Revision surgery after failed ACL reconstruction with artificial ligaments: clinical, histologic and radiographic evaluation

Synthetic ligament for anterior cruciate ligament (ACL) reconstruction has been widely used in the past. Long-term follow-up has demonstrated the unreliability of many of these devices in ACL surgery, and problems may arise for the surgeon approaching a patient with failed artificial ligament reconstruction. The aim of this study is to investigate whether revision surgery may improve clinical and radiographic outcomes in patients with failed synthetic ACL reconstruction. Fourteen patients who were treated in the past with ACL reconstruction with synthetic grafts underwent two-stage revision surgery. Follow-up averaged 4.2 years (range 2–6 years). Mean KOOS score was 75.8 (SD 10.2); IKDC score was B in two patients, C in nine and D in three. The improvement compared to preoperative status was not statistically significant (p > 0.05). Four patients were positive to Lachman and anterior drawer tests. Mean side-to-side anterior laxity averaged 4.3 mm (SD 1.2). Biopsy specimens documented the presence of foreign body granulomatous reaction, giant foreign body cells and polyethylene wear particles. The level of osteoarthritis worsened at follow-up compared to preoperative status (p < 0.05). ACL revision surgery with autografts in patients who underwent previous failed primary synthetic ligament reconstruction does not improve clinical outcomes and does not influence the natural history of knee osteoarthritis started from artificial ligament debris.     

Carvedilol induces greater control of β2- than β1-adrenoceptor-mediated inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human failing myocardium

The β-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 μM) or PDE4-selective inhibitor rolipram (1 μM) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β₁-adrenoceptors (β₂-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β₂-adrenoceptors (β₁-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from –logEC₅₀s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-β-blocker-treated patients, consistent with the previously reported β₂-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular β₂-adrenoceptors compared to β₁-adrenoceptors. The β₂-adrenoceptor-selectivity of carvedilol may provide protection against β₂-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control β₁- and β₂-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients.     

Effect of Beetroot Juice Supplementation on Aerobic Response during Swimming

The beneficial effects of beetroot juice supplementation (BJS) have been tested during cycling, walking, and running. The purpose of the present study was to investigate whether BJS can also improve performance in swimmers. Fourteen moderately trained male master swimmers were recruited and underwent two incremental swimming tests randomly assigned in a pool during which workload, oxygen uptake (VO₂), carbon dioxide production (VCO₂), pulmonary ventilation (VE), and aerobic energy cost (AEC) of swimming were measured. One was a control swimming test (CSW) and the other a swimming test after six days of BJS (0.5l/day organic beetroot juice containing about 5.5 mmol of NO₃⁻). Results show that workload at anaerobic threshold was significantly increased by BJS as compared to the CSW test (6.3 ± 1 and 6.7 ± 1.1 kg during the CSW and the BJS test respectively). Moreover, AEC was significantly reduced during the BJS test (1.9 ± 0.5 during the SW test vs. 1.7 ± 0.3 kcal·kg⁻¹·h⁻¹ during the BJS test). The other variables lacked a statistically significant effect with BJS. The present investigation provides evidence that BJS positively affects performance of swimmers as it reduces the AEC and increases the workload at anaerobic threshold.     

Buckling Sensitivity of Tow-Steered Plates Subjected to Multiscale Defects by High-Order Finite Elements and Polynomial Chaos Expansion

It is well known that fabrication processes inevitably lead to defects in the manufactured components. However, thanks to the new capabilities of the manufacturing procedures that have emerged during the last decades, the number of imperfections has diminished while numerical models can describe the ground truth designs. Even so, a variety of defects has not been studied yet, let alone the coupling among them. This paper aims to characterise the buckling response of Variable Stiffness Composite (VSC) plates subjected to spatially varying fibre volume content as well as fibre misalignments, yielding a multiscale sensitivity analysis. On the one hand, VSCs have been modelled by means of the Carrera Unified Formulation (CUF) and a layer-wise (LW) approach, with which independent stochastic fields can be assigned to each composite layer. On the other hand, microscale analysis has been performed by employing CUF-based Mechanics of Structure Genome (MSG), which was used to build surrogate models that relate the fibre volume fraction and the material elastic properties. Then, stochastic buckling analyses were carried out following a multiscale Monte Carlo analysis to characterise the buckling load distributions statistically. Eventually, it was demonstrated that this multiscale sensitivity approach can be accelerated by an adequate usage of sampling techniques and surrogate models such as Polynomial Chaos Expansion (PCE). Finally, it has been shown that sensitivity is greatly affected by nominal fibre orientation and the multiscale uncertainty features.     

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.     

Integration of municipal state,society and university efforts for sanitary risk prevention associated with Aedes aegypti mosquito in the metropolitan area of Buenos Aires,Argentina

The sanitary problem of Aedes aegypti mosquito acquires relevance around the world because it is the vector of dengue, zika, chikungunya and yellow fever. The vector is adapting to southern regions faster, and the propagation of these diseases in urban areas is a complex problem for society. We aimed to contribute to the risk prevention of disease transmission in the Metropolitan Area of Buenos Aires, through monitoring Aedes aegypti population levels and developing education campaigns with government agencies and society participation. Monitoring activities aimed to diagnose the presence of the vector and its ecology behaviour, and to generate education and prevention politics to avoid its propagation. The results show that (1) the mosquito is in the territory and it is spreading, (2) prevention activities of the municipalities are insufficient to generate an effective sanitary response and (3) it is necessary to improve the education programmes to the population about the life cycle of the vector. The integration of university, government and society improved the work of the team because it combined knowledge about vector ecology, diseases and territory characteristics.     

Managing pasireotide-associated hyperglycemia: a randomized,open-label,Phase IV study

Purpose

Pasireotide is an effective treatment for acromegaly and Cushing’s disease, although treatment-emergent hyperglycemia can occur. The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin/other permitted oral antidiabetic drugs.

Methods

Multicenter, randomized, open-label, Phase IV study comprising a core phase (≤?16-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n?=?190) or Cushing’s disease (n?=?59) received long-acting (starting 40 mg IM/28 days) or subcutaneous pasireotide (starting 600 µg bid), respectively. Patients with increased fasting plasma glucose (≥?126 mg/dL on three consecutive days) during the 16-week pre-randomization period despite metformin/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followed by liraglutide) or insulin for another 16 weeks. The primary objective was to evaluate the difference in mean change in HbA_1c from randomization to end of core phase between incretin-based therapy and insulin treatment arms.

Results

Eighty-one (32.5%) patients were randomized to incretin-based therapy (n?=?38 received sitagliptin, n?=?28 subsequently switched to liraglutide; n?=?12 received insulin as rescue therapy) or insulin (n?=?43). Adjusted mean change in HbA_1c between treatment arms was – 0.28% (95% CI – 0.63, 0.08) in favor of incretin-based therapy. The most common AE other than hyperglycemia was diarrhea (incretin-based therapy, 28.9%; insulin, 30.2%). Forty-six (18.5%) patients were managed on metformin (n?=?43)/other OAD (n?=?3), 103 (41.4%) patients did not require any oral antidiabetic drugs and 19 patients (7.6%) were receiving insulin at baseline and were not randomized.

Conclusion

Many patients receiving pasireotide do not develop hyperglycemia requiring oral antidiabetic drugs. Metformin is an effective initial treatment, followed by incretin-based therapy if needed.

ClinicalTrials.gov ID: NCT02060383.