Minor Episodes Research Articles

German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached <2ULN, and 60% of patients attained PBG levels < 2ULN (p < 0.001). These biochemical responses were not different between sub-groups (p > 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p < 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p < 0.0001) and pain (38%, p < 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p < 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment <6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT < 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health.

Neogene Hydrothermal Fe‐ and Mn‐Oxide Mineralization of Paleozoic Continental Rocks, Amerasia Basin, Arctic Ocean

AbstractRocks dredged from water depths of 1,605, 2,500, 3,300, and 3,400 m in the Arctic Ocean included Paleozoic continental rocks pervasively mineralized during the Neogene by hydrothermal Fe and Mn oxides. Samples were recovered in three dredge hauls from the Chukchi Borderland and one from Mendeleev Ridge north of Alaska and eastern Siberia, respectively. Many of the rocks were so pervasively altered that the protolith could not be identified, while others had volcanic, plutonic, and metamorphic protoliths. The mineralized rocks were cemented and partly to wholly replaced by the hydrothermal oxides. The Amerasia Basin, where the Chukchi Borderland and Mendeleev Ridge occur, supports a series of faults and fractures that serve as major zones of crustal weakness. We propose that the stratabound hydrothermal deposits formed through the flux of hydrothermal fluids along Paleozoic and Mesozoic faults related to block faulting along a rifted margin during minor episodes of Neogene tectonism and were later exposed at the seafloor through slumping or other gravity processes. Tectonically driven hydrothermal circulation most likely facilitated the pervasive mineralization along fault surfaces via frictional heating, hydrofracturing brecciation, and low‐ to moderate temperature Fe‐ and Mn‐rich hydrothermal fluids, which mineralized the crushed, altered, and brecciated rocks.

6923 Case Report: Long Standing Type 2 Diabetes with TOFI Phenotype Successfully Weaned Off One Hundred Units of Basal-Bolus Insulin Therapy With Glucagon-Like Peptide 1 Receptor Agonist Therapy

Abstract Disclosure: Y.C. Kon: None. A 60-year-old Indian male was diagnosed with type 2 diabetes in 1997. In July 2017, his fasting blood glucose level (FBGL) was 10.3 mM, paired C-peptide 719 pM, eGFR measured as more than 60 ml/min. Since Sep 2017, he had been compliant on the same stable regimen of sc insulatard 20 units om and 20 units at 10 pm, sc actrapid 20 units t.i.d premeal, PO metformin 850 mg t.i.d and PO dapagliflozin 10 mg om. In the past, he had suffered myocardial infarction, with left ventricular ejection fraction 35%, and had left anterior descending coronary artery stenting. In 2017, he had automatic cardioverter defibrillator implanted for primary arrhythmia prevention. His cardiac medications included bisoprolol fumarate 5 mg om, losartan 25 mg om, spironolactone 25 mg om, aspirin 100 mg om and high intensity statin therapy. Since 2020, his HbA1c had measured 8% to 9% with FBGL at 6 mM to 11 mM. Hence he was referred by his cardiologist in Oct 2022 to optimize glycaemic control. Once every few months, he experienced hypoglycaemic symptoms with corresponding low capillary blood glucose (CBG) of 3 mM, reversed with glucose intake. On physical examination, he weighed 81.6 kg, BMI was 25.4 kg/m2, BP 110/67 mmHg, pulse rate 69/min regular, waist circumference 106 cm. There was no acanthosis nigricans. He did not appear Cushingoid nor acromegalic. As he had “thin outside, fat inside (TOFI)” type 2 diabetes phenotype, he was started on sc liraglutide 1.8 mg om. His actrapid dose was halved to 10 units premeal, and insulatard dose halved to 10 units bid. His dapagliflozin was switched to subsidised empagliflozin 25 mg om. Subsequently, his premeal CBG measured 4 to 7 mM, bedtime CBG 4-6 mM, with occasional minor hypoglycaemic episodes with CBG at 3-4 mM. In July 2023, HbA1c measured 6.3%, FBGL was 5.5 mM and paired C-peptide measured as 554 pM. Basal insulatard was discontinued and he was switched from liraglutide to sc dulaglutide 1.5 mg once weekly. In Oct 2023, his FBGL was 5.2 mM and HbA1c had improved markedly to 5.7%. His weight had reduced from 81.6 kg to 70.0 kg, BMI decreased from 25.4 kg/m2 to 22.9 kg/m2 and waist circumference reduced from 106 cm to 97 cm. As he continued to experience occasional minor hypoglycemic episodes, actrapid insulin was discontinued. On his current therapy of sc dulaglutide 1.5 mg once weekly, PO empagliflozin 25 mg om, PO metformin 850 mg tid, and PO acarbose 50 mg t.i.d, his fasting CBG measured 6.7-7.7 mM, premeal CBG 6.4 to 10.1 mM, off all insulins and without further episodes hypoglycaemia. Conclusion: Patients with long standing “TOFI” type 2 diabetes and robust C-peptide may be trialled on GLP1-receptor agonist therapy to wean off high daily doses of insulin, thus avoiding hypoglycaemia, achieving weight and abdominal fat loss, whilst maintaining glycaemic control. This is especially important in patients with established coronary artery disease. Presentation: 6/3/2024

