Stability of class II correction with the Austro Repositioner associated with multi-brackets fixed appliances in dolichofacial patients.

BACKGROUND: The purposes of the present study were to evaluate the changes produced by the Austro Repositioner, and to assess the stability of Class II malocclusion treatment with the Austro Repositioner associated with fixed appliances and its capacity to control the vertical dimension in dolichofacial patients. METHODS: A group of patients with Class II malocclusion due to mandibular retrognathism and a dolichofacial growth pattern treated with the Austro Repositioner combined with fixed appliances were compared to a matched untreated control group of subjects with Class II malocclusion. Evaluations were made on the basis of lateral cephalograms taken at T1 (initial records), T2 (end of treatment), and T3 (1 year after treatment). Statistical comparisons were performed with paired- and two-sample t tests. RESULTS: The experimental (treated) group comprised 30 patients, 14 boys and 16 girls, and the control group comprised 30 subjects (15 boys and 15 girls) with similar ages at T1, T2 and T3. In the treated group, a significant decrease in the ANB angle was found (- 3.79 ± 1.46; p < 0.001). No significant differences were found in the maxillary skeletal measurements. In contrast, the SNB angle showed a significant increase of 3.77 ± 1.49 in the treated group compared with a nonsignificant increase of 0.77 ± 1.55 in the control group (p = 0.002). Vertical changes showed a significant decrease in the FMA angle (- 3.36 ± 1.62), while the lower anterior facial height distance and the overbite increased significantly in the treated group, reflecting a change in vertical dimensions after treatment. No significant changes were observed in either the treated or control group during the one-year posttreatment period; thus, the treatment results remained stable. CONCLUSIONS: The Austro Repositioner combined with fixed appliances could be considered an optimal treatment modality in Class II dolichofacial patients.

Advanced Female Primary Urethral Carcinoma with Nodal Extension Managed with Exclusive Use of Chemoradiotherapy: Report of a Case and Review of the Relevant Current Literature.

Primary urethral carcinoma (PUC) is a rare disease with frequent nodal metastasis at the time of diagnosis. Few risk factors have been established and overall prognosis remains poor. As of now, no clear therapeutic guidelines are established and management of advanced PUC often involves surgery which can have negative functional and psychological outcomes for the patient. Few authors have already reported the use of chemoradiotherapy alone to avoid surgery with some good short-term results. We report the case of a 48-year-old woman with advanced high-grade urothelial carcinoma of distal urethra associated to bilateral inguinal nodal metastasis. She was similarly and successfully treated using chemoradiotherapy exclusively without significant adverse effects. This experience reinforces benefits of a surgery-sparing management, when possible, as recommended in current guidelines.

Toward the Development of Potentially Healthy Low-Energy-Density Snacks for Children Based on Pseudocereal and Pulse Flours.

The main objective of this study was the development of gluten-free cracker-type snacks with a balanced supply of essential amino acids, a lower glycemic index, and a lower caloric intake that were sensorially acceptable. For this purpose, chickpea flour was replaced by quinoa (10, 20, 30, 40, and 50%) and the fat was partially (75%) replaced by chicory inulin. The flours were characterized in terms of their proximate composition, individual mineral content, particle size distribution, and functional properties. The parameters analyzed for the crackers, once baked, were the water content, water activity, weight, dimensions, color, and texture. A sensory analysis was performed as well, using the formulations containing 50% chickpea flour and 50% quinoa flour (g/100 g flour), with and without inulin, as well as those made with 100% chickpea flour. From the analysis of the raw flours, it can be concluded that snack products developed from them could be a nutritive option for children, in terms of the protein, magnesium, and fiber content. The functional properties revealed that both flours are suitable for producing doughs and baked products. The obtained results indicate that snacks made with 50% quinoa flour (g/100 g flour) and 75% chicory inulin (g/100 g high oleic sunflower oil) could be an interesting alternative for children as, in addition to offering a very interesting nutritional contribution, the energy intake from fat is reduced by 57%.

Aeroallergen immunotherapy associated with reduced risk of severe COVID-19 in 1095 allergic patients.

