Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. METHODS: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). RESULTS: Nineteen RCTs involving 17 treatment regimens were included. For the all-comers population, pembrolizumab/chemotherapy (CT) and cemiplimab were most likely the best treatments. For programmed death-ligand 1 (PD-L1) <1% nivolumab/ipilimumab with/without CT, for PD-L1 >1% and 1%-49% pembrolizumab/CT and for PD-L1 >50% cemiplimab ranked first for OS. In non-squamous (NSQ), pembrolizumab with/without CT ranked first for OS; cemiplimab ranked worse than the unselected population. In squamous (SQ), pooled hazard ratio (HR) showed a better chance in improving efficacy for combination strategy, while monotherapy did not, except for cemiplimab that ranked second. Atezolizumab/CT/bevacizumab ranked first in most subgroups for PFS. Direct comparison showed a non-statistically significant benefit of ICI regimens for the liver metastases cohort in OS, with a good ranking for pembrolizumab/CT and atezolizumab/bevacizumab/CT. Regarding brain metastases, all ICI regimens demonstrated an improvement in OS and PFS compared to CT. Nivolumab/ipilimumab/CT ranked better in this subset. CONCLUSIONS: Our meta-analysis updated on the most recent findings demonstrates that different ICI treatments rank differently in specific NSCLC settings (histology, biomarker and clinical presentation) offering a novel challenging scenario for clinical decision making and research planning.

Feasibility of a tailored ERAS programme in octogenarian patients undergoing minimally invasive surgery for colorectal cancer.

BACKGROUND: The enhanced recovery after surgery (ERAS) is nowadays a widely accepted multimodal programme of care in colorectal surgery, but still there is some reluctance in its application to very elderly patients. AIM: The aim of this study is to investigate short-term outcomes of laparoscopic resection for colorectal cancer in octogenarian patients within the ERAS programme. METHODS: Data on 162 consecutive patients aged ≥ 80 years receiving elective minimally invasive colorectal resections within ERAS programme were collected in a multicentre, retrospective database in the period 2008-2017 in Italy. Univariate and multivariate analyses were performed to assess possible risk factors for poor clinical outcomes. RESULTS: The postoperative minor morbidity rate (Clavien-Dindo 1 and 2) was 25.9%. The incidence of postoperative major morbidity rate (severe medical and surgical complications defined as Clavien-Dindo 3 and 4) accounted 6.1% and only 1.8% had an anastomotic leakage. Reoperation rate was 5.5%, perioperative 30-day mortality was 1.8%, and 30-day readmission rate was 6.8%. On average, patients were released after 6 days. A univariate analysis showed that possible risk factors for severe medical complications were: low preoperative albumin level, high Charlson Age Comorbidity Index Score and number of days in the intensive care unit (ICU); risk factors for severe surgical complications were: low preoperative albumin level; risk factors for late hospital discharge were: multivisceral resections, number of days in ICU and body mass index (BMI) > 25 kg/m2. The multivariate analysis confirmed a low level of preoperative albumin and a longer ICU stay as independent risk factors for both postoperative severe surgical complications and late hospital discharge. DISCUSSION: The minimal invasive nature of the laparoscopic approach together with a multimodal analgesia therapy, the early resumption to oral diet and mobilisation could minimize the surgical stress and play an essential role in order to reduce medical morbidity in high-risk patients. CONCLUSION: Colorectal surgery within ERAS programme in octogenarians is a safe and flexible treatment in high-volume centres.

Structure modulated charge transfer in carbon atomic wires.

sp-Hybridized carbon atomic wires are appealing systems with large property tunability. In particular, their electronic properties are intimately related to length, structure, and type of functional end-groups as well as to other effects such as the intermolecular charge transfer with metal nanoparticles. Here, by a combined Raman, Surface Enhanced Raman Scattering (SERS) investigation and first principles calculations of different N,N-dimethylanilino-terminated polyynes, we suggest that, upon charge transfer interaction with silver nanoparticles, the function of sp-carbon atomic wire can change from electron donor to electron acceptor by increasing the wire length. In addition, the insertion into the wire of a strong electrophilic group (1,1,4,4-tetracyanobuta-1,3-diene-2,3-diyl) changes the electron-accepting molecular regions involved in this intermolecular charge transfer. Our results indicate that carbon atomic wires could display a tunable charge transfer between the sp-wire and the metal, and hold promise as active materials in organic optoelectronics and photovoltaics.

