Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.

Role of structural disorder in the vibrational spectra of sol-gel γ and δ-Al2O3 nanoparticles.

Alumina nanopowders belonging to the γ and δ transition phases have been characterized by infrared and Raman spectroscopies. A quantitative interpretation of their vibrational spectra has been provided and related to their crystal structure, with particular emphasis on structural disorder and features not predicted by group-theoretical considerations. Both phases show very similar infrared dielectric functions, but with clear instances of mode-splitting in the δ phase, which are related to ordering in the tetrahedral Al positions. Raman spectroscopy was unable to resolve any modes in the sample identified as γ phase, but the full lattice vibrational region could be measured for the δ sample under UV and red excitation lines. Raman spectra are more complex than those obtained by infrared spectroscopy and cannot be completely explained by factor group analysis, in the absence of dedicated theoretical studies. Finally, the luminescent properties of these materials have been qualitatively explored and linked to disorder and substitutional impurities. In general, the results contained in this work prove that vibrational spectroscopies are powerful tools for quantitative analyses of these disordered nanomaterials and suggest the need for more theoretical work to understand their vibrational properties.

Expert recommendations about the use of gadoxetic acid in patients with liver metastases in Spain.

BACKGROUND AND AIMS: Magnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain. MATERIAL AND METHODS: This project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts. RESULTS: The experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment. CONCLUSION: The results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1 cm, thus facilitating early diagnosis of metastatic spread.

Improving Keyword-Based Topic Classification in Cancer Patient Forums with Multilingual Transformers.

Online forums play an important role in connecting people who have crossed paths with cancer. These communities create networks of mutual support that cover different cancer-related topics, containing an extensive amount of heterogeneous information that can be mined to get useful insights. This work presents a case study where users' posts from an Italian cancer patient community have been classified combining both count-based and prediction-based representations to identify discussion topics, with the aim of improving message reviewing and filtering. We demonstrate that pairing simple bag-of-words representations based on keywords matching with pre-trained contextual embeddings significantly improves the overall quality of the predictions and allows the model to handle ambiguities and misspellings. By using non-English real-world data, we also investigated the reusability of pretrained multilingual models like BERT in lower data regimes like many local medical institutions.

[Sepsis Code: dodging mortality in a tertiary hospital]. / Código Sepsis: esquivando la mortalidad en un hospital terciario.

OBJECTIVE: In the hospital of La Princesa, the "Sepsis Code" (CSP) began in 2015, as a multidisciplinary group that provides health personnel with clinical, analytical and organizational tools, with the aim of the detection and early treatment of patients with sepsis. The objective of this study is to evaluate the impact of CSP implantation on mortality and to determine the variables associated with an increase in it. METHODS: A retrospective analytical study of patients with CSP alert activation from 2015 to 2018 was conducted. Clinical-epidemiological variables, analytical parameters, and severity factors such as admission to critical care units (UCC) and the need for amines were collected. Statistical significance was established at p < 0.05. RESULTS: We included 1,121 patients. The length of stay was 16 days and 32% required admission to UCC. Mortality showed a statistically significant linear downward trend from 24% in 2015 to 15% in 2018. The predictive mortality variables with statistically significant association were lactate > 2 mmol/L, creatinine > 1.6 mg/dL and the need for amines.>5.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. CONCLUSIONS: The implementation of Sepsis Code decreases the mortality of patients with sepsis and septic shock. The presence of a lactate > 2 mmol/L, creatinine > 1.6 mg/dL and/or the need to administer amines in the first 24 hours, are associated with an increase in mortality in the patient with sepsis.

Enhanced thermal conduction by surface phonon-polaritons.

Improving heat dissipation in increasingly miniature microelectronic devices is a serious challenge, as the thermal conduction in nanostructures is markedly reduced by increasingly frequent scattering of phonons on the surface. However, the surface could become an additional heat dissipation channel if phonons couple with photons forming hybrid surface quasiparticles called surface phonon-polaritons (SPhPs). Here, we experimentally demonstrate the formation of SPhPs on the surface of SiN nanomembranes and subsequent enhancement of heat conduction. Our measurements show that the in-plane thermal conductivity of membranes thinner than 50 nm doubles up as the temperature rises from 300 to 800 kelvin, while thicker membranes show a monotonic decrease. Our theoretical analysis shows that these thickness and temperature dependencies are fingerprints of SPhP contribution to heat conduction. The demonstrated thermal transport by SPhPs can be useful as a previously unidentified channel of heat dissipation in a variety of fields including microelectronics and silicon photonics.

