Enhancing Chronic Non-Cancer Pain Management: A Systematic Review of Mindfulness Therapies and Guided Imagery Interventions.

Background and Objectives: There has been an increasing interest in the use of non-pharmacological approaches for the multidimensional treatment of chronic pain. The aim of this systematic review was to assess the effectiveness of mindfulness-based therapies and Guided Imagery (GI) interventions in managing chronic non-cancer pain and related outcomes. Materials and Methods: Searching three electronic databases (Web of Science, PubMed, and Scopus) and following the PRISMA guidelines, a systematic review was performed on Randomized Controlled Trials (RCTs) and pilot RCTs investigating mindfulness or GI interventions in adult patients with chronic non-cancer pain. The Cochrane Risk of Bias Tool was utilized to assess the quality of the evidence, with outcomes encompassing pain intensity, opioid consumption, and non-sensorial dimensions of pain. Results: Twenty-six trials met the inclusion criteria, with most of them exhibiting a moderate to high risk of bias. A wide diversity of chronic pain types were under analysis. Amongst the mindfulness interventions, and besides the classical programs, Mindfulness-Oriented Recovery Enhancement (MORE) emerges as an approach that improves interoception. Six trials demonstrated that mindfulness techniques resulted in a significant reduction in pain intensity, and three trials also reported significant outcomes with GI. Evidence supports a significant improvement in non-sensory dimensions of pain in ten trials using mindfulness and in two trials involving GI. Significant effects on opioid consumption were reported in four mindfulness-based trials, whereas one study involving GI found a small effect with that variable. Conclusions: This study supports the evidence of benefits of both mindfulness techniques and GI interventions in the management of chronic non-cancer pain. Regarding the various mindfulness interventions, a specific emphasis on the positive results of MORE should be highlighted. Future studies should focus on specific pain types, explore different durations of the mindfulness and GI interventions, and evaluate emotion-related outcomes.

Perceptions of medical students towards the role of histology and embryology during curricular review.

BACKGROUND: The continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology. METHODS: Medical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum. RESULTS: Four hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes. CONCLUSIONS: Our study contributes to the debate about the evolution of medical curriculum. Gathering the medical students' perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.

MicroRNAs in Lung Cancer Oncogenesis and Tumor Suppression: How it Can Improve the Clinical Practice?

BACKGROUND: Lung cancer (LC) development is a process that depends on genetic mutations. The DNA methylation, an important epigenetic modification, is associated with the expression of non-coding RNAs, such as microRNAs. MicroRNAs are particularly essential for cell physiology, since they play a critical role in tumor suppressor gene activity. Furthermore, epigenetic disruptions are the primary event in cell modification, being related to tumorigenesis. In this context, microRNAs can be a useful tool in the LC suppression, consequently improving prognosis and predicting treatment. CONCLUSION: This manuscript reviews the main microRNAs involved in LC and its potential clinical applications to improve outcomes, such as survival and better quality of life.

Lung cancer: a brief review of epidemiology and screening.

The global burden of lung cancer has been increasing over the past years, and is still a major threat to public health worldwide, leading to disabilities and premature mortality. Despite multifactorial cause, smoking remains as the major etiological factor, followed by occupational exposure to carcinogens, genetic predisposition and other concomitant diseases. In order to reduce the individual and social burden due to the direct and indirect costs related to the lung cancer treatment, accurate methods of screening are needed. Among those, x-ray with cytological analysis of sputum was first proposed. Nowadays, more sensitive methods such as low-dose computed tomography are being used to improve the early detection. In the future, molecular biomarkers may complement low-dose computed tomography and improve the robustness of early lung cancer detection.

Spared nerve injury model to study orofacial pain.

