Clinical Perspective Research Articles

Lessons Learned From Clinical Trials of Immunotherapeutics for COVID-19.

The COVID-19 pandemic caused by the SARS-CoV-2 virus was arguably one of the worst public health disasters of the last 100 years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic-causing agents, SARS-CoV-2 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host-pathogen interaction evolved, subsequent variants of SARS-CoV-2 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host-pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID-19 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID-19 disease.

No detectable loss of myonuclei from human muscle fibers after six weeks of immobilization following an Achilles tendon rupture.

Muscle disuse has rapid and debilitating effects on muscle mass and overall health, making it an important issue from both scientific and clinical perspectives. However, the myocellular adaptations to muscle disuse are not yet fully understood, particularly those related to the myonuclear permanence hypothesis. Therefore, in this study, we assessed fiber size, number of myonuclei, satellite cells, and capillaries in human gastrocnemius muscle after a period of immobilization following an Achilles tendon rupture. Six physically active patients (5M/1F, 43 {plus minus} 15 years) were recruited to participate after sustaining an acute unilateral Achilles tendon rupture. Muscle biopsies were obtained from the lateral part of the gastrocnemius before and after six weeks of immobilization using a plaster cast and orthosis. Muscle fiber characteristics were analyzed in tissue cross-sections and isolated single fibers using immunofluorescence and high-resolution microscopy. Immobilization did not change muscle fiber type composition nor cross-sectional area of type I or type II fibers, but muscle fiber volume tended to decline by 13% (p=0.077). After immobilization, the volume per myonucleus was significantly reduced by 20% (p=0.008). Myonuclei were not lost in response to immobilization but tended to increase in single fibers and type II fibers. No significant changes were observed for satellite cells or capillaries. Myonuclei were not lost in the gastrocnemius muscle after a prolonged period of immobilization, which may provide support to the myonuclear permanence hypothesis in human muscle. Capillaries remained stable throughout the immobilization period, whereas the response was variable for satellite cells, particularly in type II fibers.

Role of trace minerals in cow’s reproductive function and performance: a clinical theriogenology perspective*

Trace minerals (TM) have a crucial role in cattle reproduction. Although microelements are required in small amounts, their bioavailability is essential for the cow reproductive physiology, and for adequate fertility and productivity. They are particularly important for antioxidant protection against cellular damage (e.g. gametes and embryonic cells), hormone synthesis, and pregnancy maintenance. Oral TM supplementation is a common and highly recommended management practice in cattle operations. However, there is substantial variability in TM bioavailability in animals receiving oral TM supplementation. The strategic use of injectable TM supplementation (without replacing traditional oral TM supplements) before episodes of marked stress (e.g. parturition), higher metabolic demand with TM depletion (e.g. last trimester of pregnancy), active immune response (e.g. uterine involution or vaccination), and before breeding helps to maintain adequate TM and oxidative status during critical points of the reproductive program. This manuscript reviews the research-based evidence regarding the effects of TM supplementation on bovine reproduction and its impact on beef and dairy cattle reproductive performance.

Comparative Study of 3D Contact Area Percentage Between Zygomatic Implant and Bone in Different Surgical Approaches: Clinical and Biomechanical Perspectives.

Zygomatic implants, either alone or in combination with dental implant placement, have emerged as a viable surgical option for elderly patients with severe bone atrophy for occlusal restoration. This study aims to examine the biomechanical impact of the three-dimensional contact area between zygomatic implants and bone on biomechanics under different surgical methods. Using Cone Beam Computed Tomography (CBCT) images from 10 patients with severe bone atrophy, we reconstructed 3D maxillary bone models and created corresponding 3D zygomatic implant models. Two distinct surgical methods (extramaxillary or intrasinus approaches) were employed based on the position and angle of the zygomatic implant for each patient. The 3D bone-to-implant contact percentage (BIC%) was calculated, and finite element analysis with nonlinear contact was conducted to assess the relationship between 3D BIC% and surrounding bone stress for both surgical methods. The 3D BIC% of extramaxillary approach (57.63%) and intrasinus approach (56.49%) for total bone (including cortical and cancellous bone) was similar (P=0.425) in zygomatic implant surgery. In contrast, the intrasinus method exhibited higher 3D BIC% in cortical bone contact (28.08%) compared to the extramaxillary approach (21.92%) (P=0.011). The correlation between 3D BIC% and high bone stress was stronger in the intrasinus approach, likely due to increased contact area in cortical bone. The intrasinus approach led to lower bone stress and a more robust correlation between bone stress and 3D BIC%, particularly in cortical bone contact. Importantly, the coverage area of cortical bone surrounding the zygomatic implant significantly influenced biomechanical performance of the zygomatic implants.

