Cosmological Tensions and the Transitional Planck Mass Model

In this followup analysis, we update previous constraints on the Transitional Planck Mass (TPM) modified gravity model using the latest version of EFTCAMB and provide new constraints using SPT and Planck anisotropy data along with Planck CMB lensing, BAO, SNe Ia, and an $H_0$ prior from local measurements. We find that large shifts in the Planck mass lead to large suppression of power on small scales that is disfavored by both SPT and Planck. Using only SPT TE-EE data, this suppression of power can be compensated for by an upward shift of the scalar index to $n_s = 1.003 \pm 0.016$ resulting in $H_0 = 71.94^{+0.86}_{-0.85}$ kms$^{-1}$Mpc$^{-1}$ and a $\sim7\%$ shift in the Planck mass. Including Planck TT $\ell \leq 650$ and Planck TE-EE data restricts the shift to be $<5\%$ at $2\sigma$ with $H_0 = 70.65 \pm 0.66$ kms$^{-1}$Mpc$^{-1}$. Excluding the $H_0$ prior, SPT and Planck data constrain the shift in the Planck mass to be $<3\%$ at $2\sigma$ with a best-fit value of $0.04\%$, consistent with the $\Lambda$CDM limit. In this case $H_0 = 69.09^{+0.69}_{-0.68}$ kms$^{-1}$Mpc$^{-1}$, which is partially elevated by the dynamics of the scalar-field in the late universe. This differs from EDE models that prefer higher values of $H_0$ when high $\ell$ Planck TT data are excluded. We additionally constrain TPM using RSD data from BOSS DR 12 and cosmic shear, galaxy-galaxy lensing, and galaxy clustering data from DES Y1 finding both disfavor transitions close to recombination, but earlier Planck mass transitions are allowed.Comment: 25 pages, 8 figures, 8 table

Experience with regorafenib in the treatment of hepatocellular carcinoma

Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib’s efficacy in HCC that led to regorafenib’s approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib’s potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study

Angiosarcoma of the breast: a new therapeutic approach?

Introduction Angiosarcomas are highly malignant endothelial cell tumors with poor prognosis. These can be due to breast cancer itself or to subsequent therapeutic modalities. No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Presentation of the case We report the case of a 76-year-old woman who developed an exuberant and aggressive post radiation angiosarcoma of the breast and discuss different aspects of therapy for this disease. A total left mastectomy was performed, followed by a right mastectomy. The lesions into the chest wall, and multiple abdominal skin nodules were treated with local Electrochemotherapy (ECT) with intravenous bleomicin. Discussion No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Electrochemotherapy (ECT) is an efficient palliative treatment of cutaneous and subcutaneous tumor nodules. It consists of the combination of a cytotoxic drug and electroporation, using appropriate electrical parameters; destabilization of the membrane is reversible, ensuring a high survival of permeabilized cells and the delivery of non-permeant molecules inside the cell. Conclusion Due to the rarity of the disease, prospective studies concerning adjuvant or neoadjuvant therapy are limited and no evidence-based guidelines exist. The response to chemotherapy seems to be poor. Treatment with ECT in addition to systemic chemotherapy achieves a complete response in all the lesions and improving patient body image perception

Healthcare professional and manager perceptions on drivers, benefits, and challenges of telemedicine: results from a cross-sectional survey in the Italian NHS

Background: The Covid-19 pandemic provided new challenges and opportunities for patients and healthcare providers while accelerating the trend of digital healthcare transformation. This study explores the perspectives of healthcare professionals and managers on (i) drivers to the implementation of telemedicine services and (ii) perceived benefits and challenges related to the use of telemedicine across the Italian National Health Service. Methods: An online cross-sectional survey was distributed to professionals working within 308 healthcare organisations in different Italian regions. Quantitative and qualitative data were collected through a self-administered questionnaire (June-September 2021). Responses were analysed using summary statistics and thematic analysis. Results: Key factors driving the adoption of telemedicine have been grouped into (i) organisational drivers (reduce the virus spread-80%; enhance care quality and efficiency-61%), (ii) technological drivers (ease of use-82%; efficacy and reliability-64%; compliance with data governance regulations-64%) and (iii) regulatory drivers (regulations’ semplification-84%). Nearly all respondents perceive telemedicine as useful in improving patient care (96%). The main benefits reported by respondents are shorter waiting lists, reduced Emergency Department attendance, decreased patient and clinician travel, and more frequent patient-doctor interactions. However, only 7% of respondents believe that telemedicine services are more effective than traditional care and 66% of the healthcare professionals believe that telemedicine can’t completely substitute in-person visits due to challenges with physical examination and patient-doctor relationships. Other reported challenges include poor quality and interoperability of telemedicine platforms and scarce integration of telemedicine with traditional care services. Moreover, healthcare professionals believe that some groups of patients experience difficulties in accessing and using the technologies due to socio-cultural factors, technological and linguistic challenges and the absence of caregivers. Conclusions: Respondents believe that telemedicine can be useful to complement and augment traditional care. However, many challenges still need to be overcome to fully consider telemedicine a standard of care. Strategies that could help address these challenges include additional regulations on data governance and reimbursements, evidence-based guidelines for the use of telemedicine, greater integration of tools and processes, patient-centred training for clinicians, patient-facing material to assist patients in navigating virtual sessions, different language options, and greater involvement of caregivers in the care process

