Utility and Validity of the HFA-PEFF and H2FPEF Scores in Patients With Symptomatic Atrial Fibrillation.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H2FPEF scoring systems. OBJECTIVES: The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF. METHODS: The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500 mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H2FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF. RESULTS: In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82 (68.3%) had low/intermediate probability of HFpEF. Using the H2FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H2FPEF score (≥6 points) could diagnose HFpEF with a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC: 0.663 vs 0.707, respectively; P = 0.636). CONCLUSIONS: Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H2FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Exercise echocardiography to assess left atrial function in patients with symptomatic AF.

Background: Left atrial (LA) function contributes to the augmentation of cardiac output during exercise. However, LA response to exercise in patients with atrial fibrillation (AF) is unknown. We explored the LA mechanical response to exercise and the association between LA dysfunction and exercise intolerance. Methods: We recruited consecutive patients with symptomatic AF and preserved left ventricular ejection fraction (LVEF). Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET). Two-dimensional and speckle-tracking echocardiography were performed to assess LA function at rest and during exercise. Participants were grouped according to presenting rhythm (AF vs sinus rhythm). The relationship between LA function and cardiorespiratory fitness in patients maintaining SR was assessed using linear regression. Results: Of 177 consecutive symptomatic AF patients awaiting AF ablation, 105 met inclusion criteria; 31 (29.5 %) presented in AF whilst 74 (70.5 %) presented in SR. Patients in SR augmented LA function from rest to exercise, increasing LA emptying fraction (LAEF) and LA reservoir strain. In contrast, patients in AF demonstrated reduced LAEF and reservoir strain at rest, with failure to augment either parameter during exercise. This was associated with reduced VO2Peak compared to those in SR (18.4 ± 5.6 vs 22.5 ± 7.7 ml/kg/min, p = 0.003). In patients maintaining SR, LAEF and reservoir strain at rest and during exercise were associated with VO2Peak, independent of LV function. Conclusion: The maintenance of SR in patients with AF is associated with greater LA reservoir function at rest and greater augmentation with exercise compared to patients in AF. In patients in SR, reduced LA function is associated with reduced exercise tolerance, independent of LV function.

Is chest imaging needed as part of pT1a renal cell carcinoma surveillance after surgical resection?

INTRODUCTION: Following surgical excision of pT1a renal cell carcinoma (RCC), 2% to 5% will recur, with 50% to 60% being lung metastases. The ideal surveillance strategy to identify recurrences is unclear. Guidelines are mixed, with NCCN and AUA recommending surveillance via chest x-ray (CXR) at least annually for 5 years, while EAU guidelines do not specifically recommend the use of CXR. In an effort to clarify the utility of surveillance CXR, we retrospectively evaluated pT1a patients following surgical treatment at a single institution. METHODS: We performed retrospective analysis of unique patients who underwent surgical excision of pT1 RCC between January 2000 and January 2020. In addition to demographic information, we collected RCC pathology, recurrence details, and most recent chest imaging. We excluded non-RCC pathology, and patients with pulmonary nodules on baseline imaging. RESULTS: We identified 463 unique patients (mean age 58.3 years, range 23-87) that underwent surgical excision of pT1a RCC with mean follow-up of 47.6 months (range 1-201). On the most recent pulmonary surveillance imaging, 72.4% (335/463) had CXR while 27.6% (128/463) had chest CT performed. Regardless of modality, pulmonary recurrence was not detected on any surveillance imaging (0/463). CONCLUSION: In patients without baseline preoperative lung pathology, we found that there is questionable clinical value in surveillance for pulmonary recurrence after resection of pT1a RCC.

Surgical Drain-Related Small Bowel Obstruction After Open Radical Cystoprostatectomy: A Case Report.

Surgical drains are commonly used to manage intraperitoneal fluid after major surgeries, but their prophylactic use has been controversial due to potential complications. One rarely reported complication is small bowel obstruction (SBO), primarily seen in post-colorectal surgeries. We present a case of SBO following open radical cystectomy due to surgical drain placement, a complication not previously reported in urologic surgeries. The case highlights the importance of considering the risks and benefits of prophylactic drain placement. It emphasizes the need for a higher index of suspicion for SBO in patients with surgical drains who develop post-operative nausea and distention. Timely radiological imaging and clinical examination are crucial for accurate diagnosis and proper treatment.

Identification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria. OBJECTIVES: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients. METHODS: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire. RESULTS: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF. CONCLUSIONS: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Human placental hematopoietic stem cell-derived natural killer cells (CYNK) recognize and eliminate influenza A virus-infected cells.

