Impact of histone deacetylase inhibition and arimoclomol on heat shock protein expression and disease biomarkers in primary culture models of familial ALS.

Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including motor neuron disease, and amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, including the upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have a high threshold for upregulating stress-inducible HSPA1A, but constitutively express high levels of HSPA8. This study compared the expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TAR DNA binding protein 43 kDa (TDP-43)G348C, fused in sarcoma (FUS)R521G, or superoxide dismutase I (SOD1)G93A. All variants were poor inducers of Hspa1a, and reduced levels of Hspa8 mRNA and protein, indicating multiple compromises in chaperoning capacity. To promote HSP expression, cultures were treated with the putative HSP coinducer, arimoclomol, and class I histone deacetylase inhibitors, to promote active chromatin for transcription, and with the combination. Treatments had variable, often different effects on the expression of Hspa1a and Hspa8, depending on the ALS variant expressed, mRNA distribution (somata and dendrites), and biomarker of toxicity measured (histone acetylation, maintaining nuclear TDP-43 and the neuronal Brm/Brg-associated factor chromatin remodeling complex component Brg1, mitochondrial transport, FUS aggregation). Overall, histone deacetylase inhibition alone was effective on more measures than arimoclomol. As in the FUS model, arimoclomol failed to induce HSPA1A or preserve Hspa8 mRNA in the TDP-43 model, despite preserving nuclear TDP-43 and Brg1, indicating neuroprotective properties other than HSP induction. The data speak to the complexity of drug mechanisms against multiple biomarkers of ALS pathogenesis, as well as to the importance of HSPA8 for neuronal proteostasis in both somata and dendrites.

Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

In-hospital outcomes with extracorporeal membrane oxygenation alone versus combined with percutaneous left ventricular assist device.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO) is associated with increased afterload and hindered myocardial recovery. Adding a percutaneous left ventricular assist device (pLVAD) to ECMO is one strategy to unload the left ventricle. We evaluated in-hospital outcomes in cardiogenic shock patients treated with ECMO alone versus ECMO plus pLVAD. METHODS: We conducted a retrospective study using the National Inpatient Sample database from 2011 to 2019. Logistic regression analysis was performed to adjust for covariates. RESULTS: 20,171 patients were included. 16,064 (79.6 %) patients received ECMO alone and 4107 (20.4 %) patients received ECMO plus pLVAD. The ECMO plus pLVAD group had higher rates of mortality, stroke, acute kidney injury, pericardial complications, and vascular complications. After adjusting for covariates, combined therapy was associated with higher rates of mortality (OR 1.2; 95 % CI [1.1-1.3]) and stroke (OR 1.3; 95 % CI [1.2-1.5]), however lower bleeding (OR 0.7; 95 % CI [0.68-0.81]) (p < 0.001 for all). After adjusting for covariates, a subgroup analysis of 5019 patients with acute coronary syndrome cardiogenic shock (ACS-CS) demonstrated higher rates of mortality (OR 1.3; 95 % CI [1.2-1.5]) and stroke (OR 1.7; 95 % CI [1.4-2.1]; p < 0.001 for all) with combined therapy, however similar rates of bleeding compared to ECMO alone (OR 0.95; 95 % CI [0.8-1.1]; p = 0.54). CONCLUSIONS: In the overall group, ECMO plus pLVAD was associated with increased mortality and stroke, however decreased bleeding. In a sub-group of ACS-CS, ECMO plus pLVAD was associated with increased mortality and stroke, however similar rates of bleeding compared to ECMO alone.

A case report of successful rescue using veno-arterial extracorporeal membrane oxygenation: managing cerebral-cardiac syndrome.

Introduction: The presence of cerebral-cardiac syndrome, wherein brain diseases coincide with heart dysfunction, significantly impacts patient prognosis. In severe instances, circulatory failure may ensue, posing a life-threatening scenario necessitating immediate life support measures, particularly effective circulatory support methods. The application of extracorporeal membrane oxygenation (ECMO) is extensively employed as a valuable modality for delivering circulatory and respiratory support in the care of individuals experiencing life-threatening circulatory and respiratory failure. This approach facilitates a critical temporal window for subsequent interventions. Consequently, ECMO has emerged as a potentially effective life support modality for patients experiencing severe circulatory failure in the context of cerebral-cardiac syndrome. However, the existing literature on this field of study remains limited. Case description: In this paper, we present a case study of a patient experiencing a critical cerebral-cardiac syndrome. The individual successfully underwent veno-arterial-ECMO (VA-ECMO) therapy, and the patient not only survived, but also received rehabilitation treatment, demonstrating its efficacy as a life support intervention. Conclusion: VA-ECMO could potentially serve as an efficacious life support modality for individuals experiencing severe circulatory failure attributable to cerebral-cardiac syndrome.

