CaP Patients Research Articles

Community-Acquired Pneumonia in the Immunocompromised Patients: An Observational Study from a Single Center, TURKEY.

Immunocompromised hosts are underrepresented in clinical trials. The goal of the study to search for the unmet needs in the management of CAP in immunocompromised hosts. An observational study was conducted with CAP patients documented immunocompromise or those aged over 65 who have at least one chronic visceral disease. We clinically assessed the eligible patients at the time of the presentation with a follow-up assessment on day three of admission. The data were statistically analyzed to assess the impact of variables on mortality. During a 15-month study period, 140 CAP patients were observed. The overall 30-day mortality rate was 17.8%. The mortality rate was significantly higher in patients with sputum cultures positive for Pseudomonas aeruginosa, or two bacteria (p=0.049). Tachypnea was a stronger predictor of mortality. Failure to achieve a treatment response within three days of treatment identified the population with the worst outcomes. Less than half of such patients survived past one month. Dynamic response assessment emerged as potentially the strongest predictor of outcomes in CAP of susceptible hosts. We propose that immunocompromised CAP patients who fail to respond early to treatment face extremely high rates of mortality, identifying an unmet need.

Overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities

Abstract Background Evidence regarding the likelihood of overdiagnosis in prostate cancer (CaP) screening with PSA are mainly based on clinical trials, which include younger population with fewer comorbidities than those receiving the test in clinical practice. We aimed to assess the likelihood of overdiagnosis and associated variables using real-world data. Methods Retrospective cohort of men >40 years with PCa, who had been diagnosed being asymptomatic and after a positive PSA test in the previous 12 months in two hospitals (2004-2022). The probability of overdiagnosis was estimated considering the life expectancy of the Spanish male in the year 2022 and the Charlson Comorbidity Index (lead time 10 years). PSA values and Gleason score were included as independent variables. Results Of the 2,331 patients in the cohort, 1,070 (46%) met the inclusion criteria for this analysis. The median follow-up time was 5.7 years (IQR 3.2-8.6). The median age was 71 years (IQR 65-78) and 37% had more than one comorbidity. At diagnosis, the median life expectancy was 12 years (IQR 4-18) and the probability of overdiagnosis was 30.8% (IQR 17.6-52.4). Patients with PSA levels >10 mg/dl tended to be older and with more comorbidities than those with PSA levels 4-10 mg/dl, and thus, with shorter life expectancy. The median probability of overdiagnosis was higher in patients with PSA levels >10 mg/dl (41.4%, IQR 21.5-73.9) than in those with PSA levels 4-10 mg/dl (20.1%, IQR 12.8-30.4), p < 0.001. Correspondingly, patients with Gleason score ≥8 were more likely to be overdiagnosed (median 42.6%, IQR 23.6-68.6) than those with Gleason score ≤6 (median 20.1%, IQR 12.8-30.4) (p < 0.001). Conclusions In clinical practice, older patients with comorbidities showed high PSA levels and Gleason score ≥8, presenting low life expectancy at diagnosis and, therefore, high probability of overdiagnosis. This highlights the importance of considering the patient’s comorbidities when ordering a new PSA test. Key messages • A detailed assessment of the prevalence of comorbidities among CaP patients in real-life settings has significant implications for patient management. • The decision to make an early diagnosis should be based on individual life expectancy, where comorbidity is at least as important as age.

PNI score as predictor of clinical outcomes among in-hospital cap patients with and without concomitant PTB in a tertiary government hospital: a retrospective - Cohort study

PNI score as predictor of clinical outcomes among in-hospital cap patients with and without concomitant PTB in a tertiary government hospital: a retrospective - Cohort study

The unique metabolic and lipid profiles of patients with severe COVID-19 compared to severe community-acquired pneumonia: a potential prognostic and therapeutic target

