Fibrinolytic system after laparoscopic cholecystectomy

BACKGROUND: Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are the most important causes of morbility and mortality in patients submitted to surgical intervention: some peculiar factors of laparoscopic surgery can modify their risk. The aim of this study is to evaluate possible variations of the fibrinolytic system after cholecystectomy. METHODS: Eighteen patients affected by symptomatic and non-complicated gallstones have been included in this study. They were divided into two groups of nine patients each: the first group was submitted to laparoscopic cholecystectomy (LC) and the second to open cholecystectomy (OC). Antitrombin III (ATIII), fibrinogen degradation products (FDP), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) have been evaluated preoperatively and 6, 12, 24 and 48 hours after the operation. RESULTS: The levels of ATIII did not present significantly variations. The FDP in both groups were significantly increased 48 hours after open cholecystectomy. Levels of PAI instead were increased in comparison to the basal values at 6, 12, 24, 48 hours with p < 0.05; p < 0.01 and p < 0.05 respectively in patients submitted to OC, in the LC group no variations were observed; a comparison between the groups showed a significant modification (p < 0.05) only at the 12th hour. CONCLUSIONS: The early mobilization of patients in the postoperative course and the lower invasion of LC can oppose the prothrombotic effect in the lower limbs.     

The purinergic P2×7 receptor is expressed on monocytes in Behçet's disease and is modulated by TNF‐α

The P2×7 receptor (P2×7r) is expressed in innate immune cells (e.g. monocyte/macrophages), playing a key role in IL‐1β release. Since innate immune activation and IL‐1β release seem to be implicated in Behçet's disease (BD), a systemic immune‐inflammatory disorder of unknown origin, we hypothesized that P2×7r is involved in the pathogenesis of the disease. Monocytes were isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an increased P2×7r expression and Ca²⁺ permeability induced by the selective P2×7r agonist 2′‐3′‐O‐(4‐benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL‐1β release from LPS‐primed monocytes stimulated with BzATP was markedly higher in BD patients than in controls. TNF‐α‐incubated monocytes from healthy subjects almost reproduced the findings observed in BD patients, as demonstrated by the increase in P2×7r expression and BzATP‐induced Ca²⁺ intake. Our results provide evidence that in BD monocytes both the expression and function of the P2×7r are increased compared with healthy controls, as the possible result, at least in part, of a positive modulating effect of TNF‐α on the receptor. These data indicate P2×7r as a new potential therapeutic target for the control of BD, further supporting the rationale for the use of anti‐TNF‐α drugs in the treatment of the disease.     

Chronic diseases are strongly associated with sickness absences in a sample of Italian public employees

Objectives

Data on the prevalence of chronic diseases and their relationship with sickness absence in the Italian public employees are rather scarce. Therefore, in the first place, we assessed the distribution of chronic diseases in the employees of the University of Ferrara. As a next step, we investigated the possible associations between each chronic disease and cumulative days of all-cause sickness absence, and finally we investigated the odds ratio of each single chronic disease on sickness absence.

Material and Methods

A total of 514 employees, 269 sick-listed and 245 not sick-listed in 2012, were studied. Demographical/clinical characteristics and chronic diseases were obtained from all study participants during medical surveillance procedures. Sickness absence days and job seniority data were obtained from the administrative office.

Results

Gastrointestinal and psychiatric diseases were the most reported in the sick-listed sample (p = 0.01 and p = 0.02, respectively, compared to the not sick-listed). In the interquantile regression analysis, the sickness absence days were as?sociated with psychiatric diseases (β = 65.1, 95% CI: 13.2-117.1, p = 0.01) and with the presence of 2 or more chronic diseases (β = 23.3, 95% CI: 4.5–42, p = 0.02). Furthermore, the logistic regression analysis showed that the odds of sickness absence were increased 2 fold by psychiatric diseases (OR = 2.2, 95% CI: 1.01–4.93, p = 0.04), and gastrointestinal diseases (OR = 1.9, 95% CI: 1.07–3.42, p = 0.02) and, to a lesser extent, by high body mass index (OR = 1.05, 95% CI: 1–1.11, p = 0.03). Conversely, female gender reduced by half the odds of sickness absence (OR = 0.5, 95% CI: 0.3–0.8, p = 0.04).

Conclusions

This study highlights the relevant association between chronic diseases and sickness absence in Italian public employees. Our findings indicate the importance of considering the health status when designing preventive interventions aimed at decreasing sickness absences in this population.     

Erythrocyte glutathione transferase activity: a possible early biomarker for blood toxicity in uremic diabetic patients

Erythrocyte glutathione transferase (e-GST) displays increased activity in patients with renal damage and positive correlation with homocysteine (Hcy) in patients under maintenance hemodialysis. Here, we determined e-GST, Hcy, and erythrocyte catalase (e-CAT) in 328 patients affected by type 2 diabetes mellitus (T2DM), 61 diabetic non-nephropathic patients and 267 affected by diabetes and by chronic kidney disease (CKD) under conservative therapy subdivided into four stages according to K-DOQI lines. e-GST activity was significantly higher in all T2DM patients compared to the control group (7.90 ± 0.26 vs. 5.6 ± 0.4 U/g_Hb), and we observed an enhanced activity in all subgroups of CKD diabetic patients. No significant correlation or increase has been found for e-CAT in all patients tested. Mean Hcy in diabetic patients is higher than that in healthy subjects (33.42 ± 1.23 vs. 13.6 ± 0.8 μM), and Hcy increases in relation to the CKD stage. As expected, a significant correlation was found between e-GST and Hcy levels. These findings suggest that e-GST hyperactivity is not caused directly by diabetes but by its consequent renal damage. e-GST, as well as Hcy, may represent an early biomarker of renal failure.     

Postremission therapy with repeated courses of high-dose cytarabine,idarubicin, and limited autologous stem cell support achieves a very good long-term outcome in European leukemia net favorable and intermediate-risk acute myeloid leukemia

Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19–75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.     

'Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells?

We describe five primary tumors of the adenohypophysis featuring mitochondrion-rich spindle cells. The patient ages ranged from 53 to 71 years (mean 61.6 years); two were female. All presented with panhypopituitarism. Two also had visual field defect. On neuroimaging all tumors showed suprasellar extension and were indistinguishable from pituitary adenoma. None showed imaging or operative evidence of dural involvement. All were gross totally removed: four by transsphenoidal surgery and one by frontal craniotomy. Follow-up ranged from 2 to 68 months (mean 35.4 months). No recurrences were noted. The clinical workup was noncontributory in all but two patients: one (case no. 4) with an oncocytic thyroid adenoma and another (case no. 5) with squamous carcinoma of both the uterine cervix and of vocal cord. Histologically, the five tumors were composed mainly of fascicles of spindle cells with eosinophilic, granular cytoplasm. Mitoses were rare and necrosis was absent. Neoplastic cells were immunoreactive for vimentin, epithelial membrane antigen, S-100 protein, and galectin-3. Stains for pituitary hormones, synaptophysin, chromogranin, glial fibrillary acidic protein, cytokeratin CAM5.2, smooth muscle actin, CD34, and CD68 were negative. No thyroglobulin immunoreactivity was noted in the tumor of case no. 4. Ultrastructurally, the neoplastic cells contained numerous mitochondria with lamellar cristae. The neoplastic cells were linked by intermediate junctions and desmosomes. No secretory granules were noted. The histologic, immunohistochemical, and fine structural features of these tumors were unlike those of pituitary adenoma or any other primary sellar tumor. A derivation from adenohypophyseal folliculostellate cells is suggested.