Prospective case series study on the use of a novel analgosedation protocol for ultrasound-guided catheterization in Neonatal Intensive Care Unit.

Critically ill newborns admitted to Neonatal Intensive Care Unit often require a centrally inserted central catheters (CICCs) inserted by ultrasound-guided puncture of the internal jugular or brachio-cephalic vein. Achieving an appropriate level of sedation and analgesia is paramount for procedure success and patient safety, avoiding the potential risks associated with excessive deep sedation. The aim of this study is to evaluate the feasibility of a novel protocol of sedation. Data from 46 patients were prospectively collected. The feasibility was assessed throughout the monitoring of adverse events and the incidence of spontaneous movements. The procedure was completed in 100% of cases. There were no cases of escalation of the baseline ventilatory support despite the procedure and no case of hypotension, and all spontaneous movements were controlled with additional boluses when required. CONCLUSION: Our study represents the very first step towards the design of a validated protocol for analgosedation during ultrasound-guided CICC insertion in NICU. WHAT IS KNOWN: • Critically ill newborns admitted to Neonatal Intensive Care Unit often require a centrally inserted central catheter. • Achieving an appropriate level of sedation and analgesia is paramount for procedure success and patient safety, avoiding the potential risks associated with excessive deep sedation. WHAT IS NEW: • The use of this new protocol for analgosedation is able to achieve a good level of sedation and pain control without significant adverse event. • Ultrasound-guided CICC insertion can be performed even in non-ventilated newborns.

Parechovirus infection causing sepsis-like illness in newborns: a NICU approach.

Human parechovirus (HpeV) is an important emerging infection in young infants, able to cause sepsis-like disease and meningoencephalitis, especially in newborns. Among the 19 identified genotypes, HPeV1, 3 and 6 are the most common types involved in human infections; HPeV3 is the type mainly responsible for neonatal infections and for infections involving the central nervous system. Signs and symptoms overlap with those of a bacterial infection and patients are usually treated with broad spectrum antibiotics. In the majority of cases lumbar puncture shows absence of pleocytosis, even in the presence of signs of meningitis. In these cases, cerebrospinal fluid cultures are negative for bacteria but, in the absence of diagnosis of viral infection, a full and unnecessary antibiotic cycle is often continued. Moreover, high sensitivity neuroimaging, i.e., magnetic resonance, and follow-up are often missed, thus resulting in substandard care. Availability of a real time PCR assay for HPeV RNA allows rapid and sensitive diagnosis as long as the disease is suspected. In this case study, we present cases of HPeV infections in newborns requiring neonatal intensive care admission, discuss their optimal management, and highlight the most relevant findings in the literature.

Platelet isoprostane overproduction in diabetic patients treated with aspirin.

Aspirin modestly influences cardiovascular events in patients with type 2 diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to determine whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with proaggregating properties derived from arachidonic acid oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate oxidase. A cross-sectional study was performed comparing T2DM patients, treated (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic patients, matched for age, sex, atherosclerosis risk factors, and aspirin treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet recruitment, platelet isoprostane, and NOX2 activation was found in diabetic versus nondiabetic patients and in aspirin-treated diabetic patients versus nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was inhibited in all aspirin-treated patients. In the interventional study, aspirin similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic patients. These findings suggest that in aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane overproduction is associated with enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) inhibition.

TNFA gene promoter polymorphisms and susceptibility to recurrent pregnancy loss in Italian women.

The aim of this study was to investigate the relationship between serum tumor necrosis factor alpha (TNF-alpha) levels and single nucleotide polymorphisms (SNPs) of the TNFA gene promoter (-376G/A, -308G/A, and -238G/A) in 100 Italian Caucasian women with reproductive failure and 100 fertile controls. Molecular analysis of TNFA SNPs showed higher frequencies of -238G allele (P = .028) as well as the presence of a 3-loci haplotype (-376G/-308A/-238G; P = .020) in fertile controls compared to women with reproductive failure. Serum TNF-alpha levels were higher in study women compared to controls ( P = .001). Of interest, the TNFA -376G/-308A/-238G haplotype was an independent predictor of low TNF-alpha levels (P = .021) and miscarriage (P = .023) in multivariate analyses. In conclusion, these findings support the concept of an association of TNFA polymorphisms and recurrent pregnancy loss (RPL). In particular, the TNFA -238GG variant and the TNFA -376G/-308A/-238G haplotype might represent protective factors, probably through reduced TNF-alpha production and/or mediated responses.

Predictive value of thrombopath determination in women with infertility and pregnancy complications.

BACKGROUND: A condition of maternal thrombophilia, either inherited or acquired, can compromise the success of implantation and foetal survival. METHODS: Malfunctions in protein C pathway were evaluated using a novel assay [HemosIL ThromboPath (ThP)] in a case-control study of 172 women with a history of recurrent miscarriage or infertility and 86 age-matched unrelated fertile women. RESULTS: Thrombophilia was ascertained in 13% of the cases. ThP values were lower in women either with or without thrombophilia compared to controls (both p<0.0001). Abnormal ThP values (below the mean minus 1SD of controls) were found in 62% of cases compared to 12% of controls (p<0.0001). Non-thrombophilic women who achieved spontaneous pregnancy had higher ThP values compared to those who did not (p<0.05). Elevated ThP values were an independent predictor for pregnancy (p<0.01) in women without thrombophilia. A decrease of ThP values was observed during pregnancy progression, which correlated with that of protein S (p<0.05). Miscarriage or major complications occurred in women in whom ThP percent change was approximately 2-fold higher than that observed in women who achieved successful pregnancy (p<0.05). CONCLUSIONS: ThP might represent an efficient assay for screening women with pregnancy complications and might provide prognostic information during pregnancy progression.

Role of NADPH oxidase in atherosclerosis.

Reactive oxidant species (ROS) seem to play a key role in the atherosclerotic process via a series of molecular changes that lead to macrophage infiltration in the endothelium and eventually to plaque formation. ROS are also implicated in arterial dysfunction via inactivation of nitric oxide, a potent vasodilator and antiaggregating molecule produced by the endothelium. Owing to the relevance of endothelial dysfunction and vascular inflammation in the process of human atherosclerosis, a lot of effort has been directed towards discovering the ROS-generating pathways implicated in the ROS upregulation. Amongst the enzymatic pathways, NADPH oxidase is the most important enzyme responsible for ROS formation in human vessels. Experimental and clinical studies suggested a role for this enzyme in initiation and progression of atherosclerotic disease. The purpose of this review is to analyze whether the basic and clinical studies are consistent with this hypothesis and to point out if determination of NADPH oxidase is useful in the setting of the atherosclerosis to predict its progression and clinical complications.