Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Journal of Mathematical Chemistry

Texto completo: acesso restrito. p.107-116Usually the partitioning technique (PT) has been studied under two aspects: (i) as a numerical tool for solving secular equations of high order, and (ii) as a theoretical method related to the infinite‐order perturbation theory and the iteration–variation methods. Here it is shown that there exists a form of the PT equations which allows us to determine explicitly the spectrum and eigenstates of the Hamiltonian operator for different forms of potentials without the utilization of perturbative expansions or iterative equations of the type E=f(E). As a first application of the new approach, we consider the hydrogen‐atom in strong magnetic fields (B ~ 109 G)

Journal of Mathematical Chemistry

Texto completo: acesso restrito. p.1-13We show that the modified partitioning procedure can be applied to study the spherical and nonspherical Stark effect in the hydrogen atom and the spherical quadratic Zeeman effect in H-, the helium atom and He‐like ions: Li++, Be++, etc. We present ground‐state energy values for γ (in a.u.) in the interval 0.001 ≤ λ ≤ 0.2 (a.u.= 5.142·109 volts/cm) and for magnetic field γ (in a.u.) in the interval 0.1 ≤ γ ≤ 1.0 (a.u. = 2.353·109 gauss). We compare our results to values available in the literature; they are, in general, better than those obtained by other methods

Prevention of COVID-19 transmission from deceased subject: A critical point of view

On December 31, 2019, China reported to the WHO cases of pneumonia in Wuhan caused by a novel coronavirus (2019-nCoV). This escalated into an unprecedented outbreak of infections, leading the WHO to characterise it as a pandemic on March 11, 2020. The COVID-19 pandemic is rapidly evolving, and since October 9, 2021, almost 200000000 people have been infected with more than 4000000 deaths globally [1]. To reduce transmission and mortality, efforts have been made to develop vaccines against COVID-19. Since December 2020, new vaccines have been authorized to help control the spread of the virus [2]. Despite the vaccination campaign progressing successfully, our battle is not yet won, and avoiding exposure to this virus is crucial to preventing COVID-19. Person-to-person transmission occurs primarily via direct contact or through droplets spread by the infected individual coughing or sneezing [3-5]. Although the infection rate from dead bodies is unclear [4], managing them is of great importance in reducing viral transmission, especially because mortuary staff and pathologists will be exposed to potentially infective materials from cadavers, transmitted through airways, body bags, autopsy tables, and autopsy room walls [4,6]. For this reason, many societies, institutes, and governments have given general infection and prevention advice. This viewpoint aims to summarize how different countries manage the COVID-19 dead and perform autopsies and whether common prevention recommendations can be identified. The PubMed database was searched until October 9, 2021. We used keywords for: deceased covid 19, management of death covid 19, autopsy covid 19 ((deceased covid 19) AND management of death covid 19) AND autopsy covid 19). The selected articles’ references were also screened. Only documents in English were included, while reviews were excluded

Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.

Bruton's tyrosine kinase (BTK) is a member of the TEC-family kinases and crucial for the proliferation and differentiation of B-cells. We evaluated the therapeutic potential of a covalent inhibitor (JS25) with nanomolar potency against BTK and with a more desirable selectivity and inhibitory profile compared to the FDA-approved BTK inhibitors ibrutinib and acalabrutinib. Structural prediction of the BTK/JS25 complex revealed sequestration of Tyr551 that leads to BTK's inactivation. JS25 also inhibited the proliferation of myeloid and lymphoid B-cell cancer cell lines. Its therapeutic potential was further tested against ibrutinib in preclinical models of B-cell cancers. JS25 treatment induced a more pronounced cell death in a murine xenograft model of Burkitt's lymphoma, causing a 30-40% reduction of the subcutaneous tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. In a patient model of diffuse large B-cell lymphoma, the drug response of JS25 was higher than that of ibrutinib, leading to a 64% "on-target" efficacy. Finally, in zebrafish patient-derived xenografts of chronic lymphocytic leukemia, JS25 was faster and more effective in decreasing tumor burden, producing superior therapeutic effects compared to ibrutinib. We expect JS25 to become therapeutically relevant as a BTK inhibitor and to find applications in the treatment of hematological cancers and other pathologies with unmet clinical treatment

Selective Inhibition of Bruton’s Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors

Bruton’s tyrosine kinase (BTK) is a member of the TEC-family kinases and crucial for the proliferation and differentiation of B-cells. We evaluated the therapeutic potential of a covalent inhibitor (JS25) with nanomolar potency against BTK and with a more desirable selectivity and inhibitory profile compared to the FDA-approved BTK inhibitors ibrutinib and acalabrutinib. Structural prediction of the BTK/JS25 complex revealed sequestration of Tyr551 that leads to BTK’s inactivation. JS25 also inhibited the proliferation of myeloid and lymphoid B-cell cancer cell lines. Its therapeutic potential was further tested against ibrutinib in preclinical models of B-cell cancers. JS25 treatment induced a more pronounced cell death in a murine xenograft model of Burkitt’s lymphoma, causing a 30–40% reduction of the subcutaneous tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. In a patient model of diffuse large B-cell lymphoma, the drug response of JS25 was higher than that of ibrutinib, leading to a 64% “on-target” efficacy. Finally, in zebrafish patient-derived xenografts of chronic lymphocytic leukemia, JS25 was faster and more effective in decreasing tumor burden, producing superior therapeutic effects compared to ibrutinib. We expect JS25 to become therapeutically relevant as a BTK inhibitor and to find applications in the treatment of hematological cancers and other pathologies with unmet clinical treatment