Inter- and Intra-Operator Variability of Regularized Backscatter Quantitative Ultrasound for the Characterization of Breast Masses.

OBJECTIVES: Here we report on the intra- and inter-operator variability of the backscatter coefficient (BSC) estimated with a new low-variance quantitative ultrasound (QUS) approach applied to breast lesions in vivo. METHODS: Radiofrequency (RF) echo signals were acquired from 29 BIRADS 4 and 5 breast lesions in 2 sequential cohorts following 2 imaging protocols: cohort 1) radial and antiradial views, and cohort 2) short- and long-axis views. Protocol 2 was implemented after retraining and discussion on how to improve reproducibility. Each patient was scanned by at least 2 of 3 radiologists; each performed 3 acquisitions with transducer and patient repositioning in between acquisitions. BSC was estimated using a low-variance QUS approach based on regularization. Intra- and inter-operator variability of the intra-lesion median BSC was evaluated with a multifactorial ANOVA test (P-values) and the intraclass correlation coefficient (ICC). RESULTS: Inter-operator variability was only significant in the first protocol (P < .007); ICCinter = .77 (95% CI .71-.82), indicating good inter-operator agreement. In the second protocol, the inter-operator variability was not significant (P > .05) and agreement was excellent (ICCinter = .92 [.89-.94]). In both protocols, the intra-operator variability was not significant. CONCLUSIONS: Our findings demonstrate the need for standardizing image acquisition protocols for backscatter-based QUS to reduce inter-operator variability and ensure its successful translation to the characterization of suspicious breast masses.

Association of palliative care management and survival after chemotherapy discontinuation in patients with advanced pancreatic adenocarcinoma: A retrospective single-centre observational study.

BACKGROUND: Palliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients. METHODS: This retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death. RESULTS: Among the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19-64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47-0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42-0.99], p = 0.045, Cox). CONCLUSION: The study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway.

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

BACKGROUND: Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick's bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence. PATIENTS AND METHODS: A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates. RESULTS: Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P = 0.016). Sex (P = 0.53), premedication (P = 0.91), primary cancer location (P = 0.46) and chemotherapy regimen type (P = 0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P = 0.0015). CONCLUSION: This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs.

Incidence, characteristics, and mortality of infective endocarditis in France in 2011.

OBJECTIVES: We assessed the determinants of mortality in infective endocarditis (IE), using the national hospital discharge databases (HDD) in 2011. METHODS: IE stays were extracted from the national HDD, with a definition based on IE-related diagnosis codes. This definition has been assessed according to Duke criteria by checking a sample of medical charts of IE giving a predictive positive value of 86.1% (95% confidence interval (CI): 82.7% - 89.5%). The impact of heart valve surgery on survival has been studied if performed during the initial stay, and over the year of follow-up. Risk factors of in-hospital mortality were identified using logistic regression model for the initial stay and Cox Time-dependent model for the 1-year mortality. RESULTS: The analysis included 6,235 patients. The annual incidence of definite IEs was 63 cases/million residents. Staphylococci and Streptococci were the most common bacteria (44% and 45%, respectively). A valvular surgery was performed in 20% of cases, but substantial variations existed between hospitals. The in-hospital mortality was 21% (ranging 12% to 27% according to the region of patients), associated with age>70, chronic liver disease, renal failure, S. aureus, P. aeruginosa or candida infection and strokes whereas valvular surgery, a native valve IE or intraveinous drug use (right heart IE) were significantly protective for an initial death. The same factors were associated with the one-year mortality, except for valvular surgery which was associated with a 1.4-fold higher risk of death during the year post IE. CONCLUSION: We reported a high IE incidence rate. Valvular surgery was considerably less frequent in this study than in the previous published data (near 50%) whereas mortality was similar. Surgery was associated with higher survival if undergone within the initial stay. There were significant regional differences in frequency of surgery but it did not impact mortality.

Illustration of a fatal radiation-induced lung aneurysm: Is central lung stereotactic radiotherapy to be banned?

