An intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in patients with metastatic or primary brain tumors.

PURPOSE: Eribulin is an inhibitor of microtubule dynamics. It is not as highly protein bound as the taxanes and is less vulnerable to extrusion by P-glycoprotein in the blood-brain barrier (BBB). These features predict that eribulin could play an active role in managing brain tumors. Indeed, the small amount of published clinical data indicates eribulin may have some efficacy against breast cancer brain metastases. To better understand the potential of eribulin for treating brain tumors, we performed an intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in cancer patients undergoing tumor resection. METHODS: After tumor removal, two microdialysis catheters were inserted into peritumoral brain tissue. Approximately 24 h after surgery, a single dose of eribulin 1.4 mg/m2 was administered intravenously. Dialysate samples were collected continuously for 72 h, with plasma samples collected in parallel. Eribulin concentrations were analyzed by tandem mass spectrometry. RESULTS: Dialysate samples from 12 intracerebral microdialysis catheters placed in 7 study participants were included in the analysis. A statistically significant difference was observed between eribulin concentrations in brain tissue where BBB was disrupted versus intact, with a difference in mean maximum concentrations on log2 scale of 3.37 (std err = 0.59, p-value = 0.005). Nonetheless, overall brain to plasma ratios of eribulin only ranged from 0.13 to 1.99%. CONCLUSION: Although we could detect higher concentrations of eribulin in brain tissue where BBB was disrupted, intracerebral eribulin levels were not sufficient to predict eribulin would have consistent clinically meaningful activity against tumors in the brain. GOV IDENTIFIER: NCT02338037 (January 9, 2015).

Introducing Chemoselective Peptide Conjugation via N-Alkylation of Pyridyl-alanine: Solution and Solid Phase Applications.

A novel chemoselective peptide conjugation via late-stage N-alkylation of pyridyl-alanine (PAL) in the solution and solid phase, namely, NAP, is demonstrated. The method constructs functionally diverse and highly stable N-alkylated conjugates with various peptides. Notably, conjugations in the solid phase offered a more economical process. The method can provide the opportunity for dual labeling along with a cysteine handle in a peptide chain. Finally, we showcased that the antiproliferative activities of the p53 peptide (MDM2 inhibitor) could be 2-fold enhanced via NAP conjugation with the RGD peptide (selective integrin binder).

Possible Terbinafine and/or Itraconazole Induced Vasculitis - A Case Study.

INTRODUCTION: It is essential to exclude other causes, such as autoimmune diseases and bacterial infections, before attributing cutaneous/systemic vasculitis to drug use. CASE STUDY: This report discusses the case of a young man who developed multi-organ failure and cutaneous vasculitis following the use of antifungal medications (terbinafine and itraconazole) for dermatophyte infections. Tests for autoimmune diseases and infections were negative. Given his drug history and a skin biopsy indicating leukocytoclastic vasculitis, it was inferred that the vasculitis was likely drug-induced. Despite treatment with steroids, intravenous immunoglobulins, and plasmapheresis, the patient did not survive, possibly due to delayed diagnosis and treatment. CONCLUSION: In community practice, Drug-induced Vasculitis (DIV) is frequently overlooked. When patients present with skin rash, fever, and multi-organ dysfunction, DIV should be considered, particularly in the context of recent drug use. Over-the-counter antifungals, like terbinafine or itraconazole, can cause DIV and may be fatal if not promptly diagnosed and treated.

Rutin reduces inflammation and fibrosis via TGF-ß/SMAD pathways in IgA nephropathy induced rats.

AIM: Rutin is a flavonoid glycoside obtained from the plant Ruta graveolens. It was known to have immunosuppressant activities. This study was focused on effect of rutin against immunoglobulin A (IgA) nephropathy. METHODS: IgA nephropathy was induced in Sprague-Dawley rats with various inducing agents described in text. During the later part of the induction phase, rutin was administered. Control group rats did not receive any treatment or inducing agent, induced group rats received only the inducing agents, whereas treatment group received the inducing agents as well as rutin. RESULTS: During the study, various biochemical parameters pertaining to kidney function were evaluated and also, the expression of proteins and cytokines responsible for inflammation and fibrosis were assessed. The effect of rutin in IgA nephropathy was promising as treatment with rutin reduced the deposition of IgA in the glomeruli of rats. Along with this we also tried to establish the probable mechanism of action of rutin and based on the summary of the results it was concluded that rutin reduced the inflammation and fibrosis related to IgA nephropathy by inhibiting the TGF-ß/SMAD pathways and ultimately reducing the expression of α-smooth muscle actin (α-SMA). CONCLUSION: Comprehending all the above consideration, it may be safely said that that rutin alleviated inflammation and also fibrosis mediated by IgA, by suppressing the transforming growth factor-ß (TGF-ß) activities through suppressor of mothers against decapentaplegic pathways and reduced the epithelial-to-mesenchymal transition by downregulating the α-SMA which is a marker for fibrosis.

