Higher Mortality In Patients Research Articles

Predicting the long-termoutcome of patients admitted with acute heart failure to the emergency department using renal markers

Abstract Introduction Renal dysfunction is one of the most important comorbidities in patients with chronic heart failure (HF) and frequently accentuated in the setting of acute HF (AHF). Serum creatinine and blood urea nitrogen (BUN) have been classically used as markers of renal dysfunction, despite having several limitations. High (BUN)/creatinine ratio has been associated with higher mortality in patients with HF. We aimed to predict the long-term outcome of patients admitted with acute heart failure to the emergency department using renal markers. Methods 900 patients admitted to our emergency department diagnosed with AHF were retrospectively analysed. Patients were divided into 4 groups according to BUN and SCr on admission: – BUN ≤33 mg/dL and SCr ≤1.56 mg/dL (group LowBUN/LowCr), n=544; – BUN ≤33 mg/dL and SCr >1.56 mg/dl (group LowBUN/HighCr), n=25; – BUN >33 mg/dL and SCr ≤1.56 mg/dL (group HighBUN/LowCr), n=131; – BUN >33 mg/dL and SCr >1.56 mg/dL (group HighBUN/HighCr), n=200; The primary end-point of this study was the occurrence of all-cause mortality during follow-up. Results The median (IQR) BUN level on admission was 28.0 (20) mg/dL, median (IQR) SCr level on admission was 1.15 (0.73) mg/d, mean age was 81±7 years, 50.8% (n=457) were women and median follow up was 7 months. A total of 41.2% patients were diabetic, 21.7% had at least mild COPD, CAD was present in 28.9% of cases, 44.0% had valvular heart disease and 68.4% patients had atrial fibrillation. Creatinine, BUN and Cr/BUN ratio predicted survival at 6 months (p<0.05). Survival was the lowest in the group HighBUN/HighCr and the highest in the group LowBUN/LowCr. As expected, BUN/Cr ratio was the highest in group HighBUN/LowCr and the lowest in group LowBUN/HighCr. Conclusions Despite not having the highest BUN/Cr ratio, patients with BUN >33 mg/dL and SCr >1.56 mg/dL showed the worst prognosis. Funding Acknowledgement Type of funding sources: None.

ACUTE PULMONARY EMBOLISM IN PATIENTS WITH UNDERLYING HEART FAILURE

ACUTE PULMONARY EMBOLISM IN PATIENTS WITH UNDERLYING HEART FAILURE

S37 The Impact of Early Detection of Malignant Biliary Obstruction by Endoscopic Ultrasound on Clinical Outcomes After Surgical Resection

Introduction: Computerized tomography (CT) scan and endoscopic ultrasound (EUS) are the main diagnostic tools for detecting periampullary cancers. EUS allows the detection of small tumors missed by CT scan in patients presenting with bile duct obstruction. However, the impact of EUS in diagnosing small tumors on clinical outcomes is yet to be explored. This study aimed to compare the tumor recurrence rate and survival benefit of patients following pancreaticoduodenectomy (PD) for periampullary cancers detected by abdominal CT vs. EUS after negative CT. Methods: A retrospective review of the EUS and surgery database from 2009 to 2021. The patients who underwent PD for periampullary cancer were recruited. The patients were divided into CT-guided surgery group (CT group) and EUS-guided surgery group (EUS group). The clinical outcomes between the 2 groups were compared. Results: 429 patients were enrolled. 372 patients were diagnosed by CT scan, and EUS diagnosed 57 patients after CT scans failed to detect the cause of bile duct obstruction. The mean age was 64.7+ 11.9 years. The common presentations included jaundice (79.0 %) and weight loss (66.9%). Pancreatic adenocarcinoma (PDAC) was the most common cancer (43.6%), followed by ampullary cancer (32.4%), distal cholangiocarcinoma (14.2%), and duodenal cancer (9.8%). There were no differences in patient demographics between the two groups regarding age, gender, and underlying diseases. Patients in the CT group had higher serum bilirubin (p=0.025), higher serum alkaline phosphatase (p=0.047), lower serum hematocrit (p=0.043), and larger CBD diameter (p=0.005) compared to the EUS group. The T and M staging were not different between the two groups; however, the percentage of patients with nodal metastasis was higher in the CT group (p=0.014). Multivariate analysis showed a trend towards higher recurrence and 5-year mortality rate in the CT group with odds ratios (OR) of 1.33 (95% CI, 0.82-2.13) and 1.43 (95% CI, 0.84-2.42), respectively. Subgroup analysis of PDAC and cholangiocarcinoma demonstrated a significantly higher mortality rate of patients in the CT group with an OR of 2.82 (95% CI, 1.14-6.99, p=0.026) and a trend toward a higher recurrence rate after surgery with the OR of 1.45 (95% CI, 0.80-2.66) compared to the EUS group. Conclusion: EUS added a diagnostic value in the early detection of periampullary cancers, which may lead to a survival benefit, especially in PDAC and cholangiocarcinoma.

S2219 A Rare Subtype of Colorectal Cancer Presenting as a Contained Perforation

Introduction: Colonic perforation comprises 3-10% of the initial presentation of Colorectal Cancer (CRC). Signet Ring Cell Carcinoma and Mucinous Adenocarcinoma are 2 distinct subtypes which occur with a very low incidence of 10-20% and 0.9-4%, respectively. Both are usually diagnosed at an advanced stage and have an overall worse prognosis than other types of CRC. Here we present a rare case of colonic mucinous adenocarcinoma with signet ring cell features manifesting as a contained perforated intra-abdominal mass necessitating surgery. Case Description/Methods: A 60-year-old male presented with fatigue, shortness of breath and anemia with hemoglobin of 4.8 g/dL. A computed tomography (CT) scan of the abdomen and pelvis was obtained which showed an intraperitoneal mass with a central necrotic component and air, suggesting communication to the small bowel. Due to the initial concern of a possible contained perforation, colonoscopy was deferred despite the patient never having one previously. Ultimately, the patient underwent a diagnostic laparoscopy which showed a large intra-abdominal mass with a mucinous surface involving multiple parts of the small bowel and sigmoid colon. This mass was removed along with a small bowel and sigmoid colon resection. Pathology was notable for moderately differentiated mucinous adenocarcinoma of the sigmoid colon with focal signet ring features with negative margins and no evidence of lymphovascular invasion. He was eventually discharged with instructions to follow up with Oncology for further treatment. (Figure) Discussion: Mucinous adenocarcinoma is characterized by the presence of abundant extracellular mucin which accounts for at least 50% of the tumor volume. Signet ring cells have copious amounts of mucin in the cytoplasm and nuclei located at the cell periphery. These lesions are usually located in the right colon and share similar characteristics on CT imaging including segments of concentric bowel wall thickening and ulcerations. Studies have shown that even a minor signet-ring cell component in CRC was associated with higher patient mortality. This becomes evident as these tumors diffusely infiltrate the submucosa with full thickness involvement of the bowel wall and have a high propensity for pelvic, peritoneal and ovarian metastasis. Treatment centers on surgical resection with adjuvant chemotherapy showing some benefit. Our case highlights an atypical presentation of a rare subtype of CRC for which gastroenterologists should maintain a high index of suspicion.Figure 1.: (Top) Signet Ring Cells in background of mucus (from sigmoid colon) (Bottom) Computed Tomography (CT) scan showing an intra-abdominal mass with a contained perforation.

Review on middle east respiratory syndrome corona virus in camel: Its public health importance and economic impact

Middle East respiratory syndrome corona virus (MERS-CoV) is a novel lineage C beta corona virus derived from bats which can cause acute viral respiratory disease in humans and in camels. According to a WHO report, MERS cases have been reported from 27 countries and there have been 2,428 confirmed cases, resulting in 838 deaths. MERS-CoV is transmitted to humans through close contact with dromedaries and it causes asymptomatic or mild-to-severe illness in the human population. MERS-CoV uses dipeptidyl peptidase-4 (DPP4) protein in Pipistrelluspipistrellus bats for cell entry. Dromedary camels are a host reservoir species for the MERS-CoV. It is suspected that nasal mucous, sputum, saliva, milk or uncooked meat of infected camels are the main sources of transmission. Several factors such as being male and comorbid pre-existing illnesses are associated with severe disease and high mortality rates in patients with MERS. Studies in Ethiopia, Burkina Faso and Morocco reported that the prevalence of MERS-CoV sero-positivity ranges between 85.1- 99.4%, 73.2-89.9% and 48.3-100%, respectively. The clinical presentation of infected patients often indicate the presence of hemoptysis, sore throat, fever, cough, shortness of breath, and other gastrointestinal symptoms such as diarrhea and vomiting. The average incubation period of MERS-CoV is 6-7 days. No vaccine or treatment is currently available for MERS-CoV. Supportive therapy necessitates respiration and circulatory support, preservation of renal and hepatic function, and prevention of secondary infections. This seminar paper is therefore, intended to highlight the public health and economic importance of the MERS-CoV.

