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EGFR inhibitors used in the treatment of metastatic wild-RAS colorectal cancer in combination with chemotherapy are associated with dermatologic side events that are low grade in most cases. We report a case of severe cutaneous toxicity secondary to cetuximab associated with bacterial cellulitis. A 57-year-old woman with metastatic adenocarcinoma of the colon, receiving FOLFIRI and Cetuximab as a first-line treatment, presented with a severe erythematous rash and xerosis resistant to local treatment with moisturizing emollients. Few days later, the patient becomes febrile, and the rash becomes more diffuse with a sandpaper appearance on the face, neck, chest, and flexor creases with exfoliation of large areas of skin. A bacterial cellulitis secondary to a dermatologic severe toxicity of Cetuximab was suspected. The patient started on antibiotics and local treatment with good response. This is a life-threatening cutaneous toxicity of cetuximab with secondary bacterial infection. Early recognition of cutaneous side effects of EGFR inhibitors is important to prevent such type of toxicities.

The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three-phase parallel study design with a washout period of 4 weeks, in which sheep received a 4 mg/kg SC dose in phase 1, a 4 mg/kg PO administration in phase 2, and a 2 mg/kg IV administration in phase 3. Plasma RX concentrations were measured over a 48 h period for each treatment using HPLC coupled to a UV multiple wavelength detector, and the PK parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 2.64 h, 0.077 L/kg, and 0.056 L/h kg, respectively. The mean peak plasma concentrations following SC and PO administrations were 7.04 and 3.01 μg/mL, respectively. The mean bioavailability following SC and PO administrations were 45.98% and 16.58%, respectively. The SC route may be proposed for use in sheep. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in sheep.

To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease.Retrospective case series.Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations.Review of case notes, retinal imaging, electrophysiologic assessment, molecular genetic testing including protein modeling, and histologic analysis of muscle biopsy.Phenotypic characteristics of mitochondrial retinopathy.Genetic testing identified sporadic large-scale mitochondrial DNA deletions and variants in MT-TL1, MT-ATP6, MT-TK, MT-RNR1, or RRM2B. Based on retinal imaging, 3 phenotypes could be differentiated: type 1 with mild, focal pigmentary abnormalities; type 2 characterized by multifocal white-yellowish subretinal deposits and pigment changes limited to the posterior pole; and type 3 with widespread granular pigment alterations. Advanced type 2 and 3 retinopathy presented with chorioretinal atrophy that typically started in the peripapillary and paracentral areas with foveal sparing. Two patients exhibited a different phenotype: 1 revealed an occult retinopathy, and the patient with RRM2B-associated retinopathy showed no foveal sparing, no severe peripapillary involvement, and substantial photoreceptor atrophy before loss of the retinal pigment epithelium. Two patients with type 1 disease showed additional characteristics of mild macular telangiectasia type 2. Patients with type 1 and mild type 2 or 3 disease demonstrated good visual acuity and no symptoms associated with the retinopathy. In contrast, patients with advanced type 2 or 3 disease often reported vision problems in dim light conditions, reduced visual acuity, or both. Short-wavelength autofluorescence usually revealed a distinct pattern, and near-infrared autofluorescence may be severely reduced in type 3 disease. The retinal phenotype was key to suspecting mitochondrial disease in 11 patients, whereas 12 patients were diagnosed before retinal examination.Different types of mitochondrial retinopathy show characteristic features. Even in absence of visual symptoms, their recognition may facilitate the often challenging and delayed diagnosis of mitochondrial disease, in particular in patients with mild or nebulous multisystem disease.

Background The Salud Mesoamérica Initiative (SMI) is a public-private collaboration aimed to improve maternal and child health conditions in the poorest populations of Mesoamerica through a results-based aid mechanism. We assess the impact of SMI on the staffing and availability of equipment and supplies for delivery care, the proportion of institutional deliveries, and the proportion of women who choose a facility other than the one closest to their locality of residence for delivery. Methods We used a quasi-experimental design, including baseline and follow-up measurements between 2013 and 2018 in intervention and comparison areas of Guatemala, Nicaragua, and Honduras. We collected information on 8754 births linked to the health facility closest to the mother’s locality of residence and the facility where the delivery took place (if attended in a health facility). We fit difference-in-difference models, adjusting for women’s characteristics (age, parity, education), household characteristics, exposure to health promotion interventions, health facility level, and country. Results Equipment, inputs, and staffing of facilities improved after the Initiative in both intervention and comparison areas. After adjustment for covariates, institutional delivery increased between baseline and follow-up by 3.1 percentage points (β = 0.031, 95% CI -0.03, 0.09) more in intervention areas than in comparison areas. The proportion of women in intervention areas who chose a facility other than their closest one to attend the delivery decreased between baseline and follow-up by 13 percentage points (β = − 0.130, 95% CI -0.23, − 0.03) more than in the comparison group. Conclusions Results indicate that women in intervention areas of SMI are more likely to go to their closest facility to attend delivery after the Initiative has improved facilities’ capacity, suggesting that results-based aid initiatives targeting poor populations, like SMI, can increase the use of facilities closest to the place of residence for delivery care services. This should be considered in the design of interventions after the COVID-19 pandemic may have changed health and social conditions.