Patrón de Brugada en paciente tratada con amitriptilina / The Brugada pattern in a patient treated with amitriptyline

No disponible

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Assessment of myofascial medialization following posterior component separation via transversus abdominis muscle release in a cadaveric model.

PURPOSE: Posterior component separation (PCS) via the transversus abdominis release (TAR) procedure continues to gain popularity. However, neither the physiologic basis nor the extent of myofascial medialization after TAR is established. We aimed to assess both anterior and posterior rectus fascia (AF and PF) medialization following each step of the TAR procedure. METHODS: Ten fresh cadavers underwent PCS via TAR. Steps included midline laparotomy (MLL), retrorectus dissection (RRD), incision of the posterior rectus sheath (IPL), transversus abdominis muscle division (TAD), and retromuscular dissection (RMD). Medial advancement of AF and PF was measured following application of 2.5, 5.0 lb, and maximal tension to the fascial edge. Values are represented as mean advancement past midline in centimeters. RESULTS: MLL allowed advancement of 2.5, 3.7, and 4.9 cm. RRD provided advancement of 4.1, 5.9, and 7.6 cm for AF and 4.4, 6.2, and 7.5 cm for PF. IPL provided advancement of 4.2, 6.1, and 8.0 cm for AF and 4.6, 6.6, and 8.3 cm for PF. TAD provided advancement of 4.5, 6.6, and 8.6 cm for AF and 5.3, 7.5, and 9.5 cm for PF. RMD provided advancement of 5.5, 7.9, and 9.9 cm for AF and 6.9, 9.6, and 11.2 cm for PF. Overall, the complete TAR procedure provided AF advancement of 102% and PF advancement of 129%, over baseline. CONCLUSIONS: The TAR procedure provides for substantial medial advancement of both anterior and posterior myofascial components of the abdominal wall. Retromuscular dissection deep to the divided transversus abdominis muscle appears to be the key step of the procedure, allowing for effective reconstruction of very wide (≈ 20 cm) defects.

Tumor suppressor SET9 guides the epigenetic plasticity of breast cancer cells and serves as an early-stage biomarker for predicting metastasis.

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

Targeting the epigenetics of the DNA damage response in breast cancer.

Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Because the epigenetic factors involved in the DNA damage response are regulated by multiple elements, therapies to target specific components of the epigenetic machinery can be inefficient. In contrast, therapies aimed at inhibiting the methionine cycle can indirectly inhibit both DNA and protein methylation, and the wide variety of genes and pathways that are affected by these methylations make this global strategy very attractive. In the present study, we propose an adjuvant therapy that targets the epigenetics of the DNA damage response in breast cancer cells and that results in efficient apoptosis and a reduction in distant metastases in vivo. We observed that a combined therapy designed to uncouple adenosine metabolism using dipyridamole in the presence of a new synthetic antifolate, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin, simultaneously and efficiently blocked both the folic cycle and the methionine cycle in breast cancer cells and sensitized these cells to radiotherapy. The treatment impeded the recruitment of 53BP1 and BRCA1 to the chromatin regions flanking DNA double-strand breaks and thereby avoided the DNA damage responses in breast cancer cells that were exposed to ionizing radiation. In addition, this hypomethylating therapy was also efficient in reducing the self-renewal capability of breast cancer-initiating cells and induced reversion of mesenchymal phenotypes in breast cancer cells.

Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.

Idiopathic achalasia is a disease of unknown etiology. The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism. Thirty-two patients diagnosed by high-resolution manometry with achalasia were included. Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control). Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed. Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence. Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry. Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%). Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls (P < 0.001). Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors (P < 0.01). Type III achalasia patients exhibited the highest inflammatory response versus types I and II. Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls. Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.

Targeting the epigenetic machinery of cancer cells.

Cancer is characterized by uncontrolled cell growth and the acquisition of metastatic properties. In most cases, the activation of oncogenes and/or deactivation of tumour suppressor genes lead to uncontrolled cell cycle progression and inactivation of apoptotic mechanisms. Although the underlying mechanisms of carcinogenesis remain unknown, increasing evidence links aberrant regulation of methylation to tumourigenesis. In addition to the methylation of DNA and histones, methylation of nonhistone proteins, such as transcription factors, is also implicated in the biology and development of cancer. Because the metabolic cycling of methionine is a key pathway for many of these methylating reactions, strategies to target the epigenetic machinery of cancer cells could result in novel and efficient anticancer therapies. The application of these new epigenetic therapies could be of utility in the promotion of E2F1-dependent apoptosis in cancer cells, in avoiding metastatic pathways and/or in sensitizing tumour cells to radiotherapy.

Phase transformations of crystalline SiO2 versus dynamic disorder between room temperature and liquid state.

The sequence of phase transitions of crystalline silica has been probed by infrared emission spectroscopy. The lattice dynamics, deeply impacted by the low frequency dynamic disorder, exhibit with increasing temperature signs of inhomogeneous broadening of the symmetry allowed normal modes. High frequency supplementary components are also activated. The analysis with a causal Voigt dielectric function model within the framework of hard mode spectroscopy allowed a fine characterization of solid­solid phase transitions. We also report experimental evidence showing that the occurrence of the intermediate ill-defined region above 1300 K is concomitant with the reactivation of the low frequency dynamic disorder; a behavior change that on the way explains the appearance of the negative thermal expansion regime.

Castleman's Disease: A Case Report of the Unicentric Type.

Castleman's disease, or angiofollicular lymph node hyperplasia, is a relatively rare disorder characterized by the benign proliferation of lymphoid tissue related to the chronic human herpes virus 8 (HHV-8) infection and the human immunodeficiency virus (HIV). Two clinical entities have been described: a unicentric presentation with the disease confined to a single anatomic lymph node and a multicentric presentation characterized by generalized lymphadenopathy and a more aggressive clinical course. Also, three histopathological subtypes have been described: hyaline-vascular, plasma cell, and a mixed variant. Preoperative diagnosis of hyaline-vascular Castleman's disease is difficult, and the definitive result is based on postoperative pathological findings. The gold standard therapy is the complete surgical excision.

The anti-inflammatory and anti-cancer properties of epigallocatechin-3-gallate are mediated by folate cycle disruption, adenosine release and NF-kappaB suppression.

OBJECTIVE: To understand the mechanism by which (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, exerts its anti-inflammatory action. METHODS: To check our hypothesis that the anti-inflammatory properties of EGCG could be related to its antifolate action and whether adenosine and its receptors are involved in EGCG action, we investigated the EGCG-induced suppression of NF-kappaB in Caco-2 cell monolayer, which acted as a model of the human intestinal epithelium. RESULTS: We demonstrate that the anti-inflammatory properties of EGCG are associated with its antifolate activity. By using a natural stable folate we were able to reverse the EGCG suppression of TNF-alpha-induced NF-kappaB activation, the phosphorylation and degradation of IkappaBalpha and the phosphorylation of Akt in this human colon carcinoma cell line. These suppressions were mediated by the release of adenosine following disruption of the folate cycle by EGCG. By binding to its specific receptors, adenosine can modulate the Akt and NF-kappaB pathway. Moreover, EGCG produces a significant increase in a specific adenosine receptor, which could explain the suppression of the constitutive activation of NF-kappaB in colon cancer cells. CONCLUSIONS: The data suggest that by modulating NF-kappaB activation, EGCG might not only combat inflammation, but also cancer.

Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin.

BACKGROUND AND PURPOSE: The present study was designed to assess whether cyclooxygenase-2 (COX-2) activation is involved in the effects of chronic aldosterone treatment on endothelial function of mesenteric resistance arteries (MRA) from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH: Relaxation to acetylcholine was measured in MRA from both untreated and aldosterone-treated strains. Vasomotor responses to prostacyclin and U46619 were also analysed. Release of 6-oxo-prostaglandin (PG)F1alpha and thromboxane B2 (TxB2) was determined by enzyme immunoassay. COX-2 protein expression was measured by western blot. KEY RESULTS: Aldosterone reduced acetylcholine relaxation in MRA from both strains. In MRA from both aldosterone-treated strains the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively), TxA2 synthesis inhibitor (furegrelate), prostacyclin synthesis inhibitor (tranylcypromine) or TxA2/ PGH2 receptor antagonist (SQ 29 548), but not COX-1 inhibitor SC-560, increased acetylcholine relaxation. In untreated rats this response was increased only in SHR. Prostacyclin elicited a biphasic vasomotor response: lower concentrations elicited relaxation, whereas higher concentrations elicited contraction that was reduced by SQ 29 548. Aldosterone increased the acetylcholine-stimulated production of 6-oxo-PGF(1alpha) and TxB2 in MRA from both strains. COX-2 expression was higher in both strains of rats treated with aldosterone. CONCLUSIONS AND IMPLICATIONS: Chronic treatment with aldosterone impaired endothelial function in MRA under normotensive and hypertensive conditions by increasing COX-2-derived prostacyclin and thromboxane A2. As endothelial dysfunction participates in the pathogenesis of many cardiovascular disorders we hypothesize that anti-inflammatory drugs, specifically COX-2 inhibitors, could ameliorate vascular damage in patients with elevated aldosterone production.

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery.

The aim of this study was to analyze whether endogenous male sex hormones influence the release of thromboxane A2(TXA2) and its role in the electrical field stimulation (EFS)-induced response, as well as the mechanism involved. For this purpose, endothelium-denuded mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used to measure TXA2 release; EFS-induced response, nitric oxide (NO), norepinephrine (NA), and prostaglandin (PG) I2 release were also measured in the presence of the TXA2 synthesis inhibitor furegrelate. Orchidectomy increased basal and EFS-induced TXA2 release. Furegrelate decreased the EFS-induced contraction in arteries from control rats, but did not modify it in arteries from orchidectomized rats. The EFS-induced neuronal NO release and vasodilator response were increased by furegrelate in arteries from control rats, but were not modified in arteries from orchidectomized rats. Furegrelate did not modify the EFS-induced NA release or vasoconstrictor response in arteries from either control or orchidectomized rats. The EFS-induced PGI2 release was not modified by furegrelate in arteries from control rats, but was increased in arteries from orchidectomized rats. The results of the present study show that endogenous male sex hormone deprivation i) increases non-endothelial TXA2 release and ii) regulates the effect of endogenous TXA2 on the EFS-induced response through different mechanisms that, at the least, involve the NO and PGI2 systems. In arteries from control rats, inhibition of TXA2 formation decreases the EFS-induced response by increasing neuronal NO release. In arteries from orchidectomized rats, the EFS-induced response is unaltered after the inhibition of TXA2 formation, by increasing PGI2 release.

Orchidectomy increases beta-adrenoceptor activation-mediated neuronal nitric oxide and noradrenaline release in rat mesenteric artery.

BACKGROUND/AIMS: A previous study has demonstrated that endogenous male sex hormones do not alter neuronal nitric oxide (NO) release in rat mesenteric artery. However, the regulatory role of endogenous male sex hormones on noradrenaline (NA) release in rat mesenteric artery is not known. The present study was designed to analyze whether endogenous male sex hormones influence the NA release induced by electrical field stimulation (EFS), as well as the possible modification in NA and neuronal NO release by presynaptic beta-adrenoceptor activation. METHODS: For this purpose, mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used. Basal and EFS-induced neuronal NO and NA release, as well as the contractile effect induced by EFS, was measured. RESULTS: Basal and EFS-induced neuronal NO and NA release were similar in arteries from control and orchidectomized rats. The beta-adrenoceptor agonist clenbuterol did not modify EFS-induced neuronal NO and NA release in arteries from control rats. In contrast, in arteries from orchidectomized animals, clenbuterol increased both neuronal NO and NA release; this increase was prevented by incubation with the beta-adrenoceptor antagonist propranolol. However, the contractile response elicited by EFS was not modified by clenbuterol in either group of rats. CONCLUSIONS: These results show that orchidectomy does not alter the EFS-induced NA release. What is more, activation of presynaptic beta-adrenoceptors does not modify EFS-induced NA and neuronal NO release in arteries from control rats although it increases the release of both neurotransmitters in arteries from orchidectomized rats. Despite these modifications, the EFS-induced contractile response is preserved in arteries from orchidectomized rats.