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Correction to: Eur Rev Med Pharmacol Sci 2021; 25 (19): 5889-5903. DOI: 10.26355/eurrev_202110_26865. PMID: 34661247-published online on October 12, 2021. In the main text, D-dimer unit of measurement was mistakenly indicated as mg/dL rather than as ng/mL. The sentence "With regard to markers of coagulation, non-survivors showed significantly higher median levels of D-dimer as compared to survivors: 1348 mg/dL 949.5 mg/dL, respectively (p=0.03)." in its correct form is the following: "With regard to markers of coagulation, non-survivors showed significantly higher median levels of D-dimer as compared to survivors: 1348 ng/mL vs. 949.5 ng/mL, respectively (p=0.03).". In the first column of Table III (third row), D-dimer unit of measurement was mistakenly indicated as mg/dL rather than as ng/mL. Correction: "D-dimer (ng/mL)". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/26865.

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

Varicella zoster virus (VZV) is a Herpesviridae family double-stranded DNA virus that only affects humans. The first clinical manifestation appears to be varicella, typical of childhood. VZV, on the other hand, becomes latent in ganglion neurons throughout the neuroaxis after primary infection. The VZV reactivates and travels along peripheral nerve fibers in the elderly and immunocompromised individuals, resulting in Zoster. It can, however, spread centrally and infect cerebral and extracranial arteries, resulting in vasculopathy, which can lead to transient ischemic attacks, strokes, aneurysms, cavernous sinus thrombosis, giant cell arteritis, and granulomatous aortitis. Although the mechanisms of virus-induced pathological vascular remodeling are not fully understood, recent research indicates that inflammation and dysregulation of ligand-1 programmed death play a significant role. Few studies, on the other hand, have looked into the role of VZV in cardiovascular disease. As a result, the purpose of this review is to examine the relationship between VZV and cardiovascular disease, the efficacy of the vaccine as a protective mechanism, and the target population of heart disease patients who could benefit from vaccination.

Lots of meta-analysis emphasize that a great number of hospitalized patients with moderate and severe forms of COVID-19 developed acute myocardial damage, defined as an increase of cardiac biomarkers, such N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), creatine kinase-myocardial band (CK-MB) and of all type of troponins. The highest mortality rate is related with progressively increasing biomarkers levels and with a history of cardiovascular disease. In fact, the biomarkers dosage should be considered as a prognostic marker in all patients with COVID-19 disease at admission, during hospitalization and in the case of clinical deterioration. The purpose of this review is to evaluate cardiovascular prognostic factors in COVID-19 disease throughout the analysis of cardiac biomarkers to early identify the most serious patients and to optimize their outcomes.

Background: The multiple beneficial effects of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction are vastly known, but still no or few mentions have been made regarding its effects on endothelial dysfunction and arterial stiffness., Patients and Methods: To understand more deeply if sacubitril/valsartan may have a role on endothelial function and arterial stiffness, 15 patients with dilated cardiomyopathy with reduced left ventricular ejection fraction (LVEF) were evaluated through transthoracic echocardiography, peripheral arterial tonometry (EndoPAT ® ) and applanation tonometry (SphygmoCor ® Px system). These noninvasive exams were performed at the beginning of the study and after 6 months of sacubitril/valsartan treatment., Results: Aortic stiffness parameters didn't differ after 6 months of treatment. Augmentation pressure (P=0.889), augmentation index (P=0.906) and sphygmic wave velocity (P=0.263) increased slightly, but they weren't found to be statistically significant. Systolic, diastolic, and differential central arterial pressure didn't differ at the beginning and at the end of the study. RHI (reactive hyperemia index) increased significantly after 6 months (P=0.001) as well as augmentation index corrected for 75 bpm. Ejection fraction (32.21% ± 5.7 to 38.43% ± 8.4; P=0.010) and diastolic dysfunction degree (P=0.021) improved. There was an improvement in mitral regurgitation that wasn't statistically significant (P=0.116). TAPSE didn't change while pulmonary systolic arterial pressure increased, although not significantly (22.83 mmHg ± 4 to 27.33 mmHg ± 6; P=0.068) and within the normal range values., Conclusions: Even though in a study with a limited number of patients, sacubitril/valsartan improved endothelial function, left ventricular function, MR, and diastolic function significantly in patients with dilated cardiomyopathy and reduced LVEF. It showed no effects on vascular stiffness., Competing Interests: None., (AJCD Copyright © 2022.)

It has been widely reported that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) attaches human cells by using the Angiotensin Converting Enzyme 2 (ACE2) receptor, but vascular impairment described during coronavirus disease 2019 (COVID-19) infection is primarily due to the direct involvement of the endothelial cells by the virus or secondarily to the inflammatory host response is currently unknown. We therefore aimed to demonstrate in vivo the presence of endothelial dysfunction in six COVID-19 patients without cardiovascular risk factors or pre-existing cardiac condition, using the Endo-PAT 2000, a device able to measure endothelial vasodilation function in a rapid and non-invasive way. Four patients were positive for endothelial dysfunction, with RHI values between 1.13-1.56 (average value 1.32, normal values >1.67); in one of the two negative patients the reported RHI value was slightly above the cutoff (1.72). Our findings confirm that COVID-19 patients are at higher risk of developing endothelial dysfunction. In addition, our results demonstrate that endothelial impairment may occur even in the absence of cardiovascular risk factors.

The properties of metal/dioxygen species, which are key intermediates in oxidation catalysis, can be modulated by interaction with redox-inactive Lewis acids, but structural information about these adducts is scarce. Here we demonstrate that even mildly Lewis acidic alkali metal ions, which are typically viewed as innocent "spectators", bind strongly to a reactive cis- peroxo dicopper(II) intermediate. Unprecedented structural insight has now been obtained from X-ray crystallographic characterization of the "bare" Cu II 2 (μ-η 1 :η 1 -O 2 ) motif and its Li + , Na + , and K + complexes. UV-vis, Raman, and electrochemical studies show that the binding persists in MeCN solution, growing stronger in proportion to the cation's Lewis acidity. The affinity for Li + is surprisingly high (∼70 × 10 4 M -1 ), leading to Li + extraction from its crown ether complex. Computational analysis indicates that the alkali ions influence the entire Cu-OO-Cu core, modulating the degree of charge transfer from copper to dioxygen. This induces significant changes in the electronic, magnetic, and electrochemical signatures of the Cu 2 O 2 species. These findings have far-reaching implications for analyses of transient metal/dioxygen intermediates, which are often studied in situ , and they may be relevant to many (bio)chemical oxidation processes when considering the widespread presence of alkali cations in synthetic and natural environments.

Objective: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19., Patients and Methods: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020., Results: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality., Conclusions: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.

X-linked intellectual deficiency (XLID) is a widely heterogeneous group of genetic disorders that involves more than 100 genes. The mediator of RNA polymerase II subunit 12 (MED12) is involved in the regulation of the majority of RNA polymerase II-dependent genes and has been shown to cause several forms of XLID, including Opitz-Kaveggia syndrome also known as FG syndrome (MIM #305450), Lujan-Fryns syndrome (MIM #309520) and the X-linked Ohdo syndrome (MIM #300895). Here, we report on two first cousins with X-linked Ohdo syndrome with a missense mutation in MED12 gene, identified through whole exome sequencing. The probands had facial features typical of X-linked Ohdo syndrome, including blepharophimosis, ptosis, a round face with a characteristic nose and a narrow mouth. Nextera DNA Exome kit (Illumina Inc., San Diego, CA, USA) was used for exome capture. The variant identified was a c.887G > A substitution in exon 7 of the MED12 gene leading to the substitution of a glutamine for a highly conserved arginine (p. Arg296Gln). Although the variant described has been previously reported in the literature, our study contributes to the expanding phenotypic spectrum of MED12 -related disorders and above all, it demonstrates the phenotypic variability among different affected patients despite harboring identical mutations.