Current Clinical Perspectives on Takotsubo Syndrome: Comprehensive analysis of Diagnosis, Management, and Pathophysiology

Current Clinical Perspectives on Takotsubo Syndrome: Comprehensive analysis of Diagnosis, Management, and Pathophysiology

Advanced Management of Mucoceles: Clinical Perspectives and Modern Treatment Techniques

Advanced Management of Mucoceles: Clinical Perspectives and Modern Treatment Techniques

Can We Better Understand, Diagnose, and Treat Ketamine-Induced Uropathy, and Can It Be Reversed? ICI-RS 2024.

Ketamine, a versatile anesthetic, has seen increased recreational use, leading to significant health issues, including ketamine-induced uropathy (KIU). KIU manifests with lower urinary tract symptoms (LUTS) and can involve the upper urinary tract. This study aims to provide a comprehensive overview of KIU, addressing its pathophysiology, diagnostic strategies, and treatment options; and to define/identify future research priorities. During the 2024 meeting of the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, a dedicated Proposal (P) convened to explore KIU. This initiative involved a thorough review of existing literature, expert presentations, and consensus-driven discussions. The methodology ensured a comprehensive exploration of KIU from both clinical and pre-clinical perspectives, leading to actionable research recommendations. Understanding the mechanisms of KIU is crucial for developing effective treatment options targeting specific pathophysiological pathways. Key findings include bladder fibrosis driven by transforming growth factor-β1 (TGF-β1), elevated purinergic responses and upregulated P2X1 purinoceptor expression, decreased barrier function due to increased expression of antiproliferative factor (APF), and functional loss of the bladder through Cav1.2 channel blockade. Research indicates that fibrosis, typically considered irreversible, may be mitigated. However, the exact timing and extent of fibrosis initiation and its impact on long-term outcomes require further research. LUTS typically improve after ketamine cessation but relapse upon resumption, indicating a hypersensitivity mechanism involving elevated serum IgE levels. Advanced stages of KIU do not always correlate with LUTS severity, shedding light on potential systemic effects and the need for evaluating liver enzymes. Furthermore, psychological dependency on ketamine, due to its positive perceptive and mood-altering effects, complicates cessation efforts. Long-term management requires a holistic approach, integrating medical treatments and supportive measures to help patients navigate life with potentially irreversible complications. This comprehensive review spans from fundamental pathology to practical clinical management, addressing both urological and systemic complications, and bridging insights from animal models to human applications. Developing effective treatment strategies necessitates addressing both the physical and psychological aspects of ketamine dependency.

Bridging the gap: unlocking the potential of emerging drug therapies for brain metastasis.

Brain metastasis (BrM) remains an unmet clinical need in advanced cancers with an increasing incidence and poor prognosis. The limited response to various treatments is mainly derived from the presence of the substantive barrier, blood-brain barrier (BBB) and brain-tumor barrier (BTB), which hinders the access of potentially effective therapeutics to the metastatic tumor of brain. Recently, the understanding of the structural and molecular features of the BBB/BTB has led to the development of efficient strategies to enhance BBB/BTB permeability and deliver drugs across the BBB/BTB to elicit the antitumor response against BrM. Meanwhile, novel agents capable of penetrating the BBB have rapidly developed and evaluated in pre-clinical studies and clinical trials, with both targeted therapies and immunotherapies demonstrating impressive intracranial activity against BrM. In this review, we summarize the recent advances in the biological properties of the BBB/BTB, and the emerging strategies for BBB/BTB permeabilization and drug delivery across the BBB/BTB. We also discuss the emerging targeted therapies and immunotherapies against BrM tested in clinical trials. Additionally, we provide our viewpoints on accelerating clinical translation of novel drugs into clinic for patients of BrM. Although still facing challenges, we expect this review to benefit the future development of novel therapeutics specifically from clinical perspective.

