Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces. Patients with this condition are unique, necessitating distinct considerations for anesthesia and surgical teams. This review describes the etiology, prevalence, clinical presentation, and management of HNPP and presents contemporary evidence and recommendations for optimal care for HNPP patients in the perioperative period. While the incidence of HNPP is reported at 7-16:100,000, this figure may be an underestimation due to underdiagnosis, further complicating medicolegal issues. With the subtle nature of symptoms associated with HNPP, patients with this condition may remain unrecognized during the perioperative period, posing significant risks. Several aspects of caring for this population, including anesthetic choices, intraoperative positioning, and monitoring strategy, may deviate from standard practices. As such, a tailored approach to caring for this unique population, coupled with meticulous preoperative planning, is crucial and requires a multidisciplinary approach.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

The human gut microbiome in critical illness: disruptions, consequences, and therapeutic frontiers.

With approximately 39 trillion cells and over 20 million genes, the human gut microbiome plays an integral role in both health and disease. Modern living has brought a widespread use of processed food and beverages, antimicrobial and immunomodulatory drugs, and invasive procedures, all of which profoundly disrupt the delicate homeostasis between the host and its microbiome. Of particular interest is the human gut microbiome, which is progressively being recognized as an important contributing factor in many aspects of critical illness, from predisposition to recovery. Herein, we describe the current understanding of the adverse impacts of standard intensive care interventions on the human gut microbiome and delve into how these microbial alterations can influence patient outcomes. Additionally, we explore the potential association between the gut microbiome and post-intensive care syndrome, shedding light on a previously underappreciated avenue that may enhance patient recuperation following critical illness. There is an impending need for future epidemiological studies to encompass detailed phenotypic analyses of gut microbiome perturbations. Interventions aimed at restoring the gut microbiome represent a promising therapeutic frontier in the quest to prevent and treat critical illnesses.

Deep phenotyping of the lipidomic response in COVID-19 and non-COVID-19 sepsis.

BACKGROUND: Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs-CoV-2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU). METHODS: Mass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity. RESULTS: Circulating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID-19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α-III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12-HETE, exhibited relative specificity for COVID-19 and correlated with sPLA2 and the interleukin-13 receptor to drive lymphopenia, a marker of disease severity. Pro-inflammatory eicosanoids remained correlated with severity in COVID-19 28 days after admission. Amongst non-COVID ICU patients, elevations in 5- and 15-HETE and 9- and 13-HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflected disease severity in COVID-19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non-B non-T cell activation. In COVID-19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids - ChoE 18:3, LPC-O-16:0 and PC-O-30:0 - were altered specifically in COVID. LPC-O-16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi-omic inflammatory pathways and disease severity. CONCLUSIONS: A broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12-HETE and the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients and correlate with the inflammatory response to link to disease severity.

COVID-19: a modern trigger for Guillain-Barre syndrome, myasthenia gravis, and small fiber neuropathy.

COVID-19 infection has had a profound impact on society. During the initial phase of the pandemic, there were several suggestions that COVID-19 may lead to acute and protracted neurologic sequelae. For example, peripheral neuropathies exhibited distinctive features as compared to those observed in critical care illness. The peripheral nervous system, lacking the protection afforded by the blood-brain barrier, has been a particular site of sequelae and complications subsequent to COVID-19 infection, including Guillain-Barre syndrome, myasthenia gravis, and small fiber neuropathy. We will discuss these disorders in terms of their clinical manifestations, diagnosis, and treatment as well as the pathophysiology in relation to COVID-19.

Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis.

Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find a broad based lipidomic storm driven predominantly by secretory (s) phospholipase A 2 (sPLA 2 ) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD 2 and PGI 2 , and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.

Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.

