Delay In Recovery Research Articles

The Effects of Dexmedetomidine on Postoperative Sleep in Elderly Patients: A Systematic Review and Meta-Analysis

Background: Postoperative sleep disorders in elderly patients may increase the risk of postoperative delirium or cognitive dysfunction and delay recovery. Therefore, it is imperative to develop innovative approaches to prevent and treat postoperative sleep disorders.Objective: This study aims to systematically evaluate the effects of perioperative use of dexmedetomidine on postoperative sleep in elderly patients.Methods: We searched for randomized controlled trials (RCTs) in Embase, PubMed, The Cochrane library, Web of Science, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, and Google Scholar databases from the establishment of the database to November 2020. Two researchers independently screened the literature, extracted information, and assessed bias risk. They cross-checked their findings .Any discrepancies were resolved through discussion or consultation with a third party. The risk of bias in the included studies was evaluated using RevMan 5.3, and meta-analysis, sensitivity analysis, and publication bias analysis were conducted using Stata 13.0.Results: A total of 23 studies involving 2,969 patients were included in the meta-analysis. The results of the meta-analysis showed that the subjective sleep quality score of the dexmedetomidine group was lower than that of the control group on the first day after surgery, with statistical significance [SMD = −1.29, 95%CI (−1.60, −0.98), P < 0.001, I2 = 89.7%]. The incidence of postoperative sleep disorders in the dexmedetomidine group was lower than that in the control group [RR = 0.49, 95% CI (0.30, 0.79), P = 0.003, I2 = 36.2%]. The duration of ICU stay and hospitalization in the dexmedetomidine group was also shorter than that in the control group [ICU stay: SMD = −0.98, 95% CI (−1.76, −0.19), P = 0.015, I2 = 88.8%; Hospitalization: SMD = −0.56, 95% CI (−0.95, -0.16), P = 0.006, I2 = 92.7%]. In terms of adverse events, the number of patients with postoperative bradycardia in the dexmedetomidine group was higher than that in the control group [RR = 1.629, 95% CI (1.291, 2.054), P < 0. 001, I2 = 0.0%]. The number of patients with postoperative hypotension was also higher in the dexmedetomidine group than in the control group [RR = 1.328, 95% CI (1.087, 1.622), P = 0. 003, I2 =2.1%]. On the other hand, the incidence of postoperative agitation was lower in the dexmedetomidine group than that in the control group [RR =0.193, 95% CI (0.075, 0.500), P = 0. 001, I2 = 0.0%], as was the incidence of postoperative tachycardia [RR = 0.486, 95% CI (0.348, 0.678), P < 0. 001, I2 = 0.0%].Conclusion: The perioperative use of dexmedetomidine in elderly patients can effectively improve subjective postoperative sleep quality, reduce the incidence of postoperative sleep disorders, shorten ICU and hospital stay, and has favorable safety.

Apoptosis of Hematopoietic Stem Cells Contributes to Bone Marrow Suppression Following Chimeric Antigen Receptor T Cell Therapy