Harnessing a bis-electrophilic boronic acid lynchpin for azaborolo thiazolidine (ABT) grafting in cyclic peptides.

Chemical modifications of native peptides have significantly advanced modern drug discovery in recent decades. On this front, the installation of multitasking molecular grafts onto macrocyclic peptides offers numerous opportunities in biomedical applications. Here, we showcase a new class of borono-cyclic peptides featuring an azaborolo thiazolidine (ABT) graft, which can be readily assembled utilizing a bis-electrophilic boronic acid lynchpin while harnessing the inherent reactivity difference (>103 M-1 s-1) between the N-terminal cysteine and backbone cysteine for rapid and highly regioselective macrocyclization (∼1 h) under physiological conditions. The ABT-crosslinked peptides are fairly stable in endogenous environments, but can provide the linear diazaborine peptides via treatment with α-nucleophiles. This efficient peptide crosslinking protocol was further extended for regioselective bicyclizations and engineering of α-helical structures. Finally, ABT-grafted peptides were exploited in biorthogonal conjugation, leading to highly effective intracellular delivery of an apoptotic peptide (KLA) in cancer cells. The mechanism of action by which ABT-grafted KLA peptide induces apoptosis was also explored.

On-resin synthesis of Lanreotide epimers and studies of their structure-activity relationships.

Peptide drugs often accompany epimeric impurities (isomers). Therefore, efficient chemical synthesis of epimers is critical to identify them correctly and investigate their biological activities. Here, we report the rapid synthesis and structure-activity relationship (SAR) studies of eight possible epimers of a somatostatin synthetic analog (SSA), lanreotide (LAN). SPPS and the subsequent on-resin rapid disulfide closure method offered >90% conversion yield for all epimers (P1-P8). Further, we developed an analytical method to separate these epimers, which enabled the profiling of five epimeric impurities in the API, purchased for Somatuline generic formulations. In SAR studies, most LAN epimers revealed compromised antiproliferative activity, while the P7 epimer retained antiproliferative activity similar to LAN API, as supported by in silico SAR studies in detail. Additionally, P7 showed serum stability nearly identical to LAN, suggesting that drug epimers could be a potential API. Current studies will further encourage the development of novel SSA scaffolds.

Phase 1 Study of Bortezomib, Fludarabine, and Melphalan, With or Without Total Marrow Irradiation, as Allogeneic Hematopoietic Stem Cell Transplant Conditioning for High-risk or Relapsed/Refractory Multiple Myeloma.

OBJECTIVE: We conducted a phase 1 study of a conditioning regimen with or without total marrow irradiation (TMI) before allogeneic hematopoietic stem cell transplantation for patients with high-risk or refractory multiple myeloma. METHODS: Eighteen patients were enrolled on one of 2 strata. Patients with no prior radiation received TMI (900 cGy), fludarabine (FLU), and melphalan (MEL) conditioning, with bortezomib added in the second cohort (stratum I). Patients with prior radiation received FLU, MEL, and bortezomib, without TMI (stratum II). RESULTS: Eight patients were enrolled in the TMI arm (stratum I). One of 3 patients in cohort 1 experienced dose-limiting toxicity (DLT), which led to the expansion to 3 more patients with no DLT. Cohort 2 enrolled only 2 patients due to low accrual, with bortezomib, added at 0.5 mg/m 2 ; neither experienced DLT. Nine patients were enrolled in the non-TMI arm (stratum II). Three patients were enrolled in cohort 1 (bortezomib 0.5 mg/m 2 ) and none experienced DLT. Three were enrolled in cohort 2 (bortezomib 0.7 mg/m 2 ), and 1 experienced DLT; therefore, the cohort expanded to 3 more patients. One more patient experienced DLT. Median overall survival on strata I and II was 44.5 months (95% CI: 1.73-not reached) and 21.6 months (95% CI: 4.1-72.7), respectively. Median progression-free survival on strata I and II was 18.1 months (95% CI: 1.73-not reached) and 8.9 months (95% CI: 2.7-24.4), respectively. CONCLUSION: TMI 900 cGy, FLU, and MEL are considered feasible as conditioning for allogeneic stem cell transplantation and may warrant further investigation due to favorable response rates and survival.