The efficacy of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. Level I.

Catheter – related thrombosis in cancer patients: Data from the registry of thrombosis and nEoplasia of SEOM (TESEO)

BackgroundCatheter related thrombosis (CRT) is the most frequent non-infectious complication associated with central venous access devices (CVAD), with a reported incidence between 13 % and 66 % in symptomatic and asymptomatic patients, respectively, with several factors influencing its development. MethodsCRT events recorded in TESEO, an international, multicentric, and prospective cancer-associated thrombosis registry were assessed. Descriptive analyses were conducted. ResultsBetween July 2018 and December 2023, 2,567 patients were included in TESEO. Of these, 245 patients developed CRT and were included in this analysis. Mean age was 60.5 years (SD 12.3). Peripherally inserted central catheters (PICC) were present in 42.1%, totally implanted ports (PORT) in 40.9% while 17% had missing data. The most common reported comorbidities were arterial hypertension (28.6%) and dyslipidemia (28.2%). Other thromboembolism associated risk factors were present in ≤10% of patients.Venous thromboembolism (VTE) related symptoms occurred in 70.2% of cases at presentation. Pulmonary embolism (PE) was present in 6.5%, being clinically suspected in 56.2% of cases. The diagnosis was mainly unilateral (81.3%) and 50% were central. Arterial and venous rethrombosis was present in 0.8% and 4.9% of cases respectively. Minor bleeding episodes occurred in 2.5% of cases, while major/clinically relevant episodes were present in 3.6%. ConclusionsUsual VTE associated risk factors were infrequent in the TESEO registry population. CRT was symptomatic in most cases, with reduced complication rates after treatment.

Spatial Distribution of Tremor Episodes From Long‐Term Monitoring in the Northern Cascadia Subduction Zone

AbstractLarge bursts of non‐volcanic tremor (“major” tremor episodes) correlated with geodetic deformation recur regularly in the Cascadia subduction zone and are often called episodic tremor and slip (ETS). Minor episodes of tremor between ETS are ubiquitous but have been understudied. This paper assesses time‐invariant characteristics of tremor episodes of all sizes within northern Cascadia. We derive a catalog of tremor episodes ranging in size from 10 to &gt;13,000 tremor events using the results of 17 years of tremor monitoring. Minor episodes represent ∼96% of all 896 tremor episodes and their occurrence varies on 10‐km scales. Using estimates for the depth of the forearc Moho and subducting slab, we observe an association between the location of the forearc mantle corner (FMC) and tremor occurrence that leads to along‐dip modality. Bimodality, present in southern Washington and Vancouver Island, represents the segmentation of major and minor episodes up‐dip and down‐dip of the FMC, respectively. Unimodality, present in Puget Sound, results when the FMC is located near the down‐dip edge of the ETS zone and no segmentation occurs. We also use our extensive tremor episode catalog alongside three‐dimensional regional tomographic velocity models to reassess the relationship between tremor activity and low Vp/Vs signatures in the forearc. We do not find a correlation between tremor episode recurrence intervals and Vp/Vs, contrary to some previous work, suggesting that controls on silica precipitation in the forearc crust are not dominant controls of tremor episode recurrence, or that the association is not widely observable.