Chimeric antigen receptor (CAR) T cell (CAR-T) therapy represents a revolutionary treatment for patients with relapsed/refractory hematologic malignancies. However, its use can result in significant toxicities, including cytokine release syndrome (CRS), a potentially life-threatening clinical syndrome resulting from the release of proinflammatory cytokines upon T cell activation. In addition, patients who develop CRS often experience prolonged cytopenias, and those with the most severe CRS also have the longest delays in full marrow recovery. Although an association between CRS and delayed bone marrow recovery has been established, the precise mechanism underlying this phenomenon remains unknown. This study was conducted to test our hypothesis that delayed bone marrow recovery following CAR-T therapy is caused by elevation of proinflammatory cytokines, leading to apoptosis and depletion of hematopoietic stem and progenitor cells (HSPCs). SCID-beige mice bearing intraperitoneal CD19+ Raji cell tumors were treated with injection of human CD19.28z CAR T cells. Bone marrow was then harvested for analysis by flow cytometry, and HSPCs were isolated for whole-transcriptome analysis by RNA sequencing. Complete blood counts and serum cytokine levels were measured as well. A second model was developed in which SCID-beige mice were treated with murine IFN-γ (mIFN-γ), murine IL-6 (mIL-6), or both. Bone marrow was harvested, and flow cytometry assays were conducted to evaluate the degree of apoptosis and proliferation on specific HSPC populations. SCID-beige mice bearing intraperitoneal Raji cell tumors that were treated with CAR-T therapy developed CRS, with elevations of several proinflammatory cytokines, including profound elevation of human IFN-γ. Gene set enrichment analysis of RNA sequencing data revealed that genes associated with apoptosis were significantly upregulated in HSPCs from mice that developed CRS. Endothelial protein C receptor (EPCR)-negative HSCs, a subset of HSCs that is poised for terminal differentiation, was found to be specifically decreased in mice that were treated with CAR T cells. Furthermore, HSPCs were found to have increased levels of apoptosis upon treatment with mIFN-γ and mIL-6, whereas short-term HSCs and multipotent progenitors exhibited increases in proliferation with mIFN-γ treatment alone. The results from this study provide evidence that the elevation of proinflammatory cytokines following CAR-T therapy impacts the bone marrow through a combined mechanism: pluripotent HSCs that are exposed to elevated levels of IFN-γ and IL-6 undergo increased cell death, while more committed progenitor cells become more proliferative in response to elevated IFN-γ. These combined effects lead to depleted stores of repopulating HSCs and ultimately cytopenias. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Selective forwarding attack detection and network recovery mechanism based on cloud-edge cooperation in software-defined wireless sensor network

A software-defined wireless sensor network can dynamically configure the nodes in a network according to the demand of the application layer. In practical applications, such as environmental monitoring, the nodes in a wireless sensor network(WSN) are deployed in the field environment on a large scale, and the data rely on multihop transmission to reach the sink node. The data extremely easy to selective forwarding attacks during data transmission. Therefore, this study analyzes the models of selective forwarding attacks and proposes an abnormal node detection method, which includes a node behavior measurement scheme and trust-value evaluation mechanism. In addition, the application of a software-defined network (SDN) presents increasing network delay. Hence, herein a network recovery mechanism was designed based on cloud-edge cooperation to ensure the rapid recovery of the network after identifying the abnormal nodes. Moreover, experiments were conducted using simulation software and actual hardware. We verified the effectiveness of the proposed scheme. The experimental results revealed that the proposed method can effectively identify abnormal nodes, reduce the packet dropping ratio and shorten the network recovery delay by 77.2%. The research in this paper solves the security problem of SDWSN.

Comparison among complications of common intravenous anesthetic drugs during general anesthesia for patients undergoing surgery in Sulaimani city

Background: A portion of patients exhibit subsequent cognitive impairment, including memory deficits, after undergoing anesthesia. Despite the wide use and long history of anesthesia, the mechanisms of action that cause loss of consciousness and some of the side-effects, such as temporary amnesia, are not understood. Methodology: A descriptive cross-sectional study was conducted among patients undergoing surgery in Sulaimani city, and involved 368 patients. Data, in form of questionnaire, have been collected between October 15, 2021 to February 15, 2022. (SPSS) Version 22 was used to analyzed the data. Results: In this study, 185 (50.3%) were males and 183 (49%) were females, respiratory problem in the form of apnea found in (30.3%) of patients who received (propofol, fentanyl, atracurium) compared to (6.4%) of those patients who received (propofol, (ketamine and fentanyl), atracurium) this difference was significant (P-value < 0.001), (30.3%) of patients who received (propofol, fentanyl, atracurium) (5.4%) of patients who received (thiopental, fentanyl, atracurium) and p value (< 0.001). (28.7 %) of patients who received (propofol, fentanyl, atracurium) recovered late compared to (2.3 %) of patients who received (propofol, (ketamine and fentanyl), atracurium) the difference was significant (P-value < 0.001). systolic blood pressure dropped to below 120 mmhg in (64%) patients and diastolic blood pressure dropped to below 80 mmhg in (62.8%) of patients, who received (propofol, (ketamine and fentanyl), atracurium) and compared to systolic blood pressure that dropped to below 120 mmhg in (74.3%) of patients (74.3%) of patients and diastolic blood pressure dropped to below 80 mmhg in (74.3%) of patients who received (Thiopental, fentanyl, atracurium), the differences were significant (P-value < 0.001). Finally, SpO2 level of (24.3%) of patients, who received (Propofol, (ketamine and fentanyl), atracurium), dropped to below 95% while the SpO2 level of (8.2 %) of patients who received (propofol, fentanyl, atracurium), dropped to below 95% whereas the SpO2 level of (74.3%) of patients, who received (Thiopental, fentanyl, atracurium), dropped to below 95%, these differences were significant with (P-value < 0.001). Conclusion: this study concluded that (propofol, fentanyl, atracurium) can cause respiratory problem in the form of apnea and delay recovery more than the other two sets of anesthetic drugs, while (Thiopental, fentanyl, atracurium) have effect on lowering SpO2 level more than the others sets of anesthetic drugs.