Mesenchymal stem cell application in pulmonary disease treatment with emphasis on their interaction with lung-resident immune cells

Due to the vital importance of the lungs, lung-related diseases and their control are very important. Severe inflammatory responses mediated by immune cells were among the leading causes of lung tissue pathology and damage during the COVID-19 pandemic. In addition, uncontrolled immune cell responses can lead to lung tissue damage in other infectious and non-infectious diseases. It is essential to control immune responses in a way that leads to homeostasis. Immunosuppressive drugs only suppress inflammatory responses and do not affect the homeostasis of reactions. The therapeutic application of mesenchymal stem cells (MSCs), in addition to restoring immune homeostasis, can promote the regeneration of lung tissue through the production of growth factors and differentiation into lung-related cells. However, the communication between MSCs and immune cells after treatment of pulmonary diseases is essential, and investigating this can help develop a clinical perspective. Different studies in the clinical phase showed that MSCs can reverse fibrosis, increase regeneration, promote airway remodeling, and reduce damage to lung tissue. The proliferation and differentiation potential of MSCs is one of the mechanisms of their therapeutic effects. Furthermore, they can secrete exosomes that affect the function of lung cells and immune cells and change their function. Another important mechanism is that MSCs reduce harmful inflammatory responses through communication with innate and adaptive immune cells, which leads to a shift of the immune system toward regulatory and hemostatic responses.

Clinical, genomic, and proteomic perspectives in the analysis of comorbid conditions in type 2 diabetes mellitus: a retrospective study.

Type-2 Diabetes Mellitus (T2DM) affects millions globally, with escalating rates. It often leads to undiagnosed complications and commonly coexists with other health conditions. This study investigates two types of prevalent comorbidities related to T2DM-the circulatory system (DCM1) and digestive system diseases (DCM2)-using clinical, genomic and proteomic datasets. The aim is to identify new biomarkers by applying existing machine learning (ML) based techniques for early detection, prognosis and diagnosis of these comorbidities. Here, we report a cross-sectional retrospective analysis from a T2DM dataset of T2DM associated concordant comorbidities (diseases with shared pathophysiology and management) from the Diastrat cohort (a T2DM cohort) recruited at the Northern Ireland Centre for Stratified Medicine (NICSM), in Northern Ireland. In the clinical data analysis, we identified that lipidemia was shown to negatively correlate with depression in the DCM1 group while positively correlate with depression in the DCM2 group. In genomic analysis, we identified statistically significant variants rs9844730 in procollagen-lysine (PLOD2), rs73590361 in beta-1,4-N-acetyl- galactosaminyl-transferase (B4GALNT3) and rs964680 in A kinase (PRKA) anchor protein 14 (AKAP14) which appear to differentiate DCM1 and DCM2 groups. In proteomic analysis, we identified 4 statistically significant proteins: natriuretic peptides B (BNP), pro-adrenomedullin (ADM), natriuretic peptides B (NT-proBNP) and discoidin (DCBLD2) that can differentiate DCM1 and DCM2 groups and have built robust ML model using clinical, genomic, and proteomic markers (0.83 receiver operative characteristics curve area, 84% positive predictive value and 83% negative predictive value and a classification accuracy of 83%) for prediction of DCM1 and DCM2 groups. Our study successfully identifies novel clinical, genomic, and proteomic biomarkers that differentiate between circulatory and digestive system comorbidities in Type-2 Diabetes Mellitus patients. The machine learning model we developed demonstrates strong predictive capabilities, providing a promising tool for the early detection, prognosis, and diagnosis of these T2DM-associated comorbidities. These findings have the potential to enhance personalized management strategies for patients with T2DM, ultimately improving clinical outcomes. Further research is needed to validate these biomarkers and integrate them into clinical practice.

