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Competing Interests: Disclosure: The authors have no conflicts of interest to report.

The Impella 5.5 ® (Abiomed, Danvers, MA, USA) is a microaxial flow pump that promotes left ventricular unloading and improves end-organ perfusion before durable left ventricular assist device (LVAD) implantation. Thrombus formation after Impella 5.5 insertion can occur and represents a significant challenge to device explantation. Durable LVAD implantation is typically performed without aortic cross-clamping, so a dislodged thrombus can potentially embolize and lead to catastrophic events. We describe our technique to safely explant an Impella 5.5 in patients who develop a thrombus on the inflow portion of the device before surgical LVAD implantation., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: IAS is a consultant for Abiomed, Inc. (Danvers, MA, USA).

Aims: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed., Methods and Results: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality., Conclusion: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Extracorporeal life support with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to assist circulation in patients with severe cardiogenic shock or cardiac arrest. The vasoactive-inotropic score (VIS) is a standardized calculation of vasoactive medication support which uses coefficients for each medication that converts them to an equivalent value. The purpose of this study was to assess the VIS as an early prognostication tool for survival to decannulation patients on adult VA-ECMO support. This was a single-center, observational cohort study of adult patients who received VA-ECMO support compared based on their survival to decannulation. The primary endpoint was the VIS at hour 24 postcannulation. Among the 265 patients included in this study, 140 patients (52.8%) survived to decannulation of VA-ECMO. At 24 hours postcannulation, a lower VIS was observed in the group that survived decannulation (6.5 ± 7.5 vs. 12.3 ± 16.9; p < 0.001). Multivariate analysis performed also demonstrates an association between 24-hour VIS and survival to decannulation (odds ratio 0.95; 95% confidence interval, 0.91-0.95). This study suggests that the 24-hour VIS may be an early prognostic indicator in patients on VA-ECMO patients. http://links.lww.com/ASAIO/B39., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Introduction: Advanced age is a known risk factor for poor outcomes after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac support. The use of ECMO support in patients over the age of 80 is controversial, and sometimes its use is contraindicated. We aimed to assess the use of ECMO in octogenarian patients to determine survival and complication rates., Methods: A single-center, retrospective analysis was completed at a large, urban academic medical center. Patients requiring V-A ECMO support between December of 2012 and November of 2019 were included as long as the patient was at least 80 years of age at the time of cannulation. Post cardiotomy shock patients were excluded., Results: A total of 46 patients met eligibility criteria; all received V-A ECMO support. Overall, the majority of patients (71.7%; 33/46) survived to decannulation, and 43.5% (20/46) survived to discharge. Patients who were previously rescued from percutaneous interventions tend to have a better survival than other patients ( p = .06). The most common complications were renal and hemorrhagic., Conclusions: We demonstrated that advanced age alone should not disqualify patients from cannulating and supporting with V-A ECMO.

Frailty and malnutrition in patients with heart failure are barriers to durable left ventricular assist device (D-LVAD) support and heart transplantation. Moreover, cachexia in patients with advanced heart failure carries a high mortality risk. There are no guidelines for these patients other than increased caloric intake and rehabilitation. Patients suffering from cardiac cachexia and heart failure may benefit from temporary, percutaneous assist device support to improve the underlying heart disease and reverse the catabolic state. We retrospectively reviewed patients from January 2017 to January 2022. All patients who received Impella support (5.0 or 5.5, Abiomed) before D-LVAD implantation were screened. Those who met the criteria for cardiac cachexia were included. Patient demographics, nutritional and biochemical markers, and survival data were collected. A total of 14 patients were included. The majority of patients were male (85.7%) with ischemic cardiomyopathy (64.3%). Caloric intake, physical strength, and ambulation improved. Prealbumin levels improved from a median of 13.7-18.0 mg/dl ( p < 0.006) while on Impella 5.0 or 5.5 support. All patients survived to discharge and the 6 month follow-up. In conclusion, use of the Impella device improves cardiogenic shock symptoms and, consequently, may improve cachexia status prior to D-LVAD implantation., (Copyright © ASAIO 2023.)

Competing Interests: Disclosure: The authors have no conflicts of interest to disclose.

In the early 1960s, heat shock proteins (HSPs) were first identified as vital intracellular proteinaceous components that help in stress physiology and reprogram the cellular responses to enable the organism's survival. By the early 1990s, HSPs were detected in extracellular spaces and found to activate gamma-delta T-lymphocytes. Subsequent investigations identified their association with varied disease conditions, including autoimmune disorders, diabetes, cancer, hepatic, pancreatic, and renal disorders, and cachexia. In cardiology, extracellular HSPs play a definite, but still unclear, role in atherosclerosis, acute coronary syndromes, and heart failure. The possibility of HSP-targeted novel molecular therapeutics has generated much interest and hope in recent years. In this review, we discuss the role of Extracellular Heat Shock Proteins (Ec-HSPs) in various disease states, with a particular focus on cardiovascular diseases.

Background: Viral disease is a well-known cause of a significant impact on economic losses and threatens developed and developing societies. High mutation rates and the lack of ability of conventional formulations to target specific cells pose substantial hurdles to the successful treatment of viral diseases.

Methods: We conducted a preliminary search by a standard procedure. With hand searching, we conducted an advanced search across several electronic databases. After defining the selection criteria, two writers independently reviewed and evaluated the first 500 abstracts before screening the remaining 300. Since there was 97% agreement on the screening decisions, only one reviewer conducted the screening. The pre-planned data extraction process was accomplished, and the thoroughness of the description of participation techniques was assessed. Additional data extraction was carried out for articles with the most detailed illustrations. Four stakeholder representatives co-authored this systematic review.

Results: Incorporating selective carbohydrate polymers into the antiviral pharmaceutical compositions could help to manage biological complications associated with viral infections. We included 172 papers in which authors were involved in a systematic review. The present review explains the role of carbohydrate polymers (chitosan, carrageenan, alginate, cyclodextrin, dextran, and heparin) in the prevention and treatment of viral infections in terms of their source, molecular weight, surface charge, chemical composition, and structure. Additionally, the review describes the primary mechanism of drug delivery performance of carbohydrate polymers to improve the antiviral properties and pharmacokinetic behaviour of lamivudine, zidovudine, acyclovir, etc.

Conclusion: The article discussed the role of carbohydrate polymers in mitigating virus-induced associated complications like bacterial infection, cardiovascular disorder, oxidative stress, and metabolic disorder. As a result, this work will provide valuable information to scientists, researchers, and clinicians for suitable carbohydrate polymer-based pharmaceutical development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR)., Methods: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk., Results: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF had the shortest hospital stays and lowest costs. Compared with patients with diastolic HF, the risk of acute myocardial infarction (TAVR odds ratio [OR], 1.95; 95% CI, 1.20-3.19; P = .008; SAVR OR, 1.38; 95% CI, 0.98-1.95; P = .067) and cardiogenic shock (TAVR OR, 2.15; 95% CI, 1.43-3.23; P < .001; SAVR OR, 1.89; 95% CI, 1.42-2.53; P ≤ .001) was higher in patients with systolic HF, whereas the risk of permanent pacemaker implantation (TAVR OR, 0.58; 95% CI, 0.45-0.76; P < .001; SAVR OR, 0.58; 95% CI, 0.40-0.84; P = .004) was lower following aortic valve procedures. In TAVR, the risk of acute deep vein thrombosis and kidney injury was higher, although not statistically significant, in patients with systolic HF than in those with diastolic HF., Conclusion: These outcomes suggest that chronic HF types do not incur statistically significant hospital mortality risk in patients undergoing TAVR or SAVR., (© 2023 by the Texas Heart® Institute, Houston.)

Background: Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk., Methods: We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021. Patients were divided into delayed sternal closure (DSC) and primary sternal closure (PSC) groups. We used chi-squared or Fisher Exact tests, as appropriate, to compare the incidence of postoperative LVAD-related infections (mediastinal/sternal wound) and LVAD-specific infections (driveline and pump pocket) after definitive chest closure between these two groups., Results: A total of 327 patients met eligibility criteria, including 127 (39%) patients that underwent DSC and 200 (61%) patients that had a PSC. Demographic and clinical characteristics were similar except for an overrepresentation of men (87% vs. 75%, p = .016), Interagency Registry of Mechanically Assisted Circulatory Support class I-II patients (89% vs 66%, p < .001), patients with a previous sternotomy (43% vs 13%, p < .001), and patients with chronic kidney disease (55% vs 43%, p = .030) in the DSC group. The median DSC time was 24 (IQR: 24-48) hours. The incidence of LVAD-related mediastinal/sternal wound infection was similar between the DSC and PSC groups (4.7% vs 3.0%, p = .419). There was no difference between DSC and PSC groups in the incidence of driveline infection (6.3% vs 9%, p = .411) and pump pocket infection (1.6% vs 1.5%, p =.901), respectively., Conclusions: DSC does not seem to increase the incidence of LVAD-related or LVAD-specific infection rates in heart failure patients undergoing device implantation surgery., Competing Interests: Disclosure statement The authors report no conflict of interest., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Malaria is a life-threatening parasitic disease transmitted by the infected female Anopheles mosquito. The development of drug tolerance and challenges related to the drugs' pharmacodynamic and pharmacokinetic parameters limits the antimalarial therapeutics response. Currently, nanotechnology-based drug delivery system provides an integrative platform for antimalarial therapy by improving the drug physicochemical properties, combating multidrug resistance, and lowering antimalarial drug-related toxicity. In addition, surface engineered nanocarrier systems offer a variety of alternatives for site-specific/targeted delivery of antimalarial therapeutics, anticipating better clinical outcomes at low drug concentrations and low toxicity profiles, as well as reducing the likelihood of the emergence of drug resistance. So, constructing nano carrier-based approaches for drug delivery has been considered the foremost strategy to combat malaria. This review focuses on the numerous nanotherapeutic strategies utilised to treat malaria as well as the benefits of nanotechnology as a potentially effective therapeutic.

Triple-negative breast cancer (TNBC) is an extremely vicious subtype of human breast cancer having the worst prognosis along with strong invasive and metastatic competency. Hence, it can easily invade into blood vessels, and presently, no targeted therapeutic approach is available to annihilate this type of cancer. Metal complexes have successfully stepped into the anticancer research and are now being applauded due to their anticancer potency after the discovery of cisplatin. Many of these metal complexes are also well recognized for their activity toward breast cancer. As the TNBC is a very dangerous subtype and has long been a challenging ailment to treat, we have intended to develop a few brand new mixed metallic Ru(II)/Ir(III)/Re(I)-2,2'-bipyrimidine complexes [ L'Re2 ], [ L'RuRe ], and [ L'IrRe ] to abate the unbridled proliferation of TNBC cells. The potency of the complexes against TNBC cells has been justified using MDA-MB-468 TNBC cell lines where complex [ L'IrRe ] has displayed significant potency among all the three complexes with an IC 50 value of 24.12 μM. The complex [ L'IrRe ] has been competent to cause apoptosis of TNBC cells through inhibition of the G2/M phase in the cell cycle in association with a profuse amount of ROS generation and mitochondrial depolarization., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Mitochondria are critical organelles that form networks within our cells, generate energy dynamically, contribute to diverse cell and organ function, and produce a variety of critical signaling molecules, such as cortisol. This intracellular microbiome can differ between cells, tissues, and organs. Mitochondria can change with disease, age, and in response to the environment. Single nucleotide variants in the circular genomes of human mitochondrial DNA are associated with many different life-threatening diseases. Mitochondrial DNA base editing tools have established novel disease models and represent a new possibility toward personalized gene therapies for the treatment of mtDNA-based disorders.