Case report of pyoderma gangrenosum in association with orthopaedic trauma

&lt;p&gt;Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis characterized by painful skin ulcers. It is associated with various systemic diseases but is rarely associated with orthopedic conditions. We report a case of a pyogenic gangrenosum in a 40-year-old male, that occurred in association with a lower limb fracture. This patient suffered a laceration over the ankle which was the sutured initially and the fracture was managed conservatively. Later on the wound was complicated with the development of pyoderma gangrenosum. Failure to treat with antibiotics and local wound management lead to alternative diagnosis by dermatologist. Patient was successfully managed by dermatologist and fracture was managed conservatively. Such incidents of PG in association with orthopedic procedures, complicate treatment and cause delay in recovery, leading to poor patient outcome.&lt;/p&gt;

The Associations between Remission Status, Discounting Rates, and Recovery from Substance Use Disorders

Background: Recovery from substance use disorders (SUDs) requires sustained and purposeful support to maintain long-term remission. Methods: This study investigated the association between assessment of recovery capital, household chaos, delay discounting (DD) and probability discounting (PD), and remission status among individuals in recovery from SUD. Data from 281 participants from the International Quit & Recovery Registry (IQRR), an ongoing online registry that aims to study the recovery process, were included in the analysis. Results: Lower DD rates and higher recovery capital were found among those in remission compared to those not in remission after controlling for demographics. In contrast, the association of household chaos and PD with remission status were insignificant. Overall, DD accounted for 20% of the total effect between the recovery capital and the remission status. Conclusion: This study contributes to the understanding of recovery as a multidimensional process, supports DD as a behavioral marker of addiction, and suggests areas for future research.

β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity.

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient's condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.

Utilities' Need for Advanced Telecommunications

There have been an increasing number of extreme weather events worldwide over the past decade. Events previously referred to as occurring “once every 50 years” now occur more frequently and have resulted in significant loss of life and property and infrastructure damage. As these climate events become even more frequent, utilities—due to their role underpinning all economic activity—must find new ways to upgrade their infrastructure to avoid extended recovery times and delays in restoring power to customers. An important investment to speed recovery and support management of assets during severe weather events is a resilient, reliable, and secure communications network. This is the backbone of utility infrastructure. During extreme weather events, utility telecommunications infrastructure is put to the test as commercial cellular providers become unable to provide service due to electric grid outages. If utilities are using legacy technologies in conjunction with reliance on commercial communications providers, they could be without a telecommunications network when they need it most.

Recovery from persistent nutrient-N limitation following the Permian–Triassic mass extinction

Global warming, widespread oceanic anoxia and stagnation, and large perturbations of the global carbon cycle characterized the end-Permian to Middle Triassic interval. Nitrogen isotopes of marine sediments (δ15Nbulk) decreased through the Permian–Triassic transition, implying development of nitrate-limited and ammonium-dominated conditions (i.e., anaerobic marine N cycle) in Early Triassic oceans, which may have contributed to the delay in marine biotic recovery following the end-Permian mass extinction. However, the temporal evolution of the nitrogen cycle and the role of nutrient supply in marine ecosystem recovery during this interval remain poorly understand. Here, we present a new high-resolution Permian–Triassic nitrogen isotope curve from the Nanpanjiang Basin of South China. Low δ15N (−2‰ to +2‰) during the Griesbachian-to-Smithian substages (i.e., first ∼2 Myr of Early Triassic) reflects enhanced nitrogen fixation concurrently with climatic hyperwarming and expansion of oceanic anoxia. A large rise in δ15N (to +8‰) followed by a decline (to −2‰) reflects an aborted recovery of the marine N cycle during the Spathian substage of the Early Triassic. During the Middle Triassic, δ15N fluctuations between +1‰ and +4‰ during the Anisian Stage, followed by stabilization around +4‰ in the Ladinian Stage, suggest a slow stepwise re-establishment of the aerobic marine N cycle. Although both South China and northwestern Pangea experienced a transition to anaerobic N cycling during the Early Triassic, South China experienced an earlier and more rapid onset of this event as well as larger N-cycle fluctuations during the recovery interval than northwestern Pangea. Overall, N cycle changes coincided with those in paleotemperature and ocean-redox state, demonstrating an integrated response of the marine system to the extreme environmental perturbations of the Early Triassic. In summary, our results support persistence of nutrient-N-limited conditions and strong microbial N-fixation throughout the Early Triassic, with a full return to the aerobic N cycle only after stabilization of oceanic environmental conditions during the Middle Triassic.

Anaesthetic efficacy and influence on cardiovascular parameters change of intraosseous computerised anaesthesia versus inferior alveolar nerve block anaesthesia in acute irreversible pulpitis of mandibular molars: study protocol for a prospective randomised controlled trial

BackgroundIrreversible pulpitis is a highly painful inflammatory condition of the dental pulp. The recommended care is the removal of the coronal pulp (pulpotomy) for emergency treatment in multi-rooted teeth. However, achieving adequate analgesia in the case of mandibular molars presents many difficulties according to the dental literature. Intraosseous computerised anaesthesia (ICA), in particular, the QuickSleeper™ system, has already been demonstrated to be clinically efficient, but ICA is known to increase the heart rate reversibly in a manner that depends on the speed of injection. Therefore, accelerated heart rate was examined as a potential adverse effect of this injection. This trial aims to compare the cardiovascular effects and the anaesthetic efficacy of ICA versus inferior alveolar nerve block anaesthesia (IANB) in acute irreversible pulpitis of mandibular molars.MethodsThis study is a non-inferiority prospective, randomised, controlled, single-blind, two-group trial conducted at the Nantes University Hospital. The study design included two parallel arms at a ratio of 1:1 that will allocate seventy-two patients into two groups: the first group will receive QuickSleeper™ intraosseous anaesthesia; the second will receive an inferior alveolar nerve block before emergency treatment (pulpotomy). This study will include patients requiring emergency dental care under local anaesthesia with confirmed irreversible pulpitis in mandibular molars. The primary outcome is the time taken for the fluctuations in the cardiovascular parameters to return to baseline values during endodontic treatment in two different anaesthetic techniques. The secondary outcomes include efficacy of the technique, patient’s pain perception before and after care, any post-operative effects, and factors associated with the delay of recovery of cardiovascular parameters between the 2 anaesthetic techniques.DiscussionThis trial will evaluate the factors associated with heart rate increase during local anaesthesia administration. The use of blood pressure and cardiovascular measurements can be considered an asset and additional safety in managing local anaesthesia. Detecting early signs of potential adverse events (AEs), particularly patients with certain medical conditions (cardiac rhythm disorders), would suggest caution in administering anaesthesia.Trial registrationClinicalTrials.gov ID: NCT03802305 registered January 14, 2019. (version no. 1.2; 5 November 2021)

An in-hospital relapse case of an elderly COVID-19 patient on steroids

During a pandemic like the novel coronavirus infection 2019 (COVID-19), the availability of inpatient beds is always a major issue. Thus, it is extremely important to release patients from isolation efficiently in order to maintain stable bed operations. However, in clinical practice, patients may develop fever again, before or after the timing specified by the Ministry of Health, Labor and Welfare (MHLW) for lifting isolation, and hence it may be difficult to determine whether the fever is due to a delay in recovery or due to relapse. The diagnosis of relapse is based primarily on the recurrence of symptoms consistent with COVID-19 and a positive PCR result, but few reports have focused on comparing the patterns of variation in two or more blood test findings over the course of the disease. In the present study, we study a case of relapse in an elderly patient on immunosuppressive drugs. Understanding the unique patterns of variability between baseline blood test values and acute infection test values in each individual patient may serve as an adjunctive tool to help diagnose COVID-19 relapse.

