Cytomegalovirus infection in patients undergoing autologous peripheral blood stem cell transplantation

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Publication of the International Union Against Cancer

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20 -24th day of their menstrual cycle. The hypothesis that breast cancer (BC) is related to ovarian function dates back over a century. 1 Epidemiological, in vitro and in vivo studies conducted in the second half of the last century made it clear that steroid sex hormones regulate cell proliferation and play a major role in promoting BC. 2,3 Several mechanistic hypotheses for the development of BC have been proposed, 2,4 but until recently, hormone measurements by epidemiological studies have failed to corroborate any of them. Over the last decade, however, several prospective cohort studies in postmenopausal women have shown that BC development is preceded by alterations in levels of circulating sex hormones. 5 High serum levels of free and total estradiol, total testosterone and other estrogens and androgens, as well as low serum levels of sex hormone-binding globulin (SHBG), have been found to be implicated in the risk of BC. 5 Our own study also indicated that high serum levels of free testosterone are associated with the risk of BC. 6 These prospective investigations were carried out with the help of thousands of healthy women who provided blood samples for storage and future nested-in-the-cohort case-control analyses. Compared to case control studies in clinical settings, the strengths of prospective studies are that control subjects belong to the same cohort that generates the incident disease cases and that blood is collected before the diagnosis of cancer thereby excluding abnormal values that may be due to overt illness. Hormone measurements in premenopausal women are difficult to interpret because serum levels change with the menstrual cycle and because cycle length varies inter-and intra-individually. Only a few prospective investigations have addressed the role of sex hormone levels in BC before the menopause; 7-10 all considered small numbers of case women and did not produce clear results. The endocrine basis of BC in premenopause is therefore the subject of several disparate hypotheses. These include the hypothesis of Grattarola, advanced in the 1960s, 11-12 that hyperandrogenism with luteal inadequacy plays a role in the induction of BC, and of Henderson et al. The present prospective study was designed to investigate whether luteal inadequacy and hyperandrogenism increase the risk of BC in premenopausal women. We collected blood samples from premenopausal women participating in the study on Hormones and Diet in the Etiology of Breast Tumors (ORDET). 6,14 Samples were taken between the 20th and 24th day of the cycle (theoretically during the mid luteal phase). The first day of menstrual bleeding subsequent to sampling was also recorded to provide an additional data point for correctly locating the sampling day within the cycle. In these women, we analyzed the relationship between BC and serum levels of the androgens dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, androstenedione and androstanediol-glucoronide (Adiol-G), and also progesterone, 17-OH-progesterone, SHBG, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Estradiol was not considered in the present analysis because of its extraordinary intra-individual variation in premenopausal women

Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: A GIMEMA, ERIC and UK CLL FORUM study

We performed an observational study on the efficacy of bendamustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del (17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398)

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Investigation of the time-dependent failure of InGaN-based LEDs submitted to reverse-bias stress

This paper demonstrates that when InGaN LEDs are submitted to a constant reverse bias, they can show a time-dependent breakdown, that leads to the catastrophic failure of the devices. By submitting green and blue LEDs to constant voltage stress in the range between -40 V and -60 V we demonstrate that: (i) under reverse bias conditions, current is focused on localized paths, whose positions can be identified by electroluminescence measurements, and that originate from the presence of extended defects; (ii) during a constant voltage stress, the reverse current of the LEDs gradually increases; (iii) for longer stress times, all devices show a time-dependent breakdown; (iv) time-to-failure has an exponential dependence on stress voltage, and is Weibull-distributed

Bortezomib-induced muscle toxicity in multiple myeloma

Multiple myeloma (MM) accounts for ∼13% of all hematologic malignancies. Bortezomib treatment is effective in MM, but can be complicated with neurological side effects. We describe a patient with symptomatic MM who had a reversible metabolic myopathy associated with bortezomib administration and pathologically characterized by excessive storage of lipid droplets together with mitochondrial abnormalities. In a single-center prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, 7 developed muscular signs and/or symptoms. The myopathy was characterized by a proximal muscle weakness involving lower limbs and was an early complication. Complete resolution of muscle weakness occurred after treatment discontinuation. Conversely, none of the patients who received a treatment without bortezomib developed muscular symptoms. Experimental studies demonstrate that in primary human myoblasts bortezomib at low concentrations leads to excessive storage of lipid droplets together with structural mitochondrial abnormalities, recapitulating the pathologic findings observed in patient's muscle. Our data suggest that patients treated with bortezomib should be monitored for muscular signs and/or symptoms and muscle weakness should alert the clinician to the possibility of myopathy. Bortezomib-induced metabolic myopathy is a potentially reversible entity with important implications for management and treatment of patients with MM