Real-time qualitative ultrasound elastography of cervical lymph nodes in routine clinical practice: interobserver agreement and correlation with malignancy

To evaluate real-time qualitative ultrasound (US) elastography for cervical lymphadenopathy in routine clinical practice, 74 nodes (37 malignant, 37 benign) in 74 patients undergoing sonography underwent US elastography prior to fine needle aspiration for cytology. Dynamic cine loops of elasticity imaging displayed using a chromatic-scale were qualitatively scored by three independent observers for the proportion of stiff areas from ES1-4 (soft to stiff). There was fair to good interobserver agreement as indicated by weighted kappa (κ) statistic from 0.374 to 0.738. Median ES for benign and malignant nodes were 2 and 3 respectively. ES was higher in malignant nodes (p = 0.0003-0.0049, Mann Whitney U tests) although areas under receiver operating characteristic curves (0.68-0.74) indicated suboptimal discrimination. The optimal discriminatory cut-off, ES > 2, achieved only 62.2% sensitivity, 83.8% specificity and 73% accuracy for malignancy. Improvements in reliability and accuracy of real-time qualitative ultrasound elastography are required for it to be adopted into routine clinical practice.     

Diabetic neuropathy. An experimental study in alloxanised rats,with special reference to insulin therapy

Summary Sciatic nerves from 21 alloxan diabetic male albino rats and 6 control animals have been studied histopathologically after 4–6 months' hyperglycemia. Nine of the diabetic animals were uncontrolled, while the remaining 12 rats received 2.5 U insulin daily. Both groups showed a mild degree of myelin degeneration at 4 months, but at 5 and 6 months the uncontrolled diabetic group developed a significantly more severe degree of myelin and axis-cylinder degeneration than the insulin-treated group. The intraneural blood vessels were essentially normal in all animals. The role of duration and severity of hyperglycemia, with particular reference to the protective effect of early insulin therapy on nerve lesions, is discussed.

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Zusammenfassung Bei 21 alloxan-diabetischen männlichen Albinoratten und 6 Kontrolltieren wurde der Nervus ischiadicus nach 4–6 Monaten Hyperglykämie histopathologisch untersucht. Bei 9 diabetischen Ratten bestand Stoffwechselentgleisung, während die restlichen 12 täglich 2,5 E Insulin erhielten. Nach 4 Monaten zeigten beide Gruppen eine leichte Myelindegeneration, aber nach 5 und 6 Monaten hatten die unbehandelten Tiere eine signifikant schwerere Myelin- und Achsenzylinder-degeneration entwickelt als die insulinisierte Gruppe. Die intraneuralen Blutgefässe waren bei allen Tieren praktisch normal. Es wird die Rolle der Dauer und des Schweregrades der Blutzucker-erhöhung besprochen, besonders im Hinblick auf die Schutzwirkung einer frühzeitigen Insulintherapie gegenüber der Nervenläsion.

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Resumen Se han estudiado desde el punto de vista histopatológico, tras un periodo de hiperglucemia de la duración de 4 a 6 meses, los nervios ciáticos aislados de 21 ratas blancas macho, afectas de diabetes de aloxina y de 6 animales de control. De los animales diabéticos 9 fueron tratados con insulina, mientras que los remanentes 12 recibiían una dosis de 2,5 unidades diarias del hormón. En ambos grupos, al 4° mes, se podía observar una leve degeneración mielínica; al 5°–6° mes, en el grupo de ratas diabéticass no tratadas con insulina, la degeneración mielínica y del cilindroeje era significativamente más grave que en los animales no tratados. Los vasos sanguíneos intraneurales esencialmente eran normales en todos los animales.

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Résumé Des nerfs sciatiques isolés de 21 rats albinois mâles atteints de diabète alloxane et de 6 animaux d'essai ont fait l'objet d'une étude au point de vue histopathologique après une période d'hyperglycémie durant 4 à 6 mois. Des animaux atteints du diabète, 9 n'avaient pas été traités avec insuline, tandis que les douze autres reçevaient une dose de 2,5 U/die de l'hormone. Dans les deux groupes, une légère dégénération myélenique se manifestait après le 4ème mois; au 5^e–6^e mois, le groupe des rats atteints de diabète n'ayant pas été traité avec insuline présentait une dégénération myélenique et du cylindraxe bien plus graves que dans le groupe des animaux traités. Les vaisseaux du sang intraneuraux étaient essentiellement normaux chez tous les animaux.

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Riassunto Nervi sciatici isolati da 21 ratti albini maschi con diabete da allossana e da 6 animali di controllo sono stati studiati dal punto di vista istopatologico dopo un periodo di iperglicemia della durata di 4–6 mesi. Degli animali diabetici, 9 non erano trattati con insulina, mentre i rimanenti 12 ricevevano una dose di 2,5 U/die dell'ormone. In entrambi i gruppi era presente, al 4° mese, lieve degenerazione mielinica; al 5°–6° mese, nel gruppo dei ratti diabetici non trattati con insulina la degenerazione mielinica e del cilindrasse era significativamente più grave che in quello degli animali trattati. I vasi sanguigni intraneurali erano essenzialmente normali in tutti gli animali.

     

Unveiling the complex electronic structure of amorphous metal oxides

Amorphous materials represent a large and important emerging area of material’s science. Amorphous oxides are key technological oxides in applications such as a gate dielectric in Complementary metal-oxide semiconductor devices and in Silicon-Oxide-Nitride-Oxide-Silicon and TANOS (TaN-Al₂O₃-Si₃N₄-SiO₂-Silicon) flash memories. These technologies are required for the high packing density of today’s integrated circuits. Therefore the investigation of defect states in these structures is crucial. In this work we present X-ray synchrotron measurements, with an energy resolution which is about 5–10 times higher than is attainable with standard spectrometers, of amorphous alumina. We demonstrate that our experimental results are in agreement with calculated spectra of amorphous alumina which we have generated by stochastic quenching. This first principles method, which we have recently developed, is found to be superior to molecular dynamics in simulating the rapid gas to solid transition that takes place as this material is deposited for thin film applications. We detect and analyze in detail states in the band gap that originate from oxygen pairs. Similar states were previously found in amorphous alumina by other spectroscopic methods and were assigned to oxygen vacancies claimed to act mutually as electron and hole traps. The oxygen pairs which we probe in this work act as hole traps only and will influence the information retention in electronic devices. In amorphous silica oxygen pairs have already been found, thus they may be a feature which is characteristic also of other amorphous metal oxides.     

Influence of variations in CCL3L1 and CCR5 on tuberculosis in a northwestern Colombian population

We investigated the association of polymorphisms in CCR5, the major human immunodeficiency virus (HIV)-1 coreceptor, and copy number of its potent ligand CCL3L1 with tuberculosis in 298 individuals from Colombia. The CCR5-HHD haplotype, a known genetic determinant of increased susceptibility to HIV-AIDS, and a high copy number of CCL3L1, a known genetic determinant of enhanced CCL3/CCL3L1 chemokine expression, each associated with presence of tuberculosis. Furthermore, CCR5-HHD was associated with higher CCR5 gene and surface expression. These results substantiate the strong link between the pro-inflammatory effects of CCR5 and its ligands with active tuberculosis and suggest that chemokine-chemokine receptor genetic determinants may influence tuberculosis in addition to HIV/AIDS.     

Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors—A retrospective analysis

Introduction

Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources.

Aim

Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high‐titre inhibitors.

Methods

Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI.

Results

Of 19 patients, 7 were first‐time ITI and 12 were rescue ITI. Of 7 first‐time patients, 6 had at least 1 high‐risk feature for ITI failure. Four of 7 first‐time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow‐up is needed to determine final outcomes. No adverse events reported.

Conclusions

Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high‐risk first‐time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI.     

Oral Calcium Supplements Associate With Serial Coronary Calcification: Insights From Intravascular Ultrasound

ObjectivesThis study sought to evaluate and assess the extent of serial coronary artery calcification in response to oral calcium supplementation.BackgroundOral calcium supplements are frequently used despite their cardiovascular safety remaining controversial. Their effects on serial coronary calcification are not well established.MethodsIn a post hoc patient-level analysis of 9 prospective randomized trials using serial coronary intravascular ultrasound, changes in serial percentage of atheroma volume (PAV) and calcium indices (CaI) were compared in matched segments of patients coronary artery disease who were receiving concomitant calcium supplements (n = 447) and in those who did not receive supplements (n = 4,700) during an 18- to 24-month trial period.ResultsPatients (mean age 58 ± 9 years; 73% were men; 43% received concomitant high-intensity statins) demonstrated overall annualized changes in PAV and CaI with a mean of ?0.02 ± 1.9% (p = 0.44) and a median of 0.02 (interquartile range: 0.00 to 0.06) (p < 0.001) from baseline, respectively. Following propensity-weighted mixed modeling adjusting for treatment and a range of demographic, clinical, ultrasonic, and laboratory parameters (including but not limited to sex, race, baseline, and annualized change in PAV, baseline CaI, concomitant high-intensity statins, diabetes mellitus, renal function), there were no significant between-group differences in annualized changes in PAV (least-squares mean: 0.09; 95% confidence interval [CI]: ?0.20 to 0.37 vs. 0.01; 95% CI: ?0.27 to 0.29; p = 0.092) according to calcium supplement intake. Per a multivariable logistic regression model accounting for the range of covariates described, calcium supplementation independently associated with an increase in annualized CaI (odds ratio: 1.15; 95% CI: 1.05 to 1.26; p = 0.004).ConclusionsOral calcium supplementation may increase calcium deposition in the coronary vasculature independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.     

A retrospective analysis of the periprocedural management of oral anticoagulants in patients undergoing interventional radiology procedures

Limited evidence is available to guide periprocedural management of oral anticoagulants in the setting of interventional radiology (IR) procedures. For direct oral anticoagulants, therapy interruption (TI) is based on medication half-life and procedural bleeding risk. Periprocedural management of warfarin includes INR monitoring, and possible bridging with parenteral anticoagulants. It is unknown if these recommendations apply to IR procedures. To evaluate bleeding complications and thromboembolic events following periprocedural management of the factor Xa (FXa) inhibitors or warfarin in patients undergoing IR procedures. We performed a retrospective, observational study at NYU Langone Health (NYULH) of all adult patients who underwent an IR procedure from January 2015 to July 2017 and were receiving apixaban, rivaroxaban, or warfarin. Patients who were pregnant or who had a mechanical heart valve were excluded. At NYULH, TI is not required for FXa inhibitors, and an INR?<?3 is recommended for patients on warfarin undergoing low risk procedures. For moderate/high risk procedures, TI for 48 h or 72 h with reduced renal function, is recommended for FXa inhibitors, and an INR?<?1.5 is recommended for patients on warfarin. We evaluated 350 IR procedures, with a total of 174 low bleeding risk and 176 moderate/high bleeding risk. The 30-day major bleeding rate was 0.9%, clinically relevant non-major bleeding rate was 3%, minor bleeding rate was 1% and thromboembolic event rate was 1%. The periprocedural oral anticoagulation management strategy at NYULH appears safe given the low 30-day incidence of bleeding and thromboembolic events.     

The Relevance of Spastic Esophageal Disorders as a Diagnostic Category

Purpose of Review

This review addresses the similarities and differences between the spastic esophageal disorders, including jackhammer esophagus, distal esophageal spasm (DES), and type III (spastic) achalasia. The pathophysiology, diagnosis, and treatment of each separate disorder are discussed herein, with an emphasis on overlapping and discordant features.

Recent Findings

The Chicago Classification is a hierarchical organizational scheme for esophageal motility disorders, currently in its third iteration, with direct impact on the definitions of these three disorders. Complementary diagnostic tools such as impedance planimetry and novel manometric parameters continue to evolve. The suite of potential treatments for these disorders is also expanding, with progressive interest in the role of peroral endoscopic myotomy alongside established pharmacologic and mechanical interventions.

Summary

Although jackhammer esophagus, distal esophageal spasm, and type III achalasia frequently overlap in terms of their clinical presentation and available management approaches, the divergences in their respective diagnostic criteria suggest that additional study may reveal additional mechanistic distinctions that lead in turn to further refinements in therapeutic decision-making.

     

Nodal shape (S/L) and its combination with size for assessment of cervical lymphadenopathy: which cut-off should be used?

The short axis to long axis (S/L) ratio is commonly used to assess cervical lymphadenopathy; however, the cut-off value used has been limited to 0.5. The accuracy of the combination of S/L ratio and nodal size has not been documented previously. We evaluated 1143 normal cervical nodes from 95 healthy subjects, and 1441 nodes from 290 patients with proven cervical lymphadenopathy. The optimum cut-off value of the S/L ratio was determined in different regions of the neck: submental (0.5), submandibular (0.7), parotid (0.5), upper cervical (0.4), middle cervical (0.3) and posterior triangle (0.4). In the submandibular and parotid regions, the combination of the S/L ratio and short axis shows substantial improvement in diagnostic accuracy when compared to the S/L ratio alone.     

Public-private collaboration for multidrug-resistant tuberculosis control in New York City.

SETTING: An urban tuberculosis control program where an enhanced multidrug-resistant tuberculosis (MDR-TB) management plan coordinated care with multiple providers. OBJECTIVE: To evaluate treatment outcomes of primary MDR-TB patients treated by multiple providers. DESIGN: Retrospective cohort study of tuberculosis patients from 1992-1997 provided that 1) their Mycobacterium tuberculosis isolates were resistant to at least isoniazid and rifampin, and 2) they had had < or = 30 days of anti-tuberculosis treatment prior to the collection of the first MDR-TB specimen. RESULTS: More than 100 facilities and providers reported 856 MDR-TB patients. Treatment completion reached 70% among non-HIV-infected and 30% among HIV-infected persons; 57.2% of the cohort died prior to treatment completion, 26.5% completed treatment, 16.0% transferred out, refused treatment or were lost to follow-up and 0.2% are still in care. Diagnosis in the later years of the study or cavitation on chest radiograph was independently associated with increased completion among HIV-infected patients. Eight of the 227 (3.5%) patients who completed treatment relapsed (relapse rate 1.01/100 person-years), two with drug-susceptible strains. CONCLUSION: A comprehensive MDR-TB control program improved the outcomes of both HIV-infected and non-infected individuals, despite management by multiple providers. Relapse was infrequent among patients who completed the recommended regimens.