Human papillomavirus (HPV) is responsible for a multitude of lesions with high psychosocial burden. The "HPV Impact Profile" (HIP) questionnaire is one of the first and most specific tools evaluating the emotional impact of HPV. This study aimed to translate this questionnaire into Arabic and to validate it, in a sample of Lebanese female patients.The HIP questionnaire was translated to Arabic. It was then administered to 118 Lebanese women infected with HPV or screened for HPV-associated lesions, in parallel with the Hospital Anxiety and Depression Scale questionnaire. The psychometric properties of the questionnaire were studied in our sample population.The internal consistency of the HIP questionnaire was weak as Cronbach α coefficients of most of the domains were low. The study of the composite matrix resulted in the improvement of the internal consistency after the elimination of some items. Moreover, the "adapted domains" were created by reverse-scoring items with positive implications.The composite reliability and the average variance extracted of all the domains were analyzed. Analysis of discriminate validity through heterotrait-monotrait ratio of correlation ratio analyses of corresponding Hospital Anxiety and Depression Scale domains was also performed along with reliability analysis. There results were satisfying for the adapted domains.The adapted domains of the 27 items questionnaire with reverse scoring of 8 items presented with good psychometric properties, allowing their use in clinical trials and in clinical practice.

BACKGROUND AND PURPOSE: Intracranial stents for the treatment of aneurysms can be responsible for parent artery straightening, a phenomenon with potential consequences for aneurysmal occlusion. We aimed to evaluate parent artery straightening following flow-diverter stent placement in patients with intracranial aneurysms and explored the association between parent artery straightening and subsequent aneurysm occlusion. MATERIALS AND METHODS: All patients treated with flow-diverter stents for anterior circulation aneurysms located downstream from the carotid siphon between January 2009 and January 2018 were screened for inclusion. Parent artery straightening was defined as the difference (α–β) in the parent artery angle at the neck level before (α angle) and after flow-diverter stent deployment (β angle). We analyzed the procedural and imaging factors associated with parent artery straightening and the associations between parent artery straightening and aneurysmal occlusion. RESULTS: Ninety-five patients met the inclusion criteria (n = 64/95 women, 67.4%; mean age, 54.1 [SD, 11.2] years) with 97 flow-diverter stents deployed for 99 aneurysms. Aneurysms were predominantly located at the MCA bifurcation (n = 44/95, 44.4%). Parent artery straightening was found to be more pronounced in patients treated with cobalt chromium stents than with nitinol stents (P = .02). In multivariate analysis, parent artery straightening (P = .04) was independently associated with aneurysm occlusion after flow-diverter stent deployment. CONCLUSIONS: The use of flow-diverter stents for distal aneurysms induces a measurable parent artery straightening, which is associated with higher occlusion rates. Parent artery straightening, in our sample, appeared to be more prominent with cobalt chromium stents than with nitinol stents. This work highlights the necessary trade-off between navigability and parent artery straightening and may help tailor the selection of flow-diverter stents to aneurysms and parent artery characteristics.

Given the vasculopathic nature of moyamoya disease (MMD) and high susceptibility to ischemic events, patients with MMD often require surgical revascularization via an indirect or direct bypass, and analysis of disparities in receipt of appropriate management is critical.The 2012-2016 Nationwide Inpatient Sample was queried for patients admitted with a diagnosis of MMD using International Classification of Diseases codes. Patient baseline demographics, hospital characteristics, and associated symptoms were collected. Patients were grouped by receipt of bypass procedure, and propensity score matching was performed to identify socioeconomic disparities between operative and nonoperative groups.Inclusion criteria were met by 4474 patients (827 pediatric patients and 3647 adult patients). Mean (SD) age for pediatric patients was 10.4 (4.6) years and for adult patients was 40.5 (14.4) years. Among pediatric patients, Black and Hispanic/Latino patients were less likely to undergo revascularization surgery (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.21-0.78, P ≤ 0.01; OR 0.47, 95% CI 0.26-0.84, P =0.01, respectively); among adult patients, Black and Hispanic/Latino patients were similarly less likely to undergo bypass procedures (OR 0.60, 95% CI 0.49-0.72, P ≤ 0.01; OR 0.73, 95% CI 0.55-0.96, P = 0.01, respectively). Pediatric and adult patients in the lowest and next to lowest income quartiles were also less likely to receive operative treatment (pediatric patients: OR 0.61, 95% CI 0.40-0.94, P = 0.02; OR 0.64, 95% CI 0.42-0.98, P = 0.04, respectively; adult patients: OR 0.82, 95% CI 0.88-0.98, P = 0.03).Further investigation into socioeconomic disparities in adult and pediatric patients with MMD is warranted given the potential for inequities in access to appropriate intervention.

Lebanese women have been portrayed as conceited and obsessed with physical appearance and its beautification through cosmetic procedures. Despite the pervasiveness of this notion, no formal studies have been conducted to assess the true prevalence of cosmetic procedures among Lebanese women. Additionally, no data exist to elucidate trends in popularity of cosmetic procedures over time. A cross-sectional study was conducted across Lebanese universities where surveys were distributed to women aged 18-31 years to estimate the prevalence of surgical, noninvasive, and dental cosmetic procedures in young Lebanese women. The collected survey data were analyzed using the Statistical Package for the Social Sciences (SPSS). In a sample of 877 women, 44% reported having undergone at least one cosmetic procedure in their lifetime. The most popular procedures performed were laser hair removal (32%), teeth whitening (14%), and rhinoplasty (9.3%). The obtained results revealed an increasing prevalence of cosmetic procedures, mirroring global trends. A variety of factors have contributed to the increasing popularity of cosmetic procedures, namely, higher availability, better affordability, and wider social acceptance over time. (

Background To assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings. Methods The study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone–retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC. Results Mean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters. Conclusions Our study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction.