This study shows the morphological identification of anaerobic fungal strains isolated from fecal samples of goats inhabiting Turkey and the effects of various metal ions and chemicals on extracellular xylanase production. Three different anaerobic gut fungi isolated from wild goats in Turkey were identified as Neocallimastix spp. xylanase, cellulase, and lichenase production were tested in culture supernatants, and the maximum-specific activities were found as 560.42 ± 9.39, 159.70 ± 3.88, and 157.36 ± 3.83 (μmol/min/mg protein), respectively. While the optimum temperature range of exo-xylanases was found as 40-50°C, their optimum pH range was determined as 6.0-6.5. Xylanase activity decreased in metal ions and other chemical reactants based on dose. The metal ion that significantly inhibited xylanase activity was Fe +3 . It was found that the ferric ions inhibited xylanase activity in all three anaerobic gut fungi by 30%-90% depending on molarity. On the contrary, the 1 mM concentrations of the Mn +2 , Ba +2 , Co +2 , Cu +2 , Sn +2 , and Mg +2 metal ions and the ethylenediaminetetraacetic acid and β-mercaptoethanol reagents had a positive effect at rates in the range of 3%-92%. In conclusion, these findings demonstrate that anaerobic gut fungus has very stable fibrolytic enzymes that need to be separated, as well and the existence of a unique resource for industrial applications., (© 2022 Wiley-VCH GmbH.)

Background: We aimed to explore the prevalence of prolonged symptoms, pulmonary impairments and residual disease on chest tomography (CT) in COVID-19 patients at 6 months after acute illness. Methods: In this prospective, single-center study, hospitalized patients with radiologically and laboratory-confirmed COVID-19 were included. Results: A high proportion of the 116 patients reported persistent symptoms (n = 54; 46.6%). On follow-up CT, 33 patients (28.4%) demonstrated residual disease. Multivariate analyses revealed that only neutrophil-to-lymphocyte ratio was an independent predictor for residual disease. Conclusion: Hospitalized patients with mild/moderate COVID-19 still had persistent symptoms and were prone to develop long-term pulmonary sequelae on chest CT. However, it did not have a significant effect on long-term pulmonary functions.

Amid the rise of multi-drug resistance among bacterial pathogens, the drying of the development pipeline of new antibiotics is worrisome. In search of new effective alternatives, phytocompounds can be considered a good one because of their immense antimicrobial property, low toxicity and huge structural diversity. In the present study, 200 phytocompounds were targeted against two Metallo β-lactamase (MBL) enzymes (NDM-1 and VIM-1) through molecular docking and meropenem was used as a reference drug. The phytocompounds with docking score ≤-8.0 kcal/mol were screened for their pharmacokinetic properties. The three best selected phytocompounds are Coriandrinonediol, Oleanderolide and Uzarigenin. Molecular docking helps to understand binding affinity. The selected phytocompounds showed better result than meropenem. Molecular interaction study reveals their competitive mechanism of inhibition against the target proteins. Coriandrinonediol has docking score -8.3 kcal/mol (NDM-1) and -8.9 kcal/mol (VIM-1), and oleanderolide has docking score -8.2 kcal/mol (NDM-1) and -9.3 kcal/mol (VIM-1). Uzarigenin has the highest binding affinity (-10.4 kcal/mol) among the three against VIM-1 and the lowest binding affinity (-8.1 kcal/mol) against NDM-1. Molecular dynamic (MD) simulation study also supports the stability and flexibility of the above phytocompounds during the MD run. Among the abovementioned three phytocompounds, oleanderolide has given the best result against both target proteins. These phytocompounds are first time reported as MBL inhibitors and their promising in silico results encourage to promote them for further investigation for in vitro and in vivo clinical trials.Communicated by Ramaswamy H. Sarma.

Due to a number of unpleasant considerations, marketed drugs have steadily lost their importance in the treatment of cancer. In order to find a viable cancer cell diagnostic agent, we therefore focused on metal complexes that displayed target adequacy, permeability to cancer cells, high standard water solubility, cytoselectivity, and luminescent behavior. In this aspect, luminescent 11-{naphthalen-1-yl} dipyrido [3,2-a:2',3'-c] phenazine based Ru(II)/Ir(III)/Re(I) complexes have been prepared for HCT-116 colorectal cancer stem cell therapy. Our study successfully established the possible cytotoxicity of IrL complex at different doses on HCT-116 colorectal cancer stem cells (CRCSCs). Additionally, an immunochemistry analysis of the complex IrL showed that the molecule was subcellularly localized in the nucleus and other regions of the cytoplasm, where it caused nuclear DNA damage and mitochondrial dysfunction. The level of BAX and Bcl-2 was further quantified by qRT-PCR. The expression of proapoptotic BAX showed increased expression in the complex IrL -treated cell compared to the control, indicating the potential of complex IrL for apoptotic induction. Upon further validation, complex IrL was developed as an inhibitor of autophagy for the eradication of cancer stem cells.

