Search Results (106)

Background/Objectives: Perioperative hypotension during kidney transplantation poses a risk to graft function and survival. Angiotensin II (AngII) is an endogenous vasoconstrictor targeting the renin–angiotensin–aldosterone system (RAAS) to increase blood pressure. Black patients may have a different response to synthetic angiotensin II (AT2S) compared to non-Black patients, given differential expressions in renin profiles. The purpose of this study is to assess the difference between Black and non-Black patients in total vasopressor duration and usage when AT2S is first line for hypotension during kidney transplantation. Methods: A single-center, retrospective cohort study comparing Black and non-Black patients who required AT2S as a first-line vasopressor for hypotension during the perioperative period of kidney transplantation. Results: The primary outcome evaluating total usage of vasopressors found that Black patients required longer durations of vasopressors (36.9 ± 66.8 h vs. 23.7 ± 31.7 h; p = 0.022) but no difference in vasopressor amount (0.07 ± 0.1 NEE vs. 0.05 ± 0.1 NEE; p = 0.128) compared to non-Black patients. Regression analysis found that body weight was associated with the duration of vasopressors (p < 0.05), while baseline systolic blood pressure was inversely associated with it. Longer duration of vasopressors and duration of transplant surgery were associated with delayed graft function in regression analysis (p < 0.05). Conclusions: Black patients had a longer duration of vasopressors, but this was not driven by differences in usage of AT2S. As baseline weight was significantly higher in Black patients and associated with duration of usage, perhaps the metabolic differences in our Black patients led to the observed differences. Regardless, longer durations of vasopressors were associated with delayed graft function, making this an area of utmost importance for continued investigation. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

The use of temporary mechanical circulatory support in refractory heart failure cardiogenic shock (HFCS) has risen, leading to potential complications. Post-Cardiac Injury Syndrome (PCIS) from Impella insertion is rare but may result from subclavian artery manipulation and aortic irritation. We report the first case of pericarditis (PCIS) caused by Impella 5.5 insertion in an HFCS patient awaiting heart transplantation. The patient developed chest pain, tachycardia, and hypotension post-Impella insertion. Laboratory results and electrocardiograms confirmed PCIS. Treatment with Ibuprofen and Colchicine was successful. He received a heart transplant 14 days later. This case emphasizes recognizing iatrogenic pericarditis after Impella insertion and the need to avoid additional myocardial strain. Full article

Background/Objectives: Plexiform neurofibromas (pNFs) are one of the cardinal presentations of NF1 patients, often arising during early childhood. Since selumetinib was approved by the FDA in 2020, the long-term side effects and various responses of mitogen-activated protein kinase inhibitors (MEKi) in pediatric patients necessitate a new strategy. We propose that combining selumetinib with heat shock protein 90 inhibitors (HSP90i) can enhance the inhibitory effects as well as reduce the dosage of selumetinib in combination. We validated the synergistic effects and the significantly improved treatment effects of the combination of selumetinib and HSP90i in pNFs. Methods: We used drug screen data mining to predict the combination of selumetinib and HSP90i. Using cell lines and in vivo mouse models for pNFs, we tested a series of combinations with different concentrations. We validated the in vivo inhibitory effects using the transplanted tumors from DhhCreNf1^f/f mouse models. Results: We demonstrated that combining selumetinib and SNX-2112 or retaspimycin can achieve better tumor inhibition with synergistic effects. The combination significantly delays the progression of mouse pNFs. Conclusions: The combination of selumetinib and HSP90i has significant synergistic effects, provides therapeutic inhibitor effects, and reduces the selumetinib dosage in combination. Full article

Heart failure is a heterogeneous disorder that can lead to cardiogenic shock. Mechanical circulatory support (MCS) devices can replace the cardiac function in an attempt to bridge patients to transplant or they can serve as destination therapy to improve overall patient functionality and in turn quality of life. Currently utilized MCS devices include devices such as Left Ventricular Assist Devices (LVADs), Biventricular Assist Devices (BiVADs), Impella, Total Artificial Hearts (TAHs), and extracorporeal membrane oxygenation (ECMO). This literature review examines a range of studies, case reports, and meta-analyses to present current approaches to mechanical circulatory support (MCS), along with the challenges and limitations of existing devices, common complications, and overall survival and long-term outcomes following MCS therapy. Full article

