Preoperative extracorporeal membrane oxygenation for postinfarction ventricular septal defect: Case series of three patients with a literature review

The mortality rate after the development of postinfarction ventricular septal defect (VSD) remains high, despite progress in pharmacologic therapy, invasive cardiology, and surgical techniques. We present three cases of preoperative venoarterial extracorporeal membrane oxygenation as a bridge to reparative surgical repair in patients with cardiogenic shock who would otherwise require emergent cardiac surgery with an associated risk. Two patients were discharged, whereas the third patient died due to pulmonary artery rupture after a right ventricular assist device implantation, despite the fact that he had a successful bridge to reparative surgery and VSD repair. Finally, a review of the current literature concerning the use of preoperative venoarterial extracorporeal membrane oxygenation as a bridge to reparative surgery is provided.     

The association of alcohol use disorder with perioperative outcomes after primary total shoulder arthroplasty for glenohumeral osteoarthritis: a retrospective matched cohort study

BackgroundAccording to the World Health Organization, alcohol use disorder (AUD) is one of the leading mental health disorders in the United States. As the utilization of primary total shoulder arthroplasties (TSAs) continues to increase nationwide for the treatment of glenohumeral osteoarthritis (OA), studies evaluating the association of AUD with outcomes after primary TSA are warranted. Therefore, the aim of this study was to determine whether patients who undergo TSA and who have AUD have higher in-hospital lengths of stay (LOS), medical complications, and health care expenditures.MethodsThe Parts A and B 100% Medicare Claims Database were queried to identify patients who underwent primary TSA for glenohumeral OA and have AUD from January 1, 2005 to March 31, 2014. Patients were 1:5 ratio matched to a comparison cohort by age, sex, and various comorbid conditions. The query yielded 32,846 patients in the study (n = 5479) and comparison (n = 27,367) cohorts. The variables of interest include comparison of in-hospital LOS, 90-day medical complications, and day of surgery and 90-day health care costs. Welch’s t-tests were used to compare LOS, whereas multivariate logistic regression analyses were used to calculate the odds ratio (OR) of AUD on complications. A P value less than 0.001 was considered to be statistically significant.ResultsPatients with AUD had significantly longer in-hospital LOS (4 vs. 2 days, P < .0001), in addition to higher rates and odds of 90-day complications (30.44% vs. 7.94%; OR: 1.85, P < .0001) such as surgical site infections (1.15 vs. 0.24%; OR: 2.33, P < .0001), cerebrovascular accidents (5.06 vs. 1.23%; OR: 2.16, P < .0001), respiratory failures (5.79 vs. 1.52%; OR: 2.02, P < .0001), myocardial infarctions (1.53 vs. 0.43%; OR: 2.01, P < .0001), acute kidney injuries (6.55 vs. 1.34%; OR: 1.89, P < .0001), and other complications. In addition, patients in the study group incurred significantly higher day of surgery ($12,160.60 vs. $11,308.48, P < .0001) and 90-day episode of care costs ($14,493.13 vs. $13,087.55, P < .0001).ConclusionAs the prevalence of AUD continues to increase nationwide, understanding the association of AUD with outcomes after primary TSA for the treatment of glenohumeral OA is necessary. The current investigation is important as health care professionals and orthopedists can use this information to adequately educate patients on potential complications which may occur after their procedure.     

