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death - Top 30 Publications

Sudden Death from Cardiopulmonary Arrest on Arrival of a Patient with Pulmonary Tuberculosis: A Case Diagnosed by Postmortem CT and Autopsy.

Sudden death due to massive hemoptysis during management of tuberculosis occurs in a considerable number of patients. However, when massive airway hemorrhage occurs in a patient in whom tuberculosis has not been confirmed and a blood is not apparent externally on the face/body, it is difficult to immediately identify the cause of death as airway obstruction by tuberculous bleeding in the airway. We encountered an 83-year-old Japanese woman with her medical history included treatment of tuberculosis in her 20s who was in cardiopulmonary arrest on arrival (CPAOA), and the cause of sudden death could not initially be identified. Postmortem CT (PMCT) and autopsy revealed that the cause of sudden death was airway obstruction/asphyxia by tuberculous massive airway hemorrhage. Identification of the cause of death facilitated a subsequent active contact investigation and led to prevention of secondary tuberculosis infection.

The relation between household income and surgical outcome in the Dutch setting of equal access to and provision of healthcare.

The impact of socioeconomic disparities on surgical outcome in the absence of healthcare inequality remains unclear. Therefore, we set out to determine the association between socioeconomic status (SES), reflected by household income, and overall survival after surgery in the Dutch setting of equal access and provision of care. Additionally, we aim to assess whether SES is associated with cause-specific survival and major 30-day complications.

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

Hippo signaling controls cell cycle and restricts cell plasticity in planarians.

The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities in this pathway are consistently associated with human cancers. Hippo was initially implicated in the control of cell proliferation and death, and its inhibition is linked to the expansion of stem cells and progenitors, leading to larger organ size and tumor formation. To understand the mechanism by which Hippo directs cell renewal and promotes stemness, we studied its function in planarians. These stem cell-based organisms are ideal models for the analysis of the complex cellular events underlying tissue renewal in the whole organism. hippo RNA interference (RNAi) in planarians decreased apoptotic cell death, induced cell cycle arrest, and could promote the dedifferentiation of postmitotic cells. hippo RNAi resulted in extensive undifferentiated areas and overgrowths, with no effect on body size or cell number. We propose an essential role for hippo in controlling cell cycle, restricting cell plasticity, and thereby preventing tumoral transformation.

Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system increases susceptibility to age- and stress-induced neuronal dysfunction and degeneration in Drosophila.

Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1 in the maintenance of neuronal integrity in vivo by knocking down the expression of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in premature death and significantly exacerbated behavioral deficits in flies, suggesting that wfs1 has important functions in both cell types. Although wfs1 knockdown alone did not promote ER stress, it increased the susceptibility to oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and neurodegeneration. The glutamate release inhibitor riluzole significantly suppressed premature death phenotypes induced by neuronal and glial knockdown of wfs1. This study highlights the protective role of wfs1 against age-associated neurodegeneration and furthers our understanding of potential disease-modifying factors that determine susceptibility and resilience to age-associated neurodegenerative diseases.

Single-step genomic evaluation improves accuracy of breeding value predictions for resistance to infectious pancreatic necrosis virus in rainbow trout.

The aim of this study was to compare the accuracy of breeding values (EBVs) predicted using the traditional pedigree based Best Linear Unbiased Prediction (PBLUP) and the single-step genomic Best Linear Unbiased Prediction (ssGBLUP) for resistance against infectious pancreatic necrosis virus (IPNV) in rainbow trout. A total of 2278 animals were challenged against IPNV and 768 individuals were genotyped using 57 K single nucleotide polymorphism for rainbow trout. Accuracies for both methods were assessed using five-fold cross-validation. The heritabilities were higher for PBLUP compared to ssGBLUP. The ssGBLUP accuracies outperformed the PBLUP in 7 and 11% for days to death and binary survival, respectively. The ssGBLUP could be an alternative approach to improve the accuracy of breeding values for resistance against infectious pancreatic necrosis virus in rainbow trout, using information from genotyped and non-genotyped animals.

FDA-mandated Trials of LABA Safety in Asthma: Bang for the Buck?

The safety of long-acting beta-agonists (LABA) to treat asthma has been a lingering issue for the last 25 years after two large randomized trials reported an increased incidence of asthma death with salmeterol. The current dilemma is whether this risk is also increased when LABAs are given with inhaled corticosteroids (ICS). To address this, the FDA required that manufacturers conduct five large randomized trials comparing ICS-LABA combinations to ICS alone on the incidence of major asthma outcomes. The three trials that have been published to date showed that the risk of a serious asthma-related event, including asthma-related death, intubation or hospitalization, was not increased with the addition of the LABA. This finding was similar to a meta-analysis of 57 prior trials involving close to 35,000 asthma patients (RR 0.98; 95% CI: 0.57-1.68). The three trials also found a lower incidence of asthma exacerbation, as did the meta-analysis (RR 0.73; 95% CI: 0.67-0.79). Finally, there were two asthma deaths overall in the three trials under ICS-LABA versus 0 with ICS only (RR 3.00; 95% CI: 0.24-37.70), comparable to the meta-analysis finding (RR 2.96; 95% CI: 0.50-17.57). In all, the three published FDA-mandated trials to assess the safety of ICS-LABA have predictably produced the same results as the meta-analyses of prior trials, including the same lingering asthma death signal. These costly trials with no added benefit leave us no more advanced with respect to the core issue of the link between LABA use and asthma death, which still remains unresolved.

The Pēpi-Pod study: Overnight video, oximetry and thermal environment while using an in-bed sleep device for sudden unexpected death in infancy prevention.

The aim of this study was to identify the potential risks and benefits of sleeping infants in a Pēpi-Pod distributed to families with high risk of sudden unexpected death in infancy compared to a bassinet.

Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels.

Crocin improved amyloid beta induced long-term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats.

Extracellular beta-amyloid (Aβ) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP and neuronal apoptosis using in vivo Aβ models of the AD. The Aβ peptide (1-42) was bilaterally administered into the frontal-cortex using stereotaxic apparatus. Five hours post-surgery, rats were given intra-peritoneal crocin (30mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improve spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aβ-group. Passive avoidance test revealed that crocin significantly increased the step-through-latency compared to Aβ-treated alone. These learning deficits in Aβ-treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aβ. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c-Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL-positive cells in the CA1 region and decreased c-Fos in the hippocampus compared to Aβ-group. In vivo Aβ treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirm a neuroprotective action against Aβ toxicity. This article is protected by copyright. All rights reserved.

Differences in mortality in a cohort of cocaine use disorder patients with concurrent alcohol or opiates disorder.

To study mortality in a cohort of cocaine use disorder patients, and compare results in those with concurrent alcohol or opiates disorder.

Imaging of Mitochondrial and Cytosolic Ca2+ Signals in Cultured Astrocytes.

This unit provides a step-by-step protocol for constructing cell type- and mitochondria-targeted GCaMP genetically encoded Ca2+ indicators (GECIs) for mitochondrial Ca2+ imaging in astrocytes. Mitochondrial Ca2+ plays a critical role in controlling cytosolic Ca2+ buffering, energy metabolism, and cellular signal transduction. Mitochondrial Ca2+ overload contributes to various pathological conditions, including neurodegeneration and apoptotic cell death in neurological diseases. Live-cell mitochondrial Ca2+ imaging is an important approach to understand mitochondrial Ca2+ dynamics and thus cell physiology and pathology. We implement astrocyte-specific mitochondrial targeting of GCaMP5G/6s (mito-GCaMP5G/6s). By loading X-Rhod-1 into astrocytes, we can simultaneously image mitochondrial and cytosolic Ca2+ signals. This protocol provides a novel approach to image mitochondrial Ca2+ dynamics as well as Ca2+ interplay between the endoplasmic reticulum and mitochondria. © 2018 by John Wiley & Sons, Inc.

Gastrointestinal Tract Pathology in a BALB/c Niemann-Pick Disease Type C1 Null Mouse Model.

Niemann-Pick disease, type C (NPC) is a rare lysosomal storage disorder characterized by progressive neurodegeneration, splenomegaly, hepatomegaly, and early death. NPC is caused by mutations in either the NPC1 or NPC2 gene. Impaired NPC function leads to defective intracellular transport of unesterified cholesterol and its accumulation in late endosomes and lysosomes. A high frequency of Crohn disease has been reported in NPC1 patients, suggesting that gastrointestinal tract pathology may become a more prominent clinical issue if effective therapies are developed to slow the neurodegeneration. The Npc1 nih mouse model on a BALB/c background replicates the hepatic and neurological disease observed in NPC1 patients. Thus, we sought to characterize the gastrointestinal tract pathology in this model to determine whether it can serve as a model of Crohn disease in NPC1.

Translational neonatology research: transformative encounters across species and disciplines.

This paper explores the laborious and intimate work of turning bodies of research animals into models of human patients. Based on ethnographic research in the interdisciplinary Danish research centre NEOMUNE, we investigate collaboration across species and disciplines, in research aiming at improving survival for preterm infants. NEOMUNE experimental studies on piglets evolved as a platform on which both basic and clinical scientists exercised professional authority. Guided by the field of multi-species research, we explore the social and material agency of research animals in the production of human health. Drawing on Anna Tsing's concept of "collaborative survival", we show that sharing the responsibility of the life and death of up to twenty-five preterm piglets fostered not only a collegial solidarity between basic and clinical scientists, but also a transformative cross-fertilization across species and disciplines-a productive "contamination"-facilitating the day-to-day survival of piglets, the academic survival of scientists and the promise of survival of preterm infants. Contamination spurred intertwined identity shifts that increased the porosity between the pig laboratory and the neonatal intensive care unit. Of particular significance was the ability of the research piglets to flexibly become animal-infant-patient hybrids in need of a united effort from basic and clinical researchers. However, 'hybrid pigs' also entailed a threat to the demarcation between humans and animals that consolidates the use of animals in biomedical research, and efforts were continuously done to keep contamination within spatial limits. We conclude that contamination facilitates transformative encounters, yet needs spatial containment to materialize bench-to-bedside translation.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

Mechanical birth-related trauma to the neonate: An imaging perspective.

Mechanical birth-related injuries to the neonate are declining in incidence with advances in prenatal diagnosis and care. These injuries, however, continue to represent an important source of morbidity and mortality in the affected patient population. In the United States, these injuries are estimated to occur among 2.6% of births. Although more usual in context of existing feto-maternal risk factors, their occurrence can be unpredictable. While often superficial and temporary, functional and cosmetic sequelae, disability or even death can result as a consequence of birth-related injuries. The Agency for Healthcare research and quality (AHRQ) in the USA has developed, through expert consensus, patient safety indicators which include seven types of birth-related injuries including subdural and intracerebral hemorrhage, epicranial subaponeurotic hemorrhage, skeletal injuries, injuries to spine and spinal cord, peripheral and cranial nerve injuries and other types of specified and non-specified birth trauma. Understandably, birth-related injuries are a source of great concern for the parents and clinician. Many of these injuries have imaging manifestations. This article seeks to familiarize the reader with the clinical spectrum, significance and multimodality imaging appearances of neonatal multi-organ birth-related trauma and its sequelae, where applicable. Teaching points • Mechanical trauma related to birth usually occurs with pre-existing feto-maternal risk factors.• Several organ systems can be affected; neurologic, musculoskeletal or visceral injuries can occur.• Injuries can be mild and transient or disabling, even life-threatening.• Imaging plays an important role in injury identification and triage of affected neonates.

Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients.

To investigate the correlation between elevated serum sclerostin levels and chronic kidney disease outcomes for patients receiving peritoneal dialysis (PD).

Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK signaling pathways.

Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing.

Cold atmospheric pressure plasma causes protein denaturation and endoplasmic reticulum stress in Saccharomyces cerevisiae.

Cold atmospheric pressure plasma (CAP) does not cause thermal damage or generate toxic residues; hence, it is projected as an alternative agent for sterilization in food and pharmaceutical industries. The fungicidal effects of CAP have not yet been investigated as extensively as its bactericidal effects. We herein examined the effects of CAP on yeast proteins using a new CAP system with an improved processing capacity. We demonstrated that protein ubiquitination and the formation of protein aggregates were induced in the cytoplasm of yeast cells by the CAP treatment. GFP-tagged Tsa1 and Ssa1, an H2O2-responsive molecular chaperone and constitutively expressed Hsp70, respectively, formed cytoplasmic foci in CAP-treated cells. Furthermore, Tsa1 was essential for the formation of Ssa1-GFP foci. These results indicate that the denaturation of yeast proteins was caused by CAP, at least partially, in a H2O2-dependent manner. Furthermore, misfolded protein levels in the endoplasmic reticulum (ER) and the oligomerization of Ire1, a key sensor of ER stress, were enhanced by the treatment with CAP, indicating that CAP causes ER stress in yeast cells as a specific phenomenon to eukaryotic cells. The pretreatment of yeast cells at 37 °C significantly alleviated cell death caused by CAP. Our results strongly suggest that the induction of protein denaturation is a primary mechanism of the fungicidal effects of CAP.

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus.

Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown.

Risk Factors for Prolonged Postoperative Opioid Use After Spinal Fusion for Adolescent Idiopathic Scoliosis.

Opioids are commonly used after posterior spinal instrumented fusion (PSIF) for adolescent idiopathic scoliosis (AIS). Prescription opioids use can potentially lead to misuse, abuse, dependence, and overdose death. Prolonged opioid use has not been extensively studied in the postoperative AIS population. The purpose of this study is to identify risk factors associated with prolonged opioid use after PSIF for AIS.

Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma.

Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5), 5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT.

Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases.

Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P<0.001). The median OS was 15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB administration did not seem to influence the risk of radiation necrosis, intracranial control or OS. SRS combined with PB was well tolerated and achieved local control in 80% of the lesions. Prolonged OS was observed compared with that currently yielded in this population of patients. Prospective studies are required to explore further the optimal ways to combine immunotherapy and SRS.

Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP.

Thioredoxin-interacting protein has emerged as a major factor regulating pancreatic β-cell dysfunction and death, key processes in the pathogenesis of type 1 and type 2 diabetes. Accumulating evidence based on basic, preclinical, and retrospective epidemiological research suggests that TXNIP represents a promising therapeutic target for diabetes. The present review is aimed at providing an update regarding these developments.

The association of exposure to suicide-related Internet content and emergency department visits in children: A population-based time series analysis.

Suicide-related emergency department (ED) visits by children are increasing in tandem with suicide-related Internet content. Following the announcement of Amanda Todd's suicide, her YouTube video received widespread views, providing an opportunity to explore this association.

Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016.

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133-tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

Predictors of Specialized Pediatric Palliative Care Involvement and Impact on Patterns of End-of-Life Care in Children With Cancer.

Purpose The impact of specialized pediatric palliative care (SPPC) teams on patterns of end-of-life care is unknown. We sought to determine (1) which children with cancer access SPPC and (2) the impact of accessing SPPC on the risk of experiencing high-intensity end-of-life care (intensive care unit admission, mechanical ventilation, or in-hospital death). Methods Using a provincial childhood cancer registry, we assembled a retrospective cohort of Ontario children with cancer who died between 2000 and 2012 and received care through pediatric institutions with an SPPC team. Patients were linked to population-based administrative data capturing inpatient, outpatient, and emergency visits. Children were classified as having SPPC, general palliative care, or no palliative care on the basis of SPPC clinical databases, physician billing codes, or inpatient diagnosis codes. Results Of the 572 children, 166 (29%) received care from an SPPC team for at least 30 days before death, and 100 (17.5%) received general palliative care. SPPC involvement was significantly less likely for children with hematologic cancers (OR, 0.3; 95% CI, 0.3 to 0.4), living in the lowest income areas (OR, 0.4; 95% CI, 0.2 to 0.8), and living further from the treatment center (OR, 0.5; 95% CI, 0.4 to 0.5). SPPC was associated with a five-fold decrease in odds of intensive care unit admission (OR, 0.2; 95% CI, 0.1 to 0.4), whereas general palliative care had no impact. Similar associations were seen with all secondary indicators. Conclusion When available, SPPC, but not general palliative care, is associated with lower intensity care at the end of life for children with cancer. However, access remains uneven. These results provide the strongest evidence to date supporting the creation of SPPC teams.

Taking Psychedelics Seriously.

Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among people with treatment-resistant depression and anxiety, including those with serious medical conditions. Need and Clinical Considerations: Palliative care clinicians occasionally encounter patients with emotional, existential, or spiritual suffering, which persists despite optimal existing treatments. Such suffering may rob people of a sense that life is worth living. Data from Oregon show that most terminally people who obtain prescriptions to intentionally end their lives are motivated by non-physical suffering. This paper overviews the history of this class of drugs and their therapeutic potential. Clinical cautions, adverse reactions, and important steps related to safe administration of psychedelics are presented, emphasizing careful patient screening, preparation, setting and supervision.


Lung cancer is the most commonly diagnosed and death-related cancer type and is more frequent in males. Non-small cell lung cancer accounts for about 85%of all case. In this study it was aimed to research the relationship between advanced lung inflammation index (ALI) and the primary mass maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at initial diagnosis; and the prognostic value of ALI in determining the survival in metastatic non-small cell lung cancer (NSCLC) Methods: 112 patients diagnosed as stage 4 non-small lung cancer in our hospital between January 2006 and December 2013 were included in this study. ALI was calculated as body mass index (BMI) x serum albumin/neutrophil to lymphocyte ratio (NLR). The patients were divided into two groups as ALI <18 (high inflammation) and ALI ≥ 18 (low inflammation). The Log Rank Test and Cox proportional hazard model were used to identify predictors of mortality.