Severe Organ Dysfunction Research Articles

A Case of Fever of Unknown Origin -? Melioidosis Presenting as Severe Sepsis and Multiple Organ Dysfunction Syndrome

Melioidosis is an emerging infection in India1, well known for its protean clinical manifestations. We report a case of probable disseminated Melioidosis with hyperferritinemic septic shock and multi organ dysfunction syndrome. She presented as a case of PUO- with high fever- 1week, loose stools, headache and shortness of breath, to our hospital. She had a turbulent course in hospital, with fever not responding despite 2 weeks of hospitalization. Her respiratory system showed bilateral crackles. Per Abdomen examination revealed tenderness in right iliac fossa, suprapubic region and left iliac fossa, bowel sounds were sluggish. CECT chest and Abdomen showed right basal pneumonia, hydro-ureteronephrosis, with ureter showing narrowing at the region of right adnexa, PID, subcentrimetric , mesentric , and perirectal lymph nodes; rectal wall showing inflammatory changes with inflammation of mesorectal fascia . She responded well and fully recovered with injection Meropenem for 8 weeks; followed by oral Trimethoprim-Sulfamethoxazole for 3 months.

Evaluation of Antioxidant, Antibacterial and Antidiabetic Activity of <i>Juglans regia</i> Root Extract: <i>In Vitro</i> and <i>In Vivo</i> Studies

Background: Diabetes mellitus is a long-term metabolic illness that occurs due to a malfunction in the production or action of insulin. Prolonged hyperglycemia may lead to dysfunction and failure of several organs, such as the diabetic nephropathy, retinopathy and neuropathy. The incidence of diabetes and the number of patients has consistently risen over the last several decades. Juglans regia, a member of the Juglandaceae family, has been used by practitioners of folklore to treat number of illnesses. Aim: To Evaluate the antioxidant and anti-bacterial effects of a root extract from Juglans regia in in vitro studies and anti-diabetic effect Streptozotocin (STZ) induced Wistar albino rats. Methods: Qualitative phytochemical analysis, antioxidant assay were done using DPPH, antibacterial assay have been performed by using agar well diffusion method and anti-diabetic effect tested by inducing rats with STZ followed by administering methanolic root extract of Juglans regia alone and with adjuvants metformin and glipalamide. Result: The root extract of Juglans regia can decrease free radicals, possess antibacterial property in agar well diffusion method and in in-vivo studies group 2 (diabetic control) showed elevated FBS and HbA1C from day 3 to day 28 while group 3, 4, 5, 6, 7 and 8 showed significant reduction in FBS and HbA1C levels at the end of study. Safety profiles such as CBC, RFT and LFT did not show any significant difference between the groups from baseline to end of the study. Thus, methanolic root extract of Juglans regia was safe and efficacious against STZ induced rats. Conclusion: Juglans regia can reduce hyperglycemia in STZ induced diabetic rats alone and can be used as an adjuvant to Metformin and Glibenclamide. Also, it possesses anti-oxidant and anti-bacterial activity in in vitro studies.

A novel digital health approach to improving global pediatric sepsis care in Bangladesh using wearable technology and machine learning.