Stereotactic body radiation therapy is still controversial for inoperable patients with central lung lesion. We report the case of a 59-year-old woman with previous history of head and neck squamous cell carcinoma who was treated by lung stereotactic body irradiation for an inoperable lymph node in station 10R. One year after, a fibroscopy showed a necrosis of the right main bronchus mucosae and the CT showed a radio-induced aneurysm protruding into the right inferior lobular bronchus. The patient eventually died a few hours later with a massive haemoptysis. This case highlights the potential toxicity of central lung stereotactic body radiation therapy and raises the question of its legitimacy.

CT and MRI Aspects of an Abdominal Hemophilic Pseudotumor.

We report the computed tomography (CT) and magnetic resonance imaging (MRI) aspects of a rare case of a patient with a large abdominal hemophilic pseudotumor, a chronic, encapsulated, slowly expanding hematoma occurring in severe hemophilia, without involvement of iliopsoas muscles and iliac bones.

The rationale for performing MR imaging before surgery for primary hyperparathyroidism.

OBJECTIVE: The purpose of this study was to evaluate prospectively Magnetic Resonance Imaging (MRI) for the preoperative localization of hyperfunctioning parathyroid glands. DESIGN: Prospective study of 58 consecutive patients with biochemically confirmed primary hyperparathyroidism who underwent preoperative MRI. SETTING: The setting is a referral centre. PATIENTS: Fifty-six of the 58 consecutive patients (41 women, 17 men) were studied by both preoperative MRI and 99mTC MIBI scintigraphy, and two by MRI alone. The same surgeon, using the information from both MRI and 99mTC MIBI, performed surgery in 58 patients, including 19 with a history of neck surgery. Initial interpretation of each MR study was done independently by one radiologist and the surgeon and then results were compared. At surgery, the operative duration, the precise anatomical location, weight, and dimensions as well as complete histopathological evaluations of all excised glands were recorded. MAIN OUTCOME MEASURE: In addition to the prospective assessment of MRI, this study compared performance of MRI with double-phase 99mTC MIBI scintigraphy for preoperative localization of hyperfunctioning parathyroid glands. RESULTS: All patients became normocalcaemic after surgery. MRI and 99mTC MIBI imaging revealed 53 of 58 (91%) and 47 of 56 (84%) of abnormal glands, respectively. Sensitivities of MRI and 99mTC MIBI were respectively 94.3 and 88.0. Positive predictive values were 96.15 and 93.60. When MRI and 99mTC MIBI were interpreted together, the sensitivity and positive predictive values both raised to 98.10. Median operative duration was 30 minutes (ranges 20-300 minutes, mean 65). CONCLUSION: MRI has better sensitivity and positive predictive value than 99mTC MIBI scintigraphy for the detection of hyperfunctioning parathyroid glands. The combination of the two studies provides an additional increase in sensitivity and positive predictive value leading to a more precise anatomical localization of the abnormal parathyroid glands reducing both the extent of the surgical dissection and the operative duration.

[Diplopia complicating peribulbar anesthesia for cataract surgery and early use of MRI]. / Diplopie après anesthésie péribulbaire pour chirurgie de la cataracte: évaluation d'une nouvelle stratégie diagnostique incluant l'IRM précoce.

OBJECTIVE: To evaluate the early use of magnetic resonance imaging (MRI) for the diagnosis of diplopia following cataract surgery under peribulbar anaesthesia. STUDY DESIGN: Single centre prospective study. PATIENTS AND METHOD: From January 2003 to January 2005 every patient undergoing cataract surgery under peribulbar anaesthesia was included. Any patient spontaneously complaining of double vision on day 1 received a full ophthalmologic examination. When binocular diplopia was confirmed by a positive Hess-Lancaster test, the patient immediately underwent an MRI. RESULTS: During the two year period, 4805 patients underwent cataract surgery under peribulbar anaesthesia. Eight patients reported double vision on day 1 (0.16% prevalence). Clinical examination confirmed binocular diplopia and a positive Hess-Lancaster test identified the paralysed muscle. In 7 out of 8 patients, the MRI performed on the same day showed a T2 hyper intensity signal within the paralysed muscle, it was interpreted as inflammatory oedema following an accidental intra muscular injection of a myotoxic local anaesthetic. In one patient the MRI was normal, suggesting a preoperative undiagnosed diplopia having no relation to the peribulbar anaesthesia. CONCLUSION: A slit-lamp exam and a Hess-Lancaster test are necessary to confirm postoperative strabismic diplopia after cataract surgery. An early MRI can accurately distinguish postanaesthetic myotoxic diplopia from a preoperative diplopia revealed by the corrective cataract surgery.