Poor outcomes in Subarachnoid Hemorrhage (SAH) are in part due to a unique form of secondary neurological injury known as Delayed Cerebral Ischemia (DCI). DCI is characterized by new neurological insults that continue to occur beyond 72 h after the onset of the hemorrhage. Historically, it was thought to be a consequence of hypoperfusion in the setting of vasospasm. However, DCI was found to occur even in the absence of radiographic evidence of vasospasm. More recent evidence indicates that catastrophic ionic disruptions known as Cortical Spreading Depolarizations (CSD) may be the culprits of DCI. CSDs occur in otherwise healthy brain tissue even without demonstrable vasospasm. Furthermore, CSDs often trigger a complex interplay of neuroinflammation, microthrombi formation, and vasoconstriction. CSDs may therefore represent measurable and modifiable prognostic factors in the prevention and treatment of DCI. Although Ketamine and Nimodipine have shown promise in the treatment and prevention of CSDs in SAH, further research is needed to determine the therapeutic potential of these as well as other agents.

An In-Depth Analysis of Providers and Services of Cancellation in Anesthesia Reveals a Complex Picture after Systemic Analysis.

The variances in operating room (OR) cancellation rates between different service lines and operators within these service lines were assessed by reviewing the electronic medical record (EMR) covering 34,561 cases performed by 199 OR operators in 2018. We assumed that cancellations would differ between different service lines, but the between-operators variance was minimal within the service line. We hypothesized that most variability would be secondary to patient-specific (weekdays, time of year, and national holidays), seasonal and administrative issues. Of 4165 case cancellations, the majority (73.1%) occurred before the patient arrived at the hospital. A total of 60% of all cancellations were within gastroenterology, interventional cardiology, and orthopedics. Cancellation rate variability between surgeons operating within the same service line greatly varied between services from very homogenous to very diverse across providers. The top reasons for cancellation were: date change, canceled by a patient, or "no show". The highest cancellation rates occurred on Mondays and Tuesdays, in January and September, and during weeks associated with national holidays. In summary, cancellation variability must be analyzed at the level of individual specialties, operators, and time variability.

Elevated Serum Fibroblast Growth Factor 23 (FGF-23) Perseveres into a Convalescence Period After Elective Cardiac Surgery, with Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Cartilage Oligomeric Matrix Protein (COMP) Being Part of the Peri-Surgical -Pro-Arteriosclerotic Inflammatory Response.

BACKGROUND Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), cartilage oligomeric matrix protein (COMP), bone morphogenetic protein (BMP-2), and fibroblast growth factor 23 (FGF-23) are involved in inflammation, calcium deposition, and fibrosis of blood vessels. Acute changes in these factors may contribute to the progression of arteriosclerosis, especially if their elevated serum levels persist postoperatively. MATERIAL AND METHODS A total of 90 patients (79 White, 4 African American, and 7 Other) undergoing elective heart surgery were enrolled in the study. Blood was collected before surgery and after surgery at 24 hours, 7 days, and 3 months to allow for longitudinal comparisons. After the plasma isolation, several biomarkers levels were studied using an enzymatic-linked assay. Demographic and clinical information were obtained from electronic health records. RESULTS At 24 hours after surgery, RANKL (RANKLbaseline=248.7±215.7 vs RANKLt24h=376.4±329.7; P=0.035), and BMP-2 (BMP-2baseline=283.7±255.4 vs BMP-2t24h=482.4; P=0.015) were significantly elevated compared to baseline, with levels returning to baseline at 7 days. FGF-23 increased significantly from baseline (FGF-23baseline=1020±1210) to 7 days (FGF-237d=2191±5188; P=0.029) and remained significantly higher than baseline at 3 months (FGF-233m=2041±3521; P=0.044). White blood cells (WBC) remained elevated at discharge (WBCbaseline=6.8±2.1 vs WBC24h=15.0±5.3 vs WBCdischarge=8.8±3.4). IL-8 and C-reactive protein normalized at 3 months. Estimated blood loss was significantly correlated with RANKL at 24 hours (r²=0.33; P=0.035). Serum creatinine levels after surgery at 24 hours (r²=0.41; p=0.008) and 7 days (r²=0.59; P=0.000) was strongly correlated with COMP. CONCLUSIONS Persistent elevation of serum FGF-23 indicates a potential for accelerated arteriosclerosis after cardiac surgery.

Whole Blood Reactivity to Viral and Bacterial Pathogens after Non-Emergent Cardiac Surgery during the Acute and Convalescence Periods Demonstrates a Distinctive Profile of Cytokines Production Compared to the Preoperative Baseline in Cohort of 108 Patients, Suggesting Immunological Reprogramming during the 28 Days Traditionally Recognized as the Post-Surgical Recovery Period.