Sepsis is the leading cause of child death globally with low- and middle-income countries (LMICs) bearing a disproportionate burden of pediatric sepsis deaths. Limited diagnostic and critical care capacity and health worker shortages contribute to delayed recognition of advanced sepsis (severe sepsis, septic shock, and/or multiple organ dysfunction) in LMICs. The aims of this study were to 1) assess the feasibility of a wearable device for physiologic monitoring of septic children in a LMIC setting and 2) develop machine learning models that utilize readily available wearable and clinical data to predict advanced sepsis in children. This was a prospective observational study of children with sepsis admitted to an intensive care unit in Dhaka, Bangladesh. A wireless, wearable device linked to a smartphone was used to collect continuous recordings of physiologic data for the duration of each patient's admission. The correlation between wearable device-collected vital signs (heart rate [HR], respiratory rate [RR], temperature [T]) and manually collected vital signs was assessed using Pearson's correlation coefficients and agreement was assessed using Bland-Altman plots. Clinical and laboratory data were used to calculate twice daily pediatric Sequential Organ Failure Assessment (pSOFA) scores. Ridge regression was used to develop three candidate models for advanced sepsis (pSOFA > 8) using combinations of clinical and wearable device data. In addition, the lead time between the models' detection of advanced sepsis and physicians' documentation was compared. 100 children were enrolled of whom 41% were female with a mean age of 15.4 (SD 29.6) months. In-hospital mortality rate was 24%. Patients were monitored for an average of 2.2 days, with > 99% data capture from the wearable device during this period. Pearson's r was 0.93 and 0.94 for HR and RR, respectively) with r = 0.72 for core T). Mean difference (limits of agreement) was 0.04 (-14.26, 14.34) for HR, 0.29 (-5.91, 6.48) for RR, and -0.0004 (-1.48, 1.47) for core T. Model B, which included two manually measured variables (mean arterial pressure and SpO2:FiO2) and wearable device data had excellent discrimination, with an area under the Receiver-Operating Curve (AUC) of 0.86. Model C, which consisted of only wearable device features, also performed well, with an AUC of 0.78. Model B was able to predict the development of advanced sepsis more than 2.5 hours earlier compared to clinical documentation. A wireless, wearable device was feasible for continuous, remote physiologic monitoring among children with sepsis in a LMIC setting. Additionally, machine-learning models using wearable device data could discriminate cases of advanced sepsis without any laboratory tests and minimal or no clinician inputs. Future research will develop this technology into a smartphone-based system which can serve as both a low-cost telemetry monitor and an early warning clinical alert system, providing the potential for high-quality critical care capacity for pediatric sepsis in resource-limited settings.

Research Progress of Traditional Chinese Medicine in the Treatment of Sepsis Gastrointestinal Dysfunction

Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection. Further development can lead to severe sepsis, septic shock and multiple organ dysfunction or failure. Gastrointestinal dysfunction is one of the common complications. Reviewing the domestic literature, it is found that in recent years, traditional Chinese medicine has accumulated a large number of clinical research data in the treatment of sepsis gastrointestinal dysfunction, and has achieved good results. This article briefly summarizes the etiology and pathogenesis of gastrointestinal dysfunction in sepsis and the treatment of traditional Chinese medicine, in order to provide reference for further clinical research in the future.

Ivosidenib (Tibsovo)

We recommend that Tibsovo in combination with azacitidine be reimbursed by public drug plans for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an IDH1 R132 mutation who are not eligible to receive intensive induction chemotherapy, if certain conditions are met. Tibsovo in combination with azacitidine should only be covered to treat adult patients with newly diagnosed AML with an IDH1 R132 mutation who are considered ineligible for standard intensive induction chemotherapy and are aged at least 75 years; have an Eastern Cooperative Oncology Group (ECOG) performance status of 2; have severe organ dysfunction in the heart, lungs, kidneys, or liver; and/or have any other comorbidity judged to be incompatible with intensive induction chemotherapy. Tibsovo in combination with azacitidine should only be reimbursed if prescribed by clinicians with expertise in managing patients with AML in a specialized hematology or oncology clinic, and the treatment should be supervised and delivered in institutions with expertise in systemic therapy delivery. The total drug cost of ivosidenib plus azacitidine should not exceed that of venetoclax plus azacitidine. Lastly, it must be feasible to test patients for IDH1 R132

Sirt4 Overexpression Modulates the JAK2/STAT3 and PI3K/AKT/mTOR Axes to Alleviate Sepsis-Induced Acute Lung Injury.

