Chronic cholecystitis in elderly patients. Correlation of the severity of inflammation with the number and size of the stones

BACKGROUND: [corrected] The present study focused on cholecystectomized elderly patients and aimed to investigate whether inflammation in the gallbladder wall was associated with the number and size of gallstones, as well as the patients' age. PATIENTS AND METHODS: The present study included 306 cholecystectomized patients aged over 65 years. From the specimens derived from cholecystectomy, the gallstone number, the largest gallstone diameter and gallbladder wall thickness were determined. According to the histopathological examination, chronic inflammation was subdivided into mild-moderate and severe. Univariable analysis and multivariable logistic regression followed. RESULTS: Mild-moderate inflammation characterized 63.4% of the cases and severe inflammation 366%. Solitary gallstones were found in 13.1% of the cases, while multiple gallstones were found in 86.9% of the cases. The largest gallstone diameter was less than 1 cm in the majority of cases (73.2%). The gallbladder wall thickness was associated with the degree of inflammation (p < 0.001, Chi-square). In the univariable analysis, inflammation was positively associated with the diameter of the largest gallstone (p = 0.032, Chi-square), but negatively associated with the number of gallstones (p < 0.001, Chi-square) and patients' age (p = 0.008, logistic regression). The number of gallstones was negatively associated with the diameter of gallstones and positively associated with the patients' age. The diameter of the largest gallstone was negatively associated with the patients' age. In the multivariable logistic regression, the effect of age (OR = 0.95, 95% CI: 0.91-0.99) and solitary gallstones (OR = 2.66, 95% CI: 1.02-6.93) on inflammation persisted, but that of the largest gallstone diameter vanished. CONCLUSION: The elderly population presented mainly with multiple and small gallstones. Solitary gallstones and younger age were the most important predictors for severe inflammation.     

The economic burden of atherothrombosis in Greece: results from the THESIS study

The aim of this study was to estimate the total annual cost of patients with or at risk for atherothrombosis in Greece. A multicentre, cost-of-illness study was conducted between January 2007 and December 2009. In the study, 800 patients with coronary artery disease, cerebrovascular disease, or peripheral artery disease (PAD) or multiple cardiovascular risk factors (MRF) were recruited. Direct and indirect cost data were assessed at patients’ enrolment in the study, and at 6 and 12 months of follow-up. The annual total cost was €6,017/patient. This cost ranged from €10,098/patient with PAD to €1,813/patient with MRF. The annual direct health-care cost was €5,056/patient. This cost escalates from €1,623/patient with MRF to €8,697/patient with PAD. The total annual expenditures related to atherothrombosis, in Greece, were estimated to be €7.5 billion at the national level. The findings of the current study indicate the high economic burden of atherothrombosis in Greece.     

High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas

Objectives Previous studies based on standard endocrine testing have shown a variable incidence of autonomous cortisol secretion (ACS) or autonomous aldosterone secretion (AAS) in patients with single adrenal adenomas (SAA). We tested whether the use of appropriate controls and modification of standard testing, aiming at eliminating interference from endogenous ACTH, reveals previously undetected subtle ACS and AAS by SAA. Design Case control study. Patients We investigated 151 patients with SAA and 72 matched controls with normal adrenal computerized tomography. Measurements All participants had arterial blood pressure recorded, and serum cortisol and aldosterone measured before and after intravenous administration of 250 μg of ACTH, and following dexamethasone administration. Eighty‐three patients and all the controls had serum aldosterone and renin measured before and after saline infusion, and after a second saline infusion following dexamethasone administration. Results Using the mean + 2 SD values obtained from controls after dexamethasone administration and saline infusion following dexamethasone administration, normal cut‐off values for cortisol (30·11 nm ), aldosterone (67·59 pm ), and aldosterone/renin ratio (9·74 pm /mU/l) were developed. Using these cut‐off values, the estimated incidence of ACS and AAS in patients with SAA was 56·63% and 24·10%, respectively, whereas 12·05% had autonomous secretion of both cortisol and aldosterone. Systolic and diastolic arterial blood pressure correlated significantly with the aldosterone/renin ratio following ΑCTH stimulation (P < 0·0002 and P < 0·001, respectively), and after saline infusion following dexamethasone administration (P < 0·003 and P < 0·002, respectively). Conclusions By applying new cut‐offs, ACS and AAS in patients with a SAA is very common, and aldosterone secretion correlates with arterial blood pressure.     

In vitro activities of omadacycline,eravacycline, cefiderocol,apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020–2021: a multicenter study

Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020–April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC₅₀/₉₀ values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.

     

Comparative evaluation of combined-disk tests using different boronic acid compounds for detection of klebsiella pneumoniae carbapenemase-producing enterobacteriaceae clinical isolates

The accurate phenotypic detection of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae is an increasing necessity worldwide. We evaluated the performance of boronic acid combined-disk tests using as substrate imipenem or meropenem and as inhibitor of KPC production 300 μg aminophenylboronic acid (APBA), 600 μg APBA, or 400 μg phenylboronic acid (PBA). Tests were considered positive when an increase in the growth-inhibitory zone around a carbapenem disk with KPC inhibitor was 5 mm or greater of the growth-inhibitory zone diameter around the disk containing carbapenem alone. The comparison of the combined-disk tests was performed with 112 genotypically confirmed KPC-possessing Enterobacteriaceae isolates. To measure the specificity of the tests, 127 genotypically confirmed KPC-negative Enterobacteriaceae isolates that were nonsusceptible to at least one carbapenem were chosen for testing. Using disks containing imipenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 72, 92, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 64.3%, 82.1%, and 100%, respectively). Using disks containing meropenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 87, 108, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 77.7%, 96.4%, and 100%, respectively). Among KPC producers, the disk potentiation tests using meropenem and PBA demonstrated the largest differences in inhibition zones (P < 0.001). All combined-disk tests correctly identified 124 of the 127 non-KPC producers (specificity, 97.6%). This comparative study showed that PBA is the most effective inhibitor of KPC enzymes, and its use in combined-disk tests with meropenem may give the most easily interpreted results.     

Development of a quantum-dot-labelled magnetic immunoassay method for circulating colorectal cancer cell detection

AIM: To detect of colorectal cancer (CRC) circulating tumour cells (CTCs) surface antigens, we present an assay incorporating cadmium selenide quantum dots (QDs) in these paper.METHODS: The principle of the assay is the immunomagnetic separation of CTCs from body fluids in conjunction with QDs, using specific antibody biomarkers: epithelial cell adhesion molecule antibody, and monoclonal cytokeratin 19 antibody. The detection signal was acquired from the fluorescence signal of QDs. For the evaluation of the performance, the method under study was used to isolate the human colon adenocarcinoma cell line (DLD-1) and CTCs from CRC patients’ peripheral blood.RESULTS: The minimum detection limit of the assay was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a spectrofluorometer. Fluorescence-activated cell sorting analysis and Real Time RT-PCR, they both have also been used to evaluate the performance of the described method. In conclusion, we developed a simple, sensitive, efficient and of lower cost (than the existing ones) method for the detection of CRC CTCs in human samples. We have accomplished these results by using magnetic bead isolation and subsequent QD fluorescence detection.CONCLUSION: The method described here can be easily adjusted for any other protein target of either the CTC or the host.     

Structural and functional analysis of cyclophilin PpiB mutants supports an in vivo function not limited to prolyl isomerization activity

Escherichia coli cyclophilin PpiB is a peptidyl‐prolyl cis/trans isomerase (PPIase, EC: 5.2.1.8), involved in the negative modulation of various bacterial processes, such as swimming and swarming motility and biofilm formation ability. In this study, we show that PpiB possesses also a chaperone function as it can prevent the thermal denaturation of citrate synthase even with essentially eliminated PPIase activity. We demonstrate, using active site mutations, that the PPIase activity of PpiB is required in all processes, except for the negative effect on swimming, indicating a possible isomerase‐independent function. Additionally, we show that the reduced PPIase activity of PpiB does not prevent the association with all prey proteins tested and that the PPIase active site is not involved necessarily in each association. We also used a random mutagenesis approach, to identify amino acid residues apart from the catalytic site, which are necessary for PpiB function. The combination of enzymatic studies concerning the PPIase and chaperone activities of each mutant protein, with structural analyses based on 3D models, provided further insights into the effects of the mutations on the function of PpiB and showed the importance of structural features in addition to the catalytic site, for its in vivo role.     

Measuring human T cell responses in blood and gut samples using qualified methods suitable for evaluation of HIV vaccine candidates in clinical trials

The next generation of candidate HIV vaccines include replicating vectors selected for tropism to mucosal sites, where an efficacious T cell response will be required to limit T cell replication and HIV associated CD4 T cell loss. To fully assess immunogenicity of such candidates, there is a need to develop robust quality controlled analysis of gut derived HIV specific CD8+ T-cell responses. Despite obvious challenges in obtaining sufficient amounts of tissue, the highly compartmentalised nature of the mucosal immune responses, requires the assessment of CD8 T cells isolated directly from local tissue before any conclusions regarding the induction of mucosal responses are made. Here we describe the optimisation and subsequent qualification of a qualitative and quantitative polychromatic flow cytometry assay to assess antigen specific CD8+ T cells isolated from the gut, using samples from HIV positive and negative volunteers. Internal quality controls monitored over time, combined with the use of quality gating and standard operating procedures were used to demonstrate the generation of robust and reliable data.