Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Wednesday, March 16, 2022

An enhanced recovery after surgery pathway: LOS reduction, rapid discharge and minimal complications after anterior cervical spine surgery

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Abstract

Background

Enhance recovery after surgery (ERAS) is a new and promising paradigm for spine surgery. The purpose of this study is to investigate the effectiveness and safety of a multimodal and evidence-based ERAS pathway to the patients undergoing anterior cervical discectomy and fusion (ACDF).

Methods

The patients treated with the ACDF-ERAS pathway were compared with a historical cohort of patients who underwent ACDF before ERAS pathway implementation. Primary outcome was length of stay (LOS). Secondary outcomes included cost, MacNab grading, complication rates and 90-day readmission and reoperation. And perioperative factors and postoperative complications were reviewed.

Results

The ERAS protocol was composed of 21 components. More patients undergoing multi-level surgery (n ≥ 3) were included in the ERAS group. The ERAS group showed a shorter LOS and a lower cost than the conventional group. The postoperative satisfaction of patients in ERAS group was better than that in conventional group. In addition, the rate of overall complications was significantly higher in the conventional group than that in the ERAS group. There were no significant differences in operative time, postoperative drainage, or 90-day readmission and reoperation.

Conclusions

The ACDF-tailored ERAS pathway can reduce LOS, cost and postoperative complications, and improve patient satisfaction without increasing 90-day readmission and reoperation.

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Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective

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Abstract

The triumphant success of mRNA vaccines is a testimony to the important role drug delivery technologies have played in protecting billions of people against SARS-CoV-2 (or the Corona Virus Disease 2019; COVID-19). Several lipid nanoparticle (LNP) mRNA vaccines were developed and have been instrumental in preventing the disease by boosting the immune system against the pathogen, SARS-CoV-2. These vaccines have been built on decades of scientific research in drug delivery of mRNA, vaccines, and other biologicals. In this manuscript, several leading and emerging scientists in the field of drug delivery share their perspective on the role of drug delivery technologies in developing safe and efficacious vaccines, in a roundtable discussion. The authors also discussed their viewpoint on the current challenges, and the key research questions that should drive this important area of research.

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The impact of low serum cholinesterase levels on survival in patients with colorectal cancer

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Abstract

Purpose

Nutritional and inflammatory status have been associated with postoperative recurrence and poor survival in patients with colorectal cancer. The aim of the present study is to investigate the relationship between serum cholinesterase levels and postoperative outcomes among patients who underwent curative resection for colorectal cancer.

Methods

The study comprised 174 patients who had undergone curative resection for colorectal cancer. We explored the relationship between preoperative serum cholinesterase levels and disease-free survival and overall survival after curative resection. Then patients were divided into the high-cholinesterase group (n = 102) and the low-cholinesterase group (n = 72) to analyze their clinicopathological variables including other nutritional markers and systemic inflammatory responses.

Results

In multivariate analysis, lymph node metastasis (P = 0.011) and serum cholinesterase levels (P < 0.01) were independent predictors of disease-free survival, while lymph node metastasis (P = 0.013), serum cholinesterase levels (P < 0.01), and carbohydrate antigen19-9 (P = 0.022) were independent predictors of overall survival. In the low-cholinesterase group, neutrophil to lymphocyte ratio, (P = 0.021), C-reactive protein to albumin ratio (P < 0.01), and distant metastasis (P < 0.01) were higher, and prognostic nutritional index (P < 0.01) was lower compared with the high-cholinesterase group.

Conclusion

Preoperative low serum cholinesterase levels can be a prognostic factor for postoperative recurrence and poor prognosis in patients after curative resection for colorectal cancer, suggesting an important role of cholinesterase in the assessment of nutritional and inflammatory status in cancer patients.

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Embedded Computational Heart Model for External Ventricular Assist Device Investigations

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Abstract

Purpose

External cardiac assist devices are based on a promising and simple concept for treating heart failure, but they are surprisingly difficult to design. Thus, a structured approach combining experiments with computer-based optimization is essential. The latter provides the motivation for the work presented in this paper.

Methods

We present a computational modeling framework for realistic representation of the heart's tissue structure, electrophysiology and actuation. The passive heart tissue is described by a nonlinear anisotropic material law, considering fiber and sheetlet directions. For muscle contraction, an orthotropic active-strain model is employed, initiated by a periodically propagating electrical potential. The model allows for boundary conditions at the epicardium accounting for external assist devices, and it is coupled to a circulation network providing appropriate pressure boundary conditions inside the ventricles.

