Impact of Cold Ischemia on the Stability of 1H-MRS-Detected Metabolic Profiles of Ovarian Cancer Specimens.

Proton magnetic resonance spectroscopy (1H-MRS) of surgically collected tumor specimens may contribute to investigating cancer metabolism and the significance of the "total choline" (tCho) peak (3.2 ppm) as malignancy and therapy response biomarker. To ensure preservation of intrinsic metabolomic information, standardized handling procedures are needed. The effects of time to freeze (cold ischemia) were evaluated in (a) surgical epithelial ovarian cancer (EOC) specimens using high-resolution (HR) 1H-MRS (9.4 T) of aqueous extracts and (b) preclinical EOC samples (xenografts in SCID mice) investigated by in vivo MRI-guided 1H-MRS (4.7 T) and by HR-1H-MRS (9.4 T) of tumor extracts or intact fragments (using magic-angle-spinning (MAS) technology). No significant changes were found in the levels of 27 of 29 MRS-detected metabolites (including the tCho profile) in clinical specimens up to 2 h cold ischemia, besides an increase in lysine and a decrease in glutathione. EOC xenografts showed a 2-fold increase in free choline within 2 h cold ischemia, without further significant changes for any MRS-detected metabolite (including phosphocholine and tCho) up to 6 h. At shorter times (≤1 h), HR-MAS analyses showed unaltered tCho components, along with significant changes in lactate, glutamate, and glutamine. Our results support the view that a time to freeze of 1 h represents a safe threshold to ensure the maintenance of a reliable tCho profile in EOC specimens.

Fast-track protocols for patients undergoing spine surgery: a systematic review.

BACKGROUND CONTEXT: Fast-track is an evidence-based multidisciplinary strategy for pre-, intra-, and postoperative management of patients during major surgery. To date, fast-track has not been recognized or accepted in all surgical areas, particularly in orthopedic spine surgery where it still represents a relatively new paradigm. PURPOSE: The aim of this review was provided an evidenced-based assessment of specific interventions, measurement, and associated outcomes linked to enhanced recovery pathways in spine surgery field. METHODS: We conducted a systematic review in three databases from February 2012 to August 2022 to assess the pre-, intra-, and postoperative key elements and the clinical evidence of fast-track protocols as well as specific interventions and associated outcomes, in patients undergoing to spine surgery. RESULTS: We included 57 full-text articles of which most were retrospective. Most common fast-track elements included patient's education, multimodal analgesia, thrombo- and antibiotic prophylaxis, tranexamic acid use, urinary catheter and drainage removal within 24 hours after surgery, and early mobilization and nutrition. All studies demonstrated that these interventions were able to reduce patients' length of stay (LOS) and opioid use. Comparative studies between fast-track and non-fast-track protocols also showed improved pain scores without increasing complication or readmission rates, thus improving patient's satisfaction and functional recovery. CONCLUSIONS: According to the review results, fast-track seems to be a successful tool to reduce LOS, accelerate return of function, minimize postoperative pain, and save costs in spine surgery. However, current studies are mainly on degenerative spine diseases and largely restricted to retrospective studies with non-randomized data, thus multicenter randomized trials comparing fast-track outcomes and implementation are mandatory to confirm its benefit in spine surgery.

Aortic Annuloplasty: Focus on the Use of an External Teflon Ring.

Aortic annuloplasty has been clearly demonstrated to have a protective influence in aortic valve repair. Over the past 20 years, different annuloplasty concepts have been proposed by different groups. However, the most appropriate approach to enable long-term annular stability remains highly controversial. The aim of this article is to give a general overview of all types of aortic annuloplasty, particularly focusing on the use of an external Teflon ring, as proposed by our group. In this technique, external root dissection is performed in the same fashion as for reimplantation; the only difference is that it is necessary to go below the coronary ostia take-off. A series of pledgeted sutures (usually between 6 and 9 sutures) are placed at the level of the virtual basal ring. The external ring is made using a Teflon strip with a length of 8 to 9 cm, to reduce the annulus to a diameter of between 21 and 23 mm. The sub-annular sutures are then passed at the appropriate level through the Teflon strip and the strip is parachuted outside the aortic root base, passing under the coronary ostia. The two ends of the Teflon strip are tied at the level of the non-coronary sinus. Aortic annuloplasty is a crucial step to improve valve competence and stabilization. While several techniques offer good mid- to long-term results, annuloplasty with an external Teflon ring appears to be a simple and effective alternative to guarantee stable root diameters. Longer follow-up studies are needed to confirm the mid- to long-term results.

Biological Valves Impervious to Calcification: Is this Holy Grail a Cup Ready to Drink?

An indefinitely lasting bioprosthesis that does not require anticoagulation treatment is the holy grail of substitutive heart surgery. However, this goal is not yet in sight with the present state of technology. Over the past few years, tremendous advances have been achieved regarding tissue anticalcification processes, hemodynamic performance and future-proofing by ensuring compatibility with transcatheter valve-in-valve procedures. The Inspiris Resilia valve (Edwards Lifesciences, Irvine, CA) was designed to incorporate all of these enhancements. It is now leaving the experimental phase and is being tested in the real world. We present here a comprehensive review of the evolution of biological prostheses, details of new anticalcification technologies, and early results of published studies as well as the experience at the European Hospital (Rome, Italy), the site of the first European implant and a leading center in various protocols. In our two years of experience with the Inspiris Resilia, there have been no cases of structural valve deterioration, endocarditis, detachment or periprocedural complication, and gradients seem to be superior to those with the previous generation of Edwards valves. While longer-term experience is clearly needed, the results thus far are encouraging.

A composite scale to recognize abdominal pain and its variation over time in response to analgesia in rabbits.

OBJECTIVE: To refine a composite scale for pain evaluation in rabbits and evaluate it for pain variations over time. To determine the differences between objective-Centro Animali Non Convenzionali Rabbit Scale (CANCRS) and subjective-Visual Analogue Scale (VAS) in assessing abdominal pain. STUDY DESIGN: Observational case-control study. ANIMALS: A total of 86 rabbits, 47 healthy animals and 39 animals with gastrointestinal stasis syndrome (RGIS), participated in the study; of 39 animals with RGIS, 32 animals participated in the second part of the study. METHODS: In part 1, rabbits underwent pain assessments with VAS and CANCRS. In part 2, the animals underwent four pain assessments with three CANCRS. The first assessment was performed prior to pain management, the others after 30, 60 and 90 minutes. Statistics included Mann-Whitney U test for in-between group comparisons and analysis of variance to assess differences over time. Sensitivity and specificity for each variable of CANCRS were calculated to obtain weighting factors. RESULTS: CANCRS showed differences between healthy and diseased rabbits (p = 0.0001), and median scores were 5 [interquartile range (IQR): 4-6) and 9 (IQR: 7-11), respectively. VAS showed differences between healthy and diseased rabbits (p = 0.02), and median scores were 4 (IQR: 2-5.35) and 5.3 (IQR: 2.65-6.45), respectively. The cut-off scores for CANCRS and VAS for differentiation between healthy and diseased rabbits were 7 (specificity 89%, sensitivity 79%) and 4.4 (specificity 59%, sensitivity 69%), respectively. Internal validity testing of CANCRS was significant at each time point. CONCLUSIONS AND CLINICAL RELEVANCE: Some variables should be excluded from CANCRS when assessing abdominal pain. CANCRS performed better than VAS, and it detected variations in pain in response to analgesia.

Measurement of Spin Dynamics in a Layered Nickelate Using X-Ray Photon Correlation Spectroscopy: Evidence for Intrinsic Destabilization of Incommensurate Stripes at Low Temperatures.

We study the temporal stability of stripe-type spin order in a layered nickelate with x-ray photon correlation spectroscopy and observe fluctuations on timescales of tens of minutes over a wide temperature range. These fluctuations show an anomalous temperature dependence: they slow down at intermediate temperatures and speed up on both heating and cooling. This behavior appears to be directly connected with spatial correlations: stripes fluctuate slowly when stripe correlation lengths are large and become faster when spatial correlations decrease. A low-temperature decay of nickelate stripe correlations, reminiscent of what occurs in cuprates as a result of a competition between stripes and superconductivity, hence occurs via loss of both spatial and temporal correlations.

Effect of relaxin on cryopreserved beef bull semen characteristics.

This study aimed to improve the quality of cryopreserved beef bull (Piedmontese) semen by incorporation of relaxin in diluted semen before cryopreservation procedures. Semen samples were collected from 4 proven fertile bulls, using artificial vagina, once per week for 8 consecutive weeks and pooled together then diluted with Bullxcell® extender, and supplemented with different concentrations of relaxin (0 (control), 25, 50 and 100 ng/ml) before cooling, equilibration and freezing procedures. Frozen semen was thawed and assessed for motility by Computer-Assisted Sperm Analysis and vitality parameters such as acrosome, plasma membrane and DNA integrities, apoptosis, mitochondrial membrane potential, mucus penetration and SOD activity. The developmental potential of bovine embryos produced in vitro by using relaxin-treated was also investigated. In the present study, 50 and 100 ng/ml relaxin incorporation in extended bull semen before cryopreservation induced a reduction of sperm motility immediately after thawing (0h), whereas, during long incubation periods (1-2 h), relaxin showed a significant positive effect on sperm quality by improving the sperm motility and velocity parameters. Interestingly, sperm vitality was improved by 25 and 100 ng/ml relaxin and the blastocyst developmental rate was significantly increased in the 25 ng/ml relaxin group compared with controls (52/118, 44.0% vs. 32/116, 27.6%, respectively). These findings suggest a potential use of relaxin at the doses tested in the present study as an additive in the cryopreservation media of bull semen to improve sperm quality.

Diffusive dynamics during the high-to-low density transition in amorphous ice.

Water exists in high- and low-density amorphous ice forms (HDA and LDA), which could correspond to the glassy states of high- (HDL) and low-density liquid (LDL) in the metastable part of the phase diagram. However, the nature of both the glass transition and the high-to-low-density transition are debated and new experimental evidence is needed. Here we combine wide-angle X-ray scattering (WAXS) with X-ray photon-correlation spectroscopy (XPCS) in the small-angle X-ray scattering (SAXS) geometry to probe both the structural and dynamical properties during the high-to-low-density transition in amorphous ice at 1 bar. By analyzing the structure factor and the radial distribution function, the coexistence of two structurally distinct domains is observed at T = 125 K. XPCS probes the dynamics in momentum space, which in the SAXS geometry reflects structural relaxation on the nanometer length scale. The dynamics of HDA are characterized by a slow component with a large time constant, arising from viscoelastic relaxation and stress release from nanometer-sized heterogeneities. Above 110 K a faster, strongly temperature-dependent component appears, with momentum transfer dependence pointing toward nanoscale diffusion. This dynamical component slows down after transition into the low-density form at 130 K, but remains diffusive. The diffusive character of both the high- and low-density forms is discussed among different interpretations and the results are most consistent with the hypothesis of a liquid-liquid transition in the ultraviscous regime.

How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency.

On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.

An experience-based review of HIFU in functional interventional neuroradiology: transcranial MRgFUS thalamotomy for treatment of tremor.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.

External Stents for Vein Grafts in Coronary Artery Bypass Grafting: Targeting Intimal Hyperplasia.

INTRODUCTION: Progressive saphenous vein graft (SVG) failure remains a key limitation to the long-term success of coronary artery bypass grafting (CABG). SVG disease after the first year is dominated by intimal hyperplasia, which predisposes the SVG to thrombosis and accelerated atherosclerosis. The objective of this study was to review and summarize the latest experimental and clinical data on the use of mechanical external stents for vein grafts. METHODS: In January 2020, the PubMed database was searched using the terms "external stent", "CABG", "saphenous vein graft" and "intimal hyperplasia". The results were reviewed and only randomized experimental and clinical studies that analyzed the effect of external stenting on venous intimal hyperplasia were included in the analysis, together with studies that investigated the clinical benefit of external stenting. RESULTS: Eight experimental and four clinical trials met the search criteria. Controlled trials in different large animal models concluded that external stenting significantly reduced intimal hyperplasia 3-6 months post implantation, and reduced both thrombosis rates and the development of lumen irregularities. Data from randomized controlled trials with a follow-up period of 1-4.5 years supported the pre-clinical findings and demonstrated that external stents significantly reduced vein graft disease. CONCLUSION: Strong evidence indicates that supporting the vein with external stents is safe and leads to clear advantages at both the anatomical and cellular levels. With the further accumulation of consistent positive results, external stenting of SVG may become the standard of care in future CABG.

On the Integration of Agents and Digital Twins in Healthcare.