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils-IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells-M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.

Persistent Depletion of Neuroprotective Factors Accompanies Neuroinflammatory, Neurodegenerative, and Vascular Remodeling Spectra in Serum Three Months after Non-Emergent Cardiac Surgery.

We hypothesized that the persistent depletion of neuroprotective markers accompanies neuroinflammation and neurodegeneration in patients after cardiac surgery. A total of 158 patients underwent elective heart surgery with their blood collected before surgery (tbaseline) and 24 h (t24hr), seven days (t7d), and three months (t3m) post-surgery. The patients' serum was measured for markers of neurodegeneration (τau, τaup181-183, amyloid ß1-40/ß2-42, and S100), atypical neurodegeneration (KLK6 and NRGN), neuro-injury (neurofilament light/heavy, UC-HL, and GFAP), neuroinflammation (YKL-40 and TDP-43), peripheral nerve damage (NCAM-1), neuroprotection (apoE4, BDNF, fetuin, and clusterin), and vascular smoldering inflammation (C-reactive protein, CCL-28 IL-6, and IL-8). The mortality at 28 days, incidence of cerebrovascular accidents (CVA), and functional status were followed for three months. The levels of amyloid ß1-40/ß1-42 and NF-L were significantly elevated at all time points. The levels of τau, S100, KLK6, NRGN, and NCAM-1 were significantly elevated at 24 h. A cluster analysis demonstrated groupings around amyloids, KLK6, and NCAM-1. YKL-40, but not TDP-43, was significantly elevated across all time points. BDNF, apoE4, fetuin, and clusterin levels were significantly diminished long-term. IL-6 and IL-8 levles returned to baseline at t3m. The levels of CRP, CCL-28, and Hsp-70 remained elevated. At 3 months, 8.2% of the patients experienced a stroke, with transfusion volume being a significant variable. Cardiac-surgery patients exhibited persistent peripheral and neuronal inflammation, blood vessel remodeling, and the depletion of neuroprotective factors 3 months post-procedure.

Concomitant elevated serum levels of tenascin, MMP-9 and YKL-40, suggest ongoing remodeling of the heart up to 3 months after cardiac surgery after normalization of the revascularization markers.

BACKGROUND: The recovery from cardiac surgery involves resolving inflammation and remodeling with significant connective tissue turnover. Dynamics of smoldering inflammation and injury (white blood cells, platelets, CRP, IL-8, IL-6), vascular inflammation (IL-15, VEGF, RANTES), connective tissue remodeling (tenascin, MMP-9), cardiac injury and remodeling (YKL-40), and vascular remodeling (epiregulin, MCP-1, VEGF) were assessed up to 3 months after cardiac surgery. We hypothesize that at 3 months, studied markers will return to pre-surgical levels. METHODS: Patients (n = 139) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(tbaseline), 24 h later(t24h) after the first sample, 7 days(t7d), and 3 months(t3m) after tbaseline. Serum markers were measured via multiplex or ELISA. Electronic medical records (EMR) were used to extract demographical, pre-existing conditions and clinical data. Disposition (discharge home, discharge to facility, death, re-admission) was determined at 28 days and 3 months from admission. RESULTS: Not all inflammatory markers returned to baseline (CRP↑↑, leukocytosis, thrombocytosis, IL-8↓, IL-6↓). Tenascin and YKL-40 levels remained elevated even at t3m. YKL-40 serum levels were significantly elevated at t24h and t7d while normalized at t3m. VEGF returned to the baseline, yet MCP-1 remained elevated at 3 months. CCL28 increased at 3 months, while RANTES and IL-15 declined at the same time. Disposition at discharge was determined by serum MMP-9, while YKL-40 correlated with duration of surgery and APACHE II24h. CONCLUSIONS: The data demonstrated an ongoing extracellular matrix turnover at 3 months, while acute inflammation and vascular remodeling resolved only partially.

Postoperative Dynamic of Leptin and Fibroblast Growth Factor 21 in 123 Patients Recovering from Cardiac Surgery.

