Clinical Perspective Research Articles

Physician-Modified Endografts for Repair of Complex Abdominal Aortic Aneurysms: Clinical Perspectives and Medico-Legal Profiles

Physician-Modified Endografts for Repair of Complex Abdominal Aortic Aneurysms: Clinical Perspectives and Medico-Legal Profiles

A new perspective on OSAS cases with the Baveno classification

ABSTRACT Objective/Background Since the apnea-hypopnea index (AHI), which is used in the diagnosis and grading of OSAS, does not adequately reflect the clinical perspective of the disease, the Baveno classification of OSA was developed, which allows multicomponent evaluation of OSAS patients. The aim of our study was to evaluate the application of the Baveno classification in clinical practice. Patients/Methods A prospective study was performed on patients diagnosed with OSAS between January 2021 and June 2022. Patients were divided into 4 groups according to Baveno classification (Groups A-D) and three groups as mild, moderate, and severe OSAS according to AHI. Results A total of 378 patients (70% male, mean age 48.68 ± 11.81 years) were included in the study. The patients had mild (n: 75; 20%), moderate (n: 88; 23%), and severe (n: 215; 57%) OSAS. According to Baveno classification, patients were included in Groups A (n: 90; 24%), B (n: 105 (28%), C (n: 65; 17%), and D (n: 118; 31%). The mean AHIs of the Baveno groups were similar (p = 0.116). Oxygen desaturation index (ODI) was higher in Groups B and D compared to Group A. The duration of T90 desaturation was longer in Groups C and D compared to Groups A and B (p < 0.05). Conclusions The Baveno classification divided our OSAS cases into equivalent groups. One out of every four patients with mild OSAS was in Group D. This data was noteworthy in that the Baveno classification allows for the identification of symptomatic and comorbid patients with mild OSAS according to AHI and for the application of more effective treatments to these patients. Patients with comorbidities experienced oxygen desaturation for a longer period of time at night, and oxygenation deteriorated in patients with prominent symptoms. Baveno classification was found to be a more reasonable and easily applicable approach in clinical practice.

A clinical perspective on the revised criteria for diagnosis and staging of Alzheimer's disease.

A clinical perspective on the revised criteria for diagnosis and staging of Alzheimer's disease.

Toward a new clinical pragmatism: method in clinical ethics consultation.

In this paper, I leverage the pragmatist tradition in philosophy, the collective wisdom of scholarship in clinical ethics consultation, and earlier attempts to apply pragmatism in clinical ethics to develop a new vision of clinical ethics practice called New Clinical Pragmatism. It argues that clinical ethics methodology, from the New Clinical Pragmatist's perspective, amounts to the recommendation that consultants should customize a methodological approach, drawing on the various available methods, depending on the demands of the specific case, and should avoid attempts to identify a 'true' methodology but to the incoherence and inevitable failure of those attempts. I argue that pragmatism's emphasis on practical wisdom and experimentation allow the New Clinical Pragmatist to do this while avoiding irrationality in choosing methods. I discuss how the New Clinical Pragmatist gives a unique, constructive perspective on key aspects of clinical ethics consultation such as the choice of common morality vs. internal morality of medicine approaches, process standards, bioethics mediation, and narrative ethics, and suggest how New Clinical Pragmatism's relaxed approach to choice of methodology encourages consultants to balance attention to the particulars of the case with knowledge of what the many insightful scholars of clinical ethics methodology have found useful in the past. I also argue that New Clinical Pragmatism is consistent with efforts to professionalize clinical ethics consultation.

Lipids shape brain function through ion channel and receptor modulations: physiological mechanisms and clinical perspectives.

Lipids represent the most abundant molecular type in the brain with a fat content of approximately 60% of the dry brain weight in humans. Despite this fact, little attention has been paid to circumscribe the dynamic role of lipids in brain function and disease. Membrane lipids such as cholesterol, phosphoinositide, sphingolipids, arachidonic acid and endocannabinoids finely regulate both synaptic receptors and ion channels that insure critical neural functions. After a brief introduction on brain lipids and their respective properties, we review here their role in regulating synaptic function and ion channel activity, action potential propagation, neuronal development, functional plasticity and their contribution in the development of neurological and neuropsychiatric diseases. We also provide possible directions for future research on lipid function in brain plasticity and diseases.

Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adipose-liver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and FMT. Understanding the immunological mechanisms underlying in SLD is crucial for advancing clinical therapeutic strategies.

Dyskinetic Cerebral Palsy in Children: Clinical Perspectives on Common Comorbidities and Health-Related Quality of Life.

The data on specific comorbidities in children with dyskinetic cerebral palsy (DCP) is limited. We evaluated the pattern of comorbidities and health related quality of life (HRQOL) in these children and compared them between etiological and motor impairment subgroups. This cross-sectional study was conducted over 18 months in children with DCP of both sex, and age between one and 14 years. Comorbidities were assessed using standardized scales such as gross motor functioning scale (GMFCS), developmental profile-3 (DP-3), developmental behaviour checklist, sleep behaviour questionnaire (SBQ), and caregiver questionnaire. Sixty-five children with DCP were evaluated (hyperbilirubinemia n = 43, 66% and perinatal asphyxia n = 19, 29%). The majority of children were severely affected in gross motor functioning (level IV 29.2% and level V 53.8%). Epilepsy was seen in 21.5% of cases (19% in hyperbilirubinemia and 32% in asphyxia, p = 0.4). The mean age of onset of seizures was 15.4 + 20.6 months (range 2-72). Visual problems were seen in 54% of cases and included upgaze palsy, squint, refractive error, optic atrophy and cortical blindness. A significant proportion of children with hyperbilirubinemia had upgaze palsy as compared to those with perinatal asphyxia (70% vs. 32%, p 0.01). Rest of the visual problems were not significantly different between the two etiological subgroups. Drooling (87.6%), protein-energy malnutrition (66.6%), and reflux (57%) were the most common gastrointestinal problems in children with DCP. Children with DCP showed problems in social relating (33.8%), anxiety (26.2%), and self-absorbed behaviour (7.7%). However, there were no statistically significant differences between the etiological, motor impairment and age-based subgroups. Children with DCP had high scores on SBQ, suggesting sleep problems. Sleep scores were similar in the hyperbilirubinemia and perinatal asphyxia subgroups. Greater sleep problems were noted in children aged < 4y (70.6 + 10.1 vs. 56.5 + 11.3, p < 0.05 as compared to children above 4y of age) and severe motor impairments (68.2 + 11.3 vs. 57.2 + 13.1, p 0.008 as compared to mild-moderate motor impairment). Poor overall developmental scores were seen in 61.5% children and were significantly associated with GMFCS (p 0.04). The majority of children showed impairments in physical (58.5%), adaptive behaviour (58.5%), social-emotional (50.8%), cognitive (60%) and communication (52%) subscales of DP-3. Cognitive impairment was similar in the etiological (hyperbilirubinemia vs. perinatal asphyxia, p = 0.3), and motor impairment (mild-moderate vs. severe, p = 0.9) subgroups. HRQOL was significantly affected by motor impairment in positioning-transfer (p value 0.0001), and interaction-communication domains (p value 0.0001), however, there was no difference based on the etiology of hyperbilirubinemia and asphyxia. Children with DCP demonstrate several comorbidities and impaired quality of life. These are similar in hyperbilirubinemia and perinatal asphyxia cohorts, expect for significant proportion of upgaze palsy in DCP secondary to hyperbilirubinemia. Younger children have more problematic behaviour and impaired sleep quality. Severe motor disability influences the developmental outcomes, cognition, sleep and HRQOL in children with DCP.

Understanding the treatment response and resistance to targeted therapies in non-small cell lung cancer: clinical insights and perspectives

Understanding the treatment response and resistance to targeted therapies in non-small cell lung cancer: clinical insights and perspectives

A scoping review and theory-informed conceptual model of professional identity formation in medical education: Commentary from a clinical psychology perspective.

A scoping review and theory-informed conceptual model of professional identity formation in medical education: Commentary from a clinical psychology perspective.

A scoping review and theory-informed conceptual model of professional identity formation in medical education: Commentary from a clinical psychology perspective.

A scoping review and theory-informed conceptual model of professional identity formation in medical education: Commentary from a clinical psychology perspective.

A Review on the Form and Complexity of Human–Robot Interaction in the Evolution of Autonomous Surgery

As robotics and intelligence increasingly integrate into surgery, the pivotal role of human–robot interaction (HRI) in surgical procedures and outcomes becomes evident. However, debate rages over whether increasing robot autonomy will result in less human involvement. Some scholars assert that autonomy will reduce human participation, whereas others contend it will result in more complex interactions. To reveal the role of HRI in the evolution of autonomous surgery, this review systematically explores the HRI of robotic surgery with various levels of autonomy. The HRI is examined from both robotic science and clinical practice perspectives, incorporating relevant case studies. Two key components, intention detection and situation awareness, are especially concerned with a brief description of the interfaces and control strategies they rely on. Additional insights are drawn from analogous technologies in aviation, industrial robotics, and autonomous vehicles. The analysis suggests that HRI complexity tends to increase as the robot transitions from no autonomy to conditional autonomy and is predicted to subsequently decrease with a substantial shift in the interaction form when moving toward full autonomy. It is concluded by highlighting challenges from technical and clinical perspectives and delineating research trends in this rapidly evolving field.

The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives

Wilson’s disease (WD) is inherited in an autosomal recessive manner and is caused by pathogenic variants of the ATP7B gene, which are responsible for impaired copper transport in the cell, inhibition of copper binding to apoceruloplasmin, and biliary excretion. This leads to the accumulation of copper in the tissues. Copper accumulation in the CNS leads to the neurological and psychiatric symptoms of WD. Abnormalities of copper metabolism in WD are associated with impaired iron metabolism. Both of these elements are redox active and may contribute to neuropathology. It has long been assumed that among parenchymal cells, astrocytes have the greatest impact on copper and iron homeostasis in the brain. Capillary endothelial cells are separated from the neuropil by astrocyte terminal legs, putting astrocytes in an ideal position to regulate the transport of iron and copper to other brain cells and protect them if metals breach the blood–brain barrier. Astrocytes are responsible for, among other things, maintaining extracellular ion homeostasis, modulating synaptic transmission and plasticity, obtaining metabolites, and protecting the brain against oxidative stress and toxins. However, excess copper and/or iron causes an increase in the number of astrocytes and their morphological changes observed in neuropathological studies, as well as a loss of the copper/iron storage function leading to macromolecule peroxidation and neuronal loss through apoptosis, autophagy, or cuproptosis/ferroptosis. The molecular mechanisms explaining the possible role of glia in copper- and iron-induced neurodegeneration in WD are largely understood from studies of neuropathology in Parkinson’s disease and Alzheimer’s disease. Understanding the mechanisms of glial involvement in neuroprotection/neurotoxicity is important for explaining the pathomechanisms of neuronal death in WD and, in the future, perhaps for developing more effective diagnostic/treatment methods.

The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives

The Role of Glia in Wilson’s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives

Clinical outcomes of interval training in cardiovascular disease populations: A clinical perspective.

Nearly 20 years have elapsed since the first clinical trial investigated the impact of interval training on patients with cardiovascular disease (CVD). This clinical corner discusses the health outcomes of systematic reviews and meta-analyses and appropriately powered randomized controlled trials (RCTs) which have tested these interval training programs across various CVDs (i.e., coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, and cardiac implantable electronic devices). The publications included in this clinical corner have shown that interval training leads to similar or superior improvements in V̇O2peak, functional capacity, pain free walking, QoL, anxiety, depression, and endothelial function, but the magnitude of improvements across varying protocols (e.g., length and number of work periods, intensities of work periods, duration of exercise sessions, frequency of exercise sessions, duration of program) and optimal dosage for males and females is unclear across CVD conditions. The heterogeneity in protocols, physical and mental health outcome measures, and lack of sex- and gender-based analyses calls for more high-quality research in this area.

Self-Collection for HPV Testing: Potential Issues Related to Performance Measures and Quality Improvement Among Federally Qualified Health Centers.