LESÃO DE FADIGA CAUSADA POR EXERCÍCIO SOB RESISTÊNCIA ESPORTIVA

ABSTRACT Introduction Athletes are prone to local muscle fatigue due to high-intensity training and to long-term accumulation of musculoskeletal injuries. Musculoskeletal complications represent a large proportion of occupational health problems and, for this reason, have received increased attention from the sports industry. In this sense, studies on muscle fatigue should be intensified. Objective Verify muscle fatigue and injury involving the strain characteristics of lower limb joints in the eccentric and centripetal contraction of the jump. Methods A total of 691 individuals aged 20 to 40 years were selected. Fatigue was caused by active muscle contraction. The characteristic curves of active muscle contraction in different isometric, isotonic, and isokinetic training were analyzed. The degree of fatigue caused by three different sports states was tested by experimentation. The corresponding active muscle contraction characteristics were also analyzed. The potential for homeostasis at different ages was compared. Results The delay in recovery to fatigue is directly proportional to the athlete’s age. The return to post-exercise relief proportion from fatigue gradually decreases. Conclusion The experimental results showed that active muscle contraction could reduce exercise fatigue to some extent. This beneficial biochemical property of active muscle contraction is not found in people with advanced age. The findings have a guiding potential for the relief of sports fatigue. Evidence Level II; Therapeutic Studies - Investigating the result.

Co-infection dynamics of two short term diseases with effect of recovery delay

A co-infection model with two short-term diseases with delay in recovery is proposed. Here, we consider the simultaneous transmission of infection does not happen but of simultaneous recovery from both illnesses. The system consists of four epidemiological classes populations, namely: susceptible (\(S\)), an infected class with the first disease (\(I_1\)), an infected class with the second disease (\(I_2\)), co-infected class (\(I_{12}\)). We have found all possible equilibrium states, and the basic reproduction number also examined their stability without and with delay. Analytically, we have established that the local stability of equilibrium points depends on the basic reproduction number in the absence of recovery delay. But with delay, it requires some additional conditions. We have also checked the effect of delay on stability of endemic steady state numerically and showed that beyond a critical threshold value of delay parameter, the system loses its stability, and Hopf bifurcation occurs. Finally, a numerical simulation presented supports the analytical findings.

Physiological recovery of tree water relations upon drought release-response of mature beech and spruce after five years of recurrent summer drought.

As climate change progresses, the frequency and duration of drought stress events are increasing. While the mechanisms of drought acclimation of trees has received considerable attention in recent years, the recovery processes remain critically understudied. We used a unique throughfall exclusion experiment in a mature temperate mixed forest consisting of the more isohydric Norway spruce and more anisohydric European beech, to study the recovery and resilience after drought release. We hypothesized that pre-dawn water potential (ΨPD) of both species will increase within 1 day after watering, while the recovery of stomatal conductance (gs) and the reversal of osmoregulation will be significantly delayed in the more isohydric spruce. Furthermore, we hypothesized that the xylem sap flow density (udaily) will not fully recover within the growing season due to the strong drought impact. After 5 years of summer drought, trees showed significantly reduced ΨPD, udaily and increased osmoregulation in leaves, but only isohydric spruce displayed increased leaf abscisic acid concentrations. In line with our hypothesis, ΨPD and gs recovered within 1 day in beech. Conversely, isohydric spruce showed delayed increases in ΨPD and gs. The delay in recovery of spruce was partially related to the replenishment of the stem water reservoir, as indicated by the missing response of udaily at the crown base compared with DBH level upon watering. However, udaily fully recovered only in the next growing season for beech and was still reduced in spruce. Nevertheless, in both species, osmotic acclimations of leaves were reversed within several weeks. While both species displayed full resilience to drought stress in water-related physiology, the recovery time was in several cases, e.g., udaily, ΨPD and gs, shorter for beech than for spruce. With future increases in the frequency of drought events under ongoing climate change, tree species that recover more quickly will be favored.