Sepsis-induced acute lung injury (ALI) is a severe organ dysfunction characterized by lung inflammation and apoptosis. The mechanisms underlying sepsis-induced ALI remain poorly understood. Here, we determined the effects of sirtuin 4 (SIRT4) on sepsis-induced ALI. Lipopolysaccharide (LPS)-induced injury cell and cecal ligation and puncture (CLP) animal models were established. Overexpression vectors and lentiviral transfections were used to upregulate SIRT4 expression. Lung cell apoptosis, inflammation, and the levels of associated factors were evaluated. Changes in the PI3K/AKT/mTOR and JAK2/STAT3 pathways were measured, and their potential involvement was examined using LY294002 (PI3K inhibitor), 740 Y-P (PI3K agonist), AG490 (JAK2 inhibitor), and coumermycin A1 (JAK2 agonist). Lower SIRT4 expression was observed in LPS-exposed A549 cells and CLP rats. In LPS-induced A549 cells, Sirt4 overexpression enhanced cell viability, resisted apoptosis, restored the expression of apoptosis-associated proteins (HMB1, cleaved CASP3, BAX, and BCL), and reduced the secretion of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). In CLP rats, Sirt4 overexpression prolonged survival time, alleviated lung histopathological damage, reduced pulmonary edema, mitigated lung infection, decreased lung apoptosis, and lowered serum levels of inflammatory cytokines. Furthermore, Sirt4 overexpression blocked JAK2/STAT3/AKT/mTOR phosphorylation. 740 Y-P and coumermycin A1 reversed the protective effects of Sirt4 overexpression in LPS-treated A549 cells, resulting in decreased cell viability and increased apoptosis. LY294002 and AG490 enhanced the protective effects of Sirt4 overexpression in LPS-treated A549 cells. SIRT4 alleviates sepsis-induced ALI by inhibiting JAK2/STAT3/PI3K/AKT/mTOR signaling. Upregulating SIRT4 expression may serve as an innovative therapeutic approach for lung injury management in sepsis.

Effects of normal saline versus lactated Ringer’s solution on organ function and inflammatory responses to heatstroke in rats

BackgroundHeatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer’s solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.MethodsFifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.ResultsCompared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.ConclusionsNS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

Dengue fever in hyperglycemic patients: an emerging public health concern demanding eyes on the effective management strategies.

Hyperglycemia, also known as diabetes, is a metabolic disorder characterized by elevated levels of glucose in the bloodstream. It can lead to the prolonged dysfunction, injury, and deterioration of several organs. In addition, dengue is a viral illness transmitted by mosquitoes that has reached epidemic proportions worldwide. In this article, we focused on the severity of comorbidities, difficulties in managing them, and preventive measures meant to lessen the risks associated with comorbidities in diabetic patients with dengue infection. We explored a number of databases, including PubMed, Scopus, Embase, Web of Science, Google Scholar, and the Cochrane Library, for this review article using various related keywords. The findings of this review article indicate that elderly dengue patients with diabetes should be admitted to the hospital for close observation and early management using fluid therapy. An observed association exists between dengue hemorrhagic fever (DHF) and diabetes, indicating a possible consequence in this specific group. Additionally, patients with diabetes who contract dengue show elevated levels of inflammatory markers. Diabetes mellitus deteriorates the immune system, which exacerbates the progression of dengue fever. Cutting-edge technology and scientific research may assist in addressing the challenges that diabetes and dengue viruses pose in low- and middle-income countries. Implementing innovative diabetic care management is essential to ensuring consistency of care, improving a healthy lifestyle, and lowering patient risk factors and comorbidities. Dengue fever has spread to epidemic levels throughout the world. Inflammatory markers increase and the prevalence of DHF is greater in diabetes individuals with dengue infection. Given the continued growth of dengue in Asian nations, it is imperative that we concentrate our efforts and resources on providing more precise and effective treatment for this emerging issue.

