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Cardiorenal Medicine May 2024Congestion, marked by elevated cardiac filling pressures and their repercussions, is a contributing factor to morbidity and mortality in heart failure and critical... (Review)
Review
Congestion, marked by elevated cardiac filling pressures and their repercussions, is a contributing factor to morbidity and mortality in heart failure and critical illness. Relying on traditional methods for bedside evaluation often leads to inadequate decongestion and increased hospital readmissions. Point-of-care ultrasound (POCUS), particularly multi-organ POCUS, including the Venous Excess Ultrasound (VExUS), offers a promising approach in this scenario. VExUS enables the quantification of systemic venous congestion, aiding in fluid overload states by assessing inferior vena cava and venous Doppler waveforms. This comprehensive review delves into the latest developments in comprehending and evaluating congestion, shedding light on technical intricacies to enhance the effective application of VExUS. Recent studies emphasize the importance of evaluating signs of hemodynamic congestion before administering intravenous fluids, highlighting the concept of 'fluid tolerance'. Moreover, VExUS-guided decongestion significantly improves decongestion rates in acute decompensated heart failure patients with acute kidney injury. Newer studies also highlight the prognostic implications of VExUS in the general ICU cohorts not confining to cardiac surgery patients. However, performing VExUS without understanding technical pitfalls may lead to clinical errors. Technical considerations in performing VExUS include nuances related to inferior vena cava and internal jugular vein ultrasound and familiarity with Doppler principles, optimal settings, and artifacts. Additionally, local structural alterations such as those seen in liver and kidney disease impact Doppler waveforms, emphasizing the need for careful interpretation. Overall, VExUS presents a valuable tool for assessing congestion and guiding management, provided clinicians are familiar with its technical complexities and interpret findings judiciously.
PubMed: 38815571
DOI: 10.1159/000539469 -
Journal of Innate Immunity May 2024Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in... (Review)
Review
Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis respectively undergo substantial activation after sepsis. Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation", which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.
PubMed: 38815564
DOI: 10.1159/000539502 -
International Journal of Surgery Case... Apr 2024Perineal impalements, although rare, exhibit high morbidity and mortality, associated with penetrating traumas by long objects, often resulting from falls or assaults....
INTRODUCTION
Perineal impalements, although rare, exhibit high morbidity and mortality, associated with penetrating traumas by long objects, often resulting from falls or assaults. The risk of pelvic bleeding and the need for immediate intervention to preserve vital organs are characteristics of these injuries, whose severity demands a multidisciplinary approach.
CASE DESCRIPTION
A 57-year-old male patient, a victim of a 5-meter fall, suffered an extensive perineal impalement. With stable vital signs, he underwent the ATLS protocol, followed by whole-body computed tomography (WBCT), revealing a metallic object traversing the perineum, abdomen, and thorax. The surgery involved laparotomy, sternotomy, and removal of the object under direct visualization, with repair of prostatic, vesical, hepatic, and diaphragmatic injuries. The postoperative period included transfusions and urological follow-up.
DISCUSSION
Perineal impalements require immediate attention, and their approach is influenced by clinical factors and the extent of the object. The importance of preoperative evaluation with tomography, removal of the object under direct visualization, and comprehensive surgical management is highlighted. The decision for conservative treatment is reserved for less severe cases. This work has been reported in line with the SCARE criteria.
CONCLUSION
Perineal impalements demand a rapid and integrated approach to optimize survival. Object removal, often performed by exploratory laparotomy, stands out as an essential procedure. Multidisciplinary expertise is crucial for the effective management of these complex injuries.
METHODS
This work has been reported in line with the SCARE criteria.
PubMed: 38815442
DOI: 10.1016/j.ijscr.2024.109652 -
PLoS Neglected Tropical Diseases May 2024Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many...
Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many low/middle-income nations. In recent years the species has been implicated as the causative agent of nongenital cutaneous ulcers affecting children of the South Pacific Islands and West African countries. Much is still unknown about the mechanism of H. ducreyi transmission in these areas, and recent studies have identified local insect species, namely flies, as potential transmission vectors. H. ducreyi DNA has been detected on the surface and in homogenates of fly species sampled from Lihir Island, Papua New Guinea. The current study develops a model system using Musca domestica, the common house fly, as a model organism to demonstrate proof of concept that flies are a potential vector for the transmission of viable H. ducreyi. Utilizing a green fluorescent protein (GFP)-tagged strain of H. ducreyi and three separate exposure methods, we detected the transmission of viable H. ducreyi by 86.11% ± 22.53% of flies sampled. Additionally, the duration of H. ducreyi viability was found to be directly related to the bacterial concentration, and transmission of H. ducreyi was largely undetectable within one hour of initial exposure. Push testing, Gram staining, and PCR were used to confirm the identity and presence of GFP colonies as H. ducreyi. This study confirms that flies are capable of mechanically transmitting viable H. ducreyi, illuminating the importance of investigating insects as vectors of cutaneous ulcerative diseases.
