Early Pliocene Hominid Tooth from Galili, Somali Region, Ethiopia

A fossil hominid tooth was discovered during survey at Galili, Somali region, Ethiopia. The geological and faunal context indicate an Early Pliocene age. The specimen (GLL 33) consists of an almost complete lower right third molar likely representing a male individual of advanced age-at-death. Its comparative metrical, morphological and (micro)structural analysis (supported by a microtomographic record) suggests a tentative taxonomic allocation to Australopithecus cf. A. afarensis

Prognostic value of chronic kidney disease in patients undergoing left atrial appendage occlusion

AIMS Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thrombo-embolism (TE). CKD concomitantly predisposes towards a pro-haemorrhagic state. Our aim was to evaluate the prognostic value of CKD in patients undergoing percutaneous left atrial appendage occlusion (LAAO). METHODS AND RESULTS A total of 2124 consecutive AF patients undergoing LAAO were categorized into CKD stage 1+2 (n = 1089), CKD stage 3 (n = 796), CKD stage 4 (n = 170), and CKD stage 5 (n = 69) based on the estimated glomerular filtration rate at baseline. The primary endpoint included cardiovascular (CV) mortality, TE, and major bleeding. The expected annual TE and major bleeding risks were estimated based on the CHA2DS2-VASc and HAS-BLED scores. A non-significant higher incidence of major peri-procedural adverse events (1.7 vs. 2.3 vs. 4.1 vs. 4.3) was observed with worsening CKD (P = 0.14). The mean follow-up period was 13 ± 7 months (2226 patient-years). In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank P-value = 0.04), CKD stage 4 (log-rank P-value = 0.01), and CKD stage 5 (log-rank P-value = 0.001). Left atrial appendage occlusion led to a TE risk reduction (RR) of 72, 66, 62, and 41% in each group. The relative RR of major bleeding was 58, 44, 51, and 52%, respectively. CONCLUSION Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. The relative RR in the incidence of TE and major bleeding was consistent across CKD groups

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020

Background and purpose The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted. Results Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018–2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care. Conclusions Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response

Background: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. Methods: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. Results: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. Conclusions: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels

Seizure Semiology in Antibody-Associated Autoimmune Encephalitis

Kaaden T, Madlener M, Angstwurm K, et al. Seizure Semiology in Antibody-Associated Autoimmune Encephalitis. Neurology(R) neuroimmunology &amp; neuroinflammation. 2022;9(6): e200034 .BACKGROUND AND OBJECTIVES: To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab + AE) with the 3 most prevalent abs against N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD).; METHODS: Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis.; RESULTS: Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+ (67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with deja-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients.; DISCUSSION: Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology