Mechanical pump complication after HeartMate 3 implantation.

BACKGROUND: With the improvement in postoperative complications and long-term survival post LVAD, continuing to improve clinical outcomes will require efforts to decrease long-term complications. The purpose of this study is to describe the incidence of mechanical pump failure requiring surgery, which we define as pump failure secondary to either outflow graft compression, outflow graft obstruction, or pump thrombosis requiring surgical intervention. METHODS: 141 consecutive adult patients who underwent HeartMate3 Implantation using the "cut-then-sew" implantation technique between September 2015 and September 2021 were included in our study. The primary outcome measure was mechanical pump complication (outflow graft obstruction and or pump thrombosis) requiring surgical intervention. Secondary outcome measures included incidence of bleeding, stroke, renal failure, length of stay, and overall survival. Median follow up was 27.3 months. RESULTS: Eleven (7.8%) of patients developed mechanical pump complications. Six patients developed outflow graft obstruction. Five patients developed acute pump thrombosis. Median time to a mechanical complication was 828 days. Of the 11 patients who underwent surgery, 10 patients (90%) survived to discharge. Overall survival at 1, 3, and 5 years was 82.9%, 69.1% and 55.2% respectively for the entire cohort. CONCLUSION: The mechanical pump complication rate of 7.8% which is quite high may be related to duration of follow up, as the median time to mechanical complication was 828 days. This study highlights an important late complication that occurs post LVAD implantation.

Early outcomes of the suprasternal transcatheter aortic valve replacement technique.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is now an established treatment option for patients with severe aortic stenosis. The most utilized approach remains transfemoral. In patients with difficult femoral access a variety of alternate approaches have been used. Recently, suprasternal access has emerged as a viable alternate approach in patients with very complex vascular access. We describe our 30-day outcomes of patients who underwent suprasternal transcatheter aortic valve replacement (suprasternal [SS]-TAVR), which constitutes the largest single-center cohort to date. METHODS: From May 2016 to September 2021, 658 patients underwent TAVR at our institution. Of which 29 underwent SS-TAVR. We performed a retrospective analysis to evaluate early (30 days) outcomes of this procedure. Main outcomes evaluated included 30-day mortality, stroke and pacemaker rates, length of stay, readmission, and valvular function. RESULTS: All patients were alive 30 days after the procedure. The median hospital length-of-stay was 2 days. Two patients (6.9%) had a stroke on the contra-lateral side of access. Two patients (6.90%) had significant cardiac arrhythmias requiring pacemaker placement. In 30 days, one patient was readmitted (3.45%). CONCLUSIONS: Our data confirm the SS-TAVR as a feasible and safe alternative with comparable results to established approaches in patients who are unsuitable for femoral artery access and offers clinicians another access site in patients with very complex anatomy.

Suprasternal transcatheter aortic valve replacement: Modified trocar-free technique.

BACKGROUND AND AIM OF STUDY: Transcatheter aortic valve replacement is established as the standard treatment for severe aortic stenosis. Many approaches have been described, including the suprasternal technique, an alternative for patients with unsuitable femoral arteries. We now describe a trocar-free technique for the Suprasternal approach. METHODS AND RESULTS: Under endotracheal anesthesia, an incision is made above the manubrium and dissection is carried down to the innominate artery with adequate exposure for cannulation. Access site is closed with purse-string suture. The Suprasternal approach has relatively few contraindications. CONCLUSION: Our trocar-free technique is a safe and easily reproducible technique for TAVRs in patients with poor femoral access.

Suboptimal therapy following breast conserving surgery in triple-negative and HER2-positive breast cancer patients.