Results

Simulated results from an unsupported healthy and a pathological heart model are presented and reproduce accurate deformations compared to phenomenological measurements. Moreover, cardiac output and ventricular pressure signals are in good agreement too. By investigating the impact of applying an exemplary external actuation to the pathological heart model, it shows that cardiac patches can restore a healthy blood flow.

Conclusion

We demonstrate that the devised computational modeling framework is capable of predicting characteristic trends (e.g. apex shortening, wall thickening and apex twisting) of a healthy heart, and that it can be used to study pathological hearts and external activation thereof.

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ECG Signal Quality Assessments of a Small Bipolar Single-Lead Wearable Patch Sensor

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Abstract

Purpose

There is an increasing clinical interest in the adoption of small single-lead wearable ECG sensors for continuous cardiac monitoring. The purpose of this work is to assess ECG signal quality of such devices compared to gold standard 12-lead ECG.

Methods

The ECG signal from a 1-lead patch was systematically compared to the 12-lead ECG device in thirty subjects to establish its diagnostic accuracy in terms of clinically relevant signal morphology, wave representation, fiducial markers and interval and wave duration. One minute ECG segments with good signal quality was selected for analysis and the features of ECG were manually annotated for comparative assessment.

Results

The patch showed closest similarity based on correlation and normalized root-mean-square error to the standard ECG leads I, II, \({\text {V}_3}\) and \({\text {V}_4}\) . P-wave and QRS complexes in the patch showed sensitivity (Se) and positive predictive value (PPV) of at least 99.8% compared to lead II. T-wave representation showed Se and PPV of at least 99.9% compared to lead \({\text {V}_3}\) and \({\text {V}_4}\) . Mean errors for onset and offset of the ECG waves, wave durations, and ECG intervals were within 2 samples based on 125Hz patch ECG sampling frequency.

Conclusion

This study demonstrates the diagnostic capability with similar morphological representation and reasonable timing accuracy of ECG signal from a patch sensor compared to 12-lead ECG. The advantages and limitations of small bipolar single-lead wearable patch sensor compared to 12-lead ECG are discussed in the context of relevant differences in ECG signal for clinical applications.

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Portable ultrasound assessment of jugular venous pressure is an accurate method for estimating volaemic status in patients with cardiac disease

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Abstract

Purpose

The objective of this study was to determine whether ultrasound-measured jugular venous pressure (U-JVP) could accurately estimate central venous pressure (CVP).

Methods

This prospective, diagnostic, single-centre study was performed at the Cardiac Intensive Care Unit of the Northern General Hospital, Sheffield, UK. Post-cardiac surgery patients were recruited from January to May 2019. The investigators were blinded to the central venous pressure when measuring the jugular venous pressure. U-JVP and direct CVP were measured simultaneously. Measurements were taken whilst the patient was ventilated and then repeated when the patient was extubated, providing non-ventilated readings.

Results

One-hundred and fourteen consecutive participants with a male predominance of 71% and mean age of 65 ± 12 years were included in the analysis. Bland–Altman plots revealed that U-JVP marginally overestimated CVP by 0.91 mmHg (95% limits of agreement were −2.936 to 4.754) in ventilated patients and by 0.11 mmHg (95% limits of agreement between −2.481 and 2.695) in non-ventilated patients. Reasonable sensitivity and specificity of ultrasound-measured jugular venous pressure was achieved for low and high central venous pressure in both ventilated and non-ventilated patients.

Conclusion

U-JVP accurately estimates cardiac filling pressure and fluid status in patients after cardiac surgery, irrespective of their ventilatory status. Jugular venous pressure measurement by insonation is a reliable technique that can be taught to medical students and other health professionals to non-invasively estimate central venous pressure and may be useful for assessment of volaemic status in patients with heart failure.

Trial registration

ClinicalTrials.gov public (identifier NCT03815188).

