Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center. Based on FDA-required oncologic outcomes (6-month complete response rate for CIS: 50%; duration of response in responders for CIS and papillary: 30% at 12 months and 25% at 18 months), there is not currently a strong preference for one treatment over another, although the intravesical route seems to offer less toxicity. This work summarizes the evidence on the management of BCG-unresponsive NMIBC based on current scientific evidence and provides consensus recommendations on the most appropriate treatment.

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Blood-brain barrier damage associates with glia-related cytokines in the cerebrospinal fluid of patients with Multiple Sclerosis.

BACKGROUND: The presence of Blood-Brain Barrier (BBB) dysfunction is defined by albumin quotient (QALB) and characterize a group of Multiple Sclerosis (MS) patients at clinical onset. We evaluated the concentration in cerebrospinal fluid (CSF) of 87 cytokines, to better characterize the CSF inflammatory pattern in presence of BBB damage. MATERIALS AND METHOD: In an exploratory cohort, CSF cytokines were evaluated by means of Multiplex technology (Bio-Plex Pro-Human Cytokine, GF and Diabetes 27-Plex Panel, Bio-Plex Pro-Human Chemokines 40-Plex Panel, Bio-Plex Pro-Human Inflammation Assays 37-Plex Panel) in a cohort of Other Not Inflammatory Neurological Disorders (ONIND) and in cohort of patients with MS, stratified according to BBB damage into QALB+ and QALB- MS patients. In the validation cohort, we evaluated the relevant molecules in a cohort of MS patients, stratified again into QALB+ and QALB-, including also Neurofilament Light (NfL) and Chitinase 3-like 1 (CHI3L1) CSF concentration. RESULTS: While MIP-1α, CXCL-13, and CCL-22 CSF concentrations were higher in both MS groups compared to ONIND, in QALB+ MS CSF concentrations of CXCL-9 (17.85 ± 4.69 pg/mL), CXCL-10 (476.5 ± 324.3 pg/mL), and IL-16 (96.08 ± 86.17 pg/mL) were higher than in QALB- MS (8.98 ± 5368 pg/mL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.05, and 47.35 ± 36.87 pg/mL, p < 0.005, respectively) and ONIND (8.98 ± 5368 pg/mlL, p < 0.005, 281.0 ± 180.9 pg/mL, p < 0.005, and 47.35 ± 36.87 pg/mL, p < 0.001, respectively). A strong correlation was observed between CXCL-9 and CXCL-10 in all MS groups (all r>0.75, all p < 0.001). In the validation cohort again CXCL-10 CSF concentration were higher in QALB+ MS than in QALB- MS (94.25 ± 64.75 vs 153.8 ± 99.52, p < 0.05), while no difference was observed in serum. CSF NfL (1642 ± 1963 vs 3231 ± 3492 pg/mL, p < 0.05) and CHI3L1 (183.9 ± 86.62 vs 262 ± 137.5 ng/mL, p < 0.05) were increased in QALB+ MS. CONCLUSIONS: BBB damage in MS is linked to a specific CSF cytokines pattern (CXCL-9, CXCL-10, IL-16), that are also involved in astrocyte-microglia interaction. To what extent their continuous production in the CNS may mark a more severe disease course merits to be investigated.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

Limited English Proficiency Is Associated With Diabetic Retinopathy in Patients Presenting for Cataract Surgery.

Purpose: To investigate the relationship between limited English proficiency (LEP) and diabetic retinopathy (DR) in patients presenting for cataract surgery. Methods: This is a retrospective observational study of patients who underwent cataract surgery between January 2014 and February 2020. Patients who self-identified as needing or preferring an interpreter were defined as having LEP. Differences in demographics, characteristics, and outcomes including history of type 2 diabetes (T2DM), DR, preoperative best corrected visual acuity (BCVA), macular edema, and anti-vascular endothelial growth factor injections were analyzed. Statistical comparisons were assessed using logistic regression with generalized estimating equations. Results: We included 13,590 eyes. Of these, 868 (6.4%) were from LEP patients. Patients with LEP were more likely to be Hispanic (P < 0.001), female sex (P = 0.008), or older age (P = 0.003) and have worse mean BCVA at presentation (P < 0.001). Patients with LEP had a significantly higher rate of T2DM (P < 0.001), macular edema (P = 0.033), and DR (18.1% vs. 5.8%, P < 0.001). Findings remained significant when controlling for age, sex, race/ethnicity, and type of health insurance. Patients with LEP and DR were more likely to have had later stages of DR (P = 0.023). Conclusions: Patients with LEP presenting for cataract surgery had a higher rate of DR and associated complications compared to patients with English proficiency. Further studies are needed to understand how language disparities influence health and what measures could be taken to improve healthcare in this vulnerable population. Translational Relevance: Our study highlights healthcare disparities within ophthalmology and emphasizes the importance of advocating for improved healthcare delivery for patients with LEP.

