Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Minimally Invasive Approaches to Anterior Skull Base Meningiomas.

Objective Anterior skull base meningiomas include olfactory groove, planum sphenoidale, and tuberculum sellae lesions. Traditionally, standard craniotomy approaches have been used to access meningiomas in these locations. More recently, minimally invasive techniques including supraorbital and endonasal endoscopic approaches have gained favor; however there are limited published series comparing the use of these two techniques for these meningiomas. Using our patent database, we identified patients who underwent these two approaches, and conducted a retrospective chart review to compare outcomes between these two techniques. Methods A total of 32 patients who underwent minimally invasive approaches were identified: 20 supraorbital and 11 endoscopic endonasal. Radiographic images, presenting complaints and outcomes, were analyzed retrospectively. The safety of each approach was evaluated. Results The mean extent of resection through a supraorbital approach was significantly greater than that of the endoscopic endonasal approach, 88.1 vs. 57.9%, respectively ( p = 0.016). Overall, preoperative visual acuity and anopsia deficits were more frequent in the endonasal group that persisted postoperatively (visual acuity: p = 0.004; anopsia: p = 0.011). No major complications including cerebrospinal fluid (CSF) leaks or wound-related complications were identified in the supraorbital craniotomy group, while the endonasal group had two CSF leaks requiring lumbar drain placement. Length of stay was shorter in the supraorbital group (3.4 vs. 6.1 days, p < 0.001). Conclusion Anterior skull base meningiomas can be successfully managed by both supraorbital and endoscopic endonasal approaches. Both approaches provide excellent direct access to tumor in carefully selected patients and are safe and efficient, but patient factors and symptoms should dictate the approach selected.

Ventilator-assisted priming of an anaesthesia circuit (VAP technique): An exploratory study.

Background and Aims: The speed of inhalational induction depends on a variety of factors, of which priming the breathing circuit with volatile anaesthetics plays a vital role. This study compared ventilator-assisted priming (VAP) and a passive priming technique using different fresh gas flows (FGFs) in neonatal, paediatric, and adult anaesthetic circuits. Methods: In both techniques, FGF with 100% oxygen and 8% sevoflurane vaporiser concentration were set at 2 Lmin-1, 4 Lmin-1, and 8 Lmin-1, representing three groups FGF-2, FGF-4, and FGF-8, respectively. The time taken to achieve 6% sevoflurane concentration at the patient end of the circuit was measured. In addition to this, we explored various combinations of tidal volumes and respiratory rates in the VAP technique and recorded the priming time with each combination. The amount of sevoflurane consumed for priming in both techniques was also calculated. Results: VAP was three times faster than passive priming in all the FGF groups in the three circuits. In the VAP technique, the shortest priming times were similar for FGF-4 and FGF-8 (P > 0.05) but were significantly higher for FGF-2 (P = 0.001) in the three circuits. Sevoflurane consumption did not differ in FGF-2 and FGF-4 groups, whereas it doubled in the FGF-8 group using the VAP technique in all three circuits. Conclusion: The VAP technique provides a quick and effective method for priming to achieve a high anaesthetic concentration within the breathing circuit for inhalational induction.

Selective and caspase-independent cytotoxicity of bioactive glasses towards giant cell tumor of bone derived neoplastic stromal cells but not to bone marrow derived stromal cells.

Semi-malignant giant cell tumors of bone (GCTB) are associated with large osteolytic defects and significant bone destructions. Surgical resection remains the standard therapy that is, however, associated with very high recurrence rates. Bioactive glasses (BGs) that are osteogenic but under certain conditions also cytotoxic might be suitable to achieve biological reconstruction with simultaneous reduction of tumor recurrence in GCTB. In this study, a concentration and time dependent cytotoxic effect of five different BG compositions towards neoplastic GCTB cells was identified while bone marrow derived mesenchymal stromal cells were mostly unaffected. Time course and extent of the cytotoxic effect were dependent on the BG composition and were not associated with caspases activation, indicating that apoptotic mechanisms are not involved. Rather, detection of BG-induced disruption of the cell membranes and a rapid drop of intracellular HMG1 (High Mobility Group Box 1 protein) levels suggest a necrotic cell death. Notably, the cytotoxic effects were dependent on a direct contact of cells and BGs and could not be observed using indirect cultivation settings. Our data suggest that BGs might represent promising materials for the treatment of GCTB in order to reduce tumor recurrence with simultaneous enhancement of bone regeneration.

Meningioma surgical outcomes and complications in patients aged 75 years and older.

OBJECTIVE: Meningioma incidence increases with age, yet limited data exist on how comorbidities impact complication rates in elderly patients undergoing meningioma resection. The objective of this study was to report surgical outcomes and identify risk factors for perioperative complications. METHODS: We performed a retrospective study of patients 75 years and older undergoing meningioma resection. Outcomes included survival and complications. Major complications were those requiring surgical intervention or causing permanent neurological deficit. Recursive partitioning, Kaplan-Meier survival, univariate and multi-variate (MVA) analyses were performed. RESULTS: From 1996 to 2014, 103 patients with a median age of 79 years (IQR 77-83 years) underwent cranial meningioma resection. Median follow-up was 5.8 years (IQR 1.7-8.7 years). Median actuarial survival was 10.5 years. Complications occurred in 32 patients (31.1%), and 13 patients (12.6%) had multiple complications. Major complications occurred in 16 patients (15.5%). Increasing age was not a significant predictor of any (p = 0.6408) or major complication (p = 0.8081). On univariate analysis, male sex, Charlson Comorbidity Index greater than 8, and cardiovascular comorbidities were significantly associated with major complications. On MVA only cardiovascular comorbidities (OR 3.94, 95% CI 1.05-14.76, p = 0.0238) were significantly associated with any complication. All patients with major complications had cardiovascular comorbidities, and on MVA male gender (OR 3.78, 95%CI 1.20-11.93, p = 0.0212) was associated with major complications. CONCLUSIONS: Cardiovascular comorbidities and male gender are significant risk factors for complications after meningioma resection in patients aged 75 years and older. While there is morbidity associated with meningioma resection in this cohort, there is also excellent long-term survival.

Senegalin, a new phenylpropanoid and other secondary metabolites from the stem bark of Ekebergia senegalensis A. Juss. (Meliaceae).

Senegalin (1), a new phenylpropanoid has been isolated from the stem bark of Ekebergia senegalensis A. Juss. along with twelve known secondary metabolites including coumarins 2-5, 4-hydroxy-3,5-methylbenzoic acid (6), pentacyclic triterpenoids 7-9, acyclic triterpenoids 10 and 11 and steroids 12 and 13, respectively. Their structures were elucidated with the help of spectroscopic techniques including 1 D- and 2 D-NMR. The antibacterial activity of the major compounds (2, 9-11) was evaluated on five bacterial strains. However, only compounds 2 and 11 showed a weak inhibition against Bacillus subtilis and Pseudomonas agarici. Furthermore, the chemotaxonomic significance of these compounds has also been elaborated.

Effect of manganese, zinc, and copper on the biological and osteogenic properties of mesoporous bioactive glass nanoparticles.

Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro-osteogenic properties. Therefore, the concentration-dependent impact of MBGNs (composition in mol%: 70 SiO2 , 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO2 , 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow-derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn-doped MBGNs (5Mn-MBGNs) showed a small "therapeutic window" with a dose-dependent negative impact on cell viability but increasing pro-osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn-MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu-doped MBGNs (5Cu-MBGNs). Furthermore, 5Cu-MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches.

Pleural Cryobiopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural biopsy using either video-assisted thoracoscopic surgery or medical pleuroscopy is the current diagnostic criterion standard for pleural pathology with a high, yet imperfect, diagnostic yield. Cryobiopsy may provide greater tissue, increase depth of sampled tissue, and/or reduce crush artifact. However, its impact on diagnostic yield remains uncertain, and there are potential concerns regarding its safety too. We performed a systematic review and meta-analysis to investigate the same. METHODS: We performed a systematic search of MEDLINE, Embase, and Google Scholar for studies evaluating the performance of pleural cryobiopsy, assessing the quality of each study using the Quality Assessment, Data Abstraction and Synthesis-2 tool. Using inverse variance weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed specimen characteristics and complications related to the procedure. RESULTS: Seven observational studies involving 586 pleural biopsies (311 cryobiopsies and 275 flexible forceps biopsies) were evaluated. All but one study used a semi-rigid thoracoscope. Meta-analysis generated a diagnostic yield of 96.5% for cryobiopsy and 93.1% for forceps biopsy with an inverse variance-weighted OR of 1.61 (95% CI, 0.71-3.66) and an I2 of 16%. No instances of moderate to severe bleeding were reported with cryobiopsy. A funnel plot illustrated no major publication bias. CONCLUSIONS: Based on analysis of relatively homogenous observational data, pleural cryobiopsy is safe but does not increase diagnostic yield over flexible forceps biopsy. Adequately powered multicenter randomized trials are needed for further investigation.

Novel Treatment of Cerebral Vasospasm Using Solitaire Stent Retriever-Assisted Angioplasty: Case Series.

BACKGROUND: Endovascular procedures such as intraarterial (IA) vasodilator injection and balloon angioplasty are used to treat medically refractory cerebral vasospasm. The effects of IA therapy may be short lived and thus require multiple treatments. Balloon angioplasty also has limitations including transient occlusion of the spastic blood vessel, possible endothelial injury, and limited access to proximal vessels. We aim to demonstrate a novel technique using a stent retriever for the management of medically refractory vasospasm, especially in distal vessels. Compared with balloon angioplasty, stent retrievers provide a passive, self-limiting expansion of blood vessels. Other benefits over balloon angioplasty include 1) ability to simultaneously inject IA vasodilators, 2) limited contact and damage to vessel wall, 3) nonocclusive expansion, and 4) technical ease. METHODS: Fourteen blood vessels from 6 patients with symptomatic vasospasm after subarachnoid hemorrhage were identified. We injected 5 mg of IA vasodilator medication into the vasospastic segments without radiographic improvement in vessel diameter and blood flow. The stent retriever was deployed for 2-5 minutes in each vasospastic segment. RESULTS: Distal anterior and posterior circulation segments were easily accessible with the stent retriever system. It resulted in improved vessel diameter and blood flow with subsequent improvement in neurologic examination. All patients demonstrated radiographic resolution of vasospasm. No procedural-related complications were noted. CONCLUSIONS: We demonstrate the safety and efficacy of a novel technique for the treatment of medically refractory cerebral vasospasm using stent retriever angioplasty in distal vessels. Stent angioplasty can be used as an additional tool in the management of subarachnoid hemorrhage-induced cerebral vasospasm.

Are Transbronchial Cryobiopsies Ready for Prime Time?: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a lack of consensus regarding the yield and safety of transbronchial cryobiopsies for diagnosing diffuse parenchymal lung diseases (DPLD). The purpose of this study was to perform a systematic review and meta-analysis assessing the diagnostic yield and safety profile of transbronchial cryobiopsies in DPLD. METHODS: A literature search of MEDLINE, EMBASE databases, and Google Scholar was performed in August 2017. The quality of included studies was assessed using Quality Assessment, Data Abstraction and Synthesis-2 tool. Meta-analysis was performed using MedCalc (version 17.2). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies, with the number of subjects in each study representing its weight. Random effects model was used when significant heterogeneity was observed (I>40%). RESULTS: A total of 31 studies were included in the review. Of these, 27 studies with 1443 patients reported data on the performance of cryobiopsies for diagnosing DPLD. The diagnostic yield was 72.9% [95% confidence interval (CI), 67.9%-77.7%]. The pooled mean specimen size obtained by cryobiopsies was 23.4 mm (95% CI, 9.6-37.3 mm). The overall complication rate was 23.1% with bleeding and pneumothoraces being the most commonly reported complications. The incidence of significant bleeding was 14.2% (95% CI, 7.9%-21.9%), whereas pneumothorax was seen in 9.4% (95% CI, 6.7%-12.5%) of patients. Overall reported mortality was 0.3%. CONCLUSION: Our meta-analysis shows that cryobiopsies have a good diagnostic yield but a significant risk for complications. Cryobiopsy outcomes vary markedly among different centers. Further research is needed to standardize the procedure and improve its safety profile.

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring ß-Amyrenone.

Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC50 values ranging from 14.5 to 24.6 µM, with compound (1) being the most potent as compared to the positive control thiourea (IC50 = 21.6 µM). Amongst the synthetic derivatives, compound 4 was the most potent (IC50 = 17.9 µM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

Facile one-pot syntheses of new C-28 esters of oleanolic acid and studies on their antiproliferative effect on T cells.

Structure-activity relationship studies on oleanolic acid (1) have resulted in facile syntheses of its new C-28 esters 2-7 by way of one-pot reaction of 1 with a variety of alkylating agents. Oleanolic acid and its new esters were studied for their in vitro antiproliferative effect on healthy human peripheral blood mononuclear cell isolated phytohemagglutinin activated T cells. Results showed that compounds 1, 3, and 5 exhibited significant inhibitory activity on T-cell proliferation. Compound 5 was found to be the most potent, with an IC50 value of 4.249 µg/mL, among all tested compounds, and its activity could be attributed to the presence of bromine atom in the molecule.

Computed Tomography Bronchus Sign and the Diagnostic Yield of Guided Bronchoscopy for Peripheral Pulmonary Lesions. A Systematic Review and Meta-Analysis.

RATIONALE: Indeterminate peripheral pulmonary lesions (PPLs) often require tissue diagnosis. If nonsurgical biopsy techniques are considered, deciding between bronchoscopic transbronchial versus computed tomography-guided transthoracic biopsy can be difficult. The former has a low diagnostic yield with a low complication risk, whereas the latter has a better diagnostic yield but a higher complication rate. Investigators have looked at various lesion characteristics that can predict the diagnostic yield of guided bronchoscopic biopsies. Although consensus exists that larger size and proximity to the hilum increase the diagnostic yield, there is ongoing debate about the association between computed tomography bronchus sign (air-filled bronchus in close proximity of the lesion as seen on computed tomography imaging) and the diagnostic yield of guided bronchoscopic modalities. OBJECTIVES: To perform a meta-analysis and systematic review, determining the association between computed tomography bronchus sign and the diagnostic yield of guided bronchoscopy for PPLs. METHODS: MEDLINE, Embase, Scopus, and Google Scholar were searched in January 2018 for guided bronchoscopy studies that had assessed the impact of computed tomography bronchus sign on the diagnostic yield. The quality of included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 tool. Meta-analysis was performed using MedCalc (version 18). Odds ratios were used to compare yield of lesions with and without bronchus sign. Random effects model was used when significant heterogeneity was observed (I2 > 40%). RESULTS: For 2,199 lesions with computed tomography bronchus sign, the overall weighted diagnostic yield was 74.1% (95% confidence interval, 68.3-79.5%). For 971 lesions without computed tomography bronchus sign, the overall weighted diagnostic yield was 49.6% (95% confidence interval, 39.6-59.5%). The odds ratio for successfully diagnosing a lesion with computed tomography bronchus sign was 3.4 (95% confidence interval, 2.4-5.0). Possible sources of heterogeneity in the meta-analysis included differences in study designs, guidance modalities, and cancer prevalence. The odds ratio for successfully diagnosing a lesion with computed tomography bronchus sign was relatively lower for prospective studies. CONCLUSIONS: PPLs with computed tomography bronchus sign are more likely to be diagnosed with guided bronchoscopy than the lesions without computed tomography bronchus sign. Clinicians should consider this, along with the lesion size and distance from the hilum, when contemplating guided bronchoscopy for PPLs.

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1ß, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.

Kostchyienones A and B, new antiplasmodial and cytotoxicity of limonoids from the roots of Pseudocedrela kotschyi (Schweinf.) Harms.

Two new limonoids, kostchyienones A (1) and B (2), along with 12 known compounds 3-14 were isolated from the roots of Pseudocedrela kostchyi. Compound (7) was isolated for the first time from a natural source. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1-6 and 13-14 gave IC50 values ranging from 0.75 to 5.62 µg/mL for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compound 5 showed moderate potential cytotoxicity against the HEK239T cell line with an IC50 value of 22.2±0.89 µg/mL. The antiplasmodial efficacy of the isolated compounds supports the medicinal value of this plant and its potential to provide novel antimalarial drugs.

Trends in the Incidence and In-Hospital Outcomes of Cardiogenic Shock Complicating Thyroid Storm.

BACKGROUND: Thyroid storm (TS) constitutes an endocrine emergency with an incidence of up to 10% of all admissions for thyrotoxicosis. Cardiogenic shock (CS) is a rare complication of TS and very limited data exists on its incidence and outcomes. We aimed to estimate the national trends in incidence and outcomes of CS among patients admitted to US hospitals with TS. MATERIALS AND METHODS: We queried the nationwide inpatient sample for patients with the discharge diagnosis of TS between the years of 2003 and 2011. RESULTS: Based on a weighted estimate, we identified 41,835 patients with a diagnosis of TS, of which 1% developed CS. Patients with CS were more likely to have history of atrial fibrillation, alcohol abuse, preexisting congestive heart failure, coagulopathy, drug use, liver disease, pulmonary circulation disorders, valvular disorders, weight loss, renal failure, fluid and electrolyte disorders as compared to those who did not develop CS (P < 0.001 for all). We observed an increase in incidence of CS from 0.5% in 2003 to 3% in 2011 and a decrease in mortality from 60.5% in 2003 to 20.9% in 2011 (Ptrend < 0.001 for both). CONCLUSIONS: We observed that CS is a rare complication of TS, which occurs more commonly in male patients with preexisting structural and atherosclerotic heart disease, and carries a very poor prognosis. Although incidence has increased over the years, mortality from CS has steadily declined.