Summary Background Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality. Methods We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov , NCT03853824 . Findings Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported. Interpretation This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa. Funding Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists. Translations For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

Oncogenic reprogramming of cellular metabolism is a hallmark of many cancers, but our mechanistic understanding of how such dysregulation is linked to tumor behavior remains poor. In this study, we have identified dihydroceramide desaturase (DES1)-which catalyzes the last step in de novo sphingolipid synthesis-as necessary for the acquisition of anchorage-independent survival (AIS), a key cancer enabling biology, and establish DES1 as a downstream effector of HER2-driven glucose uptake and metabolism. We further show that DES1 is sufficient to drive AIS and in vitro tumorigenicity and that increased DES1 levels-found in a third of HER2+ breast cancers-are associated with worse survival outcomes. Taken together, our findings reveal a novel pro-tumor role for DES1 as a transducer of HER2-driven glucose metabolic signals and provide evidence that targeting DES1 is an effective approach for overcoming AIS. Results further suggest that DES1 may have utility as a biomarker of aggressive and metastasis-prone HER2+ breast cancer.

Background The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. Methods HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. Results We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p

Background: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). Methods: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. Results: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0-78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29-2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001). Conclusions: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay. Fundacion Interhospitalaria para la Investigacion cardiovascular, FIC. Madrid, Spain 3.487 JCR (2021) Q2, 70/143 Cardiac & Cardiovascular Systems 0.52 SJR (2021) Q2, 163/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

The prevalence and incidence of diabetes mellitus (DM) are increasing worldwide. We aim to assess mortality and socio-economic outcomes among patients hospitalized for stroke and diabetes in the US and evaluate their recent trends. We examined: in-hospital mortality, length of stay (LoS), and overall hospital charges in diabetic patients over 18 years old who were hospitalized with a stroke from 2005 to 2014, included in the National Inpatient Sample. In those patients, the mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p-trend < 0.001). Interestingly, although incident cases of stroke amongst DM patients increased from 17.4 to 20.0 /100,000 US adults (p-trend < 0.001), age-adjusted mortality for those with hemorrhagic strokes decreased from 24.3% to 19.6%, and also decreased from 3.23% to 2.48% for those with ischemic strokes (p-trend < 0.01 for both), but remained unchanged in TIAs patients. As expected, the average total charges per hospital stay almost doubled over the ten-year period, increasing from 15 970 to 31 018 USD/stay (adjusted for inflation). Nonetheless, median (IQR) LoS slightly decreased from 4 (2–6) to 3 (2–6) days (p-trend < 0.001). In total, our data show that, from 2005 to 2014, the incidence of stroke among the diabetes patient population are gradually increasing, in-hospital mortality is steadily decreasing, along with average LoS. Admission costs were up almost twofold during the same period.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-021-87320-w

Dynamic changes to the skin barrierrsquo;s molecular structure and ceramide profile are well-documented in skin conditions such as atopic dermatitis and psoriasis. Pathological and environmental factors have been shown to impair barrier integrity and demonstrate shifts in ceramide composition in the skin. However, the relationship between acute and prolonged sun exposure and its effects on skin barrier homeostasis is insufficiently investigated. This study aims to uncover new scientific evidence to elucidate the relationship of UV irradiation with the skin barrier using an ex vivo tissue model following simulated UVA/UVB exposure.nbsp;Fresh ex vivo human skin pretreated either with or without a broad-spectrum sunscreen was exposed to either a physiological or elevated UV condition. Following eight days in culture, structural and molecular changes were evaluated. UV irradiated skin displayed epidermal cell death and altered expression of key barrier proteins. TEM analysis demonstrated disruption to adherens junctions and dissociation between tissue layers following both physiological and extensive UV exposures. An effective broad-spectrum sunscreen containing essential skin ceramides completely protected the skin from such changes. This is one of the first works demonstrating a clear correlation of altered skin barrier integrity using a physiologically relevant dose in an ex vivo tissue model. Our findings also further support the additional importance and benefits of sun protection among the consumers.nbsp;J Drugs Dermatol. 20(4 Suppl):s23-28. doi:10.36849/JDD.S589D.

Purpose To investigate lipofuscin-related quantitative autofluorescence measures and their association with demographic characteristics, retinal structure, retinal function and genotype in ABCA4-related retinopathy (Stargardt disease 1). Design Cross-sectional study with age-matched healthy control subjects. Methods A total of 77 patients with ABCA4-related retinopathy and 110 control subjects underwent quantitative fundus autofluorescence (qAF) imaging using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to measure qAF as surrogate for lipofuscin accumulation. Measures of qAF were correlated with demographic characteristics, structural alterations on optical coherence tomography and fundus autofluorescence imaging, retinal function assessed by full-field electroretinography (ERG) and fundus-controlled perimetry, and genotype. Results Most patients (76.6%) had qAF levels >95% prediction interval of the age-related control group, with best discrimination between cases and control subjects in younger patients. Reduced discrimination based on qAF measures was associated with mild disease, more advanced disease with dark flecks, or older age because of the physiological age-related increase in qAF and a ceiling effect in patients. Nullizygous patients presented with high qAF levels earlier in life compared with those with at least 1 milder ABCA4 variant. Within the sectors of qAF measurements, at approximately 7-9° eccentricity, increased qAF without flecks or with only bright flecks was associated with topographically related preserved retinal thickness and fundus-controlled perimetry results, and with normal full-field ERG recordings. All 3 parameters were increasingly abnormal with the development of dark flecks and decreasing qAF. Conclusions The accumulation of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and may remain without clinically relevant effect on retinal function.

The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain.To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery.This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization.Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge.Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle.A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled.The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery.ClinicalTrials.gov Identifier: NCT04254679.

