Wearable devices as part of postoperative early warning score systems: a scoping review.

Postoperative deterioration is often preceded by abnormalities in vital parameters, but limited resources prevent their continuous monitoring in patients with no indication to ICU admission. The development of new technologies allowed the introduction of wearable devices (WDs), enabling the possibility of postoperative monitoring in surgical wards. We performed a Scoping Review to determine the current use of wearable devices as part of Continuous Remote Early Warning Score (CREWS) systems and their efficiency during postoperative period. This Scoping Review was conducted according to PRISMA-ScR guidelines. PICO framework was used before the search to define the review protocol. Systematic literature research has been performed on PubMed, MeSH, MEDLINE and Embase, considering a period between 2018 and February 2024. Prospective and retrospective studies involving patients undergoing cardiac and non-cardiac surgery are included. A total of 10 articles were included in the review. 11 different CE/FDA approved wearable devices were used in the studies analyzed. In all studies the WDs were applied the day of the surgery. The use of WDs as part of CREWS systems is feasible and safe. Furthermore, with the aid of other technologies (LoRa and Artificial Intelligence), they shorten Length of Stay (LOS) and reduce the number of ICU admissions with a reduction in healthcare costs. Continuous monitoring in surgical departments can facilitate the correct and timely identification of postoperative complications. This article is a starting point for the development of new protocols and for the application of these monitoring systems in clinical practice.

Monitoring response to cytostatic cisplatin in a HER2(+) ovary cancer model by MRI and in vitro and in vivo MR spectroscopy.

BACKGROUND: Limited knowledge is available on alterations induced by cytostatic drugs on magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters of human cancers, in absence of apoptosis or cytotoxicity. We here investigated the effects of a cytostatic cisplatin (CDDP) treatment on (1)H MRS and MRI of HER2-overexpressing epithelial ovarian cancer (EOC) cells and in vivo xenografts. METHODS: High-resolution MRS analyses were performed on in vivo passaged SKOV3.ip cells and cell/tissue extracts (16.4 or 9.4 T). In vivo MRI/MRS quantitative analyses (4.7 T) were conducted on xenografts obtained by subcutaneous implantation of SKOV3.ip cells in SCID mice. The apparent diffusion coefficient (ADC) and metabolite levels were measured. RESULTS: CDDP-induced cytostatic effects were associated with a metabolic shift of cancer cells towards accumulation of MRS-detected neutral lipids, whereas the total choline profile failed to be perturbed in both cultured cells and xenografts. In vivo MRI examinations showed delayed tumour growth in the CDDP-treated group, associated with early reduction of the ADC mean value. CONCLUSION: This study provides an integrated set of information on cancer metabolism and physiology for monitoring the response of an EOC model to a cytostatic chemotherapy, as a basis for improving the interpretation of non-invasive MR examinations of EOC patients.

Choline kinase-alpha by regulating cell aggressiveness and drug sensitivity is a potential druggable target for ovarian cancer.

BACKGROUND: Aberrant choline metabolism has been proposed as a novel cancer hallmark. We recently showed that epithelial ovarian cancer (EOC) possesses an altered MRS-choline profile, characterised by increased phosphocholine (PCho) content to which mainly contribute over-expression and activation of choline kinase-alpha (ChoK-alpha). METHODS: To assess its biological relevance, ChoK-alpha expression was downmodulated by transient RNA interference in EOC in vitro models. Gene expression profiling by microarray analysis and functional analysis was performed to identify the pathway/functions perturbed in ChoK-alpha-silenced cells, then validated by in vitro experiments. RESULTS: In silenced cells, compared with control, we observed: (I) a significant reduction of both CHKA transcript and ChoK-alpha protein expression; (II) a dramatic, proportional drop in PCho content ranging from 60 to 71%, as revealed by (1)H-magnetic spectroscopy analysis; (III) a 35-36% of cell growth inhibition, with no evidences of apoptosis or modification of the main cellular survival signalling pathways; (IV) 476 differentially expressed genes, including genes related to lipid metabolism. Ingenuity pathway analysis identified cellular functions related to cell death and cellular proliferation and movement as the most perturbed. Accordingly, CHKA-silenced cells displayed a significant delay in wound repair, a reduced migration and invasion capability were also observed. Furthermore, although CHKA silencing did not directly induce cell death, a significant increase of sensitivity to platinum, paclitaxel and doxorubicin was observed even in a drug-resistant context. CONCLUSION: We showed for the first time in EOC that CHKA downregulation significantly decreased the aggressive EOC cell behaviour also affecting cells' sensitivity to drug treatment. These observations open the way to further analysis for ChoK-alpha validation as a new EOC therapeutic target to be used alone or in combination with conventional drugs.

Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to alpha-folate receptor overexpression.

Caveolin (cav-1) and the GPI-anchored alpha-folate receptor (alphaFR) are membrane proteins both found associated to caveolar structures. Several studies in tumor cells independently reported cav-1 downregulation and alphaFR overexpression. Here we analysed the expression of the two molecules in normal and tumor ovarian samples derived from fresh specimens and from cultured cell lines. Whereas normal ovary surface epithelial cells displayed only cav-1 expression, ovarian tumor surgical samples and cell lines (COR, IGROV1, OVCAR3 and OVCA432) displayed high alphaFR and low-level or no cav-1 expression, except those cell lines (SKOV3 and SW626) with the lower alphaFR expression. SKOV3, but not two alphaFR-negative non-ovarian cell lines, exhibited down-regulation of cav-1 expression following stable alphaFR cDNA transfection. Conversely, cav-1 transfection in IGROV1 cells led to downregulated alphaFR expression, together with formation of caveolar structures and reduction of growth capability. Moreover, cav-1 expression was induced in IGROV1 cells by transfection with intracellular anti-alphaFR antibodies to downmodulate alphaFR expression. In cav-1 transfected cells, transcriptional activity of the alphaFR-specific promoter P1 was reduced by 70% and an additional specific DNA-protein complex was identified by gel-shift assay, indicating that cav-1 expression influences alphaFR gene transcription. Together these results support the notion that alphaFR and cav-1 protein expression is reciprocally regulated in ovary cancer cells.

Interaction of folate receptor with signaling molecules lyn and G(alpha)(i-3) in detergent-resistant complexes from the ovary carcinoma cell line IGROV1.

Using as a model the ovary carcinoma cell line IGROV1, we analyzed the partitioning of the glycosyl-phosphatidylinositol-anchored folate receptor into lipid rafts based on its relative detergent insolubility, with a focus on physically and functionally associated signaling molecules. A variable amount (40-60%) of folate receptor was found in low-density Triton X-100 insoluble complexes together with subunits of heterotrimeric G-proteins and the src-family non-receptor tyrosine kinases p53-56 lyn. In the same fraction the structural component of caveolae, caveolin, was not detected at the protein level, although the corresponding mRNA was detected in trace amounts. Comodulation of folate receptor and signalling molecules was observed in the detergent-insoluble complexes during cell proliferation or induced by phosphatidylinositol-specific phospholipase C treatment or by interaction with anti-folate receptor monoclonal antibodies. Moreover, complexes of folate receptor, lyn and the G(&agr;)(i-3) subunit were immunoprecipitated using either anti-folate receptor or anti-lyn antibodies. In vitro kinase assay of the immunoprecipitates revealed stimulation of phosphorylation of common and specific proteins. In particular, the p53 form of lyn appeared to be enriched and phosphorylated in the anti-folate receptor MOv19 monoclonal antibody immunoprecipitate, whereas a 40 kDa band common to anti-folate receptor and anti-lyn immunoprecipitates was the phosphorylated form of the G(&agr;)(i-3) subunit. These findings point to the functional interaction between folate receptor and associated signaling molecules.