Factores etiopatogénicos y tratamiento de la enfermedad de Müller-Weiss / Etiopathogenic factors and treatment of Müller-Weiss disease

Antecedentes y objetivo: La enfermedad de Müller-Weiss (EMW) es una anomalía poco frecuente del escafoides tarsiano. Maceira y Rochera propusieron la teoría etiopatogénica más comúnmente aceptada, en la que estarían implicados factores displásicos, mecánicos y ambientales socioeconómicos. Se pretende describir las características clínicas y sociodemográficas de los pacientes de nuestro entorno con EMW, corroborar su asociación con los factores socioeconómicos descritos previamente, estimar la influencia de otros factores descritos en el desarrollo de la EMW, así como describir el tratamiento realizado. Materiales y métodos: Estudio retrospectivo de 60 pacientes diagnosticados de EMW en 2 hospitales terciarios de Valencia (España) entre los años 2010 y 2021. Resultados: Se incluyeron 60 pacientes, 21 (35,0%) hombres y 39 (65,0%) mujeres. En 29 (47,5%) casos la afectación fue bilateral. La media de edad de inicio de la sintomatología fue de 41,9±20,3 años. Durante la infancia, 36 (60,0%) pacientes sufrieron movimientos migratorios, y 26 (43,3%) problemas dentarios. La edad media de inicio laboral fue de 14,6±4,5 años. Se trataron de forma ortopédica 35 (58,3%) casos frente a 25 (41,7%) tratados quirúrgicamente, 11 (18,3%) mediante osteotomía de calcáneo y 14 (23,3%) con artrodesis. Conclusiones: Al igual que en la serie de Maceira y Rochera, encontramos una mayor prevalencia de EMW entre los nacidos alrededor de la Guerra Civil española y el periodo de movimientos migratorios masivos acontecidos en la quinta década del siglo xx. El tratamiento sigue sin estar bien establecido.(AU)

Background and aim: Müller-Weiss disease (MWD) is a rare anomaly of the tarsal scaphoid. Maceira and Rochera proposed the most commonly accepted etiopathogenic theory, in which dysplastic, mechanical, and socioeconomic environmental factors would be involved. The aim is to describe the clinical and sociodemographic characteristics of patients with MWD in our setting, corroborate their association with the socioeconomic factors previously described, estimate the influence of other factors involved in the development of MWD, and describe the treatment carried out. Materials and methods: Retrospective study of 60 patients diagnosed with MWD in 2 tertiary hospitals of Valencia (Spain) between 2010 and 2021. Results: Sixty patients were included, 21 (35.0%) men and 39 (65.0%) women. In 29 (47.5%) cases, the disease was bilateral. The mean age of onset of symptomatology was 41.9±20.3 years. During childhood, 36 (60.0%) patients suffered migratory movements, and 26 (43.3%) had dental problems. The mean age of onset was 14.6±4.5 years. Thirty-five (58.3%) cases were treated orthopedically versus 25 (41.7%) treated surgically, 11 (18.3%) by calcaneal osteotomy, and 14 (23.3%) with arthrodesis. Conclusions: As in the series of Maceira and Rochera, we found a higher prevalence of MWD among those born around the Spanish Civil War and the period of massive migratory movements that occurred in the fifth decade of the 20th century. Treatment is still not well established.(AU)

[Translated article] Aetiopathogenic factors and treatment of Müller-Weiss disease / Factores etiopatogénicos y tratamiento de la enfermedad de Müller-Weiss