ABSTRACT Background Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment. Research design and methods Plasma samples were taken at hospital admission (baseline) and on the 5th day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS. Results 127 patients, 17 with CAP and 110 with COVID-19, were included. The analysis revealed 87 altered metabolites, suggesting changes in the metabolism of arachidonic acid, glycerolipids, glycerophospholipids, linoleic acid, pyruvate, glycolysis, among others. Most of these metabolites are involved in inflammatory, hypoxic, and thrombotic processes. At baseline, the greatest differences were found in phosphatidylcholine (PC) 31:4 (p < 0.001), phosphoserine (PS) 34:3 (p < 0.001), and phosphatidylcholine (PC) 36:5 (p < 0.001), all of which were notably decreased in COVID-19 patients. At follow-up, the most dysregulated metabolites were monomethyl-phosphatidylethanolamine (PE-Nme) 40:5 (p < 0.001) and phosphatidylcholine (PC) 38:4 (p < 0.001). Conclusions Metabolic and lipidic alterations suggest inhibition of innate anti-inflammatory and anti-thrombotic mechanisms in COVID-19 patients, which might lead to increased viral proliferation, uncontrolled inflammation, and thrombi formation. Results provide novel targets for predictive biomarkers against CAP and COVID-19. Trial registration Not applicable.

Associations Between Severe Influenza-Complicated Thromboembolism Events, Intensive Care Unit Stays and Mortality, and Associated Risk Factors: A Retrospective Cohort Study.

A retrospective cohort study was conducted, recruiting consecutive patients with TE events admitted to the ICU between December 2015 through December 2018 at our institution in Taiwan. The study included a group of 108 patients with severe influenza and a control group of 192 patients with severe community-acquired pneumonia. Associations between complicated TE, length of ICU stay, and 90-day mortality were evaluated using logistic regression analysis, and risk factors were identified using univariate and multivariate generalized linear regression analyses. TE event prevalence was significantly higher in ICU patients with severe influenza than in ICU patients with severe CAP (21.3% vs. 5.7%, respectively; p < 0.05). Patients with severe influenza who developed TE experienced a significant increase in the ratio of mechanical ventilation use, length of mechanical ventilation use, ICU stay, and 90-day mortality when compared to patients without TE (all p < 0.05). The comparison of severe CAP patients with and without TE revealed no significant differences (p > 0.05). The development of thromboembolic events in patients with severe influenza or severe noninfluenza CAP is linked to influenza infection and hypertension (p < 0.05). Furthermore, complicated TE and the severity of the APACHE II score are risk factors for 90-day mortality in ICU patients with severe influenza (p < 0.05). Patients with severe influenza and complicated TE are more likely to have an extended ICU stay and 90-day mortality than patients with severe CAP. The risk is significantly higher for patients with a higher APACHE II score. The results of this study may aid in defining better strategies for early recognition and prevention of severe influenza-complicated TE.

A radiomics model utilizing CT for the early detection and diagnosis of severe community-acquired pneumonia

BackgroundCommunity-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes.MethodsA retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35).ResultsThe radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set.ConclusionsThe radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.

MiR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

PurposeSevere community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCAP is of urgent need. The function of miR-486-5p in SCAP diagnosis and prognosis was evaluated to identify a promising biomarker for SCAP.Patients and methodsThe serum miR-486-5p in 83 patients with SCAP, 52 healthy individuals, and 68 patients with mild CAP (MCAP) patients were analyzed by PCR. ROC analysis estimated miR-486-5p in screening SCAP, and the Kaplan-Meier and Cox regression analyses evaluated the predictive value of miR-486-5p. The risk factors for MCAP patients developing SCAP were assessed by logistic analysis. The alveolar epithelial cell was treated with Klebsiella pneumonia to mimic the occurrence of SCAP. The targeting mechanism underlying miR-486-5p was evaluated by luciferase reporter assay.ResultsUpregulated serum miR-486-5p screened SCAP from healthy individuals and MCAP patients with high sensitivity and specificity. Increasing serum miR-486-5p predicted the poor outcomes of SCAP and served as a risk factor for MCAP developing into SCAP. K. pneumonia induced suppressed proliferation, significant inflammation and oxidative stress in alveolar epithelial cells, and silencing miR-486-5p attenuated it. miR-486-5p negatively regulated FOXO1, and the knockdown of FOXO1 reversed the effect of miR-486-5p in K. pneumonia-treated alveolar epithelial cells.ConclusionmiR-486-5p acted as a biomarker for the screening and monitoring of SCAP and predicting the malignancy of MCAP. Silencing miR-486-5p alleviated inflammation and oxidative stress induced by K. pneumonia via negatively modulating FOXO1.

Impact of the COVID-19 pandemic on Haemophilus influenzae infections in pediatric patients hospitalized with community acquired pneumonia

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018–2019) and during (2020–2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients’ age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.

Highly diverse sputum microbiota correlates with the disease severity in patients with community-acquired pneumonia: a longitudinal cohort study

BackgroundCommunity-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis.MethodsWe conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced.ResultsThe sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections.ConclusionCollectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

IntroductionLymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. MethodsRetrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). ResultsA total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN – group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN – patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). ConclusionConventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Relationship between neutrophil to lymphocytes ratio, red cell distribution width, procalcitonin, neutrophil to albumin ratio, and bun to albumin ratio with mortality of severe cap patients with septic shock

Background: Septic shock is one of severe community-acquired pneumonia (CAP) complication with high mortality. Various laboratory parameters had been associated with poor outcome including neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), procalcitonin, neutrophil to albumin ratio (NAR), and bun to albumin ratio (BAR). This study aimed to know the relationship between inflammatory markers with mortality of severe CAP patients with septic shock. Methods: This study is an observational analytic study using a cohort retrospective design conducted in Prof. I.G.N.G. Ngoerah General Hospital over a 3 years’ period (January 2020 to July 2023). The relative risk (RR) values showed relative risk of each parameter to mortality. Results: Of total 73 subjects, mortality was found in 68.5%. Male predominance was found (65.8%). Comorbid disease was reported in 69 subjects (94.5%), most found was cardiovascular disease (63%). Majority of the subjects did not have history of prior antibiotics use (86.3%). In multivariate analysis, it was found that NLR with cutoff ≥16.5 (p value 0.044; 95% CI 1.039-14.011; RR 3.816), procalcitonin ≥1.82 (p value 0.029; 95% CI 1.148-13.560; RR 3.945), and BAR ≥8.13 (p value 0.003; 95% CI 1.961-21.912; RR 7.399) are associated with mortality. There was no relationship between RDW ≥14.65 (p value 0.159; 95% CI 0.658-12.877) and NAR ≥4.5 (p value 0.436; 95% CI 0.429-7.106) with mortality in this study. Conclusions: Mortality of severe CAP patients with septic shock in this study is high. Higher NLR, procalcitonin, and BAR values have a significant relationship with mortality of severe CAP patients with septic shock.

Abstract PO3-01-11: Clinical Significance of HER2-low Breast Cancer

Abstract Context: Breast cancers with a HER2 immunohistochemistry (IHC) result of 1+ or 2+ and a negative amplification test (FISH), previously treated as HER2 negative, are now termed HER2-low and are being targeted for treatment. We aim to explore the clinical significance of this group. Design: 394 breast cancer cases were included from our institution from 2010. Demographic and clinicopathological data on receptors status, recurrence/metastasis, treatment, and survival was collected. HER2 was re-evaluated according to the 2018 CAP ASCO guidelines and patients were treated according to standardized protocol. HER2 +2 with positive FISH and HER2 +3 were excluded. HER2-low was compared to HER2-0. Appropriate statistical analysis was performed. Results: 394 patients (76% IDC; 8% ILC; 16% others) were included, such that 91 (23%) were HER2-0 and 303 (77%) HER2-low. Median age was 58 years (range: 25-95). Median follow-up was 54 months (range: 0.5-259). Grade 3 tumors were significantly more frequent in HER2-0 than HER-2 low (52% vs. 33%; p=0.010). Grade 3 or ILC patients had higher risk of recurrence than Grade 1 (HR 2.55; p&amp;lt; 0.001) or IDC (HR 2.03; p=0.033). After adjusting for grade, HER2-low had a significantly worse RFS than HER2-0 (HR 1.58; p=0.043). In the ER negative subgroup, HER2-low had significantly worse RFS than HER2-0 (HR 2.02; p=0.023). No differences in overall survival were seen. Conclusions: Our data showed higher recurrence in HER2-low group compared to HER2-0. This suggests that breast cancer patients with HER2- low are a separate entity and might benefit from additional targeted therapy. Table 1 Hazard regression analysis of risk factors associated with recurrence Citation Format: Fadi Zaiem, Asem AbuJamea, Mira Kheil, Anna Numi, Omar Abbas, Sanaa Awada, Ragad Almsaddi, Saleh Al-Juburi, Lauren Larson, Deepti Jain, Maya AlSaghir, Hyejeong Jang, Seongho Kim, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. Clinical Significance of HER2-low 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 PO3-01-11.