Relationship between mandibular second molar calcification stages and cervical vertebrae maturity in Italian children and young adults.

AIM: The aim of this study was to investigate the relationship between the stages of calcification of the mandibular second molar and the stages of skeletal maturity among Italian children and young adults. MATERIALS AND METHODS: Cross-sectional descriptive study. The samples were derived from panoramic radiographs and lateral cephalograms of 500 Italian subjects aged from 10 to 20 years. Dental maturity index (DM) was assessed by calcification stages of the mandibular second molars according to the Demirjian method; skeletal maturity was evaluated with cervical vertebrae maturation index (CVM) according to Hassel and Farman. The Pearson r coefficient and Spearman rank correlation coefficient were estimated to determine the relationship between DM and CVM. RESULTS: Skeletal maturation stages occurred earlier in females (about 6 months). A highly significant correlation between CVM and DM (0.78-0.86 cor according to Pearson test and 0.81-0.85 rho according to Spearman test) was found. DM stage E corresponds to phase CVM 1 and 2 (the phase prior to the growth spurt), DM stage F corresponds to the phase of pubertal growth spurt, stages CVM 2 and CVM 3; DM stage G is indicator of the growth spurt underway (CVM 3-4), but it can still be found during CVM 5 in females. CONCLUSION: The second mandibular molars can be considered reliable indicators for the evaluation of the growth phases. In case of females the end of the growth spurt it is not clearly associated with a dental maturity stage and needs to be stated with further parameters such as CVM.

Biologically effective dose and definitive radiation treatment for localized prostate cancer: treatment gaps do affect the risk of biochemical failure.

BACKGROUND AND PURPOSE: It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure. PATIENTS AND METHODS: A total of 670 patients with T1-3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72-79.2 Gy in 40-44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman's test. The Kaplan-Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram. RESULTS: Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70%). The median follow-up was 80 months (range 20-129 months). Overall, the 6-year FFBR rate was 88.3%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure. CONCLUSION: A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.

Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: a retrospective clinical study.

AIM: To ascertain if breast cancer subtypes had prognostic effect on breast cancer specific survival, distant metastases and local relapse rates in women affected by early stage breast cancer. PATIENTS AND METHODS: Data of 774 patients affected by early stage breast cancer and treated with breast-conserving therapy were reviewed. Patients were grouped, based on steroid receptor status and HER2 status as: Luminal A (ER+/PR+/HER2-), Luminal B (ER+/PR+/HER2+), Basal-like (ER-/PR-/HER2-) and HER2 (ER-/PR-/HER2+). Distribution of variables among subtypes was evaluated with Pearson's test. Survival rates were calculated with life tables; Cox regression stepwise method was used to identify predictive variables of survival. RESULTS: Median age was 55.0 years old (range 27-80) and median follow up time of 59.0 months (range 13.6-109.7). Breast cancer specific survival and distant metastases rates were different among breast cancer subtypes (both outcomes P=0.00001) but there was no difference regarding local relapse rates (P=0.07). Axillary nodes status (P=0.00001), adjuvant therapy (P=0.03) and breast cancer subtypes (P=0.03) resulted prognostic factors of breast cancer specific survival; axillary node status (P=0.00001) and breast cancer subtypes (P=0.00001) had an impact on distant metastases. Age (P=0.003), tumor size (P=0.0001), positive or close surgical margin (P=0.00001) and tumor grade 3 (P=0.049) resulted prognostic factors of local relapse. CONCLUSIONS: In our study, breast cancer subtype seems a prognostic factor of breast cancer specific survival and distant metastases rates, but not of local relapse rate. Patients could be submitted to conservative surgery, if feasible, but considering the differences in survivals, patients with worse prognosis should receive more aggressive adjuvant treatments.

Risk factors for postoperative depression in 150 subjects treated for drug-resistant focal epilepsy.

OBJECTIVE: The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. METHODS: Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. RESULTS: Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. CONCLUSIONS: Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.

Consultation-liaison psychiatry for patients with headaches.

Screening of headache patients for psychiatric disorders is needed, because of the well-known high rates of comorbidity with depression and anxiety. Screening for both depression and anxiety is highly advisable in order to identify subjects who need psychiatric consultation and therapy. Screening tools for depression and anxiety range from informal questions to self-report instruments to structured interviews and the choice is up to the clinician and the setting of the clinical evaluation. Data on psychiatric disorders and medication overuse are till now not consistent. The treatment of mood and anxiety disorders in headache patients needs to take into account the possible drug interactions with headache therapies. The collaboration between neurologists and consultation-liaison psychiatrists helps the identification of headache patients who need a psychiatric therapeutic program and follow-up.

