Ultimate Clinical Outcome Research Articles

Evaluation of serum neopterin levels in severe COVID-19 patients: An observational study.

In patients with coronavirus disease (COVID-19), a massive inflammatory response is a significant cause of morbidity and mortality. Inflammatory markers are prognostic indicators of disease severity and the ultimate clinical outcome. Several studies have demonstrated a correlation between serum levels of neopterin, which can be an immune system marker, disease severity, and poor outcomes in COVID-19 patients. Our study aimed to determine the diagnostic significance of neopterin in conjunction with routinely measured inflammatory markers in patients with severe COVID-19. Serum neopterin, C-reactive protein (CRP), albumin levels, and complete blood count were determined in 39 patients with severe COVID-19 and 30 healthy individuals. Demographic characteristics, serum neopterin levels, and other laboratory data were compared between patients and healthy volunteers and statistically analyzed. High neopterin levels were observed in patients with severe COVID-19 compared to healthy volunteers. Furthermore, albumin levels were decreased, while CRP levels were increased in patients, statistically significantly. Also, positive correlations were shown between serum neopterin levels and serum CRP levels, while negative correlations were shown between serum neopterin levels and serum albumin levels. Systemic inflammation markers, CRP/albumin ratio, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio were significantly higher, while lymphocyte/monocyte ratio was also significantly lower in patients with severe COVID-19 than in healthy volunteers. However, serum neopterin levels were not linked to the CRP/albumin ratio, the neutrophil/lymphocyte ratio, or the platelet/lymphocyte ratio. On the other hand, they were linked negatively to the lymphocyte/monocyte ratio. Our findings highlight the association between high neopterin levels and patients with severe COVID-19. Neopterin is correlated with traditional inflammatory biomarkers and may indicate general immune and inflammatory activation in patients with severe COVID-19.

Cardiac function in congenital diaphragmatic hernia

Cardiac function is known to play critical role in the pathophysiological progression and ultimate clinical outcome of patients with congenital diaphragmatic hernia (CDH). While often anatomically normal, the fetal and neonatal heart in CDH can suffer from both right and left ventricular dysfunction. Here we explore the abnormal fetal heart, early postnatal right and left ventricular dysfunction, the interplay between cardiac dysfunction and pulmonary hypertension, evaluation and echocardiographic assessment of the heart, and therapeutic strategies for managing and supporting the pathophysiologic heart and CDH. Further, we take a common clinical scenario and provide clinically relevant guidance for the diagnosis and management of this complex process.

Evaluation of Students' Proficiency in Removing Gutta-Percha Prior to Fiber Post Placement: A Retrospective Study.

This retrospective study focuses on dental students' proficiency in removing gutta-percha during fiber post space preparation, which is important for maintaining apical seal integrity in endodontically treated teeth. Emphasizing the significance of preventing further reinfection. The primary objective of this study was to assess the proficiency of undergraduate dental students in the manipulation of gutta-percha during fiber post preparation, specifically focusing on the psychomotor skills involved. In addition, the study aims to determine the predictive value of these skills on the ultimate clinical outcomes of the procedure, with particular emphasis on variations attributable to tooth type. The analysis encompassed 290 periapical radiographs obtained from endodontically treated teeth, all of which had undergone fiber post placement by undergraduate students at the College of Dentistry, Taibah University, Saudi Arabia. Postoperatively, the length of the remaining gutta-percha was measured by two experts in the field, and subsequent outcomes were classified into three categories: optimal, suboptimal, and inadequate, based on the extent of gutta-percha remaining. Students showed optimal removal rates ranging from 33.3% to 73.1%. Among the studied sample, upper anterior teeth were the highest included teeth (n=117, 40%). Remarkably, lower anterior teeth were more prone to suboptimal and inadequate gutta-percha remaining lengths (n=24, 33%). However, the chi-square test revealed no statistically significant difference in students' psychomotor skills while removing the gutta-percha and preparing the teeth to receive fiber posts across tooth types (p-value > 0.05). With the limitations of this study, more than half of the included cases show that undergraduate students of the College of Dentistry at Taibah University, Saudi Arabia, possess an optimum level of psychomotor skills in removing gutta-percha while preparing the teeth for receiving fiber posts. This study suggests enhancing the preclinical training of students by considering more training on different tooth types in relation to dental arches.