Donor to recipient (D-R) matching in lung transplantation (LTx) is firstly directed by blood group (identity or compatibility), immunological status and morphological criteria. Sex matching is ignored and impact on outcome less investigated.Systematic review of English literature using PubMed (1990-2019) was performed to evaluate the potential role of D-R matching in determining long-term outcome in patients after LTx. Search terms included (LTx) AND (sex) OR (gender) OR (matching) OR (mismatch) OR (donor characteristics) and were restricted to articles' title. Only articles directly reporting LTx survival outcome according to gender match/mismatch and D-R gender combination in LTx were included. Two authors independently extracted articles using predefined data fields, including study quality indicators. MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies applied.Nine articles were analyzed and included into this study. All studies analyzed the effect of the different D-R gender combinations on survival while seven of them investigated exclusively the role of sex matching on LTx outcome. In this latter group two out of seven showed a trend towards an overall survival advantage for sex matching LTx combination. The worst survival results were reported for F to M gender combination in 3 studies and for M to F gender combination by 1 study. No differences were reported in remaining 4 studies.This systematic review suggests that sex matching and several gender combinations could play a role in determining overall survival rate after LTx. Data deriving from unbiased studies supported that matching female-female (F-F) and male-male (M-M) could improve LTx outcome while FD-MR combination should be avoided. Unfortunately, a good part of the analyzed data are affected by bias due to confounding factors. Up-to-date immunological, hormonal and morphological factors could explain the gender-based difference in LTx outcome. Further investigations should clarify their role and importance to define the effects of gender combinations on survival.

The aim of our study is to investigate the results of constrained total hip arthroplasty as a primary treatment of intertrochanteric fractures (ITF) in elderly patients with high comorbidities. Total hip replacement (THR) with a retentive cup was performed on 73 patients with ITF over the age of 54 years who had high comorbidities and a Charlson score above five. Short- and long-term complications were determined by follow-up. Bivariate analysis was conducted in order to determine the possible determinants of mortality and factors associated with comorbidity as measured by the Charlson comorbidities index. Patient demographics that consisted of females (58.9%) (p

Thyroid nodules (TN) are common in the general population, and the clinical importance of diagnosing thyroid nodules is based on excluding the possibility of thyroid cancer, which occurs in 7-15% of cases. The thyroid gland, owing to its superficial location, is easily accessible via thermography, a noninvasive method of recording body temperature that measures infrared radiation emitted by the body surface. Therefore, this study aimed to evaluate the temperature differences between benign and malignant TN by using thermography. We conducted a cross-sectional study where 147 TN were divided into two groups: the first group included 120 benign nodules and the other included 27 malignant nodules. All the nodules were subjected to ultrasound, fine needle aspiration biopsy, and thermography. On analyzing the thermography results, the benign nodules had a higher temperature at the beginning of the thermography evaluation, and the malignant nodules showed a higher temperature in the middle and at the end (Ft). Using the relationships, it was observed that the temperature delta (ΔT), ΔT nodule/ΔT healthy, ΔT nodule minus ΔT healthy, and nodule Ft minus Ft of the healthy region were higher in malignant nodules. The ROC curve analysis of ΔT demonstrated a cutoff point of 2.38°C, with a sensitivity of 0.963 and specificity of 0.992. Malignant nodules have higher temperatures than benign nodules on thermographic evaluation. This finding suggests that thermography can be a useful tool in the diagnosis of thyroid nodules.

Objective Urodynamic testing of women is a common procedure to evaluate lower urinary tract symptoms but may cause discomfort. The objective of our study was to determine the effect of externally applied periurethral 2% lidocaine gel on pain scores after complex urodynamic testing in women. Methods This prospective, double-blinded, placebo-controlled randomized trial compared 2% lidocaine gel to water-based lubricant applied to the periurethral area before urodynamic testing in women. Discomfort was measured using a visual analog pain scale (VAS) ranging from 0 to 100. The primary outcome was the difference in VAS from baseline to 4 to 6 hours after urodynamic testing. Secondary outcomes included: VAS difference from baseline to immediately postprocedure and 24 hours after urodynamic testing; VAS scores: at baseline, immediately postprocedure, after 4-6 hours, and after 24 hours; urodynamic testing results; and any adverse events. Sixty-four women per group were needed to provide a power of 80% to detect a 10-mm difference on a 100-point VAS. Results From January 2018 to March 2019, 134 subjects were randomized, 6 subjects were excluded, which resulted in 64 subjects in both the water-based lubricant group and 2% lidocaine gel group. There was no difference in baseline demographics. There was no significant difference in the change in VAS from baseline to 4 to 6 hours after UDT (0, 0 P = 0.88). No difference in secondary outcomes was noted. Conclusions Topically applied 2% lidocaine gel does not decrease pain compared with water-based lubricant. For most women, complex urodynamic testing is not associated with any significant pain. Clinical trial registration www.ClinicalTrials.gov,-NCT03390790, "Lidocaine for Pain After Urodynamic Testing".

BACKGROUND AND PURPOSE: Intracranial hemorrhage represents a severe complication of brain arteriovenous malformation treatment. The aim of this cohort was to report the rate of hemorrhagic complications after transvenous endovascular embolization and analyze the potential angioarchitectural risk factors as well as clinical outcomes. MATERIALS AND METHODS: During an 11-year period, 57 patients underwent transvenous endovascular embolization. All cases of hemorrhagic complications were identified. We analyzed the following variables: sex, age, hemorrhagic presentation, Spetzler-Martin grade, size of the AVM before the transvenous treatment, number of venous collectors, pattern of drainage, presence of dilated veins, and technical aspects. Univariate and multivariate multiple regression analyses were performed to evaluate the potential risk factors for procedure-related hemorrhagic complications. RESULTS: Hemorrhagic complications (either intraprocedural or periprocedural) unrelated to a perforation due to micronavigation occurred in 8 (14.0%) procedures. Significant (mRS > 2) and persistent neurologic deficits were present in 2 (3.5%) patients at 6-month control. Larger nidi, especially >3 cm (P = .03), and a larger number of venous collectors have shown a statistically significant correlation with hemorrhagic complications. Only the number of venous collectors was identified as an independent predictor of hemorrhagic complications in the multivariate analysis (OR, 8.7; 95% confidence interval, 2.2–58.2) (P = .006). CONCLUSIONS: Larger nidus sizes and an increased number of venous collectors may increase the risk of hemorrhagic complications when implementing transvenous endovascular treatment of AVMs. The technique is effective and promising, especially with small nidi and single venous collectors.