Influenza A virus (IAV) infections are a significant recurrent threat to public health and a significant burden on global economy, highlighting the need for developing more effective therapies. Natural killer (NK) cells play a pivotal role in the control of pulmonary IAV infection, however, little is known about the therapeutic potential of adoptively transferred NK cells for viral infections. Here, we investigated the antiviral activity of CYNK, human placental hematopoietic stem cell-derived NK cells, against IAV infection in vitro. Virus infection induced the expression of NK cell activating ligands on respiratory epithelial cells, resulting in enhanced recognition by CYNK cells. Upon co-culture with IAV-infected epithelial cells, CYNK exhibited elevated degranulation and increased production of IFN-γ, TNF-α and GM-CSF in a virus dose-dependent manner. Furthermore, CYNK showed virus dose-dependent cytotoxicity against IAV-infected cells. The antiviral activity of CYNK was mediated by NKp46 and NKG2D. Together, these data demonstrate that CYNK possesses potent antiviral function against IAV and warrant clinical investigations for adoptive NK cell therapies against viral infections.

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with coagulopathic bleeding. Impaired thrombin generation may be an important cause of coagulopathic bleeding but is poorly measured by existing hemostatic assays. We examined thrombin generation during cardiac surgery, using calibrated automated thrombography, and its association with bleeding outcomes. METHODS: We conducted a prospective observational study in 100 patients undergoing cardiac surgery with CPB. Calibrated automated thrombography parameters were expressed as a ratio of post-CPB values divided by pre-CPB values. The association of thrombin generation parameters for bleeding outcomes was compared with conventional tests of hemostasis, and the outcomes of patients with the most severe post-CPB impairment in thrombin generation (≥ 80% drop from baseline) were compared with the rest of the cohort. RESULTS: All 100 patients were included in the final analysis, with a mean age of 63 (12) yr, 31 (31%) female, and 94 (94%) undergoing bypass and/or valve surgery. Post-CPB, peak thrombin decreased by a median of 73% (interquartile range [IQR], 49-91%) (P < 0.001) and total thrombin generation, expressed as the endogenous thrombin potential (ETP), decreased 56% [IQR, 30-83%] (P < 0.001). In patients with ≥ 80% decrease in ETP, 21% required re-exploration for bleeding compared with 7% in the rest of the cohort (P = 0.04), and 48% required medical or surgical treatment for hemostasis compared with 27% in the rest of the cohort (P = 0.04). CONCLUSIONS: Thrombin generation is significantly impaired by CPB and associated with higher bleeding severity. Clinical studies aimed at the identification and treatment of patients with impaired thrombin generation are warranted.

RéSUMé: CONTEXTE: La chirurgie cardiaque avec circulation extracorporelle (CEC) est associée à des saignements sur coagulopathie. L'altération de la génération de thrombine peut constituer une cause importante de saignement sur coagulopathie, mais elle est mal mesurée par les tests d'hémostase existants. Nous avons examiné la génération de thrombine pendant la chirurgie cardiaque à l'aide d'une thrombographie automatisée calibrée ainsi que son association avec les issues hémorragiques. MéTHODE: Nous avons réalisé une étude observationnelle prospective portant sur 100 patients bénéficiant d'une chirurgie cardiaque sous CEC. Les paramètres de thrombographie automatisée calibrée ont été exprimés sous forme du rapport entre les valeurs post-CEC divisées par les valeurs pré-CEC. L'association des paramètres de génération de thrombine pour les issues hémorragiques a été comparée aux tests conventionnels de l'hémostase, et les issues des patients présentant l'altération post-CEC la plus prononcée dans la génération de thrombine (baisse ≥ 80 % par rapport aux valeurs de base) ont été comparées au reste de la cohorte. RéSULTATS: Les 100 patients ont tous été inclus dans l'analyse finale, avec un âge moyen de 63 (12) ans, 31 (31 %) femmes et 94 (94 %) subissant une chirurgie de pontage et / ou une chirurgie valvulaire. Après la CEC, le pic de thrombine a diminué d'une médiane de 73 % (écart interquartile [ÉIQ], 49 à 91 %) (P < 0,001) et la génération de thrombine totale, exprimée en potentiel de thrombine endogène (PTE), a diminué de 56 % [ÉIQ, 30­83 %] (P < 0,001). Chez les patients présentant une diminution ≥ 80 % du PTE, 21 % ont nécessité une nouvelle exploration pour dépister les saignements, comparativement à 7 % dans le reste de la cohorte (P = 0,04), et 48 % ont nécessité un traitement médical ou chirurgical pour l'hémostase, comparativement à 27 % dans le reste de la cohorte (P = 0,04). CONCLUSION: La génération de thrombine est significativement altérée par la CEC et associée à des saignements plus graves. Des études cliniques visant à identifier et à traiter les patients présentant une altération de la génération de thrombine sont recommandées.