Physical Insights on Current Dynamics of RESURF DeMOS Designed for High-Frequency CMOS Level Shifter Application

This work investigates isothermal high-current dynamics of Drain-extended MOS (DeMOS) devices optimized for high-frequency switching applications. Gate charge optimized reduced-surface-field (RESURF) DeNMOS structures using surface-implant (P-Top) and split-gate (SG_NonSTI) have been compared with conventional DeNMOS (C_DeNMOS) to investigate the dynamics of parasitic BJT trigger and subsequent space charge modulation (SCM) under high current conditions. Comparative AC analysis at a different gate and drain bias shows quasi-saturation peaks responsible for space charge modulation under high current conditions in DeMOS devices. The transient analysis investigates the isothermal unclamped inductive switching (UIS) and reverse recovery behavior. The parasitic gate capacitances Cgg and Cgd are reduced in both P-Top and SG_NonSTI. With the lowest turn-off delay under very high current conditions in UIS simulations, SG_NonSTI shows the best switching reliability, while P-Top shows the best reverse recovery and transient switching delay performance. In addition, we have shown the application of proposed DeNMOS devices in designing a high-frequency CMOS level shifter circuit. Compared to C_DeNMOS, the highest operating frequency has increased for P-Top and SG_NonSTI DeNMOS structures by 40% and 35%, respectively.

High Response and Prolonged Treatment-Free Remission after a Short-Course of Modified Intensive Chemotherapy and Venetoclax in Elderly AML: An Updated Analysis of the Caveat Trial

Background Venetoclax (VEN) plus azacitidine has an established role in the management of older patients (pts) with AML (DiNardo, NEJM 2020). To explore the feasibility of intensive chemotherapy combined with VEN in older pts with newly diagnosed AML, we conducted the CAVEAT trial (Chua et al, JCO 2020). We now present an updated analysis of this trial (with >3 years median follow-up), reporting on the optimal dose of VEN with chemotherapy, with and without posaconazole (POSA), the deliverability of consolidation therapy, characteristics of treatment failure and observation of substantial treatment-free remission in subsets of pts using this time-limited, short-course regimen. Methods The CAVEAT study enrolled pts aged ≥65 years with de novo or secondary/therapy-related AML (sAML) considered suitable for intensive chemotherapy. Five VEN dose escalation cohorts (50-100-200-400-600 mg) were explored initially. Two additional cohorts examined the safety of adjusted dosing of VEN (50 or 100 mg) during anti-fungal prophylaxis with the strong CYP3A4 inhibitor POSA. For induction, VEN was administered over 14 days, commencing with a 7-day pre-chemo dose ramp-up, followed by a 7-day overlap with 5+2 chemotherapy (cytarabine 100mg/m2/d IVI d1-5 and idarubicin 12mg/m2 IV d2-3). Consolidation (CONS) with 2+1 chemotherapy (below), followed by up to 7 cycles of VEN monotherapy maintenance was planned. Results Data cut-off: 31MAR2022. A total of 69 pts are included in this analysis (first pt 17JUL2016, last pt 15MAY2020). Median age was 71 years (range 63-80). Poor risk features included sAML (42%), adverse karyotype (28%) and prior HMA (23%). From the dose escalation phase, the VEN 600 mg cohort was well tolerated (30-day mortality 6%). Induction with VEN-POSA (n=18) was also well tolerated (30-day mortality 0%) with 3 DLTs observed: 2 hematologic (1 in each cohort) and 1 due to pulmonary infiltrates occurring on d2 induction (suspected to be allopurinol hypersensitivity). No clinical TLS was observed. Although hematologic recovery was satisfactory after VEN-POSA induction, recovery was considerably longer in the VEN (100mg)-POSA cohort after CONS1 compared to VEN (50mg)-POSA for both neutrophils (median 64 vs 44d to 0.5 x109/L) and platelets (median not reached vs 26d to 50 x109/L). Therefore, if POSA is used concurrently, VEN 50 mg is recommended. Alternatively, if VEN 600 mg is used, POSA should commence only after completion of VEN. In the VEN 600 mg cohort, significant delays in hematological recovery were also observed after multiple rounds of attenuated CONS (VEN d1-14, bolus doses of cytarabine 100 mg/m2 d1-2, idarubicin 12 mg/m2 on d1), limiting deliverability (median CONS cycles 1; range 1-3). By intention-to-treat, the overall response (CR/CRi) rate was 73%. CR/CRi was 90% in de novo AML (vs 51% in sAML), 84% in intermediate karyotype (vs 69% in adverse), 76% and 83% in NPM1 and IDH2 mutant AML, respectively. With a median follow-up of 37 months (m), the median overall survival (OS) was 15.4m. Median OS was 31.3m in de novo AML (40% alive at 36m) and 30.3m in intermediate karyotype AML (38% alive at 36m). In the VEN 600 mg cohort, median OS was 24.1m (36% alive at 36m). As CAVEAT delivered just one intensive cycle of therapy, followed by limited post remission therapy (median time on therapy 7.7m), we next assessed the duration of treatment-free remission (TFR) among responders. Among pts achieving CR/CRi, 20/51 (39%) experienced TFR (Fig 1). The median TFR was 22.1m (range 4.6-48.3m). At data cut-off, 12 (24%) have ongoing TFR. Notably, 15/20 (75%) with TFR had an NPM1 or IDH2 mutation at diagnosis. 11 out of 14 evaluable pts with NPM1 mutation had mutation clearance by RT-qPCR, including 3 with NPM1 negative disease at time of failure (1 refractory, 2 relapse). Two pts with persistently mutated NPM1 at relapse had a concomitant FLT3-ITD or KIT mutation. The mutation landscape at relapse is shown (Fig 1) Conclusion VEN combined with modified intensive chemotherapy achieved high response rates in older pts with newly diagnosed AML. With long-term follow-up, the time-limited CAVEAT schedule enabled pts, especially with mutated NPM1 or IDH2, to experience a durable treatment-free remission. Cumulative hematological toxicity is limiting, prompting us to now explore non-anthracycline CONS (low dose cytarabine 20mg/m2 SC d1-10 + VEN 400mg d1-7, for up to 4 cycles), followed by VEN monotherapy (400mg D1-14 q28d cycle x7). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 13604: Sodium-Glucose-Cotransporter-2 Inhibitor (SGLT2i) Exposure in the Immediate Post-Acute Kidney Injury Period in Patients Hospitalized With Acute Heart Failure is Associated With Improved Outcomes

