Pulmonary sarcomatoid carcinoma; non-small cell lung cancer; EGFR mutation; MET amplification; crizotinib/gefitinib

Sepsis causes multi-organ dysfunction and is a major cause of death in intensive care units, but there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so is a potential treatment for sepsis. Recent clinical trials of high-doses of intravenous vitamin C (6-16 g/day) had variable effects. Since much higher doses are without side-effects in cancer and burns patients, we studied the effects of a mega-dose of intravenous sodium ascorbate (150 g/40 kg) in a clinically relevant ovine model of sepsis. This treatment dramatically improved the clinical state and over 3-7-h improved cardiovascular, pulmonary, hepatic and renal function and reduced body temperature. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. Clinical trials are testing the effectiveness of mega-dose vitamin C in septic patients.

During valvular surgery, abnormal coronary distribution, especially if unidentified by preoperative exams, may put coronary arteries at risk of damage. In this case report, we describe the approach to an anomalous right coronary artery during aortic valve replacement.

The efficient construction of γ-chirogenic amines has been realized via asymmetric hydrogenation of γ-branched N-phthaloyl allylamines by using a bisphosphine-Rh catalyst bearing a large bite angle. The desired products possessing different types of γ-substituents were obtained in quantitative yields and with excellent enantioselectivities (up to >99.9% ee). This protocol provided a practical method for the preparation of γ-chirogenic amine derivatives such as the famous antidepressant drug Fluoxetine (up to 50000 S/C). The mechanism calculation shows a weak interaction-promoted activation mode which is completely different from the traditional coordination-promoted activation mode in the Rh-catalyzed hydrogenation.

In this paper, we address the global asymptotic synchronization (GAS) problem of the Master-Slave fractional order multi-linked memristive neural networks (FOMMNNs). Firstly, we propose the FOMMNNs which incorporate the fractional calculus into multi-linked memristive neural networks (MMNNs) for the first time. Then, by utilizing the fractional differential inclusions and set-valued mapping theories, the addressed FOMMNNs with discontinuous state switching at the right-hand side and time-varying delays are converted into the continuous FOMMNNs. Under the frameworks of fractional Caputo derivative and fractional Fillipov solution, by the way of building up appropriate Lyapunov functionals and utilizing some synchronous analysis technology, several sufficient criteria ensuring that the Master-Slave FOMMNNs can realize global asymptotic synchronization (GAS) under two different state-feedback controllers are obtained.

A document by Giuseppe Maltese. Click on the document to view its contents.

Background: Functional mitral regurgitation (FMR) is common in patients with myocardial infarction or dilated cardiomyopathies, and portends a poor prognosis despite guideline-directed medical therapy. Surgical or transcatheter mitral repair for FMR from recent randomized clinical trials showed disappointing or conflicting results. Aims: To provide an update on the role of surgical repair in the management of FMR. Materials & Methods: A literature search was conducted utilizing PubMed, Ovid, Web of Science, Embase and Cochrane Library. The search terms included secondary/functional mitral regurgitation, ischemic mitral regurgitation, mitral repair, mitral replacement, mitral annuloplasty, transcatheter mitral repair, and percutaneous mitral repair. Randomized clinical trials over the past decade were the particular focus of this current review. Results: Recent data underlined the complexity and poor prognosis of FMR. Guideline-directed medical therapy and cardiac resynchronization, when indicated, should always be applied. Accurate assessment of the interplay between ventricular geometry and mitral valve function is essential to differentiate proportionate FMR from the disproportionate subgroup, which could be helpful in selecting appropriate transcatheter intervention strategies. Surgical repair, most commonly performed with an undersized ring annuloplasty, remains controversial. Adjunctive valvular or subvalvular repair techniques are evolving and may produce improved results in selected FMR patients. Conclusion: FMR resulted from complex valve-ventricular interaction and remodeling. Distinguishing proportionate FMR from disproportionate FMR is important in exploring their underlying mechanisms and to guide medical treatment with surgical or transcatheter interventions. Further studies are warranted to confirm the clinical benefit of appropriate surgical repair in selected FMR patients.

Noonan syndrome is a genetic multisystem disorder characterized by distinctive facial features, developmental delay, congenital heart disease, and other conditions. It is associated with mutation of genes encoding the proteins in the RAS-MAPK pathway, including PTPN11. We herein describe the first case of Noonan syndrome complicated with hepatocellular carcinoma.

