Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τετάρτη 16 Μαρτίου 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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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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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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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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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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Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response

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Abstract

Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient. Here, we investigated whether IL-22 exerted nephroprotective effects to sodium oxalate-mediated kidney damage and its potential mechanism. Crystalline kidney injury models were developed in vitro and in vivo that was often observed in clinic. We provided evidence that IL-22 could effectively decrease the accumulation of ROS and mitochondrial damage in cell and animal models and reduce the death of TECs. Moreover, IL-22 decreased the expression of the NLRP3 inflammasome and mature IL-1β in renal tissue induced by sodium oxalate. Further studies confirmed that IL-22 could play an anti-inflammatory role by reducing the levels of cytokines suc h as IL-1β, IL-18, and TNF-α in serum. In conclusion, our study confirmed that IL-22 has protective effects on sodium oxalate-induced crystalline kidney injury by reducing the production of ROS, protecting mitochondrial membrane potential, and inhibiting the inflammatory response. Therefore, IL-22 may play a potential preventive role in sodium oxalate-induced acute renal injury.

Key points

IL-22 could reduce sodium oxalate-mediated cytotoxicity and ameliorate renal injury.

IL-22 could alleviate oxidative stress and mitochondrial dysfunction induced by sodium oxalate.

IL-22 could inhibit inflammatory response of renal injury caused by sodium oxalate.

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Increased migratory activity and cartilage regeneration by superficial-zone chondrocytes in enzymatically treated cartilage explants

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Abstract

Background

Limited chondrocyte migration and impaired cartilage-to-cartilage healing is a barrier in cartilage regenerative therapy. Collagenase treatment and delivery of a chemotactic agent may play a positive role in chondrocyte repopulation at the site of cartilage damage. This study evaluated chondrocyte migratory activity after enzymatic treatment in cultured cartilage explant. Differential effects of platelet-derived growth factor (PDGF) dimeric isoforms on the migratory activity were investigated to define major chemotactic factors for cartilage.

Methods

Full-thickness cartilage (4-mm3 blocks) were harvested from porcine femoral condyles and subjected to explant culture. After 15 min or 60 min of actinase and collagenase treatments, chondrocyte migration and infiltration into a 0.5-mm cartilage gap was investigated. Cell morphology and lubricin, keratan sulfate, and chondroitin 4 sulfate expression in superficial- and deep-zone chondrocytes were assessed. The chemotactic activities of PDGF-AA, −AB, and -BB were measured in each zone of chondrocytes, using a modified Boyden chamber assay. The protein and mRNA expression and histological localization of PDGF-β were analyzed by western blot analysis, real-time reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry, and results in each cartilage zone were compared.

Results

Superficial-zone chondrocytes had higher migratory activity than deep-zone chondrocytes and actively bridged the cartilage gap, while metachromatic staining by toluidine blue and immunoreactivities of keratan sulfate and chondroitin 4 sulfate were detected around the cells migrating from the superficial zone. These superficial-zone cells with weak immunoreactivity for lubricin tended to enter the cartilage gap and possessed higher migratory activity, while the deep-zone chondrocytes remained in the lacuna and exhibited less migratory activity. Among PDGF isoforms, PDGF-AB maximized the degree of chemotactic activity of superficial zone chondrocytes. Increased expression of PDGF receptor-β was associated with higher migratory activity of the superficial-zone chondrocytes.

Conclusions

In enzymatically treated cartilage explant culture, chondrocyte migration and infiltration into the cartilage gap was higher in the superficial zone than in the deep zone. Preferential expression of PDGF receptor-β combined with the PDGF-AB dimeric isoform may explain the increased migratory activity of the superficial-zone chondrocytes. Cells migrating from superficial zone may contribute to cartilage regeneration.

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The Ali Krogius procedure for treatment of patellofemoral instability should be regarded as obsolete even in skeletally immature patients

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Abstract

Background

Several interventions are established for treating patellofemoral instability in adults. Fewer exist for pediatric patients without damaging the epiphysis. The Ali Krogius (AK) method is currently still being used. Most studies are not current and report varying results in small patient population. The aim of this study is to determine the long-term results of the AK method.

Methods

In this monocentric, retrospective study design, 33 knees in 33 patients who received the AK procedure for recurrent patellar dislocation were assessed. The average age was 20.8 years (range 6–40). The following functional scores were assessed: Kujala Score, Lysholm Score and Tegner Score. Subgroup analysis was done for patients ≤16 years of age. Available preoperative imaging was assessed for known risk factors.

Results

After an average follow-up of 7.8 years (Range 59–145 months), a total of 8 (24%) knees suffered a redislocation postoperatively. Seven of the eight dislocations occurred in patients ≤ 16 years of age. One knee (3%) was revised due to persistent pain. The median score was 86 points for the Kujala score and 90 for the Lysholm score. The median in the Tegner score was level 6. Clinically, the patellar glide was lateralized in 7 knees (21%) and an apprehension sign was triggered in 8 knees (24%).

Conclusions

Including the present study, the existing literature indicates a redislocation rate between 24 and 41% following AK. It should thus be regarded as obsolete even though it protects the epiphysis. Surgical interventions such as medial patellofemoral ligament reconstruction with femoral drilling distal to the epiphysis should be preferred.

Trial registration

Retrospectively registered: S-302/2016.

Level of evidence

III

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Acute cardiac autonomic and haemodynamic responses to leg and arm isometric exercise

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Abstract

Objectives

Acute cardiovascular responses following a single session of isometric exercise (IE) have been shown to predict chronic adaptations in blood pressure (BP) regulation. It was hypothesised that exercises which recruit more muscle mass induce greater reductions in BP compared to exercises using smaller muscle mass. To test this hypothesis, the current study aimed to compare the acute haemodynamic and autonomic responses to a single session of isometric wall squat (IWS) and isometric handgrip (IHG) training.

Methods

Twenty-six sedentary participants performed a single IWS and IHG session in a randomised cross-over design, with training composed of 4 × 2-min contractions, with 2-min rest, at 95 HRpeak and 30% MVC respectively. Haemodynamic and cardiac autonomic variables were recorded pre, during, immediately post, and 1-h post-exercise, with the change from baseline for each variable used for comparative analysis.

Results

During IWS exercise, there was a significantly greater increase in systolic BP (P < 0.001), diastolic BP (P < 0.001), mean BP (P < 0.001), heart rate (P < 0.001), and cardiac output (P < 0.001), and a contrasting decrease in baroreflex effectiveness index (BEI) and cardiac baroreceptor sensitivity (cBRS). In the 10-min recovery period following IWS exercise, there was a significantly greater reduction in systolic BP (P = 0.005), diastolic BP (P = 0.006), mean BP (P = 0.003), total peripheral resistance (TPR) (P < 0.001), BEI (P = 0.003), and power spectral density (PSD-RRI) (P < 0.001). There were no differences in any variables between conditions 1-h post exercise.

Conclusions

Isometric wall squat exercise involving larger muscle mass is associated with a significantly greater post-exercise hypotensive response during a 10-min recovery window compared to smaller muscle mass IHG exercise. The significantly greater reduction in TPR may be an important mechanism for the differences in BP response.

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