BACKGROUND Cardiac surgery triggers acute changes in serum leptin and fibroblast growth factor 21 (FGF-21). Considering their pleiotropic role in inflammation and abnormal glucose metabolism, perseverance of their abnormal serum level can have a long-term impact on recovery and end-organ failures. Long-term dynamics after cardiac surgery are unknown. MATERIAL AND METHODS Serum was collected from 123 patients before cardiac surgery (tbaseline) and 24 h (t24h), 7 days (t7d), and 3 months (t3m) later. Also, interleukin 6 (IL-6) and C-reactive protein (CRP) assessed nonspecific inflammatory responses. Neurodegeneration was gauged with serum amyloid ß1-40 and ß1-42. Demographic and clinical information, including disposition at 28 days and t3m from admission, were collected. RESULTS Serum leptin increased at t24h (leptinbaseline=613+747.9 vs leptin24h=768±718.1; P=0.0083) and decreased at t7d (leptin7d=499.5±540.2; P=0.043). FGF-21 levels increased at t24h and t7d. Cytokines normalized by t3m. Presurgical leptin levels were higher in Asians and were the primary determinant of postoperative leptin changes. Leptin levels were most elevated in patients undergoing aortic valve and arch surgery; the perioperative increase was significant only in patients with mitral valve surgery. Leptin and FGF-21 did not correlate with markers of general inflammation (CRP, IL-6), which partially resolved after t3m. Amyloid ß1-42 at t3m correlated with leptin peak at t24h. Low prehospital FGF-21 level correlated with the incidence of perioperative stroke; postoperative FGF-21 correlated with discharge to facility vs home. CONCLUSIONS Leptin and FGF-21 evolve independently from the inflammatory response in the aftermath of cardiac surgery and correlate with cardiac remodeling and neurodegeneration markers.

Serum level of total histone 3, H3K4me3, and H3K27ac after non-emergent cardiac surgery suggests the persistence of smoldering inflammation at 3 months in an adult population.

BACKGROUND: Despite clinical relevance of immunological activation due to histone leakage into the serum following cardiac surgery, long-term data describing their longitudinal dynamic are lacking. Therefore, this study examines the serum levels of histone 3 (tH3) and its modifications (H3K4me3 and H3K27ac) alongside immune system activation during the acute and convalescence phases of cardiac surgery. METHODS: Blood samples from fifty-nine individuals were collected before non-emergent cardiac surgery (tpre-op) and 24 h (t24hr), seven days (t7d), and three months (t3m) post-procedure to examine serum levels of tH3, H3K4me3, and H3K27ac. Serum heat shock protein-60 (HSP-60) was a surrogate of the cellular damage marker. Serum C-reactive protein (CRP) and interleukin 6 (IL-6) assessed smoldering inflammation. TNFα and IL-6 production by whole blood in response to lipopolysaccharide (LPS) evaluated immunological activation. Electronic medical records provided demographic, peri-operative, and clinical information. Paired longitudinal analyses were employed with data expressed as mean and standard deviation (X ± SD) or median and interquartile range (Me[IQ25; 75%]. RESULTS: Compared to pre-operative levels (tH3Pre-op = 1.6[0.33;2.4]), post-operative serum tH3 significantly (p > 0.0001) increased after heart surgery (tH324hr = 2.2[0.3;28]), remained elevated at 7 days (tH37d = 2.4[0.37;5.3]), and at 3 months (tH33m = 2.0[0.31;2.9]). Serum H3K27ac was elevated at 24 h (H3K27ac24hr = 0.66 ± 0.51; p = 0.025) and seven days (H3K27ac7d = 0.94 ± 0.95; p = 0.032) as compared to baseline hours (H3K27acPre-op = 0.55 ± 0.54). Serum H3K4me3 was significantly diminished at three months (H3K4me3Pre-op = 0.94 ± 0.54 vs. H3K27ac3m = 0.59 ± 0.89; p = 0.008). tH3 correlated significantly with the duration of anesthesia (r2 = 0.38). In contrast, HSP-60 normalized seven days after surgery. Peri-operative intake of acetaminophen, but no acetylsalicylic acid (ASA), acid, ketorolac or steroids, resulted in the significant depression of serum H3K4me3 at 24 h (H3K4me3acetom- = 1.26[0.71; 3.21] vs H3K4me3acetom+ = 0.54[0.07;1.01]; W[50] = 2.26; p = 0.021). CRP, but not IL-6, remained elevated at 3 months compared to pre-surgical levels and correlated with tH324hrs (r2 = 0.43), tH37d (r2 = 0.71; p < 0.05), H3K4me37d (r2 = 0.53), and H3K27ac7d (r2 = 0.49). Production of TNFα by whole blood in response to LPS was associated with serum tH324hrs (r2 = 0.67). Diminished H3K4me324hrs, H3K27ac24hrs, and H3K27ac3m, accompanied the emergence of liver failure. CONCLUSIONS: We demonstrated a prolonged elevation in serum histone 3 three months after cardiac surgery. Furthermore, histone 3 modifications had a discrete time evolution indicating differential immune activation.

