Title: Health Care Disparities Might Affect Black Kids' Cancer Survival
Category: Health News
Created: 5/1/2012 10:05:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: Heart Attack Survival Varies Widely Among Hospitals, Study Finds
Category: Health News
Created: 4/30/2012 6:06:00 PM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: Screening for Other Health Problems May Aid COPD Survival
Category: Health News
Created: 5/4/2012 10:05:00 AM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: Preemies' Increased Survival Comes With No Rise in Disabilities: Study
Category: Health News
Created: 4/30/2013 12:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: Dispatcher-Assisted CPR Boosts Cardiac Arrest Survival in Kids: Study
Category: Health News
Created: 4/30/2014 4:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM

Title: Low-Dose Aspirin Tied to Better Cancer Survival in Study
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM

As more evidence emerges that COVID-19 is tied to an increased risk of dangerous blood clots, new research suggests that giving patients blood thinners may improve their odds of survival.

Data from a large US cohort suggest systemic anticoagulation may confer a survival benefit in hospitalized patients without a spike in bleeding events.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

Key Points

IMMUNOLOGY AND INFLAMMATION Correction for “Treg-mediated prolonged survival of skin allografts without immunosuppression,” by Nina Pilat, Mario Wiletel, Anna M. Weijler, Romy Steiner, Benedikt Mahr, Joanna Warren, Theresa M. Corpuz, Thomas Wekerle, Kylie E. Webster, and Jonathan Sprent, which was first published June 13, 2019; 10.1073/pnas.1903165116 (Proc. Natl. Acad. Sci....

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.

High-constitutive activity of the DNA damage response protein checkpoint kinase 1 (CHK1) has been shown in glioblastoma (GBM) cell lines and in tissue sections. However, whether constitutive activation and overexpression of CHK1 in GBM plays a functional role in tumorigenesis or has prognostic significance is not known. We interrogated multiple glioma patient cohorts for expression levels of CHK1 and the oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A), a known target of high-CHK1 activity, and examined the relationship between these two proteins in GBM. Expression levels of CHK1 and CIP2A were independent predictors for reduced overall survival across multiple glioma patient cohorts. Using siRNA and pharmacologic inhibitors we evaluated the impact of their depletion using both in vitro and in vivo models and sought a mechanistic explanation for high CIP2A in the presence of high-CHK1 levels in GBM and show that; (i) CHK1 and pSTAT3 positively regulate CIP2A gene expression; (ii) pSTAT3 and CIP2A form a recursively wired transcriptional circuit; and (iii) perturbing CIP2A expression induces GBM cell senescence and retards tumor growth in vitro and in vivo. Taken together, we have identified an oncogenic transcriptional circuit in GBM that can be destabilized by targeting CIP2A.

Monoclonal antibodies (mAbs) against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, are associated with high response rates in patients with relapsed or refractory classic Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using ¹⁸F-FDG PET/CT may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a masked, centralized review, 3 independent radiologists classified PET/CT scans obtained at a median of 2.0 mo (interquartile range, 1.7–3.7 mo) after nivolumab initiation using existing criteria (i.e., 2014 Lugano classification and 2016 LYRIC). Patients were classified according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). Because the OS of patients with NMR and PMR was similar, they were grouped together. OS was estimated using the Kaplan–Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 mo. The classification was identical between Lugano and LYRIC because all 16 progression events classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC classified patients as CMR in 13 cases (29%), PMD in 16 (36%), NMR in 4 (9%), and PMR in 12 (27%). The 2-y OS probability was significantly different in patients with PMD (0.53; 95% confidence interval [95%CI], 0.32–0.87), NMR or PMR (0.80; 95%CI, 0.63–1.00), and CMR (1.00; 95%CI, 1.00–1.00) in the overall population (P = 0.02, 45 patients), as well as according to a landmark analysis at 3 mo (P = 0.05, 32 patients). Conclusion: In relapsed or refractory HL patients treated with anti-PD-1 mAbs, the first early PET/CT assessment using either Lugano or LYRIC predicted OS and allowed early risk stratification, suggesting that PET/CT might be used to develop risk-adapted strategies.

Autophagy captures intracellular components and delivers them to lysosomes for degradation and recycling. Conditional autophagy deficiency in adult mice causes liver damage, shortens life span to 3 mo due to neurodegeneration, and is lethal upon fasting. As autophagy deficiency causes p53 induction and cell death in neurons, we sought to test whether p53 mediates the lethal consequences of autophagy deficiency. Here, we conditionally deleted Trp53 (p53 hereafter) and/or the essential autophagy gene Atg7 throughout adult mice. Compared with Atg7^/ mice, the life span of Atg7^/p53^/ mice was extended due to delayed neurodegeneration and resistance to death upon fasting. Atg7 also suppressed apoptosis induced by p53 activator Nutlin-3, suggesting that autophagy inhibited p53 activation. To test whether increased oxidative stress in Atg7^/ mice was responsible for p53 activation, Atg7 was deleted in the presence or absence of the master regulator of antioxidant defense nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2^–/–Atg7^/ mice died rapidly due to small intestine damage, which was not rescued by p53 codeletion. Thus, Atg7 limits p53 activation and p53-mediated neurodegeneration. In turn, NRF2 mitigates lethal intestine degeneration upon autophagy loss. These findings illustrate the tissue-specific roles for autophagy and functional dependencies on the p53 and NRF2 stress response mechanisms.

