Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Long-Term Impact of Diabetic Retinopathy on Response to Anti-VEGF Treatment in Neovascular AMD.

Purpose: To explore the long-term effect of diabetic retinopathy on response to anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration-associated type 1 macular neovascularization (MNV) using optical coherence tomography angiography (OCTA). Methods: A total of 45 eyes with exudative neovascular age-related macular degeneration (nAMD) with type 1 MNV were included in the analysis. Among them, 24 eyes of 24 patients had no history of diabetes mellitus (DM) in their anamnesis and were assigned to the Not Diabetic group; 21 eyes of 21 patients had mild diabetic retinopathy and were included in the Diabetic group. We considered the following outcome measures: (1) best-corrected visual acuity changes; (2) central macular thickness; (3) MNV lesion area; and (4) MNV flow area. The OCTA acquisitions were performed at the following time points: (1) baseline visit, which corresponded to the day before the first injection; (2) post-loading phase (LP), which was scheduled at 1 month after the last LP injection; and (3) 12-month follow-up visit. Results: All morphofunctional parameters showed a significant improvement after the LP and at the 12-month follow-up visit. Specifically, both the Diabetic group and the Not Diabetic group displayed a significant reduction of MNV lesion areas at both the post-LP assessment (P = 0.026 and P = 0.016, respectively) and the 12-month follow-up (P = 0.039 and P = 0.025, respectively). Similarly, the MNV flow area was significantly decreased in both the Diabetic group and the Not Diabetic group at the post-LP assessment (P < 0.001 and P = 0.012, respectively) and at the 12-month follow-up (P = 0.01 and P = 0.035, respectively) compared to baseline. A smaller reduction in the MNV lesion area was observed in the Diabetic group at both the post-LP evaluation (P = 0.015) and the 12-month follow-up (P = 0.032). No other significant differences were found between the groups for the other parameters (P > 0.05). Conclusions: Our results indicated that the Diabetic group exhibited a smaller reduction in MNV lesion area after 12 months of anti-VEGF treatment. This highlights the importance of considering diabetic retinopathy as a potential modifier of treatment outcomes in nAMD management, with DM serving as a crucial risk factor during anti-angiogenic treatment.

Mathematical Modeling of Oxygen Diffusion from Capillary to Tissues during Hypoxia through Multiple Points Using Fractional Balance Equations with Memory.

The diffusion of oxygen through capillary to surrounding tissues through multiple points along the length has been addressed in many clinical studies, largely motivated by disorders including hypoxia. However relatively few analytical or numerical studies have been communicated. In this paper, as a compliment to physiological investigations, a novel mathematical model is developed which incorporates the multiple point diffusion of oxygen from different locations in the capillary to tissues, in the form of a fractional dynamical system of equations using the concept of system of balance equations with memory. Stability analysis of the model has been conducted using the well known Routh-Hurwitz stability criterion. Comprehensive analytical solutions for the differntial equation problem in the new proposed model are obtained using Henkel transformations. Both spatial and temporal variation of concentration of oxygen is visualized graphically for different control parameters. Close correlation with simpler models is achieved. Diffusion is shown to arise from different points of the capillary in decreasing order along the length of the capillary i.e. for the different values of z. The concentration magnitudes at low capillary length far exceed those further along the capillary. Furthermore with progrssive distance along the capillary, the radial distance of diffusion decreases, such that oxygen diffuses only effectively in very close proximity to tissues. The simulations provide a useful benchmark for more generalized mass diffusion computations with commercial finite element and finite volume software including ANSYS FLUENT.

Association Between Alcohol Consumption and Disability Accumulation in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Previous studies have indicated that alcohol consumption is associated with multiple sclerosis (MS) disease progression. We aimed to study the influence of alcohol consumption habits on disease progression and health-related quality of life in MS. METHODS: We categorized patients from 2 population-based case-control studies by alcohol consumption habits at diagnosis and followed them up to 15 years after diagnosis through the Swedish MS registry regarding changes in the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale 29 (MSIS-29). We used Cox regression models with 95% confidence intervals (CIs) using 24-week confirmed disability worsening, EDSS 3, EDSS 4, and physical and psychological worsening from the patient's perspective as end points. RESULTS: Our study comprised 9,051 patients with MS, with a mean age of 37.5 years at baseline/diagnosis. Compared with nondrinking, low and moderate alcohol consumption was associated with reduced risk of EDSS-related unfavorable outcomes (hazard ratios between 0.81 and 0.90) and with reduced risk of physical worsening. The inverse association was confined to relapsing-remitting MS and was more pronounced among women. High alcohol consumption did not significantly affect disease progression. The inverse relationship between low-moderate alcohol consumption and disability progression became stronger when we only included those who had not changed their alcohol consumption during follow-up (hazard ratios between 0.63 and 0.71). There were no differences in measures of disability at baseline between drinkers who continued drinking alcohol after diagnosis and those who later discontinued. Our findings speak against bias due to reverse causation. DISCUSSION: Low and moderate alcohol consumption was associated with more favorable outcomes in relapsing-remitting MS, compared with nondrinking, while there was no significant influence of high alcohol consumption on disease outcomes.

EFFECT OF THE CORRECTIONAL APPROACH ON THE REGULATION OF NEURAL FUNCTIONS IN CHILDREN WITH MENTAL DISABILITIES WITH INTERHEMISPHERIC BRAIN ASYMMETRY.

The degree of asymmetry in humans and the complication of mechanisms of interhemispheric interaction are formed mainly in the process of learning, but the impact of developmental teaching methods on the regulation of nervous functions in children with intellectual disability has been little developed. The aim of the work is to study the influence of developmental teaching methods on the regulation of nervous functions in children with mental development disorders and interhemispheric asymmetry of the brain. The information obtained in the data must be taken into account when organizing the learning process in the elementary school when working with mentally retarded children, when forming classes, when choosing programs, methods of teaching, when organizing psychological and pedagogical support. The age features of the brain associated with advanced development of right hemispheric functions are almost not used in it. Meanwhile, the active use of opportunities of the right hemispheric way of processing information, especially in elementary school, promotes the development of the child's abilities, allows to predict and increase the efficiency of school training. The functional contributions of the right and left hemispheres to the formation of the human psyche are assumed to be different because the hemispheres in their paired work function differently in time. The paired work is carried out in the present tense, so that the right hemisphere relies on the past, the left on the future tense. Therefore, the preservation of paired hemispheric functioning and structural integrity of the brain is the main condition, without which full-fledged mental activity cannot be formed.

ETIOLOGY, DIAGNOSIS AND TREATMENT OF MUSCLE-ARTICULAR DYSFUNCTION OF THE TEMPOROMANDIBULAR JOINT IN ADOLESCENCE.

Etiologic and pathogenetic aspects cause the most contentious issue in the study of temporomandibular joint (TMJ) syndrome in childhood and adolescence. Some researchers have linked the emergence of this group of diseases with abnormal occlusion, others have more emphasis on the age characteristics of a growing organism, or rather on a number of morphological and psychomotor processes arising and ending at puberty and cause physiological abnormalities in the growing organism. The aim of the study was to improve the method of complex treatment of TMJ dysfunction in adolescence by exploring its development factors with early diagnosis methods. MATERIAL AND METHODS: We have examined by clinical and radiological methods 33 patients with TMJ syndrome disorder between the ages of 11 to 18 years, 20 of them (60.6%) girls and 13 (39.4%) boys. All examined patients complained of the presence of clicks in the joint when they open mouth widely, irregular movement of the lower jaw when opening the mouth, the periodic occurrence of unilateral pain in the joint and the ear, increasing when taking rigid and solid food, which allowed us to establish the diagnosis of the TMJ syndrome. A clinical study has focused on the survey of patients, and in some cases their parents, in order to study carefully the history of life and disease, and the patient's complaints. We have found out the factors predisposing to the disease: the presence of various bad habits, family history, trauma of the lower jaw and TMJ, errors in orthodontic treatment. RESULTS: The data obtained showed that 16 (48.5%) patients had a history revealed various factors that contribute to the TMJ syndrome. The presence of various bad habits was about 38%. In addition, 13 (39.4%) patients reported the presence of emotional stress. The presence of orthodontic pathology was determined in 26 (78.8%) patients, 7 (21.2%) patients had no dentofacial disorders was not determined. The most common symptom, occurring in 27 (81.8%) patients was clicking in the joint with one or two sides, as well as excessive excursion of articular heads, occurring in 17 (51.5%) patients. A distinctive feature of TMJ syndrome manifestations in children and adolescents is relatively rare, in contrast to adults, the appearance of symptoms: pain when opening the mouth wide detected only 7 (21.2%) patients; pain in the joints - 8 (24.2%) patients; pain in the masticatory muscles - 6 (18.2%) patients. CONCLUSIONS: Based on the above, the etiological factors of musculo-articular dysfunction of the TMJ in adolescence can be not only dental anomalies, but also the presence of bad habits, disproportions in the growth of the bone and muscular skeleton and hypokinetic states caused by psychophysiological responses to chronic stress. Accordingly, treatment of patients with this pathology should be comprehensive and include not only treatment of the dental system, but also be aimed at the uniform development of the musculoskeletal system in children and at eliminating bad habits and chronic stress factors.

Current Management of Diverticulitis.

Over the last few decades, our understanding of the pathophysiology and natural history of sigmoid diverticulitis has greatly improved. This knowledge has challenged many of the traditional principles in the management for diverticulitis, such as routine antibiotic administration in all cases, number-based recommendations for elective surgery, and the necessity for an end colostomy in emergency surgery. This review will cover the breadth of management for sigmoid diverticulitis, covering both uncomplicated and complicated disease as well as elective and emergent disease presentations. New and emerging concepts in management will be highlighted with a particular focus on level-1 data, when available.

Efficient use of penile Doppler ultrasound for investigating men with erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction is the most common type of erectile dysfunction, and penile Doppler ultrasound (PDUS) is a useful tool to assess erectile hemodynamics in the clinician's effort to discuss prognosis and management strategies with the patient. AIM: We herein describe the PDUS protocol used at our center, including indications, technique, and data interpretation. METHODS: We describe our institutional experience with PDUS and discuss it in the context of a contemporary review of the literature for this investigation. OUTCOME: Our institutional PDUS protocol. RESULTS: To perform PDUS properly, adequate training, equipment, setting, technique, and interpretation are critical. The accuracy of PDUS is entirely predicated on achieving complete cavernosal smooth muscle relaxation. A redosing protocol optimizes the reliability and reproducibility of the hemodynamic data acquired during PDUS. A rigidity-based assessment is performed, and patients are scanned according to the erection rigidity achieved (full hardness) or by administration of maximum dose of the vasoactive agent. Peak systolic velocity is considered a measure of arterial inflow (normal, >30 cm/s), while end diastolic velocity evaluates the veno-occlusive mechanism (normal, <5 cm/s). After the procedure, the patient is evaluated to confirm detumescence. If the patient has a persistent penetration rigidity erection, intracavernosal phenylephrine is administered; however, if detumescence is not achieved with intracavernosal phenylephrine injections alone, corporal aspiration is potentially performed. CONCLUSION: PDUS is a valuable minimally invasive tool for erectile hemodynamics assessment and an accurate assessment of such, provided that complete cavernosal smooth muscle relaxation is achieved.

Mean nocturnal baseline impedance in gastro-esophageal reflux disease diagnosis: Should we strictly follow the Lyon 2 Consensus?

Clinical practice guidelines drive clinical practice and clinicians rely to them when trying to answer their most common questions. One of the most important position papers in the field of gastro-esophageal reflux disease (GERD) is the one produced by the Lyon Consensus. Recently an updated second version has been released. Mean nocturnal baseline impedance (MNBI) was proposed by the first Consensus to act as supportive evidence for GERD diagnosis. Originally a cut-off of 2292 Ohms was proposed, a value revised in the second edition. The updated Consensus recommended that an MNBI < 1500 Ohms strongly suggests GERD while a value > 2500 Ohms can be used to refute GERD. The proposed cut-offs move in the correct direction by diminishing the original cut-off, nevertheless they arise from a study of normal subjects where cut-offs were provided by measuring the mean value ± 2SD and not in symptomatic patients. However, data exist that even symptomatic patients with inconclusive disease or reflux hypersensitivity (RH) show lower MNBI values in comparison to normal subjects or patients with functional heartburn (FH). Moreover, according to the data, MNBI, even among symptomatic patients, is affected by age and body mass index. Also, various studies have proposed different cut-offs by using receiver operating characteristic curve analysis even lower than the one proposed. Finally, no information is given for patients submitted to on-proton pump inhibitors pH-impedance studies even if new and extremely important data now exist. Therefore, even if MNBI is an extremely important tool when trying to approach patients with reflux symptoms and could distinguish conclusive GERD from RH or FH, its values should be interpreted with caution.

What aspects do we overlook in the rehabilitation of patients with inflammatory bowel disease?

In this editorial, we comment on the article by Stafie et al. Inflammatory bowel disease (IBD) constitutes a cluster of chronic and progressive inflammatory disorders affecting the digestive system. IBD can impede an individual's capacity to perform daily activities, hinder work productivity, limit physical capabilities, and negatively impact medical outcomes. Although physical activity and structured exercise programs are becoming increasingly important in many chronic inflammatory diseases, they are not being sufficiently implemented in IBD patients. Effective prevention of future disability and drug dependence in IBD patients requires timely diagnosis and treatment of musculoskeletal problems, including sarcopenia, as well as decreased muscle strength, aerobic capacity, and bone mineral density. To improve treatment outcomes for IBD patients, it is crucial to develop individualized rehabilitation programs tailored to their unique needs. Equally critical is the active participation of pertinent departments in this process. It is imperative to highlight the significance of creating a personalized rehabilitation program with a multidisciplinary approach in IBD management.

Autoimmune Encephalitis.

OBJECTIVE: This article focuses on the clinical features and diagnostic evaluations that accurately identify patients with ever-expanding forms of antibody-defined encephalitis. Forms of autoimmune encephalitis are more prevalent than infectious encephalitis and represent treatable neurologic syndromes for which early immunotherapies lead to the best outcomes. LATEST DEVELOPMENTS: A clinically driven approach to identifying many autoimmune encephalitis syndromes is feasible, given the typically distinctive features associated with each antibody. Patient demographics alongside the presence and nature of seizures, cognitive impairment, psychiatric disturbances, movement disorders, and peripheral features provide a valuable set of clinical tools to guide the detection and interpretation of highly specific antibodies. In turn, these clinical features in combination with serologic findings and selective paraclinical testing, direct the rationale for the administration of immunotherapies. Observational studies provide the mainstay of evidence guiding first- and second-line immunotherapy administration in autoimmune encephalitis and, whereas these typically result in some clinical improvements, almost all patients have residual neuropsychiatric deficits, and many experience clinical relapses. An improved pathophysiologic understanding and ongoing clinical trials can help to address these unmet medical needs. ESSENTIAL POINTS: Antibodies against central nervous system proteins characterize various autoimmune encephalitis syndromes. The most common targets include leucine-rich glioma inactivated protein 1 (LGI1), N-methyl-d-aspartate (NMDA) receptors, contactin-associated proteinlike 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Each antibody-associated autoimmune encephalitis typically presents with a recognizable blend of clinical and investigation features, which help differentiate each from alternative diagnoses. The rapid expansion of recognized antibodies and some clinical overlaps support panel-based antibody testing. The clinical-serologic picture guides the immunotherapy regime and offers valuable prognostic information. Patient care should be delivered in conjunction with autoimmune encephalitis experts.

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

OBJECTIVE: Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. LATEST DEVELOPMENTS: Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. ESSENTIAL POINTS: It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

Paraneoplastic Neurologic Disorders.

OBJECTIVE: This article reviews the clinical presentations, neural antibody associations, and oncologic accompaniments of paraneoplastic neurologic syndromes and neurologic autoimmunity in the context of immune checkpoint inhibitor (ICI) cancer immunotherapy. LATEST DEVELOPMENTS: Neural antibody discovery has improved the diagnosis of paraneoplastic neurologic syndromes. Neural antibodies also delineate the underlying disease pathophysiology and thus inform outcomes and treatments. Neural antibodies specific for extracellular proteins have pathogenic potential, whereas antibodies specific for intracellular targets are biomarkers of a cytotoxic T-cell immune response. A recent update in paraneoplastic neurologic syndrome criteria suggests high- and intermediate-risk phenotypes as well as neural antibodies to improve diagnostic accuracy in patients with paraneoplastic neurologic syndromes; a score was created based on this categorization. The introduction of ICI cancer immunotherapy has led to an increase in cancer-related neurologic autoimmunity with distinct clinical phenotypes. ESSENTIAL POINTS: Paraneoplastic neurologic syndromes reflect an ongoing immunologic response to cancer mediated by effector T cells or antibodies. Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis, and neural antibodies aid diagnosis, focus cancer screening, and inform prognosis and therapy. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. ICI therapy has led to immune-mediated neurologic complications. Recognition and treatment lead to improved outcomes.

Pediatric Autoimmune Neurologic Disorders.

OBJECTIVE: This article discusses common principles in diagnosing and managing autoimmune neurologic conditions in children. LATEST DEVELOPMENTS: The key to improving outcomes in all patients with autoimmune neurologic diseases is making an early diagnosis, promptly initiating treatment, and identifying patients who will benefit from long-term maintenance treatment. Some neuroinflammatory syndromes can be diagnosed with an antibody biomarker (eg, aquaporin-4 antibodies, N-methyl-d-aspartate [NMDA] receptor antibodies), whereas others require clinical diagnostic criteria (eg, multiple sclerosis, opsoclonus-myoclonus syndrome). A proportion of children will be labeled as seronegative, and further investigations for other inflammatory or monogenetic etiologies need to be carried out in parallel with treating the central nervous system inflammation. Time to treatment and treatment escalation were shown to correlate with outcomes in many patients with these disorders. The choice and duration of treatment should be evaluated considering side effects and risks in the short and long terms. The presence of a highly inflammatory disease process in children supports the use of highly effective disease-modifying therapies in pediatrics. ESSENTIAL POINTS: The phenotypes of pediatric autoimmune neurologic conditions may change across different age groups, as the brain is still actively developing. In general, the presentation in children is more inflammatory, but overall disability is lower, likely because of better neuroplasticity and repair. Convincing evidence has increasingly emerged to support the biological rationale that effective immunosuppressive therapies used in adult neuroimmunology are equally effective in children.