A digital twin is a digital representation of a physical asset reproducing its data model, its behaviour and its communication with other physical assets. Digital twins act as a digital replica for the physical object or process they represent, providing nearly real-time monitoring and evaluation without being in close proximity. Although most of their concrete applications can be found mainly in the industrial context, healthcare represents another relevant area where digital twins can have a disruptive impact. The main research question tackled by this paper is about the integration of digital twins with agents and Multi-Agent Systems (MAS) technologies in healthcare. After providing an overview of the application of digital twins in healthcare, in this paper, we discuss our vision about agent-based digital twins, and we present a first case study, about the application of agent-based digital twins to the management of severe traumas.

Complementing Agents with Cognitive Services: A Case Study in Healthcare.

Personal Agents (PAs) have longly been explored as assistants to support users in their daily activities. Surprisingly, few works refer to the adoption of PAs in the healthcare domain, where they can assist physicians' activities reducing medical errors. Although literature proposes different approaches for modelling and engineering PAs, none of them discusses how they can be integrated with cognitive services in order to empower their reasoning capabilities. In this paper we present an integration model, specifically devised for healthcare applications, that enhances Belief-Desire-Intention agents reasoning with advanced cognitive capabilities. As a case study, we adopt this integrated model in the critical care path of trauma resuscitation, stepping forward to the vision of Smart Hospitals.

From digital world to real life: a robotic approach to the esophagogastric junction with a 3D printed model.

BACKGROUND: Three-dimensional (3D) printing may represent a useful tool to provide, in surgery, a good representation of surgical scenario before surgery, particularly in complex cases. Recently, such a technology has been utilized to plan operative interventions in spinal, neuronal, and cardiac surgeries, but few data are available in the literature about their role in the upper gastrointestinal surgery. The feasibility of this technology has been described in a single case of gastroesophageal reflux disease with complex anatomy due to a markedly tortuous descending aorta. METHODS: A 65-year-old Caucasian woman was referred to our Department complaining heartburn and pyrosis. A chest computed tomography evidenced a tortuous thoracic aorta and consequent compression of the esophagus between the vessel and left atrium. A "dysphagia aortica" has been diagnosed. Thus, surgical treatment of anti-reflux surgery with separation of the distal esophagus from the aorta was planned. To define the strict relationship between the esophagus and the mediastinal organs, a life-size 3D printed model of the esophagus including the proximal stomach, the thoracic aorta and diaphragmatic crus, based on the patient's CT scan, was manufactured. RESULTS: The robotic procedure was performed with the da Vinci Surgical System and lasted 175 min. The surgeons had navigational guidance during the procedure since they could consult the 3D electronically superimposed processed images, in a "picture-in-picture" mode, over the surgical field displayed on the monitor as well as on the robotic headset. There was no injury to the surrounding organs and, most importantly, the patient had an uncomplicated postoperative course. CONCLUSIONS: The present clinical report highlights the feasibility, utility and clinical effects of 3D printing technology for preoperative planning and intraoperative guidance in surgery, including the esophagogastric field. However, the lack of published data requires more evidence to assess the effectiveness and safety of this novel surgical-applied printing technology.

Individual 3-dimensional printed mold for treating hard palate carcinoma with brachytherapy: A clinical report.

This clinical report describes the use of a 3-dimensional (3D) printer to create an individual mold for delivering high-dose-rate interventional radiotherapy for hard palate cancer. The maxillary teeth and palate were scanned with an intraoral scanner (3Shape TRIOS 3). The scan was transformed into a mesh using the standard tessellation language (STL) format and aligned with Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) images using free Blue Sky Plan 4 planning software. A mold was generated by tracing a guideline around the gingival margins of the maxillary teeth and palate on the scan mesh in accordance with established parameters. All data were imported into computer-aided design (CAD) software. For this patient, 3 parallel 2.2-mm-diameter ducts were placed 10 mm from each other in the mold mesh. A CT scan of the patient's mouth with the mold in place was used for treatment planning. Treatment was delivered by means of microSelectron digital afterloading.

Endoscope-Assisted Microneurosurgery for Intracranial Aneurysms: Operative Technique, Reliability, and Feasibility Based on 14 Years of Personal Experience.