Background/Objectives: The use of angiotensin II (AT2S) as a vasopressor in patients receiving angiotensin receptor blockers (ARBs) prior to kidney transplant (KT) raises theoretical concerns. At our center, AT2S is the first-line vasopressor during KT. This study evaluated the hemodynamic and clinical effects of pre-transplant ARBs on AT2S use in KT. Methods: This single-center, retrospective cohort trial included patients with hypertension ≥ 18 years old on antihypertensive therapy who received AT2S as the first-line vasopressor peri-transplant. Patients were divided into ARB and non-ARB cohorts. Primary outcomes included total AT2S duration, time with SBP < 120 mmHg, and need for additional vasopressor support. Results: A total of 65 patients were analyzed: 22 in the ARB group and 43 in the non-ARB group. There were no significant differences in the frequency or duration of SBP < 120 mmHg or additional vasopressor requirements between groups (p > 0.05). Hospital and ICU stay length, safety, and adverse drug events were also similar. Conclusions: Contrary to theoretical concerns and observations in other distributive shock populations, no significant hemodynamic or clinical differences were observed in the response to AT2S in patients with pre-transplant ARB use. Full article

Percutaneous ventricular assist devices are utilized in cases of cardiogenic shock following acute myocardial infarction (AMI). However, the mechanism underlying the beneficial effects of LV unloading in AMI remains unclear. This study aimed to examine the impact of LV unloading on cardiac function, heart failure markers, and protein degradation (autophagy and ubiquitin–proteasome system: UPS) post AMI in rats. Nine-week-old male Lewis rats were randomized into non-AMI, AMI, non-AMI with LV unloading, and AMI with LV unloading groups. LV unloading was achieved through heterotopic heart–lung transplantation. Rats were euthanized 2 and 14 days after the procedure. Cardiac functional assessment was performed using Langendorff heart perfusion. RT-PCR and Western blot analyses were conducted using the LV myocardium. The rate pressure product was comparable between the non-AMI with LV unloading group and the AMI with LV unloading at 14 days. The atrial natriuretic factor tended to be suppressed by LV unloading. LV unloading had reducing effects on the expressions of p62, selectively degraded during autophagy, both 2 and 14 days after AMI. There was no effect on the parameters for the UPS. LV unloading has a mitigating effect on the deterioration of cardiac function following AMI. Autophagy, which was suppressed by AMI, was ameliorated by LV unloading. Full article

Background: The optimal duration of antibiotic treatment for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) bloodstream infections (BSI) in intensive care unit (ICU) is not established. We aim to evaluate the frequency and clinical outcomesof a short appropriate antibiotic treatment (≤7 days) (SAT) for ESBL-E BSI acquired in the ICU. We specifically assessed the rate of ESBL-E BSI relapse, and in-ICU mortality. Method: All patients who acquired ESBL-E BSI in three ICU in Northern France between January 2011 and June 2022 were included in a multicenter retrospective cohort study. The factors associated with prescribing short (SAT, ≤7 days) versus long (LAT, >7 days) antibiotic treatment were analyzed. To evaluate the impact of SAT on mortality in the ICU, an estimation was applied using a Cox model with a time-dependent co-variable adjusted by inverse weighting of the propensity score. Results: In total, 379 patients were included. The proportion of patients receiving a SAT was 40% in the entire cohort and 25% in survivors beyond 7 days. In bivariate analysis, the factors associated with prescribing a SAT in survivors were shorter pre-bacteremia ICU stay (p = 0.005), lower proportion of chronic renal failure history (p = 0.034), cancer (p = 0.042), or transplantation (p = 0.025), less frequent exposure to carbapenem within 3 months (p = 0.015). There was a higher proportion of septic shock (p = 0.017) or bacteremia secondary to pneumonia (p = 0.003) in the group of survivors receiving a LAT. After adjustment, no difference in survival was found between the two groups (HR: 1.65, 95%CI: 0.91–3.00, p = 0.10). Conclusion: In our cohort, one quarter of patients with ESBL-E bacteremia acquired in the ICU surviving beyond 7 days were treated with a SAT. SAT did not appear to affect survival. Patients who could benefit from a SAT need to be better identified. Full article

Background and Clinical Significance: In the clinical management of major pediatric traumatic injuries and other hypoxic conditions, lactate is widely recognized as a key indicator of tissue hypoxia and potential necrosis. However, its prognostic value remains uncertain. Several factors influence post-surgical outcomes, including the time between amputation and replantation, transport conditions, asepsis, the extent of tissue necrosis, hemorrhagic shock, coagulation disorders, and the heightened risk of contamination. Case presentation: We present this case to emphasize the utility of systemic lactate versus lactate levels in the replanted limb for monitoring post-transplantation outcomes in a pediatric patient with traumatic limb amputation. Significant fluctuations in lactate levels within the replanted limb were observed at the onset of unfavorable evolution, specifically on the seventh postoperative day, coinciding with the identification of Aspergillus spp. infection. This necessitated the use of synthetic saphenous vein grafts and Amphotericin B administration. Despite these interventions, disease progression ultimately led to limb amputation. Conclusions: Lactate levels in the replanted limb may serve as an early biomarker for assessing post-surgical evolution. However, further case reports are required to confirm its predictive value. Full article

