The effect of hyperoxia on migration of alveolar macrophages in vitro.

There is in vitro evidence to support the notion that directed migration (chemotaxis) is involved in the recruitment of alveolar macrophages in vivo. Because O2 is widely used in the treatment of pulmonary diseases, we examined the effect of hyperoxia on migration of guinea pig alveolar macrophages in vitro. Migration was measured in blind-well chambers incubated in either room air or hyperoxia. N-formyl-methionyl-phenylalanine was used to stimulate random migration and to produce directed migration. Migration was quantified by counting the number of mononuclear cells per oil immersion field that had migrated completely through a polycarbonate filter with 5-micrometer pores. The average PO2 in the cell suspensions incubated in room air was 100 mm Hg. In the hyperoxic environments, the average PO2 at 1 h was 260 mm Hg, whereas at 2 and 3 h, it was 410 and 425 mm Hg, respectively. In 6 separate experiments, there was no significant difference between the mean response to N-formyl-methionyl phenylalanine in hyperoxia and in room air after 1 h of incubation. After 2 and 3h of incubation, however, the response in hyperoxia was significantly (P less than 0.002) lower than that in room air. The decreased response in hyperoxia did not appear to result from loss of viability of responding cells, diminished adherence of cells to the filters, loss of activity of N-formyl-methionyl phenylalanine exposed to high PO2, or failure of the cells to exhibit directed migration. Instead, it appeared that hyperoxia decreased the response of alveolar macrophages primarily by impairing random migration.     

Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma

Cholangiocarcinoma(CCC) is the most aggressive malignant tumor of the biliary tract. Perihilar CCC(pCCC) is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical location makes surgical approach burden by poor results. Besides its clinical presentation, a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid missdiagnosis. Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure. During staging iter, magnetic resonance can obtain satisfactory cholangiographic images, while invasive techniques should be used if bile duct samples are needed. Consistently, to improve diagnostic potential, bile duct drainage is not necessary in jaundice, while it is indicated in refractory cholangitis or when liver hypertrophy is needed. Once resecability criteria are identified, the extent of liver resection is secondary to the longitudinal spread of CCC. While in the past type IV pCCC was not considered resectable, some authors reported good results after their treatment. Conversely, in selected unresectable cases, liver transplantation could be a valuable option. Adjuvant chemotherapy is the standard of care for resected patients, while neoadjuvant approach has growing evidences. If curative resection is not achieved, radiotherapy can be added to chemotherapy. This multistep curative iter must be carried on in specialized centers. Hence, the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.     

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)     

Increased IGF-I : IGFBP-3 ratio in patients with hepatocellular carcinoma

BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors. AIM: The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 +/- 10 and 65 +/- 7 vs. 185 +/- 6.4 microg/l, P < 0.001) and IGFBP-3 levels (1225 +/- 113 and 984 +/- 67 vs. 3017 +/ -80 microg/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels in patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 +/- 2 vs. 57 +/- 12 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 +/- 0.05 vs. 0.41 +/- 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 +/- 5.6 vs. 42 +/- 6.2 microg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 +/- 81 vs. 679 +/- 83 microg/l). CONCLUSIONS: Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure.     

Descending Perineum Syndrome: Are Abdominal Hysterectomy and Bowel Habits Linked?

PURPOSE This retrospective study evaluates the effect of abdominal hysterectomy on patients affected by descending perineum syndrome. METHODS Eighty-nine female patients affected by descending perineum syndrome and one group of 10 healthy women with normal bowel habits were studied retrospectively. Thirty-two descending perineum syndrome patients (Group 1) had received an abdominal hysterectomy for benign diseases, while 57 descending perineum syndrome patients (Group 2) had not undergone this surgery. All 99 subjects underwent clinical evaluation, computerized anorectal manometry, and defecography. RESULTS Dyschezia was found predominantly in Group 2 subjects (P < 0.05). Fecal incontinence was significantly higher in Group 1 than in Group 2 (P < 0.05). The worst anal resting pressure was found in the incontinent Group 1 patients (P < 0.01). Rectoanal intussusception was a significant defecographic sign in Group 1 subjects (P < 0.05). CONCLUSIONS Clinical evaluation and instrumental data suggested a possible link between fecal incontinence and abdominal hysterectomy in patients affected by descending perineum syndrome.     

Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy

The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r ?0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 ± 200.0 vs 20.9 ± 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.     

Analysis of the semantic representations of living and nonliving concepts: A normative study

Current feature-based semantic memory models assume that the semantic representations of concepts differ systematically across living and nonliving categories and that such differences account for the emergence of category-specific semantic deficits in brain-damaged people. To assess some of the different models' main assumptions about structural differences at the semantic feature level in the two major semantic domains, we administrated a feature-listing task to normal young volunteers on 64 concepts drawn from living and nonliving semantic categories. We investigated whether feature correlation, a variable with a crucial role in the emergence of category-specific deficits, should be computed as a concept-dependent or as a concept-independent measure, and we chose the former. We also addressed the issue of a psychological counterpart of feature production frequency. Finally, we analysed the database obtained from the feature-listing tasks, looked at cross-domain differences for correlation, feature frequency, distinctiveness, and feature type, and discussed the implications of these findings for current semantic memory models.