BACKGROUND & OBJECTIVES: There are many difficulties in generating and testing orofacial pain in animal models. Thus, only a few and limited models that mimic the human condition are available. The aim of the present research was to develop a new model of trigeminal pain by using a spared nerve injury (SNI) surgical approach in the rat face (SNI-face). METHODS: Under anaesthesia, a small incision was made in the infraorbital region of adult male Wistar rats. Three of the main infraorbital nerve branches were tightly ligated and a 2 mm segment distal to the ligation was resected. Control rats were sham-operated by exposing the nerves. Chemical hyperalgesia was evaluated 15 days after the surgery by analyzing the time spent in face grooming activity and the number of head withdrawals in response to the orofacial formalin test. RESULTS: SNI-face rats presented a significant increase of the formalin-induced pain-related behaviours evaluated both in the acute and tonic phases (expected biphasic pattern), in comparison to sham controls. INTERPRETATION & CONCLUSIONS: The SNI-face model in the rat appears to be a valid approach to evaluate experimental trigeminal pain. Ongoing studies will test the usefulness of this model to evaluate therapeutic strategies for the treatment of orofacial pain.

Complete ossification of the stylohyoid chain as cause of Eagle's syndrome: a very rare case report.

AIM: To report on a patient with Eagle's syndrome with a complete and very large ossification of the stylohyoid complex on the right side that to our best knowledge has never been published previously. BACKGROUND: Eagle's syndrome is characterized by a set of symptoms that are caused by the irritation of the neurovascular and soft-tissues caused by an elongated styloid process or ossification of stylohyoid ligament. CASE DESCRIPTION: Because of the high discomfort and pain degree as well as limitations of mandibular and head mobility and also the thickness of the ossifed stylohyoid chain, the patient was treated surgically by removing the hypertrophic segment. CONCLUSION: These symptoms subsided completely after the surgical excision of the anomaly. The elongated styloid process on the left side was symptom free. CLINICAL SIGNIFICANCE: Eagle's syndrome symptoms are not specific and can mimic those of other disorders, the syndrome must be included in the differential diagnosis of patients with pain in the orofacial, pharyngeal and cervical area.

Conservative versus Invasive Approaches in Temporomandibular Disc Displacement: A Systematic Review of Randomized Controlled Clinical Trials.

BACKGROUND: Temporomandibular disorders (TMDs) frequently cause orofacial pain and dysfunction, with treatment options spanning from conservative therapies to invasive surgical procedures. The aim of this systematic review was to analyze and compare the efficacy and safety profiles of conservative, minimally invasive interventions and surgical procedures in patients diagnosed with TMDs and disc displacement. METHODS: Following PRISMA recommendations, PubMed, Scopus, and Web of Science databases were searched for randomized clinical trials (RCT). Data were synthesized in a table and evaluated through the Cochrane risk of bias 2 (RoB 2) tool. RESULTS: Thirty-eight RCTs, most with moderate RoB, were selected. Conservative approaches, including physical therapy and occlusal devices, led to an improvement in symptoms and function. Pharmacological treatments demonstrated effectiveness in reducing pain and improving function; however, they can have undesirable side effects. Minimally invasive and invasive treatments also demonstrated efficacy, although most trials did not show their superiority to conservative treatments. CONCLUSION: The primary approach to TMDs should be a conservative, multimodal treatment plan tailored to patient complaints and characteristics. Treatment goals should focus on symptom control and functional recovery. Surgical treatment should be reserved for cases with a precise diagnosis and a clear etiology.

Pharmacogenetic Approaches in Personalized Medicine for Postoperative Pain Management.

Despite technical and pharmacological advancements in recent years, including optimized therapies and personalized medicine, postoperative pain management remains challenging and sometimes undertreated. This review aims to summarize and update how genotype-guided therapeutics within personalized medicine can enhance postoperative pain management. Several studies in the area have demonstrated that genotype-guided therapy has the ability to lower opioid consumption and improve postoperative pain. Gene mutations, primarily OPRM1, CYP2D6, CYP2C9, COMT and ABCB1, have been shown to exert nuanced influences on analgesic response and related pharmacological outcomes. This review underscores the integration of pharmacogenetic-guided personalized medicine into perioperative care, particularly when there is uncertainty regarding opioid prescriptions. This approach leads to superior outcomes in terms of postoperative pain relief and reduced morbidity for numerous patients.

Cross-cultural adaptation and validation for Portuguese (Brazilian) of the pictorial representation of illness and self measure instrument in orofacial pain patients.