Topics: Animals; Houseflies; Haemophilus ducreyi; Chancroid; Papua New Guinea; Insect Vectors; Female; Male
PubMed: 38814945
DOI: 10.1371/journal.pntd.0012194 -
PLoS Biology May 2024Zebrafish are popular research organisms selected for laboratory use due in part to widespread availability from the pet trade. Many contemporary colonies of laboratory...
Zebrafish are popular research organisms selected for laboratory use due in part to widespread availability from the pet trade. Many contemporary colonies of laboratory zebrafish are maintained in aquaculture facilities that monitor and aim to curb infections that can negatively affect colony health and confound experiments. The impact of laboratory control on the microbial constituents associated with zebrafish in research environments compared to the pet trade are unclear. Diseases of unknown causes are common in both environments. We conducted a metatranscriptomic survey to broadly compare the zebrafish-associated microbes in pet trade and laboratory environments. We detected many microbes in animals from the pet trade that were not found in laboratory animals. Cohousing experiments revealed several transmissible microbes including a newly described non-enveloped, double-stranded RNA virus in the Birnaviridae family we name Rocky Mountain birnavirus (RMBV). Infections were detected in asymptomatic animals from the pet trade, but when transmitted to laboratory animals RMBV was associated with pronounced antiviral responses and hemorrhagic disease. These experiments highlight the pet trade as a distinct source of diverse microbes that associate with zebrafish and establish a paradigm for the discovery of newly described pathogenic viruses and other infectious microbes that can be developed for study in the laboratory.
Topics: Animals; Zebrafish; Fish Diseases; Pets; Animals, Laboratory; Aquaculture
PubMed: 38814944
DOI: 10.1371/journal.pbio.3002606 -
PLoS Neglected Tropical Diseases May 2024Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver...
Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver and lungs. Although the heart is affected in only 0.02-2% of all CE cases, a considerable number of cases have been, and continue to be, published. However, due to the rare occurrence of cardiac CE and the resulting lack of clinical trials, knowledge about various aspects of the disease remains limited. To obtain a clearer picture of anatomical, clinical, diagnostic as well as therapeutic aspects of cardiac CE, we systematically reviewed the literature published between 1965 and 2022. The anatomical pattern of the affected cardiac structures follows the extension of the supplying capillary bed. The majority of patients (82.7%) are symptomatic and present with prolonged non-specific symptoms such as dyspnoea, chest pain and palpitations. Acute complications generally derive from cyst rupture, occur in 18.3% of cases and manifest as embolism, pericardial tamponade, or anaphylactic reaction in 83.2%, 17.8% and 10.9% of these cases, respectively. As for CE cysts localized in other organs, the diagnosis of cardiac CE is made by imaging. Serology plays a minor role due to its limited sensitivity. Unlike abdominal CE cysts, cardiac CE cysts are usually resected independent of their stage (active/inactive), because their presence impairs cardiac performance and carries the risk of long-term sequelae. More than 80% of patients are treated with a single surgical intervention. We found a disease-related case fatality rate of 11.1%. Since local recurrence was reported up to 108 months and secondary CE up to 72 months after surgery, patients should be followed up for a minimum of 10 years.
Topics: Humans; Echinococcosis; Animals; Heart Diseases; Echinococcus granulosus; Heart
PubMed: 38814859
DOI: 10.1371/journal.pntd.0012183 -
Kidney360 May 2024
Topics: Kidney Transplantation; Humans; Proteasome Endopeptidase Complex; Organ Preservation; Kidney; Cold Temperature
PubMed: 38814755
DOI: 10.34067/KID.0000000000000436 -
BJS Open May 2024In contrast to the well-established multimodal therapy for localized oesophageal cancer, the metastatic stage is commonly treated only with systemic therapy as current...