Thrombotic microangiopathy as a rare complication after lung transplantation

Thrombotic microangiopathy (TMA) is defined by the typical triad of severe thrombocytopenia, hemolytic anemia and endorgan dysfunction and can be characterized by the pathophysiology of ischemia-inducing microthrombi in arterioles and capillaries possibly leading to severe organ dysfunction up to acutely life-threatening endorgan damage. In terms of etiology, management, therapy and prognosis, the following manifestations are distinguished: thrombotic thrombocytopenic purpura (TTP), shigatoxin-induced hemolytic-uremic syndrome (STEC-HUS), secondary comorbidity-related TMA and atypical hemolytic-uremic syndrome (aHUS). We present the case of a 49 year old lung transplant recipient developing aHUS. The complexity of the underlying pathomechanisms of TMA, the complicated differentiation of each TMA manifestation and the complex management of aHUS in the post-transplant setting illustrate the uniqueness of this patient case.

Anaesthesiological management of pre-eclampsia and eclampsia

A new national treatment guideline from Danish Society of Anaesthesiology and Intensive Care Medicine (DASAIM) outlines the anaesthetic management of pre-eclampsia and eclampsia. Key principles involve blood pressure control, seizure treatment and prophylaxis, and restricted fluid therapy. Treatment algorithms, flow charts and checklists are provided. Anaesthetic recommendations for vaginal delivery and caesarean section are provided. Close monitoring, especially for patients with severe disease, organ dysfunction, or failure, is crucial, requiring a multidisciplinary approach, as argued in this review.

Feasibility and structural prerequisites for conversion to outpatient treatment in proctology

Despite the introduction of the diagnosis-related groups (DRG) system, costs in the German healthcare system have risen continuously for years. In order to reduce costs the federal government is aiming to shift inpatient services to the outpatient sector. Outpatient services affect many areas of medicine, including proctological operations as these are common and can often be carried out on an outpatient basis. The aim of the present work is to discuss which areas of proctology are suitable for outpatient treatment and which structural requirements are necessary. The present article is intended to provide anarrative overview with reference to the literature on the topic of outpatient care in proctology. Aliterature search was carried out using the following keywords: outpatient care, selective sector-level remuneration, day care, proctological operations, AOP catalog and hybrid DRG. In proctology, outpatient surgical care is implementable in many cases; however, not every patient is suitable for this. In addition to previous illnesses, patient compliance and the possibility of postoperative care from relatives must also be taken into account. In addition, emergency treatment must be guaranteed. Contraindications include severe heart and circulatory diseases as well as severe coagulation or organ dysfunction. Extensive abscesses, complex fistulas or sphincter reconstructions should be surgically treated in an inpatient setting. The prerequisite for successful outpatient care is to make the sector boundaries between outpatient and inpatient patient care more permeable and to adequately remunerate the interventions. In addition to the surgical indications, the prerequisites for successful proctological operations are the correct assessment of the operational capability and compliance. From an organizational and economic perspective, better networking between outpatient and inpatient treatment and equal remuneration across the sector boundaries are crucial.

Hyperoxia in Sepsis and Septic Shock: A Comprehensive Review of Clinical Evidence and Therapeutic Implications.

Sepsis and septic shock are leading causes of mortality in intensive care units, characterized by a dysregulated immune response to infection, leading to severe organ dysfunction. Oxygen therapy is a cornerstone of supportive care in sepsis management, aimed at correcting hypoxemia and improving tissue oxygenation. However, the administration of supplemental oxygen must be carefully managed to avoid hyperoxia, which can lead to oxidative stress and additional tissue damage. This review aims to comprehensively analyze the clinical evidence regarding hyperoxia in the context of sepsis and septic shock, evaluating its potential therapeutic benefits and risks and discussing the implications for clinical practice. A thorough literature review included observational studies, randomized controlled trials (RCTs), meta-analyses, and clinical guidelines. The review focuses on the pathophysiology of sepsis, the mechanisms of hyperoxia-induced injury, and the clinical outcomes associated with different oxygenation strategies. The evidence suggests that while oxygen is crucial in managing sepsis, the risk of hyperoxia-related complications is significant. Hyperoxia has been associated with increased mortality and adverse outcomes in septic patients due to mechanisms such as oxidative stress, impaired microcirculation, and potential worsening of organ dysfunction. RCTs and meta-analyses indicate that conservative oxygen therapy may be beneficial in reducing these risks, though optimal oxygenation targets remain under investigation. This review highlights the importance of careful oxygen management in sepsis and septic shock, emphasizing the need for individualized oxygen therapy to avoid the dangers of hyperoxia. Further research is required to refine oxygenation strategies, establish clear clinical guidelines, and optimize outcomes for sepsis and septic shock patients. Balancing adequate oxygenation with the prevention of hyperoxia-induced injury is crucial in improving the prognosis of these critically ill patients.