Introduction: Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) use during or immediately following Acute Heart Failure (AHF) exacerbation has shown clinical benefit including improved symptoms, lower frequencies of re-hospitalization for heart failure and death. However, effects of SGLT2i use immediately following acute kidney injury (AKI) on mortality and renal recovery in this setting are unknown. Hypothesis: Among patients admitted with AHF who sustain in-hospital AKI, exposure to SGLT2i in the immediate post-AKI period would be associated with better outcomes. Methods: Adult patients admitted across 5 hospitals between January, 2020 and April, 2022 with acute heart failure (NT-pro-BNP &gt;500ng/L and receipt of IV diuretic within 24 hours of admission) and KDIGO-defined AKI during hospitalization were included. Advanced CKD (eGFR ≤15 ml/min/1.72m2) and those prescribed SGLT2i &gt; 10 days after AKI were excluded. AKI recovery and death were compared between the exposed and unexposed cohorts using a time-varying Cox-regression analysis after adjusting for potential confounders. Results: In this retrospective cohort of 3599 individuals admitted with AHF that developed AKI during hospitalization, 293 patients received SGLT2i within the 10 days post-AKI. The median (IQR) time to AKI after admission was 24 (1.41-64.48) hours. 36.52% of the SGLT2i exposed had renal recovery pre-SGLT2i exposure. For the SGLT2i-exposed (pre-renal recovery) vs. unexposed groups, rates of 14-day renal recovery were not significantly different (adj. HR 0.99, 95% CI 0.82-1.19, p=0.90). However, the post-AKI SGLT2i-exposed group had a lower risk of death at 30 days (adj. HR 0.39, 95% CI 0.19-0.79, p=0.009) after adjustment for potential confounders. Conclusion: In a retrospective cohort of patients hospitalized with AHF with in-hospital AKI, exposure to SGLT2i within 10 days post-AKI was associated with decreased mortality and no significant delay in renal recovery.

Superficial Parasternal Intercostal Plane Blocks (SPIB) With Buprenorphine, Magnesium, and Bupivacaine for Management of Pain in Coronary Artery Bypass Grafting.