Immunogenetic aspects of erosive osteoarthritis of the hand in patients from northern Italy.

OBJECTIVES: To compare the distribution of human leucocyte antigen (HLA) class I and II alleles in patients with erosive hand osteoarthritis (EHOA) to that of patients with non-erosive hand OA (non-EHOA) and in healthy Italian Bone Marrow Donors (IBMDs), in order to evaluate possible immunogenetic associations with EHOA. In the EHOA group we also sought possible associations between HLA alleles and disease severity. METHODS: Ninety-four patients with EHOA (82 women, 12 men; mean age 61.4 ± 8.45 years) and 37 with non-EHOA (28 women, nine men; mean age 59.21 ± 9.07 years) were studied. Disease severity was measured by the number of clinically active joints (NCAJ) and by the radiographic score (RS) using the Kallman scale. HLA typing was undertaken for A, B, C, and DRB1 loci; HLA-DRB1* genotyping was determined using polymerase chain reaction (PCR) with sequence-specific primers. Frequencies were compared with those of the healthy IBMDs. RESULTS: The alleles found more frequently in EHOA patients than in non-EHOA patients and healthy controls were: A23, A26, and A29; B38, B44, and HLA DRB1*01 and *07. The RS was more severe in the EHOA compared to the non-EHOA group (63.60 ± 23.14 vs. 34.34 ± 20.24, p < 0.001). Within the EHOA group, HLA-DRB1*07 was associated with a higher RS (67.36 ± 23 vs. 64.5 ± 18.5, p = 0.029). CONCLUSION: In this study of North Italian patients affected with EHOA, the HLA-DRB1*07 allele was found to be associated with both the development and greater severity of the disease.

Is a five-category reporting scheme for thyroid fine needle aspiration cytology accurate? Experience of over 18,000 FNAs reported at the same institution during 1998-2007.

OBJECTIVE: Fine needle aspiration (FNA) has long been recognized as an essential technique for the evaluation of thyroid nodules. Although specific cytological patterns have been recognized, a wide variety of reporting schemes for thyroid FNA results have been adopted. This study reports our experience with a five-category reporting scheme developed in-house based on a numeric score and applied to a large series of consecutive thyroid FNAs. It focuses mainly on the accuracy of thyroid FNA as a preoperative test in a large subset of histologically distinct thyroid lesions. METHODS: During the 1998-2007 period, 18,359 thyroid ultrasound-guided FNAs were performed on 15,269 patients; FNA reports were classified according to a C1-C5 reporting scheme: non-diagnostic (C1), benign (C2), indeterminate (C3), suspicious (C4), and malignant (C5). RESULTS: Non-diagnostic (C1) and indeterminate (C3) FNA results totalled 2,230 (12.1%) and 1,461 (7.9%), respectively, while suspicious (C4) and malignant (C5) results totalled 238 (1.3%) and 531 (2.9%), respectively. Histological results were available in 2,047 patients, with thyroid malignancy detected in 840. Positive predictive value of FNA was 98.1% with a 49.0 likelihood ratio (LR) of malignancy in patients with a C4/C5 FNA report. CONCLUSIONS: This five-category scheme for thyroid FNA is accurate in discriminating between the virtual certainty of malignancy associated with C5, a high rate (92%) of malignancy associated with C4, and a 98% probability of a histological benign diagnosis associated with C2. Further sub-classifications of C3 may improve the accuracy of the diagnostic scheme and may help in recognizing patients eligible for a 'wait and see' management.

[Diagnostic interpretation of depressive symptoms from a psychodynamic point of view]. / Possibilità d'interpretazione diagnostica delle manifestazioni depressive in un'ottica psicodinamica.

AIMS: The principal aim of this study is: (i) to assess the rate of depressive disorders in a sample of patient in a psychotherapy service of the Department of Psychiatric Sciences and Psychological Medicine at the Sapienza University, Roma; (ii) to focus the psychopathological features of depressive patient through the SCL-90R scale; (iii) to evaluate the correlation between SCL-90R score and categorical diagnosis. MATERIALS AND METHODS: The sample of this study includes 178 patients, who came to our service for a psychotherapy. The anamnestic and clinical information were collected for each patient. Each patient is submitted to the multidimensional scale SCL-90R in the curse of the first interview. A descriptive analysis of all the data collected was made and the principal links between SCL-90 R score and categorical diagnosis were detected. RESULTS: About 46% of the patients were depressive disorders following the DSM-IVTR diagnostic criteria. About 70% of depressive patients have psychoticism pathological scores, 60% have paranoic pathological scores, 70% anxiety pathological scores and 60% interpersonal sensibility pathological scores. The depressive dimension was pathological in about 77% of anxious patient and in 87% of patient with personality disorders. CONCLUSIONS: The DSM.IVTR categorical psychiatric diagnosis might underestimate important psychopathological dimensions which are underline through a dimensional scale as the SCL-90R and through a psychodynamic diagnostic instrument.

Chromosome instability in Mediterranean Italian buffaloes affected by limb malformation (transversal hemimelia).

For several years, a genetic disease called transversal hemimelia (TH), also known as congenital amputation, has been spreading in Mediterranean Italian buffalo. TH is characterized by the lack of limb distal structures, normally developing proximally to the malformed limb and being amputated at different points distally. A sample of 13 animals affected by TH was examined using the chromosome aberration (CA) test to better characterize chromosome instability already emerging in a preliminary study where we found a significantly higher difference (P < 0.001) in the mean rate of sister chromatid exchange/cell (8.80 +/- 3.19) performed in 10 malformed animals, when compared with the control (6.61 +/- 2.73). The percentage of aneuploid cells was higher in animals with TH (12.76) than in control animals (7.85). Mean gaps are greater in cells of animals with TH (6.62 +/- 2.38) than those found in the control (2.86 +/- 1.01) and similar results were obtained in chromatid breaks (0.13 +/- 0.31 and 0.07 +/- 0.06, respectively), chromosome breaks (0.11 +/- 0.27 and 0.06 +/- 0.13, respectively) and CAs excluding gaps (0.24 +/- 0.47 and 0.13 +/- 0.18, respectively). All these differences are statistically highly significant (P < 0.001).

Increased SCE levels in Mediterranean Italian buffaloes affected by limb malformation (transversal hemimelia).

In recent years some buffalo farms in Campania have reported the birth of calves with limb malformation, especially with transversal hemimelia. We investigated 20 Mediterranean Italian buffaloes (8 males and 12 females) from one day to six months of age, of which 10 were affected by transversal hemimelia (group 1) and 10 were healthy controls (group 2). The following clinical and radiological patterns were observed in the malformed animals: hind limbs amputated, the right amputated off the second tarsus bones and the left amputated off the proximal epiphysis metatarsus, and the right thoracic limb hypoplasic (1 female); left hind limb amputated off the proximal epiphysis metatarsus (2 females and 1 male); left hind limb amputated off the third tarsus bones (1 female); left hind limb amputated off the tibia (1 female and 1 male); left hind limb amputated off the distal epiphysis metatarsus (1 female); left hind limb amputated off the first phalanx (1 male); right hind limb amputated off the proximal epiphysis metatarsus (1 male). In their malformed limbs all the animals presented more or less developed outlines of claws. The mean rate of SCE/cell in animals with transversal hemimelia was 8.80 +/- 3.19, that of the controls 6.61 +/- 2.73. The difference was statistically significant (P < 0.001).

XX/XY chimerism in cattle: clinical and cytogenetic studies.

The freemartin condition represents the most frequent form of intersexuality found in cattle, and occasionally in other species. Freemartinism arises when vascular connections occur between placentae of developing heterosexual twin foetuses, XX/XY chimerism develops, and ultimately there is masculinisation of the female tubular reproductive tract to varying degrees. The aim of this work was to report the clinical and cytogenetic studies performed in 28 cattle co-twins, 24 of which were cytogenetically chimeric (2n = 60, XX/XY), raised in the region of Campania (southern Italy). Clinical findings of the 16 freemartin females examined varied greatly, from a more female phenotype (normal body conformation with the presence of a blind-ending vagina and primordial ovarian and uterus structures) to a nearly male phenotype (body conformations with male traits and presence of primordial prepuce, penis and testicles). The 8 freemartin males, in spite of the presence of XX cells, had a normal body conformation and external genitalia and some of them were fertile. In addition to cytogenetic diagnosis we also verified chromosome fragility by testing for chromosome aberration (CA: aneuploidy, gaps, chromatid breaks, chromosome breaks and fragments) and sister chromatid exchange (SCE). Freemartins showed a higher percentage of aneuploid cells and significant statistical differences in mean values of gaps, chromatid breaks and chromosome breaks when compared with control animals. To our knowledge, this is the first time that chromosome instability has been evaluated by analyses of CA and SCE in freemartin cattle.

Information to cancer patients: a questionnaire survey in three different geographical areas in Italy.

GOALS OF WORK: The way to inform cancer patients varies widely among different countries. In most Mediterranean countries, the traditional approach has been of partial disclosure of the truth. The intent of our work was to find if the attitude in Italy has changed in recent years and if differences still exist among different geographical regions in our country. Both patients' and physicians' attitudes vary in Italy depending on geographical area. In the South, the focus is on traditional values and full involvement of patients' family, with limited communication to (and limited autonomy of) the patient. Such attitude is less pronounced in Central Italy, whereas the North is more oriented to open communication and full decisional autonomy of the patient. MATERIALS AND METHODS: Approximately 600 consecutive patients in three different centres in Northern, Central and Southern Italy (respectively, Udine, Ancona and Catanzaro) were asked to answer a 26-item questionnaire on communication aspects to investigate the quality of the information given and potential differences between geographical areas. RESULTS: Questionnaires were completed by 587 patients (median age 60 years, 57% women), mainly with gastrointestinal (32%) or breast cancer (30%). About 370 patients (63%) had active disease at time of interview. A high proportion of patients were correctly informed on diagnosis (86%) and therapy (84%). On the contrary, patients fully aware of their prognosis were only about 43%. Nevertheless, most patients (60%) stated they were completely satisfied with the information received. There were differences between geographical areas on various information aspects, with patients from Southern Italy being, in general, less informed. CONCLUSIONS: In Italy, the cultural attitude towards communication in oncology is changing on both the physician and the patient side. There are still significant geographical differences, but there is a general trend suggesting improved awareness about diagnosis and treatment, with the notable exception of prognosis.

Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance.

AIMS: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. METHODS: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). RESULTS: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. CONCLUSIONS: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer. Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined.

Health care supply for cataract in Austrian public and private hospitals.

PURPOSE: This study aims to explain spatial variability or cataract and cataract surgery in Austria. The effect of the availability of health care services on spatial variation is investigated. METHODS: A retrospective study, using routine hospital data from all Austrian public and private hospitals. Calculation of age- and gender-standardized hospitalization ratios (SHR) for all 121 Austrian districts. Poisson regression for age-specific relative risks was performed. RESULTS: The authors found high regional variability between districts and significant differences in the hospitalization rates of cataract disease and extraction between men and women. There was a significant correlation between standardized hospitalization ratios for districts and the availability of hospitals with departments of ophthalmology. There was a significant difference in length of stay for patients with cataract surgery between public and private hospitals. CONCLUSIONS: Use of routine hospital data in geographic analysis allows large regional studies on health care supply for cataract surgery. Differences in the supply by hospitals between districts depend on the availability of hospitals with departments of ophthalmology. The overall demand for cataract surgery in Austria finds its proper supply in many Austrian regions, but needs further development.

Chromosome fragility in cattle with chronic enzootic haematuria.

Chronic enzootic haematuria (CEH) is a severe syndrome due to prolonged ingestion of toxic principles of bracken fern, such as quercetin and ptaquiloside. Little information is available on chromosomal instability of cattle with access to bracken fern and suffering from CEH. In the present study, 45 cattle, aged from 7 to 12 years and pastured in the south of Italy, were cytogenetically investigated for the first time in search of both chromosomal aberrations (aneuploidy, gaps, chromatid breaks, chromosome breaks and fragments) and sister chromatid exchanges (SCEs). Of these animals, 30 (group 1) had access to bracken fern and showed signs of CEH, and 15 (group 2; control) did not. Percentage of abnormal cells (aneuploidy, chromatid breaks, chromosome breaks and fragments) was higher in animals affected by CEH (34.7%, group 1) than that (24.3%) reached in the control (group 2). The same results were achieved when including gaps. Indeed, the mean number of cells with structural aberrations excluding gaps (chromatid breaks, chromosome breaks and fragments) per cell was higher (P<0.001) in animals affected by CEH (0.16+/-0.36) than that (0.09+/-0.29) found in the control. Chromosome fragility in cells of animals affected by CEH was also confirmed when applying the SCE test: statistically higher levels (P<0.001) of SCEs were observed in animals with CEH (7.35+/-3.59 SCE/cell, group 1) than those in the control (5.40+/-2.68 SCE/cell).