Who Do We Fail to Rescue after Pancreatoduodenectomy? Outcomes Among >4000 Procedures Expose Windows of Opportunity.

OBJECTIVE: Our investigation on in-hospital mortality after 4474 pancreatoduodenectomies aimed to identify time-dependent risks as well as windows of opportunity to rescue patients from complications. BACKGROUND: Pancreatoduodenectomy is generally considered a safe procedure with a 1-10% perioperative mortality based on complexity and surgical volume. Yet, patients are susceptible for life-threatening complications particularly with extended resections. Recognition of distinct vulnerabilities over time while patients recover is required to permit focused monitoring, sophisticated resource allocation, and greatest surgical safety. METHODS: Patients who deceased in-hospital after pancreatoduodenectomy between 2003-2021 were retrieved from the institutional pancreatectomy registry and analyzed in detail with respect to their postoperative course. RESULTS: Among 4474 pancreatoduodenectomies, 156 patients deceased in-hospital (3.5%). When assessing root causes of mortality, we observed 3 different clusters of complications which were postpancreatectomy-specific (47.4%), visceral vasculature-associated (25.6%), or cardiopulmonary in origin (23.7%). The median times of root cause onset in the 3 categories were postoperative day (POD) 9, POD 4.5 (P=0.008) and POD 3 (P<0.001), and medians of in-hospital mortality were POD 31, POD 18 (P=0.009) and POD 8 (P<0.001), respectively. Intervals between root cause onset and mortality varied with medians of 23 days, 11 days (P=0.017), and 1 days (P<0.001). The 3 categories were similarly distributed between different types of surgical complexity. CONCLUSION: Postpancreatectomy-specific complications prompt almost half of in-hospital mortalities after pancreatoduodenectomy, with rather long intervals for interventions to prevent failure to rescue. In contrast, visceral vasculature-related events and cardiopulmonary complications dominate early in-hospital mortalities with short intervals until mortality, demanding rigorous management of such events or preoperative conditioning. These data externally validate a previous high-volume initiative and highlight distinct windows of opportunity to optimize perioperative safety.

Digitizing translucent object appearance by validating computed optical properties.

The optical properties available for an object are most often fragmented and insufficient for photorealistic rendering of the object. We propose a procedure for digitizing a translucent object with sufficient information for predictive rendering of its appearance. Based on object material descriptions, we compute optical properties and validate or adjust this object appearance model based on comparison of simulation with spectrophotometric measurements of the bidirectional scattering-surface reflectance distribution function (BSSRDF). To ease this type of comparison, we provide an efficient simulation tool that computes the BSSRDF for a particular light-view configuration. Even with just a few configurations, the localized lighting in BSSRDF measurements is useful for assessing the appropriateness of computed or otherwise acquired optical properties. To validate an object appearance model in a more common lighting environment, we render the appearance of the obtained digital twin and assess the photorealism of our renderings through pixel-by-pixel comparison with photographs of the physical object.

New dihydrophenanthrenes from Elatostema tenuicaudatum.

Three new dihydrophenanthrenes were isolated from the whole plant of Elatostema tenuicaudatum collected in Vietnam. These compounds were identified as 2,3,5-trihydroxy-9,10-dihydrophenanthrene (1), 2-methoxy-5-hydroxy-9,10-dihydrophenanthrene 3-O-ß-D-glucopyranoside (2), and 2,5-dihydroxy-9,10-dihydrophenanthrene 3-O-ß-D-glucopyranoside (3). Their structures were determined by HR-ESI-MS and 1D, 2D NMR spectroscopy. Furthermore, the inhibitory activities of these compounds against nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells were evaluated. Compound 1 exhibited significant inhibition of NO production, with an IC50 value of 15.8 ± 1.2 µM. This study represents the first report on the chemical compositions and biological activities of E. tenuicaudatum.

Lysine-homologue substitution: Impact on antimicrobial activity and proteolytic stability of cationic stapled heptapeptides.