65 yaş üstü hastalarda puanlama sistemlerinin şiddetli akut pankreatiti ve mortaliteyi erken öngörme açısından değerlendirilmesi

Purpose: The aim of this study is to investigate the power of disease severity scores to predict the development of Severe Acute Pancreatitis (SAP) and mortality in the early period over 65 years old diagnosed with acute pancreatitis in the emergency department. 
 Materials and Methods: We calculated RANSON (on admission) and Computed Tomography Severity Index (CTSI) in addition to Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission to the emergency department.
 Results: One hundred and sixty patients (46.9% over 80 years of age) were included in the study. We observed statistically higher length of hospitalization, longer duration of stay in the intensive care unit, SAP and higher mortality in patients over 80 years of age. When we examined the ROC curve, we determined that the AUC values of the BISAP score were highest in both SAP and mortality estimation (AUC: 0.911, 95% CI 0.861-0.962; AUC: 0.918, 95% CI 0.864-0.9722, respectively). Binary logistic analysis indicated a 4.7-fold increased risk for SAP and a 12.3-fold increased mortality for each unit increase in BISAP score value.
 Conclusion: BISAP may be a good predictor for SAP and mortality estimation on admission to the emergency department in patients over 65 years of age with acute pancreatitis.

Covid-19 Hastalarında Gelişen Solunum Yetmezliğinde Veno-venöz Ekstrakorporeal Membran Oksijenasyonu; Güney Marmara Bölgesi Tek Merkez Deneyimi

Giriş ve Amaç: Covid-19 hastalığında gelişen Akut Respiratuar Distres Sendromu (ARDS) sonucunda mekanik ventilasyon ihtiyacı ve mortalite oranları artmaktadır. Covid-19 pandemisinde, Ekstrakorporeal Membran Oksijenasyon (ECMO) destek tedavisinin rolü hala tam olarak bilinmemektedir. Bu retroprespektif çalışmada, Covid-19 nedeniyle ARDS gelişen hastalarda uyguladığımız ECMO destek tedavisinin etkinliğini değerlendirmeyi amaçladık.
 Gereç ve Yöntemler: Bursa Şehir Hastanesi Anestezi ve Reanimasyon Yoğun Bakım ünitesinde Mart 2021-Eylül 2021 tarihleri arasında ECMO desteği alan hastalar geriye dönük olarak değerlendirildi. Çalışma süresinde 12 hastada ARDS nedeniyle ECMO destek tedavisi uygulandı.
 Bulgular: 12 hastaya veno-venöz ECMO (vv-ECMO) uygulandı. Hastaların dokuzu (%75) erkek, üçü (%25) kadın ve ortalama yaş 49.4 (35-70) olarak bulundu. Hastaların hastaneye yatışından entübasyon için geçen süre ortalama 8.08 (1-23) gündü. Entübasyon gününden ECMO desteğinin başlangıcına kadar geçen süre ortalama 3.08 (1-7) gün ve ECMO desteğinin ortalama süresi 12.3 (1-23) gün olarak bulundu. Sadece 1 hasta (%8,3) dekanüle edildikten sonra taburcu oldu.
 Sonuç: ECMO destek tedavisi, Covid-19 hastalığına sekonder gelişen ARDS hastalarında yüksek mortalite ile ilişkilidir. Ancak Covid-19 hastalığında ECMO, erken dönemde uygulandığı zaman hayat kurtarıcı bir destek yöntemidir. ECMO'nun Covid-19 nedeniyle ARDS tablosundaki kritik hastalarda kurtarma tedavisi olarak faydası şu ana kadar sınırlıdır ve bu hasta grubunda kullanımını için daha çok çalışmalara ihtiyaç vardır.

