Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis

Laparoscopic management of mesenteric cyst: a case report

Mesenteric cysts are rare intra-abdominal lesions with variable clinical symptoms and signs that make pre-operative diagnosis difficult. Optimal treatment is surgical excision of the cyst with laparotomy or laparoscopy. We present a case of mesenteric cyst that was misdiagnosed as para-ovarian cyst and managed laparoscopically by gynaecologists

Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia

Background. Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). Methods. Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P=.011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P=.049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P=.047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P=.004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P=.25). Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VA

Issues arising in the construction of QSSA mechanisms: the case of reduced n-heptane/air models for premixed flames

A model reduction methodology, based on the quasi steady-state approximation (QSSA), is employed for the construction of reduced mechanisms in the case of an n-heptane/air premixed flame. Several issues related to the construction of these reduced mechanisms are discussed; such as the influence of the size of the starting skeletal mechanism, the stiffness reduction, and the truncation/simplification of (i) the expressions of the global rates and (ii) the steady-state relations. The starting point for the reduction is two skeletal mechanisms that involve 177/768 and 66/326 species/reactions, respectively [J. Prager, H.N. Najm, M. Valorani, and D.A. Goussis, Skeletal mechanism generation with CSP and validation for premixed n-heptane flames, Proc. Combust. Inst. 32 (2009), pp. 509–517] and which were derived from the detailed mechanism of Curran et al. [H.J. Curran, P. Gaffuri, W.J. Pitz, and C.K. Westbrook, A comprehensive modeling study of iso-octane oxidation, Combust. Flame 129 (2002), pp. 253–280], which involves 561/2538 species/reactions. From these two skeletal mechanisms, a number of reduced mechanisms of various sizes are produced and analysed. The validity of the reduced mechanism with the minimum size is demonstrated by considering its accuracy regarding the mass fractions of major and minor species, the temperature, and the flame speed, over a wide range of equivalence ratios and pressures

Comparison between liver transplantation and resection for hilar cholangiocarcinoma: A systematic review and meta-analysis.

BackgroundHilar cholangiocarcinoma (hCCA) is a rare and aggressive malignancy with R0 resection being currently the only option for long-term survival. With the improvement in the outcomes of liver transplantation (LT), the indications for LT have expanded to include other malignant tumors, such as hCCA. The aim of the present analysis is to demonstrate and critically evaluate the outcomes of LT compared to resection with curative intent in patients with hCCA.MethodsWe systematically searched the literature for articles published up to May 2018. The following algorithm was applied ((hilar cholangiocarcinoma) OR (perihilar cholangiocarcinoma) OR klatskin$OR (bile duct neoplasm) OR cholangiocarcinoma) AND (transplant$ OR graft$).ResultsNeoadjuvant treatment with chemotherapy and radiation therapy was far more common in the LT group, with very few patients having received preoperative therapy in the resection group (p = 0.0005). Moreover, length of hospital stay was shorter after LT than after resection (pConclusionsIn non-disseminated unresectable tumors, LT seems to have a non-inferior survival. In the same patients, neoadjuvant chemoradiotherapy and/or strict selection criteria may contribute to superior survival outcomes compared to curative-intent resection. Due to the scarcity of level 1 evidence, it remains unclear whether LT should be increasingly considered for technically resectable early stage hCCA

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

Introduction Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. Methods Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNF alpha) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNF alpha, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. Results Mortality rates of patients with apoptosis &lt;= 50% compared with patients with apoptosis &gt; 50% were 49.12% and 15.15%, respectively ( P &lt; 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis &gt; 50% compared with those patients with apoptosis &lt;= 50% ( P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis &lt;= 50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNF alpha were higher in patients with monocyte apoptosis &lt;= 50% and septic shock compared with patients with apoptosis &gt; 50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. Conclusion Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis

Trends and outcomes of simultaneous versus staged resection of synchronous colorectal cancer and colorectal liver metastases

Background: The objective of this study was to assess trends in the use as well as the outcomes of patients undergoing simultaneous versus staged resection for synchronous colorectal liver metastases.Methods: Patients undergoing resection for colorectal liver metastases between 2008 and 2018 were identified using a multi-institutional database. Trends in use and outcomes of simultaneous resection of colorectal liver metastases were examined over time and compared with that of staged resection after propensity score matching.Results: Among 1,116 patients undergoing resection for colorectal liver metastases, 690 (61.8%) patients had synchronous disease. Among them, 314 (45.5%) patients underwent simultaneous resection, while 376 (54.5%) had staged resection. The proportion of patients undergoing simultaneous resection for synchronous colorectal liver metastases increased over time (2008: 37.2% vs 2018: 47.4%; p(trend) = 0.02). After propensity score matching (n = 201 per group), patients undergoing simultaneous resection for synchronous colorectal liver metastases had a higher incidence of overall (44.8% vs 34.3%; P = .03) and severe complications (Clavien-Dindo &gt;III) (16.9% vs 7.0%; P = .002) yet comparable 90-day mortality (3.5% vs 1.0%; P = .09) compared with patients undergoing staged resection. The incidence of severe morbidity decreased over time (2008: 50% vs 2018: 11.1%; p(trend) = 0.02). Survival was comparable among patients undergoing simultaneous versus staged resection of colorectal liver metastases (3-year overall survival: 66.1% vs 62.3%; P = .67). Following simultaneous resection, severe morbidity and mortality increased incrementally based on the extent of liver resection and complexity of colectomy.Conclusion: While simultaneous resection was associated with increased morbidity, the incidence of severe morbidity decreased over time. Long-term survival was comparable after simultaneous resection versus staged resection of colorectal liver metastases. (C) 2021 Elsevier Inc. All rights reserved

Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma

Introduction Although preoperative alpha-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined. Methods Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined. Results Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP &gt; 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP &lt; 10 ng/mL (28.7% vs. 65.5%, p &lt; 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP &gt; 10 vs. &lt; 10 ng/mL: 30.1% vs. 60.2%, p &lt; 0.001) or late (18.0% vs. 78.7%, p = 0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP &gt; 10 vs. &lt; 10 ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p &lt; 0.05). After adjusting for competing risk factors, patients with rAFP &gt; 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04). Conclusion AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC