Impact of Carotid Siphon Calcification on the Course and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies.

PURPOSE: Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. METHODS: A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. RESULTS: A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). CONCLUSION: This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

Functional outcome after initial and multiple intracerebral hemorrhages in children with cerebral cavernous malformations.

BACKGROUND AND PURPOSE: We aimed to assess the course and predictors of functional outcome after single and multiple intracerebral hemorrhage (ICH) in pediatric patients with cerebral cavernous malformations (CCMs) and to conduct a risk assessment of a third bleed during the first follow-up year after second ICH. METHODS: We included patients aged ≤18 years with complete baseline characteristics, a magnetic resonance imaging dataset, ≥1 CCM-related ICH and ≥1 follow-up examination, who were treated between 2003 and 2021. Neurological functional status was obtained using modified Rankin Scale scores at diagnosis, before and after each ICH, and at last follow-up. Kaplan-Meier analysis was performed to determine the cumulative 1-year risk of third ICH. RESULTS: A total of 55 pediatric patients (median [interquartile range] age 12 [11] years) were analyzed. Univariate analysis identified brainstem cavernous malformation (BSCM; p = 0.019) as a statistically significant predictor for unfavorable outcome after second ICH. Outcome after second ICH was significantly worse in 12 patients (42.9%; p = 0.030) than after first ICH and in five patients (55.6%; p = 0.038) after a third ICH compared to a second ICH. Cumulative 12-month risk of rebleeding during the first year after a second ICH was 10.7% (95% confidence interval 2.8%-29.37%). CONCLUSIONS: Pediatric patients with a BSCM have a higher risk of worse outcome after second ICH. Functional outcome improves over time after an ICH but worsens following each ICH compared to baseline or previous ICH. Second bleed was associated with neurological deterioration compared to initial ICH, and this deteriorated further after a third ICH.

Small intracranial aneurysms of the anterior circulation: A negligible risk?

BACKGROUND AND PURPOSE: According to the International Study of Unruptured Intracranial Aneurysms, small (<7 mm) unruptured intracranial aneurysms (IAs) of the anterior circulation (aC) carry a neglectable 5-year rupture risk. In contrast, some studies report frequencies of >20% of all ruptured IAs being small IAs of the aC. This contradiction was addressed in this study by analyzing the rates and risk factors for rupture of small IAs within the aC. METHODS: Of the institutional observational cohort, 1676 small IAs of the aC were included. Different demographic, clinical, laboratory, and radiographic characteristics were collected. A rupture risk score was established using all independent prognostic factors. The score performance was checked using receiver operating characteristic curve analysis. RESULTS: Of all registered small IAs of the aC, 20.1% were ruptured. The developed small IAs of the aC (SIAAC) score (range = -4 to +13 points) contained five major risk factors: IA location and size, arterial hypertension, alcohol abuse, and chronic renal failure. In addition, three putative protective factors were also included in the score: hypothyroidism, dyslipidemia, and peripheral arterial disease. Increasing rates of ruptured IA with increasing SIAAC scores were observed, from 0% (≤-1 points) through >50% (≥8 points) and up to 100% in patients scoring ≥12 points. The SIAAC score achieved excellent discrimination (area under the curveSIAAC  = 0.803) and performed better than the PHASES (Population,Hypertension, Age, Size of the aneurysm, Earlier SAH from another aneurysm, Site of aneurysm) score. CONCLUSIONS: Small IAs of the aC carry a considerable rupture risk. After external validation, the proposed rupture risk score might provide a basis for better decision-making regarding the treatment of small unruptured IAs of the aC.

Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.

Functional neurological outcome of spinal cavernous malformation surgery.

PURPOSE: Spinal cavernous malformations (SCM) present a risk for intramedullary hemorrhage (IMH), which can cause severe neurologic deficits. Patient selection and time of surgery have not been clearly defined. METHODS: This observational study included SCM patients who underwent surgery in our department between 2003 and 2021. Inclusion required baseline clinical factors, magnetic resonance imaging studies, and follow-up examination. Functional outcome was assessed using the Modified McCormick scale score. RESULTS: Thirty-five patients met the inclusion criteria. The mean age was 44.7 ± 14.5 years, and 60% of the patients were male. In univariate analysis, the unfavorable outcome was significantly associated with multiple bleeding events (p = .031), ventral location of the SCM (p = .046), and incomplete resection (p = .028). The time between IMH and surgery correlated with postoperative outcomes (p = .004), and early surgery within 3 months from IMH was associated with favorable outcomes (p = .033). This association remained significant in multivariate logistic regression analysis (p = .041). CONCLUSIONS: Removal of symptomatic SCM should be performed within 3 months after IMH when gross total resection is feasible. Patients with ventrally located lesions might be at increased risk for postoperative deficits.

Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. METHODS: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. RESULTS: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15-8.63]; P=0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04-5.86]; P=0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18-8.99]; P=0.022 and odds ratio, 2.53 [95% CI, 1.07-5.98]; P=0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80-110.39]; P=0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%-23.6%) for the entire cohort, 30.2% (20.2%-42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%-51.1%) for children with brain stem CCM. CONCLUSIONS: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery.

PURPOSE: Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. METHODS: We included 93 female patients who underwent BC BM surgery in our institution (2008-2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. RESULTS: The median TI was 45.0 months (range: 9-334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47-61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02-0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46-12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III-IV of BC (aOR 4.82, 95% CI 1.10-21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09-98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35-15.40, p = 0.015). CONCLUSIONS: Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

The occurrence of neuropathic pain following surgery of brainstem cavernous malformations.

BACKGROUND AND PURPOSE: This study aimed to assess the occurrence and significance of postoperative neuropathic pain (NP) in patients with surgically treated brainstem cavernous malformations (BSCMs). METHODS: Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. The relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL) and life satisfaction was evaluated. RESULTS: Six out of 74 patients (8%) suffered from NP. The Leeds Assessment of Neuropathic Symptoms and Signs scores ranged from 12 to 16 (mean 14.28 ± 1.6). Visual analog scale pain was 5.2 ± 2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (life satisfaction) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient- and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of six patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results. CONCLUSION: Our findings may help to raise awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non-familial disease.

BACKGROUND AND PURPOSE: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. METHODS: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. RESULTS: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. CONCLUSIONS: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Color and translucency of milled polymethyl methacrylate crowns on non-tooth-colored interim abutments with different surface treatments.

STATEMENT OF PROBLEM: The interim rehabilitation of implants has become a necessity, particularly for those placed in the esthetic regions. However, the optical properties of computer-aided design and computer-aided manufacturing (CAD-CAM) polymethyl methacrylate (PMMA) crowns on interim abutments with different surface treatments are unclear. PURPOSE: The purpose of this in vitro study was to investigate the color and translucency of CAD-CAM PMMA crowns when different surface treatments were used on titanium interim abutments. MATERIAL AND METHODS: A maxillary dentate stone cast with a narrow-diameter implant analog at the left lateral incisor site was used. Three titanium interim abutments (blue) were divided into 3 groups according to the surface treatment they received: control (steam cleaning), opaqued (120-µm Al2O3 airborne-particle abrasion and opaque application), and airborne-particle abraded (120-µm Al2O3). Thirty PMMA crowns (A2 shade) were milled (n=10). The color coordinates of the crown-interim abutment pairs and a shade tab (A2) were measured by using a colorimeter. The color differences (ΔE00) between the crowns and the shade tab and the relative translucency parameter (RTP) values of the crowns were calculated by using the CIEDE2000 formula. One-way ANOVA was used to analyze the ΔE00 and RTP values with subsequent Tukey honestly significant difference tests (α=.05). RESULTS: The abutment surface treatment significantly affected the ΔE00 of interim crowns from the shade tab (P<.001), but no significant effect was found on RTP (P=.26). The control group had the highest ΔE00 from the shade tab (P≤.011). No significant difference (P=.14) was found between the opaqued and the ΔE00 of the airborne-particle abraded groups from the shade tab. CONCLUSIONS: The surface treatments of interim abutments affected the color of CAD-CAM PMMA crowns, which differed from that of the shade tab. The color of crowns on opaqued or airborne-particle abraded interim abutments was closer to the color of the shade tab. Abutment surface treatments did not affect the translucency of crown-interim abutment pairs.

Effect of Scanner Type and Scan Body Location on the Accuracy of Mandibular Complete-Arch Digital Implant Scans: An In Vitro Study.

PURPOSE: To compare the accuracy (trueness and precision) of scans of a newly introduced intraoral scanner (IOS) (Virtuo Vivo) and a widely used IOS (Trios 3) to a laboratory scanner (LBS) (Cares 7 SERIES) for 6 implants placed in an edentulous mandible, and to investigate the effect of scan body location on trueness. MATERIAL AND METHODS: Scanbodies were tightened on 6 implants placed in an edentulous polymethylmethacrylate mandibular model. An industrial scanner was utilized to generate a master reference model STL file. Three different scanners were used to scan the model (2 IOSs and 1 LBS), and the scans (n = 10) were exported into STL files. Best-fitting algorithm was used to superimpose test scans over the MRM-STL (nominal). ANOVA and Tukey HSD tests were performed to analyze the data (α = 0.05). RESULTS: The distance deviations in Car7-LBS scans were the highest (p < 0.001), whereas those in Tri-IOS scans were the lowest (p < 0.001). Vir-IOS had lower angular deviations than those of Tri-IOS (p = 0.031). In Vir-IOS scans, SB5 had higher distance deviations than SB2 (p = 0.029) and SB3 (p = 0.044). In Car7-LBS scans, SB1 had higher distance deviations than SB3 (p = 0.015) and SB5 (p = 0.005). In Tri-IOS scans, SB1 had higher mean distance deviations than SB2 and SB5 (p = 0.005). Vir-IOS had lower precision than Car7-LBS (distance deviation data) (p = 0.01). No difference was found among scanners for the precision of angular deviation data (p = 0.840). CONCLUSION: When trueness and precision were considered, distance and angular deviations depended on the scanner type. None of the scanners outperformed others in accuracy considering all distance and angular deviations. Scan body location affected only the trueness (distance deviations).

Modifiable Cardiovascular Risk Factors in Patients With Sporadic Cerebral Cavernous Malformations: Obesity Matters.

BACKGROUND AND PURPOSE: This study aims to assess the influence of modifiable cardiovascular risk factors on hemorrhage risk of sporadic cerebral cavernous malformations (CCMs). METHODS: From 1219 consecutive CCM patients (2003-2018), adult subjects with sporadic CCM and complete magnetic resonance imaging were included. We evaluated presence of intracerebral hemorrhage (ICH) as mode of presentation, occurrence of ICH during follow-up and risk factors arterial hypertension, diabetes, hyperlipidemia, nicotine abuse, and obesity (body mass index >30 kg/m2). Impact of risk factors on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. We performed Kaplan-Meier and Cox regression to analyze cumulative 5-year risk for (re)bleeding. RESULTS: We included 682 patients with CCM. The univariate logistic regression showed a significant relationship (odds ratio=1.938 [95% CI, 1.120-3.353], P=0.018) between obesity and ICH as mode of presentation. Multivariate adjusted logistic regression confirmed significant correlation with odds ratio=1.902 (95% CI, 1.024-3.532, P=0.042). Cox regression did not identify predictors for occurrence of (re)hemorrhage (P>0.05; hazard ratios: arterial hypertension 1.112 [95% CI, 0.622-1.990], diabetes 0.850 [95% CI, 0.208-3.482], hyperlipidemia 0.719 [95% CI, 0.261-1.981], nicotine abuse 1.123 [95% CI, 0.591-2.134], and obesity 0.928 [95% CI, 0.416-2.070]). CONCLUSIONS: This study provides evidence that obesity may be a risk factor for CCM hemorrhage. It was significantly associated with ICH as mode of presentation. Other risk factors (arterial hypertension, diabetes, hyperlipidemia, and current nicotine abuse) showed no such effect. None of the factors showed to be independent predictors for cumulative 5-year risk of (re)bleeding.

Cerebral cavernous malformations: Prevalence of cardiovascular comorbidities and allergic diseases compared to the normal population.

BACKGROUND: To determine the prevalence of cardiovascular comorbidities and allergic diseases in patients with cavernous malformations of the central nervous system compared to the normal population. METHODS: Clinical and magnetic resonance imaging data of 1352 patients with cerebral cavernous malformations (CCM) from an observational, cross-sectional, single-institutional study were analyzed and compared to an age-and-gender stratified and matched sample from a population-based, epidemiological study assessing cardiovascular risk factors in the local normal population of the same area (RECALL study). RESULTS: Of 1352 patients, 810 (60%) were female. Mean age was 40.4 ± 16 years. 221 patients (16%) suffered from familial disease. Presence of cardiovascular risk factors and intake of certain drugs in the overall cohort was mostly equal to the normal population reference sample (n = 786). The prevalence of allergic diseases was found to be significantly higher in all CCM patients compared to the normal population (30% vs. 20%, odds ratio [OR] 1.35 [1.12-1.63]) and in sporadic CCM cases compared to the normal population and familial cases (32% vs. 20% (OR 1.46 [1.19-1.78], p = 0.0001) and 22% vs. 20%, respectively). CONCLUSIONS: We present novel data on CCM using a large single-institution and population-based setup. The study elaborates disease characteristics of CCM patients in detail. For the first time, evidence for an unexplained high prevalence of allergic diseases in this patient population is described (differing between sporadic and familial cases), supporting the hypothesis that immune response is involved in the pathogenesis of CCM.

Delphi Project on the trends in Implant Dentistry in the COVID-19 era: Perspectives from Latin America.

AIM: To establish trends in Implant Dentistry in Latin America in the COVID-19 pandemic. MATERIAL AND METHODS: A steering committee and an advisory group of experts in Implant Dentistry were selected among eighteen countries. An open-ended questionnaire by Delphi methodology was validated including 64 questions, divided in 7 topics, concerning the various trends in dental implantology. The survey was conducted in two rounds, which provided the participants in the second round with the results of the first. The questionnaires were completed on August 2020, and the online meeting conference was held on September 2020. The final prediction was developed through consensus by a selected group of experts. RESULTS: A total of 197 experts from Latin America answered the first and second questionnaire. In the first round, the established threshold for consensus (65%) was achieved in 30 questions (46.87%). In the second round, performed on average 45 days later, this level was achieved in 47 questions (73.43%). Consensus was completely reached on the item "Diagnostic" (100%), the field with the lowest consensus was "Demand for treatment with dental implants" (37.5%). CONCLUSIONS: The present study in Latin America has provided relevant and useful information on the predictions in the education and practice of Implant Dentistry in the COVID-19 era. The consensus points toward a great confidence of clinicians in the biosecurity protocols used to minimize the risk of SARS-CoV-2 transmission. It is foreseen as an important change in education, with introduction of virtual reality and other simulation technologies in implant training.

Are older adults with excessive sodium intake at increased risk of hypohydration?

BACKGROUND: Sodium intake is expected to affect water needs, although compensation mechanisms may not work efficiently particularly in older adults. The aim of this cross-sectional study was to quantify the association between sodium excretion and hydration status in a representative sample of Portuguese older adults. METHODS: A cluster sampling approach was used, representing Portuguese older adults (≥65 years) according to sex, education level and region. From a sample size of 1500 participants, 1318 were eligible for the present analysis. A 24-h urine sample was collected, and volume, osmolality, creatinine and sodium were quantified. Free water reserve (FWR) was used to assess hydration status. Excessive sodium intake was defined as above 2000 mg day-1 as recommended by the World Health Organization. A multivariable binary logistic regression model was used to estimate the association between FWR and sodium excretion. Odds ratios (OR) and respective 95% confidence intervals (95% CI) were calculated. RESULTS: Excessive sodium excretion was observed in 80.0% of women and 91.5% of men, whereas hypohydration affected 10.9% of women and 23.6% of men. After adjusting for confounders, excessive sodium excretion was associated with an increased risk of hypohydration among men (OR = 2.75; 95% CI = 1.06-7.15). CONCLUSIONS: These results stress the positive association between excessive sodium intake and hypohydration in men and highlight the need for implementing strategies regarding the reduction of salt consumption and the promotion of water intake.

Prediction equations for estimating body weight in older adults.

