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IntroductionPersonality shapes the cognitive, affective, and behavioral interactions between individuals and the environment. Defensive peripersonal space (DPPS) is the projected interface between the body and the world with a protective function for the body. Previous studies suggest that DPPS displays inter-individual variability that is associated with psychiatric symptoms, such as anxiety. However, DPPS may share a link with personality traits.MethodsFifty-five healthy participants were assessed with the Personality Inventory for DSM-5 (PID-5)–Adult to evaluate personality dimensions. Subjects underwent the Hand Blink Reflex (HBR) task that estimates the DPPS limits by assessing the modulation of blink intensity in response to the median nerve stimulation. Data of the HBR was analyzed with Bayesian multilevel models, while the relationship between DPPS and personality traits was explored using network analysis.ResultsHBR was best modeled using a piecewise linear regression model, with two distinct slope parameters for electromyographic data. Network analyzes showed a positive correlation between the proximal slope and detachment personality trait, suggesting that individuals with higher scores in the detachment trait had an increased modulation of HBR, resulting in a larger extension of the DPPS.DiscussionFeatures of the detachment personality trait include avoidance of interpersonal experiences, restricted affectivity, and suspiciousness, which affect interpersonal functioning. We suggest that DPPS may represent a characteristic feature of maladaptive personality traits, thus constitute a biomarker or a target for rehabilitative interventions.

Manual dexterity is referred to as the skill to perform fine motor movements and it has been assumed to be associated to the cognitive domain, as well as the sensorimotor one. In this work, we investigated with functional near-infrared spectroscopy the cortical activations elicited by the execution of the 9-HPT, i.e., a standard test evaluating manual dexterity in which nine pegs were taken, placed into and then removed from nine holes on a board as quickly as possible. For comparison, we proposed a new active control task mainly involving the sensorimotor domain, in which the pegs must be placed and removed using the same single hole (1-HPT). Behaviorally, we found two distinct groups based on the difference between the execution time of the 9-HPT and the 1-HPT (ΔHPT). Cortical areas belonging to the network controlling reaching and grasping movements were active in both groups; however, participants showing a large ΔHPT presented significantly higher activation in prefrontal cortical areas (right BA10 and BA11) during 9-HPT and 1-HPT performance with respect to the participants with a small ΔHPT, who showed a deactivation in BA10. Unexpectedly, we observed a significant linear relationship between ΔHPT and right BA10 activity. This suggested that participants performing the 9-HPT more slowly than the 1-HPT recruited prefrontal areas implicitly exploiting the cognitive skills of planning, perhaps in search of a motor strategy to solve the test activating attentional and cognitive control processes, but this resulted not efficient and instead increased the time to accomplish a manual dexterity task.

Success and impact metrics in science are based on a system that perpetuates sexist and racist "rewards" by prioritizing citations and impact factors. These metrics are flawed and biased against already marginalized groups and fail to accurately capture the breadth of individuals' meaningful scientific impacts. We advocate shifting this outdated value system to advance science through principles of justice, equity, diversity, and inclusion. We outline pathways for a paradigm shift in scientific values based on multidimensional mentorship and promoting mentee well-being. These actions will require collective efforts supported by academic leaders and administrators to drive essential systemic change.

ObjectiveTo evaluate radiologic and clinical inflammatory activity in women with MS during pregnancy and postpartum.MethodsWe performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the University of California, San Francisco MS Center between 2005 and 2018. Proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions (primary outcome) and annualized relapse rate (ARR; secondary) were compared before and after pregnancy.ResultsWe identified 155 pregnancies in 119 women (median Expanded Disability Status Scale [EDSS] 2.0). For the 146 live birth pregnancies, prepregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p = 0.017) and increased in the 3 months postpartum (ARR 0.61, p = 0.012); and 16% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 53% had new T2 and/or Gd+ lesions postpartum compared with 32% prepregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, even for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 31%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio = 0.3, 95% confidence interval 0.1-0.9) were observed for relapses.ConclusionsBuilding on previous reports of increased relapse rate in the first 3 months postpartum, we report a significant association between inflammation on MRI and this clinical activity. We also detected postpartum radiologic activity in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

BackgroundMany patients with MS continue to have symptoms of their disease even when inflammatory activity is reduced by DMTs. Although disease activity tends to be reduced during pregnancy - especially in the third trimester - women with MS can experience ongoing symptoms during pregnancy, or new ones in the immediate postpartum period, that degrade quality of life. While many MS-related and postpartum symptoms can be improved with physical therapy (PT), there are currently no guidelines on pregnancy-related rehabilitation in MS. In this analysis, we evaluated the prevalence of PT-amenable symptoms and patterns of PT referrals in a cohort of UCSF MS Clinic patients who became pregnant.MethodsWe extracted electronic medical records (EMR) data for the year before conception, during pregnancy, and year postpartum for women with MS cared for at UCSF between 09-2005 and 08-2019. This included clinical visits, MS therapies and symptoms (as defined by the National MS Society). PT and pelvic floor PT orders and notes were also extracted.ResultsWe included 142 live birth pregnancies from 118 women. During the course of their pregnancy and within the year postpartum, 107 women (75.4%) reported at least one PT-amenable symptom. A total of 30 (28.0%) referrals were made to PT, with attendance confirmed for 10 (33.3% of referrals). Symptoms most commonly triggering a referral for PT evaluation were numbness and urinary incontinence. Falls were reported after 10 of the pregnancies; 4 resulted in a referral to PT. Forty-one women reported urinary incontinence: 11 (26.8%) were referred to PT, and 2 to pelvic floor PT. Nineteen women experienced a documented relapse during pregnancy and/or postpartum: 11 received a PT referral, and 4 attended PT.ConclusionsWhile women with MS recorded at least 1 PT-amenable symptom during or following 75.4% of their pregnancies, only 28% of these were referred to PT - and only a third attended PT. Of significance was the 4.9% referral rate for pelvic floor PT in postpartum women with a record of urinary incontinence. Pelvic floor PT is a mainstay of general postpartum care in many European countries. These data illustrate critical gaps in rehabilitation referral, access and use at the intersection of neurological conditions and pregnancy in a large US-based MS clinic. They lend support for quality improvement efforts to improve care pathways and for telerehabilitation innovations to reduce barriers to access and improve synergistic care between PT, MD and urologic care.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