Outcome of early versus delayed presentation of proximal femur fractures in children: A prospective cohort study

ObjectiveWe hypothesized that the exact time of fixation of paediatric proximal femur fractures will have an effect on the ultimate clinical and radiological outcome. This article aimed to compare the clinical–radiological outcomes in paediatric proximal femur fractures having early and delayed presentation. MethodologyA prospective cohort study was conducted from January 2019 to November 2022 in patients of age of 5 to 16 years presented with proximal femur fracture and divided into two groups: group A: early presentation, presented <48hours of injury; group B: delayed presentation, presented >48hours of injury. Patients underwent internal fixation treatment modality and followed up to assess clinical outcomes and radiological outcomes, and final outcome was assessed as per Ratliff's criteria. ResultsIn the study of 44 patients, 72.72% were male, and 27.27% were female, with male-to-female ratio to be 2.6:1. The commonest mode of injury was fall from height accounting for 52.27% followed by road traffic accidents (RTA) in 38.63%. The most common fracture type observed was Delbet type II, which was observed in 43.18%. There was significant shorter duration of surgery in group A (p-value=0.013), VAS score (p=0.045), and limb length discrepancy (p=0.022). Also, there was a statistical difference in AVN (p-value=0.0295) and growth disturbance (p-value=0.0394) between two groups. Also, there was statistically significant difference between Ratliff's criteria two groups (p-value=0.030). ConclusionEarly presentation has shorter duration of surgery, less VAS score at final follow-up, and less limb length discrepancy, less development of complications like avascular necrosis of the femoral head, and growth disturbance. Level of evidenceIII.

Impact of clonal hematopoiesis in COVID-19 patients at high risk for adverse clinical outcomes

PurposeClonal hematopoiesis (CH) describes the aging-associated expansion of mutant hematopoietic cell populations. In various cohorts, CH has been associated with increased morbidity and mortality from non-hematologic diseases such as cardiovascular disease and infections, including COVID-19. Comorbidities placing individuals at risk of complications from these disorders, such as diabetes, also increase in prevalence with age and frequently co-exist with CH. How CH interacts with other aging-associated comorbidities to impact human health remains unknown.MethodsWe assessed the impact of CH on the pre-existing end-organ damage and ultimate clinical outcomes among 242 patients hospitalized with COVID-19 at Michigan Medicine from March to June of 2020. In contrast to most previous studies, these patients skewed older with the majority having multiple comorbidities, which placed them at higher risk for end-organ damage and poor clinical outcomes.ResultsOverall CH was not significantly associated with increased COVID-19 mortality after controlling for other risk factors, although we did note a borderline-significant association specifically for non-DNMT3A CH mutations. In contrast, we observed a significant association between CH and pre-existing chronic kidney disease (CKD), which was strongest for DNMT3A mutant CH.ConclusionsThese data suggest that the clinical impact of CH is influenced by the specific gene(s) mutated and is further modified by other comorbidities and clinical risk factors frequently present in the elderly.

Venous Thromboembolism Management in Pregnant Patients

Pulmonary embolism (PE) in pregnancy accounts for 10% of maternal deaths in the United States. As maternal morbidity and mortality continue to increase, it is imperative for all specialties interfacing with pregnant patients to understand the current research and guidelines surrounding risk stratification, diagnosis, and treatments of PE in pregnancy. Given the complexity of high-risk pregnancy-associated PE (PA-PE), that is, which is associated with hemodynamic instability or collapse, and the rising popularity of new technologies to treat high-risk PA-PE in the nonpregnant population, this review aims to emphasize the differences in diagnosis, risk stratification, and management of the pregnant and nonpregnant PE patients. Furthermore, this review will cover treatment paradigms that include anticoagulation versus advanced therapies such as systemic thrombolysis, surgical embolectomy, extracorporeal membrane oxygenation, and inferior vena cava disruption as well as the more novel therapies which fall under the umbrella term of catheter-based treatments. Finally, this review will include a case-based review of 2 patients with PA-PE requiring catheter-based therapies and their ultimate clinical outcomes.