BACKGROUND
In contrast to the well-established multimodal therapy for localized oesophageal cancer, the metastatic stage is commonly treated only with systemic therapy as current international guidelines recommend. However, evidence suggesting that multimodal therapy including surgery could benefit selected patients with metastasized oesophageal cancer is increasing. The aim of this study was to investigate the survival of patients diagnosed with metastatic oesophageal cancer after different treatment regimens.
METHODS
This was a retrospective single-centre study of patients with adenocarcinoma or squamous cell carcinoma of the oesophagus with synchronous or metachronous metastases who underwent Ivor Lewis oesophagectomy between 2010 and 2021. Each patient received an individual treatment for their metastatic burden based on an interdisciplinary tumour board conference. Survival differences between different treatments were assessed using the Kaplan-Meier method, as well as univariable and multivariable Cox regression models.
RESULTS
Out of 1791 patients undergoing Ivor Lewis oesophagectomy, 235 patients diagnosed with metastases were included. Of all of the included patients, 42 (17.9%) only underwent surgical resection of their metastatic disease, 37 (15.7%) underwent multimodal therapy including surgery, 78 (33.2%) received chemotherapy alone, 49 (20.9%) received other therapies, and 29 (12.3%) received best supportive care. Patients who underwent resection or multimodal therapy including surgery of their metastatic burden showed superior overall survival compared with chemotherapy alone (median overall survival of 19.0, 18.0, and 11.0 months respectively) (P < 0.001). This was confirmed in subcohorts of patients with metachronous solid-organ metastases and with a single metastasis. In multivariable analyses, resection with or without multimodal therapy was an independent factor for favourable survival.
CONCLUSION
Surgical resection could be a feasible treatment option for metastasized oesophageal cancer, improving survival in selected patients. Further prospective randomized studies are needed to confirm these findings and define reliable selection criteria.
Topics: Humans; Esophageal Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Esophagectomy; Aged; Combined Modality Therapy; Adenocarcinoma; Kaplan-Meier Estimate; Carcinoma, Squamous Cell; Proportional Hazards Models
PubMed: 38814750
DOI: 10.1093/bjsopen/zrae054 -
ELife May 2024Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. as a notorious...
Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.
Topics: Animals; Sucrose; Larva; Moths; Sensilla; Taste; Taste Perception; Helicoverpa armigera
PubMed: 38814697
DOI: 10.7554/eLife.91711 -
Epilepsia Open May 2024GABA receptor subunit mutations pose a significant risk for genetic generalized epilepsy; however, there are over 150 identified variants, many with unknown or...
OBJECTIVE
GABA receptor subunit mutations pose a significant risk for genetic generalized epilepsy; however, there are over 150 identified variants, many with unknown or unvalidated pathogenicity. We aimed to develop in vivo models for testing GABA receptor variants using the model organism, Caenorhabditis elegans.
METHODS
CRISPR-Cas9 gene editing was used to create a complete deletion of unc-49, a C. elegans GABA receptor, and to create homozygous epilepsy-associated mutations in the endogenous unc-49 gene. The unc-49 deletion strain was rescued with transgenes for either the C. elegans unc-49B subunit or the α1, β3, and γ2 subunits for the human GABA receptor. All newly created strains were analyzed for phenotype and compared against existing unc-49 mutations.
RESULTS
Nematodes with a full genetic deletion of the entire unc-49 locus were compared with existing unc-49 mutations in three separate phenotypic assays-coordinated locomotion, shrinker frequency and seizure-like convulsions. The full unc-49 deletion exhibited reduced locomotion and increased shrinker frequency and PTZ-induced convulsions, but were not found to be phenotypically stronger than existing unc-49 mutations. Rescue with the unc-49B subunit or creation of humanized worms for the GABA receptor both showed partial phenotypic rescue for all three phenotypes investigated. Finally, two epilepsy-associated variants were analyzed and deemed to be loss of function, thus validating their pathogenicity.
SIGNIFICANCE
These findings establish C. elegans as a genetic model to investigate GABA receptor mutations and delineate a platform for validating associated variants in any epilepsy-associated gene.
PLAIN LANGUAGE SUMMARY
Epilepsy is a complex human disease that can be caused by mutations in specific genes. Many possible mutations have been identified, but it is unknown for most of them whether they cause the disease. We tested the role of mutations in one specific gene using a small microscopic worm as an animal model. Our results establish this worm as a model for epilepsy and confirm that the two unknown mutations are likely to cause the disease.
PubMed: 38813985
DOI: 10.1002/epi4.12982