Conductive polyphenol microneedles coupled with electroacupuncture to accelerate wound healing and alleviate depressive-like behaviors in diabetes

Inflammation and depression are serious complications of diabetes that interact to form a feedback loop and may hinder diabetic wound healing. They share a common pathophysiological basis of abnormal interactions between diabetic wounds and the brain. Here, we propose a strategy combining electroacupuncture (EA) stimulation of the Dazhui acupoint (GV14) with polyphenol-mediated conductive hydrogel microneedles to promote diabetic wound healing and alleviate depression through local wound–brain interactions. The conductive microneedles comprised methacrylated gelatin, dopamine (DA), DA-modified poly(3,4-ethylenedioxythiophene), and Lycium barbarum polysaccharide. EA at GV14 activated the vagus–adrenal axis to inhibit systemic inflammation while DA coupled electrical signals for long-term inhibition of local wound inflammation. EA at GV14 was also found to elevate 5-hydroxytryptamine levels in rats with diabetic wounds, consequently mitigating depressive-like behaviors. Additionally, the polyphenol-mediated conductive hydrogel microneedles, and coupled with EA stimulation promoted healing of wound tissue and peripheral nerves. This strategy regulated both local and systemic inflammation while alleviating depressive-like behaviors in diabetic rats, providing a new clinical perspective for the treatment of diabetes-related and emotional disorders.

Absolute and relative outcomes of cognitive behavior therapy for eating disorders in adults: a meta-analysis

ABSTRACT Cognitive–behavioral therapy (CBT) is the best examined treatment for eating disorders. However, previous meta-analyses of cognitive–behavioral therapy have not examined absolute outcomes, which are important from a clinical perspective. We updated a meta-analysis and conducted new searches in PubMed, Embase, PsycINFO and CINAHL. We included randomized trials comparing CBT with control conditions in adults with a diagnosed eating disorder. We used random effects models in all analyses. We included 36 trials with 44 comparisons between CBT and controls (2,809 participants), 22 trials on binge eating disorder (BED), 11 on bulimia nervosa (BN), and three on anorexia nervosa and mixed disorders. The overall effect of CBT compared to controls was g = 0.88 (95% CI: 0.71; 1.04), with high heterogeneity (I 2 = 74; 95% CI: 65; 81; PI: −0.06; 1.81) and no significant difference between BED and BN. Effects were smaller studies with low risk of bias. The absolute abstinence rate was 0.36 (95% CI: 0.31; 0.43) for CBT and 0.10 (95% CI: 0.08; 0.12) in controls. ly effective in the treatment of bulimia nervosa and binge-eating disorder, but there is also a large group of patients who do not respond sufficiently.

Effectiveness of phentolamine mesylate, vibration and photobiomodulation in reducing pain and the reversal of local anesthesia: A systematic review.

Dental anesthesia administration often triggers unpleasant sensations, particularly needle injection-related pain, which can evoke fear among patients, especially in the pediatric population. Vibration and low-level laser therapy (LLLT) have been extensively studied as potential methods for alleviating pain. Additionally, phentolamine mesylate (PM) has shown promise in reducing the duration of anesthesia. From a clinical perspective, inadequate control over the persistence of the anesthetic effect may lead to complications associated with its prolonged duration, such as self-injuries or functional impairments. This review aimed to systematically summarize and compare methods of alleviating pain during local anesthesia and reducing its duration. In November 2023, an electronic search was systematically conducted across PubMed, Web of Science, and Scopus databases using keywords (pain) AND (anesthesia) AND ((phentolamine) or (vibration) or (LLLT) OR (PBM)). The initial pool consisted of 495 records, from which 241 duplicates were eliminated. After careful examination of the remaining articles, 40 were included. The study adhered to the PRISMA guidelines. Most studies reported beneficial effects of LLLT and vibration; however, some did not corroborate these findings. Four studies had inconclusive results. Regarding anesthesia duration involving PM and LLLT, the majority of studies exhibited notable reductions, although no significant differences were revealed in 1 study. Vibration and LLLT appear to be advantageous methods in alleviating pain associated with local anesthesia administration. Phentolamine mesylate and LLLT are efficient in reversing local anesthesia.

Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective

Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective

Using case-based learning to teach evidence-based practice: A pilot study.