Graphical abstract

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Actively targeted delivery of SN38 by ultrafine iron oxide nanoparticle for treating pancreatic cancer

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Abstract

Pancreatic cancer remains one of the most lethal cancers largely due to the inefficient delivery of therapeutics. Nanomaterials have been extensively investigated as drug delivery platforms, showing improved drug pharmacodynamics and pharmacokinetics. However, their applications in pancreatic cancer have not yet been successful due to limited tumor delivery caused by dense tumor stroma and distorted tumor vasculatures. Meanwhile, smaller-sized nanomaterials have shown improved tumor delivery and retention in various tumors, including pancreatic tumors, suggesting their potential in enhancing drug delivery. An ultrafine iron oxide nanoparticle (uIONP) was used to encapsulate 7-ethyl-10-hydroxyl camptothecin (SN38), the water-insoluble active metabolite of pancreatic cancer chemotherapy drug irinotecan. Insulin-like growth factor 1 (IGF-1) was conjugated to uIONP as a ligand for targeting pancreatic cancer cells overexpressing IGF-1 receptor (IGF1R). The SN38 loadi ng and release profile were characterized. The pancreatic cancer cell targeting using IGF1-uIONP/SN38 and subsequently induced cell apoptosis were also investigated. IGF1-uIONP/SN38 demonstrated a stable drug loading in physiological pH with the loading efficiency of 68.2 ± 3.5% (SN38/Fe, wt%) and < 7% release for 24 h. In tumor-interstitial- and lysosomal-mimicking pH (6.5 and 5.5), 52.2 and 91.3% of encapsulated SN38 were released over 24 h. The IGF1-uIONP/SN38 exhibited specific receptor-mediated cell targeting and cytotoxicity Ato MiaPaCa-2 and Panc02 pancreatic cancer cells with IC50 of 11.8 ± 2.3 and 20.8 ± 3.5 nM, respectively, but not to HEK293 human embryonic kidney cells. IGF1-uIONP significantly improved the targeted SN38 delivery to pancreatic cancer cells, holding the potential for in vivo theranostic applications.

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Prostate MRI using a rigid two-channel phased-array endorectal coil: comparison with phased array coil acquisition at 3 T

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Abstract

Background

To compare image quality, lesion detection and patient comfort of 3T prostate MRI using a combined rigid two-channel phased-array endorectal coil and an external phased-array coil (ERC-PAC) compared to external PAC acquisition in the same patients.

Methods

Thirty three men (mean age 65.3y) with suspected (n = 15) or biopsy-proven prostate cancer (PCa, n = 18) were prospectively enrolled in this exploratory study. 3T prostate MRI including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) was performed using an ERC-PAC versus PAC alone, in random order. Image quality, lesion detection and characterization (biparametric PI-RADSv2.1) were evaluated by 2 independent observers. Estimated signal-to-noise ratio (eSNR) was measured in identified lesions and the peripheral zone (PZ). Patient comfort was assessed using a questionnaire. Data were compared between sequences and acquisitions. Inter/intra-observer agreement for PI-RADS scores was evaluated.

Results

Twenty four prostate lesions (22 PCa) were identified in 20/33 men. Superior image quality was found for ERC-PAC compared to PAC for T2WI for one observer (Obs.1, p < 0.03) and high b-value DWI for both observers (p < 0.05). The sensitivity of PI-RADS for lesion detection for ERC-PAC and PAC acquisitions was 79.2 and 75% for Obs.1, and 79.1 and 66.7%, for Obs.2, without significant difference for each observer (McNemar p-values ≥0.08). Inter−/intra-observer agreement for PI-RADS scores was moderate-to-substantial (kappa = 0.52–0.84). Higher eSNR was observed for lesions and PZ for T2WI and PZ for DWI using ERC-PAC (p < 0.013). Most patients (21/33) reported discomfort at ERC insertion.

Conclusion

Despite improved image quality and eSNR using the rigid ERC-PAC combination, no significant improvement in lesion detection was observed, therefore not supporting the routine use of ERC for prostate MRI.

