Programmed Death Ligand 1 Is Overexpressed in Liver Macrophages in Chronic Liver Diseases, and Its Blockade Improves the Antibacterial Activity Against Infections.

BACKGROUND AND AIMS: Bacterial infections are common and severe in cirrhosis, but their pathogenesis is poorly understood. Dysfunction of liver macrophages may play a role, but information about their function in cirrhosis is limited. Our aims were to investigate the specific profile and function of liver macrophages in cirrhosis and their contribution to infections. Macrophages from human cirrhotic livers were characterized phenotypically by transcriptome analysis and flow cytometry; function was assessed in vivo by single photon emission computerized tomography in patients with cirrhosis. Serum levels of specific proteins and expression in peripheral monocytes were determined by ELISA and flow cytometry. In vivo phagocytic activity of liver macrophages was measured by spinning disk intravital microscopy in a mouse model of chronic liver injury. APPROACH AND RESULTS: Liver macrophages from patients with cirrhosis overexpressed proteins related to immune exhaustion, such as programmed death ligand 1 (PD-L1), macrophage receptor with collagenous structure (MARCO), and CD163. In vivo phagocytic activity of liver macrophages in patients with cirrhosis was markedly impaired. Monocytes from patients with cirrhosis showed overexpression of PD-L1 that paralleled disease severity, correlated with its serum levels, and was associated with increased risk of infections. Blockade of PD-L1 with anti-PD-L1 antibody caused a shift in macrophage phenotype toward a less immunosuppressive profile, restored liver macrophage in vivo phagocytic activity, and reduced bacterial dissemination. CONCLUSION: Liver cirrhosis is characterized by a remarkable impairment of phagocytic function of macrophages associated with an immunosuppressive transcriptome profile. The programmed cell death receptor 1/PD-L1 axis plays a major role in the impaired activity of liver macrophages. PD-L1 blockade reverses the immune suppressive profile and increases antimicrobial activity of liver macrophages in cirrhosis.

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

OBJECTIVES: Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. METHODS: We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. RESULTS: wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. CONCLUSION: HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. KEY POINTS: • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis.

OBJECTIVES: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. METHODS: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. RESULTS: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. CONCLUSIONS: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.

Relationship between Vancomycin MIC and Virulence Gene Expression in Clonal Complexes of Methicillin-Susceptible Staphylococcus aureus Strains Isolated from Left-Sided Endocarditis.

Higher vancomycin MICs have been associated with more complicated courses and higher mortality rates in patients with Staphylococcus aureus bacteremia and infective endocarditis (IE). The aim of this study was to investigate whether the strains belonging to the cohort of 93 patients from a previously published study in which patients with strains with vancomycin MICs of ≥1.5 µg/ml presented higher mortality rates and systemic emboli than patients with strains with vancomycin MICs of <1.5 µg/ml had specific patterns of virulence factors, clonal complex (CC) types, or the ability to form biofilms. Vancomycin MICs were determined by Etest, and the isolates underwent spa typing to infer the CC, biofilm studies, a thrombin-induced platelet microbicidal assay, and multiplex PCR for the presence of virulence genes. We found no differences in genes encoding adhesins, toxins, or other putative virulence genes according to the vancomycin MIC group. CC30, CC34, and CC45 represented nearly half of the isolates, and there was no association with the vancomycin MIC. agr subgroups I and III predominated, with no association with the vancomycin MIC. Isolates with higher vancomycin MICs exhibited a poorer ability to form biofilms with and without the presence of vancomycin (2.03 versus 2.48 [P < 0.001], respectively, for isolates with higher vancomycin MICs and 2.60 versus 2.87 [P = 0.022], respectively, for isolates with lower vancomycin MICs). In the multivariable analysis, efb and V8 were risk factors for major emboli (adjusted odds ratio [aOR] = 7.5 and 95% confidence interval [CI] = 1.2 to 46.6 for efb, and aOR = 3.9 and 95% CI = 1.1 to 14.1 for V8), whereas no genotypic predictors of in-hospital mortality were found. No clear associations between genes encoding virulence factors, agr type, clonal complexes, mortality, and major embolic events according to vancomycin MIC group were found.

Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis.

BACKGROUND: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE). METHODS: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h). RESULTS: At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC. CONCLUSIONS: The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use.

Applicability of sentinel lymph node biopsy in papillary thyroid cancer.

BACKGROUND: The optimal surgical management of papillary thyroid cancer (PTC) for T1-T2 tumors without pre or intrasurgical evidence of lymph node metastasis (cN0) remains controversial, since approximately 40% of patients have lymph node involvement (pN1) which becomes evident when a prophylactic lymphadenectomy (PL) is performed. The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification with SPECT/CT lymphoscintigraphy imaging along with intraoperatory image techniques in early stages of PTC undergoing PL of central neck compartment (CNC). METHODS: A single-center, prospective consecutive study was designed for SLN mapping in patients with high suspicion of PTC (Bethesda V or VI) in early stage (cT1-2, cN0). Twenty-four patients underwent SLN identification with preoperative SPECT/CT and planar images (99mTc-nanocolloid albumin intratumoral injection). During surgery, SLN located in CNC was found by means of a gamma probe and portable gamma camera, and excised. Afterwards, CNC lymphadenectomy was performed in all cases without modifying the established protocol. RESULTS: SLNs were identified and accurately located in 23 (95.8%) patients. Nodal metastases (pN1) were confirmed in 9 (37.5%) patients, with one false negative case. The sensitivity was 88.9% and negative predictive value (NPV) was 93.3%, would have allowed to avoid PL in more than half of cases, a higher proportion than those found in other similar studies. No complications associated with the procedure were observed. CONCLUSIONS: Our results support that SLN biopsy by SPECT/CT along with intraoperatory image techniques is applicable in early stages of PTC (cT1-2, cN0), allowing to avoid unnecessary PL.

Diagnostic yield of 18F-FDG PET/CT in suspected diagnosis of vascular graft infection: A prospective cohort study.

BACKGROUND: Prosthetic vascular graft infection (PVGI) is a severe complication associated with high morbidity and mortality. Clinical diagnosis is complex, requiring image testing such as CT angiography or leukocyte scintigraphy, which has considerable limitations. The aim of this study was to know the diagnostic yield of PET/CT with 18F-Fluorodeoxyglucose (18F-FDG) in patients with suspected PVGI. METHODS: We performed a prospective cohort study including 49 patients with suspected PVGI, median age of 62 ± 14 years. Three uptake patterns were defined following published recommendations: (i) focal, (ii) patched (PVGI criteria), and (iii) diffuse (no PVGI criterion). RESULTS: Sensitivity, specificity, and positive and negative predictive values for 18F-FDG-PET/CT were 88%, 79%, 67%, and 93%, respectively. 18F-FDG-PET/CT identified 14/16 cases of PVGI showing a focal (n = 10) or patched pattern (n = 4), being true negative in 26/33 cases with either a diffuse pattern (n = 16) or without uptake (n = 10). Five of the seven false-positive cases (71%) showed a patched pattern and all coincided with the application of adhesives for PVG placement. CONCLUSIONS: 18F-FDG-PET/CT is a useful technique for the diagnosis of PVGI. A patched pattern on PET/CT in patients in whom adhesives were applied for prosthetic vascular graft placement does not indicate infection.

Epidemiology, Clinical Features, and Outcome of Infective Endocarditis due to Abiotrophia Species and Granulicatella Species: Report of 76 Cases, 2000-2015.

Background: Infective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE. Methods: We performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases). Results: ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)-related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23). Conclusions: GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure.

Mechanical Thrombectomy for Acute Ischemic Stroke Secondary to Infective Endocarditis.

Intravenous thrombolysis is contraindicated in acute ischemic stroke secondary to infective endocarditis. We report our initial experience in 6 cases of proximal vessel occlusion treated with mechanical thrombectomy, which was safe (no bleeding) and effective (significant early neurological improvement) and might be useful in this clinical setting.

The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-Resistant Staphylococcus aureus in a Rabbit Model of Experimental Endocarditis.

We investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies using standard (106) and high (108) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 µg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%, P = 0.046) and the decrease in the density of bacteria within the vegetations (P = 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%, P = 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%, P = 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.

AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

Prospective comparison of whole-body (18)F-FDG PET/CT and MRI of the spine in the diagnosis of haematogenous spondylodiscitis.

PURPOSE: To prospectively compare (18)F-FDG PET/CT and MRI in the diagnosis of haematogenous spondylodiscitis METHODS: The study included 26 patients (12 women, 14 men; mean age 59 ± 17 years) with clinical symptoms of infection of the spine. Patients who had had prior spinal surgery or any type of antibiotic therapy in the previous 3 months were excluded from the study. Whole-body PET/CT 60 min after injection of 4.07 MBq/kg of (18)F-FDG and an MRI scan of the spine was performed in all patients. SUVmax in an area surrounding the lesions with the suspicion of infection as well as a background SUVmean in a preserved area of the spine were calculated for quantification. Infection was diagnosed by microbiological documentation in cultures of image-guided spinal puncture fluid or blood. Infection was excluded if symptoms were absent without antimicrobial therapy during a follow-up of at least 6 months. RESULTS: Spondylodiscitis was confirmed in 18 of the 26 patients. Staphylococcus aureus was found in 8 patients, Mycobacterium tuberculosis in 4, Escherichia coli in 2 and other pathogens in 4. Of the remaining 8 patients, the diagnoses were degenerative spondyloarthropathy in 5 and vertebral fracture in 3. The sensitivity, specificity, and positive and negative predictive value were 83%, 88%, 94% and 70% for (18)F-FDG PET/CT, and 94%, 38%, 77% and 75% for MRI, respectively. The accuracies of (18)F-FDG PET/CT and MRI were similar (84% and 81%, respectively). The combination of (18)F-FDG PET/CT and MRI detected the infection in 100% of the patients with spondylodiscitis. (18)F-FDG uptake, quantified in terms of SUVmax corrected by the background SUVmean, was significantly higher in patients with spondylodiscitis than in those without infection (p < 0.001). CONCLUSION: Due to its high specificity, (18)F-FDG PET/CT should be considered as a first-line imaging procedure in the diagnosis of spondylodiscitis. Quantification of uptake in terms of SUVmax was able to discriminate infection of the spine from other processes in this series of patients.

Role of re-growth interface preparation process for spectral line-width reduction of single InAs site-controlled quantum dots.

We present growth and optical characterization measurements of single InAs site-controlled quantum dots (SCQDs) grown by molecular beam epitaxy on GaAs (001) patterned substrates by atomic force microscopy oxidation lithography. InAs SCQDs directly grown on the patterned surface were used as a seed layer and strain template for the nucleation of optically active single InAs SCQDs. The preservation of the initial geometry of the engraved pattern motifs after the re-growth interface preparation process, the lack of buffer layer growth prior to InAs seed layer deposition and the development of suitable growth conditions provide us an improvement of the SCQDs' active layer optical properties while retaining a high ratio of single occupation (89%). In this work a fivefold reduction of the average optical line-width from 870 µeV to 156 µeV for InAs SCQDs located 15 nm from the re-growth interface is obtained by increasing the temperature of the initial thermal treatment step of the re-growth interface from 490 °C to 530 °C.

One-stage revision arthroplasty using cementless stem for infected hip arthroplasties.

The objective of this retrospective study was to evaluate our results with one-stage revision using cementless femoral stem for infected hip arthroplasties. Twenty-four patients were included in the study. The acetabular component was cemented in 9 cases. In 2 patients a structured bone allograft was necessary to fill an acetabular defect. After a mean follow-up of 44.6 months, 23 patients showed no signs of infection (95.8%), the mean functional response according to the Merle d'Aubigné scale was 13.8 and the mean Harris Hip Score was 65.4. One-stage revision hip arthroplasty using cementless femoral stem was associated with a high success rate.

Reappraisal of [18F]FDG-PET/CT for diagnosis and management of cardiac implantable electronic device infections.

INTRODUCTION AND OBJECTIVES: The role of [18F]FDG-PET/CT in cardiac implantable electronic device (CIED) infections requires better evaluation, especially in the diagnosis of systemic infections. We aimed to determine the following: a) the diagnostic accuracy of [18F]FDG-PET/CT in each CIED topographical region, b) the added value of [18F]FDG-PET/CT over transesophageal echocardiography (TEE) in diagnosing systemic infections, c) spleen and bone marrow uptake in differentiating isolated local infections from systemic infections, and d) the potential application of [18F]FDG-PET/CT in follow-up. METHODS: Retrospective single-center study including 54 cases and 54 controls from 2014 to 2021. The Primary endpoint was the diagnostic yield of [18F]FDG-PET/CT in each topographical CIED region. Secondary analyses described the performance of [18F]FDG-PET/CT compared with that of TEE in systemic infections, bone marrow and spleen uptake in systemic and isolated local infections, and the potential application of [18F]FDG-PET/CT in guiding cessation of chronic antibiotic suppression when completed device removal is not performed. RESULTS: We analyzed 13 (24%) isolated local infections and 41 (76%) systemic infections. Overall, the specificity of [18F]FDG-PET/CT was 100% and sensitivity 85% (79% pocket, 57% subcutaneous lead, 22% endovascular lead, 10% intracardiac lead). When combined with TEE, [18F]FDG-PET/CT increased definite diagnosis o fsystemic infections from 34% to 56% (P=.04). Systemic infections with bacteremia showed higher spleen (P=.05) and bone marrow metabolism (P=.04) than local infections. Thirteen patients without complete device removal underwent a follow-up [18F]FDG-PET/CT, with no relapses after discontinuation of chronic antibiotic suppression in 6 cases with negative follow-up [18F]FDG-PET/CT. CONCLUSIONS: The sensitivity of [18F]FDG-PET/CT for evaluating CIED infections was high in local infections but much lower in systemic infections. However, accuracy increased when [18F]FDG-PET/CT was combined with TEE in endovascular lead bacteremic infection. Spleen and bone marrow hypermetabolism could differentiate bacteremic systemic infection from local infection. Although further prospective studies are needed, follow-up [18F]FDG-PET/CT could play a potential role in the management of chronic antibiotic suppression therapy when complete device removal is unachievable.

Purcell effect in photonic crystal microcavities embedding InAs/InP quantum wires.

The spontaneous emission rate and Purcell factor of self-assembled quantum wires embedded in photonic crystal micro-cavities are measured at 80 K by using micro-photoluminescence, under transient and steady state excitation conditions. The Purcell factors fall in the range 1.1 - 2 despite the theoretical prediction of ≈15.5 for the figure of merit. We explain this difference by introducing a polarization dependence on the cavity orientation, parallel or perpendicular with respect to the wire axis, plus spectral and spatial detuning factors for the emitters and the cavity modes, taking in account the finite size of the quantum wires.

Optimum threshold estimation based on cost function in a multistate diagnostic setting.

In the diagnostic area, the usual setting considers two populations: nondiseased and diseased. The use of the standard ROC analysis methodology is well established. Sometimes, however, diagnostic problems inherently include more than two classification states. For example, 'yes, uncertain, no' or 'low, normal, high'. Here we consider a three-normal distribution setting and derive estimators for the optimum thresholds between states based on a cost function. These estimators can be extended for clinical contexts with more than three states. This approach is well known for the two-state setting and its advantage lies in the fact that it accounts for the specific context's properties, such as disease prevalence and classification costs. Here we calculated the variance of the estimators by the use of parametric methods on nonlinear equations and we constructed confidence intervals accounting for possible uncertainty in the threshold estimation. We conducted a simulation study to assess the performance of these estimators and the confidence intervals. Comparisons with the naive threshold estimation method of joining the distributions two-by-two and applying standard ROC techniques proved that the latter method is not reliable for all parameter combinations and should be avoided.

PET/CT Integrated With CT Colonography in Preoperative Obstructive Colorectal Cancer by Incomplete Optical Colonoscopy: A Prospective Study.

AIM: The aim of this study was to evaluate if integrating whole-body PET/CT with CT colonography (PET/CTC) improves the preoperative diagnosis of obstructive colorectal cancer (CRC). METHODS: We prospectively included 47 consecutive patients (18 women and 29 men; mean age, 71 ± 14 years) suspected of having CRC by optical colonoscopy, which was not completed due to obstructive masses. To perform PET/CTC, a small caliber Foley catheter was inserted to distend the colon with CO2 insufflations. Polyps measuring 10 mm or larger were considered as high risk of malignancy. All findings were histologically confirmed. RESULTS: Colorectal cancer was localized in the sigmoid (n = 21), rectum (n = 7), rectosigmoid junction (n = 5), ascending (n = 7), descending (n = 5), and transverse (n = 2) colon. All tumors showed FDG uptake (mean ± SD SUVmax, 20.02 ± 9.9) including one synchronic tumor (SUVmax, 10.46). Forty-seven polyps were histologically confirmed as smaller than 10 mm (n = 35) and 10 mm or larger (n = 12). All 12 polyps 10 mm or larger showed FDG uptake (SUVmax range, 3.08-19.5), but only one smaller than 10 mm could be identified by PET. Pathological lymph nodes were diagnosed in 17/47 cases after surgical removal with a sensitivity and specificity for CTC and PET/CTC of 71% and 97% and 59% and 100%, respectively. Liver metastases were confirmed in 9 patients and in 4/9 along with lung metastases (n = 2) or implants (n = 2), showing a sensitivity and specificity for CTC of 89% and 100% and both 100% for PET/CTC. CONCLUSIONS: PET/CTC is a reliable technique for staging CRC and diagnosing synchronous tumors. In this series, PET/CTC was not able to identify small polyps but showed potential use for ruling out 10 mm or larger polyps at high risk of malignancy.