Abstract 6432: Co-expression of HERV-R, CCND1, BRAF, FOXA1, TMPRSS2, ATF4 and low expression of BAZ1B and KMT2D is associated with early detection and poor prognosis of prostate cancer in African Black men from Nigeria

Abstract Prostate cancer (CaP) is a heterogeneous disease characterized by features of non-aggressive, slow-growing disorders to fast-growing disease. Men of African ancestry have disproportionately higher incidence and mortality rates for CaP than men of European ancestry. While there is evidence for a higher genetic predisposition for incidence of CaP in men of African ancestry compared to men of European ancestry, there is paucity of molecular biology and transcriptomic studies on the role of Human endogenous retroviruses (HERVs) in relation to CaP-associated genes in CaP pathogenesis and prognosis. In this study, we performed bulk RNA sequencing (RNA-seq) on formalin-fixed paraffin-embeded (FFPE) CaP samples from Nigerian CaP patients to investigate the expression significance of HERV-R in relation to FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF genes. Based on this findings, we used immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) to confirm the expression pattern of the HERV-R and FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF proteins on 45 FFPE CaP and blood plasma samples, and 5 CaP-free samples from patients in Zaria, Nigeria. Most of these patients were longitudinally followed from 2017 to date. The DESeq2 procedure was used for data processing, analysis, and differential expression analysis of the aforementioned genes. We found a significant expression of HERV-R in relation with FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4, CCND1 and BRAF in the CaP from rural Africans in Nigeria. HERV-R expression was found to be associated with increased PSA level, higher Gleason grade and poor prognosis of CaP. A CaP sample from an 80-year-old patient that was histologically diagnosed to have no malignancy seen despite high PSA level of &amp;gt;100 and poor disease outcomes shows a significant cytoplasmic expression of HERV-R, indicating that HERV-R may serve as an important biomarker for early detection. Unfortunately, we lost the 80-year-old patient to late detection before revisiting his case for proper histological diagnosis and management. In addition, some histologically diagnosed BPH samples that are apparently reported to be CaP-free show stromal cells expression of HERV-R and in some cases show expression of HERV-R in the prostatic glandular areas. In contrast, stromal cells of the CaP samples show no expression of HERV-R, but strong expression in the glandular areas. This may implicate a gradual transition from benign prostatic lesion to malignant prostatic disease. HERV-R expression in CaP may have a relationship with BRAF, CCND1, FOXA1, TMPRSS2 and ATF4 genes. These findings combined together, underscore the importance of the expanded concept of HERV-R expression and CaP associated genes in early detection of CaP and prognosis. Citation Format: Faruk Mohammed, Konrad Stawiski, Halimatu Sadiya Musa, Sani Kamarudeen Owolabi, Sani Abubakar, Solomon O. Rotimi, Adoke Kasimu Umar, Yawale Iliyasu, Ahmad Bello, Folakemi T. Odedina, Clayton C. Yates, Kevin Petrie, Franklin W. Huang, Sani Ibrahim. Co-expression of HERV-R, CCND1, BRAF, FOXA1, TMPRSS2, ATF4 and low expression of BAZ1B and KMT2D is associated with early detection and poor prognosis of prostate cancer in African Black men from Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6432.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients

BackgroundSevere community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity.MethodsHere, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients.ResultsThere were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases.ConclusionThe plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

Analysis of influencing factors of serum SCCA elevation in 309 CAP patients with normal CEA,NSE and CYFRA21-1.

