-effectiveness analysis was conducted comparing single agent chemotherapy with hysterectomy using decision analysis and Markov modeling from a healthcare payer perspective in Canada. The base case was a 40-year-old patient with low-risk non-metastatic GTN that completed childbearing. Outcomes were life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and adjusted 2022 costs (CAD). Discounting was 1.5% annually and the time horizon was the patient's lifetime. Model validation included face validity, deterministic sensitivity analyses, and scenario analysis. ResultsMean costs for chemotherapy and hysterectomy arms were $34,507 and $17,363, respectively, while effectiveness measure were 30.37 QALYs and 31.04 LYs versus 30.14 QALYs and 30.82 Lys, respectively. The ICER was $74,526 (USD $54,516) per QALY. Thresholds favoring hysterectomy effectiveness were 30-day hysterectomy mortality below 0.2% and recurrence risk during surveillance above 9.2% (low-risk) and 33.4% (high-risk). Scenario analyses for Dactinomycin and Methotrexate led to similar results. Sensitivity analysis using tornado analysis found the cost to be most influenced by single agent chemotherapy cost and risk of resistance, number of weeks of chemotherapy, and probability of postoperative mortality. ConclusionCompared to hysterectomy, single agent chemotherapy as a first-line treatment costs $74,526 for each additional QALY gained. Given that this cost falls below the accepted $100,000 willingness-to-pay threshold and waitlist limitations within public healthcare systems, these results support the continued use of chemotherapy as standard of care approach for low-risk GTN.

Therapeutic developments for neurodegenerative GM1 gangliosidosis.

GM1 gangliosidosis (GM1) is a rare but fatal neurodegenerative disease caused by dysfunction or lack of production of lysosomal enzyme, β-galactosidase, leading to accumulation of substrates. The most promising treatments for GM1, include enzyme replacement therapy (ERT), substrate reduction therapy (SRT), stem cell therapy and gene editing. However, effectiveness is limited for neuropathic GM1 due to the restrictive nature of the blood-brain barrier (BBB). ERT and SRT alleviate substrate accumulation through exogenous supplementation over the patient's lifetime, while gene editing could be curative, fixing the causative gene, GLB1, to enable endogenous enzyme activity. Stem cell therapy can be a combination of both, with ex vivo gene editing of cells to cause the production of enzymes. These approaches require special considerations for brain delivery, which has led to novel formulations. A few therapeutic interventions have progressed to early-phase clinical trials, presenting a bright outlook for improved clinical management for GM1.

Changes in aorta hemodynamics in Left-Right Type 1 bicuspid aortic valve patients after replacement with bioprosthetic valves: An in-silico study.

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR.

Pulmonary Rehabilitation: A Look Back, a Look Forward.

Pulmonary rehabilitation (PR) is a comprehensive approach to the management of patients with chronic lung disease that encompasses exercise, education, and psychosocial support. The development of PR programs began in the mid-20th century with the appreciation that exercise provided real benefit in chronic lung disease and that effective disease management involved patient education focused on medications, lifestyle changes, and lifelong regular exercise. Initially PR was primarily facility-based, but today PR is extending into the home with telemedicine, and this is encouraging a real partnership of patients and professionals supporting self-management. The evidence base supporting PR as a safe and effective modality has grown exponentially over the last 4 decades, and PR is strongly endorsed by virtually all the major professional societies. Importantly, PR has also clearly been shown to be cost-effective. Challenges remain, however. Access is still very limited for a variety of reason (logistics, financial, patient motivation) that need to be addressed. More focused and personalized exercise programs and monitoring strategies that encourage a patient's lifetime commitment to the principles of PR need to be developed and refined. The opportunity to really impact important clinical outcomes exists with PR, and this needs to be exploited.

Coste-efectividad del ciclosilicato de sodio y zirconio para el tratamiento de la hiperpotasemia en pacientes con enfermedad renal crónica o insuficiencia cardiaca en España

Background and objectiveHyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K+), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K+ chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System. Materials and methodsTwo microsimulation models reflecting the natural history of CKD and HF were used. In both models, K+ levels were simulated individually. Based on efficacy (reduction of K+ levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (€, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes. ResultsSZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of € 3,616 and € 14,749, respectively, obtaining an incremental cost-utility ratio of € 7,605 /QALY in CKD and € 15,078 /QALY in HF. ConclusionsSZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain.

Cost-utility of VISITAG SURPOINT in catheter ablation of atrial fibrillation.