BackgroundThere are numerous challenges to treating co-occurring symptoms in multiple sclerosis (MS).ObjectiveTo pilot the feasibility of a novel symptom management platform, CoachMS, to monitor MS symptoms (bladder function, ambulation, and mood: BAM) and respond to changes in real-time.MethodsIn this 12-week randomized controlled pilot trial, participants' symptoms were monitored using weekly questionnaires and remote ambulatory monitoring (Fitbit Flex2®). Behavioral change principles used included shared goal setting at 2 weeks. Between weeks 2-12, the CoachMS group received targeted contact and interventions if symptoms worsened; the control group were treated through usual clinic practice. Our outcomes were feasibility (retention, adherence and acceptability; primary) and proportion of recommended treatments pursued (secondary); efficacy was explored.ResultsOf 21 participants enrolled, 13 (62%) completed the study; protocol adherence was excellent. CoachMS participants demonstrated greater follow-through with clinical recommendations than controls (OR 9.3, 95% CI (0.9, 97.6)). As a cohort, each BAM symptom tended to improve. Suicidality was detected in one control participant, resulting in urgent evaluation and hospitalization.ConclusionsThe innovative CoachMS platform was feasible and acceptable in this cohort with baseline BAM symptoms. It could represent an accessible, cost-effective tool to monitor MS symptoms in real-time; a larger trial is planned.

BackgroundTeleneurology for multiple sclerosis (MS) care was considered feasible, but utilization was limited.ObjectiveTo describe how the existing teleneurology populations at two academic MS Centers changed during the COVID-19 pandemic.MethodsIn this cross-sectional study, we captured all in-person and teleneurology visits at two academic MS Centers between January 2019 and April 2020. We compared group differences between the Centers, and COVID-related changes using T-, chi-squared Kruskal-Wallis and Fisher exact tests.Results2268 patients completed 2579 teleneurology visits (mean age 48.3 ± 13.3 years, 72.9% female). Pre-COVID, the Centers' teleneurology populations were similar for age, sex, MS type, and disability level (all p > 0.1), but differed for race (96.5% vs 80.7% white, p ≤ 0.001), MS treatment (49.1% vs 32.1% infusible, p ≤ 0.001), and median distance from Center (72 vs 186 miles, p ≤ 0.001). Post-COVID, both Centers' teleneurology populations had more black (12.7% vs 4.37%, p ≤ 0.001) and local (median 34.5 vs 102 miles, p ≤ 0.001) patients.ConclusionTeleneurology visits in 2019 reflected the organizational and local teleneurology reimbursement patterns of our Centers. Our post-COVID-19 changes illustrate the potential for payors and policy to change disparities in access to, or utilization of, remote care. Patients' perception of care quality and value following this shift warrants study.

The Locomotor System Anatomy (LSA) course, placed in the first semester of the first year of the new Master’s degree in Medicine and Surgery High Technology (MSHT) at the Sapienza University of Rome, was integrated with surgical and bioengineering content. This study investigated the educational value and the students’ perceptions of the effectiveness of these two types of integration, comparing surgical integration (SI) with engineering integration (EI). Anatomy knowledge and students’ opinions attending the LSA course in MSHT degree (n = 30) were compared with those of students (n = 32) attending another medical and surgery course not comprising EI. Data show that students in the MSHT course like in-depth SI much more than in-depth EI. However, those who like in-depth SI also like in-depth EI. Significant differences were in anatomy knowledge between the two groups in the three sections of the test. There was no significant correlation between the three test scores and the levels of liking, while there was a significant correlation between students liking SI and those liking EI. A statistically significant correlation was also found in students who correctly responded to questions on the head and trunk, with students responding correctly to questions on the upper limbs. This study will be important in optimizing the deepening of SI and EI in the LSA course.

Background: To optimize results reporting after penile cancer (PC) surgery, we proposed a Tetrafecta and assessed its ability to predict overall survival (OS) probabilities. Methods: A purpose-built multicenter, multi-national database was queried for stage I–IIIB PC, requiring inguinal lymphadenectomy (ILND), from 2015 onwards. Kaplan–Meier (KM) method assessed differences in OS between patients achieving Tetrafecta or not. Univariable and multivariable regression analyses identified its predictors. Results: A total of 154 patients were included in the analysis. The 45 patients (29%) that achieved the Tetrafecta were younger (59 vs. 62 years; p = 0.01) and presented with fewer comorbidities (ASA score ≥ 3: 0% vs. 24%; p < 0.001). Although indicated, ILND was omitted in 8 cases (5%), while in 16, a modified template was properly used. Although median LNs yield was 17 (IQR: 11–27), 35% of the patients had Tetrafecta cohort displayed significantly higher OS probabilities (Log Rank = 0.01). Uni- and multivariable logistic regression analyses identified age as the only independent predictor of Tetrafecta achievement (OR: 0.97; 95%CI: 0.94–0.99; p = 0.04). Conclusions: Our Tetrafecta is the first combined outcome to comprehensively report results after PC surgery. It is widely applicable, based on standardized and reproducible variables and it predicts all-cause mortality.