Endoscope-assisted microneurosurgery (EAM) combines endoscopic and microsurgical techniques for the treatment of deeply located intracranial lesions. During aneurysm surgery, endoscopic assistance may aid in the visualization of perforating arteries, especially when minimally invasive approaches are used. Between 2002 and 2015, a total of 183 patients with 208 intracranial aneurysms were surgically treated in our department. EAM was performed in 191 procedures. In all, 159 aneurysms were located in the anterior circulation and 49 in the posterior circulation. Of these, 135 aneurysms were ruptured. Lesions were exposed through standard skull base microsurgical approaches. The endoscope was employed during three steps: initial inspection, true operative time, and final inspection. Complications directly related to endoscopic procedures were rare; no surgical mortality was observed in this series. A retrospective analysis of each procedure showed that the usefulness of EAM depended on the anatomical location and size of the lesions. Its advantages were especially evident when dedicated scopes and holders were used.

Giant and Very Large Intracranial Aneurysms: Surgical Strategies and Special Issues.

Giant intracranial aneurysms (GIAs) and very large intracranial aneurysms (VLAs) have a poor natural history because of a high incidence of bleeding and strokes. These lesions always represent a great challenge for neurosurgeons and interventional neuroradiologists because of some peculiar intrinsic features such as size, angioarchitecture, wide neck, mass effect, intraluminal thrombosis, atherosclerotic changes, involvement of branches and perforators, and a frequent need to perform revascularization procedures. The results of a cumulative surgical series of 75 VLAs and GIAs are reported. Thirty-three aneurysms were unruptured. Sixty aneurysms underwent direct surgical treatment consisting of 56 direct clippings, 3 trappings w/o revascularization, and 1 wrapping. Fifteen aneurysms were treated by means of extracranial to intracranial (EC-IC) high-flow bypass. An mRS score ranging between 0 and 2 was observed in 54 patients, whereas an mRS of 3 was seen in 5 patients. Four patients had a severe disability (mRS 4-5) and six patients died. Aneurysm's fragmentation, with stacking and seating clips, thrombectomy, and aneurysmorrhaphy were the techniques most frequently employed. Revascularization options involving EC-IC high-flow bypass were used in cases not amenable for direct treatment. Some technical tips and special issues related to the surgical management of these complex lesions are discussed.

Surgical Treatment of Arteriovenous Malformations: Role of Preoperative Staged Embolization.

Preoperative embolization is complementary to surgery for large brain arteriovenous malformations (AVMs). From January 2005 to December 2015, 69 patients harboring an AVM were managed in our department by the same surgeon (RG). Forty one were ruptured and 65 were supratentorial. Thirty nine smaller AVMs were treated with surgery stand-alone, whereas, for 30 larger malformations, surgery was combined with adjuvant treatment involving preoperative staged embolization and/or, less frequently, radiosurgery. In all patients treated with surgery alone, complete resection of AVM was achieved. A successful preoperative partial endovascular obliteration of AVM was obtained in 24 out of 27 more complex cases, with a zero mortality rate and a very low morbidity. Here, embolization was of a certain utility in the handling of deeper feeders and nidus excision, also facilitating intraoperative hemostasis. In three cases of residuals, radiosurgery was performed. In those patient treated with a combined approach, a good overall outcome, 0-2 modified Rankin Scale (mRS), was achieved in 25 cases. Preoperative embolization proved to be a reasonable option complementary to high-grade AVMs surgery, reducing the frequency of breakthrough hemorrhages, aiding the elimination of deep feeders, and making the nidus dissection easier.

Scale-free structural organization of oxygen interstitials in La(2)CuO(4+y).

It is well known that the microstructures of the transition-metal oxides, including the high-transition-temperature (high-T(c)) copper oxide superconductors, are complex. This is particularly so when there are oxygen interstitials or vacancies, which influence the bulk properties. For example, the oxygen interstitials in the spacer layers separating the superconducting CuO(2) planes undergo ordering phenomena in Sr(2)O(1+y)CuO(2) (ref. 9), YBa(2)Cu(3)O(6+y) (ref. 10) and La(2)CuO(4+y) (refs 11-15) that induce enhancements in the transition temperatures with no changes in hole concentrations. It is also known that complex systems often have a scale-invariant structural organization, but hitherto none had been found in high-T(c) materials. Here we report that the ordering of oxygen interstitials in the La(2)O(2+y) spacer layers of La(2)CuO(4+y) high-T(c) superconductors is characterized by a fractal distribution up to a maximum limiting size of 400 mum. Intriguingly, these fractal distributions of dopants seem to enhance superconductivity at high temperature.

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career.

BACKGROUND: Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma. RESULTS: The concentrations of IL1-ß, IL-6, TNF-α in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-α in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3. CONCLUSIONS: Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-α can reliably predict radiographic progression of PTOA.