Cardiotocography pattern: not always a true friend

: Fetal well-being in labor could be assessed trough cardiotocography (CTG). Some doubts have been raised about its unequivocal applicability. Pathological CTG is in most cases connected to fetal acidosis at birth, but other potential causes must be considered in the differential diagnosis. A 31-years-old G2P1 patient referred to our Department of Obstetrics and Gynecology for her scheduled post-term CTG at 40 weeks and 3 days of gestation. The pregnancy was uneventful. CTG was classified as suspicious, and after pharmacological induction, it switched as pathological: an emergency cesarean section was performed. Venous and arterial blood sample taken from the umbilical cord were normal. The next assessments revealed that Atrial Flutter (AFL) occurred at birth. Suspicious CTG is not always associated to neonatal asphyxia. Cardiotocography can help not only in the evaluation of fetal distress, but also in the assessment of global fetal cardiac activity. The presence of a fetal heart defect should be considered when CTG is suspicious

Chemotherapy-Induced Tumor Cell Death at the Crossroads Between Immunogenicity and Immunotolerance: Focus on Acute Myeloid Leukemia

In solid tumors and hematological malignancies, including acute myeloid leukemia, some chemotherapeutic agents, such as anthracyclines, have proven to activate an immune response via dendritic cell-based cross-priming of anti-tumor T lymphocytes. This process, known as immunogenic cell death, is characterized by a variety of tumor cell modifications, i.e., cell surface translocation of calreticulin, extracellular release of adenosine triphosphate and pro-inflammatory factors, such as high mobility group box 1 proteins. However, in addition to with immunogenic cell death, chemotherapy is known to induce inflammatory modifications within the tumor microenvironment, which may also elicit immunosuppressive pathways. In particular, DCs may be driven to acquire tolerogenic features, such as the overexpression of indoleamine 2,3-dioxygensase 1, which may ultimately hamper anti-tumor T-cells via the induction of T regulatory cells. The aim of this review is to summarize the current knowledge about the mechanisms and effects by which chemotherapy results in both activation and suppression of anti-tumor immune response. Indeed, a better understanding of the whole process underlying chemotherapy-induced alterations of the immunological tumor microenvironment has important clinical implications to fully exploit the immunogenic potential of anti-leukemia agents and tune their application

Mutation analysis by direct and whole exome sequencing in familial and sporadic tooth agenesis

Dental agenesis is one of the most common congenital craniofacial abnormalities. Dental agenesis can be classified, relative to the number of missing teeth (excluding third molars), as hypodontia (1 to 5 missing teeth), oligodontia (6 or more missing teeth), or anodontia (lack of all teeth). Tooth agenesis may occur either in association with genetic syndromes, based on the presence of other inherited abnormalities, or as a non-syndromic trait, with both familiar and sporadic cases reported. In this study, we enrolled 16 individuals affected by tooth agenesis, prevalently hypodontia, and we carried out direct Sanger sequencing of paired box 9 (PAX9) and Msh homeobox 1 (MSX1) genes in 9 subjects. Since no mutations were identified, we performed whole exome sequencing (WES) in the members of 5 families to identify causative gene mutations either novel or previously described. Three individuals carried a known homozygous disease mutation in the Wnt family member 10A (WNT10A) gene (rs121908120). Interestingly, two of these individuals were siblings and also carried a heterozygous functional variant in EDAR-associated death domain (EDARADD) (rs114632254), another disease causing gene, generating a combination of genetic variants never described until now. The analysis of exome sequencing data in the members of other 3 families highlighted new candidate genes potentially involved in tooth agenesis and considered suitable for future studies. Overall, our study confirmed the major role played by WNT10A in tooth agenesis and the genetic heterogeneity of this disease. Moreover, as more genes are shown to be involved in tooth agenesis, WES analysis may be an effective approach to search for genetic variants in familiar or sporadic tooth agenesis, at least in more severe clinical manifestations

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer

Objectives: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Methods: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). Results: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. Conclusions: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. Key Points: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival

Non-specific oral and cutaneous manifestations of Coronavirus Disease 2019 in children