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully.

Abstract Background Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic ultrasound (TUS) as an imaging modality with high sensitivity for the identification of malignant pleural involvement and in order to guide pleural biopsies. Methods In this retrospective single‐center study between January 2018 and June 2022, 51 consecutive patients with impassable circumferential pleural thickening underwent TUS at the Thoracic Surgery Unit of the Vanvitelli University of Naples. Pleural biopsies were performed, and then large and multiple samples were sent to the pathological anatomy for histological examination. Results In all patients who underwent ultrasound examination, we chose the optimal point of entry to perform pleural biopsies and selected the areas of greater thickening without pleural effusion. No patient had any complications. No drainage tubes were placed after the pleural biopsies and no pneumothorax was present during the following days of hospitalization. The patients were discharged on the second postoperative day. Conclusion With TUS the precise pleural thickening localization, local infiltration, mass extent, its nature (solid, cystic or complex) and ultrasound features can be easily defined. Furthermore, ultrasound is more economical than computed tomography and avoids the risks associated with radiation. Thoracic ultrasound is an important component of the diagnostic procedure in detecting a safe entry site for biopsies of MPMs.

Background: Nephron-sparing surgery represents the gold standard treatment for organ-confined renal tumors. We present 15-years of outcomes after off-clamp laparoscopic partial nephrectomy (ocLPN). Methods: a retrospective analysis was performed on patients who underwent ocLPN between May 2001 and December 2005. Baseline demographic, clinical, pathologic, surgical, functional and survival data were collected. The Kaplan–Meier method evaluated group-specific oncologic outcomes at 5, 10 and 15 years and the log rank test assessed differences between groups. The same analysis investigated the probabilities of developing a significant renal function impairment (sRFI) and achieving ROMeS. Cox analyses identified predictors of this latter tricomposite outcome. Results: We included 63 patients whose median tumor size was 3 cm (IQR:2–4). At 15 years, the chances of developing local recurrence, metachronous renal cancers or distant metastases were 2 ± 2%, 23 ± 6% and 17 ± 5%, respectively. Consequently, disease-free, cancer-specific and overall-survival probabilities were 68 ± 6%, 90 ± 4% and 72 ± 6%. MCRSS and UCISS well predicted oncologic outcomes. Overall, nine (14%) patients experienced an sRFI and 33 (52%) achieved ROMeS. Age (HR: 1.046; p = 0.033) and malignant histology (low-risk cancers HR: 3.233, p = 0.048) (intermediate/high risk cancers HR: 5.721, p = 0.023) were independent predictors of ROMeS non-achievement. Conclusions: At 15 years from ocLPN, most of patients will experience both excellent functional and oncologic outcomes.

Measurement(s) habitat similarity • Time Series Analysis • Principal Component Technology Type(s) Habitat Representativeness Score • Cross-Correlation • Principal Component Analysis Factor Type(s) Sea-bottom and sea-surface dissolved oxygen, salinity, and temperature • Sea net primary production • Sea ice concentration • Average, minimum, maximum sea depth • Average, minimum, maximum elevation • Distance of a square marine area from land and its fraction covered by water • Indication of the belonging Large Marine Ecosystem (LME), Exclusive Economic Zone (EEZ), Marine Ecoregions of the World (MEOW), Major Ocean Basins, and Marine Protected Area (MPA) • Number of islands • Water area that lies within the shelf, slope, and abyssal zones • Tidal range extension • Coral density • Estuary and seamount presence • Carbon dioxide flux at soil • Air surface temperature • Precipitation • Difference between air surface temperature and sea surface temperature • World population density • Sediment thickness • Atmospheric concentration of methane and nitrous oxide • Earth heat flow • Distance from crust plates • Earthquake density, depth, magnitude • Groundwater resources Sample Characteristic - Environment climate system Sample Characteristic - Location Oceans and Seas • Adriatic Sea • Aegean Sea • Baltic Sea • Bay of Biscay • Black Sea • Mediterranean Sea, Eastern Basin • North Sea • Mediterranean Sea, Western Basin

Abstract Introduction Central airway tumors involving the trachea and main‐stem bronchi are a common cause of airway obstruction and a significant cause of mortality among the patients of thoracic diseases with respiratory failure. Debulking in rigid bronchoscopy is quick, safe, and effective. It can be complex and hard in patients with severe bronchial or tracheal obstruction and/or with intraluminal bleeding tumors because of inadequate distal airway control. We have used laser tube as a new technique of ventilation for severe central airway obstruction. Materials and Methods Forty‐six patients with severe airway obstruction undergoing rigid bronchoscopy from September 2020 to June 2022 at the Thoracic Surgery Department of the University L. Vanvitelli of Naples underwent placement of laser tube. Results In all patients who underwent rigid bronchoscopy with the use of the laser tube, a reduction of obstruction of more than 50% was obtained and in all patients no hypoxia (saturation