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Synthetic fused sRNA for the simultaneous repression of multiple genes

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Abstract

Efficient control over multiple gene expression still presents a major challenge. Synthetic sRNA enables targeted gene expression control in trans without directly modifying the chromosome, but its use to simultaneously target multiple genes can often cause cell growth defects because of the need for additional energy for transcription and lowering of their repression efficiency by limiting the amount of Hfq protein. To address these limitations, we present fusion sRNA (fsRNA) that simultaneously regulates the translation of multiple genes efficiently. It is constructed by linking the mRNA-binding modules for multiple targeted genes in one sRNA scaffold via one-pot generation using overlap extension PCR. The repression capacity of fsRNA was demonstrated by the construction of sRNAs to target four endogenous genes: caiF, hybG, ytfR and minD in Escherichia coli. Their cross-reactivity and the effect on cell growth were a lso investigated. As practical applications, we applied fsRNA to violacein- and protocatechuic acid–producing strains, resulting in increases of 13% violacein and 81% protocatechuic acid, respectively. The developed fsRNA-mediated multiple gene expression regulation system thus enables rapid and efficient development of optimised cell factories for valuable chemicals without cell growth defects and limiting cellular resources.

Key points

• Synthetic fusion sRNA (fsRNA)–based system was constructed for the repression of multiple target genes.

• fsRNA repressed multiple genes by only expressing a single sRNA while minimising the cellular burden.

• The application of fsRNA showed the increased production titers of violacein (13%) and protocatechuic acid (81%).

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Microbial associations for bioremediation. What does “microbial consortia” mean?

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Abstract

Microbial associations arise as useful tools in several biotechnological processes. Among them, bioremediation of contaminated environments usually takes advantage of these microbial associations. Despite being frequently used, these associations are indicated using a variety of expressions, showing a lack of consensus by specialists in the field. The main idea of this work is to analyze the variety of microbial associations referred to as "microbial consortia" (MC) in the context of pollutants biodegradation and bioremediation. To do that, we summarize the origin of the term pointing out the features that an MC is expected to meet, according to the opinion of several authors. An analysis of related bibliography was done seeking criteria to rationalize and classify MC in the context of bioremediation. We identify that the microbe's origin and the level of human intervention are usually considered as a category to classify them as natural microbial consort ia (NMC), artificial microbial consortia (AMC), and synthetic microbial consortia (SMC). In this sense, NMC are those associations composed by microorganisms obtained from a single source while AMC members come from different sources. SMC are a class of AMC in which microbial composition is defined to accomplish a certain specific task. We propose that the effective or potential existence of the interaction among MC members in the source material should be considered as a category in the classification as well, in combination with the origin of the source and level of intervention. Cross-kingdom MC and new developments were also considered. Finally, the existence of grey zones in the limits between each proposed microbial consortia category is addressed.

Key points

Microbial consortia for bioremediation can be obtained through different methods.

The use of the term "microbial consortia" is unclear in the specialized literature.

We propose a simplified classification for microbial consortia for bioremediation.

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Reproducibility of improvements in patient-reported functional ability following functional capacity evaluation

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Abstract

Background

Performance of functional capacity evaluation (FCE) may affect patients, self-efficacy to complete physical activity tasks. First evidence from a diagnostic before-after study indicates a significant increase of patient-reported functional ability. Our study set out to test the reproducibility of these results.

Methods

Patients with musculoskeletal trauma and an unclear return to work prognosis were recruited in a trauma rehabilitation center in Lower Austria. We included patient cohorts of three consecutive years (2016: n = 161, 2017: n = 140; 2018: n = 151). Our primary outcome was patient-reported functional ability, measured using the Spinal Function Sort (SFS). SFS scores were assessed before and after performing an FCE to describe the change in patient-reported functional ability (cohort study). We investigated whether the change in SFS scores observed after performing an FCE in our first cohort could be replicated in subsequent cohorts.

Results

Demographic data (gender, age and time after trauma) did not differ significantly between the three patient cohorts. Correlation analysis showed highly associated before and after SFS scores in each cohort (2016: rs = 0.84, 95% CI: 0.79 to 0.89; 2017: rs = 0.85, 95% CI: 0.81 to 0.91; 2018: rs = 0.86, 95% CI: 0.82 to 0.91). Improvements in SFS scores were consistent across the cohorts, with overlapping 95% confidence intervals (2016: 14.8, 95% CI: 11.3 to 18.2; 2017: 14.8, 95% CI: 11.5 to 18.0; 2018: 15.2, 95% CI: 12.0 to 18.4). Similarity in SFS scores and SFS differences were also supported by non-significant Kruskal–Wallis H tests (before FCE: p = 0.517; after FCE: p = 0.531; SFS differences: p = 0.931).

Conclusions

A significant increase in patient-reported functional ability after FCE was found in the original study and the results could be reproduced in two subsequent cohorts.

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