Surface Plasmon Resonance (SPR) Sensor for Cancer Biomarker Detection

A biomarker is a physiological observable marker that acts as a stand-in and, in the best-case scenario, forecasts a clinically significant outcome. Diagnostic biomarkers are more convenient and cost-effective than directly measuring the ultimate clinical outcome. Cancer is among the most prominent global health problems and a major cause of morbidity and death globally. Therefore, cancer biomarker assays that are trustworthy, consistent, precise, and verified are desperately needed. Biomarker-based tumor detection holds a lot of promise for improving disease knowledge at the molecular scale and early detection and surveillance. In contrast to conventional approaches, surface plasmon resonance (SPR) allows for the quick and less invasive screening of a variety of circulating indicators, such as circulating tumor DNA (ctDNA), microRNA (miRNA), circulating tumor cells (CTCs), lipids, and proteins. With several advantages, the SPR technique is a particularly beneficial choice for the point-of-care identification of biomarkers. As a result, it enables the timely detection of tumor markers, which could be used to track cancer development and suppress the relapse of malignant tumors. This review emphasizes advancements in SPR biosensing technologies for cancer detection.

Patient attitudes and preferences for the management of pregnancy of unknown location

ObjectiveTo understand patient attitudes and preferences when faced with the uncertainty of pregnancy of unknown location (PUL).DesignQualitative, interview-based study.SettingUniversity Hosptial.Patient(s)Patients aged >18 years sampled from the emergency department and a subspecialty fertility practice of a university hospital system.Intervention(s)Six to 8 weeks after resolution of a PUL, with an ultimate clinical outcome of either an intrauterine pregnancy, spontaneous abortion, or ectopic pregnancy. Participants underwent either surgical, medical, or expectant management.Main Outcome Measure(s)Thematic analysis of the virtual, semistructured interviews (45–60 minutes in length) conducted with participants to identify commonly expressed priorities was performed.Result(s)Interviews were completed from October 2020 to March 2021 until thematic saturation was achieved (n = 15). Resolution diagnoses included intrauterine pregnancy (26.7%, n = 4), ectopic pregnancy (40.0%, (n = 6), and spontaneous abortion (33.3%, n = 5). Moreover, 66.7% (n = 10) of the patients presented to the emergency department, whereas 33.3% (n = 5) presented to a subspecialty fertility clinic. All had desired pregnancies. Thematic analyses revealed 4 related priorities around PUL management: health of pregnancy; health of self; future fertility; and diagnostic prediction and diagnostic certainty. The relative balance of these priorities was dynamic and evolved throughout the course of management with different outcomes. A second set of themes related to logistical preferences included mental healthsupport, clarity of treatment and next steps, and continuity of care. Interrater reliability was validated with a pooled κ of >0.8. Limitations include that all participants had desired pregnancies, and the experiences of those who experienced different pregnancy outcomes may have been affected by recall bias.Conclusion(s)These data demonstrate novel themes around related priorities in patients with desired pregnancies diagnosed with a PUL previously underappreciated by clinicians. The balance of these priorities evolved throughout management with increasing information and clarity. Continually reevaluating relevant patient priorities and preferences is essential to the comprehensive management of PUL.