Preference of Coping Strategies during Stressful Situations among General People

The sensation of being overburdened, anxious, or exhausted is a common description of stress. People of all ages, genders, and circumstances can be impacted by stress, which can result in problems with their physical and mental health. At times, a little stress can be good for you. Extreme stress, however, can have negative effects on the immunological, cardiovascular, neuro-endocrine, and central neurological systems. Extreme stress can also have a devastating emotional impact. Minor episodes of stress can be managed by using one's body's inherent defenses to adjust to shifting circumstances, but persistent, excessive stress that lasts for a lengthy period of time can be physically and psychologically crippling. Coping can be defined as those thoughts and actions which we deal with a threatening situation. Coping strategies can be of various types, among which most common types are: Problem focused coping strategy, Seeking Social support coping strategy, Passive acceptance coping strategy, Avoidance coping strategy, Religious Coping strategy and Emotion focused coping strategy. This study was based on survey method technique from few sites of Kathmandu valley. Data is in quantitative nature. The questionnaire of socio-demographic variables and coping strategy was distributed among 302 participants for quantitative data. People were selected conveniently during this study. Coping check list developed by Rao, Subbakrishna and Prabhu was used for this study. In this research it was found that, for preference of type of coping strategy by total number of respondents, problem focused coping strategy had the maximum score whereas religious coping strategy had its minimum score.

A temporal investigation of experienced incivility and perpetrated counterproductive work behaviour

AbstractFollowing the principles of dynamic equilibrium theory (DET), this study examined the stable (institutional) and dynamic (episodic) components of mistreatment [experienced incivility and perpetrated counterproductive work behaviours (CWB)] using two longitudinal field samples based on a latent trait–state modelling approach. Study 1 (N = 615) leveraged a weekly lag design over four assessment points and Study 2 (N = 880) leveraged a monthly lag design over five assessment points. Across the two studies, results indicated that the majority of variance in both mistreatment constructs was institutional (i.e., individuals have meaningful set points that persist over time). Furthermore, institutional experienced incivility was positively related to institutional perpetrated CWB (i.e., the set point for experiencing incivility was positively related to the set point for perpetrating CWB). Similarly, episodic experienced incivility was concurrently associated with episodic perpetrated CWB (i.e., atypical episodes of experienced incivility were concurrently related to atypical episodes of perpetrated CWB). Interestingly, episodic experienced incivility did not have a lagged effect on future episodic perpetrated CWB, while episodic perpetrated CWB did have a lagged effect on future episodic experienced incivility. As such, for minor atypical episodes of mistreatment (i.e., incivility), we found evidence of dynamic equilibrium in that there are immediate episodic changes in other forms of mistreatment, but internal adaptive mechanisms appear to neutralize these effects over time. Meanwhile, overt atypical episodes of mistreatment (i.e., CWB) appear to have both immediate and lasting effects on other forms of mistreatment. These results have implications for DET, as well as for predicting the effectiveness of mistreatment research methodologies and interventions.

Two oscillatory components detected by forced splitting of the sleep-wake cycle in humans.

The sleep-wake cycle of human subjects was artificially split into two episodes by imposing an 8-h light and 4-h dark cycle (LD 8:4) twice a day for 7 days, which was followed by a 3-day free-running session. Sleep was permitted only in the dark period. The subjects in the ordinary group were exposed to ordinary light (ca. 500 lx) in the 8-h light period, and those in the bright light group to bright (ca. 5,000 lx) and ordinary light alternatively with bright light after the first dark period (2400-400). Split sleeps persisted in the free-running session with the major episode around the first dark period and the minor episode around the second dark period. By contrast, circadian melatonin rhythm in the free-running session significantly phase delayed in the ordinary light group, but phase advanced in the bright light group, keeping the melatonin rhythm unsplit. The length of nocturnal melatonin secretion (NMS) was significantly shortened in the bright light group. Interestingly, the falling phase of NMS advanced significantly further than the rising phase. Such a difference was not detected in the ordinary light group. Similar differences were observed in the body temperature rhythm. These findings indicated oscillatory mechanisms underlying split sleeps distinct from the circadian pacemaker and suggested an involvement of different circadian oscillators in the rising and falling phases of NMS, which is consistent with the dual oscillator model proposed for the circadian system of nocturnal rodents.NEW & NOTEWORTHY The present study demonstrated that human sleep was separated into two essentially identical components, which persisted under constant conditions, suggesting circadian oscillator underlying split-sleep episodes. The study also indicated differential light sensitivities in the rising and falling phases of circadian melatonin rhythm, indicating the involvement of two different oscillators. These results consisted of the evening and morning dual-oscillator hypothesis for the circadian pacemaker and the hierarchical model for the pacemaker and sleep-wake cycle.

Efficacy and safety of low dose, weight-based subcutaneous enoxaparin protocol in recurrent arteriovenous access thrombosis.

