A novel BRCA2 pathogenic variant c.7094_7100del (p.His2365LeufsTer9) in an Italian family with hereditary breast cancer.

BACKGROUND: Breast cancer is the most common type of malignancy and the foremost cause of tumor-related death in women. The two most well-known genes linked to hereditary breast cancer are BRCA1 (MIM#113705) and BRCA2 (MIM#600185). Germline mutations in the tumor-suppressor genes are found in a proportion of this group. CASE REPORT: Family history of breast and ovarian cancer, early-onset breast cancer, and ethnicity constitute the basic criteria for identifying cases affected by BRCA1 or BRCA2 mutations. This study reports a novel BRCA2 pathogenic variant c.7094_7100del (p.His2365LeufsTer9), identified in a family from Basilicata, Italy, with a history of hereditary breast cancer. Genetic tests are available to predict the risk of developing cancer, particularly in cases of hereditary cancer, the predisposition to cancer, and the target organs. CONCLUSIONS: The identification of this variant expands the spectrum of BRCA2 mutations associated with hereditary breast cancer and highlights the importance of genetic testing and counseling for families with a history of breast cancer.

7q35q36.3 deletion and concomitant 20q13.2q13.33 duplication in a newborn: familiar case.

OBJECTIVE: Array-CGH is a powerful tool in identifying and characterizing complex genomic rearrangements smaller than 5-10 megabase (Mb), for which classical cytogenetic approaches are not sensitive enough. The use of Array-CGH has increased of 10-20% the detection rate of unbalanced cryptic rearrangements, such as deletions and/or duplications. PATIENTS AND METHODS: We present here the first report of a patient with 7q35q36.3 microdeletion and concomitant 20q13.2q13.33 microduplication detected by array-CGH and confirmed by reiterative FISH experiments associated with dysmorphism, development delay, Long QT syndrome (LQTS), complex congenital heart disease, pulmonary hypertension, hypotonia, respiratory distress, cognitive deficit. RESULTS: We proved that this unbalanced rearrangement was due to an adjacent-1 segregation that occurred in the mother, carrier of a balanced translocation between chromosomes 7 and 20. The same unbalanced rearrangements were also found in the proband's maternal uncle, who had been given a clinical diagnosis of Dandy-Walker/Rubinstein-Taybi syndromes in the past. Given the above-mentioned observations, the proband's uncle is not affected by Dandy-Walker/Rubinstein-Taybi syndromes, but by a genomic syndrome highlighted by array-CGH. CONCLUSIONS: The Array-CGH allowed us to understand that the loss of several genes is expressed with clinical manifestations due to the concomitance of several syndromes, each related to the malfunction of a "specific disease gene". For these reasons, the genotype-phenotype correlation in these cases is more complex. This study confirms that the array-CGH is useful in identifying pathologies that were considered idiopathic until a few years ago.

16p11.2 microdeletion syndrome: a case report.

BACKGROUND: The recurrent ∼ 600 kb 16p11.2 microdeletion is among the most commonly known genetic etiologies of autism spectrum disorder, overweightness, and related neurodevelopmental disorders. CASE PRESENTATION: Our patient is a 2-year-old white girl from the first pregnancy of a non-consanguineous healthy young white couple (father 33-years old and mother 29-years old). Our patient and her parents' DNA were analyzed by comparative genomic hybridization-array platform. Comparative genomic hybridization-array analysis highlighted a ∼ 600 kb deletion in 16p11.2 region. It has a segregant nature, since it was found in the mother and in her 2-year-old daughter. The microdeletion was confirmed by fluorescence in situ hybridization analysis. CONCLUSIONS: The presented clinical case is worthy of note since the observed microdeletion is often associated with a clinical phenotype tending to overweightness, but the proband (female) was hospitalized due to poor height and weight development, and anorexia. Moreover, the segregant nature of the observed genomic abnormality has to be noted, as well as the phenotypic variability between the mother and daughter. The case described here enriches the phenotypical spectrum linked to the 16p11.2 microdeletion. For these reasons, in the presence of a suspected genetic pathology it is fundamental to study the proband from the clinical point of view, to extend the clinical observation to the parents, and to provide a good family anamnesis. In this way, it is possible to reveal the presence of a familial genetic pathology whose phenotypical outcomes can be highly variable among the members of a family.

Predictors of pressure ulcer incidence following traumatic spinal cord injury: a secondary analysis of a prospective longitudinal study.

STUDY DESIGN: Secondary analysis of data from a prospective cohort study. OBJECTIVES: The objective of this study was to identify the medical and demographic factors associated with the development of pressure ulcers during acute-care hospitalization and inpatient rehabilitation following acute spinal cord injury. SETTING: The study was carried out at acute hospitalization, inpatient rehabilitation and outpatient rehabilitation sites at a university medical center in the United States. METHODS: Adults with acute traumatic spinal cord injury (n=104) were recruited within 24-72 h of admission to the hospital. Pressure ulcer incidence was recorded. RESULTS: Thirty-nine participants out of 104 (37.5%) developed at least one pressure ulcer during acute-care hospitalization and inpatient rehabilitation. Univariate logistic regression analyses revealed significant association of pressure ulcer incidence for those with pneumonia and mechanical ventilation (P=0.01) and higher injury severity (ASIA A) (P=0.01). Multiple logistic regression showed that the odds of formation of a first pressure ulcer in participants with ASIA A was 4.5 times greater than that for participants with ASIA B, CI (1-20.65), P=0.05, and 4.6 times greater than that for participants with ASIA C, CI (1.3-16.63), P=0.01. CONCLUSION: Among individuals with acute traumatic SCI, those with high-injury severity were at an increased risk to develop pressure ulcers. Pneumonia was noted to be associated with the formation of pressure ulcers.

Asymptomatic Clostridium difficile carriage rate post-fecal microbiota transplant is low: a prospective clinical and stool assessment.

OBJECTIVES: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT). METHODS: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well. RESULTS: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129). CONCLUSIONS: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary.

Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results.

OBJECTIVE: Our study aims to demonstrate that the use in the preconceptional period until the 24th week of pregnancy of inositol and folic acid, first of all, preserves the product of conception from neural tube defects (NTDs) and then, thanks to inositol supplementation, it possibly counteracts and prevents the onset of maternal gestational diabetes (GDM). PATIENTS AND METHODS: We have collected data derived from pregnant women arrived at our laboratory, from January 2014 to January 2016, with no family history of type 2 diabetes and hypertension. The first group (n = 68 women) was treated from the preconceptional period until the 24th week of pregnancy with 1.75 g/day myo-inositol, 250 mg/day D-chiro-inositol, 12.5 mg/day Zinc pidolate, 100 mg/day methylsulfonylmethane, 120 mg/day Vitamin C and 400 mcg/day (6S)-5-methyltetrahydrofolic acid. The control group (n = 72) was only treated with 400 mcg/day folic acid. The main outcome measure was the prevalence of maternal GDM. Secondary outcome measures were the prevalence of NTDs and fetal macrosomia. RESULTS: A significant difference was found regarding body mass index (BMI), fasting oral glucose tolerance test (OGTT), after 1-h-glucose OGTT, 2-h-glucose OGTT, glycated hemoglobin (HbA1c) and serum folate, between the two groups. Five infants, in the control group, weighted greater than 4 kg. Moreover, we found a positive correlation between HbA1c and OGTT at the 24th week of pregnancy. CONCLUSIONS: This study shows the efficacy of preconceptional supplementation of inositol to reduce the risk of the onset of GDM and to confirm the importance of folic acid supplementation to avoid NTDs development. Moreover, the positive correlation between HbA1c and OGTT may be useful to consider the use of HbA1c as a single tool for GDM prevention and diagnosis in selected woman in pregnancy.

The association between U.S. Poison Center assistance and length of stay and hospital charges.

CONTEXT: Poison centers (PCs) play an important role in poison prevention and treatment. Studies show that PCs reduce system-wide cost by reducing the number of unnecessary visits to emergency departments and by providing improved patient management. However, there remains a debate regarding the impact of PCs on patient outcomes at the hospital level. OBJECTIVE: To evaluate the impact of PC involvement on length of hospitalization and total hospital charges. MATERIALS AND METHODS: We conducted a retrospective analysis of inpatient cases treated in Illinois hospitals in 2010. We linked the Illinois Poison Center database with an Illinois hospital billing dataset and controlled for important patient-level and facility-level covariates. RESULTS: In the multivariable model, length of hospitalization among PC-assisted patients was 0.58 days shorter than that of patients without PC assistance (p < 0.001). Hospital charges for PC-assisted patients in the lower quintiles were significantly higher than patients without PC assistance (+$953; p < 0.001), but were substantially lower in the most costly quintile of patients (-$4852; p < 0.001). Balancing the higher charges for treating patients with PC assistance in the lower quintiles with the savings in the highest quintile, among inpatients there is a potential cumulative decrease of $2,078 in hospital charges per 10 patients. DISCUSSION: Among the inpatient cases, PC assistance was associated with lower total charges only among the most expensive to treat. However, this outlier group is very important when discussing medical costs. It has been repeatedly shown that the majority of treatment costs are attributable to a small fraction of patients as seen in this study.