A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-γ-induced CD38 expression.

ABSTRACT: Treatment resistance of leukemia stem cells (LSCs) and suppression of the autologous immune system represent major challenges to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38pos), LSCs are frequently enriched in the CD34posCD38neg blast fraction. Here, we report that interferon gamma (IFN-γ) reduces LSCs clonogenic activity and induces CD38 upregulation in both CD38pos and CD38neg LSC-enriched blasts. IFN-γ-induced CD38 upregulation depends on interferon regulatory factor 1 transcriptional activation of the CD38 promoter. To leverage this observation, we created a novel compact, single-chain CD38-CD3 T-cell engager (BN-CD38) designed to promote an effective immunological synapse between CD38pos AML cells and both CD8pos and CD4pos T cells. We demonstrate that BN-CD38 engages autologous CD4pos and CD8pos T cells and CD38pos AML blasts, leading to T-cell activation and expansion and to the elimination of leukemia cells in an autologous setting. Importantly, BN-CD38 engagement induces the release of high levels of IFN-γ, driving the expression of CD38 on CD34posCD38neg LSC-enriched blasts and their subsequent elimination. Critically, although BN-CD38 showed significant in vivo efficacy across multiple disseminated AML cell lines and patient-derived xenograft models, it did not affect normal hematopoietic stem cell clonogenicity and the development of multilineage human immune cells in CD34pos humanized mice. Taken together, this study provides important insights to target and eliminate AML LSCs.

Trace metals and pesticides in water-sediment and associated pollution load indicators of Netravathi-Gurupur estuary, India: Implications on coastal pollution.

Various environmental indicators were used to evaluate the water and sediment quality of the Netravathi-Gurupur estuary, India, for trace metals and pesticide pollution. The descended order of studied metal concentrations (µg/L) in the water was Fe (592.71) > Mn (98.35) > Zn (54.69) > Cu (6.64) > Cd (3.24) > Pb (2.38) > Cr (0.82) and in sediment (mg/kg) was Fe (11,396.53) > Mn (100.61) > Cr (75.41) > Zn (20.04) > Cu (12.77) > Pb (3.46) > Cd (0.02). However, pesticide residues were not detected in this estuarine environment. The various metal indexes categorised the water as uncontaminated, whereas contamination factor, enrichment factor, geo-accumulation index, degree of contamination and pollution load index indicated low to moderate sediment contamination. Multivariate statistics showed that the dominance of natural sources of trace metals with little anthropogenic impact. Improvement in water/sediment quality during the study period might be due to COVID-19 imposed lockdown.

Inhibitory role of copper and silver nanocomposite on important bacterial and fungal pathogens in rice (Oryza sativa).

Rice (Oryza sativa) being among the most important food crops in the world is also susceptible to various bacterial and fungal diseases that are the major stumbling blocks in the way of increased production and productivity. The bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae and the sheath blight disease caused by Rhizoctonia solani are among the most devastating diseases of the rice crop. In spite of the availability of array of chemical control, there are chances of development of resistance. Thus, there is a need for the nanotechnological intervention for management of disease in the form of copper and silver nano-composites. The copper (CuNPs) and silver nanoparticles (AgNPs) were synthesized using green route and characterized using different high throughput techniques, i.e., UV-Vis, FT-IR, DLS, XRD, FE-SEM, TEM. The particle size and zeta potential of synthesized CuNPs and AgNPs were found 273 nm and - 24.2 mV; 95.19 nm and - 25.5 mV respectively. The nanocomposite of CuNPs and AgNPs were prepared having particle size in the range of 375-306 nm with improved stability (zeta potential - 54.7 to - 39.4 mV). The copper and silver nanoparticle composites evaluated against Xanthomonas oryzae pv. oryzae and Rhizoctonia solani were found to have higher antibacterial (inhibition zone 13 mm) and antifungal activities (77%) compared to only the copper nanoparticle (8 mm; 62% respectively). Net house trials of nano-composite formulations against the bacterial blight of rice also corroborated the potential of nanocomposite formulation. In silico studies were carried out selecting two disease-causing proteins, peptide deformylase (Xanthomonas oryzae) and pectate lyase (Rhizoctonia solani) to perform the molecular docking. Interaction studies indicatedthat both of these proteins generated better complex with CuNPs than AgNPs. The study suggested that the copper and silver nano-composites could be used for developing formulations to control these devastating rice diseases.