Antecedentes y objetivo: La enfermedad de Müller-Weiss (EMW) es una anomalía poco frecuente del escafoides tarsiano. Maceira y Rochera propusieron la teoría etiopatogénica más comúnmente aceptada, en la que estarían implicados factores displásicos, mecánicos y ambientales socioeconómicos. Se pretende describir las características clínicas y sociodemográficas de los pacientes de nuestro entorno con EMW, corroborar su asociación con los factores socioeconómicos descritos previamente, estimar la influencia de otros factores descritos en el desarrollo de la EMW, así como describir el tratamiento realizado. Materiales y métodos: Estudio retrospectivo de 60 pacientes diagnosticados de EMW en 2 hospitales terciarios de Valencia (España) entre los años 2010 y 2021. Resultados: Se incluyeron 60 pacientes, 21 (35,0%) hombres y 39 (65,0%) mujeres. En 29 (47,5%) casos la afectación fue bilateral. La media de edad de inicio de la sintomatología fue de 41,9±20,3 años. Durante la infancia, 36 (60,0%) pacientes sufrieron movimientos migratorios, y 26 (43,3%) problemas dentarios. La edad media de inicio laboral fue de 14,6±4,5 años. Se trataron de forma ortopédica 35 (58,3%) casos frente a 25 (41,7%) tratados quirúrgicamente, 11 (18,3%) mediante osteotomía de calcáneo y 14 (23,3%) con artrodesis. Conclusiones: Al igual que en la serie de Maceira y Rochera, encontramos una mayor prevalencia de EMW entre los nacidos alrededor de la Guerra Civil española y el periodo de movimientos migratorios masivos acontecidos en la quinta década del siglo xx. El tratamiento sigue sin estar bien establecido.(AU)

Background and aim: Müller-Weiss disease (MWD) is a rare anomaly of the tarsal scaphoid. Maceira and Rochera proposed the most commonly accepted etiopathogenic theory, in which dysplastic, mechanical, and socioeconomic environmental factors would be involved. The aim is to describe the clinical and sociodemographic characteristics of patients with MWD in our setting, corroborate their association with the socioeconomic factors previously described, estimate the influence of other factors involved in the development of MWD, and describe the treatment carried out. Materials and methods: Retrospective study of 60 patients diagnosed with MWD in 2 tertiary hospitals of Valencia (Spain) between 2010 and 2021. Results: Sixty patients were included, 21 (35.0%) men and 39 (65.0%) women. In 29 (47.5%) cases, the disease was bilateral. The mean age of onset of symptomatology was 41.9±20.3 years. During childhood, 36 (60.0%) patients suffered migratory movements, and 26 (43.3%) had dental problems. The mean age of onset was 14.6±4.5 years. Thirty-five (58.3%) cases were treated orthopedically versus 25 (41.7%) treated surgically, 11 (18.3%) by calcaneal osteotomy, and 14 (23.3%) with arthrodesis. Conclusions: As in the series of Maceira and Rochera, we found a higher prevalence of MWD among those born around the Spanish Civil War and the period of massive migratory movements that occurred in the fifth decade of the 20th century. Treatment is still not well established.(AU)

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

Impact of Anti-CD20 therapies on the immune homeostasis of gastrointestinal mucosa and their relationship with de novo intestinal bowel disease in multiple sclerosis: a review.

Multiple sclerosis (MS) and inflammatory bowel disease (IBD) are autoimmune disorders characterized by inflammatory episodes affecting the brain and the gastrointestinal (GI) tract, respectively. The frequent association between MS and IBD suggests that both conditions may share common pathogenic mechanisms. However, different responses to biological therapies indicate differences in immune mechanisms of inflammation. Anti-CD20 therapies are high efficacy treatments increasingly used to control inflammatory bursts in MS, but they may alter GI homeostasis and promote the development of bowel inflammation in susceptible individuals. This review analyzes the mechanistic association between immunity in MS and IBD, the effect of anti-CD20 therapies on the gut microenvironment, and provides recommendations for early detection and management of GI toxicities in the context of B-cell depletion in MS patients.

Physical examination-indicated cerclage in twin pregnancies compared with singleton pregnancies.