A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce.

A complement effect on homeostasis during infection is determined by both cytotoxic (activate complement component 5 (C5a) terminal cytotoxic complex (TCC)), and cytoprotective elements (complement factor H (FH), as well as apolipoprotein E (ApoE)). Here, we investigated the gap in knowledge in their blood milieu during SARS-CoV-2 infection with respect to the viral burden, level of tissue necrosis, and immunological response. 101 patients hospitalized with a PCR-confirmed diagnosis of COVID-19 had blood collected at H1 (48 h), H2 (3-4 Days), H3 (5-7 days), H4 (more than 7 days up to 93 days). Pre-existing conditions, treatment, the incidence of cerebrovascular events (CVA), a history of deep venous thrombosis (DVT) and pulmonary embolism (PE), and mortality was collected using electronic medical records. Plasma C5a, TCC, FH, and ApoE were considered as a complement milieu. Tissue necrosis (HMGB1, RAGE), non-specific inflammatory responses (IL-6, C-reactive protein), overall viral burden (SARS-CoV-2 spike protein), and specific immune responses (IgG, IgA, IgM directed αS- & N-proteins) were assessed simultaneously. C5a remained elevated across all time points, with the peak at 5-7 days. Studied elements of complement coalesced around three clusters: #0 (↑↑↑C5a, ↑↑TCC, ↓↓ApoE), #1 ↑C5a, ↑TCC, ↑↑↑FH); #2 (↑C5a, ↑TCC, ↑FH, ↑↑↑ApoE). The decline in FH and ApoE was a predictor of death, while TCC and C5a correlated with patient length of stay, APACHE, and CRP. Increased levels of C5a (Δ = 122.64; p = 0.0294; data not shown) and diminished levels of FH (Δ = 836,969; p = 0.0285; data not shown) co-existed with CVA incidence. C5a correlated storngly with blood RAGE and HMGB1, but not with viral load and immunological responsiveness. Remdesivir positively affected FH preservation, while convalescent plasma treatment elevated C5a levels. Three clusters of complement activation demonstrated a various milieu of ApoE & FH vs C5a & TCC in COVID-19 patients. Complement activation is linked to increased necrosis markers but not to viral burden or immune system response.

Operation analysis of the tele-critical care service demonstrates value delivery, service adaptation over time, and distress among tele-providers.

Background: Our study addresses the gaps in knowledge of the characterizations of operations by remote tele-critical care medicine (tele-CCM) service providers interacting with the bedside team. The duration of engagements, the evolution of the tele-CCM service over time, and the distress during interactions with the bedside team have not been characterized systematically. These characteristics are critical for planning the deployment of teleICU services and preventing burnout among remote teleICU providers. Methods: REDCap self-reported activity logs collected engagement duration, triggers (emergency button, tele-CCM software platform, autonomous algorithm, asymmetrical communication platform, phone), expediency, nature (proactive rounding, predetermined task, response to medical needs), communication modes, and acceptance. Seven hospitals with 16 ICUs were overseen between 9/2020 and 9/2021 by teams consisting of telemedicine medical doctors (eMD), telemedicine registered nurses (eRN), and telemedicine respiratory therapists (eRT). Results: 39,915 total engagements were registered. eMDs had a significantly higher percentage of emergent and urgent engagements (31.9%) vs. eRN (9.8%) or eRT (1.7%). The average tele-CCM intervention took 16.1 ± 10.39 min for eMD, 18.1 ± 16.23 for eRN, and 8.2 ± 4.98 min for eRT, significantly varied between engagement, and expediency, hospitals, and ICUs types. During the observation period, there was a shift in intervention triggers with an increase in autonomous algorithmic ARDS detection concomitant with predominant utilization of asynchronous communication, phone engagements, and the tele-CCM module of electronic medical records at the expense of the share of proactive rounding. eRT communicated more frequently with bedside staff (% MD = 37.8%; % RN = 36.8, % RT = 49.0%) but mostly with other eRTs. In contrast, the eMD communicated with all ICU stakeholders while the eRN communicated chiefly with other RN and house staff at the patient's bedside. The rate of distress reported by tele-CCM staff was 2% among all interactions, with the entity hospital being the dominant factor. Conclusions: Delivery of tele-CCM services has to be tailored to the specific beneficiary of tele-CCM services to optimize care delivery and minimize distress. In addition, the duration of the average intervention must be considered while creating an efficient workflow.