Numerous natural antimicrobial peptides (AMPs) exhibit a cationic amphipathic helical conformation, wherein cationic amino acids, such as lysine and arginine, play pivotal roles in antimicrobial activity by aiding initial attraction to negatively charged bacterial membranes. Expanding on our previous work, which introduced a de novo design of amphipathic helices within cationic heptapeptides using an 'all-hydrocarbon peptide stapling' approach, we investigated the impact of lysine-homologue substitution on helix formation, antimicrobial activity, hemolytic activity, and proteolytic stability of these novel AMPs. Our results demonstrate that substituting lysine with ornithine enhances both the antimicrobial activity and proteolytic stability of the stapled heptapeptide AMP series, while maintaining low hemolytic activity. This finding underscores lysine-homologue substitution as a valuable strategy for optimizing the therapeutic potential of diverse cationic AMPs.

Norepinephrine and Dobutamine-Induced Dynamic Left Ventricular Outflow Tract Obstruction Caused by Systolic Anterior Motion.

This study presents a case of norepinephrine and dobutamine-induced dynamic left ventricular outflow tract obstruction (LVOTO) caused by systolic anterior motion (SAM) in a patient experiencing acute anterior myocardial infarction (MI). In a 76-year-old patient presenting with acute MI, intensive use of norepinephrine and dobutamine may lead to the development of dynamic LVOTO and SAM. The presence of hypotension and a new cardiac murmur may suggest a mechanical complication such as acute mitral regurgitation (MR) or ventricular septal rupture (VSR). The assessment of the left ventricular outflow tract (LVOT) using echocardiography plays a critical role in the diagnosis of SAM and its associated MR and dynamic LVOTO. The patient's condition was stabilized through the cessation of inotropes and the implementation of aggressive fluid resuscitation, resulting in improved hemodynamics. In conclusion, prompt identification of the underlying pathophysiological mechanisms is imperative for effectively managing this condition and preventing hemodynamic exacerbation.

Fourteen years of cellular deconvolution: methodology, applications, technical evaluation and outstanding challenges.

Single-cell RNA sequencing (scRNA-Seq) is a recent technology that allows for the measurement of the expression of all genes in each individual cell contained in a sample. Information at the single-cell level has been shown to be extremely useful in many areas. However, performing single-cell experiments is expensive. Although cellular deconvolution cannot provide the same comprehensive information as single-cell experiments, it can extract cell-type information from bulk RNA data, and therefore it allows researchers to conduct studies at cell-type resolution from existing bulk datasets. For these reasons, a great effort has been made to develop such methods for cellular deconvolution. The large number of methods available, the requirement of coding skills, inadequate documentation, and lack of performance assessment all make it extremely difficult for life scientists to choose a suitable method for their experiment. This paper aims to fill this gap by providing a comprehensive review of 53 deconvolution methods regarding their methodology, applications, performance, and outstanding challenges. More importantly, the article presents a benchmarking of all these 53 methods using 283 cell types from 30 tissues of 63 individuals. We also provide an R package named DeconBenchmark that allows readers to execute and benchmark the reviewed methods (https://github.com/tinnlab/DeconBenchmark).

Biventricular noncompaction induced heart failure in premature newborn.

Deep intertrabecular recesses and overly pronounced trabeculations in one ventricle are the hallmarks of noncompaction cardiomyopathy (NCCM), a rare congenital cardiomyopathy but very rarely right ventricle (RV), or both ventricles may be involved. We reported a 5-day-old preterm newborn with signs of congestive heart failure that the transthoracic echocardiography (TTE) revealed deep intertrabecular recesses perfused from the left ventricle (LV) and RV cavity, as well as significantly increased wall thickness of the right ventricles and hypertrabeculations in the apical and midventricular segments.

Sleep Disorders in Patients with Severe COVID-19 Treated in the Intensive Care Unit: A Real-Life Descriptive Study in Vietnam.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients with sleep disorders may be at greater risk for respiratory exacerbation or death compared to those without. After being infected with COVID-19, patients have many symptoms related to sleep disorders, especially those with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. This study aimed to evaluate sleep disturbances in patients with severe SARS-CoV-2 infection who were treated in the Intensive Care Unit (ICU). METHODS: This cross-sectional study used the questionnaire provided by the Vietnam Sleep Disorder Study (ViSDiS) research, elaborated by the Vietnam Society of Sleep Medicine (VSSM). Seventy-seven COVID-19 patients were included. RESULTS: There was a significant difference in sleep status before and after SARS-CoV-2 infection among participants. Up to 83% of them reported experiencing insomnia after illness, 60% reported having frequent nightmares, and more than half of participants reported nocturia (p < 0.0001). More than 81.8% of patients with severe SARS-CoV-2 infection were unsatisfied with their sleep quality during hospitalization After SARS-CoV-2 infection, only 2.6% of participants felt they had good quality sleep (p < 0.0001). The majority of patients suffered from fatigue after SARS-CoV-2 infection, including a lack of energy, feeling heaviness in their limbs, aggravation of pre-existing sleep disorders, idleness, constant fatigue throughout the day, and difficulty concentrating. CONCLUSION: Sleep problems are highly prevalence among hospitalized patients with severe COVID-19 in the ICU. Healthcare providers should pay attention to sleep problems and their associated symptoms to initiate appropriate treatment to improve severe COVID-19 patients' health status and minimize the risk of death.

Acute Kidney Injury After Percutaneous Coronary Intervention Guided by Intravascular Ultrasound.

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group (66 participants). The mean ± SD contrast volume of each group was 95.2 ± 37.1 mL and 133.0 ± 36.0 mL for the ultrasound-guided and angiography-guided groups, with P < 0.0001. Intravascular imaging-guided percutaneous coronary intervention (IVUS-guided PCI) was associated with reduced acute kidney injury incidence during hospitalization: 0.0% vs. 12.12% and P = 0.049. Conclusions Intravascular ultrasound is a safe imaging tool that guides percutaneous coronary intervention and significantly reduces the rate of acute kidney injury compared to angiography alone. Patients who have a high chance of experiencing acute kidney injury benefit from using intravascular ultrasound.

Interferons and interferon-related pathways in heart disease.

Interferons (IFNs) and IFN-related pathways play key roles in the defence against microbial infection. However, these processes may also be activated during the pathogenesis of non-infectious diseases, where they may contribute to organ injury, or function in a compensatory manner. In this review, we explore the roles of IFNs and IFN-related pathways in heart disease. We consider the cardiac effects of type I IFNs and IFN-stimulated genes (ISGs); the emerging role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; the seemingly paradoxical effects of the type II IFN, IFN-γ; and the varied actions of the interferon regulatory factor (IRF) family of transcription factors. Recombinant IFNs and small molecule inhibitors of mediators of IFN receptor signaling are already employed in the clinic for the treatment of some autoimmune diseases, infections, and cancers. There has also been renewed interest in IFNs and IFN-related pathways because of their involvement in SARS-CoV-2 infection, and because of the relatively recent emergence of cGAS-STING as a pattern recognition receptor-activated pathway. Whether these advances will ultimately result in improvements in the care of those experiencing heart disease remains to be determined.

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk.

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development. EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard regression was used to test for an association between plasma protein levels and MN risk. RESULTS: We identified 115 proteins associated with MN risk of which 30% (N=34) were also associated with CH. These were enriched for known regulators of the innate and adaptive immune system. Plasma proteomics improved the prediction of MN risk (AUC=0.85, p=5×10-9) beyond clinical factors and CH (AUC=0.80). In an independent group (N=381,485), we used inherited polygenic risk scores (PRS) for plasma protein levels to validate the relevance of these proteins to MN development. PRS analyses suggest that most MN-associated proteins we identified are not directly causally linked to MN risk, but rather represent downstream markers of pathways regulating the progression of CH to MN. CONCLUSIONS: These data highlight the role of immune cell regulation in the progression of CH to MN and the promise of leveraging multi-omic characterization of CH to improve MN risk stratification.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.

Streptomyces tagetis sp. nov., a chromomycin producing bacteria isolated from the roots of Tagetes patula.