Clinical association between tacrolimus intra-patient variability and liver transplantation outcomes in patients with and without hepatocellular carcinoma

Tacrolimus is the mainstay of immunosuppression in liver transplantation to prevent rejection. However, the clinical use of tacrolimus is complicated by its narrow therapeutic window and significant intra-patient variability (IPV). High tacrolimus IPV is associated with overexposure and adverse effects, including malignancy. The effects of tacrolimus IPV in liver transplant recipients with and without hepatocellular carcinoma (HCC) are unknown. We investigated the association between tacrolimus IPV and transplant outcomes in 636 liver transplant patients. Tacrolimus IPV was determined by calculating the coefficient of variance (CV) of outpatient tacrolimus trough levels from 3 to 12 months after transplantation. High tacrolimus IPV was defined as CV > 30%. Patients were grouped according to tacrolimus IPV and HCC status. Among 636 liver transplant patients, 349 had HCC and 287 had no HCC. Overall survival in HCC patients was significantly reduced with high tacrolimus IPV (P < 0.001), whereas survival of non-HCC patients was not associated with tacrolimus IPV. Multivariable analysis confirmed the independent association between high tacrolimus IPV and overall mortality in HCC patients (HR, 3.010; 95% CI, 1.084–4.918). HCC recurred in 59 patients (16.9%) post-transplantation. After adjusting for donor/recipient factors, immunosuppression, and tumor characteristics, high tacrolimus IPV was independently associated with an increased risk of HCC recurrence (HR, 2.196; 95% CI, 1.272–3.791). High tacrolimus IPV was associated with significantly increased risks of overall mortality and HCC recurrence in liver transplant recipients with HCC.

Risk of pre-existing hyponatremia and mortality in patients with traumatic brain injury across age groups

Traumatic brain injurySodiumClinical outcomes.

Risk Factors for Mortality in Patients with Stenotrophomonas maltophilia Bloodstream Infections in Immunocompetent Patients.

This study aimed to evaluate bloodstream infections caused by Stenotrophomonas maltophilia in immunocompetent patients with respect to clinical features and risk factors for mortality. We reviewed bloodstream infections detected between January 1, 2012, and July 1, 2021, to identify nosocomial S. maltophilia bacteremia in Koşuyolu Research and Training Hospital. We identified a total of 97 patients with S. maltophilia bloodstream infections. Of these, 17 patients were excluded because of community-acquired infections (n=9), contamination with S. maltophilia (n=3), and insufficient data (n=5), with 80 (57.5% males) patients remaining for analysis. The source of infection was the respiratory tract in 28 (35%) patients. A central venous catheter was used in 60 (75%) patients, which required replacement in 23 patients within five days after detecting S. maltophilia bacteremia. On antimicrobial susceptibility testing, 71 strains were found to be susceptible and 9 (11.3%) resistant to trimethoprim-sulfamethoxazole. Thirty-day mortality was 33.8%. Non-survivors differed significantly from survivors with respect to higher rates of central venous catheters ( p=0.020), mechanical ventilation (p=0.006), urinary catheters (p=0.021), septic shock (p=0.001), hypoalbuminemia (p=0.026) and thrombocytopenia (p =0.039). S. maltophilia bacteremia was independently associated with mortality in patients with hypoalbuminemia, and replacement of central venous catheters had a protective role in reducing mortality. As with other bacterial infections, S. maltophilia bacteremia is associated with a considerably high mortality rate in patients with cardiac conditions. The replacement of the catheter seems to play a beneficial role in 30-day survival.

COVID-19 and the cardiovascular system-current knowledge and future perspectives.

The current coronavirus disease 2019 (COVID-19) pandemic has had devastating impact on populations around the world. The high mortality rates in patients with COVID-19 has been attributed to the influence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its causative viral agent, on several physiological systems in human body, including the respiratory, cardiovascular, and neurological systems. There is emerging evidence on propensity of this virus to attack cardiovascular system. However, various pathophysiological mechanisms by which SARS-CoV-2 interacts with cardiovascular system and leads to high morbidity and mortality, including cardiovascular complications, are poorly understood. This mini review aims to provide an update on the current knowledge and perspectives on areas of future research.

Complications and Mortality after CABG Surgery in Patients with Reduced Ejection Fraction

Coronary artery bypass grafting (CABG) is a complex, high-tech surgical intervention. Its success depends not only on the skill and experience of the surgeon but equally on the coherence of work and professionalism of all services involved in the operation. Severe left ventricular (LV) dysfunction after heart surgery is one of the main causes of cardiogenic shock, which is characterized by a local transient reduction of myocardial contractility (“stunned” myocardium) and/or significant cell damage caused by ischemia. In this state, systemic metabolic disorders often occur: increased concentration of free fatty acids, lactic acidosis, hypoxemia, and increased catecholamine content. General approaches to determining the risk of CABG surgery have not been definitively established. In addition, the data concerning the choice of optimal tactics in patients with a reduced ejection fraction (EF) are still limited. Relatively high early operative mortality in patients with reduced left ventricular EF requires further serious study.&#x0D; The aim. To determine the dominant complications and causes of fatal cases in patients with reduced LV contractility after CABG surgery.&#x0D; Materials and methods. The study included 210 patients with EF of 35% or less, who underwent CABG at the National Amosov Institute of Cardiovascular Surgery in the period from 01/01/2015 to 12/31/2021. Among them were 190 men (90.5%) and 20 women (9.5%). The age of the patients ranged from 29 to 83 years (61.1±8.9). Most patients underwent revascularization of three or more arteries.&#x0D; Results and discussion. In the group of patients with EF 35-30% in the postoperative period, acute heart failure (HF) occurred in 5 (3.8%) cases, respiratory failure (RF) was observed in 3 (2.3%) cases, renal failure in 3 (2.3%) cases, central nervous system (CNS) complications in 5 (3.8%). At the same time, along with the decrease in EF, the frequency of postoperative complications increased. In patients with EF below 24%, the frequency of postoperative complications increased significantly: acute HF was noted in 3 (15%) cases, RF in 5 (25%) cases, renal failure in 2 (10%) cases, CNS complications were noted in 0 (0%) cases. The duration of artificial lung ventilation increased significantly to 24.9±27.7 hours, the length of stay in the intensive care unit increased to 12.8±8 days, and the total length of stay of the patient in the hospital to 20.2±11.7 days.&#x0D; Conclusion. Based on the data we received, we concluded that: in patients with reduced LV myocardial contractility, such complications as HF, RF and renal failure, CNS complications most often occur; in addition, their frequency is higher than that in patients with preserved EF and increases with its decrease; one of the most frequent and life-threatening complications in this group of patients was acute HF; the use of intra-aortic balloon pump allows to avoid or improve treatment of HF and, at the same time, to increase survival in patients with reduced LV contractility.

Sex and ethnicity modified high 1-year mortality in patients in Singapore with newly diagnosed atrial fibrillation

We investigated sex and ethnic differences in the incidence, clinical characteristics and 1-year mortality of patients with newly diagnosed AF in a multi-ethnic population. This retrospective cohort study of patients diagnosed with AF from 2008 to 2015 was based on medical claims, casemix and subvention data submitted to the Ministry of Health. Patients with AF were matched with controls without AF for age (3-year bands), sex and ethnicity, and categorised as middle-aged (45-64 years) or elderly (≥65 years) among major ethnic groups in Singapore (Chinese, Malay and Indian). Among 40,602 adults with AF (elderly 74%), Malays had the highest age-standardised incidence rate of AF, followed by Chinese and Indians; and the rate was higher in men. Despite having the worst cardiovascular risk profile, Indians had the lowest prevalence and incidence of AF. The 1-year mortality rate after newly diagnosed AF was 22-26 deaths per 100 people. Newly diagnosed AF was independently associated with increased 1-year all-cause mortality among middle-aged (adjusted odds ratio [AOR] 9.08, 95% confidence interval [CI] 7.36-11.20) and elderly adults (AOR 3.60, 95% CI 3.40-3.80) compared with those without AF. Sex differences in mortality among patients with AF were limited to elderly adults (men: AOR 1.17, 95% CI 1.11-1.24), while Indians were associated with a 30% increased odds of mortality compared with Chinese regardless of age (middle-aged: AOR 1.27, 95% CI 1.09-1.548 elderly: AOR 1.33, 95% CI 1.22-1.45). Variations in incidence, clinical profile and 1-year mortality of patients with AF in a nationwide cohort were influenced by sex and ethnicity. Newly diagnosed AF portends a worse prognosis and is a marker of high mortality within the first year.

