Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β2-Glycoprotein I

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti–β₂-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.     

Self-reported time-to-relapse following smoking cessation: Comparison by operationalization of initial abstinence classification

Aims: Relapse rates among cigarette smokers are high. Few studies have examined time-to-relapse using survival analysis in racially/ethnically diverse smokers and initial abstinence criteria have been inconsistent or unspecified. This study compared survival curves using two common definitions of initial abstinence. We hypothesized greater relapse rates among participants abstinent for only 24 hours (h) at the end-of-therapy (EOT) compared with 7 days. Methods: Adult smokers (59% Black, 22% Hispanic and 17% White) received 8-sessions of group cognitive behavioural therapy (CBT) plus transdermal nicotine patches and were assessed monthly up to 12 months post-EOT. Participants reporting abstinence (7-day point prevalence abstinence [ppa] or 24-h ppa) at the EOT were included in Kaplan–Meier curves. Results: Of 301 participants, 120 (40%) reported 7-day ppa at the EOT and an additional 29 (10%) reported 24-h ppa only. Over the 12-month follow-up period, nearly 50% remained abstinent. Of those who resumed smoking, most relapses occurred within the first three months. Survival curves indicated that median survival was 207 and 225 days for 7-day and 24-h definitions of abstinence, respectively. The difference in time-to-relapse between participants abstinent for 24?h at the EOT versus 7-days was not significant (p?=?0.14). Conclusions: Operationalization of initial abstinence is important for relapse analyses and comparisons of survival curves across samples. Participants reported high rates of abstinence and relapse rates were relatively low. Contrary to expectations, 24-h ppa at the EOT was not associated with greater relapse than 7-day abstinence. This suggests either measure may be utilized in relapse prevention research in racially/ethnically diverse treatment-seekers.     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

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Outcomes of coronary artery bypass grafting in patients with heart failure with a midrange ejection fraction

BackgroundCoronary artery bypass grafting (CABG) improves survival in patients with heart failure and severely reduced left ventricular systolic function (LVEF). Limited data exist regarding adverse cardiovascular event rates after CABG in patients with heart failure with midrange ejection fraction (HFmrEF; LVEF > 40% and < 55%).MethodsWe analyzed data on isolated CABG patients from the Veterans Affairs national database (2010-2019). We stratified patients into control (normal LVEF and no heart failure), HFmrEF, and heart failure with reduced LVEF (HFrEF) groups. We compared all-cause mortality and heart failure hospitalization rates between groups with a Cox model and recurrent events analysis, respectively.ResultsIn 6533 veterans, HFmrEF and HFrEF was present in 1715 (26.3%) and 566 (8.6%) respectively; the control group had 4252 (65.1%) patients. HFrEF patients were more likely to have diabetes mellitus (59%), insulin therapy (36%), and previous myocardial infarction (31%). Anemia was more prevalent in patients with HFrEF (49%) as was a lower serum albumin (mean, 3.6 mg/dL). Compared with the control group, a higher risk of death was observed in the HFmrEF (hazard ratio [HR], 1.3 [1.2-1.5)] and HFrEF (HR, 1.5 [1.2-1.7]) groups. HFmrEF patients had the higher risk of myocardial infarction (subdistribution HR, 1.2 [1-1.6]; P = .04). Risk of heart failure hospitalization was higher in patients with HFmrEF (HR, 4.1 [3.5-4.7]) and patients with HFrEF (HR, 7.2 [6.2-8.5]).ConclusionsHeart failure with midrange ejection fraction negatively affects survival after CABG. These patients also experience higher rates myocardial infarction and heart failure hospitalization.     

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

Colon Cancer in Patients Under 25 Years Old: A Different Disease?

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A profile of invasive cutaneous malignant melanoma in Malta: 1993–2002

BACKGROUND: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. OBJECTIVE: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. RESULTS: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100,000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100,000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (< or = 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. CONCLUSION: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.