A novel halotolerant actinobacterium, designated as RG38T, capable of producing black extracellular melanin pigment on SP2 agar, was isolated from the roots of Tagetes patula. Comparative analysis of the 16S rRNA gene sequence revealed the highest similarity to Streptomyces collinus NBRC 12759T (99.3%). Phylogenetic analysis showed that strain RG38T clustered within the genus Streptomyces forming a monophyletic cluster with its close relatives. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and amino-acid identity (AAI) values between strain RG38T and related species within the genus Streptomyces were below the standard threshold for prokaryotic species delineation. The DNA G + C content of the strain RG38T was determined to be 73.3%. The genome size measured 7,150,598 bp comprising 17 contigs and encompassed 6,053 protein coding genes. AntiSMASH analysis of the whole genome revealed 35 putative biosynthetic gene clusters (BGCs) responsible for various secondary metabolites. Among these clusters, two gene clusters exhibited 100% similarity to the chromomycin A3, albaflavenone, and anthracimycin, respectively. These compounds were reported to possess significant anticancer and antibacterial activities. LC-MS-based analysis, coupled with further isolation studies, confirmed the production of chromomycins A2 (1), A3 (2), and their derivatives, along with their antibiotic activities. These findings underscore the potential of this novel strain as a novel resource for the discovery of diverse antimicrobial compounds. This study is the first to report an antimicrobial compound producing Streptomyces species isolated from medicinal plant T. patula. Based on a polyphasic study, the strain RG38T isolated from an unexplored habitat with a high potential for new natural products represents a novel species within the genus Streptomyces. Accordingly, we propose the name Streptomyces tagetis sp. nov. for this novel species, with the type strain is RG38T (=KCTC 49624T = TBRC 15113T).

Race and ethnicity reporting and representation in hemophilia clinical trials.

ABSTRACT: Racial and ethnic representativeness in clinical trials is crucial to mitigate disparities in outcomes; however, diversity among hemophilia trials is unknown. The aim of this study is to examine the reporting and representation of race and ethnicity in trials of people with hemophilia (PwH). In this cross-sectional study, the ClinicalTrials.gov database was queried in April 2023 for interventional clinical trials involving PwH between 2007 and 2022. The distribution of participants (observed) was compared with expected proportions based on US Hemophilia Treatment Center (HTC) and country-specific census data with observed-to-expected ratios (OERs). Of 129 trials included, 94.6% were industry sponsored, with a mean of 62 participants and mean age of 26.8 years. Overall, 52.0% (n = 66) of trials reported data on race and ethnicity, increasing from 13.9% in 2007-2012 to 22.5% in 2013-2016 to 100% in 2017-2022 (P = .001). Among these 66 trials, 65.8%, 22.8%, 5.1%, 3.9% of participants were White, Asian, Hispanic, and Black, respectively. OERs were 10% to 20% lower for White participants vs US HTC, and US, UK, and Canadian census populations and ∼75% lower for Black or Hispanic participants when compared with US HTC and US census population. OERs for Asian participants were 1.6 to 3 times higher than Canada, US, and UK census populations. The reporting of race and ethnicity in hemophilia trials has drastically improved; however, Black and Hispanic PwH remain especially underrepresented. To address these disparities, stakeholders across the clinical trial enterprise need to implement strategies to ensure equitable participation.

The Safety and Efficacy of Resolving Burr Entrapment by the Ping-Pong and Mother-in-Child Techniques.

Burr entrapment is a serious risk when performing rotational atherectomy on specific anatomical features of lesions such as tortuosity, calcification, and acute angulation. This occurrence, known as the Kokeshi phenomenon in Japanese, is caused by the burr's proximal section being unable to ablate while pulling back the burr, leaving the distal end of the burr covered in diamond crumbs capable of lesion ablation following rotation. There are reports of different approaches used to retrieve an entrapped rotablator burr. In this case, we demonstrate that the ping-pong and mother-in-child techniques, which use separate guide catheters to engage the same coronary artery wiring across the lesion afterward and deep engagement of guide extension catheter manual traction, are highly effective and secure methods for retrieval.

Acceptance and User Experiences of a Wearable Device for the Management of Hospitalized Patients in COVID-19-Designated Wards in Ho Chi Minh City, Vietnam: Action Learning Project.

BACKGROUND: Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors. OBJECTIVE: A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system. METHODS: We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail. RESULTS: In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology. CONCLUSIONS: Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period.