Squamous cell carcinoma antigen (SCCA) is one of the auxiliary diagnostic indicators of lung squamous cell carcinoma, and an increase in serum SCCA can predict the occurrence of lung squamous cell carcinoma. However, whether SCCA is also elevated in pneumonia patients without malignancy is still not clear. Therefore, we studied influencing factors of elevated serum SCCA in patients with community-acquired pneumonia. We retrospectively enrolled 309 patients who were admitted to the Respiratory department with normal serum Carcinoembryonic antigen (CEA), Neuron specific enolase (NSE), and Cytokeratin 19 fragment (CYFRA21-1) level and were diagnosed with community-acquired pneumonia (CAP). The patients' serum SCCA level, body temperature, age, sex, white blood cell (WBC) count, hypersensitive C-reactive protein (Hs-CRP) level, and serum amyloid A (SAA) were recorded. Logistic regression models were used to analyze the risk factors of SCCA elevation. The dose-response relationship between temperature and risk of SCCA increase was analyzed using Restricted cubic splines (RCS). Of the 309 patients, 143(46.3%) showed elevated SCCA levels. The logistic regression analysis revealed a significant influence of age and body temperature on elevated SCCA (P<0.05) levels. For every one-year increase in age, the probability of elevated SCCA decreased by 3% [OR=0.97,95%CI:0.95,0.99].For every 1°C increase in body temperature, the risk of elevated SCCA increased by 2.75 times [OR=3.75,95%CI:2.55,5.49].The patients were sorted into quartiles based on body temperature. Compared with patients in the Q1 of body temperature group, patients in the Q3 group were at 7.92 times higher risk [OR=7.92, 95%CI:3.27,19.16].and the risk of elevated SCCA was increased by 22.85 times in the Q4 group [OR=23.85,95%CI:8.38,67.89] after adjusting for age, gender, Hs-CRP, SAA, and WBC. RCS analysis showed there was a linear relationship between temperature index and risk of elevated SCCA. In summary, for CAP patients with normal CEA,NSE and CYFRA21-1 level, age and body temperature are influencing factors of SCCA elevation. Higher body temperature has a strong association with the occurrence of SCCA elevation.

Prostate cancer diagnosed and staged using UV-irradiated urine samples and a paper-based analytical device

The early detection of prostate cancer (CaP), one of the most common cancers in males, improves treatment efficacy. However, current methods to detect CaP are limited by specificity and sensitivity or require an invasive and unpleasant procedure. Therefore, there is a need for a novel, fast, and noninvasive CaP detection method. This proof-of-concept study aimed to diagnose CaP from urine samples by detecting the UV-induced fluorescent clusters formed in situ that reflect a urine composition specific to CaP patients using fluorescence spectroscopy. The UV-induced clusters formed upon irradiation by UV light with a wavelength of 254 nm were detected at excitation and emission wavelengths of 400 nm and 460 nm. Fifteen patients with CaP were correctly distinguished from 5 controls. The different stages of CaP could be further determined using molecular imprinting technology. Additionally, a paper-based analytical device was developed that enabled the correct identification of stage I cancer patients by fluorescent spectroscopy detection and the naked eye. In conclusion, this novel, easy-to-operate, point-of-care assay can enable early diagnosis of CaP with high accuracy and judgement of the disease stage. The simplicity, as well as versatility of the proposed method, will enable its application also to other diseases and disorders.

Clinical outcomes of comparison between type-III cap and non-cap acute coronary syndrome patients in 3 year follow up

Abstract Background Coronary artery perforation(CAP) is potentially fatal complication of percutaneous coronary intervention(PCI) in acute coronary syndrome(ACS).There is no study in literature comparing long term clinical outcomes of type III-CAP-ACS and non-CAP-ACS patients. Purpose The aim of this study was to investigate in hospital- 1-year and 3-year clinical outcomes of type III-CAP during PCI in ACS patients. Methods Data from ACS patients who had type III-CAP during PCI from January 2010 to Jaunary 2020 at different high volume centers in Turkey were collected.A retrospective cohort of 43,791 patients who underwent PCI was used:120 patients with CAP and 43,671 case-control patients were evaluated.Propensity score matching was used to evaluate the association between differing CAP. Clinical angiographic and procedural characteristics, their management and outcomes were analyzed retrospectively in 1-year and 3-year follow up.Multiple regressions were used to identify predictors of coronary perforation and its association with outcomes. Results The mean age of subjects was 66.5±11.9 years(61.8%males).Of all ACS patients were 247STEMI(37.9%), 216NSTEMI(33.2%) and 188UA(28.9%).Non significant differences were identified between the CAP and non-CAP groups in hospital follow-up for, cardiac death, major bleeding, and stent thrombosis except cerebrovascular event(p=0.003).At three year, differences remained different between myocardial infarction(MI)(p=0.038),coronary artery bypass graft(CABG)(p=0.001),stent thrombosis(ST)(p=0.002),major bleeding(p=0.029) and cerebrovascular event(CVE)(p=0.011)), was observed in the CAP/non-CAP group.Median follow-up of was 36 months.The all-cause mortality was 33.3% in CAP group versus 1.8% in non-CAP group at 1-year and 28.3% in CAP group versus 6.9% in non-CAP group at 3-years(p=0.001,p=0.001). Conclusions There was no significat difference between type-III-CAP and non-CAP group in hospital mortality.The procedural, clinical, 1 and 3-year outcomes of type III-CAP showed that relatively high risk of MI,CABG,CVE,ST and major bleeding under 1 and 3-year follow-up.Also, non-CAP ACS patients had better survival compared to type III CAP ACS patients in 3- year follow up.Figure 1Figure 2