Emerging strains of porcine epidemic diarrhoea virus (PEDv) in Mexico

As an emerging disease, the porcine epidemic diarrhoea virus has caused substantial economic losses to the pork industry in Mexico, leading to piglet mortality rates of up to 100%. For detection, sequencing and genetic characterization of the virus, 68 samples of one‐week‐old piglets from pork farms in 17 states of Mexico were analysed. In total, 53 samples were positive by real‐time RT‐PCR, confirming the presence of the virus in 15 states. Twenty‐eight samples from 10 states were amplified by endpoint RT‐PCR, and 20 sequences of the spike gene were obtained. A phylogenetic analysis based on the spike gene demonstrated that all Mexican strains are in Group II and are classified as non‐Indel‐S emerging variants. Three strains showed amino acid insertions: PEDv/MEX/GTO/LI‐DMZC15/2015 and PEDv/MEX/QRO/LI‐DMZC45/2016 showed one amino acid insertion (⁴²⁴Y⁴²⁵ and ⁴⁴⁷D⁴⁴⁸, respectively), and PEDv/MEX/QRO/LI‐DMZC49/2019 showed one and two amino acid insertions (⁴²²C⁴²³ and ⁵³⁷SQ⁵³⁸), with the second insertion in the COE region. These results provide evidence of the prevalence of emerging, non‐Indel‐S strains of the virus are currently circulating in Mexico during 2016–2018, when three of which have amino acid insertions: PEDv/MEX/GTO/IN‐DMZC15/2015 and PEDv/MEX/QRO/IN‐DMZC45/2016 have one amino acid insertion each (⁴²⁴Y⁴²⁵ and ⁴⁴⁷D⁴⁴⁸, respectively), and PEDv/MEX/QRO/IN‐DMZC49/2019 has one (⁴²²C⁴²³) and two amino acid insertions (⁵³⁷SQ⁵³⁸), the latter being in the COE region, which could generate new antigenic variants.     

High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC

Significant rational is available for specific targeting of PI3K/AKT/mTOR pathway in the treatment of non-small cell lung cancer (NSCLC). However, almost all clinical trials that have evaluated Pi3K pathway-based monotherapies/combinations did not observe an improvement of patient’s outcome. The aim of our study was therefore to define combination of treatment based on the determination of predictive markers of resistance to the mTORC1 inhibitor RAD001/Everolimus. An in vivo study showed high efficacy of RAD001 in NSCLC Patient-Derived Xenografts (PDXs). When looking at biomarkers of resistance by RT-PCR study, three genes were found to be highly expressed in resistant tumors, i.e., PLK1, CXCR4, and AXL. We have then focused our study on the combination of RAD001 + Volasertib, a PLK1 inhibitor, and observed a high antitumor activity of the combination in comparison to each monotherapy; similarly, a clear synergistic effect between the two compounds was found in an in vitro study. Pharmacodynamics study demonstrated that this synergy was due to (1) tumor vascularization decrease, increase of the HIF1 protein expression and decrease of the intracellular pH, and (2) decrease of the Carbonic Anhydrase 9 (CAIX) protein that could not correct intracellular acidosis. In conclusion, all these preclinical data strongly suggest that the inhibition of mTORC1 and PLK1 proteins may be a promising therapeutic approach for NSCLC patients.     

Geographic and Socioeconomic Disparity of Gastric Cancer Patients in Canada

Gastric cancer is the 5th most common malignancy worldwide, representing ~5–10% of all new cancer cases. Although its incidence is declining, it is estimated that 1 in 98 Canadians will develop gastric cancer in their lifetime. The epidemiology and distribution of gastric cancer throughout Canada, however, remains poorly understood. A retrospective analysis of demographic data across Canada between 1992 and 2010 was performed using 2 population-based cancer registries. The incidence of gastric cancer was examined at the levels of provinces, cities, and postal codes. In addition, 43,955 patients were diagnosed with gastric cancer in Canada between 1992 and 2010; 66% were male and the average age of diagnosis was 68.4 years. The age-adjusted incidence rate was 5.07 cases per 100,000 individuals per year. The incidence decreased over the study period by 30%. High incidence rates were identified in rural areas of Newfoundland and Labrador, New Brunswick, and Quebec. Our study found a significant association between gastric cancer incidence rates and lower socioeconomic status, as well as Hispanic ethnicity. This is the first study to provide a comprehensive analysis of the incidence of gastric carcinoma in Canada, identifying high-risk populations that may benefit from increased primary and secondary prevention.     

The leaf ionome as a multivariable system to detect a plant's physiological status

The contention that quantitative profiles of biomolecules contain information about the physiological state of the organism has motivated a variety of high-throughput molecular profiling experiments. However, unbiased discovery and validation of biomolecular signatures from these experiments remains a challenge. Here we show that the Arabidopsis thaliana (Arabidopsis) leaf ionome, or elemental composition, contains such signatures, and we establish statistical models that connect these multivariable signatures to defined physiological responses, such as iron (Fe) and phosphorus (P) homeostasis. Iron is essential for plant growth and development, but potentially toxic at elevated levels. Because of this, shoot Fe concentrations are tightly regulated and show little variation over a range of Fe concentrations in the environment, making them a poor probe of a plant's Fe status. By evaluating the shoot ionome in plants grown under different Fe nutritional conditions, we have established a multivariable ionomic signature for the Fe response status of Arabidopsis. This signature has been validated against known Fe-response proteins and allows the high-throughput detection of the Fe status of plants with a false negative/positive rate of 18%/16%. A “metascreen” of previously collected ionomic data from 880 Arabidopsis mutants and natural accessions for this Fe response signature successfully identified the known Fe mutants frd1 and frd3. A similar approach has also been taken to identify and use a shoot ionomic signature associated with P homeostasis. This study establishes that multivariable ionomic signatures of physiological states associated with mineral nutrient homeostasis do exist in Arabidopsis and are in principle robust enough to detect specific physiological responses to environmental or genetic perturbations.     

Predictors of depression and life satisfaction in visually impaired people

Background: Visual impairment can lead loss of functional ability, necessity of accommodations and assistive technologies or having to rely on others for help. This can bring about feelings of sadness, dependency, inadequacy, and fear, which can put a person at risk for depression and affect one’s satisfaction with life.

Purpose: The aim of this study was to examine the effects of socio-demographic factors, disability-related factors, optimism, pessimism, self-esteem and social support on depression, and life satisfaction in visually impaired people.

Methods: A total of 94 visually impaired people completed the measures of socio-demographic and disability-related characteristics, optimism and pessimism, self-esteem, social support, depression and life satisfaction, administered by the authors. Correlational and hierarchical regression analysis was used to examine the relations and test the model for predicting depression and life satisfaction.

Results: The results have shown that depression was negatively related to the level of education, optimism, self-liking, self-competence, support from friends, family and coworkers, and positively related to comorbidity and pessimism. Life satisfaction was positively related to education, socio-economic status, optimism, self-liking, self-competence and support from friends, family and coworkers, and negatively to pessimism. Results have further shown that depression levels were predicted by education, comorbidity, optimism and self-liking, and that self-liking mediated the relationship between optimism and depression. Life satisfaction was predicted by optimism, pessimism, self-liking, friends’ support, and depression. Further analysis suggested that the path from optimism to life satisfaction goes through self-liking, friends’ support, and depression. Pessimism showed indirect effects through self-liking but also had direct effects on life satisfaction.

Conclusions: Focusing on optimism, pessimism, self-esteem, and social functioning of visually impaired is important in preventing depression and promoting life satisfaction, and should be a part of rehabilitation practices.

• Implications for Rehabilitation

• Screening for depression and mental health problems should be a part of rehabilitation process.

• Changes in the perception of future outcomes should be monitored and addressed throughout rehabilitation process in order to boost realistic optimism and prevent discouragement and hopelessness.

• Frequent feedback and positive reinforcement about a persons’ progress and ability should be given throughout rehabilitation process in order to promote positive view of oneself and prevent self-esteem problems.

• Visually impaired people should be encouraged to socialise outside of their families and participate in social activities. This can be integrated in rehabilitation process as a part of everyday homework.

     

MITOCHONDRIAL ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS : I. LOCALIZATION OF THE ANTIGEN TO MITOCHONDRIAL MEMBRANES

The antigen reacting with complement-fixing antibodies in the sera of patients with primary biliary cirrhosis was localized predominantly in the mitochondrial fraction of tissue homogenates obtained by differential centrifugation. Purified mitochondrial preparations had a high content of the antigen whereas purified lysosomes failed to fix complement with PBC sera. Analysis of a number of fractionation experiments showed a high correlation between antigen content and the mitochondrial enzyme succinic dehydrogenase in all fractions. There was much poorer correlation with lysosomal and micrososomal enzyme markers. The patterns of staining obtained with a fluorescein conjugate of IgG from a PBC patient closely paralleled those obtained with a histochemical method for the demonstration of succinic dehydrogenase, further confirming the mitochondrial localization of the antigen. Staining was brightest in cells containing mitochondria with well-developed cristae. Studies on mitochondria fragmented by osmotic lysis, hexane, lysolecithin, and ultrasound suggest that the antigen is associated with the mitochondrial inner membranes.