Posterior component separation with TAR: lessons learned from our first consecutive 52 cases.

Patients with complex incisional hernia (IH) is a growing and challenging category that surgeons are facing in daily practice and represent indeed a technical challenge for most of them. The posterior component separation with TAR (PCS-TAR) has become the procedure of choice to repair most complex abdominal wall defects, including those with loss of domain, subxiphoid, subcostal, parastomal or after trauma and sepsis treated initially with "open abdomen" and in those scenarios in which the fascia closure was not performed to avoid an abdominal compartment syndrome. Most recent studies showed that the PCS-TAR represents a valid procedure in recurrent IH. The purpose of our study is to evaluate the reproducibility of the PCS-TAR, describing our experience, our surgical technique and the rate of postoperative complications and recurrences in a cohort of consecutive patients. 52 consecutive patients with complex IH, who underwent PCS-TAR at "Betania Hospital and Ospedale del Mare Hospital" in Naples between May 2014 and November 2019 were identified from a prospectively maintained database and reviewed retrospectively. There were 36 males (69%) and 16 females (31%) with a mean age of 57.88 (range 39-76) and Body mass index (BMI kg/m2) of 31.2 (24-45). More than half of patients (58%) were active smokers. Mean defect width was 13.6 cm (range 6-30) and mean defect area was about 267.9 cm2. Mean operative time was 228 min. Posterior fascial closure was reached in all cases, while anterior fascial closure only in 29 cases (56%). Mean hospital stay was 5.7 days. 27% of patients developed minor complications (Clavien-Dindo grade I-II) and one case (1.9%) major complication (Clavien-Dindo III). Seroma was registered in 23% of cases. SSI was reported to be 3.8% with no deep wound infection. Recurrence rate was 1.9% in a mean follow-up of 28 months. In Univariate analysis Bio-A surface > 600 cm2 and drain removal at discharge were significantly associated with major complications, while in a multivariate analysis only Bio-A surface > 600 cm2 was related. Considering univariate analysis for recurrences, number of drains, SSO, Clavien-Dindo score > 2 and defect area were significantly associated with recurrence, while in a multivariate analysis no variables were related. PCS-TAR is an indispensable tool in managing complex ventral hernias associated with a low rate of SSO and recurrence. Tobacco use, obesity and comorbidities cannot be considered absolute contraindications to PCS-TAR. Peri and postoperative management of complications and drainages have an impact on short term outcomes. Based on these outcomes, posterior component separation with transversus abdominis release has become our method of choice for the management of patients with complex ventral hernia requiring open hernia repair in selected patients.

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy.

BACKGROUND: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings. AIM: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital. METHODS: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods. FINDINGS: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response. CONCLUSION: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment.

HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Hepatitis C virus genetic variability and the presence of NS5B resistance-associated mutations as natural polymorphisms in selected genotypes could affect the response to NS5B inhibitors.

Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed the NS5B polymerase genetic variability in circulating HCV genotypes/subtypes and its impact on the genetic barrier for the development of resistance to clinically relevant nucleoside inhibitors (NIs)/nonnucleoside inhibitors (NNIs). The study included 1,145 NS5B polymerase sequences retrieved from the Los Alamos HCV database and GenBank. The genetic barrier was calculated for drug resistance emergence. Prevalence and genetic barrier were calculated for 1 major NI and 32 NNI resistance variants (13 major and 19 minor) at 21 total NS5B positions. Docking calculations were used to analyze sofosbuvir affinity toward the diverse HCV genotypes. Overall, NS5B polymerase was moderately conserved among all HCV genotypes, with 313/591 amino acid residues (53.0%) showing ≤1% variability and 83/591 residues (14.0%) showing high variability (≥25.1%). Nine NNI resistance variants (2 major variants, 414L and 423I; 7 minor variants, 316N, 421V, 445F, 482L, 494A, 499A, and 556G) were found as natural polymorphisms in selected genotypes. In particular, 414L and 423I were found in HCV genotype 4 (HCV-4) (n = 14/38, 36.8%) and in all HCV-5 sequences (n = 17, 100%), respectively. Regardless of HCV genotype, the 282T major NI resistance variant and 10 major NNI resistance variants (316Y, 414L, 423I/T/V, 448H, 486V, 495L, 554D, and 559G) always required a single nucleotide substitution to be generated. Conversely, the other 3 major NNI resistance variants (414T, 419S, and 422K) were associated with a different genetic barrier score development among the six HCV genotypes. Sofosbuvir docking analysis highlighted a better ligand affinity toward HCV-2 than toward HCV-3, in agreement with the experimental observations. The genetic variability among HCV genotypes, particularly with the presence of polymorphisms at NNI resistance positions, could affect their responsiveness to NS5B inhibitors. A pretherapy HCV NS5B sequencing could help to provide patients with the full efficacy of NNI-containing regimens.

[Surgical treatment and prognostic factors in colorectal cancer]. / Trattamento chirurgico e fattori prognostici nel cancro colo-rettale.

AIM: The aim of this study was to make a contribution to improve the care of patients with colorectal cancer by optimizing times and methods of the follow-up; particular attention is given to factors which may be important for the prognosis and for the quality of life in the immediate postoperative period. METHODS: The study includes all the patients with colorectal cancer who underwent laparotomic surgical treatment from 1996 to 2003. The total number of patients was 226 with an average age of 65 years; male to female ratio was 1.57:1. According to the stage of tumor, an adjuvant radiotherapeutic and/or chemiotherapeutic treatment was associated to surgery. RESULTS: On the basis of the preoperative staging and tumor localization, our patients underwent: 3 total colectomies, 57 right hemicolectomies, 137 left hemicolectomies, 6 Hartmann resections, 19 Miles resections, 4 transverse resections. CONCLUSION: The results obtained show that the 5-year overall survival is particularly influenced by the stage and the factors which directly or indirectly affect the primary tumor; thus the prognostic factors which should be considered for the survival and in the follow-up of these patients are: stage, grading and nodal involvement of the tumor.

Different types of noise in leaky integrate-and-fire model of neuronal dynamics with discrete periodical input.

Different variants of stochastic leaky integrate-and-fire model for the membrane depolarisation of neurons are investigated. The model is driven by a constant input and equidistant pulses of fixed amplitude. These two types of signal are considered under the influence of three types of noise: white noise, jitter on interpulse distance, and noise in the amplitude of pulses. The results of computational experiments demonstrate the enhancement of the signal by noise in subthreshold regime and deterioration of the signal if it is sufficiently strong to carry the information in absence of noise. Our study holds mainly to central neurons that process discrete pulses although an application in sensory system is also available.

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P < 0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

A Brownian simulation model of glutamate synaptic diffusion in the femtosecond time scale.

To gain a better understanding of the elementary unit of synaptic communication between hippocampal neurons, we simulated the release of glutamate from a single pre-synaptic vesicle and its diffusion into the synaptic cleft. Diffusion of glutamate was simulated by a Brownian model based on Langevin equations. The model was implemented for parallel computer simulation and tested under different conditions of glutamate release and different geometrical and physical characteristics of the synaptic cleft. All the tested parameters have shown to be important for the synaptic responses. The results show that the synaptic transmission efficacy is influenced by many different geometrical parameters and, as a consequence, the quality of the excitatory postsynaptic response can be very different in the same synapse. The variability in the quantal response found by several authors can also be explained by physical parameters other than by variations in the quantal content of the synaptic vesicle as proposed by these authors.

A Brownian model of glutamate diffusion in excitatory synapses of hippocampus.

We simulated the diffusion of glutamate, following the release of a single vesicle from a pre-synaptic terminal, in the synaptic cleft by using a Brownian diffusion model based on Langevin equations. The synaptic concentration time course and the time course of quantal excitatory post-synaptic current have been analyzed. The results showed that they depend on the number of receptors located at post-synaptic membrane. Their time course are dependent both on the total number of the post-synaptic receptors and on the eccentricity of the pre-synaptic glutamate vesicle.

The Müller-Lyer illusion in interpolated figures.

The Müller-Lyer patterns formed by separate dots have been used as stimuli in an experiment on visual perception to assess the influence of the number of dots composing the figures on the magnitude of the illusion. As predicted by our model, based on the Image Function theory, an increase was noted in the magnitude of illusion when the number of dots composing the arrowheads was increased. It follows from the model that filtering of the input image plays a central role in the formation of the illusion.

Threshold effect in visual perception of geometrical figures.

Filtering of the input image has been shown to play a central role in several aspects of visual perception. In our experiments in visual perception of the area of geometrical figures the orientation in random dot patterns, and some visual illusions, we have shown that a threshold effect inferred from the filtering of the input image produces a perceptual error. This error has been explained by using the concept of Image Function. The present paper is a brief review of our experimental results and of the models we have proposed.

Wounds from civilian and military centerfire rifles.

This article explores the differences between rimfire and centerfire rifles and the differences in ammunition used. Permanent and temporary cavity wound tracks are explained. Radiographs, intermediary targets, and assault rifles are also discussed.

Centerfire frangible ammunition: wounding potential and other forensic concerns.

Recently developed frangible ammunition of copper particulate construction in .38 Special, 9 mm, and .223 calibers was evaluated for wounding performance by firing into pigs' heads. The ability to match fired bullets with the corresponding gun was also examined. Results showed that wounds caused by 9-mm and .38 Special frangible bullets were comparable in severity to those caused by regular service ammunition of the same caliber. The recovered 9-mm and .38 Special bullets demonstrated class characteristics but not the individual rifling marks necessary for bullet-to-gun matching. High-velocity .223-caliber rifle bullets fragmented extensively within target tissues, causing severe wounding. Radiologic examination of resulting wounds showed images strikingly similar to the lead "snowstorm" picture caused by high-velocity hunting ammunition.

Visual perception of area and hypnotic susceptibility.

The visual perception of area of geometrical figures was compared for subjects of high and low hypnotizability in experiments with direct comparison of two different geometrical figures. The Stanford Hypnotic Susceptibility Scale (Form C) was used to assess subjects' hypnotizability. No differences between 17 highly hypnotizable and 10 low hypnotizable subjects were found. Present results were also compared with those previously obtained for subjects of unknown hypnotizability. The model based on the Image Function Theory proposed earlier to explain the errors in area estimation committed by subjects of unknown hypnotizability was confirmed as a general rule.

A computer program to study the area perception of squares and rectangles.

A computerized approach to study the visual perception of rectangles and squares is proposed. A program has been used for comparison of these two figures when one of them is fixed in size while the other is varied actively by a subject to match the area of the fixed one. The final errors on area and on perimeter made by the subject are computed for each pair of presented figures. The program is menu driven and thus easy to use by the investigator. Since the task procedure is very simple and non-obtrusive to the subjects, it can be used both for children and adults as well as for normal and brain impaired subjects in order to study some perceptive and cognitive functions. This program recognizes the most common graphics cards used by computers running under MS-DOS to adjust the parameters of the presented figures according to the pixel resolution of the graphics card. Quick-BASIC was used to write the program which was compiled by Microsoft Professional Basic 7.0 compiler.

Incidence of coronary thrombosis in sudden death due to coronary artery disease.

Acute coronary thrombosis does not play a major role in the causation of sudden unexpected death due to coronary artery disease. In a study of 500 consecutive autopsies of individuals aged 20-99 years, dying suddenly and unexpectedly of coronary artery disease, only 67 (13.4%) showed an acute thrombosis. In contrast, studies of hospitalized patients with acute transmural infarction of the myocardium showed a rate of coronary artery occlusion > 80%.