Monday, November 16, 2020

Prophylactic administration of tirofiban for preventing thromboembolic events in flow diversion treatment of intracranial aneurysms

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Background

Flow diverter (FD) is widely used in the treatment of intracranial aneurysms. However, thromboembolic events (TEs) continue to be the major complications during the periprocedural phase. To evaluate the safety and efficacy of the prophylactic use of tirofiban, combined with the conventional dual antiplatelet therapy (DAT), as a new antiplatelet protocol in patients with intracranial aneurysms treated with FDs.

Methods

At least 3–5 days before the procedure, daily DAT were administrated to the pat ients. Tirofiban was administered as an intravenous bolus (5 µg/kg) over a 3 min period during or immediately after FD deployment, followed by a 0.05 µg/kg/min maintenance infusion for 24–48 hours. Periprocedural TEs and hemorrhagic events (HEs) were recorded.

Results

A total of 331 patients were included, including 229 (69.2%) who received tirofiban administration (tirofiban group) and 102 (30.8%) who received only DAT (non-tirofiban group). Periprocedural TEs occurred in 12 (3.6%) patients, including eight (7.8%) in the non-tirofiban group and four (1.7%) in the tirofiban group. In multivariate analysis, patients receiving tirofiban administration had significantly lower TEs as compared with those who received only DAT (P=0.004). Balloon angioplasty and longer procedure time (>137 min) were also risk factors for TEs. Also, no increase was observed in the rate of HEs related to tirofiban administration.

Conclusions

The current study suggested that prophylactic admi nistration of tirofiban combined with conventional oral DAT seems safe and efficient for preventing TEs during FD treatment of unruptured intracranial aneurysms. Balloon angioplasty and prolonged procedure are associated with a high risk of TEs.

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Endovascular management of torcular dural sinus malformations in children: the role of straight sinus occlusion

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Background

Torcular dural sinus malformations (tDSMs) with arteriovenous shunts are rare congenital intracranial vascular malformations that carry a high rate of neurologic impairment and death in the neonatal, infant and young pediatric population. Their impact on brain venous drainage, especially the deep venous system, is one of the key factors in the clinical prognosis and natural history of the disease. We describe our therapeutic strategy for tDSMs, disconnecting the reflux into the deep venous system by per forming an endovascular straight sinus occlusion.

Methods

Among all children with dural sinus malformations seen between 2002 and 2020, we retrospectively reviewed those with tDSM in whom straight sinus occlusion had been performed.

Results

Our databank included nine patients with tDSM that were embolized. Mean age at the clinical onset was 8.9±9.6 months (min–max=0–31). Five patients presented a significant reflux in the straight sinus on digital subtraction angiography. Those patients were initially clinically worse (mean modified Rankin Scale (mRS) 3.8) than those who did not present with reflux (mean mRS 2.25), this reflux being responsible for intraventricular hemorrhage in three patients. The reflux was suppressed by transarterial embolization in one patient and by transvenous straight sinus occlusion in four patients. Staged endovascular treatment resulted in a complete cure in six patients without complications, and clinical improvement in all patients.

Con clusion

Straight sinus occlusion is a feasible technique that needs to be considered in the treatment strategy for tDSM with deep venous reflux in order to avoid or minimize brain damage.

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Clinical Predictors of Transient versus Persistent Neonatal Hyperinsulinism

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Introduction: Hyperinsulinism (HI), the most common neonatal cause of persistent hypoglycemia, can be associated with prolonged hospitalizations and risk for long-term neurological sequelae. Rapid identification of transient versus persistent forms of HI is crucial to optimize management. Objectives: The aims of the study were to assess the ability of clinical and biochemical features at presentation to predict transient versus persistent HI, and to evaluate differences in hospital outcomes. Methods: This study is a retrospective review of 79 infants with HI admitted to the Hospital for Sick Children, Toronto, from 2012 to 2017. Patients were classified into 3 groups: transient and the 2 persistent forms, diazoxide responsive and diazoxide unresponsive (DU). Results: Infants with birth weight #x3e;90th percentile had an 8-fold increased risk of having a persistent form of HI (OR 8.8, 95% CI 2.5–30) and a 21-fold increase d risk of having a DU form of HI (OR 21.1, 95% CI 4.9–91.8). The majority of children with transient HI and a birth weight #x3e;90th percentile were born to mothers with gestational diabetes. There were no other useful clinical or biochemical presenting features that differentiated the groups. There were significant differences in outcome measures, with the DU children more likely to require gastrostomy tube insertion and have an extended length of hospital admission. Conclusion: A higher birth weight in the absence of maternal gestational diabetes is highly associated with a persistent form of HI. Given the marked difference in clinical outcomes between groups, expedited genetic testing should be considered in infants with this presentation to inform clinical management.
Horm Res Paediatr
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Amelioration of systemic inflammation in advanced chronic liver disease upon beta-blocker therapy translates into improved clinical outcomes

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Objective

Systemic inflammation promotes the development of clinical events in patients with advanced chronic liver disease (ACLD). We assessed whether (1) non-selective beta blocker (NSBB) treatment initiation impacts biomarkers of systemic inflammation and (2) whether these changes in systemic inflammation predict complications and mortality.

Design

Biomarkers of systemic inflammation, that is, white blood cell count (WBC), C reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) were determined at sequential hepatic venous pressure gradient (HVPG) measurements without NSBB and under stable NSBB intake. The influence of NSBB-related changes in systemic inflammation on the risk of decompensation and liver-related death was analysed using competing risk regression.

Results

Our study comprised 307 stable patients with ACLD (Child-A: 77 (25.1%), Child-B: 161 (52.4%), Child-C: 69 (22.5%), median HVPG: 20 (IQR 17–24) mm Hg) including 231 (75.2%) with decompensated disease.

WBC significantly decreased upon NSBB therapy initiation (median: –2 (IQR –19;+13)%, p=0.011) in the overall cohort. NSBB-related reductions of WBC (Child-C: –16 (–30;+3)% vs Child-B: –2 (–16;+16)% vs Child-A: +3 (–7;+13)%, p<0.001) and of CRP (Child-C: –26 (–56,+8)% vs Child-B: –16 (–46;+13)% vs Child-A: ±0 (–33;+33)%, p<0.001) were more pronounced in advanced stages of cirrhosis. The NSBB-associated changes in WBC correlated with changes in CRP (Spearman's =0.228, p& lt;0.001), PCT (=0.470, p=0.002) and IL-6 (=0.501, p=0.001), but not with changes in HVPG (=0.097, p=0.088).

An NSBB-related decrease in systemic inflammation (ie, WBC reduction ≥15%) was achieved by n=91 (29.6%) patients and was found to be an independent protective factor of further decompensation (subdistribution HR, sHR: 0.694 (0.49–0.98), p=0.038) in decompensated patients and of liver-related mortality in the overall patient cohort (sHR: 0.561 (0.356–0.883), p=0.013).

Conclusion

NSBB therapy seems to exert systemic anti-inflammatory activity as evidenced by reductions of WBC and CRP levels. Interestingly, this effect was most pronounced in Child-C and independent of HVPG response. An NSBB-related WBC reduction by ≥15% was associated with a decreased risk of further decompensation and death.

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Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?

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Background

Biallelic variants in PNPT1 cause a mitochondrial disease of variable severity. PNPT1 (polynucleotide phosphorylase) is a mitochondrial protein involved in RNA processing where it has a dual role in the import of small RNAs into mitochondria and in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This, in turn, prevents the activation of type I interferon response. Detailed neuroimaging findings in PNPT1-related disease are lacking with only a few patient s reported with basal ganglia lesions (Leigh syndrome) or non-specific signs.

Objective and methods

To document neuroimaging data in six patients with PNPT1 highlighting novel findings.

Results

Two patients exhibited striatal lesions compatible with Leigh syndrome; one patient exhibited leukoencephalopathy and one patient had a normal brain MRI. Interestingly, two unrelated patients exhibited cystic leukoencephalopathy resembling RNASET2-deficient patients, patients with Aicardi-Goutières syndrome (AGS) or congenital CMV infection.

Conclusion

We suggest that similar to RNASET2, PNPT1 be searched for in the setting of cystic leukoencephalopathy. These findings are in line with activation of type I interferon response observed in AGS, PNPT1 and RNASET2 deficiencies, suggesting a common pathophysiological pathway and linking mitochondrial diseases, interferonopathies and immune dysregulations.