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

BackgroundEndometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging.MethodsGene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment.ResultsGene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm.ConclusionOverall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.

Multifocal candidiasis can be considered a form of invasive candidiasis in critically non-neutropenic patients

Candida infections can be serious in intensive care unit (ICU) patients, as Candida is an organism that specially colonizes the digestive system. In immunocompromised patients, treatment is protocolized, but in non-neutropenic patients, it is not well established. On the other hand, the treatment of this type of infection is not absent of adverse effects. The prevalence of fungal infections, especially candidiasis, and its mortality in the ICU is high, mainly due to the lack of diagnosis and absence of treatment criteria, because they are often detected in the disseminated candidiasis phase, such as candidemia. One of the indicators of the progression of the disease is the presence of Candida in more than two different foci, named Candida multifocality, within the concept of invasive candidiasis. In fact, the invasive fungal diseases in adult patients i intensive care unit (FUNDICU) project was created to optimize the management of candidiasis. The management of candidiasis in ICU patients first requires the identification of patients at high risk of candidiasis, which must be performed based on the evidence of immune dysregulation, higher severity index (acute physiologic assessment and chronic health evaluation and multiple organ dysfunction syndrome), long ICU stays or other factors such as mechanical ventilation or us of broad-spectrum antibiotics. To increase detection and dispense the appropriate antifungal at an early stage, it is necessary to include the concept of multifocality in invasive candidiasis with screening of different foci. Antifungal treatment reduces mortality both overall and attributable to Candida. Detecting a high invasive candidiasis risk is a patient safety concept and should be treated as such. Identifying patients (critically non-neutropenic adult patients with severe multiple organ dysfunction syndrome and the first isolation of Candida spp. in a study sample of possible secondary infection) and demonstrating invasive candidiasis (multifocal or disseminated) require urgent initiation of antifungal treatment to minimize mortality attributable to invasive candidiasis in the ICU and eliminate mortality rates above 50%.

Early detection of low QRS voltage and its association with mortality in patients with sepsis

Various electrocardiographic changes occur during sepsis, but data on the clinical importance of a low QRS voltage in sepsis are still limited. We aimed to evaluate the association between low QRS voltage identified early in sepsis and mortality in patients with sepsis. Between September 2019 and December 2020, all consecutive adult patients diagnosed with sepsis in the emergency room or general ward at Samsung Medical Center were enrolled. Patients without a 12-lead electrocardiogram recorded within 48 h of recognition of sepsis were excluded. In 432 eligible patients, 12-lead electrocardiogram was recorded within the median of 24 min from the first recognition of sepsis, and low QRS voltage was identified in 115 (26.6%) patients. The low QRS group showed more severe organ dysfunction and had higher levels of N-terminal pro-brain natriuretic peptide. The hospital mortality was significantly higher in the low QRS voltage group than in the normal QRS voltage group (49.6% vs. 28.1%, p < 0.001). Similarly, among the 160 patients who required intensive care unit admission, significantly more patients in the low QRS group died in the intensive care unit (35.9% vs. 18.2%, p = 0.021). Low QRS voltage was associated with increased hospital mortality in patients with sepsis.