Introduction Management of post-operative pain after cardiac surgery continues to be a challenge; inadequate management of pain can lead to increased morbidity, impaired physical function with potential delay in recovery, increased perioperative and chronic opioid consumption, increased cost of care, and a decreased quality of life. This study aimed to evaluate the effect of adding buprenorphine and magnesium to bupivacaine for superficial parasternal intercostal plane blocks (SPIB) on pain and opioid consumption in the first 24 hours after coronary artery bypass grafting (CABG). Methods Patients undergoing CABG were divided into the following four groups: saline SPIB, SPIB with bupivacaine (BPVC), SPIB with bupivacaine and buprenorphine (BPVC+BPRN), and SPIB with bupivacaine, buprenorphine, and magnesium (BPVC+BPRN+MG).The primary outcomes were pain scores and opioid consumption after SPIB; the secondary outcomes were post-operative nausea and vomiting, time to extubation, and length of stay (LOS) in the intensive care unit and hospital. Results One hundred thirty-four eligible patients undergoing CABG were randomized to either the saline (n=27), BPVC (n=20), BPVC+BPRN (n=24), or BPVC+BPRN+MG (n=29) group. All of the intervention groups combined (BPVC, BPVC+BPRN, and BPVC+BPRN+MG) had decreased pain scores and decreased opioid consumption when compared to the saline group; although not statistically significant, visual analog scale (VAS) scores trended downward at most time points with BPVC versus saline, BPVC+BPRN versus BPVC, and BPVC+BPRN+MG versus BPVC+BPRN. There was no difference among the study groups in the incidence of post-operative nausea and/or vomiting (PONV), time to extubation, hospital LOS, and ICU LOS. Conclusion In this prospective, double-blind, placebo-controlled trial, we found that SPIB with local anesthetic is effective at reducing VAS scores and opioid consumption after CABG. Further study is needed to determine whether the addition of adjuvants can further improve pain control and opioid consumption.

Factors Associated with Heart Rate Recovery in People with Chronic Obstructive Pulmonary Disease: An Analytical Cross-Sectional Study

Introduction: Heart rate recovery (HRR) delay is a marker of cardiac autonomic dysfunction. In people with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation programs, assessing HRR could have prognostic utility, yielding valuable information for setting treatment goals and targets in therapeutic interventions. Therefore, this study aimed to establish the sociodemographic, pulmonary function, and functional aerobic capacity differences in people with COPD with normal and abnormal HRR during the 6-minute walk test (6MWT) and explore factors associated with abnormal HRR. Method: Analytical cross-sectional study. Sociodemographic, anthropometric characteristics, pulmonary function, aerobic capacity, BODE index, and Hospital Anxiety and Depression Scale (HADS) were assessed in COPD patients. An HRR cut-off point of 14 beats or more was used to define HRR delay. Results: Of 128 patients included, 89 (69.5%) showed abnormal HRR. Patients with abnormal HRR were classified with higher overweight/obesity, lower resting SpO2 and lower distance walked, predicted percentage, and estimated VO2 in the 6MWT, with more significant symptoms at one minute after the end of the test (dyspnea and fatigue). In the multivariate regression model adjusted for age, sex, resting heart rate, and FEV1, findings showed that distance walked in the 6MWT (OR 0.994, p-value=0.010), fatigue at 1 minute (OR 2.12, p-value=0.000), and HADS depression domain (OR 0.87, p-value=0.018) are factors associated with HRR. Conclution: In outpatients with COPD, HRR relates to the distance walked in the 6MWT, fatigue, and depression measured with the HADS.

Effect of early morning awakening in major depressive disorder

Patients with the major depressive disorder usually manifest with sleep disturbance. Early morning awakening is more closely related to major depressive disorder than other sleep disturbances. This study aimed to assess the effect of early morning awakening in treating patients with major depressive disorder. The eligible patients were divided into two groups according to whether they woke up at 2-4 a.m: early morning awakening and non-early morning awakening group. All patients were assessed using the Hamilton Depression Scale, Hamilton Anxiety Scale, and Repeatable Battery for the Assessment of Neuropsychological Status scores at baseline and the fourth week. Twenty-one men and 31 women (mean age 25.13 ±10.67 years) were enrolled. There was a significant main effect of early morning awakening in the Hamilton Depression Scale (P = 0.04) and Hamilton Anxiety Scale (P = 0.01) at the fourth week after treatment. But there was no significant difference in cognitive changes between the two groups. In conclusion, a major depressive disorder with early morning awakening may result in statistically and clinically significant delay in recovery.