Ultrasound-Assisted, Catheter-Directed Thrombolysis for Acute Intermediate/High-Risk Pulmonary Embolism: Design of the Multicenter USAT IH-PE Registry and Preliminary Results.

Catheter-based revascularization procedures were developed as an alternative to systemic thrombolysis for patients with intermediate-high- and high-risk pulmonary embolisms. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow-up. Secondary endpoints were short- and mid-term changes in the echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high-risk PE (86%), were mostly female (57%), and had a mean age of 63.7 ± 14.5 years, and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one, the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 h and at follow-up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74), while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, of whom 4.9% were BARC ≥ 3. Preliminary results from the USAT IH-PE registry showed a low incidence of PH, improvement in RV function, and a safe profile.

Clinical and Prognostic Implications of Estimating Glomerular Filtration Rate by Three Different Creatinine-Based Equations in Older Nursing Home Residents.

Background: According to the international literature, the percentage of nursing home (NH) residents with renal insufficiency is very high, ranging between 22 and 78%. Diminished kidney function represents a risk factor for drug overdosage, adverse drug reactions, end-stage renal disease, disability, morbidity, and mortality. Several studies suggested that screening for chronic kidney disease (CKD) in high-risk and older populations may represent a cost-effective approach to reducing progression to renal failure and CKD mortality. Objective: This study aimed (i) to investigate to what extent CKD may be staged interchangeably by three different creatinine-based estimated glomerular filtration rate (eGFR) equations in a sample of older adults living in long-term care facilities; (ii) to investigate factors explaining differences among eGFR equations; and (iii) to compare the predictivity of different creatinine-based eGFR equations with respect to all-cause mortality. Methods: A total of 522 residents aged 65 years and older participated in a prospective cohort study of 9 long-term care facilities in Calabria. eGFR was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Berlin initiative study (BIS), and full age spectrum (FAS) equations. Disability in at least one activity of daily living (ADL), depression, cognitive impairment, comorbidity, and malnutrition was considered in the analysis. Statistical analysis was carried out by Bland-Altman analysis, and 2-year mortality was investigated by Kaplan-Meier curves and Cox regression analysis. Results: Depending on the adopted equation, the prevalence of NH residents with impaired renal function (eGFR < 60 ml/min/1.73 m2) ranged between 58.2% for the CKD-EPI and 79.1% for the BIS1 equation. The average difference between BIS and FAS was nearly negligible (0.45 ml/min/1.73 m2), while a significant bias was detected between CKD-EPI and BIS and also between CKD-EPI and FAS (6.21 ml/min/1.73 m2 and 6.65 ml/min/1.73 m2, respectively). Although the eGFR study equations had comparable prognostic accuracy in terms of mortality risk, BIS and FAS were able to reclassify NH residents pertaining to a low-risk group with CKD-EPI, and this reclassification improves the discriminative capacity of CKD-EPI with respect to overall mortality. Conclusion: Despite the relatively good correlation between eGFRs calculated using all adopted equations, the findings in this study reported clearly demonstrated that CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people and particularly in institutionalized and frail older subjects.

Portal Steal Syndrome From a Large Linton's Splenorenal Shunt after Liver Transplantation: Successful Endovascular Management Through Off-Label Application of a 30 mm Amplatzer Cardiac Plug.

A 34-year-old patient underwent liver transplantation for progressive hepatic failure in the setting of congenital hepatic fibrosis. In past medical history, the patient had undergone splenectomy with proximal Linton's splenorenal surgical shunt creation for symptomatic portal hypertension with hypersplenism. The patient developed an early allograft dysfunction, with radiologic evidence of a reduced portal flow associated to portal steal from the patent surgical shunt. The patient was successfully treated through endovascular placement of a 30 mm Amplatzer cardiac plug at the origin of the splenic vein.

CT and MRI radiomics of bone and soft-tissue sarcomas: a systematic review of reproducibility and validation strategies.

