RESPONSE TO ORTHOSTATIC STRESS PREDICTS OFFICE-DAYTIME BLOOD PRESSURE DIFFERENCE, BUT NOT NOCTURNAL BLOOD PRESSURE FALL IN MILD ESSENTIAL HYPERTENSIVES: RESULTS OF THE HARVEST TRIAL

1. The aim of the present study was to evaluate whether postural blood pressure (BP) change could predict office-daytime BP disparity and the nocturnal BP fall in young, mild essential hypertensives. We investigated 411 males aged between 18 and 45 years with never treated borderline to mild hypertension. BP was measured three times after a 5 min rest in the supine position and thereafter three times after 2 min of standing. The mean of six BP measurements obtained during two visits in the lying position was defined as office BP. 2. Twenty-four hour ambulatory BP monitoring was performed with either the A and D TM-2420 model 7 or the ICR Spacelabs 90207. BP values were averaged for day—and nighttime periods. The nocturnal BP fall was defined as the difference between the average day—and night-time BP. 3. The standing-lying difference was significantly inversely correlated with the office-daytime difference for both systolic blood pressure (SBP) (r = -0.34, P 0.001) and diastolic blood pressure (DBP) (r = -0.24, P 0.001). These correlations did not change when the obese subjects (body mass index > 30 kg/m²) were excluded from the analysis. No significant correlation between standing-lying difference and nocturnal BP fall was found. 4. Our results indicate that white coat hypertension assessed as the office-daytime BP disparity is partially related (in a negative fashion) to the BP reaction to standing. The postural BP change does not predict nocturnal BP fall in young, mild essential hypertensives.     

Relative influence of different disulphate disaccharide clusters on the HCII-mediated inhibition of thrombin by dermatan sulphates of different origins

Besides the major monosulphated disaccharide sequences (IdoA-GalNAc4SO₃), dermatan sulphates (DS) contain the oversulphated sequences (IdoA2SO₃-GalNAc4SO₃) and (IdoA-GalNAc4,6SO₃), the concentration of which is correlated with the HCII-mediated inhibition of thrombin by DS. The effect of the chemical removal of the sulphate groups on the HCII-mediated activity was studied. The base-catalyzed sulphate group displacement from IdoA2SO₃ residues, leading to formation of the epoxyde aGulA, is a 1st order reaction. When the content of sequences (IdoA-GalNAc4,6SO₃) is higher than that of sequences (IdoA2SO₃-GalNAc4SO₃), removal of the sulphate groups from Ido2SO₃ reduces the HCII activity less than when the latter sequences prevail. (IdoA-GalNAc4,6SO₃) cooperates with (IdoA2SO₃-GalNAc4SO₃) in the activation of the HCII. Also the removal of 6-SO₃ groups from GalNAc4,6SO₃, in absence of IdoA2SO₃-GalNAc4SO₃, considerably reduces the activity. A low molecular mass natural fraction rich in IdoA2SO₃ as well as glucuronic acid, having higher electrophoretic mobility than the higher molecular mass DS which contains less glucuronic acid, is remarkably active.     

DNA methylation variations in familial female and male breast cancer

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as ‘cytoskeletal part’, ‘keratin filament’ and ‘intermediate filament’. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term ‘cytoskeletal protein binding’. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis.     

Long-term complete response in metastatic poorly-differentiated neuroendocrine rectal carcinoma with a multimodal approach: A case report

BACKGROUNDNeuroendocrine gastrointestinal tumors (NETs) are rare and have different natural behaviors. Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective. Poorly differentiated neuroendocrine carcinomas (NECs) represent only 5%-10% of digestive NETS. Due to aggressive growth and rapid metastatic diffusion, early diagnosis and a multidisciplinary approach are mandatory. The role of surgery and radiotherapy in this setting is still debated, and chemotherapy remains the treatment of choice.CASE SUMMARYA 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3 (Ki67 index > 90%) on May 2015 and initially treated with 3 cycles of first-line chemotherapy, but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection. In September 2015, the first post-surgery total-body computed tomography (CT) scan showed an early pelvic disease relapse. Therefore, systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response. This was followed by pelvic radiotherapy (50 Gy). On April 2016, a CT scan and 18F-fluorodeoxyglucose positron emission tomography imaging showed a complete response (CR) of the pelvic lesion, but pathological abdominal inter-aortocaval lymph nodes were observed. Due to disease progression of abdominal malignant nodes, the patient received radiotherapy at 45 Gy, and finally obtained a CR. As of January 2021, the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSIONThis case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.     

Surveillance of toxic exposures: the pilot experience of the Poison Control Centers of Milan, Pavia and Bergamo in 2006

Between 1 February and 31 March 2006, the Poison Control Centers (PPC) active in Lombardy collaborated with an integrated surveillance system carried out in Piedmont during the Olympic Games 2006. The collaborating PPC notified to the system 697 human cases of exposure occurred in Piedmont during the observation period. Among these cases, 70% were exposed accidentally, 40% were 6 years old or younger, and 45% reported at least a clinical effect. The agents more frequently reported were: cleaning substances (household) (110 cases), fumes/gases/vapors (63 cases, comprising 38 cases accidentally exposed to carbon monoxide), and sedative/hypnotics/antipsychotics (53 cases). Although very limited, the available observations focused the attention on specific hazards and were able to highlight the potential of a toxic exposure surveillance system based on the information reported by the Italian PPC.     

Malignant Skin Cancer Excision in Combined Therapy with Electro-Chemotherapy and Dermal Substitute

Squamous cell carcinoma (SCC) is the second most common malignancy skin cancer. It is characterized by abnormal, accelerated growth of squamous cells (SCs). SCC occurs when DNA damage from exposure to ultraviolet radiation or other damaging agents trigger abnormal changes in the SCs, presenting as painless lesions on areas of high sun exposure, such as the dorsum of the hand and upper extremity. For most skin SCC, the surgical excision alone is standard practice. However, recent efforts in new treatment strategies have involved around adjuvant or concomitant electrochemotherapy (ECT). ECT is a non-thermal tumor ablation modality, safe and effective on any type of solid tumor. An 87-year-old patient affected by hand SCC with invasion of deep structures including tendons was treated with neoadjuvant intra-tumoral ECT sessions followed by a selective surgical removal and reconstruction of the substance loss with collagen dermal template (CDT). Two neoadjuvant intra-tumoral ECT procedures, at distance of 3 months, with the aim to reduce the tumor size before a selective surgery, were performed. This study shows that combined surgical selective excision with ECT and CDT is a valid technique for the extended-deep dorsal hand tumor lesions reconstruction.