Correlation Between Duration of Hypertension and Level of Adherence to Hypertensive

Hypertension is a major cause of premature death worldwide.16,95% citizen were diagnosed with hypertension and Balowerti area had the highest cases in Kediri City. The adherence to antihypertensive medications is a key component to control blood pressure levels. Poor adherence to these medications leads to the development of hypertensive complications and increase risk of cardiovascular events which in turn reduces the ultimate clinical outcome. Duration of hypertension status is one of the factors that affect the level of adherence. Previously, there were several similar studies with varying results. This study is needed to give early intervention to reduce complications and patient mortality. Aim: This study aims to find the correlation between the duration of hypertension and the level of adherence to antihypertensive medication in Balowerti Public Health Center Kediri. A cross-sectional study was carried out to 106 patients with hypertension in the work area of Balowerti Public Health Center, Kediri, East Java, Indonesia using accidental sampling. Morisky Medication Adherence Scale (MMAS-8) questionnaire was used to measure the level of adherence to antihypertensive medication. Data were analysed with the Spearman correlation test. Results: This study showed a significant correlation between the duration of hypertension and the level of adherence to antihypertensive medication (p =0.011, p &lt; 0,05). Duration of hypertension was significantly correlated with the level of adherence to antihypertensive medication. The longer duration of hypertension, the lower level of adherence to antihypertensive medication

Clinical significance of unfavorable findings in intermediate-risk prostate cancer patients for predicting treatment outcomes after contemporary, dose-escalated multimodal radiotherapy.

Few studies have documented the long-term oncological outcomes of favorable and unfavorable intermediate-risk (IR) prostate cancer patients treated via contemporary high-dose irradiation. We analyzed the ultimate clinical outcomes of such patients using the current risk sub-stratification schema. We included 693 patients with localized IR prostate cancer treated via low-dose-rate brachytherapy (LDR-BT) with or without external beam radiation (EBRT) and with or without androgen-deprivation therapy (ADT) in a single institution. Treatment outcomes (biochemical recurrence-free survival [BCRFS] and clinical progression-free survival [CPFS]) were compared according to the numbers of unfavorable findings. Out of the 693 IR patients, 292 (42.1%) exhibited favorable disease; the remaining 401 (57.9%) exhibited unfavorable disease. Compared with favorable IR status, unfavorable IR status was associated with shorter BCRFS and CPFS (p < 0.001 and p < 0.001, respectively). Patients with two to threeunfavorable factors experienced the worst oncological outcomes (p < 0.001 and p < 0.001). Although patients with one or no unfavorable factors responded similarly to LDR-BT monotherapy, this treatment modality was insufficient for preventing biochemical and clinical progression in patients with multiple unfavorable findings. Long-term treatment outcomes indicate that patients with IR disease scheduled for LDR-BT should undergo multimodal irradiation if they exhibit two or more unfavorable factors at diagnosis.

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms.

Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs.

P22. Recurrent CSF leak following repair of incidental durotomy in lumbar spinal stenosis surgery

P22. Recurrent CSF leak following repair of incidental durotomy in lumbar spinal stenosis surgery

Clipping of unruptured intracranial aneurysms in patients older than sixty: An age-based analysis

ObjectiveThe diagnosis of unruptured intracranial aneurysms (UIAs) is being made more frequently in elderly patients. The goal of this study is to evaluate complications and clinical outcome in patients ≥ 60 years-old who underwent clipping of UIAs. MethodsWe performed a retrospective cohort study. Clinical outcome (modified Rankin scale score) was determined at the latest clinical follow-up. Complications and outcomes were compared between age groups (60–69, 70–80) and subgroups (60–64, 65–69, 70–74, and >75). ResultsThe study population consisted of 255 patients (range 60–80 years-old) who underwent 262 clipping procedures for UIAs. Mean follow-up duration was 15.6 months (± 27.5). Major complications occurred in 20 patients (7.6%) and mortality in 3 patients (1.1%). Medical complications occurred in 26 patients (10%). Mean length of hospital-stay was 4.7 days (± 5.8). 89.6% were discharged to home. 87.8% had a favorable clinical outcome. The 70–80 age group had significantly more complications (P = 0.03) than the 60–69 group and a significantly longer hospital stay (6.02 vs. 4.3 days, P = 0.04). The older group was less likely to discharge to home and more likely to require rehabilitation (P = 0.002). Favorable clinical outcome did not significantly differ between the two groups (85.7% vs. 88.4%, P = 0.56). There was a trend for increasing complications from the younger to older subgroups (P = 0.008) and a reduction in the likelihood to discharge to home (P < 0.0001). The rate of ultimate favorable clinical outcome did not differ significantly between subgroups (P = 0.79). ConclusionAlthough complications, length of hospital-stay, and discharge to non-home destinations increase with older age, the majority of patients ≥ 60 may have favorable clinical outcomes.

Association of XPD Lys751Gln gene polymorphism with susceptibility and clinical outcome of colorectal cancer in Pakistani population: a case-control pharmacogenetic study.

XPD Lys751Gln polymorphism may modulate inter-individual variation in repair capacity of DNA, which may enhance a person's susceptibility to develop colorectal cancer (CRC). The analysis of XPD Lys751Gln polymorphism may provide important information for identifying high-risk individuals and for selecting the most appropriate treatment for poor prognostic CRC patients. The overall objective was to find out the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer and the ultimate clinical outcomes. In this study a total of 300 subjects (CRC and Controls), were genotyped for XPD Lys751Gln. Using PCR-RFLP methods, the association of XPD Lys751Gln gene polymorphism with the risk of having a colorectal cancer was studied. In addition to overall risk assessment, genotyping results were also investigated with respect to the lifestyle risk factors, patients treated with oxaliplatin-based chemotherapy and clinicopathological characteristics. The overall correlation between the XPD Lys751Gln genetic variation and the CRC risk was observed to be significant with both the homozygous variant genotype Gln/Gln as well as heterozygous genotype Lys/Gln being associated with the increased risk of CRC. Additional stratified analyses revealed that XPD Lys751Gln variants remarkably increased risk of CRC in males and younger individuals (≤ 50years), Naswar users (8.09-fold) and high intake of red meat. Our findings suggest that the relationship between the XPD Lys751Gln variants and lifestyle factors modulates the risk for CRC in Pakistani population.

55. Early deformity development following decompressive surgery for lumbar spinal stenosis

BACKGROUND CONTEXT Decompressive surgery for symptomatic lumbar spinal stenosis is predictable and effective in providing relief of radiculopathy and neurogenic claudication. Decompression alone, without fusion, is generally reserved for patients with preserved lordosis and no evidence of instability. On occasion, spinal deformity and instability can occur following decompressive surgery and may lead to disabling symptoms and the need for revision surgery inclusive of an instrumented fusion. PURPOSE The purpose of this study was to evaluate the extent and nature of symptomatic deformity development occurring within one year following decompressive surgery for lumbar spinal stenosis. Multiple clinical and radiographic factors were assessed for their effect upon deformity development. Additionally, the ultimate clinical outcomes of patients who underwent revision surgery for deformity development were compared to a cohort of patients who had not developed a deformity after undergoing decompressive surgery during the same time period. STUDY DESIGN/SETTING Retrospective cohort study of prospectively collected data from a single institution. PATIENT SAMPLE A total of 425 patients underwent decompressive surgery over a 5-year period (2012-2016) for symptomatic lumbar spinal stenosis by one of four surgeons at a single spine center. All patients had preserved lordosis (no antero-, lateral, or retrolisthesis) on preoperative, upright radiographs and none had evidence of instability on flexion-extension films. All patients underwent open, multilevel laminectomies with lateral recess and foraminal decompression to address neural compression noted on preoperative MRI. OUTCOME MEASURES Pre- and postoperative VAS (back pain), VAS (leg pain), Oswestry Disability Index, and specific queries of patient satisfaction with surgery and willingness to repeat the index surgery. The indication for additional surgery early in the postoperative period ( METHODS Patients undergoing lumbar decompressive surgery were followed postoperatively at 6 weeks, 3 months, 6 months, and 1 year. If a patient developed a symptomatic deformity within the first year which required additional surgery, they were identified and compared to a cohort of patients who also underwent decompressive surgery over the same 5-year period but did not develop a postoperative deformity. RESULTS A total of 425 patients underwent a multilevel lumbar decompression for spinal stenosis over a 5-year period. Nineteen patients (4%) developed pain and radiographic evidence of a deformity within one year that necessitated an additional surgery in the form of an instrumented fusion. Back pain was present in all 19 patients and recurrent radicular pain was present in 16 of 19 patients (84%). Significant factors for development of a deformity included age 30 (p=.03), and fluid within multiple facet joints noted on preop MRI (p=.04). Notable factors that approached, but did not reach significance included patients with 4-level laminectomies (p=.05), osteoporosis (p=.05), and chronic, preoperative corticosteroid use (p=.05). Notable factors that were not significant included presence of congenital stenosis, type of preoperative employment (sedentary vs physically demanding), use of postoperative bracing, or duration of preoperative symptoms (greater or less than one year). When compared with a cohort of patients who did not develop a deformity, the deformity patients had poorer VAS (back) and ODI scores at 6 months following their revision surgery. By 1 year, and thereafter to 5 years postoperatively, the two cohorts had similar VAS (back and leg) and ODI scores and the percentage of patients in each cohort who had overall improvement in each outcome measure (VAS back, VAS leg, ODI) were similar in both cohorts. As well, there were no significant differences at 2-5 years postop in patient-reported satisfaction rates or willingness to repeat index surgery. CONCLUSIONS Deformity development within the first year following decompressive surgery for lumbar spinal stenosis was found to be an uncommon event, occurring in 4% of consecutive patients treated at a single spine center over a 5-year period. Younger, obese patients and those with greater than 3 levels decompressed were more likely to develop deformities, as were patients with fluid noted within multiple facet joints on preoperative MRI. However, long-term follow-up reveled no ultimate difference in outcomes of patients who required additional surgery for deformity development, including patient satisfaction and willingness to repeat the index lumbar decompressive procedure. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Clinical correlation of vein graft adaptation

While we revascularize our patients using venous bypass, we seldom think of the complex process that is set into place the minute that we remove arterial control and reperfuse the limb. Yet once arterial blood enters the venous graft, adaptation of the graft to its new environment is triggered. This adaptation plays a significant role in graft patency, clinical durability, and ultimate clinical outcomes. Although vein graft remodeling has been widely studied in both animal and clinical models much about this process remains poorly understood.

Addition of Chinese herbal remedy, Tongguan Capsules, to the standard treatment in patients with myocardial infarction improve the ventricular reperfusion and remodeling: Proteomic analysis of possible signaling pathways

Ethnopharmacological relevanceTongguan Capsules (TGC), a patented Chinese herbal remedy containing Salvia miltiorrhiza, Astragalus membranaceus, Borneolum syntheticum and Grasshopper, has been previously tested in the experimental model of animal hearts subjected to ischemia/reperfusion injury and its cardioprotective effect has been described. Aim of the studyThis clinical trial was aimed at investigation whether the administration of TGC to patients suffered myocardial infarction (MI), would diminish dilation of the left ventricular (LV) and reduce development of the adverse clinical consequences. MethodsEligible patients were enrolled and randomized 1:1 to TGC (4.5 g/d for 6 months) superimposed on standard treatment for MI, or the control group receiving the standard protocol alone. The outcomes of this trial were valued after 6 months and reported as a mean change from the baseline in LV end-systolic volume index (LVESVI) and as a frequency of MI recurrence, target-vessel revascularization, severity of heart failure or significant arrhythmia that required the additional therapy within 6 months. In addition, arrays with a panel of specific antibodies were used to assess levels of major cytokines and other pathophysiologic markers, that prompted conclusions about the mechanisms of the ultimate clinical outcomes in both patient's subgroups. ResultsMeaningfully, obtained results indicated that MI patients randomly assigned to the TGC treatment, demonstrated a significant reduction of LVESVI (−4.03 ± 0.73 vs. 1.59 ± 0.43 mL/m2, P < 0.001) and a lower incidence of the major adverse cardiovascular events (5.45% vs. 11.44%, P = 0.033). Meaningfully, those patients consistently demonstrated lower serum levels of major inflammatory cytokines, as well as reduced levels of markers of myocardial apoptosis and fibrosis. ConclusionAddition of TGC to the current conventional treatment of MI patients, significantly reduced their adverse LV remodeling and contributed to the more positive clinical outcome. Trial registrationChiCTR-IPR-17011618.

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures.

Nitric oxide (NO), which is synthesized by the enzyme NO synthase (NOS), is a versatile endogenous molecule with multiple biological effects on many tissues and organs. In dental pulp tissue, NO has been found to play multifaceted roles in regulating physiological activities, inflammation processes, and tissue repair events, such as cell proliferation, neuronal degeneration, angiogenesis, and odontoblastic differentiation. However, there is a deficiency of detailed discussion on the NO-mediated interactions between inflammation and reparative/regenerative responses in wounded dental pulp tissue, which is a central determinant of ultimate clinical outcomes. Thus, the purpose of this review is to outline the current molecular understanding on the roles of Janus-faced molecule NO in dental pulp physiology, inflammation, and reparative activities. Based on this knowledge, advanced physicochemical techniques designed to manipulate the therapeutic potential of NOS and NO production in endodontic regeneration procedures are further discussed. Impact statement The interaction between inflammation and reparative/regenerative responses is very important for regenerative endodontic procedures, which are biologically based approaches intended to replace damaged tissues. Inside dental pulp tissue, endogenous nitric oxide (NO) is generated mainly by immunocompetent cells and dental pulp cells and mediates not only inflammatory/immune activities but also signaling cascades that regulate tissue repair and reconstruction, indicating its involvement in both tissue destruction and regeneration. Thus, it is feasible that NO acts as one of the indicators and modulators in dental pulp repair or regeneration under physiological and pathological conditions.

Chapter 11 - Cognitive reserve

Cognitive reserve is a latent construct theorized to account for the discrepancy between observed brain deterioration and ultimate clinical outcomes. This review outlines the theoretical development of the reserve concept and presents major trends within epidemiological and neuroimaging research literatures in support of such a construct. Particular focus is placed on the implications for cognitive aging and dementia.

Early return to playing professional football following fixation of 5th metatarsal stress fractures may lead to delayed union but does not increase the risk of long-term non-union.

5th metatarsal stress fractures are frequently encountered in professional football. There is concern that early return to play following intra-medullary screw fixation may lead to an increased risk of delayed union. The purpose of the study was to assess whether an early return to play after surgical fixation of 5th metatarsal fractures in professional football players is a risk factor for delayed union and the effect of this on the ultimate clinical outcome. Retrospective review of prospectively collected data of a series of 37 professional football players following intramedullary screw fixation of 5th metatarsal stress fractures. End points included time of return to play and to radiological union of the fracture. At a minimum follow-up of 24 months the mean return to play was 10.5 weeks and mean time to complete radiological union was 12.7 weeks. Return to play at 8 weeks or less resulted in a higher risk of delayed radiological union (24% at 3 months), but this neither prevented the athlete from continuing to play football nor did it affect the ultimate risk of non-union (3% overall). A re-fracture occurred in 1 patient (3%) at 10 months who previously had complete radiographic union at 9 weeks. Intramedullary screw fixation of 5th metatarsal stress fractures leads to a predictable time of return to play and a low rate of non-union. If players return to play at 8 weeks or less a persistent line may be expected in up to a quarter of patients. However, if asymptomatic this radiological finding does not mean that athletes must avoid playing football as ultimately a good outcome is expected with low rates of non-union and refracture. Case series, Level IV.