BACKGROUND: Feature reproducibility and model validation are two main challenges of radiomics. This study aims to systematically review radiomic feature reproducibility and predictive model validation strategies in studies dealing with CT and MRI radiomics of bone and soft-tissue sarcomas. The ultimate goal is to promote achieving a consensus on these aspects in radiomic workflows and facilitate clinical transferability. RESULTS: Out of 278 identified papers, forty-nine papers published between 2008 and 2020 were included. They dealt with radiomics of bone (n = 12) or soft-tissue (n = 37) tumors. Eighteen (37%) studies included a feature reproducibility analysis. Inter-/intra-reader segmentation variability was the theme of reproducibility analysis in 16 (33%) investigations, outnumbering the analyses focused on image acquisition or post-processing (n = 2, 4%). The intraclass correlation coefficient was the most commonly used statistical method to assess reproducibility, which ranged from 0.6 and 0.9. At least one machine learning validation technique was used for model development in 25 (51%) papers, and K-fold cross-validation was the most commonly employed. A clinical validation of the model was reported in 19 (39%) papers. It was performed using a separate dataset from the primary institution (i.e., internal validation) in 14 (29%) studies and an independent dataset related to different scanners or from another institution (i.e., independent validation) in 5 (10%) studies. CONCLUSIONS: The issues of radiomic feature reproducibility and model validation varied largely among the studies dealing with musculoskeletal sarcomas and should be addressed in future investigations to bring the field of radiomics from a preclinical research area to the clinical stage.

Dataset of the experimental behavior of an asymmetric self-centering dissipative device.

The paper presents the whole dataset obtained during an experimental test campaign executed on the prototype of a new re-centering dissipative device, characterized by an asymmetric behavior, for the seismic protection of buildings. The experimental tests were performed on two different configurations: on the single prototype of the device (configuration 1) and one in which two prototypes are placed within a steel frame in an inverted V bracings configuration (configuration 2). The experimental tests were executed in displacement control, applying cyclic loading histories. Data are mainly reported in terms of force-displacement cyclic curves for the single prototype in the configuration 1 and for the whole braced system in the configuration 2.

Endovascular Treatment of Acute Posttransplant Portal Vein Thrombosis Due to Portal Steal From Mesocaval And Coronary Portosystemic Shunts.

The management of portosystemic shunts in liver transplant recipients relies on appropriate perioperative study. There are several strategies for shunt handling, ranging from preoperative interventional procedures to intraoperative surgical interruption or embolization. Appropriate management often results in a successful outcome, although wrong decisions could lead to serious consequences. Here, we report a liver transplant recipient with grade 2 portal vein thrombosis associated with 2 large portosystemic shunts (coronary and mesocaval), which were managed intraoperatively via thrombectomy without shunt ligation. Acute portal vein thrombosis developed early after transplant due to portal steal syndrome. The patient underwent a successful endovascular shunt embolization, with prompt restoration of hepatopetal portal flow and resolution of the portal steal. Use of interventional radiology in perioperative management of transplant patients has recently gained wider importance; our case reported here is particularly suggestive of the good outcomes of a multidisciplinary approach to a threatening complication such as postoperative acute portal vein thrombosis.

Experimental tests on real-scale EBF structures with horizontal and vertical links.

The paper presents data achieved during an experimental test campaign executed on real-scale one storey/one bay EBF steel structures with vertical and horizontal links. Experimental tests were executed in displacement control by applying cyclic loading histories following ECCS45 protocol and constant amplitude-imposed displacements. Data provide indications concerning the energy dissipated by each prototype during tests, the corresponding shear force - angular distortion curves of the dissipative link and, besides, the force-displacement behavior of the steel prototypes until failure.

Dataset on the cyclic experimental behavior of Steel frames with Reinforced Concrete infill Walls.