This study aims to evaluate the safety and efficacy of a short-term, low dose, weight-based subcutaneous enoxaparin protocol (SEP) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis. Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied. The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days (p < 0.001). After adjusting for the type of thrombolytic agent, use of adjunct thrombectomy device, cutting balloon, drug-coated balloon, and stent graft, SEP remained a significant factor associated with longer thrombosis-free patency (HR 0.166: 95% CI 0.070-0.392, p < 0.001). SEP appears to be a feasible and safe thromboprophylaxis method to improve thrombosis-free patency for AV access with recurrent thrombosis.

Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. Single-center, retrospective study, 2010-2019. Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. None. Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

Brown Sequard syndrome in a patient with Klippel-Feil syndrome following minor trauma: a case report and literature review

BackgroundThere are some cases of Klippel-Feil syndrome with spinal cord injury in clinical work. However, there is no literature report on Brown-Sequard syndrome after trauma. We report a case of Brown-Sequard syndrome following minor trauma in a patient with KFS type III. Her Brown-Sequard syndrome is caused by Klippel-Feil syndrome.Case presentationWe found a 38-year-old female patient with KFS in our clinical work. She was unconscious on the spot following a minor traumatic episode. After treatment, her whole body was numb and limb activity was limited. Half an hour later, she felt numb and weak in the right limb and weak in the left limb. She had no previous hypertension, diabetes, or coronary heart disease. After one-month treatment of medication, hyperbaric oxygen, rehabilitation, and acupuncture in our hospital, her muscle strength partially recovered, but the treatment effect was still not satisfactory. Then, she underwent surgical treatment and postoperative comprehensive treatment, and rehabilitation training. She was able to take care of herself with assistance, and her condition improved from grade B to grade D according to the ASIA (ASIA Impairment Scale) classification.ConclusionKFS, also known as short neck deformity, is a kind of congenital deformity characterized by impaired formation and faulty segmentation of the cervical spine, often associated with abnormalities of other organs. The cervical deformity in patients with KFS can alter the overall mechanical activity of the spine, as well as the compensatory properties of the spine for decelerating and rotatory forces, thus increasing the chance of spinal cord injury (SCI) following trauma. Many mechanisms can make patients more susceptible to injury. Increased range of motion of the segment adjacent to the fused vertebral body may lead to slippage of the adjacent vertebral body and altered disc stress, as well as cervical instability. SCI can result in complete or incomplete impairment of motor, sensory and autonomic nervous functions below the level of lesion. This woman presented with symptoms of BSS, a rare neurological disorder with incomplete SCI. Judging from the woman’s symptoms, we concluded that previously she had KFS, which resulted in SCI without fracture and dislocation following minor trauma, with partial BSS.After the comprehensive treatment of surgery, hyperbaric oxygen, rehabilitation therapy, and neurotrophic drugs, two years later, we found her symptoms significantly improved, with ASIA Impairment Scale from grade B to grade D, and her ability to perform activities of daily living with aids.

The benefits of early continuous renal replacement therapy in critically ill patients with acute kidney injury at high-altitude areas: a retrospective multi-center cohort study

Severe hypoxia would aggravate the acute kidney injury (AKI) in high-altitude areas and continuous renal replacement therapy (CRRT) has been used to treat critically ill patients with AKI. However, the characteristics and outcomes of CRRT in critically ill patients at AKI in high altitudes and the optimal timing of CRRT initiation remain unclear. 1124 patients were diagnosed with AKI and treated with CRRT in the ICU, comprising a high-altitude group (n = 648) and low-altitude group (n = 476). Compared with the low-altitude group, patients with AKI at high altitude showed longer CRRT (4.8 vs. 3.7, P = 0.036) and more rapid progression of AKI stages (P < 0.01), but without any significant minor or major bleeding episodes (P > 0.05). Referring to the analysis of survival and kidney recovery curves, a higher mortality but a lower possibility of renal recovery was observed in the high-altitude group (P < 0.001). However, in the high-altitude group, the survival rate of early CRRT initiation was significantly higher than that of delayed CRRT initiation (P < 0.001). The findings showed poorer clinical outcomes in patients undergoing CRRT for AKI at high altitudes. CRRT at high altitudes was unlikely to increase the adverse events. Moreover, early CRRT initiation might reduce the mortality and promote renal recovery in high-altitude patients.

A high-resolution study of planktonic foraminifera during the Holocene at the Tilos-Symi sea basin in the SE Aegean Sea

High-resolution data for planktonic foraminifera and their groups of ecological interest, including Herbivores and Carnivores, combined with benthic foraminifera and a great variety of biogeochemical indices from the SE Aegean sediment core ST5, contribute to a detailed study concerning major and minor climatic episodes during Holocene. The ST5 sediment record, retrieved from the Tilos-Symi marine basin, evidences the impact of the nearby land, the local climate, and the Rhodes Gyre imprint on the eastern Mediterranean water circulation. Pronounced environmental changes are detected during a preconditioning period of ~400 years before the onset of sapropel S1 deposition and during the deposition phases S1a (10.0–8.4 ka BP) and S1b (8.0–6.1 ka BP). Major freshwater influx episodes (10.5 ka BP, 9.2–8.9 ka BP, 7.4 ka BP, 4.5–4.3 ka BP, and few additional during the Late-Holocene) are revealed, prominent oxygen deficiency time intervals (including a distinct brief anoxic period) as well as several drier, cooler and warmer climatic events. Herbivore planktonic foraminifera alternate their dominance with the Carnivores at the preconditioning period before the S1 onset and at the Late-Holocene (2.0–1.5 ka BP) when conditions of good seawater circulation, oxygenation, and productivity alternate with stratified low oxygenation waters and high freshwater influx from the land.

The “Super-Active” Accretion Phase of T CrB has Ended

The symbiotic recurrent nova T CrB erupted for the second and last recorded time in 1946. Following the outburst, the accretion rate onto its WD has remained rather low with only occasional and minor flaring episodes, until in late 2014 it entered a “super-active” phase (SAP) that peaked in 2016 April: the flux radiated by Balmer lines increased by two orders of magnitude, accompanied by the appearance of strong He i, He ii, and many other emission lines. Following the sharp maximum, the intensity of the emission lines has been steadily decreasing, reaching back to pre-SAP levels by mid-2023. The end of SAP is also confirmed by the drop of B-band brightness to pre-SAP conditions and the simultaneous re-appearance of a large-amplitude flickering. This suggests that the accretion disk has emptied from the extra material that has driven the “super active” state and has completed its transfer onto the WD, setting the stage for a new and probably imminent nova eruption.

The Magic Circle: Visually Representing the Woman of Endor (ovot)

The interaction between Saul and the woman of Endor is a minor episode, not only within the first book of Samuel, but in the Tanakh as a whole. The woman, whose actions drive the narrative, is not named nor is very much known about her. All that the text reveals are her gender, domicile location, familiarity with the law (Saul’s ban on ovot and yid’onim), and culinary possessions (flour and a calf). Through linguistic connotation her age range is surmisable: she is neither maiden nor elderly. Of her specific abilities, little is actually known as it is totally unclear what she did exactly that caused connection between the living Saul and deceased Samuel. Yet this woman, and the language used that describes her in a few verses without substantive information, have singularly driven wildly polarizing visual representations of the female thaumaturge for centuries. The artistically rendered visage of the Endoran ranges from the crone of gothic nightmares to hypersexual femme fatale, to gregarious earth mother, to occult adept perfecting her craft. Despite her shifting guise, one aspect remains consistent throughout the majority of images: the visual translation (or mistranslation) of ovot.&#x0D;

Efficacy and safety of direct oral anticoagulants in children in real clinical practice

Introduction. As well as standard anticoagulants, direct oral anticoagulants (DOAC) have been approved for treatment of thromboembolism in children, recently. Several clinical trials provide promising data on efficacy and safety of DOAC in children and young adults. But further studies aimed at evaluating the efficacy and safety of these drugs in children and adolescents are still needed.The aim of the study is to evaluate the safety and effectiveness of the use DOACs in children.Materials and methods. We have retrospectively analyzed the medical records of patients (0–17 years) of from 2013 to 2022 at our tertiary care Centre and selected patients, who were treated with apixaban, rivaroxaban or dabigatran for more than 14 days. Patients with arterial thrombosis, children, who were treated with combined anticoagulant therapy and those who were unable for follow-up were excluded. We assessed the rates of bleeding and recurrent venous thromboembolism (VTE).Results. There were 67 patients, who were treated with DOAC in our center. Patients were divided into 2 groups: those, who received prophylactic anticoagulation (group 1 – 6 patients), and patients, who received DOAC therapy after venous thromboembolism (group 2 – 61 patients). The median follow-up time was 46 (25–365) days in the group 1, and 4 months (2 weeks – 36 month) in the group 2. There were no VTE episodes and 1 minor bleeding in group 1, while 1 (2 %) major, 4 (6 %) minor bleeding episodes in group 2. There were 4 (6 %) patients with recurrent VTE in group 2.Conclusion. The majority of patients in this study received rivaroxaban (79 %). We found a moderately increased recurrence rate of VTE, which could be the result of a long follow-up period, and a comparable rate of bleeding, all of which were associated with rivaroxaban therapy. In the future, of particular interest, in our opinion, are prospective studies of DOACs as primary antithrombotic prophylaxis, as well as secondary prophylaxis in the highest-risk groups, and the results of an analysis of their use in real clinical practice.