Clinical studies have demonstrated the safety, efficacy, and efficiency of VISITAG SURPOINT® (VS), which provides important lesion markers during catheter ablation (CA) of atrial fibrillation (AF). The present study evaluated the cost-effectiveness of CA with VS compared to CA without VS in AF from the publicly-funded German and Belgium healthcare perspectives. We constructed a two-stage cost utility model that included a decision tree to simulate clinical events, costs, and utilities during the first year after the index procedure and a Markov model to simulate transitions between health states throughout a patient's lifetime. Model inputs included published literature, a meta-analysis of randomized controlled trials AF outcomes, and publicly available administrative data on costs. Deterministic and probabilistic sensitivity analyses were conducted to determine the robustness of the model. CA with VS was associated with lower per patient costs vs CA without VS (Germany: €3295 vs. €3936, Belgium: €3194 vs. €3814) and similar quality-adjusted life-years (QALYs) per patient (Germany: 5.35 vs. 5.34, Belgium: 5.68 vs. 5.67). CA with VS was the dominant ablation strategy (incremental cost-effectiveness ratios: Germany: €-52,455/QALY, Belgium: €-50,676/QALY). The model results were robust and not highly sensitive to variation to individual parameters with regard to QALYs or costs. Freedom from AF and procedure time had the greatest impact on model results, highlighting the importance of these outcomes in ablation. CA with VS resulted in cost savings and QALY gains compared to CA without VS, supporting the increased adoption of VS in CA in Germany and Belgium.

Smart connected insulin dose monitoring technologies versus standard of care: a Canadian cost-effectiveness analysis.

Aim: There is growing interest in novel insulin management systems that improve glycemic control. This study aimed to evaluate the cost-effectiveness of smart connected insulin re-usable pens or caps for disposable insulin pens versus pens without connected capabilities in the management of adult patients with Type 1 diabetes (T1DM) from a Canadian societal perspective. Materials & methods: The IQVIA Core Diabetes Model was utilized to conduct the analyses. Applying data from a non-interventional study, the connected insulin device arm was assumed to result in greater reductions (-0.67%) in glycated hemoglobin from baseline and fewer non-severe hypoglycemic events (-32.87 events/patient annually). Macro- and micro-vascular risks were predicted using the Epidemiology of Diabetes Interventions and Complications study data. Direct and indirect costs and utilities were sourced from literature. Key model outcomes included life years and quality-adjusted life-years (QALYs). Both costs and effects were annually discounted at 1.5% over a 60-year time horizon. Uncertainty was explored in scenario and probabilistic sensitivity analyses (PSA). Results: The connected insulin pen device was associated with lower mean discounted total costs (CAD221,943 vs 266,199; -CAD44,256), improvement in mean life expectancy (25.78 vs 24.29; +1.49years) and gains in QALYs (18.48 vs 16.74; +1.75 QALYs) over the patient's lifetime. Most scenario analyses confirmed the base case results. The PSA showed dominance in 99.5% of cases. Conclusion: For adults with T1DM in Canada, a connected insulin pen device is likely to be a cost-effective treatment option associated with greater clinical benefits and lower costs relative to a standard re-usable or disposable pen.

Оценка радиационных рисков на индивидуальном уровне при многократном прохождении компьютерной томографии на современных компьютерных томографах

Technological developments, as well as software upgrades to existing computerized tomography (CT) scanners, require a continuous review of the methods for estimating radiation risk from CT procedures. According to the International Commission on Radiological Protection (ICRP), such assessments should be based on absorbed doses in organs and tissues exposed to radiation. This work is devoted to the study of the influence of various characteristics of the CT (manufacturer, type of scanner, etc.) on the evaluation of radiation risks on the example of multiple exposures in standard CT procedures. As an example, the value of lifetime attribute risk (LAR) and lifetime attributable risk fraction (LARF) for 5 CT scans during the life of a woman aged 20, 25, 30, 45 and 50 years is estimated. The lifetime attributable risk of possible cancer induction was estimated according to the ICRP mathematical model (Publication 103) and using the medical and demographic characteristics of the Russian population, as well as scan protocol data for typical CT scanners of selected models. The results were obtained with the use of old and updated conversion factors for the DLP (Dose Length Product – a measure of the absorbed radiation dose for the whole CT examination) parameter to organ doses from a particular procedure. The lifetime attributable risk of possible cancer induction calculated using organ doses derived from old conversion factors was compared with the risk calculated with data for modern CT scanners with updated conversion factors. The LAR was evaluated over time for one CT examination, two, three, four and five different procedures during the patient's lifetime. It was found that to date such factor as software updates in the field of optimisation of scanning protocols or the CT scanner manufacturer still do not has a significant impact on the radiation risks associated with specific diagnostic procedures. The methods developed by the authors for calculating absorbed doses and radiation risks can be used in planning CT examinations and optimising patient dose loads on any modern CT scanners.

Children with Rare Nager Syndrome-Literature Review, Clinical and Physiotherapeutic Management.

Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the SF3B4 gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient's lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient's benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures.

Contemporary issues in the management of dental trauma.

Contemporary diagnosis and management of traumatic dental injuries requires a multifaceted understanding of the pathological and psychological impact over a patient's lifetime. The legacy of dental trauma injuries can have repercussions for the dentition and supporting tissues, requiring complicated multidisciplinary clinical input. Foresight is required to ensure optimal aesthetic and functional outcomes. Mitigating risks and maximising benefits in patients presenting with polytrauma can be challenging, but if optimally managed at the acute presentation, the long-term burden to the patient and the clinician is reduced. This paper aims to discuss the contemporary clinical dilemmas, challenges and controversies related to the management of dental trauma.