Excessive cleavage of von Willebrand factor multimers by ADAMTS13 may predict the progression of transplant-associated thrombotic microangiopathy

BackgroundTransplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of hematopoietic stem cell transplantation and is characterized by severe thrombocytopenia, hemolytic anemia, and organ dysfunction. In response to several possible triggers, dynamic multimetric change in von Willebrand factor (VWF) may contribute to inducing microthrombi in circulation in TA-TMA. ObjectivesBy performing VWF multimer analysis and measuring VWF-degradation product (DP), we unraveled the relationship between multimeric changes in circulating VWF and the pathogenesis of TA-TMA. MethodsThis study analyzed 135 plasma samples from 14 patients who underwent allogeneic hematopoietic stem cell transplantation at a single institute. VWF-associated markers, namely VWF:antigen (VWF:Ag), VWF-DP/VWF:Ag ratio, VWF:ristocetin cofactor activity, VWF:ristocetin cofactor activity/VWF:Ag ratio, and ADAMTS13 activity, were analyzed in these samples collected every 7 days. ResultsThere were 2 patients with definite thrombotic microangiopathy (TMA) and 6 patients who presented with probable TMA that did not progress to definite TMA. Each plasma sample was classified into 3 groups: definite TMA, probable TMA, and non-TMA. VWF multimer analysis showed the absence of high-molecular-weight VWF multimers in probable TMA, whereas the appearance of unusually large VWF multimers was observed in definite TMA. The median value of the VWF-DP/VWF:Ag ratio in probable TMA was elevated to 4.17, suggesting that excessive cleavage of VWF multimers by VWF cleaving enzyme, ADAMTS13, resulted in the loss of high-molecular-weight VWF multimers. ConclusionDuring the transition from probable to definite TMA, drastic VWF multimer changes imply a switch from bleeding to thrombotic tendencies. Extensive VWF-DP and VWF multimer analyses provided novel insights.

Clinical Characteristics and Prognosis of Older Patients with Coronavirus Disease 2019 Requiring Mechanical Ventilation.

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

Inflammatory subphenotypes previously identified in ARDS are associated with mortality at intensive care unit discharge: a secondary analysis of a prospective observational study

BackgroundIntensive care unit (ICU)-survivors have an increased risk of mortality after discharge compared to the general population. On ICU admission subphenotypes based on the plasma biomarker levels of interleukin-8, protein C and bicarbonate have been identified in patients admitted with acute respiratory distress syndrome (ARDS) that are prognostic of outcome and predictive of treatment response. We hypothesized that if these inflammatory subphenotypes previously identified among ARDS patients are assigned at ICU discharge in a more general critically ill population, they are associated with short- and long-term outcome.MethodsA secondary analysis of a prospective observational cohort study conducted in two Dutch ICUs between 2011 and 2014 was performed. All patients discharged alive from the ICU were at ICU discharge adjudicated to the previously identified inflammatory subphenotypes applying a validated parsimonious model using variables measured median 10.6 h [IQR, 8.0–31.4] prior to ICU discharge. Subphenotype distribution at ICU discharge, clinical characteristics and outcomes were analyzed. As a sensitivity analysis, a latent class analysis (LCA) was executed for subphenotype identification based on plasma protein biomarkers at ICU discharge reflective of coagulation activation, endothelial cell activation and inflammation. Concordance between the subphenotyping strategies was studied.ResultsOf the 8332 patients included in the original cohort, 1483 ICU-survivors had plasma biomarkers available and could be assigned to the inflammatory subphenotypes. At ICU discharge 6% (n = 86) was assigned to the hyperinflammatory and 94% (n = 1397) to the hypoinflammatory subphenotype. Patients assigned to the hyperinflammatory subphenotype were discharged with signs of more severe organ dysfunction (SOFA scores 7 [IQR 5–9] vs. 4 [IQR 2–6], p < 0.001). Mortality was higher in patients assigned to the hyperinflammatory subphenotype (30-day mortality 21% vs. 11%, p = 0.005; one-year mortality 48% vs. 28%, p < 0.001). LCA deemed 2 subphenotypes most suitable. ICU-survivors from class 1 had significantly higher mortality compared to class 2. Patients belonging to the hyperinflammatory subphenotype were mainly in class 1.ConclusionsPatients assigned to the hyperinflammatory subphenotype at ICU discharge showed significantly stronger anomalies in coagulation activation, endothelial cell activation and inflammation pathways implicated in the pathogenesis of critical disease and increased mortality until one-year follow up.