Improving Healthcare Workers' Adherence to Surgical Safety Checklist: The Impact of a Short Training

Background: Although surgery is essential in healthcare, a significant number of patients suffer unfair harm while undergoing surgery. Many of these originate from failures in non-technical aspects, especially communication among operators. A surgical safety checklist is a simple tool that helps to reduce surgical adverse events, but even if it is fast to fill out, its compilation is often neglected by the healthcare workers because of unprepared cultural background. The present study aims to value the efficacy of a free intervention, such as a short training about risk management and safety checklist, to improve checklist adherence. Methods: In March 2019, the medical and nursing staff of the General Surgical Unit attended a two-lesson theoretical training concerning surgical safety and risk management tools such as the surgical safety checklist. The authors compared the completeness of the surgical checklists after and before the training, considering the same period (2 months) for both groups. Result: The surgical safety checklists were present in 198 cases (70.97%) before the intervention and 231 cases (96.25%) after that. After the training, the compilation adherence increased for every different type of healthcare worker of the unit (surgeons, nurses, anesthetists, and scrab nurses). Furthermore, a longer hospitalization was associated with a higher surgical checklist adherence by the operators. Conclusions: The results showed that a free and simple intervention, such as a two-lesson training, significantly stimulated the correct use of the surgical safety checklist. Moreover, the checklist adherence increased even for the operators who did not attend the training, maybe because of the positive influence of the colleagues' positive behaviors. As the results were promising with only two theoretical lessons, much more can be done to build a new safety culture in healthcare

Localization and detection of visual stimuli in monkeys with pulvinar lesions

Since the pulvinar receives a major ascending projection of the superior colliculus, pulvinar lesions might produce behavioral impairments resembling those that follow colliculus lesions. To test this possibility, we examined the effect of pulvinar lesions in monkeys on the localization and detection of brief light flashes, a task in which monkeys with colliculus lesions are severely impaired. Some of the pulvinar-lesioned monkeys showed localization impairments similar to those in monkeys with colliculus lesions. However, histological analyses of the lesions suggested that these deficits were related not to the pulvinar damage per se, but rather to interruption of corticotectal fibers that pass through the pulvinar. We conclude that the pulvinar is not critical for the ability to locate and detect brief visual stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46551/1/221_2004_Article_BF00238622.pd

Trisonomia 9 in pazienti affetti da MPN PH-: aspetti clinici e laboratoristici

Le neoplasie mieloproliferative ( MPN), comprendenti la Policitemia vera (PV), la Trombocitemia essenziale (TE) e la Mielofibrosi idiopatica (MFI), sono disordini clonali Philadelphia negativi caratterizzati, nel 20% dei casi, da anomalie cromosomiche ricorrenti. La trisomia 9 rappresenta la seconda anomalia cromosomica pi\uf9 frequente nelle MPN dopo la delezione 20q. Abbiamo eseguito l\u2019analisi citogenetica su aspirato midollare di una casistica monocentrica di 325 pazienti affetti da MPN; tutti i pazienti sono risultati Ph-, la trisomia 9 \ue8 stata riscontrata in 13 pazienti (9 affetti da PV e 4 da TE), in 10 casi come unica anomalia cromosomica, in un caso associata a trisomia 8 e in 2 casi in un cariotipo pi\uf9 complesso. Sono state analizzate le caratteristiche cliniche e di laboratorio e l\u2019evoluzione di malattia, al fine di individuare se tale anomalia citogenetica avesse delle particolari stigmate. I pazienti sono stati seguiti regolarmente per un periodo medio di 10,6 anni (range 1- 23 anni). L\u2019et\ue0 media alla diagnosi era 62 anni e il rapporto M:F di 1,2:1. I dati di laboratorio mostravano un valore medio di emoglobina di 16,7 g/dl, un numero medio di globuli bianchi di 9657/mmc, mentre la conta piastrinica media era di 690000/mmc. Il dosaggio dell\u2019 eritropoietina serica \ue8 risultato ridotto in tutti i pazienti e tutti presentavano la mutazione JAK2 V617F (carica allelica media 47,1%). E\u2019 interessante notare che nei pazienti affetti da TE, i valori di emoglobina alla diagnosi, pur non essendo sufficienti per porre diagnosi di PV erano comunque ai limiti superiori di norma. Dei 4 pazienti con TE, 3 (75%) sono evoluti a distanza di anni in PV, evento relativamente raro. I dati ottenuti evidenziano una maggior frequenza della trisomia 9 nei pazienti con PV rispetto alle altre neoplasie mieloproliferative ed inoltre sottolineano come i pazienti con TE portatori di tale alterazione citogenetica, abbiano un fenotipo simil-PV e un aumentato rischio di evoluzione in franca PV. Non \ue8 stata osservata trisomia 9 nelle Mielofibrosi. E\u2019 inoltre da segnalare che sul braccio corto del cromosoma 9 \ue8 stato mappato il gene JAK-2, gene che risulta mutato frequentemente nelle MPN Ph- e soprattutto nelle PV di cui rappresenta un marker molecolare