OBJECTIVE: The aim of this study was to compare pregnancy outcomes of physical examination-indicated cerclage in twin and singleton pregnancies with bulging membranes. METHODS: All women with bulging membranes in the second trimester of pregnancy who were admitted to La Fe University and Polytechnic Hospital from January 2009 to January 2022 were included. A total of 128 participants were enrolled, 102 singleton pregnancies and 26 twin pregnancies. All patients underwent an amniocentesis to rule out intra-amniotic inflammation (IL-6 < 2.6 ng/mL). Cerclage was placed in the absence of intra-amniotic inflammation. RESULTS: Compared with singleton gestations, twin pregnancies displayed a significantly higher prevalence of nulliparity and assisted reproductive techniques. The incidence of intra-amniotic inflammation/infection was similar in both groups (68.62% in singleton vs. 65.38% in twin pregnancies). The average gestational age of delivery without cerclage in singleton gestations was 23.83 weeks (95% CI 22.82-24.84) and in twin pregnancies, it was 23.69 weeks (95% CI 21.8-25.57). The average gestational age at delivery among patients with cerclage was 37.27 weeks (95% CI 35.35-39.19) in singleton gestations and 36 weeks (95% CI 33.51-38.63) in twin pregnancies, with no significant differences. Time from diagnosis to delivery in patients with IL-6 < 2.6 ng/mL was 79.88 days, and in those with IL > 2.6 ng/mL was 10.87 days. Gestational age at delivery was significantly higher in both singleton and twin pregnancies with cerclage, compared with those without cerclage (log-rank p < .001). CONCLUSIONS: Singleton and twin pregnancies with bulging membranes behave similarly when cerclage is placed in the absence of intraamniotic inflammation/infection.

[Translated article] Aetiopathogenic factors and treatment of Müller-Weiss disease.

BACKGROUND AND AIM: Müller-Weiss disease (MWD) is a rare anomaly of the tarsal scaphoid. Maceira and Rochera proposed the most commonly accepted etiopathogenic theory, in which dysplastic, mechanical, and socioeconomic environmental factors would be involved. The aim is to describe the clinical and sociodemographic characteristics of patients with MWD in our setting, corroborate their association with the socioeconomic factors previously described, estimate the influence of other factors involved in the development of MWD, and describe the treatment carried out. MATERIALS AND METHODS: Retrospective study of 60 patients diagnosed with MWD in 2 tertiary hospitals of Valencia (Spain) between 2010 and 2021. RESULTS: Sixty patients were included, 21 (35.0%) men and 39 (65.0%) women. In 29 (47.5%) cases, the disease was bilateral. The mean age of onset of symptomatology was 41.9±20.3 years. During childhood, 36 (60.0%) patients suffered migratory movements, and 26 (43.3%) had dental problems. The mean age of onset was 14.6±4.5 years. Thirty-five (58.3%) cases were treated orthopedically versus 25 (41.7%) treated surgically, 11 (18.3%) by calcaneal osteotomy, and 14 (23.3%) with arthrodesis. CONCLUSIONS: As in the series of Maceira and Rochera, we found a higher prevalence of MWD among those born around the Spanish Civil War and the period of massive migratory movements that occurred in the fifth decade of the 20th century. Treatment is still not well established.

Evaluating expertise in forensic anthropology.

The medicolegal system relies on the ability of experts and non-experts alike to make judgments about expertise and use those judgments to reach consequential decisions. Given the lack of standard criteria, mandatory certification, or licensure for establishing expertise required to practice forensic anthropology and testify as an expert witness, we sought to understand how individuals assess and identify expertise in forensic anthropology by using a social science tool called the Imitation Game. This tool assesses immersion in a specific area of study via discourse, with the premise that some individuals lacking expertise themselves imitate or attempt to pass as experts. For this project we recruited volunteers with varying expertise in forensic anthropology to participate in interviews which asked questions about the practice and structure of the discipline. Those interviews were transcribed, anonymized, and evaluated by other recruited individuals with varying expertise in forensic anthropology. Results found that judges who were experts in forensic anthropology performed better than non-expert judges in determining who was not an expert in forensic anthropology based on their anonymized responses; however, nearly half of the non-experts were still able to pass as experts in forensic anthropology. The difficulties in assessing expertise based on discourse interactions demonstrates the value and need for well-defined credentials and mandatory certification to practice forensic anthropology. This study demonstrates that accurately identifying expertise in forensic anthropology may be challenging for both experts and non-experts, especially when relying solely on interactional expertise rather than formal assessments of competency which directly elucidate contributory expertise.