Efficacy and safety of bowel cleansing solutions for colonoscopy: a prospective observational study.

BACKGROUND: The most critical factor determining the quality of colonoscopy results is the extent of bowel cleansing. AIM: This observational post-marketing study evaluated the efficacy, acceptability and safety of a range of the most commonly used bowel cleansing solutions in routine clinical practice. PATIENTS: Patients undergoing diagnostic, preventive or follow-up colonoscopy were recruited from 7 centres in Italy, Spain and Greece. METHODS: Quality of bowel preparation was assessed on a 5-point scale and included evaluation of visible bowel surface area and the amount and consistency of residual fluid. Patients evaluated ease of use and palatability. RESULTS: A total of 437 patients took part. Klean-Prep, the most commonly used preparation in this evaluation, achieved the highest score for quality of bowel cleansing and was rated as good or excellent in 72.0% of patients. In dosage-compliant patients, Klean-Prep showed better results in comparison to Fleet Phosphosoda (p < 0.05) in the maximum bowel level reached in the intestine during colonoscopy examinations. All of the bowel cleansing solutions were well tolerated. CONCLUSION: The polyethylene glycol-based preparations provided the most adequate cleansing and, of these, Klean-Prep provided the highest "good" or "excellent" level of bowel preparation.

Correlation between family history of colorectal cancer and pathological and clinical features of the disease.

Familial aggregation of colorectal cancer occurs even among sporadic cases that are not part of defined genetic syndromes. First-degree relatives of patients with "sporadic" colorectal cancer have a three- to fourfold increased risk of the same cancer. The aim of the present study is to investigate the relationship between a first-degree family history of colorectal cancer and the pathological and clinical features of the tumor (site, Dukes' stage, age at diagnosis, sex, and patient survival). Four hundred and sixty-one patients with colorectal cancer were evaluated (250 males and 211 females) and information obtained on their family history of cancer. Sex, age, and stage of disease were the only parameters that correlated significantly with survival. No relationship between family history of colorectal cancer and the prognostic variables was observed.

LH-RH analogue treatment in adenocarcinoma of the pancreas: a phase II study. Gruppo Ligure per lo Studio del Pancreas.

In this phase II study, we treated 7 patients, all males, with stage III or IV pancreatic cancer with goserelin (an LH-RH analogue). Goserelin was administered at a dose of 3.6 mg every 4 weeks. The tumour response was assessed by measuring lesions with US- or CT-scan studies, according to WHO criteria. No response was observed. The median survival was 8 months in locally unresectable tumours and 4 months in advanced disease. The accrual was actually stopped at 7 cases because there were no responses in either of our series or in those published during our study. The authors conclude that the treatment with LH-RH analogue alone cannot be recommended for further studies.

[Colorectal adenocarcinoma in patients with familial anamnesis positive for malignant neoplasms of the large intestine]. / Adenocarcinoma del colon-retto in pazienti con anamnesi familiare positiva per neoplasie maligne del grosso intestino.

Familial aggregation of colorectal cancer occurs also among sporadic cases that are not part of defined genetic syndromes. First degree relatives of patients with "sporadic" colorectal cancer have a 3-4 fold increased risk of the same cancer. The aim of the present study is to investigate the relationship between a first degree family history of colorectal cancer and pathological and clinical features of the tumor (site, Dukes' stage, age at diagnosis, sex and survival of patients). 461 patients with colorectal cancer were evaluated (250 males and 211 females) after obtaining informations about their family history of cancer. 52 (11.25%) of them reported to have at least one close relative affected by intestinal cancer. Sex, age and stage of the disease are the only parameters that significantly affect survival. No relationship between family history of colorectal cancer and prognostic variables was observed.