AIMS: To translate the Pictorial Representation of Illness and Self Measure (PRISM) instrument from German to Portuguese (Brazilian) and adapt it to the Brazilian cultural context, and then assess its reliability and validity in orofacial pain patients. METHODS: The PRISM was translated to Portuguese then back-translated to German. The translated PRISM was evaluated by a multidisciplinary committee and administered as a pre-test to 30 Portuguese-speaking orofacial pain patients. Psychometric properties were obtained after testing 116 orofacial pain patients. Validity was obtained through correlation analyses of scores obtained from PRISM and other psychometric tests, including the Numerical Pain Scale (NPS), Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HAD). RESULTS: The adapted instrument showed high levels of reliability, proven by means of the test-retest procedure, and calculation of the Intraclass Correlation Coefficient (ICC = 0.991). Significant correlations were found between PRISM and the other tests. Correlation with NPS was moderate (-0.42), whereas correlations with ISI (-0.24), HAD-anxiety (-0.25), and HAD-depression (-0.22) were weak. CONCLUSION: The cross-cultural adaptation process of PRISM was successful and the adapted version offers reliable and valid psychometric properties in the Brazilian context.

Outcomes of a QST Protocol in Healthy Subjects and Chronic Pain Patients: A Controlled Clinical Trial.

Chronic pain is an important cause of disability with a high burden to society. Quantitative sensory testing (QST) is a noninvasive multimodal method used to discriminate the function of nerve fibers. The aim of this study is to propose a new, reproducible, and less time-consuming thermal QST protocol to help characterize and monitor pain. Additionally, this study also compared QST outcomes between healthy and chronic pain subjects. Forty healthy young/adult medical students and fifty adult/elderly chronic pain patients were evaluated in individual sessions including pain history, followed by QST assessments divided into three proposed tests: pain threshold, suprathreshold, and tonic pain. In the chronic pain group, a significantly higher pain threshold (hypoesthesia) and a higher pain sensibility (hyperalgesia) were demonstrated at threshold temperature when compared to healthy participants. The sensitivity to the suprathreshold and tonic stimulus did not prove to be significantly different between both groups. The main results demonstrated that the heat threshold QST tests can be helpful in evaluating hypoesthesia and that the sensitivity threshold temperature test can demonstrate hyperalgesia in individuals with chronic pain. In conclusion, this study demonstrates the importance of using tools such as QST as a complement to detect changes in several pain dimensions.

Maxilla Reconstruction with Xenograft Blocks to Allow Implant Rehabilitation: A Case Report.

Reducing patient morbidity is one of the challenging goals of proper surgical techniques. The rehabilitation success begins with a good surgical plan. Scientifically proven biomaterials are excellent options to overcome the lack of autologous bone for maxillary reconstructions. This case report presents a clinical case of maxillary reconstruction combining guided bone regeneration with xenograft blocks and maxillary sinus elevation. This technique achieved maxillary rehabilitation with a fixed implant-supported prosthesis of a challenging case. The clinical case has an 18-month follow-up with no major complications and excellent clinical and radiographic results.

A Randomized Clinical Trial Comparing Implants Placed in Two Different Biomaterials Used for Maxillary Sinus Augmentation.

The objective of this study was to compare marginal bone loss, surgical and clinical complications, and dental implant survival rate in bilateral maxillary sinus augmented by autologous or porcine xenograft. A randomized controlled clinical trial using split-mouth design enrolled 12 consent adult patients (59.7 ± 8.7 years), who received bilateral maxillary sinus floor augmentation for oral rehabilitation with implant-supported prosthesis. Each patient received both the autologous bone from the mandible (control) or porcine xenograft (test) during the random bilateral sinus lift surgery. A total of 39 dental implants were placed in the posterior maxilla of the 12 patients after 6 months, being rehabilitated after the respective osseointegration period. Both graft materials demonstrated a high implant survival rate at 12 months: 95% for the xenograft side, only 1 implant without osseointegration, and 100% for the autologous side. Radiographic bone loss was low and similar for both groups: control group with a mean of 0.063 ± 0.126, and test group with a mean of 0.092 ± 0.163. No major surgical-related complications have occurred. Only one patient had several prosthetic complications due to fractures of prosthetic components. The maxillary sinus augmentation procedure, both with autologous bone and porcine xenograft materials, is an excellent clinical option procedure for the prosthetic rehabilitation of atrophic maxillae, with low marginal bone loss after one year follow-up, few clinical complications, and a high implant survival rate.