Abstract Background No single and thoroughly validated imaging method in monitoring of cryoablated renal cell carcinoma (RCC) is available. The purpose of our study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (pCT) in evaluating the hemodynamic response of RCC. Methods 15 patients (14 male, 1 female; age range, 43-81 years; mean age, 62 years) with cryoablated RCC via a transperitoneal approach, underwent to pCT 6-8 months after cryo-therapy. pCT was performed for 65 seconds after intravenous injection of contrast medium (80 mL, 370 mg iodine per millilitre, 4 mL/sec). Perfusion parameters (Time/Density curve; Blood flow, BF; Blood Volume, BV; Mean Transit Time, MTT; Permeability-Surface Area Product, PS) were sampled in the cryoablated tumor area and in ipsilateral renal cortex using deconvolution-based method. A tumor was considered to be not responsive to treatment by CT evidence of pathological contrast enhancement in the cryoablated area or renal mass persistence compared with the preoperative CT control. Written informed consent was obtained from all participants before the study. Results After cryotherapy, successfully ablated tumor (n = 13) showed decrease in BV (5,39 +/- 1,28 mL/100 g), BF (69,92 +/- 20,12 mL/100 g/min) and PS (16,66 +/- 5,67 mL/100 g/min) value and increased value of MTT (25,35 +/- 4,3 sec) compared with those of normal renal cortex (BV: 117,86 +/- 31,87 mL/100 g/min; BF: 392,39 +/- 117,32 mL/100 g/min; MTT: 18,02 +/- 3,6 sec; PS: 81,68 +/- 22,75 mL/100 g/min). In one patient, assessment of perfusion parameters was not feasible for breathing artifacts. One tumor showed poor response to treatment by the evidence of nodular contrast enhancement in the region encompassing the original lesion. Two typical enhancement patterns were obtained comparing the Time-Density curves of responsive and not responsive ablated tumors. Conclusion Perfusion CT seems to be a feasible and promising technique in monitoring the effects of cryoablation therapy.

ObjectivesTo identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere.Study designThe Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected.ResultsWe enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P = .09), or in experiencing portal hypertension (28% vs 21%; P = .16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P = .04. Development of portal hypertension was associated with a reduced height Z-score.ConclusionsPortal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A history of neonatal cholestasis is a weak predictor of severe disease.

Background and purposeMR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations.Materials and methodsTwenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM.ResultsThe orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions.ConclusionsNODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.

We present a case of ovarian torsion due to a nine-centimeter cystic ovarian teratoma diagnosed on transabdominal point-of-care ultrasound (POCUS). A 29-year-old female presented with abrupt onset of 10/10 left lower quadrant pain for one hour. She had a known left-sided ovarian cyst. Patient was normotensive, not tachycardic, and afebrile. Bimanual exam showed a seven-centimeter left, adnexal mass. POCUS revealed a nine-centimeter cystic structure in the left adnexa with a three-centimeter echogenic focus, consistent with a dermoid plug. A radiology-performed transvaginal ultrasound confirmed the left sided mass with absent blood flow. Emergent diagnostic laparoscopy showed the cyst was torsed twice and was found to contain adipose tissue and hair on pathologic evaluation consistent with a benign cystic teratoma. The patient did well postoperatively and was discharged the next day. Ovarian torsion is a gynecologic surgical emergency. The characteristic appearance of a cyst with “dermoid plug” in the appropriate clinical setting can lead to earlier diagnosis and treatment.

We compared the perioperative outcomes of open (ORC) vs. robot-assisted (RARC) radical cystectomy in the treatment of pT4a MIBC. In total, 212 patients underwent ORC (102 patients, Group A) vs. RARC (110 patients, Group B) for pT4a bladder cancer. Patients were prospectively followed and retrospectively reviewed. We assessed operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of stay, transfusion rate, and oncological outcomes. Preoperative features were comparable. The mean operative time was 232.8 vs. 189.2 min (p = 0.04), and mean EBL was 832.8 vs. 523.7 mL in Group A vs. B (p = 0.04). An intraoperative transfusion was performed in 32 (31.4%) vs. 11 (10.0%) cases during ORC vs. RARC (p = 0.03). The intraoperative complications rate was comparable. The mean length of stay was shorter after RARC (12.6 vs. 7.2 days, p = 0.02). Postoperative transfusions were performed in 36 (35.3%) vs. 13 (11.8%) cases (p = 0.03), and postoperative complications occurred in 37 (36.3%) vs. 29 (26.4%) patients in Groups A vs. B (p = 0.05). The positive surgical margin (PSM) rate was lower after RARC. No differences were recorded according to the oncological outcomes. ORC and RARC are feasible treatments for the management of pT4a bladder tumors. Minimally invasive surgery provides shorter operative time, bleeding, transfusion rate, postoperative complications, length of stay, and PSM rate.

Adrenalectomy is commonly considered a curative treatment in case of adrenal gland as site of metastasis. In the present study, we evaluated the impact of primary tumor histology on survival outcomes after a minimally invasive adrenal mastectomy for a solitary metachronous metastasis. From May 2004 to August 2020, we prospectively collected data on minimally invasive adrenalectomies whose pathological examination showed a metastasis. All patients only received metastasectomies that were performed with curative intent, or to achieve non-evidence of disease status. Adjuvant systemic therapy was not administered in any case. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. Univariable and multivariable Cox regression analyses were applied to identify independent predictors of CSS. Out of 235 laparoscopic and robotic adrenalectomies, the pathologic report showed metastases in 60 cases. The primary histologies included 36 (60%) renal cell carcinoma (RCC), 9 (15%) lung cancer, 6 (10%) colon cancer, 4 (6.7%) sarcoma, 3 (5%) melanoma and 2 (3.3%) bladder cancer. RCC displayed significantly longer survival rates with a 5-year CSS of 55.9%, versus 22.8% for other histologies (log-rank p = 0.01). At univariable analysis, disease-free interval (defined as the time from adrenalectomy to evidence of disease progression) < 12 months and histology were predictors of CSS (p = 0.003 and p < 0.001, respectively). At multivariable Cox analysis, the only independent predictor of CSS was primary tumor histology (p = 0.005); patients with adrenal metastasis from colon cancer and bladder cancer showed a 5.3- and 75.5-fold increased risk of cancer death, respectively, compared to patients who had RCC as primary tumor histology. Oncological outcomes of adrenal metastasectomies are strongly influenced by primary tumor histology. A proper discussion of the role of surgery in a multidisciplinary context could provide optimal treatment strategies.