A comprehensive evaluation indicator system is needed to provide a integrated assessment of the degree of sloped cropland degradation. We employed bibliometrics to perform statistical analysis on research studies involving cropland degradation. Frequency analysis was then used to identify high-frequency indicators with which to construct a total index set (TIS) for evaluation of the degree of sloped cropland degradation in black soil region. In addition, soil measurement data from sloped cropland in Baiquan and Keshan Counties, Heilongjiang province, China, were used as a basis to construct a minimum index set (MIS). The TIS included A-horizon thickness, clay content, organic matter content, pH, slope gradient, ridge-slope angle, gully density, bulk density, large water-stable aggregate content, soil cation exchange capacity, and crop yield. The first six of these were included in the MIS. In the studied area, undegraded soil, mildly degraded soil, and moderately degraded soil and above accounted for 7%, 48% and 45% of investigated sloped croplands, respectively. Slope gradient is one of the main factors affecting soil degradation. Soil degradation mainly presented as worsening of soil physicochemical characteristics. In addition, downslope and small-angle ridge cultivation are benefit for soil organic matter maintenance and the soil structure and nutrient retention capacity is better than soil with contour or large-angle ridge cultivation. The reason might be that downslope and small-angle ridge cultivation are usually employed on soil with small slope. The study results provide a scientific basis for improving the quality and productivity of sloped cropland in black soil region.

Objective: Description of the use of corticosteroids for the management of parapneumonic pleural effusion in children. Methods: Retrospective monocenter cohort study of all children hospitalized with a discharge diagnosis of parapneumonic pleural effusion during a 15-year period. Results: We documented 97 cases of parapneumonic effusion during the study period, with a median age (interquartile range (IQR)) of 43 (33-61) months. Most of the children benefited from an evacuation of the pleural effusion (89/97, 91.8%): 21 patients (21.6%) were treated with needle thoracocentesis only, while a chest tube was inserted in 68 children (70.1%). Thirty-two patients (33%) were treated with intrapleural fibrinolysis. Fifty-five children (56.7%) received corticosteroids for persistent fever. The median time (IQR) between hospital admission and initiation of corticosteroids was 5.5 (4-7) days. When corticosteroids were initiated, children were febrile since 9 (IQR 8-11) days. The fever ceased in a median (IQR) of 0 (0-1) day after corticosteroids initiation. Only 1 patient required a video-assisted thoracoscopy that was provided because of morphological reasons (morbid obesity). No children treated with corticosteroids required surgery. All children were discharged alive from hospital. The median (IQR) hospital length of stay was 11 (8-14) days, with no difference between children with and without corticosteroids. Conclusion: Our results indicate that corticosteroids could be associated with a significant reduction in the use of surgical procedures and with a prompt clinical improvement. Corticosteroids could thus offer a non-invasive therapeutic alternative for children with parapnemonic effusions when antibiotics and pleural drainage are considered a failure.

BACKGROUND. Mitral valve (MV) repair with MitraClip system is a safe treatment option for high-risk patients with significant mitral regurgitation (MR). We aimed to characterize, by three-dimensional echocardiography (3D-E), changes occurring in MV after implantation of third generation MitraClip XTR device, with specific reference to the underlying MR mechanism (functional vs. degenerative, FMR vs DMR). METHODS. We prospectively enrolled 59 patients, who underwent intra-procedural 3D-E before and after device deployment. Three-D datasets were analysed off-line, using a dedicated semiautomatic software, to obtain parametric quantification of mitral anatomy. RESULTS. Post-procedural MR of mild or lesser degree was achieved in 40 patients (68%), with no differences between FMR and DMR (p 0.9). After MitraClip XTR implantation, the FMR group experienced an immediate annular resizing, with reduction of antero-posterior diameter (p 0.024) and sphericity index (p 0.017), next to a recovery of physiological saddle-shape, defined by lower non-planar angle (p ≤0.001) and higher annulus height to commissural width ratio (p ≤0.001). On the opposite, the DMR group revealed a significant decrease of maximum annular velocity (p 0.027), addressing a mechanic effect of the device deployment. Finally, baseline anterior mitral leaflet angle was found as the strongest independent predictor of acute procedural result (OR 0.91, [CI 0.84-0.99], p = 0.030). CONCLUSIONS. MitraClip XTR implantation acts in restoring the original mitral geometry, with distinctive effects according to MR mechanism. Three-D parametric quantification of MV sheds new light on changes occurring in the valvular apparatus, and helps identifying possible new predictors of acute procedural success.

Species interactions and mechanisms affect plant coexistence and community assembly. Despite increasing knowledge of kin recognition and allelopathy in regulating interspecific and intraspecific interactions among plants, little is known about whether kin recognition mediates allelopathic interference. We used allelopathic rice cultivars with the ability for kin recognition grown in kin vs. non-kin mixtures to determine their impacts on paddy weeds in field trials and a series of controlled experiments. We experimentally tested potential mechanisms of the interaction via altered root behavior, allelochemical production, and soil microbial community composition, as well as carbon and nitrogen partitioning in the weeds. We consistently found that the establishment and growth of paddy weeds were more inhibited by kin mixtures compared to non-kin mixtures. The effect was driven by kin recognition that induced altered root placement, established similar soil microbial communities, and altered weed carbon and nitrogen partitioning. Importantly, genetic relatedness enhanced the production of intrusive roots towards weeds and reduced the production of rice allelochemicals. These findings suggest that relatedness allows allelopathic plants to discriminate their neighboring collaborators (kin) or competitors and then adjust their growth, competitiveness and chemical defense accordingly.