BackgroundBlebs are important secondary structures of intracranial aneurysms associated with increased rupture risk and can affect local wall stress and hemodynamics. Mechanisms of bleb development and evolution are not clearly understood. We investigate the relationship between blebs with different wall characteristics and local hemodynamics and rupture sites.MethodsBlebs with different wall appearances in intra-operative videos were analyzed with image-based computational fluid dynamics. Thin red blebs were compared against thick atherosclerotic/hyperplastic white/yellow blebs. Rupture points were identified in videos of ruptured aneurysms harboring blebs.ResultsThin blebs tended to be closer to the inflow than atherosclerotic blebs of the same aneurysm (P=0.0234). Blebs near the inflow had higher velocity (P=0.0213), vorticity (P=0.0057), shear strain rate (P=0.0084), wall shear stress (WSS) (P=0.0085), and WSS gradient (P=0.0151) than blebs far from the inflow. In a subset of 12 ruptured aneurysms harboring blebs, rupture points were associated with thin blebs in 42% of aneurysms, atherosclerotic blebs in 25%, and were away from blebs in the remaining 33%.ConclusionsNot all blebs are equal; some have thin translucent walls while others have thick atherosclerotic walls. Thin blebs tend to be located closer to the inflow than atherosclerotic blebs. Blebs near the inflow are exposed to stronger flows with higher and spatially variable WSS than blebs far from the inflow which tend to have uniformly lower WSS. Aneurysms can rupture at thin blebs, atherosclerotic blebs, and even away from blebs. Further study of wall failure in aneurysms with different bleb types is needed.

Secondary intracerebral hemorrhage (SICH) score is used to predict risk of intracranial hemorrhage (ICH) associated vascular lesions. However, it has low clinical utility in identifying patients without need for neurovascular imaging. This study aims to develop a modified scoring system to capture patients with low risk of underlying vascular pathology, thereby decreasing need for vascular imaging and its associated morbidity.A retrospective analysis of 994 patients with atraumatic ICH over 8 years was conducted, excluding known underlying pathology, subarachnoid hemorrhage, or lack of vascular imaging. Using a multivariate logistic regression model, independent predictors of vascular pathology were identified and utilized toward developing a modified Secondary Intracerebral Hemorrhage (mSICH) score.Of 575 patients identified, 60 (10.4%) had underlying vascular etiology. Statistically significant predictors of vascular pathology included age; female sex; admission systolic blood pressure160 mm Hg; locations other than basal ganglia, thalamus, pons, or midbrain; presence of high-risk imaging features; and proximity to large vessel-containing cisterns. The mSICH score correlated with an increasing incidence of vascular pathology [0-1 (0%), 9 (4.3%), 12 (9.7%), 21 (40.4%), 6 (33.3%), 8 (88.9%), and 4 (100%)] and had a significantly higher number of patients receiving scores with 0% incidence of vascular lesions compared with the SICH score [159 (27.6%) versus 12 (2.1%); P0.001)].The mSICH score can more accurately predict risk of underlying vascular pathology of ICH and identify patients with lowest risk of vascular pathology. This may minimize the cost and associated risks of invasive cerebrovascular imaging.

Background and purpose Pre-surgical embolization of large intracranial meningioma has been demonstrated to decrease blood loss and to improve the resectability of the tumor. Few reports have evaluated the risk and benefits of using Onyx in this indication. The objective of our study was to assess the efficiency and safety of pre-surgical embolization in a consecutive series of intracranial meningioma using Onyx. Materials and methods We conducted a retrospective study of consecutive patients treated from 2010 to 2018 with pre-surgical embolization with Onyx for intracranial histologically-proven meningioma. Safety was evaluated by a report of the complications related to the procedure while efficacy was assessed on angiographic and histopathologic criteria. Results Forty-four meningioma in 44 patients treated with pre-surgical embolization were included in this study. Proximal artery occlusion was obtained in 97.6% (41/42) of the cases and good intra-tumoral penetration was achieved in 75.6% (31/41). Embolic agent inside blood vessels was identified in 63.5% (28/44) of cases. Embolization-induced necrosis was present in 79.6% (35/44) of cases. Six complications have been encountered (13.6%); 3 were stated as minor complications (6.8%) and 3 as major occurring in case of trans-ophthalmic route (6.8%). Conclusions The present work is to date the largest study to evaluate intracranial meningioma embolization using Onyx. Onyx's allowed good intra-tumoral penetration and proximal artery occlusion in most cases but carries a higher risk of complication in case of ophthalmic supply.

Adult-onset noncirrhotic hyperammonemia (NCH) is poorly understood and has a high morbidity and mortality. To elucidate the etiology and management of NCH, we performed a retrospective analysis of 23 adults (median age 51) with NCH treated between 2014 and 2020 at two academic medical centers. Hyperammonemia was diagnosed in all cases during the evaluation of altered mental status, with 22% presenting with seizures. Peak ammonia levels were >200 μmol/L in 70% of cases. Defects in ammonia metabolism were assessed using urea cycle biochemical testing, germline genetic testing, and testing for urease-producing infectious agents. Ammonia metabolism defects in these cases appear attributable to four major sources: (a) infection with urease-producing organism (n = 5); (b) previously undiagnosed inborn errors of metabolism (IEMs) (n = 4); (c) clinical exposures causing acquired urea cycle dysfunction (n = 6); and (d) unexplained acquired urea cycle dysfunction (uaUCD) (n = 8), as evidenced by biochemical signatures of urea cycle dysfunction without a genetic or clinical exposure. Severe protein malnutrition appeared to be a reversible risk factor for uaUCD. Overall, 13% of our cohort died prior to resolution of hyperammonemia, 26% died after hyperammonemia resolution, 57% survived after having reversible neurological changes, and 4% survived with irreversible neurological changes. Renal replacement therapy for ammonia clearance was often utilized for patients with an ammonia level above 250 μmol/L and patients were frequently empirically treated with antibiotics targeting urea-splitting organisms. Our study demonstrates that acquired urea cycle dysfunction, IEMs and urease-producing infections are major sources of adult-onset NCH and highlights successful management strategies for adult-onset NCH.