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Prevalence and frequency of menstrual cycle symptoms are associated with availability to train and compete: a study of 6812 exercising women recruited using the Strava exercise app

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Objectives

The menstrual cycle can affect sports participation and exercise performance. There are very few data on specific menstrual cycle symptoms (symptoms during various phases of the cycle, not only during menstruation) experienced by exercising women. We aimed to characterise the most common symptoms, as well as the number and frequency of symptoms, and evaluate whether menstrual cycle symptoms are associated with sporting outcomes.

Methods

6812 adult women of reproductive age (mean age: 38.3 (8.7) years) who were not using combined hormonal contraception were recruited via the Strava exercise app user database and completed a 39-part survey. Respondents were from seven geographical areas, and the questions were translated and localised to each region (Brazil, n=892; France, n=1355; Germany, n=839; Spain, n=834; UK and Ireland, n=1350; and USA, n=1542). The survey captured exercise behaviours, current menstrual status, presence and frequency of menstrual cycle symptoms, medication use for symptoms, perceived effects of the menstrual cycle on exercise and work behaviours, and history of hormonal contraception use. We propose a novel Menstrual Symptom index (MSi) based on the presence and frequency of 18 commonly reported symptoms (range 0–54, where 54 would correspond to all 18 symptoms each occurring very frequently).

Results

The most prevalent menstrual cycle symptoms were mood changes/anxiety (90.6%), tiredness/fatigue (86.2%), stomach cramps (84.2%) and breast pain/tendern ess (83.1%). After controlling for body mass index, training volume and age, the MSi was associated with a greater likelihood of missing or changing training (OR=1.09 (CI 1.08 to 1.10); p≤0.05), missing a sporting event/competition (OR=1.07 (CI 1.06 to 1.08); p≤0.05), absenteeism from work/academia (OR=1.08 (CI 1.07 to 1.09); p≤0.05) and use of pain medication (OR=1.09 (CI 1.08 to 1.09); p≤0.05).

Conclusion

Menstrual cycle symptoms are very common in exercising women, and women report that these symptoms compromise their exercise participation and work capacity. The MSi needs to be formally validated (psychometrics); at present, it provides an easy way to quantify the frequency of menstrual cycle symptoms.

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Injury incidence and burden in a youth elite football academy: a four-season prospective study of 551 players aged from under 9 to under 19 years

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Objective

Investigate the incidence and burden of injuries by age group in youth football (soccer) academy players during four consecutive seasons.

Methods

All injuries that caused time-loss or required medical attention (as per consensus definitions) were prospectively recorded in 551 youth football players from under 9 years to under 19 years. Injury incidence (II) and burden (IB) were calculated as number of injuries per squad season (s-s), as well as for type, location and age groups.

Results

A total of 2204 injuries were recorded. 40% (n=882) required medical attention and 60% (n=1322) caused time-loss. The total time-loss was 25 034 days. A squad of 25 players sustained an average of 30 time-loss injuries (TLI) per s-s with an IB of 574 days lost per s-s. Compared with the other age groups, U-16 players had the highest TLI incidence per s-s (95% CI lower-upper): II= 59 (52 to 67); IB=992 days; (963 to 1022) and U-18 players had the greatest burden per s-s: II= 42.1 (36.1 to 49.1); IB= 1408 days (1373 to 1444). Across the cohort of players, contusions (II=7.7/s-s), sprains (II=4.9/s-s) and growth-related injuries (II=4.3/s-s) were the most common TLI. Meniscus/cartilage injuries had the greatest injury severity (95% CI lower-upper): II= 0.4 (0.3 to 0.7), IB= 73 days (22 to 181). The burden (95% CI lower-upper) of physeal fractures (II= 0.8; 0.6 to 1.2; IB= 58 days; 33 to 78) was double than non-physeal fractures.

Summary

At this youth football academy, each squad of 25 playe rs averaged 30 injuries per season which resulted in 574 days lost. The highest incidence of TLI occurred in under-16 players, while the highest IB occurred in under-18 players.

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Tick-transmitted thogotovirus gains high virulence by a single MxA escape mutation in the viral nucleoprotein

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by Jonas Fuchs, Alexander Oschwald, Laura Graf, Georg Kochs

Infections with emerging and re-emerging arboviruses are of increasing concern for global health. Tick-transmitted RNA viruses of the genus Thogotovirus in the Orthomyxoviridae family have considerable zoonotic potential, as indicated by the recent emergence of Bourbon virus in the USA. To successfully infect humans, arboviruses have to escape the restrictive power of the interferon defense system. This is exemplified by the high sensitivity of thogotoviruses to the antiviral action of the interferon-induced myxovirus resistance protein A (MxA) that inhibits the polymerase activity of incoming viral ribonucleoprotein complexes. Acquiring resistance to human MxA would be expected to enhance the zoonotic potential of these pathogens. Therefore, we screened a panel of 10 different thogotovirus isolates obtained from various parts of the world for their sensitivity to MxA. A single isolate from Nigeria, Jos virus, showed resistance to the antiviral action of MxA in cell cul ture and in MxA-transgenic mice, whereas the prototypic Sicilian isolate SiAr126 was fully MxA-sensitive. Further analysis identified two amino acid substitutions (G327R and R328V) in the viral nucleoprotein as determinants for MxA resistance. Importantly, when introduced into SiAr126, the R328V mutation resulted in complete MxA escape of the recombinant virus, without causing any viral fitness loss. The escape mutation abolished viral nucleoprotein recognition by MxA and allowed unhindered viral growth in MxA-expressing cells and in MxA-transgenic mice. These findings demonstrate that thogotoviruses can overcome the species barrier by escaping MxA restriction and reveal that these tick-transmitted viruses may have a greater zoonotic potential than previously suspected.
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Intestinal Pseudo-Obstruction as the Initial Clinical Presentation in Systemic Lupus Erythematosus: A Rare and Severe Disorder

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Intestinal pseudo-obstruction (IPO) is a rarely recognized complication of systemic lupus erythematosus (SLE). We present a 36-year-old African American female, with only known past medical history of anemia, admitted for frequent vomiting, abdominal distension, abdominal pain, diarrhea, and fever that had been ongoing for 5 days. Laboratory results revealed leukopenia and thrombocytopenia. Imaging revealed dilated small bowel loops, abdominal ascites, as well as mild bilateral hydroureteronephrosis without obstructing calculus. Serologic testing confirmed a diagnosis of SLE. The patient was placed on immunosuppressive therapy and responded well. IPO has previously been described as a rare finding in patients with SLE, with bilateral hydroureteronephrosis and lupus interstitial cystitis having been note d as common concomitant factors. One must have a high level of suspicion to recognize it as being one of the initial clinical presentations. Early recognition and appropriate management preclude unnecessary invasive procedures that do not take into account the pathophysiology of the condition and allow for appropriate management and return of peristaltic function.
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A Rare Complication of Noncompliance Status Post-Transhiatal Esophagectomy and Esophago-Gastroanastomosis

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Gastropleural fistulas are a complication of peptic ulcers in hiatal hernias, trauma, infections, surgical complications, and malignancy. Presenting symptoms may include gastric and chest pain with respiratory failure in the setting of pneumonitis, hydropneumothorax, or tension pneumothorax. We describe a 57-year-old male with a history of transhiatal esophagectomy and esophago-gastroanastomosis who presented in the setting of dyspnea and dark orogastric tube output. Upper endoscopy revealed multiple gastric ulcers with a dominant ulceration communicating with an adjacent space, and a fistulous tract was demonstrated on computed tomography chest, confirming a gastropleural fistula, a rare life-threatening condition.
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Randomness for Nucleotide Sequences of SARS-CoV-2 and Its Related Subfamilies

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The origin and evolution of SARS-CoV-2 has been an important issue in tackling COVID-19. Research on these topics would enhance our knowledge of this virus and help us develop vaccines or predict its paths of mutations. There are many theoretical and clinical researches in this area. In this article, we devise a structural metric which directly measures the structural differences between any two nucleotide sequences. In order to explore the mechanisms of how the evolution works, we associate the nucleotide sequences of SARS-CoV-2 and its related families with the degrees of randomness. Since the distances between randomly generated nucleotide sequences are very concentrated around a mean with low variance, they are qualified as good candidates for the fundamental reference. Such reference could then be app lied to measure the randomness of other Coronaviridae sequences. Our findings show that the relative randomness ratios are very consistent and concentrated. This result indicates their randomness is very stable and predictable. The findings also reveal the evolutional behaviours between the Coronaviridae and all its subfamilies.
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