Capturing Sialyl-glycan on Live Cancer Cells by Tailored Boronopeptide.

Boronic acid-containing molecules are substantially popularized in chemical biology and medicinal chemistry due to the broad spectrum of covalent conjugations as well as interaction modules offered by the versatile boron atom. Apparently, the WGA peptide (wheat germ agglutinin, 62-73), which shows a considerably low binding affinity to sialic acid, turned into a selective and >5 folds potent binder with the aid of a suitable boronic acid probe installed chemoselectively. In silico studies prompted us to install BA probes on the cysteine residue, supposedly located in close proximity to the bound sialic acid. In vitro studies revealed that the tailored boronopeptides show enhanced binding ability due to the synergistic recognition governed by selective non-covalent interactions and cis-diol boronic acid conjugation. The intense binding is observed even in 10 % serum, thus enabling profiling of sialyl-glycan on cancer cells, as compared with the widely used lectin, Sambucus nigra. The synergistic binding mode between the best boronopeptide (P3) binder and sialic acid was analyzed via 1 H and 11 B NMR.

Study of Drug Delivery Using Purely Organic Macrocyclic Containers-Cucurbit[7]uril and Pillararene.

An impaired immune system is the root of various human ailments provoking the urge to find vehicle-mediated quick delivery of small drug molecules and other vital metabolites to specific tissues and organs. Thus, drug delivery strategies are in need of improvement in therapeutic efficacy. It can be achieved only by increasing the drug-loading capacity, increasing the sustained release of a drug to its target site, easy relocation of drug molecules associated with facile complexation-induced properties of molecular vehicles, and high stimuli-responsive drug administration. Supramolecular drug delivery systems (SDDS) provide a much needed robust yet facile platform for fabricating innovative drug nanocarriers assembled by thermodynamically noncovalent interaction with the tunable framework and above-mentioned properties. Measures of cytotoxicity and biocompatibility are the two main criteria that lie at the root of any promising medicinal applications. This Review features significant advancements in (i) supramolecular host-guest complexation using cucurbit[7]uril (CB[7]), (ii) encapsulation of the drug and its delivery application tailored for CB[7], (iii) self-assembly of supramolecular amphiphiles, (iv) supramolecular guest relay using host-protein nanocavities, (v) pillararene (a unique macrocyclic host)-mediated SDDS for the delivery of smart nanodrugs for siRNA, fluorescent molecules, and insulin for juvenile diabetes. Furthermore, fundamental questions and future hurdles related to smart SDDS based on CB[7] and pillararenes and their future promising breakthrough implementations are also distinctly outlined in this Review.

Sulfonyl Diazaborine 'Click' Chemistry Enables Rapid and Efficient Bioorthogonal Labeling.

Finding an ideal bioorthogonal reaction that responds to a wide range of biological queries and applications is of great interest in biomedical applications. Rapid diazaborine (DAB) formation in water by the reactions of ortho-carbonyl phenylboronic acid with α-nucleophiles is an attractive conjugation module. Nevertheless, these conjugation reactions demand to satisfy stringent criteria for bioorthogonal applications. Here we show that widely used sulfonyl hydrazide (SHz) offers a stable DAB conjugate by combining with ortho-carbonyl phenylboronic acid at physiological pH, competent for an optimal biorthogonal reaction. Remarkably, the reaction conversion is quantitative and rapid (k2 >103  M-1 s-1 ) at low micromolar concentrations, and it preserves comparable efficacy in a complex biological milieu. DFT calculations support that SHz facilitates DAB formation via the most stable hydrazone intermediate and the lowest energy transition state compared to other biocompatible α-nucleophiles. This conjugation is extremely efficient on living cell surfaces, enabling compelling pretargeted imaging and peptide delivery. We anticipate this work will permit addressing a wide range of cell biology queries and drug discovery platforms exploiting commercially available sulfonyl hydrazide fluorophores and derivatives.

