Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer

A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of neratinib as MST1 inhibitor with potent effects on β-cell survival represents a promising approach for causative diabetes therapy. Here we report a case of robust glycemia and HbA1c normalization in a patient with breast cancer-T2D comorbidity under neratinib, a potent triple kinase inhibitor of HER2/EGFR and MST1. The patient, aged 62 years, was enrolled in the plasmaMATCH clinical trial and received 240 mg neratinib once daily. Neratinib therapy correlated with great improvement in glucose and HbA1c both to physiological levels during the whole treatment period (average reduction of random glucose from 13.6 ± 0.4 to 6.3 ± 0.5 mmol/l and of HbA1c from 82.2 ± 3.9 to 45.6 ± 4.2 mmol/mol before and during neratinib). 18 months later, when neratinib was withdrawn, random glucose rapidly raised together with high blood glucose fluctuations, which reflected in elevated HbA1c levels. This clinical case reports the combination of HER2/EGFR/MST1-inhibition by neratinib for the pharmacological intervention to effectively restore normoglycemia in a patient with poorly controlled T2D and suggests neratinib as potent therapeutic regimen for the cancer-diabetes comorbidity

Development of a New Tool for 3D Modeling for Regenerative Medicine

The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume

Endoscopic enucleation of the prostate with Thulium Fiber Laser (ThuFLEP). A retrospective single-center study

Purpose: The aim of the present, retrospective study was to describe our initial experience and early outcomes of Thulium Fiber Laser enucleation of the prostate (ThuFLEP) with the use of the FiberDust™ (Quanta System, Samarate, Italy) in patients with benign prostate hyperplasia. Methods: From June 2022 to April 2023, all patients who underwent endoscopic enucleation of the prostate at Urology Department of the University Hospital of Patras were included. A single surgeon utilizing the same standardized operative technique performed all the surgeries. The primary endpoints included the uneventful completion of the operation, the surgical time and any minor or major complication observed intra- or post-operatively. Results: Twenty patients with benign prostate hyperplasia were treated with ThuFLEP. All the surgeries were completed successfully and uneventfully. The enucleation phase of the operation was completed in a mean time of 45 ± 9.1 min, while the average time needed for the morcellation was 17.65 ± 3.42 min. No significant complications were observed intra- or post-operatively. The average hemoglobin drop was calculated to be 0.94 ± 0.71 g/dL. Conclusions: All the operations were successfully and efficiently completed with the use of the FiberDust™ (Quanta System, Samarate, Italy) in ThuFLEP. Significant blood loss or major complications were not observed

Minimal invasive treatment of urethral strictures: An experimental study of the effect of Paclitaxel coated balloons in the wall of strictured rabbit’s urethra

Purpose: The aim of this study is the evaluation of the distribution of Paclitaxel (PTX) released by a coated balloon in the layers of rabbit’s urethra. Methods: 18 rabbits were included. A Laser Device was used for the stricture formation. After two weeks, dilation of the strictured urethra was performed by using Advance 35LP PTA balloons and Advance 18 PTX PTA balloons. The experimental models were divided into 3 groups. The group Α included two rabbits without any intervention except for the stenosis procedure. Group B compromised six rabbits that underwent dilation with Advance 35LP PTA balloons. Group C consisted of 10 rabbits to which dilation with both Advance 35LP PTA balloons and Advance 18 PTX PTA balloons was applied. Histological evaluation and Immunohistochemistry were performed on all specimens. Results: Inflammation, fibrosis and ruptures were detected in the specimens of the study. In specimens of Group C the decrease of inflammation and fibrosis rate was greater. Anti-PTX antibody was detected in the epithelium, lamina propria and smooth muscle layer of all specimens of urethras that have been harvested immediately and 1 day after the dilation with Advance 18 PTX PTA balloon and it was not observed in any layer of the urethral wall of the rest of the examined specimens of Group C. Conclusions: PTX’s enrichment was detected in the smooth muscle layer of all specimens that have been harvested immediately and 24h after the dilation with Advance 18 PTX PTA balloons. PTX may play an inhibitive role in the recurrence of the stenosis

Feasibility study of a novel robotic system for transperitoneal partial nephrectomy: An in vivo experimental animal study

