Most blood cancers are incurable and typically follow unpredictable remitting-relapsing pathways associated with varying need for treatment, which may be distressing for patients. Our objective was ...to conduct a qualitative study to explore understanding among patients with such malignancies, including the explanations given by HCPs and the impact of uncertain trajectories, to generate evidence that could guide improvements in clinical practice.
The study is set within a population-based patient cohort (the Haematological Malignancy Research Network), in which care is delivered across 14 hospitals according to national guidelines. In-depth interviews were conducted with 35 patients with chronic lymphocytic leukaemia, follicular lymphoma, marginal zone lymphoma or myeloma; and 10 accompanying relatives. Purposive sampling ensured selection of information-rich participants and the data were interrogated using reflective thematic analysis.
Rich data were collected and four themes (11 sub-themes) were identified: 1) Knowledge and understanding of chronic haematological malignancies; 2) Incurable but treatable; 3) Uncertainty about the future; and 4) Treatable (but still incurable): Impact on patients. Patients had rarely heard of blood cancer and many expressed difficulty understanding how an incurable malignancy that could not be removed, was treatable, often for long periods. While some were reassured that their cancer did not pose an immediate survival threat, others were particularly traumatised by the uncertain future it entailed, suffering ongoing emotional distress as a result, which could be more burdensome than any physical symptoms. Nonetheless, most interviewees understood that uncertain pathways were caused by the unpredictability of their disease trajectory, and not information being withheld.
Many participants lacked knowledge about chronic haematological malignancies. HCPs acted to reassure patients about their diagnosis, and while this was appropriate and effective for some, it was less so for others, as the cancer-impact involved struggling to cope with ongoing uncertainty, distress and a shortened life-span.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk ...patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123 ). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers. Funding British Heart Foundation and Chief Scientist Office (Scotland).
Based on the profile of genetic alterations occurring in tumor samples from selected diffuse large B-cell lymphoma (DLBCL) patients, 2 recent whole-exome sequencing studies proposed partially ...overlapping classification systems. Using clustering techniques applied to targeted sequencing data derived from a large unselected population-based patient cohort with full clinical follow-up (n = 928), we investigated whether molecular subtypes can be robustly identified using methods potentially applicable in routine clinical practice. DNA extracted from DLBCL tumors diagnosed in patients residing in a catchment population of ∼4 million (14 centers) were sequenced with a targeted 293-gene hematological-malignancy panel. Bernoulli mixture-model clustering was applied and the resulting subtypes analyzed in relation to their clinical characteristics and outcomes. Five molecular subtypes were resolved, termed MYD88, BCL2, SOCS1/SGK1, TET2/SGK1, and NOTCH2, along with an unclassified group. The subtypes characterized by genetic alterations of BCL2, NOTCH2, and MYD88 recapitulated recent studies showing good, intermediate, and poor prognosis, respectively. The SOCS1/SGK1 subtype showed biological overlap with primary mediastinal B-cell lymphoma and conferred excellent prognosis. Although not identified as a distinct cluster, NOTCH1 mutation was associated with poor prognosis. The impact of TP53 mutation varied with genomic subtypes, conferring no effect in the NOTCH2 subtype and poor prognosis in the MYD88 subtype. Our findings confirm the existence of molecular subtypes of DLBCL, providing evidence that genomic tests have prognostic significance in non-selected DLBCL patients. The identification of both good and poor risk subtypes in patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) clearly show the clinical value of the approach, confirming the need for a consensus classification.
•Robust subtypes of DLBCL are identified by model-based clustering of genetic mutations in a large (n = 928) population-based cohort.•With full follow-up data available for all sequenced patients, the prognostic significance of these subtypes is identified.
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Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen.
This ...retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients' subsequent clinical course.
There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8-74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5-45.32) for ICU admission (p<0.001). A patient's respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88-99).
In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemiology of lymphomas Roman, Eve; Smith, Alexandra G
Histopathology,
January 2011, Letnik:
58, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Roman E & Smith A G (2011) Histopathology 58, 4–14 Epidemiology of lymphomas
Epidemiological reports on lymphomas often begin, and sometimes end, by stating that little is known about the causes of ...the condition(s) under study. This is slowly changing as information on the pathological diversity of subtypes accumulates. This review examines the epidemiology of lymphomas, focusing on the impact of the latest World Health Organization (WHO) classification. Use of appropriate disease classifications is critical to the research process, but many studies conducted in previous decades have been hampered by the need to aggregate data into the broad lymphoma groupings of Hodgkin and non‐Hodgkin, either because primary source information was recorded in that way, or because diagnostic standards were inconsistently applied. Population‐based data on age and gender are presented using the latest WHO classification, revealing considerable subtype heterogeneity. Aetiological factors highlighted include the unexplained male bias that is strikingly evident for many subtypes across all ages, and the relationship with autoimmune disease, which, although often associated with increased lymphoma risk, is generally more common in females. This is an exciting time for epidemiological research into haematological malignancies, where the application of modern disease classifications is beginning to discriminate between subtypes revealing features that future aetiological hypotheses should seek to address.
Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral ...striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.
In molecular evolutionary analyses, short DNA sequences are used to infer phylogenetic relationships among species. Here we apply this principle to the study of bacterial biosynthesis, enabling the ...targeted isolation of previously unidentified natural products directly from complex metagenomes. Our approach uses short natural product sequence tags derived from conserved biosynthetic motifs to profile biosynthetic diversity in the environment and then guide the recovery of gene clusters from metagenomic libraries. The methodology is conceptually simple, requires only a small investment in sequencing, and is not computationally demanding. To demonstrate the power of this approach to natural product discovery we conducted a computational search for epoxyketone proteasome inhibitors within 185 globally distributed soil metagenomes. This led to the identification of 99 unique epoxyketone sequence tags, falling into 6 phylogenetically distinct clades. Complete gene clusters associated with nine unique tags were recovered from four saturating soil metagenomic libraries. Using heterologous expression methodologies, seven potent epoxyketone proteasome inhibitors (clarepoxcins A–E and landepoxcins A and B) were produced from these pathways, including compounds with different warhead structures and a naturally occurring halohydrin prodrug. This study provides a template for the targeted expansion of bacterially derived natural products using the global metagenome.
Background
To determine short‐ and long‐term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic ...neuroendocrine tumor (pNET).
Methods
The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi‐institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.
Results
A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000‐2004: 9.3% vs 2013‐2016: 54.8%; P < 0.01). In the matched cohort (n = 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200 mL, P < 0.001), lower incidence of Clavien‐Dindo ≥ III complications (12.1% vs 24.8%, P = 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P = 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5‐year cumulative recurrence, 10.1% vs 31.1%, P < 0.001), yet equivalent overall survival (OS) rate (5‐year OS, 92.1% vs 90.9%, P = 0.550) compared with patients who underwent OPD.
Conclusion
Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long‐term OS.
Background and Objectives
Lack of high‐level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its ...non‐standard of care use.
Methods
Patients with primary GEP NETs who underwent curative‐intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence‐free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts.
Results
In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five‐year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor‐specific characteristics (RFS P < .01).
Conclusions
Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high‐risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.
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