The antimicrobial activity and essential oil constituents of the leaves and trunks of Aquilaria banaensis P.H.Hô (Thymelaeceae) from Vietnam.

The aim of the present paper was to report the chemical constituents and antimicrobial activity of essential hydrodistilled from the leaves and trunk of Aquilaria banaensis P.H.Hô (Thymelaeceae) from Vietnam. The essential oils were analysed comprehensively for their constituents by using Gas chromatography coupled with Mass spectrometry (GC/MS). The antimicrobial activity was determined by agar well diffusion and broth microdilution methods. The leaf essential oil comprised mainly of sesquiterpenes while fatty acids constitutes the bulk of the trunk essential oil. The main constituents of the leaf essential oil were ß-caryophyllene (17.11%), α-selinene (10.99%), α-humulene (8.98%), ß-selinene (8.01%), ß-guaiol (6.69%) and ß-elemene (5.65%). However, hexadecanoic acid (48.46%), oleic acid (19.80%) and tetradecanoic acid (5.32%) were the major compounds identified in the trunk essential oil. The trunk essential oil displayed antimicrobial activity against Staphylococcus aureus, with the minimum inhibitory concentration (MIC) value of about 256.0 µg/mL.

Pancreaticoduodenectomy with superior mesenteric artery first-approach combined total meso-pancreas excision for periampullary malignancies: A high-volume single-center experience with short-term outcomes.

Backgrounds/Aims: Pancreaticoduodenectomy (PD) is the only radical treatment for periampullary malignancies. Superior mesenteric artery (SMA) first approach combined with total meso-pancreas (MP) excision was conducted to improve the oncological results. There has not been any previous research of a technique that combines the SMA first approach and total MP excision with a detailed description of the MP macroscopical shape. Methods: We prospectively assessed 77 patients with periampullary malignancies between October 2020 and March 2022 (18 months). All patients had undergone PD with SMA first approach combined total MP excision. The perioperative indications, clinical data, intra-operative index, R0 resection rate of postoperative pathological specimens (especially mesopancreatic margin), postoperative complications, and follow-up results were evaluated. Results: The median operative time was 289.6 min (178-540 min), the median intraoperative blood loss was 209 mL (30-1,600 mL). Microscopically, there were 19 (24.7%) cases with metastatic MP, and five cases (6.5%) with R1-resection of the MP. The number of lymph nodes (LNs) harvested and metastatic LNs were 27.2 (maximum was 74) and 1.8 (maximum was 16), respectively. Some (46.8%) patients had pancreatic fistula, but mostly in grade A, with 7 patients (9.1%) who required re-operations. Some 18.2% of cases developed postoperative refractory diarrhea. The rate of in-hospital mortality was 1.3%. Conclusions: The PD with SMA first approach combined TMpE for periampullary malignancies was effective in achieving superior oncological statistics (rate of MP R0-resection and number of total resected LNs) with non-inferior short-term outcomes. It is necessary to evaluate survival outcomes with long-term follow-up.

Heart Rate Variability Measured from Wearable Devices as a Marker of Disease Severity in Tetanus.

Tetanus is a disease associated with significant morbidity and mortality. Heart rate variability (HRV) is an objective clinical marker with potential value in tetanus. This study aimed to investigate the use of wearable devices to collect HRV data and the relationship between HRV and tetanus severity. Data were collected from 110 patients admitted to the intensive care unit in a tertiary hospital in Vietnam. HRV indices were calculated from 5-minute segments of 24-hour electrocardiogram recordings collected using wearable devices. HRV was found to be inversely related to disease severity. The standard deviation of NN intervals and interquartile range of RR intervals (IRRR) were significantly associated with the presence of muscle spasms; low frequency (LF) and high frequency (HF) indices were significantly associated with severe respiratory compromise; and the standard deviation of differences between adjacent NN intervals, root mean square of successive differences between normal heartbeats, LF to HF ratio, total frequency power, and IRRR, were significantly associated with autonomic nervous system dysfunction. The findings support the potential value of HRV as a marker for tetanus severity, identifying specific indices associated with clinical severity thresholds. Data were recorded using wearable devices, demonstrating this approach in resource-limited settings where most tetanus occurs.