This paper presents the experimental data on the cyclic behavior of Steel frames with Reinforced Concrete infill Walls (SRCW). Two specimens, characterized by a different shear studs distribution, have been tested: the first one is provided with shear studs positioned only in the four corners of the steel frame; the second one presents shear studs all distributed along the perimeter of the steel frame except for the zone of the dissipative fuses. The overall setup, loading protocol, collapse mechanisms, force-displacement curves for both the whole system and the main single components are described for the two tested prototypes.

Cooled tip radiofrequency ablation of benign thyroid nodules: preliminary experience with two different devices.

BACKGROUND: Thyroid nodules are very common in general population. Even if benign, they may require a treatment in case of symptoms or cosmetic concerns. In the last years, minimally invasive treatments alternative to surgery have been developed, in particular ultrasound (US) guided radiofrequency ablation (RFA). METHODS: Twenty-four patients (9 males; 15 females; mean age 57.9 years) were treated and divided in two groups (A and B) according to the RFA needle used (18 gauge needle, AMICA; 17 gauge needle, COVIDIEN). Nodules and patients characteristics, together with procedural data were registered pre-treatment and at 1-month follow-up. US visibility of the needle, volume of the nodules, symptoms and cosmetic concerns, complications were registered. RESULTS: Visibility of the needle was not significantly different in the two groups (P=0.0787). At 1 month the mean volume of the nodules dropped from 37.1 to 25 mL in group A and from 23.2 to 15.4 mL in group B; shrinkage rate (36.9% and 39.5%, respectively) was not significantly different (P=0.3137). Symptoms decreased from 3.1 to 1.4 in group A and from 4 to 1.6 in group B: no significant differences in reductions were observed (P=0.3305). Cosmetic score decreased from 3.7 to 3.4 in group A and from 3.9 to 3.6 in group B: no significant differences in reductions were observed (P=0.96). Total complication rate (18.2% in group A vs. 23.1% in group B) did not showed significant differences (P=0.5049). CONCLUSIONS: The two systems used in our study resulted equivalent in terms of US needle visibility, efficacy, symptom/cosmetic relief, safety. More patients and a longer follow-up are necessary to confirm our results.

Influence of Tension Stiffening on the Flexural Stiffness of Reinforced Concrete Circular Sections.

Within this paper, the assessment of tension stiffening effects on a reinforced concrete element with the circular sections subjected to axial and bending loads is presented. To this purpose, an enhancement of an analytical model already present within the actual technical literature is proposed. The accuracy of the enhanced method is assessed by comparing the experimental results carried out in past research and the numerical ones obtained by the model. Finally, a parametric study is executed in order to study the influence of axial compressive force on the flexural stiffness of reinforced concrete elements that are characterized by a circular section, comparing the secant stiffness evaluated at yielding and at maximum resistance, considering and not considering the effects of tension stiffness.

Prediction of chronic damage in systemic lupus erythematosus by using machine-learning models.

OBJECTIVE: The increased survival in Systemic Lupus Erythematosus (SLE) patients implies the development of chronic damage, occurring in up to 50% of cases. Its prevention is a major goal in the SLE management. We aimed at predicting chronic damage in a large monocentric SLE cohort by using neural networks. METHODS: We enrolled 413 SLE patients (M/F 30/383; mean age ± SD 46.3±11.9 years; mean disease duration ± SD 174.6 ± 112.1 months). Chronic damage was assessed by the SLICC/ACR Damage Index (SDI). We applied Recurrent Neural Networks (RNNs) as a machine-learning model to predict the risk of chronic damage. The clinical data sequences registered for each patient during the follow-up were used for building and testing the RNNs. RESULTS: At the first visit in the Lupus Clinic, 35.8% of patients had an SDI≥1. For the RNN model, two groups of patients were analyzed: patients with SDI = 0 at the baseline, developing damage during the follow-up (N = 38), and patients without damage (SDI = 0). We created a mathematical model with an AUC value of 0.77, able to predict damage development. A threshold value of 0.35 (sensitivity 0.74, specificity 0.76) seemed able to identify patients at risk to develop damage. CONCLUSION: We applied RNNs to identify a prediction model for SLE chronic damage. The use of the longitudinal data from the Sapienza Lupus Cohort, including laboratory and clinical items, resulted able to construct a mathematical model, potentially identifying patients at risk to develop damage.

International consensus conference on open abdomen in trauma.

BACKGROUND: A part of damage-control laparotomy is to leave the fascial edges and the skin open to avoid abdominal compartment syndrome and allow further explorations. This condition, known as open abdomen (OA), although effective, is associated with severe complications. Our aim was to develop evidence-based recommendations to define indications for OA, techniques for temporary abdominal closure, management of enteric fistulas, and methods of definitive wall closure. METHODS: The literature from 1990 to 2014 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-analyses] protocol. Seventy-six articles were reviewed by a panel of experts to assign grade of recommendations (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] system, and an international consensus conference was held. RESULTS: OA in trauma is indicated at the end of damage-control laparotomy, in the presence of visceral swelling, for a second look in vascular injuries or gross contamination, in the case of abdominal wall loss, and if medical treatment of abdominal compartment syndrome has failed (GoR B, LoE II). Negative-pressure wound therapy is the recommended temporary abdominal closure technique to drain peritoneal fluid, improve nursing, and prevent fascial retraction (GoR B, LoE I). Lack of OA closure within 8 days (GoR C, LoE II), bowel injuries, high-volume replacement, and use of polypropylene mesh over the bowel (GoR C, LoE I) are risk factors for frozen abdomen and fistula formation. Negative-pressure wound therapy allows to isolate the fistula and protect the surrounding tissues from spillage until granulation (GoR C, LoE II). Correction of fistula is performed after 6 months to 12 months. Definitive closure of OA has to be obtained early (GoR C, LoE I) with direct suture, traction devices, component separation with or without mesh. Biologic meshes are an option for wall reinforcement if bacterial contamination is present (GoR C, LoE II). CONCLUSION: OA and negative-pressure techniques improve the care of trauma patients, but closure must be achieved early to avoid complications.

Microwave ablation for thyroid nodules: a new string to the bow for percutaneous treatments?

BACKGROUND: Thyroid nodules are a fairly common finding in general population and, even if most of them are benign, a treatment can be however necessary. In the last years, non surgical minimally invasive techniques have been developed to treat this pathology, starting from percutaneous ethanol injection (PEI), to laser ablation (LA), radiofrequency ablation (RFA) and, most recently, microwave ablation (MWA). METHODS: We reviewed all medical literature searching in pubmed.gov the terms "microwave" & "thyroid". We found three original studies concerning MWA treatment, for a total of 263 patients (mean age 51.0 years; range, 15-80 years; male to female ratio 2.55) and 522 nodules. RESULTS: A total of 522 nodules (338 solid, 22 cystic, 162 mixed) in 263 patients were treated. Studies have shown a mean reduction in volume of thyroid nodules ranging from 45.9% to 65%. No study reported a significant and definitive change in laboratory parameters, except for one case (Heck et al.). No studies have reported major complications after procedure. CONCLUSIONS: MWA is a new, promising technique among the minimally invasive treatments of thyroid nodules. Actually, the larger diameter of MW antenna seems to be the major limiting factor in the use of this technique. More studies are necessary to evaluate feasibility, safety and efficacy of the procedure.

Alexithymia and cancer pain: the effect of psychological intervention.

BACKGROUND: Alexithymia is likely to be involved in the pain experience of cancer patients, but the extent to which psychological interventions may modify both pain and alexithymia is unclear. METHODS: A group of 52 consecutive cancer patients were enrolled in a 6-month multicomponent psychological intervention trial, and compared to 52 control patients who received standard medical care. Validated scales for pain, alexithymia, coping with disease, illness behavior, psychological distress, and psychosocial functioning were administered at baseline and 6 months later. RESULTS: Pain was strongly associated with alexithymia and several psychological dimensions. Although at baseline patients in the intervention group had worse psychological and somatic health, at follow-up their level of pain intensity, alexithymia, and somatic concerns had significantly improved compared to control patients. Patients in the intervention group showed dramatic improvements in pain perception, alexithymia, and other psychological variables, while control patients showed an unexpected significant worsening of alexithymia, depression, and adjustment to disease. Multiple regression showed that psychological intervention and alexithymia were both independently associated with the reduction in pain perception. CONCLUSIONS: These findings confirm the close association between alexithymia and pain, and show that multicomponent psychological intervention may significantly reduce both alexithymia and cancer pain. Although the present findings need replication, they should strongly encourage clinicians to provide patients with psychological interventions targeting alexithymic difficulties and helping patients to cope better with both feelings and somatic perception.

A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells.

Organisms exposed to ionizing radiation are mainly damaged by free radicals, which are generated by the radiolysis of water contained in the cells. Recently a significant reduction of tissue injury from irradiation damage was demonstrated by using MnSOD-plasmid/liposome treatments in the protection of murine lung. In this study we show that a new active recombinant human MnSOD (rMnSOD), easily administered in vivo, not only exerts the same radioprotective effect on normal cells and organisms as any MnSOD, but it is also radiosensitizing for tumor cells. In addition, we show how healthy animals, exposed to lethal doses of ionizing radiation and daily injections with rMnSOD, were protected from radiodamage and were still alive 30 days after the irradiation, while animals treated with only PBS solution, in the absence of rMnSOD, died after 7-8 days from the radiotreatments. The molecular analysis of all irradiated tissues revealed that the antiapoptotic AVEN gene appeared activated only in the animals treated in the presence of rMnSOD. The data suggest that rMnSOD deserves to be considered as a pharmaceutical tool for making radiotherapy more selective on cancer cells and to prevent and/or cure the accidental damage derived from exposure to ionizing radiation.

The immunomodulatory protein SV-IV protects serum-deprived cells against apoptosis but not against G0/G1 arrest: possible implications for the survival of implanting embryo.

Serum deprivation induced in human lymphoblastoid Raji cells oxidative stress-associated apoptotic death and G0/G1 cell cycle arrest. Addition into culture medium of the immunomodulatory protein Seminal vesicle protein 4 (SV-IV) protected these cells against apoptosis but not against cycle arrest. The antiapoptotic activity was related to: (1) decrease of endocellular reactive Oxygen species (ROS) (2) increase of mRNAs encoding anti-oxidant enzymes (catalase, G6PD) and antiapoptotic proteins (survivin, cox-1, Hsp70, c-Fos); (3) decrease of mRNAs encoding proapoptotic proteins (c-myc, Bax, caspase-3, Apaf-1). The biochemical changes underlaying these effects were probably induced by a protein tyrosine kinase (PTK) activity triggered by the binding of SV-IV to its putative plasma membrane receptors. The ineffectiveness of SV-IV to abrogate the cycle arrest was accounted for by its downregulating effects on D1,3/E G1-cyclins and CdK2/4 gene expression, ppRb/pRb ratio, and intracellular ROS concentration. In conclusion, these experiments: (1) prove that SV-IV acts as a cell survival factor; (2) suggest the involvement of a PTK in SV-IV signaling; (3) point to cell cycle-linked enzyme inhibition as responsible for cycle arrest; (4) provide a model to dissect the cycle arrest and apoptosis induced by serum withdrawal; (5) imply a possible role of SV-IV in the survival of hemiallogenic implanting embryos.

Chronic administration of bumetanide upregulates calbindin D28k mRNA and protein abundance in rat distal convoluted tubules.

BACKGROUND/AIMS: Calbindin D28k has been reported to be involved in transcellular calcium transport along the rat distal convoluted tubule (DCT). It has also been shown that administration of bumetanide is associated with hypercalciuria. The experiments reported here were designed to verify whether chronic infusion of this diuretic affects the gene expression and protein abundance of calbindin D28k along rat kidney DCT. METHODS: Bumetanide was subcutaneously infused by an osmotic minipump for 7 days at a rate of 1.5 mg x h(-1) x kg(-1). cDNA was synthesized from total RNA extracted from DCT microdissected from collagenase-treated kidneys. RESULTS: Calbindin D28k mRNA abundance, quantified by competitive PCR, was found to be 13.7 +/- 1.9 amol x ng(-1) total RNA in DCT of control rats (n = 4) as compared to 24.2 +/- 2.4 amol x ng(-1) total RNA in DCT of bumetanide- treated rats (n = 5) (p < 0.01). This effect was associated with a 52% increase (p < 0.005) in calbindin D28k protein abundance, as detected by Western blot performed on tissue slices from renal cortex (n = 4). CONCLUSION: These data not only demonstrate that bumetanide upregulates the mRNA and protein abundance of calbindin D28k in rat DCT, but also suggest that DCT calcium reabsorption is increased following the administration of this loop diuretic.

Transglutaminase-mediated polyamination of vasoactive intestinal peptide (VIP) Gln16 residue modulates VIP/PACAP receptor activity.

Previous data showing an increase of receptor binding activity of [R16]VIP, a vasoactive intestinal peptide (VIP) structural analogue containing arginine at the position 16 of its amino acid sequence, have pointed out the importance of a positive charge at this site. Here, the functional characterization of three VIP polyaminated adducts (VIPDap, VIPSpd, and VIPSpm), obtained by a transglutaminase-catalysed reaction between the VIP Gln16 residue and 1,3-diaminopropane (Dap), spermidine (Spd), or spermine (Spm), is reported. Appropriate binding assays and adenylate cyclase enzymatic determinations have shown that these VIP adducts act as structural VIP agonists, both in vitro and in vivo. In particular, their IC50 and EC50 values of human and rat VIP/pituitary adenylate cyclase activating peptide (PACAP)1 and VIP/PACAP2 receptors indicate that VIPDap is a VIP agonist, with an affinity and a potency higher than that of VIP, while VIPSpd and VIPSpm are also agonists but with affinities lower than that of VIP. These findings suggest that the difference in adduct agonist activity reflects the differences in the positive charge and carbon chain length of the polyamine covalently linked with the VIP Gln16 residue. In addition, the data obtained strongly suggest that the length of polyamine carbon chain could be critical for the interaction of the agonist with its receptor, even though possible hydrophobic interaction cannot be ruled out. In vivo experiments on murine J774 macrophage cell cultures have shown the ability of these compounds to stimulate the inducible nitric oxide synthase activity at the transcriptional level.

Protein SV-IV promotes nitric oxide production not associated with apoptosis in murine macrophages.

SV-IV (seminal vesicle protein no. 4) is a potent immunomodulatory and anti-inflammatory secretory protein (Mr 9758) produced in large amounts by the rat seminal vesicle epithelium. Here we show that this protein possesses the ability to upregulate in J774 macrophages the expression of the gene coding for the inducible nitric oxide synthase (iNOS). The increase in NO production consequent on the marked enhancement of iNOS activity was not associated with apoptotic damage of the SV-IV-treated cells. In the same experimental model, however, LPS induced upregulation of iNOS coupled with an increase in NO production and marked apoptotic death. Differences in the ability of SV-IV and LPS to control the life/ death signal balance in target cells via trans-membrane activation of apoptotic (mediated by TNF-alpha and NO/iNOS system) and anti-apoptotic (mediated by bcl-2, c-myc, etc.) pathways are suggested to be the basis of the apoptotic fate of the experimentally treated cells. In addition, considering the important role played by NO in the process of mammalian reproduction, SV-IV may be involved in the fine tuning of NO concentration in the female genital tract mucosa via an SV-IV-mediated control of iNOS gene expression in local macrophages.