Background

COPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.

PURPOSE

The prognosis of older patients with dizziness in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness.

Background and objectives

This study aimed to investigate the association between in-hospital trajectories of serum sodium and risk of in-hospital and 1-year mortality in patients in hospital.

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and a lower abundance of CD14⁺CD33⁺CD85j⁺ cells had improved overall survival [median overall survival, range (days) 271, 43–1,247] compared with patients with a lower abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and higher abundance of CD14⁺CD33⁺CD85j⁺ cells (77, 24–1,247 days; P = 0.0442). The results from this prospective–retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

Purpose:

Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.

Purpose:

To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

Patients with HPV16⁺ cervical cancer and high T-cell responses to an HPV16 vaccine survived longer.

Background:

Asian Americans are at higher risk for noncardia gastric cancers (NCGC) relative to non-Hispanic Whites (NHW). Asian Americans are genetically, linguistically, and culturally heterogeneous, yet have mostly been treated as a single population in prior studies. This aggregation may obscure important subgroup-specific cancer patterns.

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

Spencer's ideas laid the groundwork for social Darwinism, but scholars say there was much more to the Victorian Age thinker than that

Treating hospitalized COVID-19 patients with anticoagulants -- blood thinners that slow down clotting -- may improve their chances of survival, researchers report. The study could provide new insight on how to treat and manage coronavirus patients once they are admitted to the hospital.

The boss of Airbus has warned that it is "bleeding cash" at such a rapid rate during the coronavirus lockdowns that its survival is in doubt.

1. Evidence Builds Linking Anticoagulation to COVID-19 Survival  Medscape
2. Blood thinners may boost survival rates of Covid-infected patients: Study  ETHealthworld.com
3. Coronavirus blood-clot mystery intensifies  Nature.com
4. Coronavirus: Blood thinners could boost survival chances of patients  The Independent
5. Blood thinners may help COVID-19 patients  ABC27
6. View Full coverage on Google News

No longer able to walk hundreds of miles to create his hand-drawn maps, the Beijing-based artist Fuller is charting his thoughts – and the global crisis – while stuck indoors

I’m interested in the psychology of a place and how it makes you feel. So I don’t really see myself as a map-maker – even though I draw maps. It’s about the process of travelling through a place to capture a sense of it. First, I walk for hundreds of miles and make all sorts of notes, and then take thousands of photos to use as triggers for my memory.

I walked more than 840 miles around Beijing when researching the map that became part of my Purposeful Wandering series. I circumnavigated the city and then walked around each ring road. Beijing (where I’ve lived for three years) is built on a Central Axis, and the map is, too. A lot of the drawing is literal, but I also built in personal experiences, references, visual puns and semiotics.

Gary Neville has made a "significant" donation to help non-league outfit Brighouse Town in their battle to survive.

Alan Pardew has told ADO Den Haag to keep the survival bonus he is entitled to, and has instead encouraged the club to donate it to the Dutch health service.

EXCLUSIVE: As BBC documentary The Primates hits our screens, experts warn there are only a few ways

A new discovery in mice shows the innate immune system has 'memory,' previously thought to be a unique feature of the adaptive immune system. Blocking this memory prevented transplanted organs from being rejected, providing a way to more specific drugs that could lengthen organ transplant survival.

Some of the scariest, true-life stories you can tell over a campfire or a beer—featuring shark attacks, snake bites, spider bites, and lightning strikes.

A restaurant owner in small-town Michigan wonders whether the government is as much of a threat as the coronavirus itself.

- Libtayo decreased the risk of death by 32.4% compared to chemotherapy

This wilderness explorer transformed this van into a mobile, solar-powered home that has all the amenities.

Climate change is already killing people around the world. Now the British Medical Association has vowed to do something about it.

A beautiful film celebrates doing things, like starting a fire entirely by hand, that are no longer necessary. There are lessons for us all.

Dr Aluvihare

Lindsey Marvel, 38, moved to New York because, she said, "I'm literally going big or going home." Now she's going home to Tulsa, Oklahoma. The effect that Covid-19 has had not just on her personal life, but on the city she loves, was simply too much.

CNBC's Diana Olick reports on a woman's tough decision to flee Brooklyn, New York for Oklahoma.

Firms in Gulf Cooperation Council countries are facing "very severe liquidity problems" and "very uncertain times" amid the coronavirus crisis, says Gabriel Chahine of AlixPartners.