Aliphatic and Olefinic Fat Suppression in the Orbit Using Polarity-altered Spectral and Spatial Selective Acquisition (PASTA) with Opposed Phase.

PURPOSE: Fatty acid composition of the orbit makes it challenging to achieve complete fat suppression during orbit MR imaging. Implementation of a fat suppression technique capable of suppressing signals from saturated (aliphatic) and unsaturated (olefinic or protons at double-bonded carbon sites) fat would improve the visualization of an optical nerve. Furthermore, the ability to semi-quantify the fractions of aliphatic and olefinic fat may potentially provide valuable information in assessing orbit pathology. METHODS: A phantom study was conducted on various oil samples on a clinical 3 Tesla scanner. The imaging protocol included three 2D fast spin echo (FSE) sequences: in-phase, polarity-altered spectral and spatial selective acquisition (PASTA), and a combination of PASTA with opposed phase in olefinic and aliphatic chemical shift. The results were validated against high-resolution 11.7T NMR and compared with images acquired with spectral attenuated inversion recovery (SPAIR) and chemical shift selective (CHESS) fat suppression techniques. In-vivo data were acquired on eight healthy subjects and were compared with the prior histological studies. RESULTS: PASTA with opposed phase achieved complete suppression of fat signals in the orbits and provided images of well-delineated optical nerves and muscles in all subjects. The olefinic fat fraction in the olive, walnut, and fish oil phantoms at 3T was found to be 5.0%, 11.2%, and 12.8%, respectively, whereas 11.7T NMR provides the following olefinic fat fractions: 6.0% for olive, 11.5% for walnut, and 12.6% for fish oils. For the in-vivo study, on average, olefinic fat accounted for 9.9% ± 3.8% of total fat while the aliphatic fat fraction was 90.1% ± 3.8%, in the normal orbits. CONCLUSION: We have introduced a new fat suppression technique using PASTA with opposed phase and applied it to human orbits. The purposed method achieves an excellent orbital fat suppression and the quantification of aliphatic and olefinic fat signals.

Physical Exercise Alters Egress Pathways for Intrinsic CSF Outflow: An Investigation Performed with Spin-labeling MR Imaging.

PURPOSE: Cerebrospinal fluid (CSF) clearance is essential for maintaining a healthy brain and cognition by removal of metabolic waste from the central nervous system. Physical exercise has been shown to improve human health; however, the effect of physical exercise on intrinsic CSF outflow in humans remains unexplored. The purpose of this study was to investigate intrinsic CSF outflow pathways and quantitative metrics of healthy individuals with active and sedentary lifestyles. In addition, the effect of exercise was investigated among the sedentary subjects before and after 3 weeks of physical activity. METHODS: This study was performed on 18 healthy adults with informed consent, using a clinical 3-Tesla MRI scanner. We classified participants into two groups based on reported time spent sitting per day (active group: < 7 hours sitting per day and sedentary group: ≥ 7 hours sitting per day). To elucidate the effect of exercise, sedentary individuals increased their activity to 3.5 hours for 3 weeks. RESULTS: We show that there are two intrinsic CSF egress pathways of the dura mater and lower parasagittal dura (PSD). The adults with an active lifestyle had greater intrinsic CSF outflow metrics than adults with a more sedentary lifestyle. However, after increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was particularly notable at the lower PSD, where outflow metrics were highest among the active group. CONCLUSION: Our findings describe the relationship between physical activity and intrinsic CSF outflow and show a potential selective outflow pathway with increasing physical activity in the lower PSD pathway, potentially from the perivascular space or cortical venous subpial space.

Etiopathogenic factors and treatment of Müller-Weiss disease. / Factores etiopatogénicos y tratamiento de la enfermedad de Müller-Weiss.