Prolonged post-ictal atrial fibrillation following seizures.

It is well known that several types of cardiac arrhythmias can occur after a seizure, with ictal sinus tachycardia being the most common. However, post-ictal atrial fibrillation (PIAF) is a rare phenomenon with significant clinical implications. We describe the case of an epilepsy patient with prolonged PIAF. Our case is that of a 62-year-old female with seizure onset at 51 years of age. She had a left hemispheric meningioma that was resected with ongoing seizures. She described frequent episodes of chest fluttering lasting for several hours post-ictally. During video-EEG monitoring (VEEG), she had a typical seizure with staring and word finding difficulty. This was associated with the occurrence of atrial fibrillation with rapid ventricular rate that lasted 18 hours. We discuss the relation between seizures and prolonged PIAF as it relates to the need for anticoagulation, use of appropriate antiseizure medications, and the possible association with SUDEP.

Calcified facial and maxillary arteries: Incidental radiographic findings indicative of Mönckeberg arteriosclerosis.

BACKGROUND AND OVERVIEW: Mönckeberg arteriosclerosis is a disease of unknown etiology characterized by dystrophic calcifications within the tunica media of small- and medium-sized arteries, leading to reduced arterial compliance. The authors report a case discovered incidentally on dental radiographs. CASE DESCRIPTION: A 78-year-old man with a complex medical history was seen for routine oral health care. Panoramic and bite-wing radiographs revealed a tortuous, linear calcification in the area of the left mandibular first molar anterior to the angle of the mandible and suggestive of a calcified facial artery. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Medical radiologists have used the presence of arterial calcifications to determine the severity and prognosis of such diseases as primary hyperparathyroidism, secondary hyperparathyroidism, coronary artery disease, and diabetes. The presence of Mönckeberg arteriosclerosis on dental radiographs can help oral health care professionals identify patients with undiagnosed systemic disease.

Rates, Predictors, and Impact of Smoking Cessation after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

BACKGROUND: Smoking cessation after a first cardiovascular event reduces the risk of recurrent vascular events and mortality. This systematic review and meta-analysis aimed to summarize data on the rates, predictors, and the impact of smoking cessation in patients after a stroke or transient ischemic attack (TIA). METHODS: MEDLINE, EMBASE and Web of Science were searched to identify all published studies providing relevant data through May 20, 2021. Random-effects meta-analysis method was used to pool proportions. Some findings were summarized narratively. RESULTS: Twenty-five studies were included. The pooled smoking cessation rates were 51.0% (8 studies, n = 1738) at 3 months, 44.4% (7 studies, n = 1920) at 6 months, 43.7% (12 studies, n = 1604) at 12 months, and 49.8% (8 studies, n = 2549) at 24 months or more of follow-up. Increased disability and intensive smoking cessation support programs were associated with a higher likelihood of smoking cessation, whereas alcohol consumption and depression had an inverse effect. Two studies showed that patients who quit smoking after a stroke or a TIA had substantially lower risk of recurrent stroke, death, and a composite of stroke, myocardial infarction, and death. CONCLUSION: Smoking cessation in stroke survivors is associated with reduced recurrent vascular events and death. About half of smokers who experience a stroke or a TIA stop smoking afterwards. Those with low post-stroke disability, who consume alcohol, or have depression are less likely to quit. Intensive support programs can increase the likelihood of smoking cessation.

Race-insurance disparities in prostate patients' magnetic resonance imaging biopsies and their subsequent cancer care: a New York State cohort study.