In patients undergoing aortic valve surgery, preoperative reduced left ventricular ejection fraction is not uncommon and is associated with poor outcomes. Mechanical circulatory support (MCS) may be preemptively used in patients presenting with high periprocedural risk. The Impella 5.5 is a percutaneous left ventricular assist device that has been increasingly used in various cardiac surgeries. In this article, we present a step-by-step guide, safeguards, and pitfalls on how to replace the aortic valve and preserve this transaortic MCS device for postoperative support in patients with concomitant aortic valve pathology and left ventricular dysfunction., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: Carcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement surgery appears to decrease all-cause mortality in patients with advanced CnHD, few studies have investigated the outcomes of patients after valve replacement., Methods: We conducted a multi-institution retrospective registry of patients who received both tricuspid and pulmonic bioprosthetic valve (TV/PV) replacements for advanced CnHD from November 2005 to March 2021. Patients were followed post-operatively with echocardiographic studies every 3 months. Carcinoid valvular heart disease scores were used to monitor valve degeneration. Neuroendocrine tumor treatment, their administration times, and associations with echocardiographic findings were recorded., Results: Of 87 patients with CnHD, 22 patients underwent simultaneous surgical TV and PV replacement. In 6 patients (27.3%), increased PV V max was the first echocardiographic manifestation of valve degeneration in the setting of occult neurohormonal release. Post-operative telotristat ethyl and peptide receptor radionuclide therapy appeared to stabilize PV V max . The PV V max showed consistent elevation in the entire patient population when compared to baseline, while bioprosthetic TV echocardiographic parameters were relatively unchanged throughout. Post-operative warfarin therapy did not affect the rate of PV degeneration, and no major bleeding was recorded during or after post-operative anticoagulation therapy., Conclusion: Bioprosthetic valve degeneration is common in CnHD. Monitoring with echocardiographic studies every 3 months, focusing on PV velocities, could identify patients with occult disease that very likely promotes valve degeneration. Novel neuroendocrine tumor therapies may have a beneficial impact on valve degeneration., Competing Interests: SH consulting for TerSera and research funding from TerSera. DH consulting for TerSera, ITM, AAA/Novartis, Ipsen, Camurus, Amryt, Crinetics, and Alphamedix and research funding from ITM, AAA/Novartis, Tarveda, Thermo Fisher Scientific, and Genentech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Honan, Hassan, Deswal, Herrmann, Song, Monlezun, Halperin, Mahvash, Dasari, Koutroumpakis, Akay, Balanescu, de Armas, Patel, Nathan, Kar, Marmagkiolis, Lopez-Mattei, Patel, Gregoric, Yao and Iliescu.)

Skin cancer, including basal cell carcinoma, melanoma, and squamous cell carcinoma, is conventionally treated by surgery, phototherapy, immunotherapy, and chemotherapy. For decades, surgical removal of malignant cancers has favored patients' therapeutic options. However, multiple aspects, such as the patient's comorbidities, the anatomical location of the lesion, and possible resistance to recurrent excisions, can influence the decision to conduct surgery. Therefore, topical and transdermal therapy may be a more appropriate option, allowing for higher therapeutic levels at the site of action and reducing toxicity than systemic therapy. The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, physicochemical drug characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In recent years, unquestionable signs of progress have been demonstrated to circumvent these challenges. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review specifically addresses the progress in transdermal delivery systems for melanoma and nonmelanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Use of prolonged femoral intra-aortic balloon pump support limits the mobility of patients awaiting heart transplant. We assessed the safety and outcomes of a structured, tilting physical therapy protocol in patients supported by intra-aortic balloon pumps while awaiting transplant., Methods: We retrospectively reviewed five years of transplant patients. Eighteen patients received femoral intra-aortic balloon support, a heart transplant, and met all eligibility criteria. We compared complications and outcomes between patients who received the structured, tilting physical therapy (Protocol Group) and those that received standard of care (Control Group)., Results: Complications were not significantly different between groups. The majority of the Protocol Group were discharged to home (10/12), while half (3/6) of the Control Group were discharged to a rehabilitation facility. Post-transplant length of stay was significantly less in the Protocol Group (median 16 vs. 28 days, p = 0.03)., Conclusion: Despite the small number analyzed, the data indicates that the structured, tilting physical therapy protocol led to a significantly reduced length of stay post-transplantation. Importantly, use of the protocol did not result in access site complications, thrombosis, or arrhythmias in the majority of the patients., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Oral mucositis is a serious issue in patients receiving oncological therapies. Mucosal protectants considered to be one of the preferred choices used in the management of mucositis. However, the protective efficacy of currently available mucosal protectants has been significantly compromised due to poor retention, lack of lubrication, poor biodegradability, and inability to manage secondary complications. Chitosan is a promising material for mucosal applications due to its beneficial biomedical properties. Chitosan is also anti-inflammatory, anti-microbial, and capable of scavenging free radicals, makes it a good candidate for the treatment of oral mucositis. Additionally, chitosan's amino polysaccharide skeleton permits a number of chemical alterations with better bioactive performance. This article provides a summary of key biological properties of chitosan and its derivatives that are useful for treating oral mucositis. Current literature evidence shows that Chitosan has superior mucosal protective properties when utilised alone or as delivery systems for co-encapsulated drugs.

Breast cancer (BC) is the deadliest malignant disorder globally, with a significant mortality rate. The development of tolerance throughout cancer treatment and non-specific targeting limits the drug's response. Currently, nano therapy provides an interdisciplinary area for imaging, diagnosis, and targeted drug delivery for BC. Several overexpressed biomarkers, proteins, and receptors are identified in BC, which can be potentially targeted by using nanomaterial for drug/gene/immune/photo-responsive therapy and bio-imaging. In recent applications, magnetic iron oxide nanoparticles (IONs) have shown tremendous attention to the researcher because they combine selective drug delivery and imaging functionalities. IONs can be efficaciously functionalised for potential application in BC therapy and diagnosis. In this review, we explored the current application of IONs in chemotherapeutics delivery, gene delivery, immunotherapy, photo-responsive therapy, and bio-imaging for BC based on their molecular mechanism. In addition, we also highlighted the effect of IONs' size, shape, dimension, and functionalization on BC targeting and imaging. To better comprehend the functionalization potential of IONs, this paper provides an outline of BC cellular development. IONs for BC theranostic are also reviewed based on their clinical significance and future aspects.Graphical Abstract[Formula: see text].

