Colorectal cancer (CRC) incidence in the United States is declining rapidly overall but, curiously, is increasing among young adults. Age-specific and birth cohort patterns can provide etiologic ...clues, but have not been recently examined.
CRC incidence trends in Surveillance, Epidemiology, and End Results areas from 1974 to 2013 (n = 490 305) were analyzed by five-year age group and birth cohort using incidence rate ratios (IRRs) and age-period-cohort modeling.
After decreasing in the previous decade, colon cancer incidence rates increased by 1.0% to 2.4% annually since the mid-1980s in adults age 20 to 39 years and by 0.5% to 1.3% since the mid-1990s in adults age 40 to 54 years; rectal cancer incidence rates have been increasing longer and faster (eg, 3.2% annually from 1974-2013 in adults age 20-29 years). In adults age 55 years and older, incidence rates generally declined since the mid-1980s for colon cancer and since 1974 for rectal cancer. From 1989-1990 to 2012-2013, rectal cancer incidence rates in adults age 50 to 54 years went from half those in adults age 55 to 59 to equivalent (24.7 vs 24.5 per 100 000 persons: IRR = 1.01, 95% confidence interval CI = 0.92 to 1.10), and the proportion of rectal cancer diagnosed in adults younger than age 55 years doubled from 14.6% (95% CI = 14.0% to 15.2%) to 29.2% (95% CI = 28.5% to 29.9%). Age-specific relative risk by birth cohort declined from circa 1890 until 1950, but continuously increased through 1990. Consequently, compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer (IRR = 2.40, 95% CI = 1.11 to 5.19) and quadruple the risk of rectal cancer (IRR = 4.32, 95% CI = 2.19 to 8.51).
Age-specific CRC risk has escalated back to the level of those born circa 1890 for contemporary birth cohorts, underscoring the need for increased awareness among clinicians and the general public, as well as etiologic research to elucidate causes for the trend. Further, as nearly one-third of rectal cancer patients are younger than age 55 years, screening initiation before age 50 years should be considered.
The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's ...pathologic features.
To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.
Prospective cohort study.
Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.
The first 12 consecutive COVID-19-positive deaths.
Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated.
Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (
= 10) or outpatient sector (
= 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.
Limited sample size.
The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.
University Medical Center Hamburg-Eppendorf.
To develop and validate a radiomics nomogram for preoperative prediction of lymph node (LN) metastasis in patients with colorectal cancer (CRC).
The prediction model was developed in a primary cohort ...that consisted of 326 patients with clinicopathologically confirmed CRC, and data was gathered from January 2007 to April 2010. Radiomic features were extracted from portal venous-phase computed tomography (CT) of CRC. Lasso regression model was used for data dimension reduction, feature selection, and radiomics signature building. Multivariable logistic regression analysis was used to develop the predicting model, we incorporated the radiomics signature, CT-reported LN status, and independent clinicopathologic risk factors, and this was presented with a radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. An independent validation cohort contained 200 consecutive patients from May 2010 to December 2011.
The radiomics signature, which consisted of 24 selected features, was significantly associated with LN status (P < .001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included the radiomics signature, CT-reported LN status, and carcinoembryonic antigen level. Addition of histologic grade to the nomogram failed to show incremental prognostic value. The model showed good discrimination, with a C-index of 0.736 (C-index, 0.759 and 0.766 through internal validation), and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (C-index, 0.778 95% CI, 0.769 to 0.787) and good calibration. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful.
This study presents a radiomics nomogram that incorporates the radiomics signature, CT-reported LN status, and clinical risk factors, which can be conveniently used to facilitate the preoperative individualized prediction of LN metastasis in patients with CRC.
In December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited.
We sought to ...evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19.
Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020, to February 5, 2020, were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients.
We identified 269 (49.1%) of 548 patients as severe cases on admission. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-α), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19.
Patients with older age, hypertension, and high lactate dehydrogenase level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have a high risk of death.
Multiorgan and Renal Tropism of SARS-CoV-2 Puelles, Victor G; Lütgehetmann, Marc; Lindenmeyer, Maja T ...
The New England journal of medicine,
08/2020, Letnik:
383, Številka:
6
Journal Article
Intraoperative hypotension is a common side effect of general anaesthesia and might lead to inadequate organ perfusion. It is unclear to what extent hypotension during noncardiac surgery is ...associated with unfavourable outcomes.
We conducted a systematic search in PubMed, Embase, Web of Science, and CINAHL, and classified the quality of retrieved articles according to predefined adapted STROBE and CONSORT criteria. Reported strengths of associations from high-quality studies were classified into end-organ specific injury risks, such as acute kidney injury, myocardial injury, and stroke, and overall organ injury risks for various arterial blood pressure thresholds.
We present an overview of 42 articles on reported associations between various absolute and relative intraoperative hypotension definitions and their associations with postoperative adverse outcomes after noncardiac surgery. Elevated risks of end-organ injury were reported for prolonged exposure (≥10 min) to mean arterial pressures <80 mm Hg and for shorter durations <70 mm Hg. Reported risks increase with increased durations for mean arterial pressures <65–60 mm Hg or for any exposure <55–50 mm Hg.
The reported associations suggest that organ injury might occur when mean arterial pressure decreases <80 mm Hg for ≥10 min, and that this risk increases with blood pressures becoming progressively lower. Given the retrospective observational design of the studies reviewed, reflected by large variability in patient characteristics, hypotension definitions and outcomes, solid conclusions on which blood pressures under which circumstances are truly too low cannot be drawn. We provide recommendations for the design of future studies.
(PROSPERO ID). CRD42013005171.
Ibrutinib, an inhibitor of Bruton's tyrosine kinase, and venetoclax, an inhibitor of B-cell lymphoma 2 protein, have been approved for patients with chronic lymphocytic leukemia (CLL). Preclinical ...investigations have indicated potential synergistic interaction of their combination.
We conducted an investigator-initiated phase 2 study of combined ibrutinib and venetoclax involving previously untreated high-risk and older patients with CLL. All patients had at least one of the following features: chromosome 17p deletion, mutated
, chromosome 11q deletion, unmutated
, or an age of 65 years or older. Patients received ibrutinib monotherapy (420 mg once daily) for 3 cycles, followed by the addition of venetoclax (weekly dose escalation to 400 mg once daily). Combined therapy was administered for 24 cycles. Response assessments were performed according to International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Minimal residual disease was assessed by means of multicolor flow cytometry in bone marrow (sensitivity, 10
).
A total of 80 patients were treated. The median age was 65 years (range, 26 to 83). A total of 30% of the patients were 70 years of age or older. Overall, 92% of the patients had unmutated
,
aberration, or chromosome 11q deletion. With combined treatment, the proportions of patients who had complete remission (with or without normal blood count recovery) and remission with undetectable minimal residual disease increased over time. After 12 cycles of combined treatment, 88% of the patients had complete remission or complete remission with incomplete count recovery, and 61% had remission with undetectable minimal residual disease. Responses were noted in older adults and across all high-risk subgroups. Three patients had laboratory evidence of tumor lysis syndrome. The adverse-event profile was similar to what has been reported with ibrutinib and venetoclax.
In this study, combined venetoclax and ibrutinib was an effective oral regimen for high-risk and older patients with CLL. (Funded by AbbVie and others; ClinicalTrials.gov number, NCT02756897.).
Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group ...previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility.
A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively.
Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation (
< .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively.
Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).
Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia.
To assess whether tramadol use, when compared with codeine use, is ...associated with an increased risk of hospitalization for hypoglycemia.
A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results.
Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score-adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis.
The cohort included 334,034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 95% CI, 1.09-2.10), particularly elevated in the first 30 days of use (OR, 2.61 95% CI, 1.61-4.23). This 30-day increased risk was confirmed in the cohort (HR, 3.60 95% CI, 1.56-8.34) and case-crossover analyses (OR, 3.80 95% CI, 2.64-5.47).
The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.
Older adults with acute myeloid leukemia (AML) who are not fit for standard chemotherapy historically have poor outcomes. Approximately 12-15% of older patients with AML harbor isocitrate ...dehydrogenase 2 (IDH2) gene mutations. Enasidenib is an oral inhibitor of mutant IDH2 proteins. Among 39 patients with newly diagnosed mutant-IDH2 AML who received enasidenib monotherapy in this phase I/II trial, median age was 77 years (range 58-87) and 23 patients (59%) had had an antecedent hematologic disorder. The median number of enasidenib treatment cycles was 6.0 (range 1-35). The most common treatment-related adverse events were indirect hyperbilirubinemia (31%), nausea (23%), and fatigue, decreased appetite, and rash (18% each). Treatment-related grade 3-4 cytopenias were reported for eight patients (21%); there was no treatment-related grade 3-4 infections. Twelve patients achieved a response (overall response rate 30.8% 95% CI 17.0%, 47.6%), including seven patients (18%) who attained complete remission. At a median follow-up of 8.4 months, the median duration of any response was not reached (NR). Median overall survival for all patients was 11.3 months (95% CI 5.7, 15.1), and was NR for responders. Oral, outpatient targeted treatment with enasidenib may benefit older adults with newly diagnosed mutant-IDH2 AML who are not candidates for cytotoxic regimens.
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