Case Report: A Rare Case of Iodixanol-Induced Anaphylactic Shock in Cerebral Angiography.

Background: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography. Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report. Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment. Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.

Adverse reactions of piperacillin: A literature review of case reports.

Aim: This study aimed to summarize case reports of adverse drug reactions (ADRs) caused by piperacillin and explore their effects on human organs in real-world settings. Method: Case reports of piperacillin ADRs were collected by searching databases such as PubMed, Embase, Web of Science, CNKI, WanFang, and VIP from inception to December 2022. Results: A total of 170 patients were ultimately included. The results revealed that ADRs caused by piperacillin were primarily associated with the entire body, followed by the blood system, skin and soft tissues, and the nervous system. The most frequently reported cases included anaphylactic shock, drug fever, rash, and thrombocytopenia. The most severe ADRs were identified as anaphylactic shock and bullous epidermal necrolysis. Furthermore, a comparison was made between systemic adverse reactions caused by piperacillin as a single drug and two composite preparations of piperacillin/ß-lactamase inhibitor. ADRs not mentioned in the instructions included convulsions or hallucinations and Kounis syndrome (KS). Conclusion: This review suggests that the most severe ADRs associated with piperacillin are toxic epidermal necrolysis and anaphylactic shock. Rare ADRs caused by piperacillin, such as myoclonic jerks, hallucinations, and KS, were identified. The most common symptom with domestic preparations of piperacillin/sulbactam and piperacillin sodium was dyspnea.

Methodology for awakening the potential secondary metabolic capacity in actinomycetes.

Secondary metabolites produced by actinomycete strains undoubtedly have great potential for use in applied research areas such as drug discovery. However, it is becoming difficult to obtain novel compounds because of repeated isolation around the world. Therefore, a new strategy for discovering novel secondary metabolites is needed. Many researchers believe that actinomycetes have as yet unanalyzed secondary metabolic activities, and the associated undiscovered secondary metabolite biosynthesis genes are called "silent" genes. This review outlines several approaches to further activate the metabolic potential of actinomycetes.

Duodenal gastrointestinal stromal tumor presenting with life-threatening upper GI bleeding in a young patient: A case report and literature review.

Key Clinical Message: Duodenal GISTs are rare and challenging tumors. Acute life-threatening upper GI bleeding is a possible presentation of duodenal GISTs. Surgery is the standard treatment for localized duodenal GISTs. Imatinib is an effective adjuvant therapy for duodenal GISTs. Abstract: GIST is the most common mesenchymal neoplasm of the gastrointestinal tract, accounting for 1%-2% of gastrointestinal tumors. They originate from the interstitial cells of Cajal and are rare in patients younger than 30 years. The stomach is the most common site, followed by the small intestine and colon. GISTs are caused by a gain-of-function mutation in the proto-oncogene receptor tyrosine kinase, with activating mutations in KIT being the most common. Most GISTs are asymptomatic. Even if gastrointestinal bleeding is the most common complication life-threatening hemorrhage is extremely uncommon. We present a case of a 31-year-old male patient presented with massive active hematemesis and melena with hemorrhagic shock. The patient presented with massive hematemesis and melena of 1 h duration. Endoscopy showed pulsating active bleeding from the third part of the duodenum which was difficult to manage via endoscopy. Histopathologic evaluation showed spindle cell type GIST. Intraoperatively, there was a nodular mass with active bleeding on the third part of the duodenum. Duodenectomy with end-to-end anastomosis was done. Discharged with no postoperative complication and was put on imatinib. There are considerable challenges that arise in the diagnosis and treatment of duodenal gastrointestinal stromal tumors (GISTs) when they present with life-threatening upper gastrointestinal hemorrhage. In order to achieve the best possible outcomes for patients, it is crucial to have a comprehensive understanding of the clinical presentation, diagnostic methods, and treatment approaches.

NLRP3 Cys126 palmitoylation by ZDHHC7 promotes inflammasome activation.

Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and understanding how NLRP3 inflammasome is regulated can provide strategies to treat inflammatory diseases. Here, we demonstrate that NLRP3 Cys126 is palmitoylated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7), which is critical for NLRP3-mediated inflammasome activation. Perturbing NLRP3 Cys126 palmitoylation by ZDHHC7 knockout, pharmacological inhibition, or modification site mutation diminishes NLRP3 activation in macrophages. Furthermore, Cys126 palmitoylation is vital for inflammasome activation in vivo. Mechanistically, ZDHHC7-mediated NLRP3 Cys126 palmitoylation promotes resting NLRP3 localizing on the trans-Golgi network (TGN) and activated NLRP3 on the dispersed TGN, which is indispensable for recruitment and oligomerization of the adaptor ASC (apoptosis-associated speck-like protein containing a CARD). The activation of NLRP3 by ZDHHC7 is different from the termination effect mediated by ZDHHC12, highlighting versatile regulatory roles of S-palmitoylation. Our study identifies an important regulatory mechanism of NLRP3 activation that suggests targeting ZDHHC7 or the NLRP3 Cys126 residue as a potential therapeutic strategy to treat NLRP3-related human disorders.

Characteristics of High-Performing Hospitals in Cardiogenic Shock Following Acute Myocardial Infarction.

Cardiogenic shock after acute myocardial infarction (AMI-CS) carries significant mortality despite advances in revascularization and mechanical circulatory support. We sought to identify the process-based and structural characteristics of centers with lower mortality in AMI-CS. We analyzed 16,337 AMI-CS cases across 440 centers enrolled in the National Cardiovascular Data Registry's Chest Pain-MI Registry, a retrospective cohort database, between January 1, 2015, and December 31, 2018. Centers were stratified across tertiles of risk-adjusted in-hospital mortality rate (RAMR) for comparison. Risk-adjusted multivariable logistic regression was also performed to identify hospital-level characteristics associated with decreased mortality. The median participant age was 66 (interquartile range 57 to 75) years, and 33.0% (n = 5,390) were women. The median RAMR was 33.4% (interquartile range 26.0% to 40.0%) and ranged from 26.9% to 50.2% across tertiles. Even after risk adjustment, lower-RAMR centers saw patients with fewer co-morbidities. Lower-RAMR centers performed more revascularization (92.8% vs 90.6% vs 85.9%, p <0.001) and demonstrated better adherence to associated process measures. Left ventricular assist device capability (odds ratio [OR] 0.78 [0.67 to 0.92], p = 0.002), more frequent revascularization (OR 0.93 [0.88 to 0.98], p = 0.006), and higher AMI-CS volume (OR 0.95 [0.91 to 0.99], p = 0.009) were associated with lower in-hospital mortality. However, several such characteristics were not more frequently observed at low-RAMR centers, despite potentially reflecting greater institutional experience or resources. This may reflect the heterogeneity of AMI-CS even after risk adjustment. In conclusion, low-RAMR centers do not necessarily exhibit factors associated with decreased mortality in AMI-CS, which may reflect the challenges in performing outcomes research in this complex population.

Use of percutaneous mechanical circulatory support for right ventricular failure.

BACKGROUND: Utilization of right ventricular mechanical circulatory support (RV-MCS) devices has been limited by a lack of recognition of RV failure as well as a lack of availability and experience with RV-MCS. AIMS: We report a single-center experience with the use of percutaneous RV-MCS and report predictors of adverse outcomes. METHODS: This was a single-center retrospective cohort study. Data from consecutive patients who received RV-MCS for any indication between June 2015 and January 2022 were included. Data on baseline comorbidities, hemodynamics, and laboratory values were collected. The primary outcome was in-hospital mortality analyzed as a logistic outcome in a multivariable model. These variables were further ranked by their predictive value. RESULTS: Among 58 consecutive patients enrolled, the median age was 66 years, 31% were female and 53% were white. The majority of the patients (48%) were hospitalized for acute on chronic heart failure. The majority of the patients were SCAI SHOCK Stage D (67%) and 34 (64%) patients had MCS placed within 24 h of the onset of shock. Before placement of RV-MCS, median central venous pressure (CVP) and RV stroke work index were 20 mmHg and 8.9 g m/m2, respectively. Median serum lactate was 3.5 (1.6, 6.2) mmol/L. Impella RP was implanted in 50% and ProtekDuo in the remaining 50%. Left ventricular MCS was concomitantly used in 66% of patients. Twenty-eight patients (48.3%) died. In these patients, median serum lactate was significantly higher (4.1 [2.3, 13.0] vs. 2.2 [1.4, 4.0] mmol/L, p = 0.007) and a trend toward higher median CVP (24 [18, 31] vs. 19 [14, 24] mmHg, p = 0.052). In the multivariable logistic model, both serum lactate and CVP before RV-MCS placement were independent predictors of in-hospital mortality. Serum lactate had the highest predictive value. CONCLUSION: In our real-world cohort, 52% of patients treated with RV-MCS survived their index hospitalization. Serum lactate at presentation and CVP were the strongest predictors of in-hospital mortality.

Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Expression of Heat Shock Protein 70 (HSP70) and Astacin Genes of Strongyloides stercoralis as well as HSP70 and HSP17.1 Genes of S. ratti in Adult and Larval Stages of S. stercoralis.

Background: Uncovering the roles and characteristics of pathogenesis-related molecules can help us develop novel management methods in parasitology. In this study, we studied the expression levels of Strongyloides stercoralis heat shock protein70 (HSP70) (Sst-hsp-70) and astacin (Sst-ast) as pathogenesis-related genes as well as the expression of S. ratti HSP70 and HSP17.1 (Sra-hsp-70, Sra-hsp-17.1) in the larvae and adult stages of S. stercoralis. Methods: A hyperinfection isolate of S. stercoralis from Gilan Province, northern Iran was cultivated on nutrient agar. After a couple of days, parasites in different stages of life were collected, and total RNA was extracted. The expression levels of astacin and HSP genes were compared by real-time PCR. Results: Statistically higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in L3 larvae than in adults were observed. However, the expression level of Sra-hsp-17.1 was non-significantly lower in the larval stage than in adult worms. Conclusion: Higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in the larval stages of S. stercoralis suggest the potential role of these enzymes in parasite cutaneous invasion and pathogenesis. However, higher expression of Srahsp-17.1 in adult forms is probably involved in resistance and survival mechanisms. The similarity in gene expression between S. stercoralis and S. ratti can provide helpful hints to better understand strongyloidiasis from various perspectives, including pathogenesis, proper diagnosis, and targeted treatment.

Cardiac index and heart rate as prognostic indicators for mortality in septic shock: A retrospective cohort study from the MIMIC-IV database.

Background: Septic shock is a life-threatening condition that can lead to organ dysfunction and death. In the ICU, monitoring of cardiac index (CI) and heart rate (HR) is commonly used to guide management and predict outcomes in septic shock patients. However, there is a lack of research on the association between CI and HR and the risk of mortality in this patient population. Therefore, the aim of this study was to investigate the relationship between different levels of CI and HR and mortality in septic shock patients. Methods: Data analysis was obtained from the MIMIC-IV version 2.0 database. Sepsis and septic shock were primarily defined by sepsis-3, the third international consensus on sepsis and septic shock. CI was computed using cardiac output (CO) and body surface area (BSA). To evaluate the incidence of CI with respect to each endpoint (7-, 14-, 21-, and 28-day mortality), a restricted cubic spline curve function (RCS) was used. The optimal cutoff value for predicted mortality was determined using the Youden index. Analyses of KM curves, cox regression, and logistic regression were conducted separately to determine the relationship between various CI and HR and 28-day mortality. Results: This study included 1498 patients with septic shock. A U-shaped relationship between CI levels and risk of mortality in septic shock was found by RCS analysis (p < 0.001). CI levels within the intermediate range of 1.85-2.8 L/min/m2 were associated with a mortality hazard ratio (HR) < 1. In contrast, low CI (HR = 1.87 95% CI: 1.01-3.49) and high CI (HR = 1.93 95% CI: 1.26-2.97) had a significantly increased risk of mortality. The AUC for heart rate prediction of mortality by Youden index analysis was 0.70 95%CI:0.64-0.76 with a cut-off value of 93.63 bpm. According to the characteristics of HR and CI, patients were divided into six subgroups HR↓+CI intermediate group (n = 772), HR↓+CI↓ group (n = 126), HR↓+CI↑ group (n = 294), HR↑+CI intermediate group (n = 132), HR↑+CI↓ group (n = 24), and HR↑+CI↑ group (n = 150). The KM curves, COX regression, and logistic regression analysis showed that the survival rates the of HR↓+CI intermediate group, HR↓+CI↓ group, and HR↓+CI↑ were higher than the other groups. The risk factors of HR↑+CI intermediate group, HR↑+CI↓, and HR↑+CI↑ with ICU 28-day mortality were HR = 2.91 (95% CI: 1.39-5.97), HR = 3.67 (95% CI: 1.39-11.63), and HR = 5.77 (95% CI: 2.98-11.28), respectively. Conclusion: Our retrospective study shows that monitoring cardiac index and heart rate in patients with septic shock may help predict the organismal response and hemodynamic consequences, as well as the prognosis. Thus, healthcare providers should carefully monitor changes in these parameters in septic shock patients transferred to the ICU for treatment.

Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines.

Maintaining tissue perfusion in sepsis depends on vascular integrity provided by the endothelial glycocalyx, the critical layer covering the luminal surface of blood vessels. The glycocalyx is composed of proteoglycans, glycosaminoglycans, and functional plasma proteins that are critical for antithrombogenicity, regulating tone, controlling permeability, and reducing endothelial interactions with leukocytes and platelets. Degradation of the glycocalyx in sepsis is substantial due to thromboinflammation, and treatments for sepsis and septic shock may exacerbate endotheliopathy via additional glycocalyx injury. As a result, therapeutic strategies aimed at preserving glycocalyx integrity should be considered, including modifications in fluid volume resuscitation, minimizing catecholamine use, controlling hyperglycemia, and potential use of corticosteroids and anticoagulants. In this review, we explore treatment strategies aligned with the recommendations outlined in the Surviving Sepsis Campaign Guidelines 2021 with a special emphasis on evidence regarding glycocalyx protection.

Post-Traumatic Intracranial Pseudoaneurysm Presenting as Epistaxis.

Background: Epistaxis is a frequent presenting complaint in the Emergency Department (ED). Roughly 60% of the population will suffer from epistaxis in their lifetime. The most common causes of epistaxis include nose picking, facial trauma, foreign bodies, and coagulopathies. There are other causes that are much less common, such as intracranial pseudoaneurysms. There are multiple causes that precipitate intracranial pseudoaneurysm formation, with head trauma accounting for less than 1% of inciting events. Case Report: A 24-year-old female with history of traumatic brain injury with associated skull fractures due to a gunshot wound to the head 6 months prior presented to the ED in hemorrhagic shock secondary to epistaxis. After stabilization with the administration of blood products, Computed Tomography with Angiography (CTA) imaging of the head and neck was obtained and revealed a 3.1 × 2.2 × 2.5 cm pseudoaneurysm of the cavernous portion of the right internal carotid artery penetrating through the base of the skull into the ethmoidal sinus. The patient was taken for formal angiography by interventional radiology-and a partially thrombosed daughter sac of the initial aneurysm was identified and believed to be the source of the hemorrhage. The aneurysm was successfully coiled and occluded using ONYX embolization. Postoperatively, the patient returned to her baseline mental status without any acute complaints. The patient was discharged back to her nursing home 2 days later with a 3-week follow-up CTA revealing persistent occlusion of the aneurysm and a patent internal carotid artery. Conclusion: Awareness and consideration of intracranial vascular etiology for common complaints in the emergency room, such as Epistaxis, especially in patients with any history of head injury/trauma, known intracranial aneurysms or prosthetic devices from prior surgery may help guide decision-making in managing critically ill patients.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer: A systematic review and meta-analysis.

BACKGROUND: Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed in many cancers. The prognostic significance of HSPs and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, are poorly understood. AIM: To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer. METHODS: A systematic review was conducted in accordance with PRISMA recommendations (PROSPERO: CRD42022370653), on Embase, PubMed, Cochrane, and LILACS. Cohort, case-control, and cross-sectional studies of patients with esophagus or esophagogastric cancer were included. HSP-positive patients were compared with HSP-negative, and the endpoints analyzed were lymph node metastasis, tumor depth, distant metastasis, and overall survival (OS). HSPs were stratified according to the HSP family, and the summary risk difference (RD) was calculated using a random-effect model. RESULTS: The final selection comprised 27 studies, including esophageal squamous cell carcinoma (21), esophagogastric adenocarcinoma (5), and mixed neoplasms (1). The pooled sample size was 3465 patients. HSP40 and 60 were associated with a higher 3-year OS [HSP40: RD = 0.22; 95% confidence interval (CI): 0.09-0.35; HSP60: RD = 0.33; 95%CI: 0.17-0.50], while HSF1 was associated with a poor 3-year OS (RD = -0.22; 95%CI: -0.32 to -0.12). The other HSP families were not associated with long-term survival. HSF1 was associated with a higher probability of lymph node metastasis (RD = -0.16; 95%CI: -0.29 to -0.04). HSP40 was associated with a lower probability of lymph node dissemination (RD = 0.18; 95%CI: 0.03-0.33). The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis. CONCLUSION: The expression levels of certain families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Diagnostic and Management Considerations in a High-Risk Pregnant Patient With Ischemic Cardiomyopathy.