Patients with severe refractory hypoxemic respiratory failure may benefit from extracorporeal membrane oxygenation (ECMO) for salvage therapy. The Coronavirus disease 2019 (COVID-19) pandemic offered three high-volume independent ECMO programs at a large medical center the chance to collaborate to optimize ECMO care at the beginning of the pandemic in Spring 2020. Between March 15, 2020, and May 30, 2020, 3,615 inpatients with COVID-19 were treated at the Texas Medical Center. During this time, 35 COVID-19 patients were cannulated for ECMO, all but one in a veno-venous configuration. At hospital discharge, 23 (66%) of the 35 patients were alive. Twelve patients died of vasodilatory shock (n = 9), intracranial hemorrhage (n = 2), and cannulation-related bleeding and multiorgan dysfunction (n = 1). The average duration of ECMO was 13.6 days in survivors and 25.0 days in nonsurvivors ( p < 0.04). At 1 year follow-up, all 23 discharged patients were still alive, making the 1 year survival rate 66% (23/35). At 2 years follow-up, the overall rate of survival was 63% (22/35). Of those patients who survived 2 years, all were at home and alive and well at follow-up., Competing Interests: Disclosure: B.A. reports funding from ALung Technologies, CytoDyn, and CSL Behring as Primary Investigator. F.M. serves as a consultant for Portola Pharmaceuticals. S.C. has served on advisory boards for Edwards Lifesciences, Baxter Pharmaceuticals, and LaJolla Pharmaceuticals. The remaining authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial resistance to currently available antimicrobials. Metal nanoparticles represent a new perspective in treating AMR due to their unique mechanisms, such as disrupting bacterial cell membrane potential and integrity, biofilm inhibition, reactive oxygen species (ROS) formation, enhancing host immune responses, and inhibiting RNA and protein synthesis by inducing intracellular processes. Metal nanoparticles (MNPs) properties such as size, shape, surface functionalization, surface charges, and co-encapsulated drug delivery capability all play a role in determining their potential against multidrug-resistant bacterial infections. Silver, gold, zinc oxide, selenium, copper, cobalt, and iron oxide nanoparticles have recently been studied extensively against multidrug-resistant bacterial infections. This review aims to provide insight into the size, shape, surface properties, and co-encapsulation of various MNPs in managing multidrug-resistant bacterial infections., Competing Interests: Declaration of Competing Interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. All the authors involved in this paper entitled “Metal Nanoparticles Against Multi Drug Resistance Bacteria” declared no conflict of interest, (Copyright © 2022. Published by Elsevier Inc.)

The Impella CP (Abiomed Inc., Danvers, MA) is widely used in cardiac catheterization laboratories for patients presenting with cardiogenic shock, but it is also known to cause significant hemolysis. The risk of hemolysis can be reduced by properly positioning the device, ensuring an adequate volume status, and using full anticoagulation strategies; however, in some cases hemolysis persists. We present a case series of eight patients that were diagnosed with cardiogenic shock, underwent Impella CP placement, and then suffered from refractory hemolysis which was treated by upgrading the Impella device to the 5.0 or 5.5 version. Fifty percent (4/8) of the patients in this series were already receiving continuous renal replacement therapy, and the levels of plasma free hemoglobin (pFHb) and lactate dehydrogenase continued to increase after the implantation of the Impella CP. The median time between Impella CP placement and the diagnosis of refractory hemolysis was 16.5 hours (interquartile range [IQR], 8.0-26.0). The median time between the diagnosis of hemolysis to Impella upgrade was 6.0 hours (IQR, 4.0-7.0). A total of 87.5% (7/8) of patients experienced a drop in pFHb to below 40 mg/dl at 72 hours post-Impella upgrade, and they were discharged without any further need of dialysis. One patient expired due to irreversible multiple organ failure. We propose that early identification of hemolysis by close monitoring of pFHb and upgrading to the Impella 5.5 reduces hemolysis, prevents further kidney damage, and significantly improves clinical outcomes., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Previously, we used the gene-breaking transposon to create 1200 transgenic zebrafish strains tagging protein-coding genes (Ichino et al., 2020), including the lrpprc locus. Here, we present and characterize a new genetic revertible animal model that recapitulates components of Leigh Syndrome French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the LRPPRC gene, involved in mitochondrial mRNA polyadenylation and translation. lrpprc zebrafish homozygous mutants displayed biochemical and mitochondrial phenotypes similar to clinical manifestations observed in patients, including dysfunction in lipid homeostasis. We were able to rescue these phenotypes in the disease model using a liver-specific genetic model therapy, functionally demonstrating a previously under-recognized critical role for the liver in the pathophysiology of this disease., Competing Interests: AS, MW, RC, MS, JA, SH, BK, AT, NI, WL, JY, YD, YD, JL, WL, PL, DO, SF, KC, XX, SE No competing interests declared, (© 2022, Sabharwal, Wishman, Cervera et al.)

There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation., Methodology and Study Design: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were grouped according to the presence of AMI and compared., Results: We identified 47 patients with truncated outcomes after the first OHT. The median age was 59 years, 36 patients (76%) were male, 25 patients (53%) had a prior history of cardiac operation, and 21 patients (45%) were supported with a durable assist device before OHT. Of those, AMI was identified in 22 (47%) patients (AMI group), and 25 patients had no AMI (non-AMI group). Groups were comparable in baseline and perioperative data. Histopathological observations in AMI group included a non-significant higher incidence of antibody-mediated rejection Grade 1 or higher (pAMR ≥ 1) (32% vs. 12%, P = 0.154), and non-significant lower incidence of severe acute cellular rejection (ACR ≥ 2R) (32% vs. 40%, P = 0.762). Clinical observations in the AMI group found a significantly higher occurrence of severe primary graft dysfunction (68% vs. 20%, P = 0.001) and a highly significant shorter duration from transplantation to death or re-transplantation (42 days [IQR 26, 120] vs. 1,133 days [711-1,664], P < 0.0001). Those patients had a significantly higher occurrence of cardiac-related deaths (64% vs. 24%, P = 0.020). No difference was observed in other outcomes., Conclusion: In heart transplant recipients with a truncated postoperative course leading to either death or re-transplantation, AMI in endomyocardial biopsies was a common pathological phenomenon, which correlated with the clinical occurrence of severe primary graft dysfunction. Those patients had significantly shorter survival times and higher cardiac-related deaths. The presence of AMI suggests a truncated course after OHT., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 McDonald, Mihalj, Zhao, Nathan, Matejin, Ottaviani, Jezovnik, Radovancevic, Kar, Gregoric and Buja.)