Transplanting shock induced by mechanical transplanting technique in dry land has a negative effect on the growth and grain yield of rapeseed (Brassica napus L.). We hypothesized that foliar nitrogen (N) supplementation plays a positive role in improving rapeseed transplanting survival rate and yield. The aim of the study was to elucidatethe morphological and physiological mechanisms of foliar N supplementation in rapeseed responding to transplanting shock. Through a 1-year pot experiment and a 2-year field experiment, foliar N supplementation at concentrations of 0, 2.5, 5.0, and 7.5 g N m⁻² was set up to investigate the regulation of foliar N supplementation on the carbon (C) and N structure of seedlings before transplanting. Then we investigated the responses of morphological and physiological changes of shoot, root regeneration ability, transplanting survival rate, and grain yield to transplanting shock. The results showed that foliar N supplementation prior to transplanting increased the short-term activities of GS, GOGAT, and GDH, may improve the conversion of soluble sugar to soluble protein, increased N accumulation, and lowered the C:N ratio of rapeseed seedlings. Rapeseed seedlings with a low C:N ratio showed greater potential for root development after transplanting. Moreover, appropriate foliar N supplementation (2.5–5.0 g N m⁻²) not only up-regulated the positive feedback of osmoregulatory substances and antioxidant system for improving stress resistance, but also enhanced the synergistic growth of shoot and root by increasing root growth potential during transplanting shock. Therefore, the transplanting survival rate increased by 13.81–19.20%, and the grain yield increased by 25.15–30.56%. The optimal foliar N supplementation before transplanting may be used as a simple and effective agricultural measure to alleviate the negative effects of transplanting shock on rapeseed. Full article

Extracorporeal membrane oxygenation (ECMO), an advanced life support method, was developed to treat severe cardiac and pulmonary failure in critically ill patients. ECMO was previously used to treat ARDS, cardiogenic shock, and after heart or lung transplant. It has since become a versatile therapeutic and surgical tool. When conventional methods fail, this technique works well for high-risk procedures such as tracheal resections, ventricular tachycardia ablations, and complicated percutaneous coronary interventions. These uses demonstrate ECMO’s ability to oxygenate and stabilize the hemodynamics in challenging clinical circumstances. Clinical studies report survival rates exceeding 60% in ECMO-assisted thoracic surgeries, underscoring its efficacy in these settings. Recent advancements, such as portable ECMO systems and artificial intelligence-driven management tools, have further enhanced the safety and effectiveness of ECMO, enabling its use in diverse clinical environments. However, challenges remain, particularly in patient selection, resource allocation, and addressing ethical dilemmas. The integration of standardized protocols and technological innovations has mitigated complications such as vascular injury and infection, contributing to improved patient outcomes. This review examines ECMO applications and integration into multidisciplinary care, its configurations, and its growing role outside the intensive care unit in elective thoracic and cardiac surgery, trauma, and non-cardiac high-risk procedures. Full article

Endoscopic management of benign pancreaticobiliary disorders encompasses a range of procedures designed to address complications in gallstone disease, choledocholithiasis, and pancreatic disorders. Acute cholecystitis is typically treated with cholecystectomy or percutaneous drainage (PT-GBD), but for high-risk or future surgical candidates, alternative decompression methods, such as endoscopic transpapillary gallbladder drainage (ETP-GBD), and endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD), are effective. PT-GBD is associated with significant discomfort as well as variable adverse event rates. EUS-GBD leverages lumen-apposing metal stents (LAMS) for direct access to the gallbladder, providing the ability to treat an inflamed GB internally. Choledocholithiasis is primarily managed with ERCP, utilizing techniques to include balloon extraction, mechanical lithotripsy, or advanced methods such as electrohydraulic or laser lithotripsy in cases of complex stones. Altered anatomy from bariatric procedures like Roux-en-Y gastric bypass may necessitate specialized approaches, including balloon-assisted ERCP or EUS-directed transgastric ERCP (EDGE). Post-operative complications, including bile leaks and strictures, are managed endoscopically using sphincterotomy and stenting. Post-liver transplant anastomotic and non-anastomotic strictures often require repeated stent placements or advanced techniques like magnetic compression anastomosis in refractory cases. In chronic pancreatitis (CP), endoscopic approaches aim to relieve pain and address structural complications like pancreatic duct (PD) strictures and calculi. ERCP with sphincterotomy and stenting, along with extracorporeal shock wave lithotripsy (ESWL), achieves effective ductal clearance for PD stones. When traditional approaches are insufficient, direct visualization with peroral pancreatoscopy-assisted lithotripsy is utilized. EUS-guided interventions, such as cystgastrostomy, pancreaticogastrostomy, and celiac plexus blockade, offer alternative therapeutic options for pain management and drainage of peripancreatic fluid collections. EUS plays a diagnostic and therapeutic role in CP, with procedures tailored for high-risk patients or those with complex anatomy. As techniques evolve, endoscopic management provides minimally invasive alternatives for patients with complex benign pancreaticobiliary conditions, offering high clinical success and fewer complications. Full article