BackgroundEndovascular embolization of cerebral arteriovenous malformations (AVM) with liquid n-butyl cyanoacrylate (n-BCA) serves multiple purposes including AVM occlusion and flow reduction in preparation for other treatment modalities. The objective was to study the clinical, structural, and angiographic factors affecting complications associated with AVM treatment by sequential n-BCA embolizations for nidal occlusion versus quantitative flow reduction in preparation for surgical resection or radiosurgery.MethodsWe performed a retrospective review of all patients who underwent endovascular embolization of cerebral AVM at our institution between 1998 and 2019, during which time the technique of traditional embolization evolved to a strategy of targeted sequential flow reduction guided by serial flow imaging based on quantitative magnetic resonance angiography, in conjunction with a shift away from nidal penetration.ResultsAmong 251 patients, 47.8% of patients presented with ruptured AVM. On average, each patient underwent 2.4 embolizations, for a total of 613 sessions. Major morbidity related to embolization occurred in 18 (7.2%) patients, but this occurred disproportionately in the traditional embolization strategy (n=16, 8%) in contrast with the flow-targeting strategy (n=2, 3.8%). Four patients (1.6%) died in the overall group, and these all occurred with the traditional embolization strategy (2% of 199 patients); no deaths occurred in the flow-targeting strategy (n=52).ConclusionEmbolization with n-BCA targeted to sequential flow reduction and feeder occlusion with limited nidal penetration prior to definitive surgical or radiosurgical treatment can be safely performed with low overall morbidity and mortality.

Purpose To investigate quantitatively lipofuscin-associated fundus autofluorescence in patients with macular and cone/cone–rod dystrophies (MD/CCRDs). Design Prospective, single-center, case-control study. Participants Two hundred thirty patients with MD/CCRDs who had undergone genetic testing and 110 control participants without any eye disease. Methods Participants were examined using quantitative fundus autofluorescence (qAF) imaging with a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference (modified Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). Mean qAF values were obtained by averaging measurements from an 8-segment ring centered on the fovea (qAF8) and compared with controls. Main Outcome Measures The qAF8 levels. Results Elevated qAF8 values were a frequent finding (n = 105 [45%]) and associated with ABCA4 (n = 73 [70%]), PRPH2 (n = 9 [9%]), CERKL (n = 3 [3%]), PROM1 (n = 2 [2%]), CRX (n = 1 [1%]), and CDHR1 (n = 1 [1%]) mutations. Reduced qAF8 values were rare (n = 15 [7%]) and found predominantly among patients with MERTK (n = 3 [20%]) and RDH5 (n = 2 [13%]) mutations. Patients with normal qAF8 values (n = 110 [48%]) showed high genotypic heterogeneity. For various genes including ABCA4, PRPH2, CDHR1, and PROM1, higher qAF8 measures were associated with specific phenotypes and genotypes. For instance, qAF8 values were normal in PRPH2-related central areolar chorioretinal dystrophy but increased in PRPH2-related Stargardt-like retinopathy. Accordingly, high qAF8 levels were associated with specific genetic causes and mutation detection rates in characteristic but genetically heterogenous clinical phenotypes, such as a Stargardt-like flecked fundus, bull’s eye maculopathy, or pattern dystrophy. In genetically unsolved cases (16 with elevated, 35 with normal, 7 with reduced qAF values), qAF8 was used to support or reject ambiguous results of genetic testing, to suggest underlying pathogenic pathways, and to predict disease in otherwise healthy participants. Conclusions Quantitative fundus autofluorescence imaging revealed characteristic qAF levels in association with certain gene mutations and in participants without detected mutations. These findings indicate that qAF may facilitate differential diagnostics of MD/CCRDs and may offer novel pathogenetic insights that may be of particular value for the assessment of future treatment approaches.

Objective Preclinical evidence with nilotinib, a US Food and Drug Administration (FDA)-approved drug for leukemia, indicates improvement in Alzheimer's disease phenotypes. We investigated whether nilotinib is safe, and detectable in cerebrospinal fluid, and alters biomarkers and clinical decline in Alzheimer's disease. Methods This single-center, phase 2, randomized, double-blind, placebo-controlled study investigated the safety, tolerability, and pharmacokinetics of nilotinib, and measured biomarkers in participants with mild to moderate dementia due to Alzheimer's disease. The diagnosis was supported by cerebrospinal fluid or amyloid positron emission tomography biomarkers. Nilotinib 150 mg versus matching placebo was taken orally once daily for 26 weeks followed by nilotinib 300 mg versus placebo for another 26 weeks. Results Of the 37 individuals enrolled, 27 were women and the mean (SD) age was 70.7 (6.48) years. Nilotinib was well-tolerated, although more adverse events, particularly mood swings, were noted with the 300 mg dose. In the nilotinib group, central nervous system (CNS) amyloid burden was significantly reduced in the frontal lobe compared to the placebo group. Cerebrospinal fluid Aβ40 was reduced at 6 months and Aβ42 was reduced at 12 months in the nilotinib group compared to the placebo. Hippocampal volume loss was attenuated (-27%) at 12 months and phospho-tau-181 was reduced at 6 months and 12 months in the nilotinib group. Interpretation Nilotinib is safe and achieves pharmacologically relevant cerebrospinal fluid concentrations. Biomarkers of disease were altered in response to nilotinib treatment. These data support a larger, longer, multicenter study to determine the safety and efficacy of nilotinib in Alzheimer's disease. ANN NEUROL 2020 ANN NEUROL 2020;88:183-194.

Background The treatment of aortic infections is complex, and the material of reconstruction remains discussed. Several alternatives were suggested in the literature. The current consensus is the use of biological material. The aim of this study was to evaluate the short-term results of bovine pericardium xenografts. Methods Between November 2016 and June 2019, we included consecutively all the patients presenting with native aortic infections in which arterial reconstruction was carried out with tubular bovine pericardium grafts sutured longitudinally. We collected the preoperative, peroperative, and postoperative clinical, radiological, biological, and bacteriological characteristics. The recurrence of infection, the graft failures, and the morbimortality were analyzed. Results Twelve patients including three women were treated. Their mean age was 68.4 ± 9 years. They presented 2 thoracic, 4 thoracoabdominal, 4 abdominal, and 2 aortoiliac aneurysms. The diagnosis was made using angio-CT in all the cases and was confirmed by positron emission tomography (PET) scan in 7 cases and blood cultures in 9 cases. Peroperative cultures were positive in 11 cases. Antibiotics were given in 9 patients before operation for a median duration of 9 (3–19) days and in all the patients postoperatively for a median duration of 42 (1–540) days. The median follow-up was 355 (98–839) days. Six medical complications occurred, including 2 (16.6%) leading to death in the immediate postoperative period. No reoperation was needed. The PET scan returned positive in 1/10 cases (10%) during the follow-up. The diameter of the grafts was preserved, without any defect observed on the angio-CT. Conclusions Short-term results showed a mechanical resistance to infection of the bovine pericardium. This biological material offers a promising alternative with multiple advantages including availability, simplicity of preparation, and adaptability to the various locations of the aortic infection.

BackgroundChild and adolescent injury is one of the leading causes of child death globally with a large proportion occurring in Low- and Middle-Income Countries (LMICs). Similarly, the Eastern Mediterranean Region (EMR) countries borne a heavy burden that largely impact child and adolescent safety and health in the region. We aim to assess child and adolescent injury morbidity and mortality and estimate its burden in the Eastern Mediterranean Region based on findings from the Global Burden of Disease (GBD), Injuries and Risk Factors study 2017.MethodsData from the Global Burden of Disease GBD 2017 were used to estimate injury mortality for children aged 0–19, Years of Life Lost (YLLs), Years lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs) by age and sex from 1990 to 2017.ResultsIn 2017, an estimated 133,117 (95% UI 122,587-143,361) children died in EMR compared to 707,755 (95% UI 674401.6–738,166.6) globally. The highest rate of injury deaths was reported in Syria at 183.7 (95% UI 181.8–185.7) per 100,000 population. The leading cause of injury deaths was self-harm and interpersonal violence followed by transport injury. The primary cause of injury DALYs in EMR in 2017 was self-harm and interpersonal violence with a rate of 1272.95 (95% UI 1228.9 – 1319.2) almost 3-times the global rate.ConclusionAlmost 19% of global child injury related deaths occur in the EMR. Concerted efforts should be integrated to inform policies and adopt injury preventive strategies to reduce injury burden and promote child and adolescent health and well-being in EMR countries.

Diabetes triggers peripheral nerve alterations at a structural and functional level, collectively referred to as diabetic peripheral neuropathy (DPN). This work highlights the role of the liver X receptor (LXR) signaling pathway and the cross talk with the reactive oxygen species (ROS)–producing enzyme NADPH oxidase-4 (Nox4) in the pathogenesis of DPN. Using type 1 diabetic (T1DM) mouse models together with cultured Schwann cells (SCs) and skin biopsies from patients with type 2 diabetes (T2DM), we revealed the implication of LXR and Nox4 in the pathophysiology of DPN. T1DM animals exhibit neurophysiological defects and sensorimotor abnormalities paralleled by defective peripheral myelin gene expression. These alterations were concomitant with a significant reduction in LXR expression and increase in Nox4 expression and activity in SCs and peripheral nerves, which were further verified in skin biopsies of patients with T2DM. Moreover, targeted activation of LXR or specific inhibition of Nox4 in vivo and in vitro to attenuate diabetes-induced ROS production in SCs and peripheral nerves reverses functional alteration of the peripheral nerves and restores the homeostatic profiles of MPZ and PMP22. Taken together, our findings are the first to identify novel, key mediators in the pathogenesis of DPN and suggest that targeting LXR/Nox4 axis is a promising therapeutic approach.

Fall of the elderly person is a public health problem. The objectives of our study were to evaluate the relevance of systematically performing in emergency a computed tomography (CT) scan for fall in the elderly person, to identify specific criteria predicting the appearance of lesions.We performed a retrospective analysis of 500 consecutive patients aged 65 and over, who underwent an emergency head CT scan for fall from their height. Outcome at the end of the acute care, clinico-biological data and delays between trauma an d CT were collected, and crossed with a detection of head lesion on the CT scan.Of 500 patients, 38 (7.6%) had traumatic lesions depicted on the CT scan and 267 (53.4%) were hospitalized after the CT scan. Three (0.6%) had been operated for urgent head surgery. Nine of the 38 (23.6%) patients with traumatic lesion returned home. Presence of a lesion depicted on the CT scan was not correlated with the orientation of the patient (P 0.0001). Post-traumatic injury was significantly associated with male sex (RR = 2.19, P = 0.0217), consciousness impairment (RR = 1.56, P 0.0001), focal neurological deficit (RR = 6.36, P = 0.0362) and past history of post-traumatic brain injury (RR = 7.17, P = 0.0027). Anticoagulant therapy was not associated with increased risk of traumatic lesions (P = 0.3315). ROC analysis determined that a 5-hours time-interval between head trauma and CT allowed optimal detection of lesions.The systematic indication of an emergency head CT scan for fall in elderly patients presents a low diagnostic and therapeutic yield and is not relevant. Male sex, consciousness impairment, focal neurological deficit, past history of post-traumatic brain injury and time-interval between head trauma and CT are statistically related to the presence of lesions and should therefore be taken into account.

OBJECTIVE Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time. RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001). CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

Background Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). Methods A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs’ apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. Results Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p Conclusion Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.

To report a case of multiple evanescent white dot syndrome (MEWDS) associated with acute progression of lacquer cracks in high myopia.A 41-year-old female patient with high myopia developed typical signs, symptoms, and disease course of MEWDS in her right eye. At the same time, the same eye showed progression of lacquer cracks when compared to images taken 2 months prior. Retinal imaging findings characteristic of MEWDS were most obvious on fundus autofluorescence, whereas alterations on color fundus photography, optical coherence tomography, fluorescein, and indocyanine green angiography were very mild, probably because of the myopia-related fundus pathology.We present a case of MEWDS co-occurring with acute progression of lacquer cracks. This adds to the increasing evidence that impaired integrity of the retinal pigment epithelium-Bruch's membrane complex may be a factor in causing MEWDS, possibly by exposing otherwise isolated antigens. The anatomy in a highly myopic eye may make it challenging to diagnose MEWDS-associated fundus changes.ZIEL: Bericht einer Assoziation von Multiple Evanescent White Dot Syndrome (MEWDS) mit akuter Progression von Lacksprüngen bei hoher Myopie. KASUISTIK: Eine 41-jährige hochmyope Patientin entwickelte am rechten Auge die typischen Zeichen, Symptome und den Krankheitsverlauf von MEWDS. Im Vergleich zu Fundusbildern, die 2 Monate zuvor aufgenommen wurden, zeigte sich am rechten Auge gleichzeitig eine Progression von Lacksprüngen. Die für MEWDS charakteristischen Netzhautbefunde waren am deutlichsten in der Fundusautofluoreszenzuntersuchung zu erkennen, wohingegen sich nur geringe Veränderungen in der Fundusfotografie, optischen Kohärenztomografie sowie in der Fluorescein- und Indocyaningrünangiografie zeigten, wahrscheinlich aufgrund der myopiebedingten Funduspathologie. SCHLUSSFOLGERUNG: Wir berichten einen MEWDS-Fall, der mit einer akuten Progression von Lacksprüngen bei hoher Myopie einhergeht. Dies bestärkt die Annahme, dass eine gestörte Integrität des retinalen Pigmentepithel-Bruch-Membran-Komplexes ein pathogenetischer Faktor bei der Entwicklung von MEWDS sein kann, möglicherweise durch Exposition von ansonsten isolierten Antigenen. Die Anatomie eines stark myopen Auges kann die Diagnose MEWDS-assoziierter Fundusveränderungen erschweren.

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.

BackgroundTraditional fishing communities are strongholds of ethnobiological knowledge but establishing to what degree they harbor cultural consensus about different aspects of this knowledge has been a challenge in many ethnobiological studies.MethodsWe conducted an ethnobiological study in an artisanal fishing community in northeast Brazil, where we interviewed 91 community members (49 men and 42 women) with different type of activities (fishers and non-fishers), in order to obtain free lists and salience indices of the fish they know. To establish whether there is cultural consensus in their traditional knowledge on fish, we engaged a smaller subset of 45 participants in triad tasks where they chose the most different fish out of 30 triads. We used the similarity matrices generated from the task results to detect if there is cultural consensus in the way fish were classified by them.ResultsThe findings show how large is the community’s knowledge of fish, with 197 ethnospecies registered, of which 33 species were detected as salient or important to the community. In general, men cited more fish than women. We also found that there was no cultural consensus in the ways fish were classified.ConclusionsBoth free-listing and triad task methods revealed little cultural consensus in the way knowledge is structured and how fish were classified by community members. Our results suggest that it is prudent not to make assumptions that a given local community has a single cultural consensus model in classifying the organisms in their environment.

The human papillomavirus (HPV) has been associated with an important psychosocial impact. This impact has been poorly evaluated in developing countries, mostly because of the lack of instruments to quantify it. The HIP questionnaire aims to measure HPV-associated affective burden. Our team has previously translated this questionnaire to Arabic and used it to assess the impact of HPV on Lebanese women.While the HIP is a specific tool to evaluate the emotional impact of HPV, the Hospital Anxiety and Depression Scale questionnaire consists of 2 scales, anxiety and depression, and assess the psychological distress in nonpsychiatric patients. The HPV impact profile and Hospital Anxiety and Depression Scale questionnaires were administered to 118 Lebanese women with an HPV-related presentation, aiming to determine which aspect of these women's lives was mostly affected. The association with different sociodemographic factors was also assessed.Feelings of "concerns and worries" were mostly strongly felt in our population except for women with genital warts who were more concerned with the risk of transmission and the impact on their partners. All women had predominant feelings of anxiety.Religion was a statistically significant influencing factor and employment a protective factor. Muslim women demonstrated significant adverse affects on HPV impact profile domains that included: "sexual impact," "self-image," "interaction with doctors," and "health control/life impact."Different women perceive the diagnosis of HPV and HPV-related lesions differently. In this study, employment was found to play a protective role, but the biggest influencers were social and religious beliefs.