A Survey of Tele-Critical Care State and Needs in 2019 and 2020 Conducted among the Members of the Society of Critical Care Medicine.

The study's objective was to assess facilitators and barriers of Tele-Critical Care (TCC) perceived by SCCM members. By utilizing a survey distributed to SCCM members, a cross-sectional study was developed to analyze survey results from December 2019 and July 2020. SCCM members responded to the survey (n = 15,502) with a 1.9% response rate for the first distribution and a 2.54% response rate for the second survey (n = 9985). Participants (n = 286 and n = 254) were almost equally distributed between non-users, providers, users, and potential users of TCC services. The care delivery models for TCC were similar across most participants. Some consumers of TCC services preferred algorithmic coverage and scheduled rounds, while reactive and on-demand models were less utilized. The surveys revealed that outcome-driven measures were the principal form of TCC performance evaluation. A 1:100 (provider: patients) ratio was reported to be optimal. Factors related to costs, perceived lack of need for services, and workflow challenges were described by those who terminated TCC services. Barriers to implementation revolved around lack of reimbursement and adequate training. Interpersonal communication was identified as an essential TCC provider skill. The second survey introduced after the onset pandemic demonstrated more frequent use of advanced practice providers and focus on performance measures. Priorities for effective TCC deployment include communication, knowledge, optimal operationalization, and outcomes measurement at the organizational level. The potential effect of COVID-19 during the early stages of the pandemic on survey responses was limited and focused on the need to demonstrate TCC value.

Pilot of rapid implementation of the advanced practice provider in the workflow of an existing tele-critical care program.

Incorporating the advanced practice provider (APP) in the delivery of tele critical care medicine (teleCCM) addresses the critical care provider shortage. However, the current literature lacks details of potential workflows, deployment difficulties and implementation outcomes while suggesting that expanding teleCCM service may be difficult. Here, we demonstrate the implementation of a telemedicine APP (eAPP) pilot service within an existing teleCCM program with the objective of determining the feasibility and ease of deployment. The goal is to augment an existing tele-ICU system with a balanced APP service to assess the feasibility and potential impact on the ICU performance in several hospitals affiliated within a large academic center. A REDCap survey was used to assess eAPP workflows, expediency of interventions, duration of tasks, and types of assignments within different service locations. Between 02/01/2021 and 08/31/2021, 204 interventions (across 133 12-h shift) were recorded by eAPP (nroutine = 109 (53.4%); nurgent = 82 (40.2%); nemergent = 13 (6.4%). The average task duration was 10.9 ± 6.22 min, but there was a significant difference based on the expediency of the task (F [2; 202] = 3.89; p < 0.022) and type of tasks (F [7; 220] = 6.69; p < 0.001). Furthermore, the eAPP task type and expediency varied depending upon the unit engaged and timeframe since implementation. The eAPP interventions were effectively communicated with bedside staff with only 0.5% of suggestions rejected. Only in 2% cases did the eAPP report distress. In summary, the eAPP can be rapidly deployed in existing teleCCM settings, providing adaptable and valuable care that addresses the specific needs of different ICUs while simultaneously enhancing the delivery of ICU care. Further studies are needed to quantify the input more robustly.