The American Speech-Language-Hearing Association (ASHA) promotes the use of evidence-based practice (EBP) in the provision of clinical services by speech-language pathologists (SLPs). Therefore, training in the EBP process is vital in the education of future SLPs. Case-based learning (CBL) has been found effective in facilitating transfer of knowledge and skills in various fields; however, its utilisation to teach EBP to SLP students is understudied. This phenomenological investigation explores the use of CBL, an active learning strategy that gives students the opportunity to practice application of knowledge to realistic scenarios, to teach EBP to graduate SLP students. Graduate SLP students worked in small groups to complete an article review activity centred around an assigned hypothetical clinical case. Students submitted article review papers and written reflections on their learning process. The written reflections and review papers were analysed using qualitative content analysis to understand students' approach to clinical cases and their perspectives on the CBL approach. Analysis of the papers and reflections indicated that students tended to rely heavily on scientific evidence for clinical decision making, often to the exclusion of clinical expertise or client perspectives. Students reported that the project was applicable to their future clinical practice. Further, they reported learning from multiple sources, including the instructor, class discussion and their peers. Results indicate that graduate SLP students found CBL activities beneficial for learning the principles of EBP. Students specifically indicated an appreciation for the realistic nature of the activities. Future applications are examined.

Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease

Hemoglobinopathies, namely β-thalassemia and sickle cell disease (SCD), are hereditary diseases, characterized by molecular genetic aberrations in the beta chains of hemoglobin. These defects affect the normal production of hemoglobin with severe anemia due to less or no amount of beta globins in patients with β-thalassemia (quantitative disorder), while SCD is a serious disease in which a mutated form of hemoglobin distorts the red blood cells into a crescent shape at low oxygen levels (qualitative disorder). Despite the revolutionary progress in recent years with the approval of gene therapy and gene editing for specific patients, there is an unmet need for highlighting the mechanisms influencing hemoglobin production and for the development of novel drugs and targeted therapies. The identification of the transcription factors and other genetic modifiers of hemoglobin expression is of utmost importance for discovering novel therapeutic approaches for patients with hemoglobinopathies. The aim of this review is to describe these complex molecular mechanisms and pathways affecting hemoglobin expression and to highlight the relevant investigational approaches or pharmaceutical interventions focusing on restoring the hemoglobin normal function by linking the molecular background of the disease with the clinical perspective. All the associated drugs increasing the hemoglobin expression in patients with hemoglobinopathies, along with gene therapy and gene editing, are also discussed.

Screening for Adverse Childhood Experiences: A Critical Appraisal.

Adverse childhood experiences (ACEs) are common and can impact health across the life course. Thus, it is essential for professionals in child- and family-serving roles, including pediatric and adult primary care clinicians, to understand the health implications of childhood adversity and trauma and respond appropriately. Screening for ACEs in health care settings has received attention as a potential approach to ACEs identification and response. Careful examination of the existing evidence on ACEs screening and consideration, from a clinical and ethical perspective, of the potential benefits, challenges, and harms is critical to ensuring evidence-informed practice. In this critical appraisal, we synthesize existing systematic and scoping reviews on ACEs screening, summarize recent studies on the ability of ACEs to predict health outcomes at the individual level, and provide a comprehensive overview of potential benefits, challenges, and harms of ACEs screening. We identify gaps in the existing evidence base and specify directions for future research. We also describe trauma-informed, relational care as an orientation and perspective that can help pediatric and primary care clinicians to sensitively assess for and respond to ACEs and other potentially traumatic experiences. Overall, we do not yet have sufficient evidence regarding the potential benefits, challenges, and harms of ACEs screening in health care and other settings. In the absence of this evidence, we cannot assume that screening will not cause harm and that potential benefits outweigh potential harms.

Extending Complexity to Word-Final Position via Telepractice: Intervention Effects for English-Speaking Children With Speech Sound Disorder.

Phonologically complex targets (e.g., [pl-]) are understood to facilitate widespread gains following speech sound intervention, and yet, available research largely features word-initial clusters. The present study investigates intervention effects following treatment of complex clusters presented in word-final position. Importantly, this allows for an added layer of complexity via suffixes that mark tense and agreement. Eight English-speaking children with speech sound disorder (SSD; 3;3-6;9 [years;months]) participated in 18 one-on-one intervention sessions. Intervention was completed via telepractice, as were all pre- and post-intervention assessments. Intervention targets were word-final two-element consonant clusters that were unknown to the child prior to intervention. Targets were presented in verbs that were either monomorphemic (i.e., [-ks]; they mix) or bimorphemic (i.e., [-ks]; she pick/3s, marked for third-person singular). All participants demonstrated change across multiple phonological measures. More stringently, six of eight participants demonstrated generalization to untreated sounds and untreated words immediately following intervention, including four of four children with monomorphemic targets. Importantly, positive changes for children with both target types were observed following a relatively short course of intervention (18 sessions over 6 weeks), and mastery of the target cluster was not required for phonological growth to occur. Results align with available work featuring word-initial complex targets and indicate that word-final consonant clusters are feasible, effective targets for English-speaking children with SSD. Findings similarly affirm the use of telepractice to deliver research-based interventions. Speech-language pathologists may thus integrate these findings with their clinical judgment and client perspectives to implement such targets in clinical practice.