Introduction: Allergen immunotherapy (AIT) brings along changes in the immune system, restoring dendritic cell function, reducing T2 inflammation and augmenting the regulatory cell activation. Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, interferes with the immune system causing immune suppression during the first phase and over-activation in more advanced disease. We decided to explore the interaction of both in a real-world observational trial. Methods: We registered COVID-19 outcomes in patients with allergic disorders in Latin America, treated with and without AIT. The registry was conducted during the first 1.3 years of the pandemic, with most of the data collected before COVID-19 vaccination was concluded in most countries. Data collection was anonymous via a web-based instrument. Ten countries participated. Results: 630/1095 (57.6%) of the included patients received AIT. Compared to patients without AIT, those treated with AIT had a reduced risk ratio (RR) for COVID-19 lower respiratory symptoms (RR 0.78, 95% CI: 0.6703-0.9024; p = 0.001662) and need for oxygen therapy (RR 0.65, 95% CI: 0.4217-0.9992; p = 0.048). In adherent patients on maintenance sublingual immunotherapy/subcutaneous immunotherapy (SLIT/SCIT) the RR reduction was larger [RR = 0.6136 (95% CI 0.4623-0.8143; p < 0.001) and RR: 0.3495 (95% CI 0.1822-0.6701; p < 0.005), respectively]. SLIT was slightly more effective (NS). We excluded age, comorbidities, level of health care attendance, and type of allergic disorder as confounders, although asthma was related to a higher frequency of severe disease. When analyzing patients with allergic asthma (n = 503) the RR reduction favoring AIT was more pronounced with 30% for lower respiratory symptoms or worse (RR 0.6914, 95% CI 0.5264 to 0.9081, p = 0.0087) and 51% for need of oxygen therapy or worse (RR 0.4868, 95% CI 0.2829-0.8376, p = 0.0082). Among severe allergic patients treated with biologics (n = 24) only 2/24 needed oxygen therapy. There were no critical cases among them. Conclusion: In our registry AIT was associated with reduced COVID-19 severity.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review.

BACKGROUND: Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH. METHODS: On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date. Studies included participants with a CH diagnosis who received corticosteroid and local anaesthetic suboccipital region injections. Outcomes were change in the frequency/severity/duration of attacks; proportion of participants responding to treatment, time to attack freedom from an attack, change in attack bout length and/or the presence of adverse effects after GON blockade. Risk of bias was assessed with the Cochrane Risk of Bias V.2.0 (RoB2)/Risk of Bias in Non-randomized Studies - of Interventions (ROBINS- I) tools and a specific tool for case reports/series. RESULTS: Two RCTs, eight prospective and eight retrospective studies, and four case reports were included in the narrative synthesis. Every effectiveness study found a significant response in one or more of frequency/severity/duration of individual attacks or proportion of patients responding to treatment (47.8%-100.0%). There were five instances of potentially irreversible adverse effects. A higher injectate volume and use of concurrent prophylaxis may be associated with an increased likelihood of response. Methylprednisolone may have the best safety profile of available corticosteroids. DISCUSSION: GON blockade is safe and effective for CH prevention. Higher injectate volumes may improve likelihood of response, and the likelihood of serious adverse events may be reduced by using methylprednisolone. PROSPERO REGISTRATION NUMBER: CRD42020208435.

Non-invasive neuromodulation of the cervical vagus nerve in rare primary headaches.

Primary headache disorders can be remarkably disabling and the therapeutic options available are usually limited to medication with a high rate of adverse events. Here, we discuss the mechanism of action of non-invasive vagal nerve stimulation, as well as the findings of the main studies involving patients with primary headaches other than migraine or cluster headache, such as hemicrania continua, paroxysmal hemicrania, cough headache, or short-lasting neuralgiform headache attacks (SUNCT/SUNA), in a narrative analysis. A bibliographical search of low-prevalence disorders such as rare primary headaches retrieves a moderate number of studies, usually underpowered. Headache intensity, severity, and duration showed a clinically significant reduction in the majority, especially those involving indomethacin-responsive headaches. The lack of response of some patients with a similar diagnosis could be due to a different stimulation pattern, technique, or total dose. The use of non-invasive vagal nerve stimulation for the treatment of primary headache disorders represents an excellent option for patients with these debilitating and otherwise refractory conditions, or that cannot tolerate several lines of preventive medication, and should always be considered before contemplating invasive, non-reversible stimulation techniques.

Differences between Sexes and Speed Levels in Pelvic 3D Kinematic Patterns during Running Using an Inertial Measurement Unit (IMU).

This study aimed to assess the 3D kinematic pattern of the pelvis during running and establish differences between sexes using the IMU sensor for spatiotemporal outcomes, vertical acceleration symmetry index, and ranges of motion of the pelvis in the sagittal, coronal, and transverse planes of movement. The kinematic range in males was 5.92°-6.50°, according to tilt. The range of obliquity was between 7.84° and 9.27° and between 9.69° and 13.60°, according to pelvic rotation. In females, the results were 6.26°-7.36°, 7.81°-9.64°, and 13.2°-16.13°, respectively. Stride length increased proportionally to speed in males and females. The reliability of the inertial sensor according to tilt and gait symmetry showed good results, and the reliability levels were excellent for cadence parameters, stride length, stride time, obliquity, and pelvic rotation. The amplitude of pelvic tilt did not change at different speed levels between sexes. The range of pelvic obliquity increased in females at a medium speed level, and the pelvic rotation range increased during running, according to speed and sex. The inertial sensor has been proven to be a reliable tool for kinematic analysis during running.