Normalized difference vegetation index sensor-based nitrogen management in bread wheat (Triticum aestivum L.): Nutrient uptake, use efficiency, and partial nutrient balance.

The present experiment was conducted to assess the impact of fixed and variable doses (using a normalized difference vegetation index-sensor) of nitrogen (N) on wheat yields, nutrient uptake, nitrogen use efficiency, and soil nitrogen balance through the optimization of nitrogen dose. There were 10 treatments based on fixed and variable doses with different splits, and each treatment was replicated three times under a randomized complete block design. The treatments comprised fixed doses of 120 and 150 kg N ha-1 with different splits; variable doses based on sensor readings after application of 60, 90, and 120 kg N ha-1; 225 kg N ha-1 as a nitrogen-rich control; and no application of nitrogen as the absolute control. It was revealed that the application of a basal dose of 60 kg N ha-1 and another 60 kg N ha-1 at the crown root initiation stage followed by a sensor-guided N application significantly improved wheat grain yields and grain nitrogen uptake. However, straw nitrogen uptake was highest in N-rich plots where 225 kg N ha-1was applied. It was found that any curtailment in these doses at basal and crown root initiation stages followed by nitrogen application using a normalized difference vegetation index sensor later could not bring about higher crop yields. On average, wheat crops responded to 152-155 kg N ha-1 in both years of the study. Partial factor productivity along with agronomic and economic nitrogen use efficiency showed a declining trend with an increased rate of N application. Apparent N recovery values were comparable between normalized difference vegetation index sensor-based N application treatments and treatments receiving lesser N doses. Soil N status decreased in all the treatments except the nitrogen-rich strip, where there was a marginal increase in soil N status after the wheat crop harvest in the rotation. Partial nitrogen balance was negative for all the treatments except the control. From these 2-year field trials, it can be concluded that applying a normalized difference vegetation index sensor could be an essential tool for the rational management of fertilizer nitrogen in wheat grown in eastern sub-Himalayan plains.

Leveraging IFNγ/CD38 regulation to unmask and target leukemia stem cells in acute myelogenous leukemia.

Elimination of drug-resistant leukemia stem cells (LSCs) represents a major challenge to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38pos), the presence of CD34 and lack of CD38 expression (CD34posCD38neg) are immunophenotypic features of both LSC-enriched AML blasts and normal hematopoietic stem cells (HSCs). We report that IFN-γ induces CD38 upregulation in LSC-enriched CD34posCD38neg AML blasts, but not in CD34posCD38neg HSCs. To leverage the IFN-γ mediated CD38 up-regulation in LSCs for clinical application, we created a compact, single-chain CD38-CD3-T cell engager (CD38-BIONIC) able to direct T cells against CD38pos blasts. Activated CD4pos and CD8pos T cells not only kill AML blasts but also produce IFNγ, which leads to CD38 expression on CD34posCD38neg LSC-enriched blasts. These cells then become CD38-BIONIC targets. The net result is an immune-mediated killing of both CD38neg and CD38pos AML blasts, which culminates in LSC depletion.

Leflunomide Confers Rapid Recovery from COVID-19 and is Coupled with Temporal Immunologic Changes.

Background: Vaccines for SARS-CoV-2 have been considerably effective in reducing rates of infection and severe COVID-19. However, many patients, especially those who are immunocompromised due to cancer or other factors, as well as individuals who are unable to receive vaccines or are in resource-poor countries, will continue to be at risk for COVID-19. We describe clinical, therapeutic, and immunologic correlatives in two patients with cancer and severe COVID-19 who were treated with leflunomide after failing to respond to standard-of-care comprising remdesivir and dexamethasone. Both patients had breast cancer and were on therapy for the malignancy. Methods: The protocol is designed with the primary objective to assess the safety and tolerability of leflunomide in treating severe COVID-19 in patients with cancer. Leflunomide dosing consisted of a loading dose of 100 mg daily for the first three days, followed by daily dosing, at the assigned dose level (Dose Level 1: 40 mg, Dose Level -1, 20 mg; Dose Level 2, 60 mg), for an additional 11 days. At defined intervals, serial monitoring of blood samples for toxicity, pharmacokinetics, and immunologic correlative studies were performed, as well as nasopharyngeal swabs for PCR analysis of SARS-CoV-2. Results: Preclinically, leflunomide impaired viral RNA replication, and clinically, it led to a rapid improvement in the two patients discussed herein. Both patients completely recovered, with minimal toxicities; all adverse events experienced were considered unrelated to leflunomide. Single-cell mass-cytometry analysis showed that leflunomide increased levels of CD8+ cytotoxic and terminal effector T cells and decreased naïve and memory B cells. Conclusions: With ongoing COVID-19 transmission and occurrence of breakthrough infections in vaccinated individuals, including patients with cancer, therapeutic agents that target both the virus and host inflammatory response would be helpful despite the availability of currently approved anti-viral agents. Furthermore, from an access to care perspective, especially in resource-limited areas, an inexpensive, readily available, effective drug with existing safety data in humans is relevant in the real-world setting.