[Revelation of an acute lymphoblastic leukemia in the delivery room]. / Leucémie aiguë lymphoblastique néonatale: une affection rare à révélation immédiate en salle de naissance.

Acute leukemia is uncommon in neonates and has a much poorer prognosis than in older children. We report on a case of acute lymphoblastic leukemia observed in a neonate who had bleeding and hepatosplenomegaly at birth, which justified intensive care during the first postnatal week. Despite early appropriate treatment, the patient died at 7 months of age. We present here physical and laboratory findings, which indicate a grim prognosis. These criteria should be considered carefully in order to ensure a realistic information for the parents and appropriate decisions.

[CSF levels and diagnostic utility of cerebrospinal fluid beta2-microglobulin]. / Valeurs usuelles et utilité diagnostique de la beta2-microglobuline dans le liquide céphalorachidien.

CSF levels of beta2-microglobulin reflect immune activation and lymphoid cell turnover in CNS. There were proposed as a reliable marker of lymphoproliferative disorders in central nervous system in viral infections, inflammatory diseases, autoimmune diseases and malignancies. The aims of this study were to measure beta2-microglobulin on the automate Vidas of bioMérieux in 122 paired CSF and serum from control patients. We evaluated whether or not the elevated levels beta2-microglobulin in CSF can be a useful marker for diagnosis of lymphoproliferative disorders in 108 patients with neurological diseases. The concentrations of beta2-microglobulin in the CSF and sera from control patients were respectively 1.3 +/- 0.5 mg/L and 2 +/- 0.6 mg/L. The normal CSF to serum beta2-microglobulin ratio was 0.6 +/- 0.19. A CSF to serum beta2-microglobulin ratio greater than 1 was closely associated with intrathecal synthesis beta2-microglobulin in CNS lymphoproliferative disorders. Elevation of CSF beta2-microglobulin ratio is a sensitive marker of central nervous system disease activity by infiltrating lymphocytes in intracranial lymphomas (10/10) and paraneoplastic neurological syndromes (2/3).

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia.

Reciprocal rearrangements of the MLL gene are among the most common chromosomal abnormalities in both Acute Lymphoblastic and Myeloid Leukemia. The MLL gene, located on the 11q23 chromosomal band, is involved in more than 40 recurrent translocations. In the present study, we describe the development and validation of a biochip-based assay designed to provide a comprehensive molecular analysis of MLL rearrangements when used in a standard clinical pathology laboratory. A retrospective blind study was run with cell lines (n=5), and MLL positive and negative patient samples (n=31), to evaluate assay performance. The limits of detection determined on cell line data were 10(-1), and the precision studies yielded 100% repeatability and 98% reproducibility. The study shows that the device can detect frequent (AF4, AF6, AF10, ELL or ENL) as well as rare partner genes (AF17, MSF). The identified fusion transcripts can then be used as molecular phenotypic markers of disease for the precise evaluation of minimal residual disease by RQ-PCR. This biochip-based molecular diagnostic tool allows, in a single experiment, rapid and accurate identification of MLL gene rearrangements among 32 different fusion gene (FG) partners, precise breakpoint positioning and comprehensive screening of all currently characterized MLL FGs.

Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement.

BACKGROUND: Postoperative bladder distension and urinary retention are commonly underestimated. Ultrasound enables accurate measurement of bladder volume and thus makes it possible to determine the prevalence of postoperative bladder distension. METHODS: Using ultrasound, we measured the volume of the bladder contents at the time of discharge from the recovery room in 177 adult patients who had undergone thoracic, vascular, abdominal, orthopaedic or ENT surgery. RESULTS: Forty-four per cent of the patients had a bladder volume >500 ml and 54% of the 44%, who had no symptoms of bladder distension, were unable to void spontaneously within 30 min. The risk factors for urinary retention were age >60 yr (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.01-4.38), spinal anaesthesia (OR 3.97, 95% CI 1.32-11.89) and duration of surgery >120 min (OR 3.03, 95% CI 1.39-6.61). CONCLUSION: Before discharge from the recovery room it seems worthwhile to systematically check the bladder volume with a portable ultrasound device in patients with risk factors.

Multiplex fluorescent RT-PCR to quantify leukemic fusion transcripts.

The detection of chimeric transcripts derived from aberrant chromosomal fusion events provides an exceptionally valuable toolfor the diagnosis of leukemia. We have developed a simple, inexpensive, reproducible, and automated method to quantify RT-PCR products. Our approach utilizesfluorescent PCRfor the co-ampification of the specific fusion transcript with an internal control (HPRT). We have also combined the advantages of real-time quantitative PCR, namely continuous fluorescent detection of PCR products with the low cost of an endpoint assay by examining in a novel manner the amount offluorescent PCR product generated during the exponential phase of amplification. This has been achieved by using the automated loading and quantification capacity of a laser-induced fluorescence capillary electrophoresis system, the ABI PRIsMS 310A, so that we can effectively monitor amplification during the exponential phase cheaply, reproducibly, and in a sensitive manner. We have carefully verified our new technique using five leukemia cell lines, each expressing a differentfusion transcript. Specificity and reproducibility (cy within 10%) have been examined and demonstrate the excellent precision of our technology. The high sensitivity levels of at least 10(-4) to 10(-6) obtainedfor the serial dilutions of the five cell lines validate the choice of our fluorescent PCR as a comparable method to other more complicated and expensive methods. Our results have allowed us to quantify PCR products and the amount of chimeric mRNA originating from the translocation breakpoint. We demonstrate that our novelfluorescent method is useful to detect and quantify residual leukemic cells in patients undergoing therapy.

Polyphenols from alcoholic apple cider are absorbed, metabolized and excreted by humans.

We determined the uptake and excretion of low doses of polyphenols in six subjects who each consumed 1.1 L of an alcoholic cider beverage. Over a 24-h period, no phloretin was detected in plasma (detection limit = 0.036 micromol/L), but 21 +/- 5% of the dose (4.8 mg) was excreted in the urine. In contrast, from a low dose of 1.6-mg quercetin equivalents, no quercetin was found in urine or plasma, but 3'-methyl quercetin was detected in plasma [C(max) (maximum concentration) = 0.14 +/- 0.19 micromol/L; range: 0 to 0.44 micromol/L]. No flavanol monomers (dose of free (+)-catechin and (-)-epicatechin = 3.5 mg) were detected in urine or plasma (detection limit: 0.01 micromol/L). Caffeic acid (total dose including esters = 11 mg) was detected only in plasma within 2 h, with C(max) = 0.43 +/- 0.3 micromol/L (range: 0.18 to 0.84 micromol/L). An almost 3-fold increase in hippuric acid was detected in 24-h urine (74 +/- 29 micromol/L; range: 38-116 micromol/L), compared with a prestudy value of 19 +/- 9 micromol/L. These data show that polyphenols are taken up from cider, that phloretin is excreted in the urine and suggest that low doses of quercetin are extensively methylated in humans.

Histological and neurotrophic changes triggered by varying models of bladder inflammation.

PURPOSE: We determined whether bladder inflammation causes elevated expression of nerve growth factor by bladder parenchymal cells, leading to alterations in neurons innervating the bladder. To answer this question biochemical, histological and neuronal size data were obtained in rats following various experimental models of bladder inflammation. MATERIALS AND METHODS: Chemical (2.5% formalin), immune (lipopolysaccharide 2 x 104 cfu/ml.) and mechanical (chromic catgut) inflammation was evaluated at various times and compared to control bladders. Hematoxylin and eosin, and Giemsa staining was done to characterize inflammation and quantify mast cells in the bladder. Nerve growth factor protein and messenger RNA were assayed in the bladder and major pelvic ganglion using 2-site enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. Retrograde axonal tracing was done to size bladder neurons in the major pelvic and dorsal root ganglia. RESULTS: All forms of inflammation increased bladder weight and produced diffuse hyperplasia, intramural edema, acute and chronic inflammatory cells, infiltration and mastocytosis. Generally bladder inflammation resulted in a 50% increase in nerve growth factor and 52% to 58% enlargement of peripheral neurons. CONCLUSIONS: Inflammation results in altered nerve growth factor content of the bladder, and morphological changes in sensory and motor neurons innervating the bladder. Such neuroplasticity may be a possible explanation for the association of bladder inflammation with long-term symptoms and pain after inflammation subsides.