Update in Immunotherapy for Advanced Non-Small Cell Lung Cancer: Optimizing Treatment Sequencing and Identifying the Best Choices.

The introduction of immunotherapy has brought about a paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). It has not only significantly improved the prognosis of patients but has also become a cornerstone of treatment, particularly in those without oncogenic driver mutations. Immune checkpoint inhibitors (ICIs) play a crucial role in the treatment of lung cancer and can be classified into two main groups: Anti-cytotoxic T lymphocyte antigen-4 (Anti-CTLA-4) and anti-T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti-PD-L1). Certainly, the landscape of approved first line immunotherapeutic approaches has expanded to encompass monotherapy, immunotherapy-exclusive protocols, and combinations with chemotherapy. The complexity of decision-making in this realm arises due to the absence of direct prospective comparisons. However, a thorough analysis of the long-term efficacy and safety data derived from pivotal clinical trials can offer valuable insights into optimizing treatment for different patient subsets. Moreover, ongoing research is investigating emerging biomarkers and innovative therapeutic strategies that could potentially refine the current treatment approach even further. In this comprehensive review, our aim is to highlight the latest advances in immunotherapy for advanced NSCLC, including the mechanisms of action, efficacy, safety profiles, and clinical significance of ICI.

Systematic Review of Platelet-Rich Plasma for Low Back Pain.

BACKGROUND: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. RESULTS: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. CONCLUSIONS: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

Treatment Sequencing Strategies in Lung Cancer.

BACKGROUND: The advances in the lung cancer screening methods and therapeutics, together with awareness towards deleterious habits, such as smoking, is increasing the overall survival with better quality of life for the patients. However, lung cancer is still one of the most common and fatal neoplasm with a high incidence and consequently burden to public health worldwide. Thus, based on guidelines and recent phases II and III clinical trials studies, this manuscript summarizes the current treatment sequencing strategies in lung cancer. METHODS: A comprehensive search of related articles was performed focused on phases II and III clinical trials studies. RESULTS: The lung cancer management should take into consideration the tumor characteristics, histology, molecular pathology and be discussed in a multidisciplinary team. Lung cancer treatment options comprises surgery whenever possible, radiotherapy associate with/or chemotherapy and immunotherapy as monotherapy, or combined with chemotherapy and best palliative care. CONCLUSIONS: The screening predictability in more patients, smoking reduction, early diagnosis, better disease understanding and individualized, more effective and tolerable therapeutics are related to an increasing in overall survival and quality of life. In the near future improvement of personalized therapy in precision medicine is expected, enhancing new predictive biomarkers, optimal doses and optimal treatment sequencing as well as anti-cancer vaccines development.

Relationship between Postoperative Pain and Sociocultural Level in Major Orthopedic Surgery.

Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are associated with moderate to severe postoperative pain (POP). POP is theoretically predictable and may be influenced by sociocultural differences. This study aimed to identify the relationship between POP and the sociocultural level of the patient undergoing THA or TKA. Methods: Prospective study, involving informed-consenting adults conducted through consulting patient's clinical processes, preoperative and postoperative questionnaires. Demographic and anthropometric data, type of surgery, ASA classification, sociocultural level of the patient, and POP were assessed. Results: 95 patients, all Caucasian and natural from the north of the Portugal, were included. Younger women undergoing TKA reported higher levels of POP. In females, the ASA 3 physical condition was also associated with higher mean pain intensity. Patients with preoperative chronic pain, without depression diagnosis, and unsatisfied with the current profession showed higher levels of reported POP. Retirees, with lower school degree, reported higher levels of minimal pain. Conclusions: Job satisfaction, type of surgery, body mass index, presence of chronic pain, and the absence of depression were identified as the main predictors of pain after THA or TKA.

Neuronal injury marker ATF-3 is induced in primary afferent neurons of monoarthritic rats.