Rapid and Highly Productive Assembly of a Disulfide Bond in Solid-Phase Peptide Macrocyclization.

Here we report a highly efficient disulfide-driven peptide macrocyclization in 15 min on a solid support using persulfate as a crucial additive in iodine-mediated oxidative cyclization. The method eliminates the side products of classical iodine-mediated peptide cyclization. It is operationally simple and convenient for cyclizing small to lengthier peptides embodying popular cysteine building blocks in a single step.

Geochemical distribution and forms of phosphorus in the surface sediment of Netravathi-Gurupur estuary, southwestern coast of India.

Estuaries are the most productive transition ecosystem and phosphorus (P) plays an important role in these ecosystems. Therefore, in the present study, sequential extraction method was used to determine the abundance of five sediment P fractions (calcium (Ca-P), Iron (FeP), aluminum (AlP), exchangeable (Ex-P) and organic (OrgP) bound P) in Netravathi-Gurupur estuary, India. Total phosphorus (TP) content varied from 435-810 mg/kg (non-monsoon) and 258-699 mg/kg (monsoon). Inorganic P was dominant part. Different P fractions followed similar order (Fe-P > Ca-P > Al-P > Org-P > Ex-P) with respect to seasons. FeP was dominant fraction, indicating probable anthropogenic stress. Sediment may act as source of P as bioavailable P constituted 40-69.2 % of TP. Molar ratio of OC to Org-P in sediment indicated terrestrial sources of organic matter. However, the estimated phosphorus pollution index were lower than one except a few cases indicating less ecological risk with respect to sedimentary TP load.

Compelling Cyclic Peptide Scaffolds for Antitubercular Action: An Account (2011-21) of the Natural Source.

Natural cyclic peptide scaffolds are indispensable in medicinal chemistry, chemical biology, and drug discovery platforms due to their chemical diversity, structural integrity, proteolytic stability and biocompatibility. Historically, their isolation and profound understanding of target engagement have been identified as lead pharmacophore discovery. Natural cyclic peptides are the largest class of pharmacologically active scaffold, in which most show activity against drug-resistant Mycobacterium tuberculosis (Mtb). Nevertheless, eight recently discovered cyclic peptide scaffolds exhibit promising antitubercular activity among numerous naturally occurring antitubercular peptides, and they are amenable scaffolds to drug development. We examined their biological origin, scaffolds, isolations, chemical synthesis, and reasons for biological actions against Mtb. Understanding these peptide scaffold details will further allow synthetic and medicinal chemists to develop novel peptide therapeutics against tuberculosis-infected deadly diseases. This review emphasizes these cyclic peptides' in vitro and in vivo activity profiles, including their structural and chemical features.

Cardiovascular Complications of Obstructive Sleep Apnea in the Intensive Care Unit and Beyond.

Obstructive sleep apnea (OSA) is a common disease with a high degree of association with and possible etiological factor for several cardiovascular diseases. Patients who are admitted to the Intensive Care Unit (ICU) are incredibly sick, have multiple co-morbidities, and are at substantial risk for mortality. A study of cardiovascular manifestations and disease processes in patients with OSA admitted to the ICU is very intriguing, and its impact is likely significant. Although much is known about these cardiovascular complications associated with OSA, there is still a paucity of high-quality evidence trying to establish causality between the two. Studies exploring the potential impact of therapeutic interventions, such as positive airway pressure therapy (PAP), on cardiovascular complications in ICU patients are also needed and should be encouraged. This study reviewed the literature currently available on this topic and potential future research directions of this clinically significant relationship between OSA and cardiovascular disease processes in the ICU and beyond.