The Old and the New: Cardiovascular and Respiratory Alterations Induced by Acute JWH-018 Administration Compared to Δ9-THC-A Preclinical Study in Mice.

Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, the present study investigated the cardio-respiratory (MouseOx Plus; EMKA electrocardiogram (ECG) and plethysmography TUNNEL systems) and vascular (BP-2000 systems) effects induced by 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018; 0.3-3-6 mg/kg) and Δ9-tetrahydrocannabinol (Δ9-THC; 0.3-3-6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3-6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ9-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect at the tested dose range. These effects were prevented by both treatment with selective CB1 (AM 251, 6 mg/kg) and CB2 (AM 630, 6 mg/kg) receptor antagonists and with the mixture of the antagonists AM 251 and AM 630, even if in a different manner. Cardio-respiratory and vascular symptoms could be induced by peripheral and central CB1 and CB2 receptors stimulation, which could lead to both sympathetic and parasympathetic systems activation. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management.

Management of a patient with factor X deficiency with FEIBA: a case report

Abstract Hereditary factor X (FX) deficiency is a rare autosomal recessive disorder that increases bleeding tendencies, ranging from epistaxis to intracranial haemorrhage (ICH), which can be life-threatening. Single factor concentrates are recommended for treating rare bleeding disorders; however, in India most people with FX deficiency are treated with fresh frozen plasma (FFP). We report a case of FX deficiency in a child with a history of intracranial bleeding who was found to have a novel mutation in the F10 gene. Although managed with weekly prophylactic FFP infusions, he continued to experience regular bleeding including two further instances of ICH. Other therapeutic options were unavailable or unaffordable. When the Indian Government added FEIBA to the essential drug list, a decision was made to try FEIBA prophylaxis to better manage his bleeding. In 2019, he was started on a weekly dose of FEIBA, 500 IU (20 IU/ kg and his prophylactic FFP transfusion regimen was stopped. His bleeding episodes started to reduce after two months of starting FEIBA prophylaxis. Over the last three years he has had only four minor bleeding episodes and has remained completely free of major bleeding. He is now able to receive home-based therapy and his prognosis can be considered to be improved. FEIBA may be a useful medicinal therapy for FX-deficient patients who suffer severe haemorrhagic episodes in countries where plasma-derived factor X (pdFX) is not available.

Development of a Bayesian event tree for short-term eruption onset forecasting at Taupō volcano

Taupō volcano, located within the Taupō Volcanic Zone (TVZ) in the central North Island of Aotearoa-New Zealand, is one of the world’s most active silicic caldera systems. Silicic calderas such as Taupō are capable of a broad and complex range of volcanological activity, ranging from minor unrest episodes to large destructive supereruptions. A critical tool for volcanic risk management is eruption forecasting. The Bayesian Event Tree for Eruption Forecasting (BET_EF) is one probabilistic eruption forecasting tool that can be used to produce short-term eruption forecasts for any volcano worldwide. A BET_EF model is developed for Taupō volcano, informed by geologic and historic data. Monitoring parameters for the model were obtained through a structured expert elicitation workshop with 30 of Aotearoa-New Zealand’s volcanologists and volcano monitoring scientists. The eruption probabilities output by the BET_EF model for Taupō volcano’s 17 recorded unrest episodes (between 1877 and 2019) were examined. We found time-inhomogeneity in the probabilities stemming from both the changes over time in the monitoring network around Taupō volcano and increasing level of past data (number of non-eruptive unrest episodes). We examine the former issue through the lens of the latest episodes, and the latter by re-running the episodes assuming knowledge of all 16 other episodes (calibration to 2021 data). The time variable monitoring network around Taupō volcano and parameter weights had a substantial impact on the estimated probabilities of magmatic unrest and eruption. We also note the need for improved monitoring and data processing at Taupō volcano, the existence of which would prompt updates and therefore refinements in the BET_EF model.