Overexpression of folate binding protein in ovarian cancers.

The high affinity folate binding protein (FBP) is overexpressed in ovarian cancers. However, its role in the pathogenesis and biological behaviour of these neoplasms is not clearly understood. Using the monoclonal antibody (MAb) MOv 18 and cytofluorimetric analysis, we investigated FBP expression in frozen neoplastic tissues from 136 patients diagnosed with epithelial ovarian cancer. FBP values were compared with clinico-pathological characteristics (age, stage, histologic grade, histologic type, DNA ploidy, percentage of S-phase cells, and previous chemotherapeutic treatment). Some amount of FBP overexpression was observed in 122 of the 136 tumours examined. The overall mean value of FBP fluorescence index (FBP FI) was 5.6 (median 2.7; min 0.8--max, 78.9). By univariate analysis, FBP FI was overexpressed to a higher degree in ovarian neoplasms with high histologic grade, advanced stage, serous histology, aneuploid status, and high percentage of cells in S-phase. Of the total number (136) of cases, 106 had all the parameters assessed and were thus selected for stepwise selection procedure. The only significant independent variable was the percentage of S-phase cells, which accounted for about 31% of variance of FBP FI. Our results indicate that FBP is associated with parameters of biological aggressiveness in ovarian cancers.

Simultaneous activity of two different mechanisms of folate transport in ovarian carcinoma cell lines.

We investigated whether the folate receptor alpha-isoform (FR alpha), which is overexpressed on ovarian carcinoma cells, is functionally active in internalizing the physiological form et folate, 5-methyl tetrahydrofolate (THF). Six ovarian tumor cell lines, expressing different levels of FR alpha (COR > > OVCAR3 > IGROV1 > OVCAR4 > SKOV3 > OVCAR5), were maintained in folate-depleted medium and internalization of 10 nM evaluated as acid-resistant radioactivity at 0 degree and 37 degrees C. The amount of 5-methyl[1H]THF present in this fraction was not strictly related to the number of membrane receptors, since even cell lines with low FR alpha expression, e.g., OVCAR4, showed efficient internalization. Time-course studies indicated that, whereas no uptake was detected at 0 degree C, at 37 degrees C the internalized fraction showed a slow and constant increase, until 4 h. At this time the internalized radioactivity represented < 50% of the total bound in COR, OVCAR3 and IGROV1 cells, whereas the other cell lines tested internalized fourfold more folate than their surface binding capacity. The incubation in the presence of a concentration (50 nM) of 5-methyl[3H]THF, which best ensures receptors saturation on cells with highest FR levels (COR and OVCAR3), had slight effect on surface binding of all the tested cell lines, including IGROV1 and SKOV3. In contrast, the increase of the uptake was more pronounced, particularly in SKOV3 cells. These results, together with the accumulation curves of folic acid (FA) and 5-methylTHF at 37 degrees C, suggested the presence of a molecule on ovarian carcinoma cells with high affinity for reduced folates, possibly a reduced folate carrier (RFC). Measurement of radioactivity present in the supernatant of IGROV1 and SKOV3 cells, subjected to hypotonic lysis and cell fractionation, further indicated that 5-methyl[3H]THF was translocated to the cytosol and, despite differences in membrane levels of FR alpha expression this internalized fraction was similar in both cell lines. Inhibition experiments to selectively block FR alpha or RFC activity showed a differential sensitivity of the two pathways depending on the cell line examined. Internalization was more consistently inhibited on IGROV1 than on SKOV3 cells by treatments that disrupt FR alpha activity, e.g., incubation with excess FA and phosphatidylinositol specific phospholipase C, whereas Probenecid, which preferentially inhibits the carrier-mediated pathway, showed a strong inhibitory effect on both cell lines. These findings suggest that the internalization of 5-methylTHF in these tumor cells depends not only on the level of overexpressed FR alpha, but another transport route, with features characteristic for RFC, is functional and participates in folate uptake.

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies.

The alpha-folate receptor (FR) is selectively overexpressed in 90% of nonmucinous ovarian carcinomas, whereas no expression is detectable in normal ovarian surface epithelium (OSE). Indirect evidence suggests that FR expression is associated with tumor progression and affects cell proliferation. To evaluate better the role of FR, we developed an approach based on intracellular expression of single-chain (sc) antibodies (intrabody) to downmodulate membrane expression of FR in ovary cancer cells. IGROV-1 and SKOV3 ovarian carcinoma cell lines were transfected with an anti-FR intrabody. Transfectants and parental cells were tested for FR, integrins and anti-FR intrabody expression by fluorescence-activated cell sorting (FACS), reverse transcription and polymerase chain reaction (RT-PCR) and/or immunoblotting. Cell growth characteristics and adhesion properties were evaluated in liquid, semisolid and organotypic cultures. The anti-FR scFv inhibited FR expression from 60 to 99%. At physiological concentrations of folate, proliferation varied directly as a function of FR expression. FR downmodulation was accompanied by reduced colony-forming ability in soft agar, morphological change of the cells, significant enhanced adhesion to laminin or Matrigel, a two- to three-fold increase in alpha6beta4 integrin expression, and a marked reduction in laminin production. In three-dimensional organotypic cultures, anti-FR intrabody-transfected IGROV1 cells grew as a single-ordered layer, reminiscent of normal OSE growth in vivo. In conclusion, the anti-FR intrabody reverses the transformed phenotype in ovary cancer cells and may provide an efficient means to inhibit selectively the growth of these cells.

Diphtheria: epidemiological update and review of prevention and control strategies.

The importance of anti-diphtheria immunity in adults through periodic booster doses of vaccine is now increasing after last years diphtheria outbreaks in Newly Independent States (NIS) and Algeria and a few cases found in Europe and USA. Diphtheria cases notified in Italy between 1991-1994 have been reported. In 1995 WHO outlined the need to review vaccination schedules against diphtheria in all countries where gaps occur in the immunity of adults. The main sero-epidemiological studies performed in adults and vaccination schedules against diphtheria in some industrialized countries have been examined. Actual situation and control strategies adopted by WHO in the NIS and implications for other countries have been briefly presented. Finally, guidelines for management, investigation and control of diphtheria have been reported, including CDCs recommendations.

Relationship between folate-binding protein expression and cisplatin sensitivity in ovarian carcinoma cell lines.

It has been suggested that sensitivity of ovarian carcinomas to cisplatin is in part related to an endogenous folate deficiency. In this work, we investigated whether overexpression of the folate-binding protein (FBP), a receptor involved in folate transport, might be associated with cisplatin sensitivity. The results obtained on a panel of ten ovarian carcinoma cell lines that overexpress different levels of the FBP showed a statistically significant relationship between FBP overexpression and cisplatin responsiveness, with the most sensitive cell lines expressing higher FBP levels on their membrane than the less sensitive ones. The relationship was observed both in cells growing in standard medium-containing high-folate concentrations (2.3 microM) and in cells adapted to growth in low-folate (20 nM) medium. Analysis of two cisplatin-resistant cell lines derived from the cisplatin-sensitive IGROV1 ovarian carcinoma cell line indicated that resistance was associated with a significant decrease in FBP expression. However, the receptor does not appear to be directly responsible for drug sensitivity per se as different cell lines transfected with FBP cDNA did not become more sensitive to the drug. Together, the data suggest the possible predictive value of FBP in ovarian carcinoma, as higher levels of expression can be indirectly but significantly associated with increased drug sensitivity.

[Serum C3 as a screening factor in the primary prevention of myocardial infarct]. / Il C3 sierico come fattore di selezione nella prevenzione primaria dell'infarto miocardico.

This study addresses the possible use of serum C3 (third component of the complement system) to select the subjects to be submitted to diet or drug therapy in the primary prevention of myocardial infarction. C3 is synthesized by macrophages, which are the main cells involved in atheroma formation, and an association between serum C3 and the risk of myocardial infarction has recently been found in the male sex. We have studied 332 men aged 45-75 years, who had no cardiovascular disease at any time before blood sampling. In their sera C3 measurement was performed by nephelometry. The 4 year follow-up was known for all of these subjects: in particular, 11 had a myocardial infarction. The average LDL cholesterol (LDL-C) levels in the whole population were rather high (162.2 +/- 45.8 (1 SD) mg/dl). As standard treatment criteria (A), those suggested for primary prevention by the National Cholesterol Education Program panel of experts were adopted: diet if LDL-C > or = 160 mg/dl, or LDL-C > or = 130 mg/dl + 2 additional risk factors; drugs if, after diet, LDL-C > or = 190 mg/dl, or LDL-C > or = 160 mg/dl + 2 risk factors. This scheme was compared with two models of treatment which included the measurement of serum C3. According to the first of such models (B), diet should be prescribed when C3 levels are within the high third of distribution (> or = 135 mg/dl) with LDL-C > or = 100 mg/dl, and drugs should be given if, after diet, serum C3 is > or = 135 mg/dl with LDL-C > or = 130 mg/dl. The second model based on C3 (C) is of combined type since, in addition to model B criteria, it also suggests to prescribe a diet if LDL-C > or = 190 mg/dl, while drugs should be given if, after diet, LDL-C levels persist > or = 190 mg/dl. The effect of diet has been simulated by assuming a 10% decrease in LDL-C levels. According to all of these criteria, the subjects to treat with diet with the models A, B and C would have been, respectively, 71, 27 (p < 0.0001 vs mod A) and 45% (p < 0.0001 vs mod A) of the whole population, including among them, respectively, 82, 82 and 100% of the future myocardial infarctions. After diet, according to the three models A, B and C -29, 20 (p = 0.0117 vs mod A) and 30% of the whole population should have been treated with drugs, including, respectively, 54, 64 and 82% of the future myocardial infarctions. In conclusion, the use of criteria based on serum C3, with respect to more traditional guidelines, might allow a more precise identification of the subjects to submit to diet and drug treatment in the primary prevention of myocardial infarction.

'Normolipidemic' tendinous and tuberous xanthomatosis.

BACKGROUND: Multiple tendinous and tuberous xanthomas are characteristically associated with hyperlipidemic states. However, normolipidemic tendinous and tuberous xanthomas have been reported in the literature, with normal levels of cholesterol, cholestanol and plant sterols. OBJECTIVE AND METHOD: To delineate the disorder and to suggest its likely origin, a case of apparently normolipidemic severe tuberous and tendinous xanthomatosis was studied. Several lipoprotein and lipid analyses, clinical tests and histological studies were performed over a period of 5 years in the propositus and his family. RESULTS: At the first lipid analysis, no quantitative or qualitative alterations of the lipoprotein fractions or of the apoproteins AI, B, CII, CIII, E were detected in the propositus and xanthomatosis was classified as normolipidemic. During the follow-up, the patient showed a nonconstant hypertriglyceridemia and/or hypercholesterolemia associated with the presence of small and dense VLDL and LDL. An increase in apo-B was observed. There was an unusual quantity of conjugated dienes of arachidonic acid in the plasma and in the LDLs of the patient, present only in small traces in the control population. The family study and the long follow-up of the lipid analysis of the propositus were compatible with the diagnosis of familial combined hyperlipidemia. CONCLUSION: Our data highlight the importance of a critical review of studies regarding normolipidemic xanthomatosis, since only after an extensive follow-up and sequential analyses of lipoprotein fractions is it possible to exclude the presence of time variables and complex lipoprotein abnormalities.