Activating transcription factor 3 (ATF-3) expression has been associated with several signaling pathways implicated in cellular stress response in many cell types and is usually regarded as a neuronal damage marker in dorsal root ganglia (DRG). We investigated ATF-3 expression in primary afferents in the monoarthritic (MA) model of chronic inflammatory joint pain. Immunohistochemistry revealed that ATF-3 is highly induced mainly in small and medium neurons, especially at 2 and 4 days of MA in L(5) DRGs. Colocalization with calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4) demonstrated that ATF-3-immunoreactive cells are mainly peptidergic. The lack of significant differences in ATF-3 and pAkt colocalization indicated that ATF-3 is probably not involved in a pAkt-mediated survival pathway. Anti-inflammatory (ketoprofen) administration failed to reverse ATF-3 induction in MA rats, but significantly increased CGRP expression. These data suggest that ATF-3 expression is definitely involved in MA, actually marking injured neurons. Some degree of neuronal damage seems to occur right from the first days of disease, mainly affecting small-to-medium peptidergic neurons. The intra-articular injection of complete Freund's adjuvant and the generation of a neuroinflammatory environment seem to be the plausible explanation for the local nerve damage.

Analysis of the morphology and composition of tooth apices apicectomized using three different ablation techniques.

OBJECTIVES: To investigate apicectomies performed using burs, a CO2 laser or an Er:YAG laser and to evaluate the following aspects: morphology of apicectomized surfaces, presence of failures at the dentin/obturation material interface (marginal fit) of the apical portions of the root canals, and the proportions of chemical elements in the apicectomized surfaces. STUDY DESIGN: Twenty-four teeth were divided into three groups of eight and each group underwent apicectomy by one of three different ablation techniques: bur, CO2 laser or Er:YAG laser. The morphology of the apicectomized surfaces was then analyzed using scanning electron microscopy and their chemical composition was analyzed by energy dispersive spectroscopy. RESULTS: Surfaces produced with ablation by bur exhibited less surface irregularities and better marginal fit, while ablation with the CO2 laser caused intense surface carbonization and failures in obturation material fit. CONCLUSIONS: Our results suggest that, taking into consideration their clinical application, ablation of tooth apices using burs proved to be the best option among those tested here.

Pain as the fifth vital sign-A comparison between public and private healthcare systems.

BACKGROUND: The assessment of pain as the fifth vital sign (P5VS) is of paramount importance since it leads to the management of undertreated pain, consequently reducing suffering, readmissions and emergency department visits after hospital discharge. OBJECTIVE: To evaluate the implementation of P5VS in public and private hospitals. METHODS: Data analysis on validated questionnaires was sent to all 171 Portuguese hospitals via an official letter. RESULTS: When compared to private hospitals, public hospitals presented a higher adherence to the process related to the P5VS. It has demonstrated superiority in the charts properly placed to record P5VS, in the number of emergency departments recording P5VS, in the regularity of audits, and in the existence of guidelines and staff training on pain assessment and management. CONCLUSION: The standardization of both evaluation and recording of pain intensity constitutes a measure of good clinical practice. Public hospitals demonstrated better commitment to these procedures that should be properly carried out in all health care institutions.

Advantages of Porcine Xenograft over Autograft in Sinus Lift: A Randomised Clinical Trial.

This study aimed to compare the performance of intra-oral autologous bone grafts versus porcine xenografts in a two-step lateral window sinus lift. This split-mouth randomised controlled trial sequentially enrolled 12 patients with a 6-month follow-up. For each patient, a simultaneous randomised bilateral maxillary sinus lift was performed and filled with autologous bone from the mandible (control) or a porcine xenograft (test). A bone biopsy sample was collected during the implant placement for histological and histomorphometric analysis. CT scans were performed at the beginning and at the end of the trial to assess radiological evolution. A comparison of initial and six-month CT scans indicated statistically significant increases in bone level for both materials (7.8 ± 2.4 mm for autologous and 8.7 ± 2.2 mm for xenograft, p < 0.05), and there were no significant differences between the performance of the two materials over time (p = 0.26). The histological analysis showed various stages of the remodelling process and no cells or other signs of inflammation or infection were visible in both groups. The porcine xenografts presented similar results for the studied variables when compared to autologous bone, being a reasonable alternative for a sinus lift.