Activation of cardiac renin-angiotensin system in unstable angina

AbstractOBJECTIVESThe aim of this study was to investigate the activity of the cardiac renin-angiotensin system (RAS) in unstable angina (UA).BACKGROUNDAngiotensin (Ang) II locally produced by continuously operating cardiac RAS may affect the pathophysiology of UA.METHODSIn 35 patients with UA, 32 with stable effort angina (SA) and 21 with atypical chest pain (controls), cardiac RAS was investigated during coronary angiography after five days of Holter monitoring by combining the measurement of aorta-coronary sinus gradient for Ang I and Ang II with the kinetics study of 125I-Ang I. Messenger RNAs (mRNA) for all the components of RAS were also quantified with the reverse transcriptase-polymerase chain reaction (RT-PCR) and localized by in situ hybridization in myocardial biopsy specimens from patients who underwent aorta-coronary bypass surgery.RESULTSCardiac Ang II generation was higher in patients with UA than it was in patients with SA or in controls (p < 0.001) due to increased de novo cardiac Ang I formation and its enhanced fractional conversion rate to Ang II. Messenger RNA levels for angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and Ang II type 1 (AT1) subtype receptors were higher in patients with UA (p < 0.01) than they were in patients with SA or in control hearts. Messenger RNAs for AGTN and ACE were almost exclusively expressed on endothelial and interstitial cells. Angiotensin II formation was correlated with ischemia burden (p < 0.001). However, the amount of Ang II formed and the expression levels of mRNAs for AGTN, ACE and AT1 were not related to the time that had elapsed since the last anginal attack.CONCLUSIONSIn patients with UA, cardiac RAS is activated, resulting in increased Ang II formation. Myocardial ischemia is essential for RAS activation, but it is unlikely to be a direct and immediate cause of RAS activation

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

PCA3 urinary test versus 1H-MRSI and DCEMR in the detection of prostate cancer foci in patients with biochemical alterations

Aim: To compare the prostate antigen 3 (PCA3) test with 1H-magnetic resonance spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCEMR) combined examination in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen (PSA) levels and prior negative random transrectal ultrasound (TRUS)-guided biopsy. Patients and Methods: Forty-three patients with a first random biopsy negative for prostate adenocarcinoma, persistent elevated PSA and negative digital rectal examination were recruited. All the patients were submitted to MRSI examination (MRSI-DCEMR) and were submitted to an attentive prostate massage in order to perform PCA3 assay. Afterwards, 10-core laterally-directed random TRUS-guided prostate biopsy was performed. Results: The overall sensitivity and specificity of a PCA3 score ≥35 for positive biopsy were 76.9% and 66.6%, respectively, with a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 625%; as for MRSI sensitivity and specificity were, respectively, 92.8% and 86.6% with a PPV of 92.8% and a NPV of 86.6%. Receiver operating characteristic (ROC) analysis rates were 0.755 for PCA3 and 0.864 for MRSI. Conclusion: Combined MRSI/DCEMR can better improve the cancer detection rate in patients with prior negative TRUS-guided biopsy and altered PSA serum levels than PCA3. Optimization of MRSI will allow more precise diagnosis of local invasion and improved bioptical procedures

Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers

The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERa expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ER\u3b1-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERa-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC

PCA3 urinary test versus 1H-MRSI and DCEMR in the detection of prostate cancer foci in patients with biochemical alterations

Aim: To compare the prostate antigen 3 (PCA3) test with 1H-magnetic resonance spectroscopic imaging (1HMRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCEMR) combined examination in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen (PSA) levels and prior negative random transrectal ultrasound (TRUS)-guided biopsy. Patients and Methods: Forty-three patients with a first random biopsy negative for prostate adenocarcinoma, persistent elevated PSA and negative digital rectal examination were recruited. All the patients were submitted to MRSI examination (MRSI-DCEMR) and were submitted to an attentive prostate massage in order to perform PCA3 assay. Afterwards, 10-core laterally-directed random TRUSguided prostate biopsy was performed. Results: The overall sensitivity and specificity of a PCA3 score ≥35 for positive biopsy were 76.9% and 66.6%, respectively, with a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 62.5%; as for MRSI sensitivity and specificity were, respectively, 92.8% and 86.6% with a PPV of 92.8% and a NPV of 86.6%. Receiver operating characteristic (ROC) analysis rates were 0.755 for PCA3 and 0.864 for MRSI. Conclusion: Combined MRSI/DCEMR can better improve the cancer detection rate in patients with prior negative TRUSguided biopsy and altered PSA serum levels than PCA3. Optimization of MRSI will allow more precise diagnosis of local invasion and improved bioptical procedures

Clinicopathological features of the overall series.

<p>Clinicopathological features of the overall series.</p

Effect of KAAD-cyclopamine and GANT58 on Hh pathway in human ovarian carcinoma cells.

<p>(<b>A</b>) Three human ovarian carcinoma cell lines, A2780, SKOV-3, and OVCAR-3 were subjected to immunostaining with antibody against Gli1. All of three cell lines express Gli1. Protein expression was also confirmed by western blot analysis. β-Actin was used as a loading control. (<b>B</b>) Cells were cultured in 2% FBS medium and treated with 2, 5 and 10 µM KAAD-cyclopamine (K) or GANT58 for 48 h. KAAD-cyclopamine treatment inhibits cell proliferation in all of three cell lines whereas GANT58 does not affect cell growth. Shown are cell number expressed as percentage of DMSO-treated cells (mean ± SD from three different experiments; *P<0.05, **P<0.01, ***P<0.001, t test). (C) Gli1 mRNA expression was evaluated by Q-PCR analysis in ovarian cancer cells treated with 10 µM KAAD-cyclopamine for 48 h. Data are expressed as fold change vs. each respective Control (CTRL), taken as calibrator for comparative quantitation analysis of mRNA levels. Each sample was measured in triplicate, the experiment was repeated 2 times with similar results. Graphics show mean ± SD.</p

Univariate and Multivariate analysis of factors affecting OS in advanced serous ovarian cancer.

<p>OS = Overall Survival. HR = Hazard ratio. CI = confidence interval. *Ps were derived from the COX proportional hazards model. Only variables with p-value ≤0.2 in the univariate analysis were included in multivariate model. χ² of the model = 14.3; p value = 0.0025.</p