For organ-confined prostate cancer, socioeconomic factors influencing Magnetic Resonance Imaging (MRI)-guided biopsy utilization and downstream prostate cancer patients' care are unknown. This retrospective, observational cohort study used the New York Statewide Planning and Research Cooperative System (SPARCS) billing-code driven database to examine the impact of prostate patients' socioeconomic characteristics on prostate cancer care defined as initial biopsy, 2-month post-biopsy cancer diagnoses, and within 1-year cancer-related intervention, controlling for other risk factors. From 2011-2017, the population studied (n = 18,253) included all New York State-based, male, residents aged 18 to 75 without a prior prostatectomy receiving a first-time biopsy; 760 such patient records in 2016 were removed due to data quality concerns. Major exposures included patient age, race, ethnicity and insurance. The major outcome included receipt of MRI biopsy versus standard biopsy and for these sub-populations, subsequent 2-month post-biopsy metastatic versus non-metastatic prostate cancer diagnosis and within 1-year prostate cancer treatment (prostatectomy with or without radiation versus prostatectomy-only) were compared using dichotomous (primary) and time-to-event (secondary) endpoints. Of 17,493 patients with a first-time prostate biopsy, 3.89% had MRI guided biopsies; of the 17,128 patients with no pre-biopsy cancer diagnosis, the subsequent prostate cancer diagnosis rate was 42.59%. For 6,754 non-metastatic prostate cancer patients with 1-year follow-up, 1,674 (24.79%) received surgery (with or without radiation) and 495 (7.33%) received radiation-only. Holding other factors constant, multivariable regression models identified that race-insurance was a primary predictor of MRI-guided biopsy use. Compared to commercially insured White patients, Black patients across all insurance categories received MRI-guided biopsies less frequently; Commercially insured and self-pay Black patients also had increased chance of prostate cancer diagnosis. Across all insurers, Black patients had lower likelihood of prostatectomies. In contrast, Black and White patients with government insurance were more likely to have within 1-year radiation-only treatments versus commercially insured White patients. Thus, across the prostate cancer care continuum, race-insurance affected prostate cancer-related service utilization. Future research should evaluate the generalizability of these New York State findings.

2020 American College of Rheumatology Guideline for the Management of Gout.

OBJECTIVE: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. METHODS: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. RESULTS: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. CONCLUSION: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

Thrombin generation and bleeding in cardiac surgery: a clinical narrative review.

This narrative review discusses the role of thrombin generation in coagulation and bleeding in cardiac surgery, the laboratory methods for clinical detection of impaired thrombin generation, and the available hemostatic interventions that can be used to improve thrombin generation. Coagulopathy after cardiopulmonary bypass (CPB) is associated with excessive blood loss and adverse patient outcomes. Thrombin plays a crucial role in primary hemostasis, and impaired thrombin generation can be an important cause of post-CPB coagulopathy. Existing coagulation assays have significant limitations in assessing thrombin generation, but whole-blood assays designed to measure thrombin generation at the bed-side are under development. Until then, clinicians may need to institute therapy empirically for non-surgical bleeding in the setting of normal coagulation measures. Available therapies for impaired thrombin generation include administration of plasma, prothrombin complex concentrate, and bypassing agents (recombinant activated factor VII and factor eight inhibitor bypassing activity). In vitro experiments have explored the relative potency of these therapies, but clinical studies are lacking. The potential incorporation of thrombin generation assays into clinical practice and treatment algorithms for impaired thrombin generation must await further clinical development.

RéSUMé: Ce compte rendu narratif discute du rôle de la génération de thrombine dans la coagulation et le saignement en chirurgie cardiaque, des méthodes de laboratoire pour le dépistage clinique d'une génération de thrombine altérée et des interventions hémostatiques disponibles qui peuvent être utilisées pour améliorer la génération de thrombine. Une coagulopathie après la circulation extracorporelle (CEC) est associée à des pertes de sang excessives et à des complications pour les patients. La thrombine joue un rôle essentiel d'hémostase primaire, et une génération de thrombine altérée peut constituer une cause importante de coagulopathie post-CEC. Les analyses de coagulation existantes comportent d'importantes limites en ce qui touche à l'évaluation de la génération de thrombine, mais des analyses de sang complet conçues pour mesurer la génération de thrombine au chevet sont en cours d'élaboration. En attendant, les cliniciens pourraient devoir amorcer un traitement de manière empirique pour prendre en charge les saignements non chirurgicaux dans un contexte de valeurs de coagulation mesurées normales. Les traitements disponibles pour une génération de thrombine altérée comprennent l'administration de plasma, de concentrés de complexe prothrombinique, et d'agents de contournement (bypass) (facteur VII recombinant activé et activité de contournement de l'inhibiteur du facteur VIII). Des expériences in vitro ont exploré l'activité thérapeutique relative de ces traitements, mais les études cliniques manquent. L'intégration potentielle d'analyses de génération de thrombine dans la pratique clinique et d'algorithmes de traitement pour une génération de thrombine altérée doit attendre des développements cliniques plus poussés.