Ischemic heart disease is an important cause of heart failure in pregnancy. Involvement of a cardio-obstetrics team is crucial for managing high-risk pregnant patients with cardiovascular disease. We present a case of cardiogenic shock in a pregnant woman unmasking underlying multivessel obstructive coronary artery disease.

Application of the HRE-S to 140 horses with trigeminal-mediated headshaking and the association of clinical signs with diagnosis, therapy, and outcome.

Background: Horses with trigeminal-mediated headshaking (TMHS) exhibit different headshaking patterns (HSPs), electric shock-like jerking, signs of nasal irritation, and painful facial expressions. The History Rest and Exercise Score (HRE-S) was developed to objectively clarify the severity of the condition in affected horses. This score considers the history and severity of clinical signs at rest and exercise. This study aimed to assess the frequency of different clinical signs and their individual associations with diagnosis, treatment, and outcome in horses diagnosed with TMHS.The clinical records of horses presented with headshaking (HS) at the Clinic for Horses, University of Veterinary Medicine Hannover, between 2006 and 2021 were assessed retrospectively for clinical signs, diagnosis, and treatment. A total of 140 horses were included in the study. Video recordings were evaluated using the HRE-S and compared to the score described by Talbot. Following discharge, owners were interviewed via telephone about the outcome. Correlations between the presence and severity of clinical signs, diagnosis, and outcome were evaluated. Results: The following clinical signs were significantly correlated with a higher HRE-S and grade by Talbot: HS at walk (independently of HSP) (52.9%, 74/140), increased total number of demonstrated HSP (independent of the dominant HSP) (more than one HSP per horse in 91.4%, 128/140), signs of nasal irritation (75.9%, 104/137), painful facial expression (67.8%, 80/118), and electric shock-like jerking (77.5%, 107/138). Diagnosis and outcome do not correlate with the presence of the above-mentioned clinical signs. Conclusion: The HRE-S was confirmed as a valid tool to evaluate disease severity in a cohort of 140 horses with HS. Additionally, clinical signs identified as indicators for higher disease severity may have a stronger negative effect on patient welfare, but they do not correlate with diagnosis or outcome.

Extracorporeal shock wave lithotripsy, ureterolithotripsy, and percutaneous nephrolithotripsy challenges in managing spinal cord neuropathy patients. Lessons learned from a scoping review.

Introduction: We aim to review the outcomes of shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotripsy (PCNL) for renal and ureteral stones in spinal cord neuropathy patients (SNP). Material and methods: A literature search was performed on 8th March 2023 using PubMed, EMBASE, and Google Scholar with no date limit. Preclinical/animal studies, reviews, letters to the editor, case reports, and meeting abstracts were excluded. Only English papers were accepted. Results: Thirty-five articles were accepted. Five studies focused on SWL, 17 on PCNL, and 6 on ureteroscopy. The remaining articles employed more than one procedure. Stone composition has shifted from struvite to the more common calcium phosphate. SWL showed a very poor stone-free rate (SFR) likely due to challenges in patient positioning, stone visualization, localization, and inability to pass fragments spontaneously. Flexible ureteroscopy and PCNL were associated with a high incidence of infectious complications, long hospital stays, high blood transfusion rate, and intensive care admissions. There were also cases of death. Both procedures were challenging due to genitourinary reconstruction, scoliosis and kyphosis, rib-cage deformity, lower limb contractures, and severe comorbidity which also affected anesthesia. SFR was lower than in non-neurological patients. Conclusions: SWL, ureterolithotripsy, and PCNL should be considered challenging procedures in SNP due to positioning issues, an increased risk of intra and peri-operative morbidity, and even mortality. Computed tomography should be recommended to assess residual fragments as it becomes imperative to minimize a re-intervention in SNP who should be preferably treated in referral centers.