Effectiveness of a Supervised Group-Based Otago Exercise Program on Functional Performance in Frail Institutionalized Older Adults: A Multicenter Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Because of its high prevalence and association with negative health-related outcomes, frailty is considered one of the most important issues associated with human aging and its mitigation is among the essential public health goals for the 21st century. However, very few studies have focused on institutionalized older adults, despite the knowledge that frailty can be reversible when identified and treated from its earliest stages. Therefore, the objective of this study was to evaluate the effects of a supervised group-based multicomponent exercise program intervention with or without oral nutritional supplementation on functional performance in frail institutionalized older adults. METHODS: This was a multicenter randomized controlled trial study with a 6-month intervention period. A total of 111 frail institutionalized older adults (75 years or older) who met at least 3 of the 5 Fried frailty criteria were randomly allocated to the control group (CG; n = 34, mean age = 87.3 ± 5.3 years), a supervised group-based multicomponent Otago Exercise Program group (OEP; n = 39, mean age = 86 ± 5.9 years), or a supervised group-based multicomponent exercise program intervention with oral nutritional supplementation (OEP+N; n = 38, mean age = 84.9 ± 6 years). Measurements included the Timed Up and Go test (TUG), Berg Balance Scale (BBS), Short Physical Performance Battery, repeated chair stand test (STS-5), handgrip strength (HGS), 10-m walking test, and 6-minute walking test, both at baseline and after the 6-month intervention period. RESULTS AND DISCUSSION: The between-group analysis by 2-way analysis of covariance showed significant improvement in the TUG [{OEP vs CG: -8.2 seconds, 95% CI [-13.3 to -2.9]; P < .001}; {OEP vs OEP+N: -7.3 seconds, 95% CI [-12.4 to -2.2]; P = .002}], BBS [{OEP vs CG; 8.2 points, 95% CI [5.2 to 11.2]; P < .001}; [{OEP+N vs CG: 4.6 points, 95% CI [1.6 to 7.6]; P < .001}; {OEP vs OEP+N: 3.5 points, 95% CI [0.6 to 6.5]; P = .011}], and HGS [{OEP vs CG: 3.4 kg, 95% CI [1.5 to 5.3]; P < .001}; {OEP+N vs CG: 3.6 kg, 95% CI [1.7 to 5.5]; P < .001}]. Additionally, the within-group analysis showed a significant improvement in the TUG (-6.9 seconds, 95% CI [-9.8 to -4.0]; P < .001) and BBS (4.3 points, 95% CI [2.6 to 5.9]; P < .001) in the OEP group. A significant decrease in the BBS and HGS was shown in the CG. CONCLUSIONS: A 6-month supervised group-based multicomponent exercise intervention improved the levels of mobility, functional balance, and HGS in frail institutionalized older adults. Further research will be required to evaluate the nutritional supplementation effects on functional performance to better determine its clinical applicability for tackling frailty.

Spanish validation of the pure procrastination scale: dimensional structure, internal consistency, temporal stability, gender invariance, and relationships with personality and satisfaction with life.

The objective of the current study was to adapt and validate the pure procrastination scale (PPS) for the Spanish adult population. Procrastination can have numerous consequences in daily life, making it essential to have reliable and valid instruments for measuring procrastination. Thus, this study was conducted to address this need. The sample consisted of 596 adults aged 18-83 years (M = 35.25, SD = 13.75). In addition to the PPS, participants completed two procrastination measures, namely the irrational procrastination scale and the decisional procrastination questionnaire, alongside the Big Five inventory and the satisfaction with life scale. The results of the confirmatory factor analysis revealed a three-factor structure of the PPS. The examination of the reliability of scores in terms of internal consistency and temporal stability showed satisfactory results for the PPS scores. Moreover, gender invariance was observed at the scalar level. Finally, the PPS scores correlated with other measures of procrastination, personality traits, and satisfaction with life in the expected direction and magnitude. In conclusion, the Spanish PPS offers valid and reliable scores when administered to adult population.

Pathophysiology and Therapy of Associated Features of Migraine.

Migraine is a complex and debilitating disorder that is broadly recognised by its characteristic headache. However, given the wide array of clinical presentations in migraineurs, the headache might not represent the main troublesome symptom and it can even go unnoticed. Understanding migraines exclusively as a pain process is simplistic and certainly hinders management. We describe the mechanisms behind some of the most disabling associated symptoms of migraine, including the relationship between the central and peripheral processes that take part in nausea, osmophobia, phonophobia, vertigo and allodynia. The rationale for the efficacy of the current therapeutic arsenal is also depicted in this article. The associated symptoms to migraine, apart from the painful component, are frequent, under-recognised and can be more deleterious than the headache itself. The clinical anamnesis of a headache patient should enquire about the associated symptoms, and treatment should be considered and individualised. Acknowledging the associated symptoms as a fundamental part of migraine has permitted a deeper and more coherent comprehension of the pathophysiology of migraine.

Assessment of the Volatile Profiles and Identification of Differentiating Aromas of Wild Undervalued Plants.

Wild edible plants have played an important role in traditional diets, including the Mediterranean diet. Many of these plants have acquired an undervalued status, since they are under-appreciated in terms of their nutritional, organoleptic qualities, or their seasonality. However, some of these species are still used in local gastronomy for their aromatic and taste characteristics. This study has investigated the quantitative and qualitative aromatic characteristics of seven undervalued wild plants that determine their organoleptic characteristics. Volatiles of the fresh leaves of each species have been determined by head-space solid-phase microextraction, a sensitive and solvent-free technique, coupled with gas chromatography and mass spectrometry. A total of 37 compounds with remarkable quantitative and qualitative differences were identified. In general, benzenoids and monoterpenoids were the most abundant groups, while branched unsaturated hydrocarbons, fatty alcohols, and sesquiterpenoids were the minor groups. Benzyl nitrile, benzyl isothiocyanate, p-cymene, and 2-hexenal were the main individual volatiles, while benzyl alcohol, eugenol, and α-copaene were the differentiating aromas. The results display that the undervalued species studied could be a suitable choice to include as new environmentally friendly crops, providing a double benefit to producers, because they are a possible way to achieve sustainable production systems, and they are an alternative for consumers, because these plants provide flavors that have high organoleptic qualities.

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD. METHODS: Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB+ /CB- ) and the history of previous severe exacerbations (Ex+ /Ex- ). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ). RESULTS: A total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB- group and 0.050 in the CB+ group). In contrast, between-group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex- subjects and 0.072 in the Ex+ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB- /CB+ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex- /Ex+ trait did not disclose differences in connectivity between network nodes (diseases). CONCLUSIONS: The multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Erenumab in chronic migraine: Experience from a UK tertiary centre and comparison with other real-world evidence.

BACKGROUND AND PURPOSE: Chronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene-related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real-world data in tertiary settings. METHODS: We audited our first 92 patients (n = 73 females) with severely disabling chronic migraine who were given monthly erenumab 70 mg sc for 6 months between December 2018 and December 2019. RESULTS: At 3 months, monthly migraine days were significantly reduced by a median of 4 days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported. CONCLUSIONS: Our real-world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.

New Generation Gepants: Migraine Acute and Preventive Medications.

Migraine is a debilitating disease whose clinical and social impact is out of debate. Tolerability issues, interactions, contraindications, and inefficacy of the available medications make new options necessary. The calcitonin-gene-related peptide (CGRP) pathway has shown its importance in migraine pathophysiology and specific medications targeting this have become available. The first-generation CGRP receptor antagonists or gepants, have undergone clinical trials but their development was stopped because of hepatotoxicity. The new generation of gepants, however, are efficacious, safe, and well tolerated as per recent clinical trials. This led to the FDA-approval of rimegepant, ubrogepant, and atogepant. The clinical trials of the available gepants and some of the newer CGRP-antagonists are reviewed in this article.

Case Report: Transformation of Visual Snow Syndrome From Episodic to Chronic Associated With Acute Cerebellar Infarct.

Visual snow syndrome is a novel neurological condition characterized by a panfield visual disturbance associated with several additional symptoms. Although it is usually a continuous and primary disorder, cases of intermittent visual snow have been described in the literature, as well as rare secondary forms. This report is the first description of a case of intermittent visual snow syndrome, which transformed into a persistent form following a posterior circulation stroke due to vertebral artery dissection. At 1 and 2 years after experiencing the acute cerebellar infarct, the patient's only neurological sequalae was visual snow. This case provides a description of how visual snow syndrome may be caused by an underlying brain disorder, and highlights the importance of the cerebellum in the pathophysiology of this relatively unknown condition. It further shows evidence of how existing predispositions might be relevant to the development of visual snow, in certain subjects and following specific circumstances.