Keratin 17 is a sensitive and specific biomarker of urothelial neoplasia.

There is a clinical need to identify novel biomarkers to improve diagnostic accuracy for the detection of urothelial tumors. The current study aimed to evaluate keratin 17 (K17), an oncoprotein that drives cell cycle progression in cancers of multiple anatomic sites, as a diagnostic biomarker of urothelial neoplasia in bladder biopsies and in urine cytology specimens. We evaluated K17 expression by immunohistochemistry in formalin-fixed, paraffin embedded tissue specimens of non-papillary invasive urothelial carcinoma (UC) (classical histological cases), high grade papillary UC (PUC-LG), low grade papillary UC (PUC-HG), papillary urothelial neoplasia of low malignant potential (PUNLMP), and normal bladder mucosa. A threshold was established to dichotomize K17 status in tissue specimens as positive vs. negative, based on the proportion of cells that showed strong staining. In addition, K17 immunocytochemistry was performed on urine cytology slides, scoring positive test results based on the detection of K17 in any urothelial cells. Mann-Whitney and receiver operating characteristic analyses were used to compare K17 expression between histologic diagnostic categories. The median proportion of K17 positive tumor cells was 70% (range 20-90%) in PUNLMP, 30% (range 5-100%) in PUC-LG, 20% (range 1-100%), in PUC-HG, 35% (range 5-100%) in UC but staining was rarely detected (range 0-10%) in normal urothelial mucosa. Defining cases in which K17 was detected in ≥10% of cells were considered positive, the sensitivity of K17 in biopsies was 89% (95% CI: 80-96%) and the specificity was 88% (95% CI: 70-95%) to distinguish malignant lesions (PUC-LG, PUC-HG, and UC) from normal urothelial mucosa. Furthermore, K17 immunocytochemistry had a sensitivity of 100% and a specificity of 96% for urothelial carcinoma in 112 selected urine specimens. Thus, K17 is a sensitive and specific biomarker of urothelial neoplasia in tissue specimens and should be further explored as a novel biomarker for the cytologic diagnosis of urine specimens.

Pulmonary manifestations of large, medium, and variable vessel vasculitis.

The hallmark of vasculitis is autoimmune inflammation of blood vessels and surrounding tissues, resulting in an array of constitutional symptoms and organ damage. The lung is commonly targeted in the more familiar ANCA-associated small vessel vasculitidies, but large and medium vessel vasculitides, including Takayasu arteritis, giant cell arteritis, polyarteritis nodosa, Behcet's disease, and necrotizing sarcoid granulomatosis, may also feature prominent pulmonary involvement. Pulmonary manifestations of these conditions include pulmonary arterial aneurysms, pulmonary hypertension, diffuse alveolar hemorrhage, pulmonary nodules, and parenchymal infiltrates. An understanding of the diverse manifestations of vasculitis and a high index of clinical suspicion are essential to avoid delays in disease recognition that may result in permanent or life threatening morbidity. In this review, we outline the general clinical manifestations, pulmonary manifestations, diagnostic workup, imaging findings, and treatment of medium, large, and variable vessel vasculitides.

Vitamin D status and its relation to exercise performance and iron status in young ice hockey players.

OBJECTIVES: The aim was to examine the association between serum vitamin D concentration and isometric strength of various muscle groups, vertical jump performance, and repeated sprint ability in young ice hockey players. The secondary aim was to determine the association between vitamin D deficiency and indices of iron status. METHODS: Fifty male ice hockey players (17.2±0.9 years) participated in this cross-sectional study. Exercise performance was evaluated using isometric strength measures of upper and lower extremities, vertical jump performance and repeated sprint ability (RSA). Blood samples were collected for the determination of serum 25-hydroxyvitamin D (25(OH)D) and multiple indicies of iron status. RESULTS: The mean serum 25(OH)D concentration was 30.4 ng·ml-1 and ranged from 12.5 to 91.4 ng·ml-1. Eleven participants (22%) had vitamin D deficiency and 20 athletes (40%) had vitamin D insufficiency. Serum 25(OH)D concentration was not positively correlated with isometric muscle strength, vertical jump performance, or RSA after adjusting for age, training experience, fat mass, fat free mass and height. Serum 25(OH)D concentration was not associated with indices of iron status. CONCLUSION: Vitamin D insufficiency is highly prevalent in ice hockey players, but 25(OH)D concentration but it is not associated with exercise performance or indices of iron status.