We have developed a one pot three component synthetic protocol for half-sandwich Ru(II)- p -cymene dipyrido[3,2- a :2',3'- c ]phenazine analogues for selective cancer therapy under light irradiation. On average, the cytotoxicity of all the complexes is indeed doubled upon light irradiation and also exhibited significant photo and dark selectivity against cancer cells with respect to normal cells. Out of five Ru(II) complexes (RuL1-RuL5), [(η 6 - p -cymene)Ru II Cl(K 2 - N , N -11-nitrodipyrido[3,2- a :2',3'- c ]phenazine]PF 6 (RuL4) exhibited the best phototoxicity (lowest IC 50 under light irradiation). Intracellular ROS generation was studied by the 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. Moreover, these complexes exhibited a strong serum albumin and DNA binding capacity. These complexes also exhibited good stability in 10% DMSO-buffer and under 1 mM GSH conditions. Overall, the remarkable photocytotoxic efficacy of new Ru(II)- p -cymene dipyrido[3,2- a :2',3'- c ]phenazine analogues (RuL1-RuL5) makes them potential photochemotherapeutics as an alternative of current PDT agents.

The transcatheter aortic valve replacement procedure is used in patients with aortic stenosis. Transcatheter aortic valve replacement devices are quite versatile; thus, they are increasingly being used for nonaortic applications, such as tricuspid valve-in-valve implantation. This case series describes a transcatheter aortic valve replacement procedure in 4 patients with anatomic challenges (eg, aortic tortuosity, high valvular calcium burden, highly calcified bicuspid valve, low coronary artery takeoff, left main coronary artery occlusion, and large aortic annulus) and a fifth patient who had a failed tricuspid bioprosthesis and underwent a tricuspid valve-in-valve implantation with the Edwards SAPIEN 3 transcatheter heart valve (Edwards Lifesciences). All procedures required adjustments to the standard protocol, and each procedure was successful. The critical, technical adjustments in the deployment technique and preprocedural planning of the procedures are detailed to provide a road map for other cardiologists who encounter similar challenges., (© 2022 by the Texas Heart® Institute, Houston.)

Molineria recurvata (MR) has been traditionally used to manage diabetes mellitus in India. However, the molecular mechanism of MR on the diabetic-induced nephropathy has not been clearly investigated. Thus, this study investigates the protective effects of the MR extract on nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was instigated by a single intraperitoneal injection of STZ (45 mg/kg) in male Sprague-Dawley rats. Once the diabetes was successfully induced, the MR extract (200 mg/kg/day) or metformin (200 mg/kg/day) was orally administered for 14 days. Renal function, morphology changes and levels of inflammatory cytokines were measured. Blood glucose concentrations were considerably reduced in STZ-induced diabetic rats following treatment with the MR extract. The administration of the MR extract substantially restored the abnormal quantity of the oxidative DNA damage marker 8-hydroxy-2'-deoxy-guanosine (8-OHdG), malondialdehyde, glutathione, oxidized glutathione, superoxide dismutase, catalase, interleukin (IL)-1β, IL-6, IL-10, and transforming growth factor-β (TGF-β). The urinary excretion of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), selenium binding protein 1 (SBP1), and pyruvate kinase M2 (PKM2) was significantly reduced in diabetes rats after administration of the MR extracts. In the kidneys of STZ-induced diabetic rats, the MR extracts markedly downregulated the expression of fibronectin, collagen-1, and α-smooth muscle actin (α-SMA). In particular, the MR extracts markedly increased the level of SIRT1 and SIRT3 and reduced claudin-1 in the kidney. These results suggest that the MR extracts exhibits therapeutic activity in contrast to renal injury in STZ-induced diabetic rats through repressing inflammation and oxidative stress.

In the present study, the extracted volatiles from dried leaf and fruit of Piper longum were analysed by gas chromatography-mass spectrometry (GC-MS) and each detected 53 constituents having 92.41% and 96.31% of the total volatiles respectively. E -nerolidol (19.56%), β -pinene (17.07%) and α -pinene (6.8%) were main constituents in leaf volatiles whereas the fruit volatiles dominated by germacrene-D (23.38%), 8-heptadecene (8.95%) and β -caryophyllene (8.20%). Antioxidant potential of the volatiles were assessed by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assays. The fruit volatiles revealed higher radical scavenging activities as compared to leaf. The samples were also evaluated against multidrug resistant (MDR) isolates including one non MDR fungal strain. The fruit volatiles showed a very strong activity against Acinetobacter baumannii than others whereas leaf volatiles possessed strong activity against Klebsiella pneumoniae as compared to other strains. Thus, the dried fruits can be exploited for drug development towards therapeutic purpose.