Effect size of Dna-j heat shock protein family B member 9 (DNAJB9) biomarker in kidney biopsy specimens on kidney outcomes in fibrillary glomerulonephritis

Background. Fibrillary glomerulonephritis is a rare glomerular disease that presents with hypertension, hematuria, nephrotic syndrome and renal insufficiency. The purpose of this research was to assess effect of DNAjB9 staining marker in kidney biopsy specimens on kidney outcomes. Materials and methods. In this analytic (experimental) clinical study with randomized clinical trial design in meta-analysis article, 72 patients with biopsy-proven fibrillary glomerulonephritis were investigated. Clinical features, laboratory data at initial presentation, management and outcomes were collected. The paper has written based on searching PubMed Central and Google Scholar to identify potentially relevant articles. Median, percentage, mean ± standard deviation (SD), two-tailed t and Chi-square, two proportion difference meta-analysis and Kaplan-Meier analysis were used for statistical evaluation. Moreover, relative risk, odds ratio, Spearman’s correlation for statistical analyses were used. Results. The median and interquartile range of age of patients with fibrillary nephropathy at the time of diagnosis were 55 and 18 years, respectively. There was no statistically significant difference between two sex groups of males and females in current research (p-value: 0.35). There was significant statistical correlation between elevated serum creatinine level and time of last serum creatinine measurement with p-value of 0.01 and confidence interval (CI) of 0.7820 to –0.1258 during follow-up. Relative risk of kidney failure progression to kidney replacement therapy (↑ ≥ 2-fold in serum creatinine or dialysis or kidney transplant) in DNAjB9-positive (group I) and DNAjB9-negative patients (group II) was assessed 2.67 with 95% CI of 1.128 to 6.3044 and p-value of 0.025. Odds ratio of kidney failure progression to kidney replacement therapy (↑ ≥ 2-fold in serum creatinine or dialysis or kidney transplant) was assessed 4.33 with 95% CI of 0.9464 to 19.8417 and p-value of 0.058. There was statistically significant difference when comparing group I and group II for mortality probability (Kaplan-Meier analysis) during follow-up (P &lt; 0.0001). Conclusions. The present study revealed high mortality in DNAjB9-negative (8/64, 12.5%) versus DNAjB9-positive patients (0/8) with statistically significant level. Relative risk and odds ratio of kidney failure progression to kidney replacement therapy were assessed 2.67 and 4.33, respectively.

Neuropsychiatric manifestations are associated with increased mortality in Indian patients with lupus: A single centre retrospective observational study

To study the prevalence of different NPSLE manifestations in our cohort and to compare clinical and immunological features and outcomes including mortality of patients with NPSLE and SLE controls without NP involvement. This was a retrospective study in a tertiary care referral centre. All patients of SLE seen in the last 10 years and fulfilling the SLICC criteria with neuropsychiatric manifestations as per the ACR definitions were included. Patients of SLE without NP involvement were sequentially assigned as controls in a ratio of 1:2. Of the 769 patients diagnosed with SLE from Jan 2011 to December 2020, 128 (16.6%) had NPSLE manifestations as per the ACR definitions. The commonest NPSLE manifestation was seizures (6.5%) followed by cerebrovascular accident (3.9%). NPSLE manifestation occurred at the first presentation of SLE in 99/128 (77.3%) patients and 58 (45.3%) patients had more than one NPSLE manifestation. Lupus anticoagulant and anticardiolipin antibody were tested in 120 patients and were positive in 16 (13.3%) and 12 (10%), respectively. No difference was found in anti-ribosomal p, lupus anticoagulant and anticardiolipin antibodies between the cases and controls. Twenty-one (16.4%) deaths occurred in patients with NPSLE (median follow-up of 40 months) as compared to 13 (5%) in controls (median follow-up of 32 months) (p = <0.001). The cumulative survival of patients with NPSLE was lower as compared to controls (p < 0.001). Relapse of NPSLE was seen in 11(8.6%) patients and was associated with mortality (p = 0.017). Seizures and cerebrovascular accidents are the commonest NPSLE syndromes in our patients. The presence of NPSLE was associated with high mortality in Indian patients with lupus.

UPLC/Q-TOF MS-Based Urine Metabonomics Study to Identify Diffuse Axonal Injury Biomarkers in Rat.

Diffuse axonal injury (DAI) represents a frequent traumatic brain injury (TBI) type, significantly contributing to the dismal neurological prognosis and high mortality in TBI patients. The increase in mortality can be associated with delayed and nonspecific initial symptoms in DAI patients. Additionally, the existing approaches for diagnosis and monitoring are either low sensitivity or high cost. Therefore, novel, reliable, and objective diagnostic markers should be developed to diagnose and monitor DAI prognosis. Urine is an optimal sample to detect biomarkers for DAI noninvasively. Therefore, the DAI rat model was established in this work. Meanwhile, the ultraperformance liquid chromatography quadrupole-time-of-flight hybrid mass spectrometry- (UPLC/Q-TOF MS-) untargeted metabolomics approach was utilized to identify the features of urine metabolomics to diagnose DAI. This work included 57 metabolites with significant alterations and 21 abnormal metabolic pathways from the injury groups. Three metabolites, viz., urea, butyric acid, and taurine, were identified as possible biomarkers to diagnose DAI based on the great fold changes (FCs) and biological functions during DAI. The present study detected several novel biomarkers for noninvasively diagnosing and monitoring DAI and helped understand the DAI-associated metabolic events.

P243 Case series of Cryptococcal Meningitis—Experience in North Western India over 1 year (2021–22)

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveCryptococcosis is an opportunistic fungal infection causing high morbidity and mortality in patients, preferentially affecting immunocompromised. It can cause a wide array of clinical manifestation, which includes meningitis, pulmonary, as well as disseminated infection. Cryptococcus neoformans causes more than 90% cases of cryptococcal meningitis.MethodologyWe performed a retrospective review of patients with confirmed cryptococcal meningitis during 1 year period from 2021 to 2022 in tertiary care center, AIIMS Jodhpur. We assessed clinical, radiological, microbiological, and biochemical parameters along with treatment provided and outcomes of the patient.ResultsOf 189 patients screened for suspected cryptococcal meningitis, 6 were microbiologically confirmed positive. All the patients were immunocompromised, of which four were HIV positive and one was a solid organ transplant recipient on immunosuppression and one was old TB Meningitis. Most common symptom was headache and altered sensorium (100%). Radiological findings showed 30% had no significant abnormality. CSF examination revealed average CSF protein 97.6 (63-163), CSF chloride 103.3 (108-132), sugar 36.33 (1-68), with predominant lymphocytes. All the patients were microbiologically confirmed by CSF cryptococcal latex test. A total of 4/5 patients received amphotericin B (3 mg/kg) with fluconazole (1200 mg) for 2 weeks in the induction phase followed by fluconazole consolidation phase and maintenance phase. Of the five patients, four patients survive with a good response to the treatment with one fatality.ConclusionThrough our case series we emphasize the fact that Cryptococcal meningitidis may present with non-significant radiological features. Thus, the differential diagnosis of C. meningitidis must always be thought of when an immunocompromised patient presents with headaches and other signs and symptoms involving the central nervous system.

Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions.

Venous leg ulcers, diabetic foot ulcers, and pressure ulcers are complex chronic wounds with multifactorial etiologies that are associated with high patient morbidity and mortality. Despite considerable progress in deciphering the pathologies of chronic wounds using "omics" approaches, considerable gaps in knowledge remain, and current therapies are often not efficacious. We provide a comprehensive overview of current understanding of the molecular mechanisms that impair healing and current knowledge on cell-specific dysregulation including keratinocytes, fibroblasts, immune cells, endothelial cells and their contributions to impaired reepithelialization, inflammation, angiogenesis, and tissue remodeling that characterize chronic wounds. We also provide a rationale for further elucidation of ulcer-specific pathologic processes that can be therapeutically targeted to shift chronic nonhealing to acute healing wounds.

WELLENS' SYNDROME: A DANGEROUS HEART INFREQUENCY

Wellens syndrome is an acute coronary syndrome with a high risk of life-threatening myocardial ischaemic disease. It should be emphasised that it is not always an acute process, and may manifest itself over periods of weeks and result in an Impending Acute Myocardial Infarction of the anterior wall. The aim of this research lies in the importance of detecting this pathology in a timely manner, because, although it is infrequent, it has a high mortality rate in patients who present it and do not have an early detection. KEY WORDS: wellens syndrome. inverted t-waves. coronary revascularisation. acute myocardial infarction.

IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice

BackgroundCardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms.MethodsIn this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40–/– mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40–/– mice to explore their effects on LPS-induced cardiac dysfunction.ResultsThe results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40−/− mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65.ConclusionIL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC.