Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange: A Diagnostic Scoring System.

BACKGROUND: This study evaluated appropriate thresholds for serum biomarkers, synovial fluid white blood cell (SF-WBC) count, and synovial fluid neutrophil (polymorphonuclear leukocyte [PMN]) percentage to predict infection in a patient group who underwent definitive reimplantation after receiving a continuous course of antibiotic therapy for chronic knee periprosthetic joint infection (PJI). These thresholds were then used to generate a scoring system to predict recurrence (or persistence) of infection. METHODS: The study included 153 patients with a median age of 73 years (range, 46 to 91 years) who underwent 2-stage revision for chronic knee PJI. Staphylococci were identified at baseline in 107 (70%) of the patients. After the 96-week follow-up period, 12% (19) of the 153 patients had recurrence of the PJI. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of common serum biomarkers and SF aspiration before reimplantation, and the area under the curve (AUC) was evaluated. Variables that were significantly different between patients with and without infection recurrence were evaluated using a multivariable logistic regression model. A half-integer-point scoring system was created based on the final beta coefficients. RESULTS: Regarding the prediction of recurrent infection, a D-dimer level of >1110 ng/mL yielded a sensitivity of 74%, specificity of 61%, and AUC of 0.69; an SF-WBC count of >934 cells/µL showed a sensitivity of 68%, specificity of 90%, and AUC of 0.79; and an SF-PMN percentage of >52% showed a sensitivity of 73%, specificity of 90%, and AUC of 0.82. The beta coefficients were approximated to 1.5 for the D-dimer level and to 2 for the SF-WBC count and SF-PMN percentage. A total score of >2 was used to classify patients with a high risk of infection recurrence. The ability to discriminate infection recurrence was demonstrated by an AUC of 0.90 (95% confidence interval: 0.82 to 0.99). CONCLUSIONS: Patients with a score of >2 on our proposed scoring system based on serum biomarkers, SF-WBC count, and SF-PMN percentage should not undergo reimplantation, as they are at a high risk for recurrent PJI. Patients with a score of ≤2 can undergo definitive reimplantation with the lowest risk of recurrence. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.

AIM: To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. METHODS AND RESULTS: One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ 1, 2, 4, and 6 h after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 h after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N = 32) as compared with patients not receiving morphine (N = 98; PRU = 187 [70-217]) vs. 73 [7-187]; P = 0.012). In patients with morphine, 1-h PRU values were similar between study groups (192 [114-236] vs. 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-h PRU values were not significantly different between study groups (69 [8-152] vs. 110 [6-193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4, and 6 h after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. CONCLUSIONS: There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.

The combined evaluation of fibrinogen and D-dimer levels are a helpful tool to exclude periprosthetic knee infection.

This retrospective study was undertaken to (i) define the most appropriate thresholds for serum d-dimer and fibrinogen for differentiating aseptic failure from periprosthetic joint infection (PJI) and (ii) evaluate the predictive value of our d-dimer and fibrinogen threshold compared to previously proposed thresholds. This observational cohort study included consecutive patients who had undergone total knee arthroplasty (TKA) revision between January 2019 and December 2020. International Consensus Meeting diagnostic criteria were used to identify patients affected by the prosthetic infection. Receiver operating characteristic curve analyses assessed the predictive value of the parameters, and the areas under the curves were evaluated. We included 125 patients with a median age of 69 years (53-82) affected by painful TKA. Fifty-seven patients (47%) had PJI. Patients with PJI had higher median d-dimer, fibrinogen, ESR, and CRP when compared to patients believed to be free of PJI. The best threshold values for d-dimer and fibrinogen were 1063 ng/ml (sensitivity 0.72, specificity 0.74) and 420 mg/dl (sensitivity 0.67 and specificity 0.82), respectively. A d-dimer level >1063 ng/ml combined with a fibrinogen level >420 mg/dl had a sensitivity of 0.52, and a specificity of 0.90. We found that an increased d-dimer beyond 1063 ng/ml showed a better predictive value than the previously proposed threshold. The combined determination of d-dimer and fibrinogen displayed high specificity and should be considered an excellent tool to rule out an infection. The accuracy of the proposed cutoffs is more effective than previously reported.

Drug-drug interactions between antithrombotics and direct-acting antivirals in hepatitis C virus (HCV) patients: A brief, updated report.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease affecting over 71 million people worldwide. An increased incidence of atherothrombotic events [e.g. coronary artery disease (CAD), atrial fibrillation (AF)] has been observed in HCV seropositive patients. On the other hand, an increased bleeding risk is another clinical issue, particularly in subjects with liver cirrhosis, gastroesophageal varices, portal hypertension, thrombocytopenia and alcohol consumption. The introduction and progressively greater use of direct-acting antivirals (DAAs) (instead of protease and polymerase inhibitors) during the last decade has enabled a sustained virological response to be achieved in a significant percentage of patients. However, due to the high cardiovascular risk profile in HCV-infected patients, the concomitant use of antithrombotic therapies is often required, bearing in mind the possible contraindications. For example, despite better pharmacokinetic and pharmacodynamic properties compared with vitamin K-antagonists, plasma level fluctuations of direct oral anticoagulants (DOACs) due to pathological conditions (e.g. chronic kidney diseases or hepatic cirrhosis) or drug-drug interactions (DDIs) may be of great importance as regards their safety profile and overall clinical benefit. We aimed to examine and briefly summarize the significant DDIs observed between antithrombotic and HCV antiviral drugs.

Not-high before-treatment platelet reactivity in patients with STEMI: prevalence, clinical characteristics, response to therapy and outcomes.

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI.We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4-6 hours and 8-12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR.Overall, 20% patients had NHPR. Age and male gender both resulted independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point. However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; p = .017) as compared with the NHPR group.In conclusion, a significant proportion of patients presenting with STEMI has a baseline NHPR that is associated with better in-hospital outcomes as compared with patients with HPR. Further studies are needed to better elucidate the potential therapeutic implications of NHPR in terms of secondary prevention.

Impact of glucose-6-phosphate dehydrogenase deficiency on the severity of coronary atherosclerosis in patients with acute coronary syndromes.

AIMS: The impact of glucose-6-phosphate dehydrogenase (G6PD) deficiency on coronary atherosclerosis has not been clearly investigated so far. We aimed to assess the effects of G6PD deficiency on the extent and complexity of coronary atherosclerosis in a large unselected cohort of consecutive patients with acute coronary syndromes (ACS). METHODS: We studied 623 consecutive patients presenting with ACS and undergoing coronary angiography and percutaneous coronary intervention (PCI). G6PD activity was quantitatively measured in all individuals using a biochemical assay based on the G6PD/6GPD ratio in erythrocytes. Individuals were defined as deficient when the ratio was less than 0.80. The severity and complexity of coronary atherosclerosis were assessed by SYNTAX score at baseline angiography. RESULTS: Fifty-six patients (9%) showed G6PD deficiency. Severe (i.e. enzymatic activity < 0.10) G6PD deficiency was detected in 33 (5.3%) individuals, mainly of male sex (n = 32). Overall, the cardiovascular risk profile was similar between patients with G6PD deficiency and controls. Patients with G6PD deficiency showed similar severity and complexity of coronary atherosclerosis as compared to control patients; accordingly, the SYNTAX score (15 vs. 14.5, P = 0.90, respectively, in G6PD-deficent patients and controls), and all its components were similar between deficient individuals and controls. The only independent predictor of a SYNTAX score of more than 22 was patients' age (odds ratio 1.035, 95% confidence interval 1.018-1.051; P < 0.001). CONCLUSION: G6PD deficiency does not impact on the extent and complexity of coronary atherosclerosis assessed by coronary angiography in patents presenting with ACS.

Synovial Cell Count Before Reimplantation Can Predict the Outcome of Patients with Periprosthetic Knee Infections Undergoing Two-stage Exchange.

BACKGROUND: Although synovial fluid can be used to diagnose periprosthetic joint infections (PJI) effectively, only the cutoff values adopted at the time of PJI diagnosis have been standardized, and few data are currently available about effectiveness of synovial fluid examination before definitive reimplantation. QUESTIONS/PURPOSES: We asked: (1) What are the most appropriate thresholds for synovial fluid leukocyte counts (WBC) and neutrophil percentage (PMN percentage) in a patient group undergoing definitive reimplantation after an uninterrupted course of antibiotic therapy for chronic PJI? (2) What is the predictive value of our synovial WBC and PMN percentage threshold compared with previously proposed thresholds? METHODS: In all, 101 patients with PJI were evaluated for inclusion from January 2016 to December 2018. Nineteen percent (19 of 101) of patients were excluded because of the presence of a chronic inflammatory disease, acute/late hematogenous infection, low amount of synovial fluid for laboratory investigations or infection persistence after spacer placement, and adequate antibiotic therapy. Finally, 81% (82 of 101) of patients with a median (range) age of 74 years (48 to 92) undergoing two-stage revision for chronic TKA infection, who were followed up at our institution for a period 96 weeks or more, were included in this study. The patients did not discontinue antibiotic treatment before reimplantation and were treated for 15 days after reimplantation if intraoperative cultures were negative. No patient remained on suppressive treatment after reimplantation. Synovial fluid was aspirated aseptically with a knee spacer in place to evaluate the cell counts before reimplantation. Thirteen percent (11 of 82) of patients had persistent or recurrent infection, defined as continually elevated erythrocyte sedimentation rate or C-reactive protein levels coupled with local signs and symptoms or positive cultures. The synovial fluid WBC counts and PMN percentage from the 11 patients with persistent or recurrent PJI were compared with the 71 patients who were believed to be free of PJI. Receiver operating characteristic (ROC) curve analyses assessed the predictive value of the parameters, and the areas under the curves (AUCs) were evaluated. The sensitivities, specificities, and positive and negative predictive values were determined for the WBC count and PMN percentage. Patients with persistent or recurrent infection had higher median WBC counts (471 cells/µL versus 1344 cells/µL; p < 0.001) and PMN percentage (36% versus 61%; p < 0.001) than did patients believed to be free of PJI. RESULTS: ROC curve analysis identified the best threshold values to be a WBC count of 934 cells/µL or more (sensitivity 0.82 [95% CI 0.71 to 0.89], specificity 0.82 [95% CI 0.71 to 0.89]) as well as a PMN percentage of at least 52% (sensitivity 0.82 [95% CI 0.71 to 0.89] and specificity 0.78 [95% CI 0.67 to 0.86]. We found no difference between the AUCs for the WBC count and the PMN percentage (0.87 [95% CI 0.79 to 0.96] versus 0.84 [95% CI 0.73 to 0.95]. Comparing the sensitivities and specificities of the synovial fluid WBC count and PMN percentage proposed by other authors, we find that a PMN percentage more than 52% showed better predictive value than previously reported. CONCLUSION: Based on our findings, we believe that patients with WBC counts of at least 934 and PMN percentage of 52% or more should not undergo reimplantation but rather a repeat debridement, as their risk of persistent or recurrent PJI appears prohibitively high. The accuracy of the proposed cutoffs is better than previously reported. LEVEL OF EVIDENCE: Level III, diagnostic study.

[Coronary wire entrapment and unintended extraction of a just deployed stent]. / Intrappolamento di guida coronarica e rimozione non intenzionale di stent appena impiantato.

A 53-year-old male was admitted to our department for unstable angina. Coronary angiography showed a subocclusive stenosis in the ostial-proximal tract of an intermediate branch in the context of a left dominance system. We proceeded with an ad hoc percutaneous coronary intervention considering this intermediate branch lesion in the setting of a bifurcation (Medina 0,0,1), where the proximal and distal main branches were represented by the left main and left anterior descending (LAD) arteries, respectively. After pre-dilation of the intermediate branch lesion, we advanced a "safety balloon" in order to protect the LAD branch and, simultaneously, we deployed a 3.0/22 mm drug-eluting stent in the intermediate branch. After in-stent post-dilation, we felt a strong resistance during the guidewire removal from the LAD indicating a wire entrapment. After a vigorous traction of the jailed guidewire, we observed the accidental removal of the just deployed stent from the guiding catheter. We re-advanced a guidewire on the LAD and a 3.25/23 mm drug-eluting stent was successfully implanted on the intermediate branch. We briefly discuss the occurred complication and some technical aspects regarding this case.

Coronary Guidewire Fracture Into a Radial Artery Loop: A New Complication in the Transradial Era?

To date, complete fracture of a coronary wire into a radial artery loop has never been reported. We describe the occurrence of a new complication in the transradial intervention era.

Accuracy of Fine Needle Cytology in Histological Prediction of Papillary Thyroid Carcinoma Variants: a Prospective Study.

Fine needle cytology (FNC) is a crucial procedure in the preoperative diagnosis of thyroid tumors. Papillary thyroid carcinoma (PTC), in its classic variant (cPTC), is the most common malignant neoplasm of the thyroid. Several histological variants of PTC have been described, each one with its own characteristics and prognosis. The ability of FNC to identify the variants represents a challenge even for a skilled pathologist. The aim of this study was to evaluate the diagnostic cytological accuracy of FNC in PTC and to look for specific features that could predict the different variants. This was a single center prospective study on 128 patients who received a diagnosis of PTC on FNC. The smears were blindly reviewed by two cytopathologists to create a frequency score (0, 1, 2, 3) of the features for each variant. The cytological parameters were divided into three groups: architectural, nucleo-cytoplasmic, and background features. Univariate analysis was performed by chi-square test with Yates correction and Fisher exact test as appropriate. Multiple regression analysis was performed among the variables correlated at the linear correlation. The correlation study between cytology and histology showed an accuracy of FNC in classic, follicular, and oncocytic PTC variants of 63.5, 87.5, and 87% respectively. Familiarity with cytological features may allow an early diagnosis of a given PTC variant on FNC samples. This is fundamental in a preoperative evaluation for the best surgical approach and subsequent treatment.

Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.

Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy.

Absence of BRAF gene mutation in non-melanoma skin tumors.

Basal cell carcinoma (BCC) is the most common skin cancer, and its incidence is increasing. It was proposed that the RAS oncogene significantly contributes to skin cancer development. Numerous BRAF mutations have been detected in melanoma biopsy specimens and cell lines. For the first time, in the present study, tumor biopsy specimens from 78 patients with BCC were screened for BRAF mutation within exons 11 and 15. Our results indicate that the BRAF gene does not appear to be frequently mutated in nonmelanoma skin tumors such as BCC. These data suggest that other gene alterations may cause tumor development.