BACKGROUND AND AIM: Müller-Weiss disease (MWD) is a rare anomaly of the tarsal scaphoid. Maceira and Rochera proposed the most commonly accepted etiopathogenic theory, in which dysplastic, mechanical, and socioeconomic environmental factors would be involved. The aim is to describe the clinical and sociodemographic characteristics of patients with MWD in our setting, corroborate their association with the socioeconomic factors previously described, estimate the influence of other factors involved in the development of MWD, and describe the treatment carried out. MATERIALS AND METHODS: Retrospective study of 60 patients diagnosed with MWD in 2 tertiary hospitals of Valencia (Spain) between 2010 and 2021. RESULTS: Sixty patients were included, 21 (35.0%) men and 39 (65.0%) women. In 29 (47.5%) cases, the disease was bilateral. The mean age of onset of symptomatology was 41.9±20.3 years. During childhood, 36 (60.0%) patients suffered migratory movements, and 26 (43.3%) had dental problems. The mean age of onset was 14.6±4.5 years. Thirty-five (58.3%) cases were treated orthopedically versus 25 (41.7%) treated surgically, 11 (18.3%) by calcaneal osteotomy, and 14 (23.3%) with arthrodesis. CONCLUSIONS: As in the series of Maceira and Rochera, we found a higher prevalence of MWD among those born around the Spanish Civil War and the period of massive migratory movements that occurred in the fifth decade of the 20th century. Treatment is still not well established.

Comparison of cataract surgery outcomes in English proficient and limited English proficiency patients.

PURPOSE: To determine differences in cataract surgery outcomes between English proficient (EP) and limited English proficiency (LEP) patients. SETTING: Sue Anschutz-Rodgers Eye Center, Aurora, Colorado. DESIGN: Retrospective. METHODS: Patients who underwent phacoemulsification at the Sue Anschutz-Rogers Eye Center between January 2014 and February 2020 were included. Patients who self-identified as needing or preferring an interpreter in medical encounters were defined as LEP. Differences in surgical characteristics and outcomes including cataract maturity, surgical complexity, and surgical complications were analyzed. RESULTS: 868 eyes (6.4%) were identified from LEP patients. LEP patients were more likely to have mature cataracts (5.1% vs 2.3%, P < .0001). LEP patients' surgeries were more likely to be considered complex (27.8% vs 15.3%, P < .0001) and use higher cumulative dissipated energy (mean of 9.5 [SD = 9.5] vs 7.2 [SD = 7.1], P < .0001). Preoperative visual acuity was worse in LEP patients (logMAR 0.566 [SD = 0.64] vs 0.366 [SD = 0.51], P < .0001) but showed greater improvement after surgery (logMAR 0.366 [SD = 0.54] vs 0.254 [SD = 0.41], P < .0001). There were no significant differences in operative time, intraoperative or postoperative complications. More LEP patients were on steroids 4 weeks postoperatively when compared with EP patients (14.6% vs 10.1%, P < .0002). LEP patients were less likely to undergo subsequent YAG capsulotomy (7.3% vs 12.8%, P < .0001). CONCLUSIONS: Disparities in cataract outcomes between EP and LEP patients was demonstrated. Further research into ophthalmic health disparities for LEP patients is needed to understand the root causes and how they can be addressed.

An Anthropological Investigation of the Sociocultural and Economic Forces Shaping Dental Crowding Prevalence.

OBJECTIVE: The aim of the current study is to explore country of origin and social race category differences in dental crowding prevalence through an anthropological approach. DESIGN: Data were collected from individuals within five countries (Australia, China, Japan, South Africa, United States; n = 1008) and seven social race groups in two countries (American Black, American White, Latinx, and Indigenous in the United States, South African Black, South African White, and South African Coloured; n = 654). Statistical significance between groups was assessed with a Kruskal-Wallis test, while a Dunn's post-hoc test identified which groups significantly differed. RESULTS: Results indicate South Africa is characterized by the lowest frequencies of dental crowding, with Coloured South Africans yielding the highest and Black South Africans displaying the lowest frequencies. Individuals in the United States exhibited relatively high levels of minor dental crowding. American Blacks had lower crowding levels, while the Indigenous group had high levels of severe crowding. Individuals within China and Japan exhibited higher relative prevalence of severe crowding. CONCLUSIONS: Overall, significant differences exist in dental crowding prevalence across countries and social race categories using an anthropological grading system to assess crowding. These differences are likely impacted by sociocultural (aesthetic preferences) and economic (access to dental care) factors.

Mobility and kinship in the world's first village societies.