Nutritional Composition, Bioactive Compounds, and Volatiles Profile Characterization of Two Edible Undervalued Plants: Portulaca oleracea L. and Porophyllum ruderale (Jacq.) Cass.

Wild edible plants are an important source of healthy food and have played an important role in traditional Mediterranean diets. In this paper, quality characteristics were typified in Portulaca oleracea L. and Porophyllum ruderale (Jacq.) Cass, undervalued plants inherent to the spring-summer season in the Valencian coastal region. Nutritional composition and bioactive compounds were analyzed and compared between plants in wild and organic cultivation conditions. Proximate analysis was carried out according to Association of Official Analytical Chemists methods. Total antioxidants were measured as 2.2-diphenyl-1-picrylhydrazyl hydrate and total polyphenols content via the Folin-Ciocalteu procedure. The HS-SPME technique was used to characterize the volatiles profile, and the polyphenol profile was evaluated by HPLC. The most important microelement was iron. Total antioxidants ranged from 4392.16 to 7315.00 µmol Trolox·equivalents 100 g-1 fw, and total phenolic content ranged from 99.09 to 391.18 mg gallic acid equivalents·100 g-1 fw. Results show that the content of antioxidants and phenols was higher in wild species than in cultivated ones. The volatiles profile revealed that P. ruderale was rich in monoterpenoids (48.65-55.82%), and fatty alcohols were characteristic in P. oleracea species (16.21-54.18%). The results suggest that both plants could be healthy foods and could have new sustainable agro-ecological potential for the local commercial sector.

A Secretory Vesicle Failure in Parkinson's Disease Occurs in Human Platelets.

OBJECTIVE: The presence of elevated dopamine (DA) and its major metabolites in the cytosol of neurons has been associated with their vulnerability in Parkinson's disease (PD). Over 99% of the cell's amines are confined to secretory vesicles (SVs), making these structures fundamental in the regulation of cytosolic DA levels. SVs of platelets use similar, if not the same mechanisms to accumulate serotonin in SVs as dopaminergic neurons do to store DA. Hence, any functional defects in platelets probably mirrors events in DA neurons. METHODS: We have isolated fresh platelets from the blood of 75 PD patients, 116 matched controls and 24 patients with Parkinsonism, assaying serotonin handling (basal content, accumulation, secretion and spontaneous leakage). RESULTS: We found a dramatic decrease in the serotonin content and uptake by SVs, as well as decreased thrombin-induced release by platelets from PD patients but not in those from most Parkinsonism cases. Platelets from PD patients also failed to retain serotonin in SVs. INTERPRETATION: These findings indicate a functional impairment in the handling of amines by SVs in PD patients. This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022.

Effects of global postural reeducation on postural control, dynamic balance, and ankle range of motion in patients with hallux abducto valgus. A randomized controlled trial.

Hallux abducto valgus (HAV) is a common musculoskeletal disorder that has been addressed surgically. Nevertheless, the manual therapy approach may play an important role in the management of this condition. The present study aimed to determine the effectiveness of global postural reeducation (GPR) in subjects with symptomatic mild to moderate HAV in static postural control, dynamic stability, and ankle dorsiflexion range of motion (DFROM). A total of 80 patients with mild to moderate symptomatic HAV were allocated to the intervention group (GPR) or control group (CG) (no treatment) for 8 weeks. Outcome measures were assessed at baseline at 4 and 8 weeks including static postural control (Romberg test), dynamic balance (Star Excursion Balance Test [SEBT]), and ankle DFROM (Weight-Bearing Lunge Test [WBLT]). No improvements were observed at 4 weeks, but there were improvements at 8 weeks in: static postural control mediolateral displacement (X) of center of pressure (CoP) in both eyes open (EO) and eyes closed (EC): XEO (t(36) = 2.892, p = .006, d = 0.67); XEC (t(68) = 2.280, p = .026, d = 054); and velocity (V) of CoP displacement: VEO (t(68) = 2.380, p = .020, d = 0.57); VEC (t(36) = 2.057, p = .047, d = 0.37). It were also improvements in: WBLT (t(36) = -2.869, p = .007, d = 0.54) and SEBT at three directions (anterior, ANT; posteromedial, PM; and posterolateral, PL): SEBT.ANT (t(36) = -2.292, p = .028, d = 0.23); SEBT.PM (t(36) = -4.075, p < .001, d = 0.43); SEBT.PL (t(62) = -3.506, p = .001, d = 0.34). The present study showed that GPR compared to the CG might be effective in enhancing ankle function including postural control, dynamic balance, and DFROM.

Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification.