Major and minor complications in Veress needle (VN) and direct trocar insertion (DTI) for laparoscopic closed-entry techniques: an updated systematic review and meta-analysis.

OBJECTIVE: Direct insertion of the trocar is an alternative method to Veress needle insertion for the creation of pneumoperitoneum. We conducted a systematic review and meta-analysis to compare these two entry closed techniques. DATA SOURCE: A systematic review of the literature was done on PubMed, MEDLINE, Embase, Scopus, and EBSCO. METHODS: The literature search was constructed until May 01, 2022, around search terms for "Veress," "direct trocar," "needle," "insertion," and "laparoscopic ways of entry." This systematic review was reported according to the PRISMA Statement 2020. RESULTS: Sixteen controlled trials (RCTs) and 5 observational studies were included in the systematic review. We found no significant differences in the risk of major complication during the access manoeuvres between DTI and VN: bowel injuries (OR = 0.76, 95% CI: 0.24-2.36, P = 0.63), major vascular injuries (OR = 1.74, 95% CI 0.56-5.38, P = 0.34), port site hernia (OR = 2.41, 95% CI: 0.28-20.71, P = 0.42). DTI has a lower risk of minor complications such as subcutaneous emphysema (OR = 5.19 95% CI: 2.27-11.87, P < 0.0001), extraperitoneal insufflation (OR = 5.93 95% CI: 1.69-20.87, P = 0.006), omental emphysema (OR = 18.41, 95% CI: 7. 01-48.34, P < 0.00001), omental bleeding (OR = 2.32, 95% CI: 1.18-4.55, P = 0.01), and lower number of unsuccessful entry or insufflation attempts (OR = 2.25, 95% CI: 1.05-4.81, P = 0.04). No significant differences were found between the two groups in terms of time required to achieve complete insufflation (MD = - 15.53, 95% CI: - 91.32 to 60.27, P = 0.69), trocar site bleeding (OR = 0.66, 95% CI, 0.25-1.79, P = 0.42), and trocar site infection (OR = 1.19, 95% CI, 0.34-4.20, P = 0.78). CONCLUSION: There were no statistically significant differences in the risk of major complications during the access manoeuvres between DTI and VN. A lower number of minor complications were observed in DTI compared with those in Veress access.

Characterization of the Shells in Layer-By-Layer Nanofunctionalized Particles: A Computational Study.

Drug delivery carriers are considered an encouraging approach for the localized treatment of disease with minimum effect on the surrounding tissue. Particularly, layer-by-layer releasing particles have gained increasing interest for their ability to develop multifunctional systems able to control the release of one or more therapeutical drugs and biomolecules. Although experimental methods can offer the opportunity to establish cause and effect relationships, the data collection can be excessively expensive or/and time-consuming. For a better understanding of the impact of different design conditions on the drug-kinetics and release profile, properly designed mathematical models can be greatly beneficial. In this work, we develop a continuum-scale mathematical model to evaluate the transport and release of a drug from a microparticle based on an inner core covered by a polymeric shell. The present mathematical model includes the dissolution and diffusion of the drug and accounts for a mechanism that takes into consideration the drug biomolecules entrapped into the polymeric shell. We test a sensitivity analysis to evaluate the influence of changing the model conditions on the total system behavior. To prove the effectiveness of this proposed model, we consider the specific application of antibacterial treatment and calibrate the model against the data of the release profile for an antibiotic drug, metronidazole. The results of the numerical simulation show that ∼85% of the drug is released in 230 h, and its release is characterized by two regimes where the drug dissolves, diffuses, and travels the external shell layer at a shorter time, while the drug is released from the shell to the surrounding medium at a longer time. Within the sensitivity analysis, the outer layer diffusivity is more significant than the value of diffusivity in the core, and the increase of the dissolution parameters causes an initial burst release of the drug. Finally, changing the shape of the particle to an ellipse produces an increased percentage of drugs released with an unchanged release time.

Dissolution of irregularly-shaped drug particles: mathematical modelling.

The prediction of drug dissolution profiles is crucial for elucidating the pharmacokinetic behaviour of drugs and the bioavailability of dosage forms. In this work, we develop a mathematical model to describe the dissolution process of irregularly shaped particles. We use a complete dissolution model that accounts for both surface kinetics and convective diffusion. The mechanistic relationship between the mass transfer coefficient and the local curvature is derived from the fundamental physical laws governing these processes. Our model theoretically shows that the dissolution rate depends nonlinearly on the surface curvature. The subsequent recrystallization process in the bulk fluid is also considered. The main result of this work is its simplicity, since only two coupled nonlinear ordinary differential equations are needed to describe the dissolution process. Another remarkable advantage is the possibility to determine the model parameters using common independent techniques, so that the importance of the wettability of solids on the dissolution process can be evaluated. Finally, the proposed model demonstrated the importance of particle shape in describing the experimental dissolution data of theophylline monohydrate.

Acute toxic exposures in children: analysis of a three year registry managed by a Pediatric poison control Center in Italy.

INTRODUCTION: Acute pediatric poisoning is an emerging health and social problem. The aim of this study is to describe the characteristics of a large pediatric cohort exposed to xenobiotics, through the analysis of a Pediatric Poison Control Center (PPCc) registry. METHODS: This study, conducted in the Pediatric Hospital Bambino Gesù of Rome, a reference National Pediatric Hospital, collected data of children whose parents or caregivers contacted the PPCc by phone (group "P"), or who presented to the Emergency Department (group "ED"), during the three-year period 2014-2016. Data were prospectively and systematically collected in a pre-set electronic registry. Comparisons among age groups were performed and multivariable logistic regression models used to investigate associations with outcomes (hospital referral for "P", and hospital admission for "ED"group). RESULTS: We collected data of 1611 children on group P and 1075 on group ED. Both groups were exposed to both pharmaceutical and non-pharmaceutical agents. Pharmaceutical agent exposure increased with age and the most common route of exposure was oral. Only 10% among P group were symptomatic children, with gastrointestinal symptoms. Among the ED patients, 30% were symptomatic children mostly with gastrointestinal (55.4%) and neurologic symptoms (23.8%). Intentional exposure (abuse substance and suicide attempt), which involved 7.7% of patients, was associated with older age and Hospital admission. CONCLUSIONS: Our study describes the characteristics of xenobiotics exposures in different paediatric age groups, highlighting the impact of both pharmacological and intentional exposure. Furthermore, our study shows the utility of a specific PPCc, either through Phone support or by direct access to ED. PPCc phone counselling could avoid unnecessary access to the ED, a relevant achievement, particularly in the time of a pandemic.

Mathematical modelling of drug delivery from pH-responsive nanocontainers.

Targeted drug delivery systems represent a promising strategy to treat localised disease with minimum impact on the surrounding tissue. In particular, polymeric nanocontainers have attracted major interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of materials capable of responding to the biochemical alterations of the environment. While experimental methodologies can provide much insight, the generation of experimental data across a wide parameter space is usually prohibitively time consuming and/or expensive. To better understand the influence of varying design parameters on the release profile and drug kinetics involved, appropriately-designed mathematical models are of great benefit. Here, we developed a continuum-scale mathematical model to describe drug transport within, and release from, a hollow nanocontainer consisting of a core and a pH-responsive polymeric shell. Our two-layer mathematical model accounts for drug dissolution and diffusion and includes a mechanism to account for trapping of drug molecules within the shell. We conduct a sensitivity analysis to assess the effect of varying the model parameters on the overall behaviour of the system. To demonstrate the usefulness of our model, we focus on the particular case of cancer treatment and calibrate the model against release profile data for two anti-cancer therapeutical agents. We show that the model is capable of capturing the experimentally observed pH-dependent release.

Modeling drug delivery from multiple emulsions.

We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multilayer droplet where the drug kinetics are described by a pure diffusive process through different liquid shells. The multilayer problem is described by a system of diffusion equations coupled via interlayer conditions imposing continuity of drug concentration and flux. Mass resistance is imposed at the outer boundary through the application of a surfactant at the external surface of the droplet. The two-dimensional problem is solved numerically by finite volume discretization. Concentration profiles and drug release curves are presented for three typical round-shaped (circle, ellipse, and bullet) droplets and the dependency of the solution on the mass transfer coefficient at the surface analyzed. The main result shows a reduced release time for an increased elongation of the droplets.

Local membrane length conservation in two-dimensional vesicle simulation using a multicomponent lattice Boltzmann equation method.

We present a method for applying a class of velocity-dependent forces within a multicomponent lattice Boltzmann equation simulation that is designed to recover continuum regime incompressible hydrodynamics. This method is applied to the problem, in two dimensions, of constraining to uniformity the tangential velocity of a vesicle membrane implemented within a recent multicomponent lattice Boltzmann simulation method, which avoids the use of Lagrangian boundary tracers. The constraint of uniform tangential velocity is carried by an additional contribution to an immersed boundary force, which we derive here from physical arguments. The result of this enhanced immersed boundary force is to apply a physically appropriate boundary condition at the interface between separated lattice fluids, defined as that region over which the phase-field varies most rapidly. Data from this enhanced vesicle boundary method are in agreement with other data obtained using related methods [e.g., T. Krüger, S. Frijters, F. Günther, B. Kaoui, and J. Harting, Eur. Phys. J. 222, 177 (2013)10.1140/epjst/e2013-01834-y] and underscore the importance of a correct vesicle membrane condition.

Multiple-component lattice Boltzmann equation for fluid-filled vesicles in flow.

We document the derivation and implementation of extensions to a two-dimensional, multicomponent lattice Boltzmann equation model, with Laplace law interfacial tension. The extended model behaves in such a way that the boundary between its immiscible drop and embedding fluid components can be shown to describe a vesicle of constant volume bounded by a membrane with conserved length, specified interface compressibility, bending rigidity, preferred curvature, and interfacial tension. We describe how to apply this result to several, independent vesicles. The extended scheme is completely Eulerian, and it represents a two-way coupled vesicle membrane and flow within a single framework. Unlike previous methods, our approach dispenses entirely with the need explicitly to track the membrane, or boundary, and makes no use whatsoever of computationally expensive and intricate interface tracking and remeshing. Validation data are presented, which demonstrate the utility of the method in the simulation of the flow of high volume fraction suspensions of deformable objects.

Multi-scale interaction of particulate flow and the artery wall.

We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a continuum fluid), and proceed to propose, then validate all the key components in a multiply-coupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state.

Low-dose sequential combined spinal-epidural anaesthesia in elective Stark caesarean section: a preliminary cohort study.

AIM: To compare combined spinal-epidural anaesthesia (CSE) VS spinal anaesthesia (SA) in caesarean section (CS) performed by Stark method. MATERIAL AND METHODS: 200 women were prospectively studied before undergoing to a Stark CS in two groups: 95 patients were assigned to a local anaesthesia by SA (first group) and 105 women to CSE anaesthesia (second group). After a pre-load of 500 ml of plasma expander in both groups, SA was performed at the L1-L2 interspace with an injection of 5 ml of levobupivacaine 0.15%, with a 5 mcg of Sufentanil. The CSE was performed by a spinal-epidural injection at the L1-L2 interspace, primarily by 4 ml of levobupivacaine 0.125% and 5 mcg of Sufentanil, then by 3-7 mL of xilocaine carbonate 0.5% plus 1 mcg/ml of Sufentanil. Successively a CS by Stark method was performed in both groups. The recorded anaesthesiologic side effects in two groups were: motor block, intraoperative discomfort, vomiting, bradycardia and hypotension. Statistical evaluation was by Z-Test referred to the comparison of 2 portions with great, independent samples. RESULTS: In the group with CSE anaesthesia, the prevalence of side effects was less than in the group treated with SA, where the prevalence of the motor block and intraoperative discomfort were greater and statistically significant (p<0.001); so as the vomiting and bradycardia were all in a major percentage in SA group, but only significant for hypotension (p<0.001). CONCLUSIONS: These preliminary data show that the association between CS and CSE anaesthesia in elective CS by Stark method allow to have less intra and post-operative side effects; further studies need to provide specific details on the anaesthetic and surgical techniques, to tailor and optimize both in each patient to select for surgery.

Capillary filling in microchannels with wall corrugations: a comparative study of the Concus-Finn criterion by continuum, kinetic, and atomistic approaches.

We study the impact of wall corrugations in microchannels on the process of capillary filling by means of three broadly used methods: computational fluid dynamics (CFD), lattice Boltzmann equations (LBE), and molecular dynamics (MD). The numerical results of these approaches are compared and tested against the Concus-Finn (CF) criterion, which predicts pinning of the contact line at rectangular ridges perpendicular to flow for contact angles of theta > 45 degrees . Whereas for theta = 30, 40 (no flow), and 60 degrees (flow) all methods are found to produce data consistent with the CF criterion, at theta = 50 degrees the numerical experiments provide different results. Whereas the pinning of the liquid front is observed both in the LB and CFD simulations, MD simulations show that molecular fluctuations allow front propagation even above the critical value predicted by the deterministic CF criterion, thereby introducing a sensitivity to the obstacle height.

Mathematical modelling of NABD release from endoluminal gel paved stent.

Coronary restenosis consists of the partial/total re-occlusion of the artery lumen following percutaneous transluminal angioplasty (PTCA). In order to match this pathology, PTCA is followed by the implantation of rigid scaffolds (stent or coated stent) aimed to contrast the most important mechanical (coronary wall elastic recoil and late remodelling) and biological (smooth muscle cells iper-proliferation) factors leading to restenosis. In the light of the clinical problems recently arisen about the use of traditional coated stents, this paper proposes a theoretical study to comprehend the release kinetics of novel anti-proliferative drugs, i.e. nucleic acid based drugs (NABD), complexed with the proper delivery agent (DA). The release of NABD-DA is supposed to occur from a double gel layer adhering to coronary wall and embedding the stent. The proposed mathematical model assumes that diffusion, convection and cellular internalisation/metabolism are the leading mechanisms ruling drug spreading in the coronary wall. In addition, stent void fraction, positioning (totally embedded or totally out of the coronary wall) and continuous or discontinuous character of the gel layer are other three important model parameters. In order to generalise the results, stent geometry is idealised as a series of not connected, equally spaced, rings positioned in the stented zone. In correspondence of stent strut, drug transport cannot occur. The most important outcomes of this study are that, in the usual void fraction range (0.7-0.9), stent presence does not sensibly affect NABD-DA release kinetics. In addition, whereas stent positioning in the continuous gel configuration (totally embedded or totally out of coronary wall) is not very important, in the discontinuous case, it becomes relevant. Finally, this study evidences that a proper mixture of NABD complexed with different (in dimensions and kind) DA can ensure an almost constant NABD coronary concentration for several months, as requested by clinical observations.

Epidemiological and virological characterization of a large community-wide outbreak of hepatitis A in southern Italy.

A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.

Legionnaires' disease outbreak in Rome, Italy.

Between August and October 2003, 15 cases of Legionnaires' disease were detected in the 9th district of Rome. To identify possible sources of Legionella exposure, a matched case-control study was conducted and environmental samples were collected. Hospital discharge records were also retrospectively analysed for the period July-November 2003, and results were compared with the same period during the previous 3 years. The case-control study revealed a significantly increased risk of disease among those frequenting a specific department store in the district (OR 9.8, 95% CI 2.1-46.0), and Legionella pneumophila was isolated from the store's cooling tower. Genotypic and phenotypic analysis of human and environmental isolates demonstrated that the cluster was caused by a single strain of L. pneumophila serogroup 1, and that the cooling tower of the store was the source of infection. The increased number of hospital admissions for microbiologically undiagnosed pneumonia during the study period may indicate that some legionellosis cases were not identified.

[Prevention and treatment of congenital toxoplasmosis: organization protocol]. / Prevenzione e trattamento della toxoplasmosi congenita. Modello organizzativo.

AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). METHODS: Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. CONCLUSION: The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.