Around 10,000 y ago in southwest Asia, the cessation of a mobile lifestyle and the emergence of the first village communities during the Neolithic marked a fundamental change in human history. The first communities were small (tens to hundreds of individuals) but remained semisedentary. So-called megasites appeared soon after, occupied by thousands of more sedentary inhabitants. Accompanying this shift, the material culture and ancient ecological data indicate profound changes in economic and social behavior. A shift from residential to logistical mobility and increasing population size are clear and can be explained by either changes in fertility and/or aggregation of local groups. However, as sedentism increased, small early communities likely risked inbreeding without maintaining or establishing exogamous relationships typical of hunter-gatherers. Megasites, where large populations would have made endogamy sustainable, could have avoided this risk. To examine the role of kinship practices in the rise of megasites, we measured strontium and oxygen isotopes in tooth enamel from 99 individuals buried at Pinarbasi, Boncuklu, and Çatalhöyük (Turkey) over 7,000 y. These sites are geographically proximate and, critically, span both early sedentary behaviors (Pinarbasi and Boncuklu) and the rise of a local megasite (Çatalhöyük). Our data are consistent with the presence of only local individuals at Pinarbasi and Boncuklu, whereas at Çatalhöyük, several nonlocals are present. The Çatalhöyük data stand in contrast to other megasites where bioarchaeological evidence has pointed to strict endogamy. These different kinship behaviors suggest that megasites may have arisen by employing unique, community-specific kinship practices.

Bilateral choroidal effusions and angle closure in the setting of systemic capillary leak syndrome from HLA-directed vaccine and pembrolizumab therapy for squamous cell carcinoma.

Purpose: Immunotherapy has become an important addition to oncology treatment plans in recent years. As these therapies become more widely employed, many unique side effects have been reported. In ophthalmology the most well-documented side effects of immune checkpoint inhibitors (ICI) include uveitis, macular edema and dry eye syndrome. This manuscript describes a rare case of bilateral choroidal effusions and secondary angle narrowing in the setting of systemic capillary leak syndrome (SCLS) from an HLA-directed vaccine and an ICI, pembrolizumab, for the treatment of stage IV squamous cell carcinoma (SCC) of the lung. Observations: A 67-year-old male with a history of stage IV SCC of the lung status-post pneumonectomy presented to the emergency department due to functional decline, anasarca, and dyspnea after receiving an HLA-directed vaccine in combination with pembrolizumab. Extensive workup revealed that his symptoms were secondary to SCLS. Ophthalmology was consulted due bilateral choroidal detachments seen on magnetic resonance imaging. B-scan ultrasound and ultrasound biomicroscopy revealed large, non-appositional choroidal effusions with anterior rotation of the ciliary body. Given minimal response to oral steroid therapy, sub-Tenon's triamcinolone acetonide, atropine, and intraocular pressure-lowering eyedrops were initiated with a good response. Conclusions and Importance: Choroidal effusions and secondary angle closure can be rare complications of SCLS in the setting of ICIs. Clinicians must be aware of the potentials side effects of ICI therapy, as these medications become more commonly used.

A hospital incident reporting system (2016-2019): Learning from notifier's perception on incidents' risk, severity and frequency of adverse events.

Incident reporting systems (IRSs) are considered safety culture promoters. Nevertheless, they have not been contemplated to monitor professionals' perception about patient safety related risks. This study aims to describe the characteristics and evolution of incident notifications reported between 2016 and 2019 in a high complexity reference hospital in Barcelona and explores the association between notifications' characteristics and notifier's perception about incidents severity, probability of occurrence and risk. The main analysis unit was notifications reported. A descriptive analysis was performed and taxes by hospital activity were calculated. Odds ratios were obtained to study the association between the type of incident, the moment of incident, notifiers' professional category, reported incident's severity, probability and incidents' calculated risk. Through the study period, a total of 6379 notifications were reported, observing an annual increase of notifications until 2018. Falls (21.22%), Medical and procedures management (18.91%) and Medication incidents (15.49%) were the most frequently notified. Departments reporting the highest number of notifications were Emergency room and Obstetrics & Gynaecology. Incident type and notifiers' characteristics were consistently included in the models constructed to assess risk perception. Pharmaceutics were the most frequent notifiers when considering the proportion of staff members. Notification patterns can inform professionals' patient risk perception and increase awareness of professionals' misconceptions regarding patient safety.