BACKGROUND: Assessing body weight in older adults may be challenging. Hence, the present study aimed to develop and cross-validate updated and reproducible equations to estimate body weight in a large sample of older adults, namely among the older-old. METHODS: In total, 1456 individuals aged ≥ 65 years, from the Nutrition UP 65 study, were included in the present analysis. The participants were randomly assigned to one of two sub-samples: development (n = 991) and validation samples (n = 465). Prediction equations using height, mid-upper arm circumference (MUAC), waist circumference (WC), calf circumference (CC) and triceps skinfold thickness (TST) were generated for the development sample using multiple regression analysis and then validated using the validation sample. RESULTS: The model with five predictor variables generated the following equations: females 65-79 years: -114.682 + 0.522 × height (cm) + 0.620 × MUAC (cm) + 0.517 × WC (cm) + 0.893 × CC (cm) + 0.111 × TST (mm) (adjusted r2  = 0.883, standard error of the estimate (SEE) = 4.4); females ≥ 80 years: -110.806 + 0.494 × height (cm) + 0.637 × MUAC (cm) + 0.500 × WC (cm) + 0.986 × CC (cm) + 0.021 × TST (mm) (adjusted r2  = 0.890, SEE = 3.9); males 65-79 years: -114.875 + 0.558 × height (cm) + 0.073 × MUAC (cm) + 0.671 × WC (cm) + 0.717 × CC (cm) + 0.182 × TST(mm) (adjusted r2  = 0.820, SEE=5.0); and males ≥ 80 years: -128.789 + 0.546 × height (cm) + 0.202 × MUAC (cm) + 0.612 × WC (cm) + 1.236 × CC (cm) + 0.093 × TST (mm) (adjusted r2  = 0.906, SEE = 3.5). CONCLUSIONS: Body weight can be estimated with good accuracy in older adults using these sex- and age-specific equations generated from regression models using three to five anthropometric predictor variables.

Handgrip Strength and Its Association With Hydration Status and Urinary Sodium-to-Potassium Ratio in Older Adults.

Objective: Older adults present higher risk of functional disability detected by handgrip strength and an increased risk of poor health conditions, such as dehydration and low values of the sodium-to-potassium (Na/K) ratio. This study aimed to quantify the association of hydration status and Na/K ratio with handgrip strength, based on the urinary excretion of older adults.Methods: A cross-sectional study was conducted in 735 older adults ≥ 65 years old. Handgrip strength was measured with a Jamar Dynamometer and low values were defined according to body mass index and to sex-specific cutoff points. The hydration status was evaluated based on free water reserve. Sodium and potassium intake were evaluated after converting 24-hour urinary sodium and potassium excretion, respectively. A logistic regression model was used to estimate the probability of presenting low handgrip strength, according to risk of hypohydration and to quartiles of Na/K, stratified by sex and adjusted for potential confounders.Results: The adjusted odds ratio (OR) for presenting low handgrip strength was higher in women at risk of hypohydration, but this association was not found in men. Both women and men with the highest values of Na/K ratio presented higher adjusted OR for low handgrip strength (OR in women was 2.03; 95% confidence interval [CI]: 1.12-3.68, and in men was 2.19; 95% CI: 1.11-4.29).Conclusions: The risk of hypohydration was directly associated with low handgrip strength in older women. In older adults, higher values of urinary Na/K ratio were also directly associated with low handgrip strength.

Rhizobium tropici CIAT 899 copA gene plays a fundamental role in copper tolerance in both free life and symbiosis with Phaseolus vulgaris.

Rhizobium tropici CIAT 899 is a facultative symbiotic diazotroph able to deal with stressful concentrations of metals. Nevertheless the molecular mechanisms involved in metal tolerance have not been elucidated. Copper (Cu2+) is a metal component essential for the heme-copper respiratory oxidases and enzymes that catalyse redox reactions, however, it is highly toxic when intracellular trace concentrations are surpassed. In this study, we report that R. tropici CIAT 899 is more tolerant to Cu2+ than other Rhizobium and Sinorhizobium species. Through Tn5 random mutagenesis we identify a R. tropici mutant strain with a severe reduction in Cu2+ tolerance. The Tn5 insertion disrupted the gene RTCIAT899_CH17575, encoding a putative heavy metal efflux P1B-1-type ATPase designated as copA. Phaseolus vulgaris plants inoculated with the copA::Tn5 mutant in the presence of toxic Cu2+ concentrations showed a drastic reduction in plant and nodule dry weight, as well as nitrogenase activity. Nodules induced by the copA::Tn5 mutant present an increase in H2O2 concentration, lipoperoxidation and accumulate 40-fold more Cu2+ than nodules formed by the wild-type strain. The copA::Tn5 mutant complemented with the copA gene recovered the wild-type symbiotic phenotypes. Therefore, the copA gene is essential for R. tropici CIAT 899 to survive in copper-rich environments in both free life and symbiosis with P. vulgaris plants.