Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis

BACKGROUND: Breast cancer is a genetically complex disease, which involves the accumulation of various structural and numerical chromosomal aberrations. AIM: To assess the numerical status of chromosomes 16 and X by interphase cytogenetics, in 114 women with primary invasive breast carcinomas, in relation to clinicopathological parameters, patients' overall survival and indices of cell growth (c-erbB-2, topoisomerase IIalpha (topoIIalpha)) and cell survival (caspase-3, bcl-2). Experimental design: Chromogenic in situ hybridisation with pericentromeric probes was performed for molecular analysis, while oestrogen and progesterone receptors, cerbB-2, topoIIalpha, caspase-3 and bcl-2 expression was immunohistochemically detected (ABC/HRP). The results were statistically assessed by univariate and multivariate analyses. RESULTS: Polysomy of chromosomes 16 and X was detected as the predominant aberration (73.7% and 57.9%, respectively). Gain of chromosome 16 copies was associated with high nuclear grade (p = 0.009), increased tumour size (p = 0.041), advanced stage (p = 0.002), the expression of topoIIalpha (p = 0.005) and worse overall survival by multivariate analysis (p = 0.032). Chromosome X polysomy was increased in ductal carcinomas of high histological grade (p = 0.008), in high nuclear grade tumours (p = 0.001), and was associated with the expression of topoIIalpha (p = 0.005), loss of caspase-3 (p = 0.036) and impaired prognosis of ductal carcinomas (p = 0.041). CONCLUSIONS: Polysomy of chromosomes 16 and X was reported as the predominant alteration in phenotypically aggressive breast tumours, characterised by poor differentiation, increased growth potential and impaired prognosis, whereas gain of chromosome X in particular is probably implicated in cell survival.     

Engagement with INSPIRE,an Online Program for Hematopoietic Cell Transplantation Survivors

In a secondary analysis of a randomized controlled trial (RCT), we examined participants' engagement with INSPIRE, a personalized online program for hematopoietic cell transplantation (HCT) survivors that focuses on cancer-related distress, depression, fatigue, and health care needs. We approached all adult, 3- to 18-year HCT survivors treated for hematologic malignancy without relapse or second cancer in the previous 2 years for participation in an RCT with either immediate or delayed access to INSPIRE. Participants with immediate access could view the online material at any time. Data included page view tracking, medical records, and patient-reported outcomes, including the Short Form 36 and Cancer and Treatment Distress (CTXD) measures. Of 1322 eligible HCT survivors, 771 (58%) completed the baseline assessment, and 451 received immediate INSPIRE access and were included in analyses. The cohort was 56% male, with a mean age of 52 ± 12.2 years, and 26% received an autologous transplant. Most (77%) logged into the INSPIRE site at least once, and 48% viewed ≥8?pages. Survivors who viewed ≥2?pages were more likely to be age ≥40 years (relative risk [RR], 1.41; 95% confidence interval [CI], 1.10 to 1.80), to be female (RR, 1.22; 95% CI, 1.07 to 1.40), to have chronic graft-versus-host disease (RR, 1.28; 95% CI, 1.08 to 1.51), to be less than 10 years post-HCT (RR, 1.19; 95% CI, 1.01 to 1.39), and to have moderate CTXD distress (RR, 1.34; 95% CI, 1.14 to 1.57). Engagement did not differ by race, education, income, rural/urban residence, computer experience, donor type, or depression (all P?≥?.50). The INSPIRE online program was widely used, including by those who often have reduced access to care after treatment.     

Pre‐ and postoperative magnetic resonance imaging (MRI) findings in patients treated with laparoscopic sacrocolpopexy. Is it a safe procedure for all patients?

Introduction

Laparoscopic sacrocolpopexy (LSCP) is a reference operation for apical compartment prolapse repair. Aim of this study is to describe the early and midterm postoperative MRI findings of the lumbosacral region (LSR) in patients undergoing LSCP and to detect any imaging changes that the presence of the mesh may cause on patients with preexisting degenerative disease of the LSR.

Methods

Patients with POP‐Q grade III and IV uterovaginal or vaginal vault prolapse who were considered eligible for LSCP were invited to participate. An MRI of the LSR was performed preoperatively and then 3 and 12 months postoperatively. Patients with vaginal vault prolapse underwent LSCP, while women with uterovaginal prolapse were treated with the vaginally assisted laparoscopic sacrocolpopexy (VALS).

Results

A total of 30 patients were included in the study; 18 (60%) underwent LSCP and 12 (40%) VALS. On preoperative MRIs, 83.3% (25/30) of patients had degenerative changes and 70% (21/30) reported having low back pain (LBP). Postoperative MRIs did not reveal any imaging changes compared to the preoperative MRI findings both for patients with or without preexisting degenerative abnormalities of the LSR. No significant changes in the LBP score were observed postoperatively.

Conclusions

Any bone marrow or soft‐tissue changes at MRIs of the LSR early after the insertion of a synthetic mesh, does not constitute an expected postoperative finding and should raise the suspicion of an ongoing inflammatory or infectious spinal process (spondylodiscitis). Additionally, LSCP seems to be a safe surgical approach for women with preexisting degenerative disease of the LSR.     

Transplant‐associated thrombotic microangiopathy: Incidence,prognostic factors,morbidity, and mortality in allogeneic hematopoietic cell transplantation

Renewed interest has emerged in transplant‐associated thrombotic microangiopathy (TA‐TMA) with novel prognostic, diagnostic, and treatment algorithms. We aimed to investigate the incidence, prognostic factors, morbidity, and mortality of TA‐TMA in allogeneic hematopoietic cell transplantation (HCT) recipients. We enrolled consecutive HCT recipients (1990‐2017). Among 758 patients, 116 (15.5%) were diagnosed with TA‐TMA. In the multivariate analysis, TBI‐based conditioning, viral infections, acute and chronic GVHD remained independent predictors of TA‐TMA. With a median follow‐up of 23 (range 0.1‐329) months, TA‐TMA resulted in significantly lower overall survival (OS). In the multivariate analysis, TA‐TMA remained an independent predictor of OS, along with relapse, acute, and chronic GVHD. Among 116 TA‐TMA patients, 70 developed renal (56) and/or neurologic (26) dysfunction that would be necessary for TA‐TMA diagnosis according to the Bone Marrow Transplant Clinical Trials Network criteria. TA‐TMA patients with renal dysfunction showed increased rates of acute GVHD, but no difference in OS compared to patients without renal dysfunction. However, neurologic dysfunction resulted in significantly lower OS. In conclusion, TA‐TMA is associated with increased morbidity and mortality in allogeneic transplant recipients. Successful prevention and treatment strategies of infections and GVHD need to be timely employed to improve survival in this complex setting.     

Venom immunotherapy in patients with allergic reactions to insect stings

Introduction: Allergy to Hymenoptera (Apis mellifera, Vespula species, Polistes species, Vespa crabro) venom can be safely and effectively treated by venom immunotherapy (VIT), which in the 40 years since its introduction has been able to prevent reactions to stings, and to treatment as well, though systemic reactions, occasionally severe, are possible.

Areas covered: We reviewed the recent literature on VIT by searching in PubMed for the terms ‘venom immunotherapy’ and ‘Hymenoptera venom immunotherapy’ to highlight the current status of VIT and the likely development in the coming years.

Expert commentary: VIT, provided the correct choice of the venom and adequate venom preparations and maintenance doses are used, is a treatment of great value in preventing systemic reactions to Hymenoptera stings. A 5-year duration ensures a prolonged tolerance to stings following VIT discontinuation, unless patients suffer from mastocytosis. In fact, due to reports of fatal reactions after stopping VIT, patients with mastocytosis, or with very severe reactions to stings, need an indefinite duration of treatment.     

The Prevalence of Malnutrition in Oncology Patients in a Greek General Hospital. Evaluation Using Anthropometric and Laboratory Measurements

Background and Purpose

The incidence of malnutrition in oncology patients is high, and it depends on the type, location and stage of the tumor and on the treatment. In this empirical study, we aimed to evaluate the prevalence of malnutrition in adults with cancer in a Greek general hospital and to investigate the relationship between objective and subjective nutritional assessment of the patients.

Methods

We assessed the nutritional status of 88 oncology patients within 48 hours of admission, using the three nutrition screening tools Subjective Global Assessment (SGA), Nutritional Risk Screening 2002 (NRS 2002) and Malnutrition Screening Tool (MST). The degree of malnutrition was determined using anthropometric measurements and laboratory nutrition-related parameters.

Results

In this Greek hospital, the rate of malnutrition risk in patients with cancer varied, ranging from 35.3% to 45.5%, depending on the nutrition screening tool used. Men, elderly patients and patients with gastric cancer were demonstrated to be at higher risk of malnutrition. Malnourished patients showed significant weight loss, with anorexia being the main gastrointestinal symptom. The objective laboratory nutrition parameters did not always indicate nutritional deficiency, but the anthropometric measurements showed a decrease in these patients.

Conclusions

The problem of malnutrition among Greek oncology patients appears to be significant and there is a need for further efforts in its detection and management.

     

Caregivers of advanced cancer patients: feelings of hopelessness and depression

To investigate whether the advanced cancer patients' caregivers' depression and hopelessness are affected by patients' demographic and clinical characteristics and by caregivers' sociodemographic variables. Moreover, the relation between cancer patients' and caregivers' depression and hopelessness was assessed. One hundred five patients with advanced cancer receiving palliative care and 96 caregivers were enrolled in the study. The patients and their caregivers completed the Beck Depression Inventory and the Beck Hopelessness Scale while researchers recorded data on demographic characteristics, disease status, and treatment regimen. The analysis showed that significant associations were found between patient male sex and caregiver's depression (P = .007) and hopelessness (P = .002), between patient family status and caregiver's depression (P = .031) and hopelessness (P = .001), and between patient radiotherapy treatment and caregiver's hopelessness (P = .017). Moreover, statistically significant correlation was found between patient's and caregiver's depression (P = .041). Generalized estimating equations showed that the patients characteristics that predicted caregivers' hopelessness were family status (P = .017), radiotherapy (P = .025), and the caregiver's relation to patient (P = .059). The findings suggest that caregiver's hopelessness is predicted by cancer patient's characteristics and that patient's depression is correlated to that of caregiver. The findings provide a base for future research.     

The effect of a commercial competitive exclusion product on the selection of enrofloxacin resistance in commensal E. coli in broilers

The effect of a competitive exclusion product (Aviguard®) on the selection of fluoroquinolone resistance in poultry was assessed in vivo in the absence or presence of fluoroquinolone treatment.

Two experiments using a controlled seeder-sentinel animal model (2 seeders: 4 sentinels per group) with one-day-old chicks were used. For both experiments, as soon as the chicks were hatched, the birds of two groups were administered Aviguard® and two groups were left untreated. Three days later, all groups were inoculated with an enrofloxacin-susceptible commensal E. coli strain. Five days after hatching, two birds per group were inoculated with either a bacteriologically fit or a bacteriologically non-fit enrofloxacin-resistant commensal E. coli strain. In experiment 2, all groups were orally treated for three consecutive days (days 8–10) with enrofloxacin. Throughout the experiments, faecal excretion of all inoculated E. coli strains was determined on days 2, 5, 8, 11, 18 and 23 by selective plating (via spiral plater). Linear mixed models were used to assess the effect of Aviguard® on the selection of fluoroquinolone resistance.

The use of Aviguard® (P?E. coli when no enrofloxacin treatment was administered. However, this beneficial effect disappeared (P?=?0.37) when the birds were treated with enrofloxacin. Similarly, bacterial fitness of the enrofloxacin-resistant E. coli strain used for inoculation had an effect (P?P?=?0.70).

Thus, enrofloxacin treatment cancelled the beneficial effects from administrating Aviguard® in one-day-old broiler chicks and resulted in an enrofloxacin-resistant flora.

RESEARCH HIGHLIGHTS

• The effect of Aviguard® on the selection of enrofloxacin resistance was assessed in vivo.

• Without enrofloxacin, Aviguard® reduced the selection of enrofloxacin resistance.

• When enrofloxacin was administered, it cancelled the beneficial effect of Aviguard®.

     

Hydrolyzed Poly(2‐plenyl‐2‐oxazoline)s in Aqueous Media and Biological Fluids

Hydrolyzed poly(2‐phenyl‐2‐oxazoline)s (PPhOx) are synthesized by partial hydrolysis of PPhOx in order to produce self‐assembling copolymers with chargeable and hydrophobic units. The resulting poly(ethylene imine‐co‐2‐phenyl‐2‐oxazoline) [P(EI‐co‐PhOx)] amphiphilic copolymers contain phenyl‐oxazoline and ethylene imine segments in a random sequence and their chemical structure is confirmed by ¹H NMR and attenuated total reflection‐Fourier transform infrared spectroscopy. Static and dynamic light scattering experiments show that in aqueous solutions the random copolymers associate into aggregates of sizes in the range between 50 and 200 nm depending on the solution conditions and hydrophobic content. The positive charge of the nanoaggregates that is caused by protonation of the amine nitrogen is confirmed by zeta potential measurements. Self‐assembly in phosphate buffered saline results in large aggregates. The aggregates are proved to interact with fetal bovine serum proteins. This investigation shows that hydrolyzed phenyl oxazoline‐based copolymers provide stable amphiphilic nanoparticles able to interact with biological macromolecules for biotechnological and pharmaceutical applications.