Coronavirus Disease 2019 (COVID-19) seems to affect children only marginally, as a result, there is less knowledge of its manifestations in childhood. The purpose of this retrospective cross-sectional study was to investigate the oral and cutaneous manifestations in children affected by COVID-19. All the medical records of children with COVID-19 admitted to the Pediatric Clinic- ASST Spedali Civili of Brescia from March to April 2020 were reviewed. The following data were recorded: age, temperature, clinical presentation, oral mucosa lesions, taste alteration and cutaneous lesions. The medical records of twenty-seven pediatric patients (mean age 4,2 years + 1,7) were analyzed. The clinical presentation of the disease mainly included elevated body temperature and cough. The following oral lesions were recorded: oral pseudomembranous candidiasis (7.4 %), geographic tongue (3.7%), coated tongue (7.4 %) and hyperaemic pharynx (37 %). Taste alteration was reported by 3 patients. Six patients presented cutaneous flat papular lesions. As for our paediatric sample, COVID-19 resulted to be associated with non-specific oral and cutaneous manifestations

Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: Results from the ITACa trial

Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized "Italian Trial in Advanced Colorectal Cancer (ITACa)" to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at -80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma

Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease

Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease.Case presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit.Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. © 2013 Casadei Gardini et al.; licensee BioMed Central Ltd

Dental trauma and bicycle safety: A report in Italian children and adolescents

OBJECTIVE:This retrospective study aims to analyze the pattern of oro-facial trauma from bicycle accidents in Italian children and adolescents, focusing on the safety devices used. METHODS: The medical records of 1405 patients of the Dental Clinic of the University of Brescia, between the age of 0 to 18, who experienced a dento-facial trauma from the use of a bicycle, were analyzed. Data regarding age, gender, weight, height, dominant hand, type of bicycle, use of safety devices, location and type of dental trauma, teeth involved, bone fractures and soft tissue lesions were recorded. Statistical analysis was performed. RESULTS: The majority of the traumatic events occurred in children within the 8-10 years of age-range; 1085 teeth were injured, of which 975 permanent teeth (89.9%) and 110 primary teeth (10.1%). The most common dental lesions were the coronal fractures (complicated and not complicated) while the most frequently involved teeth were the upper central incisors; 11% of patients were also treated for maxillo-facial fractures. A protective helmet was worn only in 3% of the cases; not one patient wore a mouth-guard. The use of helmets was more frequent in children and adolescents riding racing-bikes competitively, compared to those who were mountain bikers (p < 0.05). CONCLUSIONS: Bicycle accidents can have serious oro-facial consequences. Therefore, national and regional efforts should be made in Italy to promote head and mouth protection in cycling

IMPACT OF PHYSICAL EXERCISE ON PSYCHOLOGICAL WELL-BEING AND PSYCHIATRIC DISORDERS

Background: Physical exercise is one of the major features of human health, as it is involved in several physiological processes and related to major benefits in reducing body fat, myocardial infarction, hypertension and insulin resistance risk. Physical exercise also plays a positive role in achieving psychological well-being that can be defined as a state of happiness and serenity, with low levels of distress, overall good physical and mental health and outlook and a good quality of life. Aim of the paper: To review the positive effects of physical activity on psychological well-being and its possible neurobiological underpinnings, as well as its impact on several neuropsychiatric disorders, such as depression, anxiety, eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, schizophrenia and some neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Methods: The PubMed, Scopus, Embase, PsycINFO and Google Scholar databases were searched for full text articles published in the latest thirty years on the benefits that physical activity exerts on psychological well-being. Objectives: This study aims to identify the common and differential elements of the DLD (SLI) and LD through a quantitative and qualitative analysis. Results: An impressive amount of data support the positive role of physical activity on psychological well-being and a large amount of research has focused on its beneficial effects in improving the symptoms of the main neuropsychiatric disorders, while highlighting its usefulness as an adjuvant option to psychopharmacological treatments and psychotherapy. In particular, exercise would deeply affect CNS morphology and function, through heterogeneous mechanisms including, amongst the others, the production of hormones, neurotransmitters and neurotrophins, the promotion of angiogenesis and neuroplasticity, and the regulation of gene expression. Conclusion: Literature indicates that the promotion of physical activity may work like an adjunctive and/or augmentation strategy to enhance drugs or psychological treatments, or even as an alternative option in major depression