Background: High-Intensity Focused Ultrasound (HIFU) has emerged as a precise and non-invasive modality for tissue ablation and healing. This study presents a detailed dermoscopic analysis of skin healing post-High-Intensity Focused Ultrasound (HIFU) treatment, focusing on common benign skin lesions, such as seborrheic keratosis, sebaceous hyperplasia, vascular lesions, and sebaceous nevi. Methods: Prior to HIFU treatment, a comprehensive assessment was conducted, integrating ultrasound scanning and clinical evaluations. The TOOsonix System ONE-M was employed for HIFU treatments, with parameters tailored to each lesion type. Results: A common pattern observed across all lesions includes initial whitening post treatment, followed by scab formation and the development of a pink area with reparative vessels. This study, however, highlights distinct differences in fibrosis patterns and healing timelines across different lesion types. Each lesion type exhibited unique fibrosis patterns post treatment. Flatter variants of seborrheic keratosis healed within a month, displaying hypopigmentation and reparative vessels, alongside a distinct lattice fibrosis pattern in more verrucous forms, which took about two months to heal. Sebaceous hyperplasia, characterized by rapid healing within three weeks, demonstrated fibrosis with pink areas and perpendicular white lines, concluding with a slight depression. Vascular lesions varied in healing time based on depth, with superficial ones showing whitening and crust formation, while deeper lesions had vessel occlusion and size reduction accompanied by concentric fibrotic bands. Sebaceous nevi presented the longest healing duration of three months, characterized by amorphous white-gray structures, scab formation, and the emergence of pink areas with branching vessels, leading to clear skin with reduced white lines. Conclusions: in conclusion, this meticulous clinical evaluation highlights the unique healing characteristics and timelines for each skin lesion type treated with HIFU. These insights are invaluable for optimizing follow-up assessments, identifying potential complications, and refining treatment protocols. By providing detailed insights into the healing timelines and patterns for different types of lesions, patients can be better informed about their post-treatment journey.

(1) Background: Less than 30% of patients with muscle-invasive bladder cancer (MIBC) receive neoadjuvant chemotherapy (NAC), and reasons for underuse remain unclear. One potential explanation is the concern for the increased risk of perioperative morbidity and mortality. The aim of this study is to investigate the impact of NAC on the risk of detrimental perioperative outcomes in patients with MIBC treated with radical cystectomy (RC). (2) Methods: We identified patients receiving RC for MIBC (T2-4a N0 M0) from 2016 to 2022. Moreover, 1:1 propensity score matching (PSM) was applied between RC alone versus RC plus NAC, and our analysis tested the association between NAC status and peri-operative outcomes. (3) Results: Among the 317 patients treated with RC for identified MIBC, 98 (31%) received NAC. Patients treated with NAC were younger (median yr. 64 vs. 71; p < 0.001), with a lower Charlson Comorbidity Index (3 vs. 4; p > 0.001), and received more frequently continent urinary diversion (61 vs. 32%, p < 0.001). About 43% of patients in each group were treated with robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). After PSM, no differences were detected for the outcomes considered. (4) Conclusions: NAC is not associated with a higher rate of perioperative complications, including patients who received RARC with ICUD.

Introduction: Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. Evidence Acquisition: On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: (“prostate cancer” OR “prostate tumor”) AND (“active surveillance”) AND (“physical activity” OR “physical exercise” OR “physical intensive activity” OR “intensive exercise”) AND (“lifestyle”). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. Evidence Synthesis: We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. Conclusion: Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.

Communication campaigns are expected to contribute to increase the efficacy of nutritional warnings. In this context, the aims of the present work were (a) to evaluate how citizens perceive different types of messages for a communication campaign and (b) to determine if personal characteristics such as gender, age, and educational level, as well socioeconomic and nutritional status, moderate how citizens perceive such campaign messages. A series of graphic pieces were designed for each of the following three types of messages: promotion of informed food choices; raising awareness of the negative health consequences of excessive consumption of sugar, fat, and sodium; and promotion of healthy food choices. An online study was conducted with 774 participants, who were randomly assigned to one of the three types of messages. The participants' self-reported perception of the graphic pieces was evaluated using 7-point Likert-type scales. After completing the evaluation task, the participants proceeded to a series of choices. This was implemented to evaluate whether exposure to different types of messages affected hypothetical food choices. Results revealed that messages related to the promotion of healthy eating were perceived as the most adequate as part of a communication campaign and had the potential to encourage more healthful hypothetical choices in the experimental task. However, gender, age, and nutritional status moderated the influence of the type of message on the participants' perception, meaning that different groups perceived different types of messages as the most adequate. The results from the present work stress the need to include different types of messages in a communication campaign to target individuals with different motivations and characteristics.

PURPOSEMultiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce.PATIENTS AND METHODSWe analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older.RESULTSThere were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival.CONCLUSIONIn conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.

Priming is a learning process that refers to behavioral changes caused by previous exposure to a similar stimulus. Motor imagery (MI), which involves the mental rehearsal of action representations in working memory without engaging in actual execution, could be a strategy for priming the motor system. This study investigates whether MI primes action execution in Multiple Sclerosis (MS). Here, 17 people with MS (PwMS) and 19 healthy subjects (HS), all right-handed and good imaginers, performed as accurately and quickly as possible, with a pencil, actual or mental pointing movements between targets of small (1.0 × 1.0 cm) or large (1.5 × 1.5 cm) size. In actual trials, they completed five pointing cycles between the left and right targets, whereas in mental trials, the first 4 cycles were imagined while the fifth was actually executed. The fifth cycle was introduced to assess the MI priming effect on actual execution. All conditions, presented randomly, were performed with both dominant (i.e., right) and non-dominant arms. Analysis of the duration of the first 4 cycles in both actual and mental trials confirmed previous findings, showing isochrony in HS with both arms and significantly faster mental than actual movements (anisochrony) in PwMS (p

IntroductionLittle is known about Quality of Life within the first court of unvaccinated COVID-19 pregnant women exposed to the pandemic stressor. Primary aim of this study was to evaluate 1 year after hospital discharge HRQoL in a cohort of COVID-19 unvaccinated pregnant patients with COVID-19.Methodsin this prospective observational study, all COVID-19 positive pregnant women at any gestational age, admitted to the Obstetric Department at the University Hospital of Udine, Italy, from 1 March 2020 to 1 March 2021, requiring or not oxygen supplementation due to SARS-CoV2 pneumonia were evaluated. Patients with a history of neurological or psychiatric disease, those with a previous abortion, and those who refused to provide written informed consent were excluded from the study. We investigated pregnant positive COVID-19 women Health-related quality of life (HRQoL) with the Short-Form Health Survey-36 (SF-36) and Post-traumatic Stress-Disorder (PTSD) with the Impact of Event Scale-Revised (IES-R).Results62 pregnant women respected the inclusion criteria of the study, and data from 33 patients were analyzed. The mean age was 32 ± 6 years, with a median gestational age of 38 weeks [IQR 34–40]. 15.2% of patients required oxygen therapy through noninvasive respiratory support (with high flow nasal cannula) for a median of 9 days [IQR 6–12]. The median Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were 50.2 [IQR 46.7–53.7] and 56.0 [IQR 46.8–60.6] respectively. Ten patients out of 33 (30%) tested positive for PTSD. Maternal age, gestational age, and history of cardiac-pulmonary-kidney disease significantly affected HRQoL at multivariable analysis.DiscussionIn COVID-19 pregnant unvaccinated women some physical impairments reducing HRQoL are still present 1 year after hospital discharge. Previous medical history such as history of cardiac-pulmonary-kidney disease significantly affected HRQoL. Long and repeated follow-up should be pursued in this category of patients.Clinical trial registration:ClinicalTrials.gov, Identifier NCT04860687.

Objective: Recto-urethral fistulae (RUF) and recto-vesical fistulae (RVF) are usually related to prostate cancer (PCa) treatment, mainly radical prostatectomy (RP), and a 0.53–9% fistulization rate was observed. Although conservative management is attempted, spontaneous healing is anecdotal and surgical management is often required. Most authors suggested an open approach as less common alternative, due to higher morbidity [1]. Nowadays robotic-assisted surgery represents a viable option. Patients and surgical procedure: we report the case of 71 years-old men who developed an RVF after robot-assisted RP for a Prognostic-Grade-Group 3, pT3bN0 PCa. A conservative attempt, including a transurethral catheter and a colostomy was unsuccessful. A transanal closure according to the Latzko technique was subsequently attempted without results. Then, a robot-assisted transperitoneal repair was planned. Results: before surgery, ureteral stents were positioned. The patient was placed in a low lithotomy position and trocars were arranged as per conventional robot-assisted pelvic surgery. A wide cystotomy was performed at the dome so that the fistula could be visualized and a Pollack catheter was inserted through it. Then, the recto-vesical space was developed, mainly with blunt dissection and cold scissors. The fistulous tract was excised both from the rectal and bladder sides. A double-layer interrupted suture was performed to close both the anterior aspect of the rectum and the bladder. The water tightness of the bladder was assessed with saline solution. An omental flap was then placed between the rectum and the bladder to separate the two suture lines. Conclusions: although over 40 techniques have been described which all share the basic principles for urinary fistula surgical repair, there is no consensus on the optimal treatment. In the last decades, most cases were managed through a transperineal or transanal open approach. With the introduction of robotic surgical systems, the transabdominal approach could be considered a viable option.

The ability to predict the weight of objects is important for skilled and dexterous manipulation during activities of daily living. The observation of other people moving objects might represent an important source of information on object features and help to plan the correct motor interaction with it. In aging, an impaired ability to evaluate the object weight might have negative drawbacks in term of the safety of the person. The aim of this study was to investigate the role of aging in the ability to discriminate the object weight during action observation. Twenty older adults (Old) and twenty young subjects (Young) performed a two-interval forced-choice task consisting in the observation of a couple of videos showing an actor moving a box of different weights. The observer had to evaluate which video showed the heavier box. Handgrip strength was acquired from all subjects. Sensitivity analysis was performed and psychometric curves were built on participants’ responses. The results showed a diminished sensitivity in the object weight discrimination in Old than in Young group. The analysis of the psychometric curves revealed that this impairment pertained both the light and heavy boxes and the minimum difference to discriminate different weights was greater in Old than in Young. At last, the sensitivity and the discrimination ability significantly correlated with individuals’ handgrip strength. These findings allow us to deeply characterize the impairments older adults have in discriminating the weight of an object moved by another individual.

Obesity is associated with gastrointestinal (GI) tract and central nervous system (CNS) disorders. High-fat diet (HFD) feeding-induced obesity in mice induces dysbiosis, causing a shift toward bacteria-derived metabolites with detrimental effects on metabolism and inflammation: events often contributing to the onset and progression of both GI and CNS disorders. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with beneficial effects in mouse models of GI and CNS disorders. However, the mechanisms underlining its enteroprotective and neuroprotective effects still need to be fully understood. Here, we aimed to study the effects of PEA on intestinal inflammation and microbiota alterations resulting from lipid overnutrition. Ultramicronized PEA (30 mg/kg/die per os) was administered to HFD-fed mice for 7 weeks starting at the 12th week of HFD regimen. At the termination of the study, the effects of PEA on inflammatory factors and cells, gut microbial features and tryptophan (TRP)-kynurenine metabolism were evaluated. PEA regulates the crosstalk between the host immune system and gut microbiota via rebalancing colonic TRP metabolites. PEA treatment reduced intestinal immune cell recruitment, inflammatory response triggered by HFD feeding, and corticotropin-releasing hormone levels. In particular, PEA modulated HFD-altered TRP metabolism in the colon, rebalancing serotonin (5-HT) turnover and reducing kynurenine levels. These effects were associated with a reshaping of gut microbiota composition through increased butyrate-promoting/producing bacteria, such as Bifidobacterium, Oscillospiraceae and Turicibacter sanguinis, with the latter also described as 5-HT sensor. These data indicate that the rebuilding of gut microbiota following PEA supplementation promotes host 5-HT biosynthesis, which is crucial in regulating intestinal function.

IntroductionIt has been estimated that 19,880 new cases of ovarian cancer had been diagnosed in 2022. Most epithelial ovarian cancer are sporadic, while in 15%–25% of cases, there is evidence of a familial or inherited component. Approximately 20%–25% of high-grade serous carcinoma cases are caused by germline mutations in the BRCA1 and BRCA2 genes. However, owing to a lack of effective early detection methods, women with BRCA mutations are recommended to undergo bilateral risk-reducing salpingo-oophorectomy (RRSO) after childbearing. Determining the right timing for this procedure is a difficult decision. It is crucial to find a clinical signature to identify high-risk BRCA-mutated patients and determine the appropriate timing for performing RRSO.MethodsIn this work, clinical data referred to a cohort of 184 patients, of whom 7.6% were affected by adnexal tumors including invasive carcinomas and intraepithelial lesions after RSSO has been analyzed. Thus, we proposed an explainable machine learning (ML) ensemble approach using clinical data commonly collected in clinical practice to early identify BRCA-mutated patients at high risk of ovarian cancer and consequentially establish the correct timing for RRSO.ResultsThe ensemble model was able to handle imbalanced data achieving an accuracy value of 83.2%, a specificity value of 85.3%, a sensitivity value of 57.1%, a G-mean value of 69.8%, and an AUC value of 71.1%.DiscussionIn agreement with the promising results achieved, the application of suitable ML techniques could play a key role in the definition of a BRCA-mutated patient-centric clinical signature for ovarian cancer risk and consequently personalize the management of these patients. As far as we know, this is the first work addressing this task from an ML perspective.

This contribution presents an assessment at a regional (island) scale of the beach erosion due to storm events under Climate Change. The approach adopted to assess beach erosion at the island scale consisted of three modules. First, the location, dimensions and other attributes of the Cypriot beaches were recorded on the basis of widely-available satellite imagery. Secondly, sea levels and waves were modeled along the coast under different climatic scenarios and dates in the 21st century. Finally, using these projections beach retreat due to the relative mean sea level rise (RSLR) and extreme sea levels (ESLs) was estimated using ensembles of analytical and numerical cross-shore morphodynamic models, respectively. Extreme sea levels (ESLs) were projected to (a) increase by up to 60% in 2100 from their baseline (2000) levels, and (b) vary along the coast, with the highest ESLs (and corresponding waves) projected for the southern and western coasts. The mostly narrow Cypriot beaches (91% recorded maximum widths of < 50 m) showed increased exposure to erosion. In 2100, about 47% and 72% (based on the median model estimates) of the 241 unprotected Cypriot beaches will be permanently eroded, due to mean sea level rise (SLR), to 50% of their present maximum width, depending on the scenario. In addition to the long-term erosion due to SLR, severe storm erosion is projected by 2050 even under the RCP4.5 scenario; the 100-year extreme sea level event (ESL100) may overwhelm (at least temporarily) 49% of the currently unprotected Cypriot beaches without effective adaptation responses, with the most exposed beaches located along the northern coast. As the beach carrying capacity and hedonic value will be severely compromised, effective adaptation policies and technical measures will be urgently required.

Introduction This project explored the feasibility of implementing an innovative cross-curricular framework using an adaptive learning (AL) platform and telehealth simulations. Objective To determine the feasibility of implementing an innovative cross-curricular framework using an AL platform and telehealth simulations. Methods A mixed-method pilot study was conducted using novel AL modules, adaptive case studies, and telehealth simulation. Results Quantitative data analysis demonstrated significant correlations within and across demographics using the Technology Acceptance Model (TAM) and Simulation Effectiveness Tool-Modified (SET-M). Specifically, significant correlations are evident between TAM ease of use items 1–6, 8, and 10 and TAM usefulness 1, 3, and 9, with SET-M items 3 and 5–15. Thematic analysis revealed that participants felt that the overall project was worthwhile and increased confidence in telehealth. Conclusion Participants found the technology used in this study was easy and useful, and they indicated a positive experience with telehealth simulation. Overall, this study demonstrated that implementation of AL using our paradigm is feasible and supports further investigation into implementing a cross-curricular framework using an AL platform and telehealth simulations.

Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-κB) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-β1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood-brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein-Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.

ObjectiveThe Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects evaluates familial frontotemporal lobar degeneration (FTLD) kindreds with MAPT, GRN, or C9orf72 mutations. Objectives were to examine whether health-related quality of life (HRQoL) correlates with clinical symptoms and caregiver burden, and whether self-rated and informant-rated HRQoL would correlate with each other.MethodsIndividuals were classified using the Clinical Dementia Rating (CDR® ) Scale plus National Alzheimer's Coordinating Center (NACC) FTLD. HRQoL was measured with DEMQOL and DEMQOL-proxy; caregiver burden with the Zarit Burden Interview (ZBI). For analysis, Pearson correlations and weighted kappa statistics were calculated.ResultsThe cohort of 312 individuals included symptomatic and asymptomatic individuals. CDR® plus NACC FTLD was negatively correlated with DEMQOL (r = -0.20, P = .001), as were ZBI and DEMQOL (r = -0.22, P = .0009). There was fair agreement between subject and informant DEMQOL (κ = 0.36, P

ObjectiveTo review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases.MethodsWe systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women.ResultsDrug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (

BackgroundMany women with multiple sclerosis (MS) report fluctuating symptoms across their menstrual cycle. Oral contraceptives (OCs) alter hormonal levels across the menstrual cycle. While cyclic OCs administer hormones for 21 days, followed by a week of placebo, continuous OCs can administer continuous doses of hormones for up to 3 months. Previous studies have suggested that OC use is associated with lower MS-related inflammation. We hypothesized that due to reduced hormonal fluctuations, women with MS might experience less inflammatory activity (clinical relapses+MRI) on continuous OCs than on cyclic OCs.MethodsWe performed a retrospective analysis of prospectively collected data. For women with MS aged 18-50 seen at the UCSF Center for MS and Neuroinflammation, we extracted data on OC use from the Electronic Medical Records (EMR). All variables were confirmed using manual clinical chart review. We identified 19 women with relapsing forms of MS on continuous OCs and matched them (2:1 when possible) to women on cyclic OCs for OC formulation, age, MS duration and DMT type. Inflammatory activity in the two groups was then compared using log-rank tests (time to new relapse, new T2-weighted lesion formation, and gadolinium-enhancing lesion formation) and t-tests (annualized relapse rate). We also performed subgroup analyses in women with at least 1 year (N = 28) and 2 years (N = 21) of clinical observation. A power calculation was performed.ResultsThere was no difference in time to relapse (p = 0.50) between continuous and cycling OC users. However, continuous OC users showed a statistical trend to longer time to T2 lesion formation (p = 0.09) and longer time to contrast-enhancing lesion formation (p = 0.05). In patients with at least 1 year of observation, there was a significant difference in time to T2 lesion formation (p = 0.03) and time to contrast-enhancing lesion formation (p = 0.02).ConclusionIn this exploratory study, women on continuous OCs showed a trend towards less inflammatory activity on MRI relative to women on cyclic OCs. This difference was not reflected in relapse rates. We estimate that 342 patients would be required for an adequately powered cohort study to evaluate such an effect. Our findings provide reassurance that for women using continuous OCs to alleviate menstrual fluctuations in symptoms, there is not an increase in MS-related inflammatory activity.

IntroductionThe Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations.MethodsWe examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.ResultsAsymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.DiscussionImaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

IntroductionSome models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset.MethodsWe created dementia risk scores in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic versus demented participants. The score's predictive value was tested in a separate group who were followed up longitudinally (stable vs. converted to dementia) using Cox proportional regressions with dementia risk score as the predictor.ResultsCross-validated logistic regression achieved good separation of asymptomatic versus demented (accuracy = 90%, SE = 0.06). Atrophy scores predicted conversion from asymptomatic or mildly/questionably symptomatic to dementia (HR = 1.51, 95% CI: [1.16,1.98]).DiscussionIndividualized quantification of baseline brain atrophy is a promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers.

IntroductionIt is important to establish the natural history of familial frontotemporal lobar degeneration (f-FTLD) and provide clinical and biomarker data for planning these studies, particularly in the asymptomatic phase.MethodsThe Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects protocol was designed to enroll and follow at least 300 subjects for more than at least three annual visits who are members of kindreds with a mutation in one of the three most common f-FTLD genes-microtubule-associated protein tau, progranulin, or chromosome 9 open reading frame 72.ResultsWe present the theoretical considerations of f-FTLD and the aims/objectives of this protocol. We also describe the design and methodology for evaluating and rating subjects, in which detailed clinical and neuropsychological assessments are performed, biofluid samples are collected, and magnetic resonance imaging scans are performed using a standard protocol.DiscussionThese data and samples, which are available to interested investigators worldwide, will facilitate planning for upcoming disease-modifying therapeutic trials in f-FTLD.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Introduction: In-service exam scores are used by residency programs as a marker for progress and success on board exams. Conference curriculum helps residents prepare for these exams. At our institution, due to resident feedback a change in curriculum was initiated. Our objective was to determine whether assigned Evidence-Based Medicine (EBM) articles and Rosh Review questions were non-inferior to Tintinalli textbook readings. We further hypothesized that the non-textbook assigned curriculum would lead to higher resident satisfaction, greater utilization, and a preference over the old curriculum.Methods: We collected scores from both the allopathic In-training Examination (ITE) and osteopathic Emergency Medicine Residency In-service Exam (RISE) scores taken by our program’s residents from both the 2015-2016 and 2016-2017 residency years. We compared scores pre-curriculum change (pre-CC) to scores post-curriculum change (post-CC). A five-question survey was sent to the residents regarding their satisfaction, preference, and utilization of the two curricula.Results: Resident scores post-CC were shown to be non-inferior to their scores pre-CC for both exams. There was also no significant difference when we compared scores from each class post-CC to their respective class year pre-CC for both exams. Our survey showed significantly more satisfaction, utilization, and preference for this new curriculum among residents.Conclusion: We found question-based learning and Evidence-Based Medicine articles non-inferior to textbook readings. This study provides evidence to support a move away from textbook readings without sacrificing scores on examinations.