After demonstrated myocardial recovery in patients with durable left ventricular assist device (LVAD) support, the device may occasionally be explanted. A 38-year-old female with nonischemic cardiomyopathy underwent implantation of an LVAD as a bridge-to-transplant therapy. After one year, the patient demonstrated sufficient myocardial recovery allowing the LVAD to be explanted. A Teflon felt strip plug was created and placed within the apical sewing ring to occlude the opening into the left ventricle. Eleven years later, the patient presented with recurrence of severe heart failure. Due to morbid obesity, the patient was not a heart transplant candidate. Therefore, a second LVAD was implanted with a concomitant gastric sleeve procedure. When the plug was surgically removed from the sewing ring, no thrombus was observed; however, the ventricular surface was completely endothelialized. The patient recovered without any complications, was discharged from the hospital, and is currently listed for a heart transplant. This case demonstrates remission from heart failure lasting for more than a decade. If a second LVAD is needed due to exacerbation of severe heart failure, it can be safely introduced through the previous sewing ring after removing the Teflon plug., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Mitochondria are a dynamic eukaryotic innovation that play diverse roles in biology and disease. The mitochondrial genome is remarkably conserved in all vertebrates, encoding the same 37-gene set and overall genomic structure, ranging from 16,596 base pairs (bp) in the teleost zebrafish ( Danio rerio ) to 16,569 bp in humans. Mitochondrial disorders are amongst the most prevalent inherited diseases, affecting roughly 1 in every 5000 individuals. Currently, few effective treatments exist for those with mitochondrial ailments, representing a major unmet patient need. Mitochondrial dysfunction is also a common component of a wide variety of other human illnesses, ranging from neurodegenerative disorders such as Huntington's disease and Parkinson's disease to autoimmune illnesses such as multiple sclerosis and rheumatoid arthritis. The electron transport chain (ETC) component of mitochondria is critical for mitochondrial biology and defects can lead to many mitochondrial disease symptoms. Here, we present a publicly available collection of genetic mutants created in highly conserved, nuclear-encoded mitochondrial genes in Danio rerio . The zebrafish system represents a potentially powerful new opportunity for the study of mitochondrial biology and disease due to the large number of orthologous genes shared with humans and the many advanced features of this model system, from genetics to imaging. This collection includes 15 mutant lines in 13 different genes created through locus-specific gene editing to induce frameshift or splice acceptor mutations, leading to predicted protein truncation during translation. Additionally, included are 11 lines created by the random insertion of the gene-breaking transposon (GBT) protein trap cassette. All these targeted mutant alleles truncate conserved domains of genes critical to the proper function of the ETC or genes that have been implicated in human mitochondrial disease. This collection is designed to accelerate the use of zebrafish to study many different aspects of mitochondrial function to widen our understanding of their role in biology and human disease.

Metal complexes have gradually been attracting interest from researchers worldwide as potential cancer therapeutics. Driven by the many side effects of the popular platinum-based anticancer drug cisplatin, the tireless endeavours of researchers have afforded strategies for the design of appropriate metal complexes with minimal side effects compared to cisplatin and its congeners to limit the unrestricted propagation of cancer. In this regard, transition metal complexes, especially rhenium-based complexes are being identified and highlighted as promising cancer theranostics, which are endowed with the ability to detect and annihilate cancer cells in the body. This is attributed the amazing photophysical properties of rhenium complexes together with their ability to selectively attack different organelles in cancer cells. Therefore, this review presents the properties of different rhenium-based complexes to highlight their recent advances as anticancer agents based on their cytotoxicity results., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: An inter-institutional collaboration between a quaternary hospital (QH) with a high volume of cardiac surgery and a community-based, tertiary hospital (TH) with a newly established cardiac surgery program was established., Methods: We retrospectively reviewed data of patients admitted to the TH between September 2015 and June 2017 for cardiac surgery. The decision to transfer a patient to the QH was based on a Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score of ≥ 3%, the potential need for hemodialysis, and other risk factors. The same team of surgeons performed operations at both hospitals. We analyzed the perioperative outcomes of the patients and the referral pattern., Results: A total of 116 patients met eligibility criteria; 105 underwent surgery at the TH, while 11 were transferred to the QH. Among the 11 patients transferred to the QH, eight had a score of  3% (median = 8.2 [IQR 5.7-25.0]). The patients transferred to the QH prior to surgery had a significantly higher STS-PROM score (P = ≤ .001). Overall, the mortality of patients who underwent surgery at the TH was 0.9% (1/105); while surgeries at the QH had a mortality rate of 0% (0/11)., Conclusion: The collaborative effort between high-volume cardiac surgery programs and emerging community-based hospitals showed acceptable outcomes in perioperative cardiac surgical mortality. Elevated STS-PROM scores (>3%), previous sternotomy and anticipation of coagulopathy, and low left ventricular ejection fraction or dilated ventricles are factors that influenced the need to transfer from a TH to QH.

Background: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation., Study Design: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed., Results: Fifteen patients from a large Level I trauma center met the criteria. The median PaO 2 /FiO 2 ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%)., Conclusions: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

The United States Food and Drug Administration restricts the use of implantable cardiac pressure monitors to patients with New York Heart Association (NYHA) class III heart failure (HF). We investigated whether single-pressure monitoring could predict survival in HF patients as part of a model constructed using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial. We validated survival models in 204 patients, using all-cause 180-day mortality. Two levels of model complexity were tested: 1) a simplified 1-pressure model based on pulmonary artery mean pressure ([PAM]1P) (information obtainable from an implanted intracardiac monitor alone), and 2) a pair of 5-variable risk score models based on right atrial pressure (RAP) + pulmonary capillary wedge pressure (PCWP) ([RAP+PCWP]5V) and on RAP + PAM ([RAP+PAM]5V). The more complex models used 5 dichotomous variables: a congestion index above a certain threshold value, baseline systolic blood pressure of <100 mmHg, baseline blood urea nitrogen level of ≥ 34 mg/dL, need for cardiopulmonary resuscitation or mechanical ventilation, and posttreatment NYHA class IV status. The congestion index was defined as posttreatment RAP+PCWP or posttreatment RAP+PAM, with congestion thresholds of 34 and 42 mmHg, respectively (median pulmonary catheter indwelling time, 1.9 d). The 5-variable models predicted survival with areas under the curve of 0.868 for the (RAP+PCWP)5V model and 0.827 for the (RAP+PAM)5V model, whereas the 1-pressure model predicted survival with an area under the curve of 0.718. We conclude that decongestion as determined by hemodynamic assessment predicts survival in HF patients and that it may be the final pathway for treatment benefit despite improvements in pharmacologic intervention since the ESCAPE trial., (© 2022 by the Texas Heart® Institute, Houston.)