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs). Full article

Background/Objectives: Heart failure is the leading cause of hospital admission and mortality. Racial disparities have been demonstrated in various cardiovascular disorders; however, the data for in-hospital outcomes, complications, and procedural rates are limited. Methods: Utilizing the National Inpatient Sample (NIS) database, this retrospective cohort study included adult patients admitted with a principal diagnosis of heart failure. Coding for race and ethnicity in the NIS combines self-reported race and ethnicity provided by the data source into 1 data element (“RACE”). We compared the outcomes between various racial groups, focusing on mortality, the length of stay (LOS), hospital charges, and complications. Differences in the utilization of advanced therapies, including implantable cardiac defibrillators, cardiac resynchronization therapy (CRT), ventricular assist devices (VADs), and heart transplant, were also analyzed. Results: Out of 1,107,860 patients hospitalized with heart failure, 715,345 (64.57%) patients were White, 244,394 (22.06%) patients were Black, and 97,063 (8.31%) patients were Hispanic. Compared to White people, the odds of in-hospital mortality were lower among Black (aOR 0.74; 95% CI 0.68–0.81; p < 0.001) and Hispanic (aOR 0.78; 95% CI 0.69–0.88; p < 0.001) people. Complication rates including cardiogenic shock were found to be significantly lower in Black people (aOR 0.86; 95% CI 0.77–0.96; p < 0.001) and in Hispanic (aOR 0.72; 95% CI 0.63–0.81; p < 0.001) people. The rates of acute respiratory failure were also lower in Black (aOR 0.72; 95% CI 0.69–0.74; p < 0.001) and Hispanic (aOR 0.77; 95% CI 0.73–0.81; p < 0.001) people as opposed to White people. However, Black people were found to have higher rates of acute kidney injury (aOR 1.11; 95% CI 1.07–1.14; p < 0.001) and cardiac arrest (aOR 1.17; 95% CI 1.03–1.34; p = 0.02) compared to White people. Black people were less likely to receive advanced interventions, including cardiac resynchronization therapy (aOR 0.71; 95% CI 0.60–0.83; p < 0001), a ventricular assist device (aOR 0.45; 95% CI 0.34–0.59; p < 0.001), and heart transplants (aOR 0.57; 95% CI 0.42–0.77; p < 0.001), than White people. Hispanic people were found to have lower rates of ventricular assist device (aOR 0.49; 95% CI 0.33–0.72; p < 0.001) use than White people. Conclusions: These findings highlight significant racial disparities in mortality, secondary outcomes, and advanced therapy utilization in heart failure admissions. Further research is needed to identify the root factors for these disparities in order to guide targeted interventions to reduce this racial gap. Full article

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder, often complicated by cardiogenic shock, a life-threatening condition marked by severe cardiac output failure. Managing cardiogenic shock in HCM patients presents unique challenges due to the distinct pathophysiology of the disease, which includes dynamic left ventricular outflow tract obstruction, diastolic dysfunction, and myocardial ischemia. This review discusses current and emerging therapeutic strategies tailored to address the complexities of HCM-associated cardiogenic shock and other diseases with similar pathophysiology that provoke left ventricular outflow tract obstruction. We explore the role of pharmacological interventions, including the use of vasopressors and inotropes, which are crucial in stabilizing hemodynamics but require careful selection to avoid exacerbating the outflow obstruction. Additionally, the review highlights advancements in mechanical circulatory support devices such as extracorporeal membrane oxygenation (ECMO) and left ventricular assist devices (LVADs), which have become vital in the acute management of cardiogenic shock. These devices provide temporary support and bridge patients to recovery, definitive therapy, or heart transplantation, which remains a critical option for those with end-stage disease. Furthermore, the review delves into the latest research and clinical trials that are refining these therapeutic approaches, ensuring they are optimized for HCM patients. The impact of these treatments on patient outcomes, including survival rates and quality of life, is also critically assessed. In conclusion, this review underscores the importance of a tailored therapeutic approach in managing cardiogenic shock in HCM patients, integrating pharmacological and mechanical support strategies to improve outcomes in this high-risk population. Full article