Abstract PO1-05-14: Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer

Abstract Background: Visceral crisis (VC) in metastatic breast cancer (BC) is defined as severe organ dysfunction, as assessed by signs and symptoms, laboratory tests, and rapid disease progression. The management of this condition is currently based on limited retrospective evidence and expert opinions, since VC has been a common exclusion criterion in clinical trials. There is a paucity of real-world data regarding the management of BC VC. We aim to evaluate the survival outcomes and prognostic factors of first-line palliative chemotherapy for VC in a tertiary cancer center in Brazil. Methods: Data were retrospectively collected from patients with metastatic BC diagnosed with VC between 2017 and 2022 in a single cancer center. Our analysis focused on patients receiving first-line chemotherapy for VC. Patients with hormone receptor-positive BC could have been previously treated with endocrine therapy for metastatic disease. CDK4/6 inhibitors were not available in the cancer center during the study period. Prognostic factors associated with survival were evaluated through univariate and multivariable analyses, using the Cox regression model. Results: A total of 106 patients with VC were evaluated. Among them, 58.5% (62 patients) had not received any previous line of chemotherapy in the metastatic setting before the diagnosis of VC (1st line cohort). Median overall survival (mOS) in the total population was 1.7 months, significantly distinct from the 1st line cohort, which had a mOS of 4.9 months (p &amp;lt; 0.001). Focusing on the 1st line cohort, the most common type of VC was pulmonary (40.3%), followed by hepatic (24.2%), and medullary infiltration (21%). 66.1% of patients had HR+HER2- (mOS 9.3 months), 19.3% HER2+ (mOS 4.5 months), and 11.3% triple-negative BC (TNBC) (mOS 1.5 months). Most patients were treated for VC based on systemic therapy combinations (59.7%), while 32.2% received monochemotherapy, and 8.1% were managed with best supportive care (BSC) alone. In the population receiving multidrug therapy, the mOS was 9.3 months, compared to 4.9 months with monochemotherapy and 0.7 months in patients undergoing BSC. Nevertheless, the type of treatment received was not associated with OS in the multivariable analysis. In the multivariable analysis, the prognostic factors associated with worse mOS were TNBC subtype, hepatic VC), and ECOG-PS &amp;gt; 2. (Table). Among patients with hepatic VC, 73.7% died during the same hospitalization and 60.5% received chemotherapy within 30 days prior to death. Conclusions: Patients with VC due to BC have a poor prognosis, even in the context of first-line chemotherapy. Factors such as ECOG-PS, BC subtype, and VC type should be taken into account when discussing the expected outcomes of this life-threatening condition. Taking these factors into account can help physicians to differentiate patients who are more likely to benefit from systemic oncologic treatment from those for whom such therapy would be futile or potentially harmful. Median overall survival according to baseline characteristics and multivariable analysis (1st line cohort, n=62) Citation Format: Matheus de Oliveira Andrade, Vitor Hugo Felix, Renata Colombo Bonadio, Laura Testa. Outcomes of first-line chemotherapy for visceral crisis in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-14.

Circulating immune profile in granulomatosis with polyangiitis reveals distinct patterns related to disease activity

Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity.The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively.Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA+CCR5+CCR6−CCR7+/lowCD127−HLA-DR+CD2− classical monocytes and a lower frequency of CD45RA−CCR5-/lowCCR6−CCR7−CD127−HLA-DR+CD2+/− classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity.These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.