Beyond a constant proton relative biological effectiveness: A survey of clinical and research perspectives among proton institutions in Europe and the United States.

Although proton relative biological effectiveness (RBE) depends on factors like linear energy transfer (LET), tissue properties, dose, and biological endpoint, a constant RBE of 1.1 is recommended in clinical practice. This study surveys proton institutions to explore activities using functionalities beyond a constant proton RBE. Research versions of RayStation integrate functionalities considering variable proton RBE, LET, proton track-ends, and dirty dose. A survey of 19 institutions in Europe and the United States, with these functionalities available, investigated clinical adoption and research prospects using a 25-question online questionnaire. Of the 16 institutions that responded (84% response rate), 13 were clinically active. These clinical institutions prescribe RBE=1.1 but also employ planning strategies centered around special beam arrangements to address potentially enhanced RBE effects in serially structured organs at risk (OARs). Clinical plan evaluation encompassed beam angles/spot position (69%), dose-averaged LET (LETd) (46%), and variable RBE distributions (38%). High ratings (discrete scale: 1-5) were reported for the research functionalities using linear LETd-RBE models, LETd, track-end frequency and dirty dose (averages: 4.0-4.8), while LQ-based phenomenological RBE models dependent on LETd scored lower for optimization (average: 2.2) but congruent for evaluation (average: 4.1). The institutions preferred LET reported as LETd (94%), computed in unit-density water (56%), for all protons (63%), and lean toward LETd-based phenomenological RBE models for clinical use (>50%). Proton institutions recognize RBE variability but adhere to a constant RBE while actively mitigating potential enhancements, particularly in serially structured OARs. Research efforts focus on planning techniques that utilize functionalities beyond a constant RBE, emphasizing standardized LET and RBE calculations to facilitate their adoption in clinical practice and improve clinical data collection. LETd calculated in unit-density water for all protons as input to adaptable phenomenological RBE models was the most suggested approach, aligning with predominant clinical LET and variable RBE reporting.

Comparison of Cognitive Functions Between Individuals With Chronic Low Back Pain With High and Low Pain Catastrophizing and Pain-free Controls: A Cross-sectional Study.

Researchers suggested that the interruptive effects of chronic pain on cognitive functions may be modulated by the level of pain catastrophizing (PC). However, in individuals with chronic low back pain (CLBP), domains of cognitive function that may be affected by the level of PC remain largely unclear. Therefore, this study aimed to compare cognitive functions between individuals with CLBP with high and low PC and pain-free controls. This cross-sectional study examined cognitive functions of 42 individuals with CLBP and 21 pain-free controls. The PC scale was used to stratify participants with CLBP into high and low PC. Participants performed 5 cognitive tests from the Cambridge Neuropsychological Test Automated Battery, namely 5-choice reaction time, rapid visual processing, spatial working memory, attention switching task, and stop signal task. The statistical analyses revealed that compared with individuals with CLBP with low PC and pain-free controls, individuals with high PC demonstrated greater values of the between errors ( P =0.01), reaction latency ( P <0.001), and stop signal reaction time variables ( P =0.004, 0.003, respectively) but lower values of probability of hit ( P =0.02, 0.01, respectively), A' ( P =0.01, <0.001, respectively), and percent correct trials variables ( P =0.002, <0.001, respectively). The results of the current study showed deficits in sustained attention, working memory, cognitive flexibility, and inhibitory control in individuals with CLBP with high PC. From a clinical perspective, therapeutic interventions targeting PC should be considered to decrease catastrophic thinking about pain in individuals with CLBP. Additional research is warranted to explore cognitive functioning as an outcome of these interventions in individuals with CLBP.