Bullying-induced dyspnoea in children: a case seriesIan P. Sinha 1,2Claire Hepworth 1Sujata De 1Sunil D. Sharma 1Ian Street 1Philip J. Lawrence 1Thomas Hampton* 1,21 Alder Hey Children’s Hospital, Liverpool, UK2 Division of Child Health, University of Liverpool, UK*Corresponding author ([email protected])Dear EditorWe conduct a multidisciplinary complex breathlessness clinic for children1. We conduct spirometry before and after a treadmill exercise test (until the child is breathless), continuous nasal laryngoscopy, pulse oximetry, and calculation of maximal oxygen consumption (VO2max). Here we describe a series of children who presented with troublesome breathlessness that appeared to be caused, or exacerbated by, being bullied.Case 1 (14 year old white female): She was a highly competitive sportsperson, but was recently unable to train or compete. She described her breathlessness as ‘air getting stuck in her throat’, and had a non-specific cough. She had frequent admissions to hospital, treated as presumed asthma attacks. The referring clinician felt her asthma was of insufficient severity to cause her problems. She had no documented obstruction on spirometry in clinic, nor and Fractional Exhaled Nitric Oxide (FeNO) was normal. In clinic she managed a few minutes of running, before suddenly stopping. There was no evidence of exercise-induced bronchoconstriction or exercise-induced laryngeal obstruction (EILO), but she had features of dysfunctional breathing (DB). On questioning she described feeling bullied by parents of other children in her sports team, whom she described as overcritical and disparaging. She was taught breathing exercise and referred to psychological services. Her symptoms and asthma attacks improved, and she recommenced competitive sports.Case 2 (10 year old white female): She had a chronic wet cough since the age of six months. She underwent flexible bronchoscopy which identified mild tracheobronchomalacia. She recently described breathlessness on mild exertion that was disproportionate to the degree of tracheobronchomalacia. Physiological testing never demonstrated airways obstruction, or raised FeNO. In clinic she started running but stopped within minutes, with no physiological evidence of increased work of breathing or bronchoconstriction. Laryngoscopy was normal. On questioning she described that she was bullied at school. Specifically, she described that children would not sit near her because of her cough. She was followed up in respiratory physiotherapy clinic, and her symptoms and exercise tolerance improved.Case 3 (13 year old white female): She had no medical diagnoses at the time of testing, but previously had tonsillectomy because of recurrent tonsillitis. She described breathlessness on exertion. She stopped running very suddenly, as soon as she felt breathless on the treadmill. The breathlessness started as discomfort underneath her ribs and in her throat. Spirometry and laryngoscopy were normal before and after exercise. She had apical breathing and hyperventilation at rest, suggestive of dysfunctional breathing. She described being bullied at school. She did not attend follow up sessions with physiotherapy and was discharged from the service.Case 4 (9 year old black male): He was treated for mild asthma which had, until recently, been well controlled. He had become withdrawn, and was not enjoying playing sports despite previously being very athletic. On questioning he described suffering significant and long-standing racial bullying at school. He discussed this with the teachers but his symptoms seemed to develop after he felt like his complaints were not taken seriously. His breathlessness and exercise tolerance improved temporarily after enrolling in a community sports program for children with asthma 2, and he was much better after moving school.Across these cases, we identified common themes:The character and severity of the breathlessness was out of keeping with their underlying diagnoses, and was intensely unpleasant. All children described non-specific and variable symptoms of pain in their abdomen, joints, or chest.They appeared withdrawn, unhappy, and lacking in self-confidence. They had slouched posture, and spoke quietly.They had very sudden and surprising termination of exercise after starting to feel breathless, with no significant physiological evidence of increased work of breathing – we noticed a stark difference compared with other children who saw breathlessness as a challenge and would continue to run long after showing signs of tachypnoea and tachycardia.In all cases, it was the healthcare professionals who raised the subject of bullying. The children had felt that they had raised concerns about being bullied but felt these were dismissed.When children engaged with physiotherapy, we noticed improvements. The children were relieved when we did not find significant anatomical or physiological diagnoses, and all agreed their breathlessness was caused by bullying.We feel that these patterns relate to a phenotype of childhood dyspnoea specifically related to bullying. Anxiety is associated with tachypnoea, but in our experience the pattern of breathing in these children was different: their shallow, rapid breathing at rest was felt to be related to a slouched posture causing restriction, and all had a sudden cessation to exercise after very minimal exertion. We suggest these are manifestations, specifically, of low self-esteem. It was notable that they described the breathlessness as intensely uncomfortable. The neural pathways involved in driving respiration, and sensing breathlessness, are complex, and we postulate that they are affected by low self-esteem.This, to our knowledge, is the first description of bullying-induced dyspnoea in children, as a separate phenomenon to anxiety-related hyperventilation. There may be crossover with other psychological, physiological and anatomical problems, and further research is warranted. Having asthma is a risk factor for being bullied3, and bullying is associated with worse asthma control4. A recent review has also identified possible associations between bullying and the development of childhood asthma5. It is important ask about bullying when taking a history from a child with unexplained or disproportionate breathlessness.

Bronchopulmonary dysplasia is a relatively common and severe complication of prematurity, and its pathogenesis remains ambiguous. Revolutionary advances in microbiological analysis techniques, together with the growing sophistication of the gut-lung axis hypothesis, have resulted in more studies linking gut microbiota dysbiosis to the occurrence and development of bronchopulmonary dysplasia. The present article builds on current findings to examine the intrinsic associations between gut microbiota and bronchopulmonary dysplasia. The gut microbiota affects bronchopulmonary dysplasia via several potential mechanisms including alteration of the gut-lung axis, promotion of inflammation and the ensuing growth effects, therefore these are also investigated. By evaluating the potential mechanisms, new therapeutic targets and potential therapeutic modalities for BPD can be identified from a microecological perspective.

Currently, the only widely accepted indication for interventional treatment in cases of pulmonary embolism is hemodynamic instability or cardiogenic shock. However, the presence of a right-heart thrombus along with a pulmonary embolism is a poor prognostic indicator, and catheter-directed thrombolysis with the use of thrombolytic agents should also be considered in this circumstance. Optimal management of right heart thrombus and high-risk pulmonary embolism is still uncertain. Herein, we present the case of an 81-year-old woman who presented at our hospital after progressive dyspnea and a syncopal event. The transthoracic echocardiography showed massive bilateral pulmonary, right ventricular, and mobile atrial thrombus and also right-sided enlargement. The patient was successfully treated with acoustic pulse thrombolysis using the EKOS EkoSonic system and echocardiography revealed complete resolution of her right-heart thrombus and her high-risk pulmonary embolism 2 days later.

Abdominal wall endometrioma is an extremely rare entity with a precise incidence of 0.07%–0.47% remaining an insidious cause of usually delayed diagnosis. Differential diagnosis should include that rare condition and ultrasonography remains a pivotal tool to unravel that enigma as well.

In this paper, we are concerned with the problem of counting the multiplicities of a zero-dimensional regular set's zeros. We generalize the squarefree decomposition of univariate polynomials to the so-called pseudo squarefree decomposition of multivariate polynomials, and then propose an algorithm for decomposing a regular set into a finite number of simple sets. From the output of this algorithm, the multiplicities of zeros could be directly read out, and the real solution isolation with multiplicity can also be easily produced. As a main theoretical result of this paper, we analyze the structure of dual space of the saturated ideal generated by a simple set as well as a regular set. Experiments with a preliminary implementation show the efficiency of our method.

Background Pregnancy and liver cirrhosis is a rare but increasing combination. Liver cirrhosis can raise the chance of maternal and fetal mortality and morbidity, although the exact risks remain unclear. Objective To provide a systematic literature review and meta-analysis on maternal, fetal and obstetric complications among pregnant women with liver cirrhosis. Search strategy We performed a systematic literature search in the databases PubMed/MEDLINE and EMBASE (Ovid) from inception through 25 January 2021. Selection criteria Studies including pregnancies with liver cirrhosis and controls were eligible. Data collection and analysis Two reviewers independently evaluated study eligibility. We used the random-effects model for meta-analysis. Main results Our search yielded 3118 unique papers. We included 11 studies, including 2912 pregnancies in women with cirrhosis from 1982-2020. Seven studies were eligible for inclusion in the meta-analysis. The overall maternal mortality rate was 0.89%. Maternal mortality and variceal hemorrhage decreased comparing recent and older studies. Most cases of maternal mortality due to variceal hemorrhage (70%) occurred during vaginal delivery. Pregnant women with liver cirrhosis had a higher chance of preterm delivery (OR 6.7 95% CI 5.1- 9.1), cesarean section (OR 2.6, 95% CI 1.7-3.9), preeclampsia (OR 3.8, 95% CI 2.2-6.5) and small for gestational age neonates (OR 2.6, 95% CI 1.6-4.2) compared to the general obstetric population. Subgroup-analyses could not be conducted. Conclusions Liver cirrhosis in pregnant women is associated with serious increases in maternal mortality and obstetric and fetal complications. Large international prospective studies are needed to identify risk factors for unfavorable outcome.