Most incident cases of cervical cancer in the United States are attributable to inadequate screening. Federally qualified health centers (FQHCs) serve a large proportion of women who are low-income, have no insurance, and are underserved-risk factors for insufficient cervical cancer screening. FQHCs must maintain quality measures to preserve their accreditation, address financial reimbursements, and provide quality care. Implementation of human papillomavirus (HPV) self-collection can improve cervical cancer screening coverage within FQHCs. To understand perspectives from clinical personnel on current cervical cancer screening rates at FQHCs in North Carolina and the impact of implementing HPV self-collection among underscreened patients on screening rates and performance measures. The study used focus groups and key informant interviews. Coding-based thematic analysis was applied to both focus group and interview transcripts. Emergent themes regarding perspectives on self-collection implementation were mapped onto Consolidated Framework for Implementation Research (CFIR) constructs to identify future barriers and facilitators to implementation. Two FQHCs in North Carolina and a cloud-based videoconferencing platform. Six FQHCs in North Carolina; 45 clinical and administrative staff from the 6 FQHCs; 1 chief executive officer (n = 6), 1 senior-level administrator (n = 6), 1 chief medical officer (n = 6), and 1 clinical data manager (n = 6) from each FQHC. Achievement of clinical perspectives. Societal-, practice-, and patient-level factors currently contribute to subpar cervical cancer screening rates. HPV self-collection was expected to improve screening uptake among underscreened women at FQHCs, and thus quality and performance measures, by offering an alternative screening approach for in-clinic or at-home use. Implementation barriers include financial uncertainties and HPV self-collection not yet a Food and Drug Administration-approved test. HPV self-collection has potential to improve cervical cancer screening quality and performance measures of FQHCs. For a successful implementation, multilevel factors that are currently affecting low screening uptake need to be addressed. Furthermore, the financial implications of implementation and approval of HPV self-collection as a test for cervical cancer screening quality measures need to be resolved.

Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.

Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.

Safety Implications of Modulating Nuclear Receptors: A Comprehensive Analysis from Non-Clinical and Clinical Perspectives

The unintended modulation of nuclear receptor (NR) activity by drugs can lead to toxicities amongst the endocrine, gastrointestinal, hepatic cardiovascular, and central nervous systems. While secondary pharmacology screening assays include NRs, safety risks due to unintended interactions of small molecule drugs with NRs remain poorly understood. To identify potential nonclinical and clinical safety effects resulting from functional interactions with 44 of the 48 human-expressed NRs, we conducted a systematic narrative review of the scientific literature, tissue expression data, and used curated databases (OFF-X™) (Off-X, Clarivate) to organize reported toxicities linked to the functional modulation of NRs in a tabular and machine-readable format. The top five NRs associated with the highest number of safety alerts from peer-reviewed journals, regulatory agency communications, congresses/conferences, clinical trial registries, and company communications were the Glucocorticoid Receptor (GR, 18,328), Androgen Receptor (AR, 18,219), Estrogen Receptor (ER, 12,028), Retinoic acid receptors (RAR, 10,450), and Pregnane X receptor (PXR, 8044). Toxicities associated with NR modulation include hepatotoxicity, cardiotoxicity, endocrine disruption, carcinogenicity, metabolic disorders, and neurotoxicity. These toxicities often arise from the dysregulation of receptors like Peroxisome proliferator-activated receptors (PPARα, PPARγ), the ER, PXR, AR, and GR. This dysregulation leads to various health issues, including liver enlargement, hepatocellular carcinoma, heart-related problems, hormonal imbalances, tumor growth, metabolic syndromes, and brain function impairment. Gene expression analysis using heatmaps for human and rat tissues complemented the functional modulation of NRs associated with the reported toxicities. Interestingly, certain NRs showed ubiquitous expression in tissues not previously linked to toxicities, suggesting the potential utilization of organ-specific NR interactions for therapeutic purposes.

Imaging of pediatric glioneuronal and neuronal tumors.

Glioneuronal tumors (GNTs) are an expanding group of primary CNS neoplasms, commonly affecting children, adolescents and young adults. Most GNTs are relatively indolent, low-grade, WHO grade I lesions. In the pediatric age group, GNTs have their epicenter in the cerebral cortex and present with seizures. Alterations in the mitogen-activated protein kinase (MAPK) pathway, which regulates cell growth, are implicated in tumorigenesis. Imaging not only plays a key role in the characterization and pre-surgical evaluation of GNTs but is also crucial role in follow-up, especially with the increasing use of targeted inhibitors and immunotherapies. In this chapter, we review the clinical and imaging perspectives of common pediatric GNTs.

Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: a microbiological and clinical perspective.

Pseudomonas aeruginosa is one of the most common nosocomial pathogens and part of the top emergent species associated with antimicrobial resistance that has become one of the greatest threat to public health in the twenty-first century. This bacterium is provided with a wide set of virulence factors that contribute to pathogenesis in acute and chronic infections. This review aims to summarize the impact of multidrug resistance on the virulence and fitness of P. aeruginosa. Although it is generally assumed that acquisition of resistant determinants is associated with a fitness cost, several studies support that resistance mutations may not be associated with a decrease in virulence and/or that certain compensatory mutations may allow multidrug resistance strains to recover their initial fitness. We discuss the interplay between resistance profiles and virulence from a microbiological perspective but also the clinical consequences in outcomes and the economic impact.