Cytotoxic chemotherapy preceding apheresis of peripheral blood progenitor cells can affect the early reconstitution phase of naive T cells after autologous transplantation

Transient T cell immunodeficiency is a common complication following hematopoietic stem cell transplantation. In breast cancer patients transplanted with autologous peripheral blood progenitor cells (PBPC) harvested after cytotoxic treatment with either cyclophosphamide or epirubicin plus paclitaxel, we evaluated T cells infused in grafts and in peripheral blood during the early reconstitution phase. We found that PBPC grafts harvested after treatment with epirubicin plus paclitaxel contained substantially larger numbers of T cells with less altered composition than after cyclophosphamide. Three months after high-dose cytotoxic chemotherapy, the numbers and the kinetics of circulating naive T cells, but not of memory and CD28- T cells, correlated positively with the number of naive T cells infused PBPC grafts. Finally, retrospective analysis of two cohorts of patients transplanted in different clinical settings with PBPC grafts harvested following cyclophosphamide or epirubicin plus paclitaxel showed apparently different susceptibilities to develop endogenous varicella zoster virus reactivation in the first year after high-dose cytotoxic chemotherapy. On the whole, these data indicate that number and composition of T cells in PBPC grafts vary according to the former cytotoxic therapy, and suggest that autologous transfer of T cells may accelerate the early T cell reconstitution phase and possibly ameliorate immune competence in patients rendered lymphopenic by high-dose chemotherapy.     

Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers

Journal of Neurology - Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of...     

The role of the ear,nose and throat specialist in diagnosing headaches

Neurological Sciences - The revised International Headache Society classification (2004) represents a very good reference also for ear, nose and throat (ENT) specialists and can be largely shared....     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.     

Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy

The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients (≥?65 years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-positive breast cancer patients given hypofractionated whole-breast radiotherapy from June 2009 to September 2016. Baseline comorbidities considered in the hypertension-augmented Charlson Comorbidity Index (hCCI) were retrospectively retrieved. Total hCCI scores were classified as no comorbidity (hCCI?=?0), low burden of comorbidity (hCCI?=?1), and high burden of comorbidity (hCCI?≥?2). Competing risk analysis was used to estimate the 5-year cumulative incidence of HT discontinuation. Fine and Gray models were used to estimate the adjusted subhazard ratio (SHR) of HT discontinuation by hCCI score. HT was initially prescribed for 85.6% of patients and almost all of them (468/471) took it for at least one month. It was subsequently discontinued by 45 patients (9.6%), for an overall 5-year cumulative incidence of 11.7%. The 5-year cumulative incidence of HT discontinuation rose from 3.9% in the youngest age group (65–69 years) to 23.3% in the oldest (≥?80 years) (p?=?0.005). Baseline comorbidity had some effect on the likelihood of discontinuing HT, but only among patients with a low burden of comorbidity (hCCI?=?1, SHR 2.00, 95%CI 0.95–4.20). Adherence to HT was better in our sample than in the literature, probably because patients were selected and motivated to continue HT. This confirms the importance of communication with patients to improve adherence to HT. We confirmed the association between HT discontinuation and older age, while comorbidity had a limited influence.     

Cognitive deficits and their relationship to other neurological complications in chronic alcoholic patients.

In randomly selected chronic alcoholics hospitalised for the first time for detoxification a high prevalence (68%) of cognitive deficits was found. Peripheral neuronal damage was seen in 74%, autonomic neuronal damage in 24%. Cognitive deficits were not correlated with age, daily ethanol intake, duration of alcohol abuse or severity of liver damage. There was no correlation of peripheral, autonomic and central nervous system damage. Alcohol-induced damage of the nervous system is a common complication of chronic alcoholism, whose clinical importance often obscures possible concomitant liver damage.     

Breast cancer in the elderly: the role of adjuvant radiation therapy

PURPOSE: To evaluate available data on breast conserving surgery (BCS) with or without radiation therapy (RT), and alternative options (e.g. Tamoxifen alone) (Tam), focusing specifically on the older patients. METHODS AND MATERIALS: The MEDLINE was searched for the terms elderly, BCS, adjuvant/postoperative RT, Tamoxifen, and randomized trials from 1992 to 2002. RESULTS: Authors reviewed papers of general interest on the elderly and breast cancer (BC), meta-analysis, randomized trials on BCS+/-RT and Tam+/-surgery without RT, retrospective non-randomized trials, and reported on prognostic factors for local recurrence in BCS alone, including biomarkers, attempts made to define a low-risk group, and methods of modification of the current, protracted standard adjuvant RT course. CONCLUSIONS: Postoperative RT after BCS has a firm rationale; in current clinical practice, if the BCS+RT is medically appropriate and the patient shares the choice, after a full information of the available options and their implications, it is clinically sound to propose this approach. However, there is controversy whether a subgroup of elderly patients could be safely spared: in this setting a randomized trial is clearly warranted.     

Long-lasting induction of Notch2 in the hippocampus of kainate-treated adult mice

Notch proteins are involved in cell fate specification during development in tissues including brain. Little is known about their function in adulthood. Recently, Notch receptors have been hypothesized to play a role in neurodegeneration and in particular in Alzheimer's disease (Notch1) and CADASIL (Notch3). Here we show that another family member (Notch2) is constitutively expressed in adult mouse hippocampus in DG and not in CA1 and CA3 neurons. Treatment with kainic acid resulted in marked Notch2 induction in pyramidal neurons of CA1 and in a subpopulation of CA3 neurons surviving the lesion and protein expression was still detectable 6 weeks after drug treatment. These results suggest Notch2 involvement in the response of postmitotic neurons to excitotoxic stimuli.     

Extremity Soft Tissue Sarcoma: Adding to the Prognostic Meaning of Local Failure

Background We explored the prognostic meaning of local relapse and surgical margins in adult soft tissue sarcoma of the extremities. Methods Out of a series of 1017 patients with extremity soft tissue sarcoma treated over 20 years, we picked a group of 238 patients operated on at our institution for their first local relapse: 88 after their primary operation performed at the same center and 150 elsewhere. At operation for relapse, margins were microscopically negative in 77% and 75% of patients, respectively. Median follow-up was 107 months. Results The 10-year mortality rate was 22% in the absence of local relapse, whereas in locally relapsing patients it was 54% and 43%, respectively, for patients first operated on at our institute and for those who were not. The hazard ratio of positive versus negative surgical margins was 1.7 for cause-specific death and 2.1 for distant metastases in patients first operated on at our institute, as opposed to 1.2 and 1.3 for the others. Conclusions Local relapse was an unfavorable prognostic factor. In the face of a consistent surgical policy for local relapse in a single-institution setting, patients relapsing after the first operation performed at our institution received rescue treatment less frequently than those previously operated on outside a referral center. This is likely due to an inherently higher tumor aggressiveness. In the presence of such a higher aggressiveness, the adequacy of surgical margins at operation for first relapse seemed more critical prognostically. This may have clinical and speculative implications. Presented at the Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006, Atlanta, GA (USA) (abstract 9565).