COVID-19 pandemic has emerged as a global threat with its highly contagious and mutating nature. Several existing antiviral drugs has been worked on, without proper results and meanwhile the virus is mutating rapidly to create more infectious variant. In order to find some alternatives, phytocompounds can be opted as good one. In this study, three hundred phytocompounds were screened virtually against two viral proteins namely main protease and spike protein. Molecular docking and dynamic simulation study was used to find binding affinity, structural stability and flexibility of the complex. Pharmacokinetic properties were studied through ADMET analysis. To understand energy variation of the complex structure free energy landscape analysis was performed. Among three hundred phytocompounds virtual screening, three phytocompounds were selected for detailed molecular interaction analysis. Oleanderolide, Proceragenin A and Balsaminone A, showed strong binding affinity against both the target proteins and reflected conformational stability throughout the MD run. Oleanderolide, proceragenin A and balsaminone A has docking score -9.4 kcal/mol, -8.6 kcal/mol, and -8.1 kcal/mol respectively against main protease and same -8.3 kcal/mol docking score against spike protein. These three phytocompounds has high gastrointestinal absorption capacity. They were unexplored till now for their antiviral activity. Their promising in silico results suggests that they can be promoted in the long run for development of new antiviral drugs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

For the first time, we present a novel technique that enables the exchange of the Impella CP (Abiomed Inc., Danvers, Massachusetts, USA) to the Impella 5.5 (Abiomed Inc.) with no interruption of mechanical support in patients with minimal left ventricular reserve. Specifically, the aortic valve is crossed with the Impella 5.5 whereas the Impella CP is still functioning within the left ventricle. The Impella 5.5 is then initiated, and the Impella CP is weaned. Finally, the Impella CP is pulled out into the descending aorta. This exchange provides continuous support with no hemodynamic disarrangement., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Herein, we have introduced a series of half-sandwich Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for brain cancer therapy. Among all the synthesized complexes, [(η 6 - p -cymene)Ru II (κ 2 - N , N -4,7dimethyl phenanthroline)(PTA)]·2PF 6 (4c) and [(η 6 - p -cymene)Ru II (κ 2 - N , N -4,7diphenyl phenanthroline)(PTA)]·2PF 6 (4d) showed outstanding potency against the T98G, LN229 and U87MG cancer cells. The antiproliferative activity of these complexes was reinforced by neurosphere, DNA intercalation, agarose gel electrophoresis, cell cycle analysis and time-dependent ROS detection assays. The real-time reverse transcription (RT)-polymerase chain reaction (PCR) study showed that complex 4c inhibited the TNF-α-induced NF-κB phosphorylation in glioma cells. Moreover, the in vivo biodistribution of complex 4c in different organs and the morphological patterns of widely used zebrafish embryos due to toxic effects have been evaluated., Competing Interests: “There are no conflicts to declare”., (This journal is © The Royal Society of Chemistry.)

Foot drop in the absence of limb ischemia is a chronic complication in peripheral venoarterial extracorporeal membrane oxygenation (V-A ECMO) survivors; however, there is little published regarding the incidence and functional outcomes of this condition. Common peroneal nerve is the most common cause of foot drop, a condition that leads to significant debility and requires extensive physical therapy and rehabilitation, thereby affecting the patient's quality of life. We completed a retrospective review of 153 patients who received femoral cannulation for V-A ECMO support for greater than 1 hour. The incidence of foot drop in our V-A ECMO population was 7.8% (12/153). Importantly, only two patients with foot drop were discharged home. The majority (10/12) of patients with foot drop required in-patient rehabilitation; five patients were nonambulatory, and five patients required an ankle foot orthosis assistive device. This study identifies foot drop as a relevant complication in peripherally cannulated V-A ECMO survivors and provides an initial incidence rate. By raising awareness of this complication in the V-A ECMO population, an early diagnosis is possible, which can enable appropriate rehabilitation. Prospective trials are needed to identify possible risk factors of foot drop and methods to reduce this complication of V-A ECMO., Competing Interests: Disclosure: The authors declare no funding and conflicts of interest to report., (Copyright © ASAIO 2021.)

A class of plant defense and storage proteins, including Putranjiva roxburghii PNP protein (PRpnp), belongs to PNP-UDP family. The PRpnp and related plant proteins contain a disrupted PNP-UDP domain as revealed in previous studies. In PRpnp, the insert disrupting the domain contains the trypsin inhibitory site. In the present work, we analyzed native PRpnp (nPRpnp) complex formation with trypsin and inosine using SAXS experiments and established its dual functionality. Results indicated a relatively compact nPRpnp:Inosine structure, whereas trypsin complex showed conformational changes/flexibility. nPRpnp also exhibited a strong anti-cancer activity toward breast cancer (MCF-7), prostate cancer (DU-145) and hepatocellular carcinoma (HepG2) cell lines. MCF-7 and DU-145 were more sensitive to nPRpnp treatment as compared to HepG2. However, nPRpnp treatment showed no effect on the viability of HEK293 cells indicating that nPRpnp is specific for targeting the viability of only cancer cells. Further, acridine orange, DAPI and DNA fragmentation studies showed that cytotoxic effect of nPRpnp is mediated through induction of apoptosis as evident from the apoptosis-associated morphological changes and nuclear fragmentation observed after PRpnp treatment of cancer cells. These results suggest that PRpnp has the potential to be used as an anticancer agent. This is first report of anticancer activity as well as SAXS-based analysis for a PNP enzyme with trypsin inhibitory activity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)