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review

IntroductionCommunity-acquired pneumonia (CAP) is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA) having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. ObjectiveThe purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. Material and methodsAn online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. ResultsA total of 70 articles were found to have been published, 13 (18.8%) having been included and 57 (81.4%) excluded. Cohort studies were predominant, having totaled 16 in number (20.7%) as compared to one sole cross-sectional study (3.5%). ConclusionsThe experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.

Analysis of clinical characteristics and risk factors of community-acquired pneumonia complicated by parapneumonic pleural effusion in elderly patients

BackgroundCommunity-acquired pneumonia (CAP) patients usually present with parapneumonic pleural effusion (PPE), which complicates the treatment of pneumonia. This study aims to investigate the clinical characteristics and risk factors of elderly CAP patients hospitalised with PPE.MethodsThe clinical data of 132 elderly patients with CAP were retrospectively analysed. A total of 54 patients with PPE (PPE group) and 78 patients without PPE (NPPE group) were included in this study. Clinical data, laboratory examinations, treatments and other relevant indicators were collected. Univariate analysis and multivariate logistic regression analysis will be used to explore the possible risk factors for PPE.ResultsThe proportion of PPE in elderly patients with CAP was 40.9%. PPE patients were significantly more likely to be older, have comorbid neurological diseases, experience chest tightness, and have a lasting fever (P < 0.05). In contrast to NPPE patients, the total number of lymphocytes, serum albumin and blood sodium levels in the PPE group were significantly lower (P < 0.05). The blood D-dimer, C-reactive protein and CURB-65 score of PPE patients were significantly higher (P < 0.05) than those of NPPE patients. Multivariate logistic regression identified chest tightness (OR = 3.964, 95% CI: 1.254–12.537, P = 0.019), long duration of fever (OR = 1.108, 95%CI: 1.009–1.217, P = 0.03), low serum albumin (OR = 0.876, 95%CI: 0.790– 0.971, P = 0.012) or low blood sodium (OR = 0.896, 95%CI: 0.828–0.969, P = 0.006) as independently associated with the development of parapneumonic pleural effusion in the elderly.ConclusionThis study has identified several clinical factors, such as chest tightness, long duration of fever, low serum albumin, and low blood sodium, as risk factors for the development of pleural effusion in elderly patients with CAP. Early identification and prompt management of these patients can prevent inappropriate treatment and reduce morbidity and mortality.

Validation of Epstein criteria and development of a nomogram for active surveillance in a contemporary Chinese population.

To evaluate the Epstein criteria for insignificant prostate cancer (CaP) prediction in a contemporary Chinese population, and to develop a risk model with combined clinical and systematic biopsy and targeted biopsy parameters for active surveillance. A total of 249 CaP patients with biopsy Gleason score (GS) of 6 were included. One hundred and one patients were eligible for insignificant CaP on final pathology (GS ≤6 and organ-confined). Diagnostic tests were used to validate the ability of the 2 Epstein criteria. Univariate and multivariate regression analyses were performed to identify predictors of insignificant CaP for the development of predictive models. Receiver operating characteristics analysis was used to select the best model, followed by risk nomogram construction and internal validation. There were 47 patients met EC1 and 61 met EC2, with pathological upgrading rates of 36% and 41%, respectively, and 70% (71/101) and 64% (65/101) were missed, with areas under the curve of 0.591 and 0.594, respectively. Four prediction models were developed using regression analysis, and model 2 incorporating age, prostate-specific antigen density, maximum percentage of core involvement at systematic biopsy, and percentage of positive cores at targeted biopsy showed the best diagnostic value (area under the curve = 0.731, sensitivity 62.4%, specificity 77.0%) and was used to construct the nomogram. Calibration curves and decision curve analysis demonstrated favorable calibration (mean absolute error 0.048) and clinical benefits of the novel nomogram. The Epstein criteria need to be revised by incorporating targeted biopsy parameters to improve diagnostic performance, and a novel nomogram was developed with better prediction of insignificant CaP.