PURPOSE: To assess potential disparities in guideline-concordant care delivery among women with early-stage triple-negative and HER2-positive breast cancer treated with breast conserving therapy. METHODS: Women ≥ 40 years old diagnosed with pT2N0M0 triple-negative or HER2-positive breast cancer treated with primary surgery and axillary staging between 2012 and 2017 were identified using the National Cancer Database (NCDB). The primary outcome was receipt of adjuvant systemic therapy and radiation concordant with current guidelines. Multivariable log-binomial regression was used to assess the prevalence of optimal therapy use across patient and cancer characteristics. Kaplan-Meier curves were used to assess 5-year overall survival. Multivariable Cox proportional hazards regression was used to compare the impact of optimal therapy on 5-year mortality. RESULTS: 11,785 women were included with 7,843 receiving optimal therapy. Receipt of optimal therapy decreased with age even after adjusting for comorbidities and cancer characteristics; other sociodemographic factors were not associated with differences in receipt of optimal therapy. Among patients who did not receive adjuvant systemic therapy, most were not offered the treatment (49%) or refused (40%). Overall 5-year survival was higher among women who received optimal therapy (89% [95% CI 88.0-89.3] vs. 66% [95% CI 62.9-68.5]). Patients who received suboptimal therapy were over twice as likely to die within 5 years of their diagnosis (adjusted HR 2.44, 95% CI 2.12-2.82). CONCLUSION: Age is the primary determinant of the likelihood of a woman to receive optimal adjuvant therapies in high-risk early-stage breast cancer. Patients who did not receive optimal therapy had significantly diminished survival.

LRR-RLK family from two Citrus species: genome-wide identification and evolutionary aspects.

BACKGROUND: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. RESULTS: We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR-RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. CONCLUSIONS: This work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species.

Facial expressions to identify post-stroke: A pilot study.

BACKGROUND AND OBJECTIVE: Timely stroke treatment can limit brain damage and improve outcomes, which depends on early recognition of the symptoms. However, stroke cases are often missed by the first respondent paramedics. One of the earliest external symptoms of stroke is based on facial expressions. METHODS: We propose a computerized analysis of facial expressions using action units to distinguish between Post-Stroke and healthy people. Action units enable analysis of subtle and specific facial movements and are interpretable to the facial expressions. The RGB videos from the Toronto Neuroface Dataset, which were recorded during standard orofacial examinations of 14 people with post-stroke (PS) and 11 healthy controls (HC) were used in this study. Action units were computed using XGBoost which was trained using HC, and classified using regression analysis for each of the nine facial expressions. The analysis was performed without manual intervention. RESULTS: The results were evaluated using leave-one-our validation. The accuracy was 82% for Kiss and Spread, with the best sensitivity of 91% in the differentiation of PS and HC. The features corresponding to mouth muscles were most suitable. CONCLUSIONS: This pilot study has shown that our method can detect PS based on two simple facial expressions. However, this needs to be tested in real-world conditions, with people of different ethnicities and smartphone use. The method has the potential for a computerized assessment of the videos for use by the first respondents using a smartphone to perform screening tests, which can facilitate the timely start of the treatment.

The Change of Vocal Tract Length in People with Parkinson's Disease.

Hypokinetic dysarthria is one of the early symptoms of Parkinson's disease (PD) and has been proposed for early detection and also for monitoring of the progression of the disease. PD reduces the control of vocal tract muscles such as the tongue and lips and, therefore the length of the active vocal tract is altered. However, the change in the vocal tract length due to the disease has not been investigated. The aim of this study was to determine the difference in the apparent vocal tract length (AVTL) between people with PD and age-matched control healthy people. The phoneme, /a/ from the UCI Parkinson's Disease Classification Dataset and the Italian Parkinson's Voice and Speech Dataset were used and AVTL was calculated based on the first four formants of the sustained phoneme (F1-F4). The results show a correlation between Parkinson's disease and an increase in vocal tract length. The most sensitive feature was the AVTL calculated using the first formants of sustained phonemes (F1). The other significant finding reported in this article is that the difference is significant and only appeared in the male participants. However, the size of the database is not sufficiently large to identify the possible confounding factors such as the severity and duration of the disease, medication, age, and comorbidity factors.Clinical relevance-The outcomes of this research have the potential to improve the identification of early Parkinsonian dysarthria and monitor PD progression.

Hydralazine-Induced Fulminant Liver Failure Requiring Urgent Liver Transplant: Common Drug With Rare Complication.

Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.

Management of Major Injuries to the Bile Duct at a Hepatobiliary Specialty Referral Center.

INTRODUCTION: Aim is to evaluate geographical and demographic factors influencing management of bile duct injuries occurring during cholecystectomy in a tertiary hepato-pancreato-biliary center in Southeast US. METHODS: All referrals for biliary injuries during cholecystectomy, between Jan 2017 and December 2020 were included. RESULTS: 19 patients were identified with a median age of 59 (47-65), average BMI of 30.3 (18-49), and the prevalence of diabetes mellitus, hypertension and cardiovascular disease of 11%, 47% and 16%, respectively. The average transfer distance was 76 miles (8-102) and median transfer time was 3 days (1-12). 16 (84%) had Strasberg E injury, with 4 (21%) having a concomitant vascular injury (3 - right hepatic artery, 1 - right portal vein). Two (10.5%) were managed non-operatively, immediate surgical repair was performed in 2 (10.5%) and 15 (78.9%) patients underwent a delayed repair with a median of 87 days (69-118) from injury to repair. Median operative time was 5 hours (4-7), blood loss was 150 mL (100-200) and hospital stay was 8 days (6-12). DISCUSSION: Factors including distance between hospitals, delays in patient transfer due to bed availability and transportation, play a role in the decision-making towards delayed repair. The delayed repair has the benefit of medical optimization of our high-risk patients' population.

Tabular data augmentation for video-based detection of hypomimia in Parkinson's disease.

BACKGROUND AND OBJECTIVE: This paper presents a method for the computerized detection of hypomimia in people with Parkinson's disease (PD). It overcomes the difficulty of the small and unbalanced size of available datasets. METHODS: A public dataset consisting of features of the video recordings of people with PD with four facial expressions was used. Synthetic data was generated using a Conditional Generative Adversarial Network (CGAN) for training augmentation. After training the model, Test-Time Augmentation was performed. The classification was conducted using the original test set to prevent bias in the results. RESULTS: The employment of CGAN followed by Test-Time Augmentation led to an accuracy of classification of the videos of 83%, specificity of 82%, and sensitivity of 85% in the test set that the prevalence of PD was around 7% and where real data was used for testing. This is a significant improvement compared with other similar studies. The results show that while the technique was able to detect people with PD, there were a number of false positives. Hence this is suitable for applications such as population screening or assisting clinicians, but at this stage is not suitable for diagnosis. CONCLUSIONS: This work has the potential for assisting neurologists to perform online diagnose and monitoring their patients. However, it is essential to test this for different ethnicity and to test its repeatability.

Investigation of the Familial Risk of Rheumatic Heart Disease with Systematic Echocardiographic Screening: Data from the PROVAR+ Family Study.

We aimed to use echocardiographic (echo) screening to evaluate the risk of Rheumatic Heart Disease (RHD) among the relatives of patients with advanced RHD, who were enrolled in the University Hospital's outpatient clinics from February 2020 to September 2021. Consenting first-degree relatives were invited for echo screening using handheld devices (GE VSCAN) by non-physicians, with remote interpretation. Matched controls (spouses, neighbors) living in the same household were enrolled in a 1:5 fashion. A standard echo (GE Vivid-IQ) was scheduled if abnormalities were observed. In 16 months, 226 relatives and 47 controls of 121 patients were screened, including 129 children, 77 siblings and 20 parents. The mean age was 40 ± 17 years, 67% of the patients were women, and 239 (88%) lived with the index case for >10 years. Echo findings suggestive of RHD were confirmed in zero controls and 14 (7.5%) relatives (p = 0.05): 11 patients had mild/moderate mitral regurgitation, and four were associated with mitral stenosis and abnormal morphology. Two patients had mild aortic regurgitation and abnormal morphology, which were associated with mild aortic and mitral stenosis, and two patients with advanced RHD had bioprostheses in the mitral (2) and aortic (1) positions. In conclusion, first-degree relatives of individuals with clinical RHD are at greater risk of having RHD, on top of socioeconomic conditions.

A singular value decomposition approach for improved taxonomic classification of biological sequences.

BACKGROUND: Singular value decomposition (SVD) is a powerful technique for information retrieval; it helps uncover relationships between elements that are not prima facie related. SVD was initially developed to reduce the time needed for information retrieval and analysis of very large data sets in the complex internet environment. Since information retrieval from large-scale genome and proteome data sets has a similar level of complexity, SVD-based methods could also facilitate data analysis in this research area. RESULTS: We found that SVD applied to amino acid sequences demonstrates relationships and provides a basis for producing clusters and cladograms, demonstrating evolutionary relatedness of species that correlates well with Linnaean taxonomy. The choice of a reasonable number of singular values is crucial for SVD-based studies. We found that fewer singular values are needed to produce biologically significant clusters when SVD is employed. Subsequently, we developed a method to determine the lowest number of singular values and fewest clusters needed to guarantee biological significance; this system was developed and validated by comparison with Linnaean taxonomic classification. CONCLUSIONS: By using SVD, we can reduce uncertainty concerning the appropriate rank value necessary to perform accurate information retrieval analyses. In tests, clusters that we developed with SVD perfectly matched what was expected based on Linnaean taxonomy.

Targeting CD38-dependent NAD+ metabolism to mitigate multiple organ fibrosis.

The processes underlying synchronous multiple organ fibrosis in systemic sclerosis (SSc) remain poorly understood. Age-related pathologies are associated with organismal decline in nicotinamide adenine dinucleotide (NAD+) that is due to dysregulation of NAD+ homeostasis and involves the NADase CD38. We now show that CD38 is upregulated in patients with diffuse cutaneous SSc, and CD38 levels in the skin associate with molecular fibrosis signatures, as well as clinical fibrosis scores, while expression of key NAD+-synthesizing enzymes is unaltered. Boosting NAD+ via genetic or pharmacological CD38 targeting or NAD+ precursor supplementation protected mice from skin, lung, and peritoneal fibrosis. In mechanistic experiments, CD38 was found to reduce NAD+ levels and sirtuin activity to augment cellular fibrotic responses, while inhibiting CD38 had the opposite effect. Thus, we identify CD38 upregulation and resulting disrupted NAD+ homeostasis as a fundamental mechanism driving fibrosis in SSc, suggesting that CD38 might represent a novel therapeutic target.

Disclosing ambiguous gene aliases by automatic literature profiling.

BACKGROUND: Retrieving pertinent information from biological scientific literature requires cutting-edge text mining methods which may be able to recognize the meaning of the very ambiguous names of biological entities. Aliases of a gene share a common vocabulary in their respective collections of PubMed abstracts. This may be true even when these aliases are not associated with the same subset of documents. This gene-specific vocabulary defines a unique fingerprint that can be used to disclose ambiguous aliases. The present work describes an original method for automatically assessing the ambiguity levels of gene aliases in large gene terminologies based exclusively in the content of their associated literature. The method can deal with the two major problems restricting the usage of current text mining tools: 1) different names associated with the same gene; and 2) one name associated with multiple genes, or even with non-gene entities. Important, this method does not require training examples. RESULTS: Aliases were considered "ambiguous" when their Jaccard distance to the respective official gene symbol was equal or greater than the smallest distance between the official gene symbol and one of the three internal controls (randomly picked unrelated official gene symbols). Otherwise, they were assigned the status of "synonyms". We evaluated the coherence of the results by comparing the frequencies of the official gene symbols in the text corpora retrieved with their respective "synonyms" or "ambiguous" aliases. Official gene symbols were mentioned in the abstract collections of 42 % (70/165) of their respective synonyms. No official gene symbol occurred in the abstract collections of any of their respective ambiguous aliases. In overall, querying PubMed with official gene symbols and "synonym" aliases allowed a 3.6-fold increase in the number of unique documents retrieved. CONCLUSIONS: These results confirm that this method is able to distinguish between synonyms and ambiguous gene aliases based exclusively on their vocabulary fingerprint. The approach we describe could be used to enhance the retrieval of relevant literature related to a gene.

MST (molecular serotyping tool): a program for computer-assisted molecular identification of Escherichia coli and Shigella O antigens.

Escherichia coli and Shigella O antigens can be inferred using the rfb-restriction fragment length polymorphism (RFLP) molecular test. We present herein a dynamic programming algorithm-based software to compare the rfb-RFLP patterns of clinical isolates with those in a database containing the 171 previously published patterns corresponding to all known E. coli/Shigella O antigens.

Evaluation of a linear spectral mixture model and vegetation indices (NDVI and EVI) in a study of schistosomiasis mansoni and Biomphalaria glabrata distribution in the state of Minas Gerais, Brazil.

This paper analyses the associations between Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) on the prevalence of schistosomiasis and the presence of Biomphalaria glabrata in the state of Minas Gerais (MG), Brazil. Additionally, vegetation, soil and shade fraction images were created using a Linear Spectral Mixture Model (LSMM) from the blue, red and infrared channels of the Moderate Resolution Imaging Spectroradiometer spaceborne sensor and the relationship between these images and the prevalence of schistosomiasis and the presence of B. glabrata was analysed. First, we found a high correlation between the vegetation fraction image and EVI and second, a high correlation between soil fraction image and NDVI. The results also indicate that there was a positive correlation between prevalence and the vegetation fraction image (July 2002), a negative correlation between prevalence and the soil fraction image (July 2002) and a positive correlation between B. glabrata and the shade fraction image (July 2002). This paper demonstrates that the LSMM variables can be used as a substitute for the standard vegetation indices (EVI and NDVI) to determine and delimit risk areas for B. glabrata and schistosomiasis in MG, which can be used to improve the allocation of resources for disease control.

CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels.

Decreased NAD+ levels have been shown to contribute to metabolic dysfunction during aging. NAD+ decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD+ homeostasis. Here we show that an increase in CD38 in white adipose tissue (WAT) and the liver during aging is mediated by accumulation of CD38+ immune cells. Inflammation increases CD38 and decreases NAD+. In addition, senescent cells and their secreted signals promote accumulation of CD38+ cells in WAT, and ablation of senescent cells or their secretory phenotype decreases CD38, partially reversing NAD+ decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD+ through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that, through its ecto-enzymatic activity, decreases levels of NMN and NAD+.

Erratum: Correction Notice: Two Different Methods of Quantification of Oxidized Nicotinamide Adenine Dinucleotide (NAD+) and Reduced Nicotinamide Adenine Dinucleotide (NADH) Intracellular Levels: Enzymatic Coupled Cycling Assay and Ultra-performance Liquid Chromatography (UPLC)-Mass Spectrometry.

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Erratum: Correction Notice: Measuring CD38 Hydrolase and Cyclase Activities: 1,N6-Ethenonicotinamide Adenine Dinucleotide (ε-NAD) and Nicotinamide Guanine Dinucleotide (NGD) Fluorescence-based Methods.

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Genetic variability in the 5' UTR and NS5A regions of hepatitis C virus RNA isolated from non-responding and responding patients with chronic HCV genotype 1 infection.

Sequence variation among different hepatitis C virus (HCV) isolates has adaptive significance and reflects the modes and intensities of selection mechanisms operating on the virus. In this work, we sought to investigate using classical population genetics parameters, the genetic variability of HCV genotype 1 using the 5' UTR and NS5A regions from treatment non-responding and responding groups of patients. Both regions showed low genetic variability and the 5' UTR showed neutral deviation. No differences were observed in the nonsynonymous/synonymous nucleotide substitution ratio among groups for NS5A. The analysis of molecular variance test of the 5' UTR region showed an 11.94% variation among groups. Phylogenetic analysis showed no correlation between sequence variations and therapeutic responses.