Purpose: To evaluate the safety and feasibility of partial nephrectomy with the use of the novel robotic system in an in vivo animal model. Methods: Right partial nephrectomy was performed in female pigs by a surgical team consisting of one surgeon and one bedside assistant. Both were experienced in laparoscopic surgery and trained in the use of the novel robotic system. The partial nephrectomies were performed using four trocars (three trocars for the robotic arms and one as an assistant trocar). The completion of the operations, set-up time, operation time, warm ischemia time (WIT) and complication events were recorded. The decrease in all variables between the first and last operation was calculated. Results: In total, eight partial nephrectomies were performed in eight female pigs. All operations were successfully completed. The median set-up time was 19.5 (range, 15-30) minutes, while the estimated median operative time was 80.5 minutes (range, 59-114). The median WIT was 23.5 minutes (range, 17-32) and intra- or postoperative complications were not observed. All variables decreased in consecutive operations. More precisely, the decrease in the set-up time was calculated to 15 minutes between the first and third attempts. The operative time was reduced by 55 minutes between the first and last operation, while the WIT was decreased by 15 minutes during the consecutive attempts. No complications were noticed in any operation. Conclusions: Using the newly introduced robotic system, all the advantages of robotic surgery are optimized and incorporated, and partial nephrectomies can be performed in a safe and effective manner

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10(9) cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Implementation of a Topology Independent MAC (TiMAC) Policy on a Low-Cost IoT System

The emerging new paradigm under the fifth generation of wireless communications technologies (5G) and high expectations for massively expanding today&rsquo;s Internet of Things (IoT) under 5G, are expected to support a large plurality of low-cost devices for an all-increasing number of new IoT applications. Many emerging IoT applications are going to take advantage of techniques and technologies that have high demands from low-cost devices in terms of processing large amounts of data and communication. For example, in systems based on fog computing technology, low-cost devices have to assign some of their limited resources for processing purposes. Considering the drawbacks emerging from using low-cost devices and the fact that many applications are in need for time-constrained approaches, TDMA-based Medium Access Control (MAC) policies need to be revisited and implemented in low-cost devices of today. In this sense, a policy independent of the underlying topology, TiMAC policy, is considered here and is implemented in low-cost devices using 433 MHz RF modules. Even though the implementation is limited by synchronization issues and a small number of nodes, the obtained experimental results demonstrate the potential for employing TDMA-based MAC policies on IoT systems consisting of low-cost devices

Self-Healing of Semantically Interoperable Smart and Prescriptive Edge Devices in IoT

Smart homes enhance energy efficiency without compromising residents’ comfort. To support smart home deployment and services, an IoT network must be established, while energy-management techniques must be applied to ensure energy efficiency. IoT networks must perpetually operate to ensure constant energy and indoor environmental monitoring. In this paper, an advanced sensor-agnostic plug-n-play prescriptive edge-to-edge IoT network management with micro-services is proposed, supporting also the semantic interoperability of multiple smart edge devices operating in the smart home network. Furthermore, IoT health-monitoring algorithms are applied to inspect network anomalies taking proper healing actions/prescriptions without the need to visit the residency. An autoencoder long short-term memory (AE-LSTM) is selected for detecting problematic situations, improving error prediction to 99.4%. Finally, indicative evaluation results reveal the mitigation of the IoT system breakdowns

Training of Deep Convolutional Neural Networks to Identify Critical Liver Alterations in Histopathology Image Samples

Nonalcoholic fatty liver disease (NAFLD) is responsible for a wide range of pathological disorders. It is characterized by the prevalence of steatosis, which results in excessive accumulation of triglyceride in the liver tissue. At high rates, it can lead to a partial or total occlusion of the organ. In contrast, nonalcoholic steatohepatitis (NASH) is a progressive form of NAFLD, with the inclusion of hepatocellular injury and inflammation histological diseases. Since there is no approved pharmacotherapeutic solution for both conditions, physicians and engineers are constantly in search for fast and accurate diagnostic methods. The proposed work introduces a fully automated classification approach, taking into consideration the high discrimination capability of four histological tissue alterations. The proposed work utilizes a deep supervised learning method, with a convolutional neural network (CNN) architecture achieving a classification accuracy of 95%. The classification capability of the new CNN model is compared with a pre-trained AlexNet model, a visual geometry group (VGG)-16 deep architecture and a conventional multilayer perceptron (MLP) artificial neural network. The results show that the constructed model can achieve better classification accuracy than VGG-16 (94%) and MLP (90.3%), while AlexNet emerges as the most efficient classifier (97%)