Purpose: Despite the advancements in the reinforcement and closure techniques available, complex abdominal wall reconstruction (CAWR) remains a challenging surgical undertaking with considerable risk of postoperative complications. Biological meshes were developed that may help to complement standard closure techniques and offer an alternative to synthetic meshes, which carry significant risks with their use in complex cases., Patients and Methods: A total of 114 patients underwent surgical treatment for CAWR with a Permacol™ (a biologic surgical implant). The study objective was to evaluate the short-term (6 months), mid-term (12-24 months), and long-term (36 months) clinical outcomes (through 36 months) associated with the use of a biologic surgical implant in these cases., Results: The cumulative hernia recurrence rate was 18.7% (17/91) at 24 months and 22.4% (19/85) at 36 months. Twelve (14.1%) subjects required reoperation for hernia repair within 36 months for repair of recurrent hernias. Between 6- and 36-months post-surgery, patients reported improvement in their Carolina comfort scale (CSS) measures of severity of pain, sensation of mesh, and movement limitations., Conclusion: A biologic surgical implant can provide long-term benefit to complex abdominal wall repairs in patients staged grade III according to the Ventral Hernia Working Group (VHWG)., Competing Interests: Mr Pasquale Giordano reports personal fees from Medtronic, outside the submitted work. Professor Marco Montorsi reports personal fees from Baxter, outside the submitted work. Dr Ben Griffiths reports non-financial support and personal fees from Medtronic. The authors report no other conflicts of interest in this work., (© 2021 Gossetti et al.)

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Introduction: Mesh repair is one of the most popular technique for the treatment of abdominal wall hernias, resulting in lower recurrence rates. However, it is associated with a high risk of mesh-related complications. The aim of the present study is to assess the impact of biomaterials on the intra-abdominal organs, in terms of adhesions and visceral complications, in a series of patients undergoing re-do surgery at our abdominal wall unit., Materials and Methods: We reviewed the clinical records of 301 patients who undergone laparotomy between June 2008 and May 2018, selecting 67 patients with one or more previous prosthetic abdominal wall repair (AWR)., Results: The average number of previous repairs was 1.6 with a mean time interval of 66 months from the last repair. Clinical presentation included hernia recurrence (69%), mesh infection (26%), infection and recurrence (10%), and fistula (1%). Adhesions were intraoperatively observed in all patients, except for eight cases. Mesh was completely removed in 43 patients, partially in four. Postoperative complications were observed in 39% of cases, including wound dehiscence, hematoma, seroma, and mesh infection., Conclusions: Long-term implant results in abdominal wall repair and are not completely known, and literature is still lacking on this topic. Re-do surgery for subsequent pathological events may represent a way to increase our knowledge.

Multidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.

Genetic dynamics underlying cancer progression are largely unknown and several genes involved in highly prevalent illnesses (e.g., hypertension, obesity, and diabetes) strongly concur to cancer phenotype heterogeneity. To study genotype-phenotype relationships contributing to the mutational evolution of colorectal cancer (CRC) with a focus on liver metastases, we performed genome profiling on tumor tissues of CRC patients with liver metastatic disease and no co-morbidities. We studied 523 cancer-related genes and tumor-immune microenvironment characteristics in primary and matched metastatic tissues. We observed a loss of KRAS and SMAD4 alterations and a high granzyme-B+ T-cell infiltration when the disease did not progress. Conversely, gain in KRAS , PIK3CA and SMAD4 alterations and scarce granzyme-B+ T-cells infiltration were observed when the tumor evolved towards a poly-metastatic spread. These findings provide novel insights into the identification of tumor oligo-metastatic status, indicating that some genes are on a boundary line between these two clinical settings (oligo- vs. poly-metastatic CRC). We speculate that the identification of these genes and modification of their evolution could be a new approach for anti-cancer therapeutic strategies.

We introduce here the spin-resolved version of the charge displacement function, which is applied to two competing pathways of proton-coupled electron transfer in oxidation catalysis (hydrogen-atom transfer, concerted proton-coupled electron transfer). The difference in charge displacement between the two mechanisms is directly observable and can be translated to electron flow using this new analysis tool.

Steroidal C7β alcohols and their respective esters have shown significant promise as neuroprotective and anti-inflammatory agents to treat chronic neuronal damage like stroke, brain trauma, and cerebral ischemia. Since C7 is spatially far away from any functional groups that could direct C-H activation, these transformations are not readily accessible using modern synthetic organic techniques. Reported here are P450-BM3 mutants that catalyze the oxidative hydroxylation of six different steroids with pronounced C7 regioselectivities and β stereoselectivities, as well as high activities. These challenging transformations were achieved by a focused mutagenesis strategy and application of a novel technology for protein library construction based on DNA assembly and USER (Uracil-Specific Excision Reagent) cloning. Upscaling reactions enabled the purification of the respective steroidal alcohols in moderate to excellent yields. The high-resolution X-ray structure and molecular dynamics simulations of the best mutant unveil the origin of regio- and stereoselectivity., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration. These insights provide novel information in oligometastatic CRC biology and new perspectives for cancer monitoring and anti-cancer therapeutic strategies.

The use of meshes in inguinal hernia repair (IHR) has gained popularity but new complications have been observed. Mesh-related visceral complications (MRVCs) are generally considered rare and hence are not studied in depth. We carried out a thorough literature search and collected 101 clinical reports published from 1992 to 2018. The reported complications seem to have tripled in the last decade. Ninety-seven cases met the inclusion criteria and they were subdivided into four groups (group A-onlay IHR, group B-3-D IHR, group C-preperitoneal IHR, group D-laparoscopic IHR) to be analyzed, according to the herniorraphy technique. Every prosthetic IHR can be followed by MRVCs but, according to the present review, the highest incidence is related to laparoscopic repairs, the lowest to Lichtenstein technique. Time-to-event was shorter in case of preperitoneal position of the prosthesis than when the mesh was implanted over the transversalis fascia. Urinary bladder involvement predominantly occurred after laparosopic IHR. A pathogenic correlation between the most frequently complained clinical signs and the previous mesh herniorraphy was rarely reported. The diagnosis was generally made at laparotomy, which was usually performed as an emergency. Removing the infected mesh and resecting or suture repairing the involved viscera was the challenging surgical treatment. Prevention of MRVCs after inguinal hernia repair appears to be an important significant issue. It is important to pay attention to the choice of a proper implantation site, avoiding direct contact between the mesh and viscera, and to select a proper device.

Millions of abdominal wall repair procedures are performed each year for primary and incisional hernias both in the European Union and in the United States with extremely high costs. Synthetic meshes approved for augmenting abdominal wall repair provide adequate mechanical support but have significant drawbacks (seroma formation, adhesion to viscera, stiffness of abdominal wall, and infection). Biologic scaffolds (i.e., derived from naturally occurring materials) represent an alternative to synthetic surgical meshes and are less sensitive to infection. Among biologic scaffolds, extracellular matrix scaffolds promote stem/progenitor cell recruitment in models of tissue remodeling and, in the specific application of abdominal wall repair, have enough mechanical strength to support the repair. However, many concerns remain about the use of these scaffolds in the clinic due to their higher cost of production compared with synthetic meshes, despite having the same recurrence rate. The present review aims to highlight the pros and cons of using biologic scaffolds as surgical devices for abdominal wall repair and present possible improvements to widen their use in clinical practice., Competing Interests: The authors declare no conflict of interest.

The use of copper for C-H bond functionalization, compared to other metals, is relatively unexplored. Herein, we report a synthetic protocol for the regioselective hydroxylation of sp 2 and sp 3 C-H bonds using a directing group, stoichiometric amounts of Cu and H 2 O 2 . A wide array of aromatic ketones and aldehydes are oxidized in the carbonyl γ-position with remarkable yields. We also expanded this methodology to hydroxylate the β-position of alkylic ketones. Spectroscopic characterization, kinetics, and density functional theory calculations point toward the involvement of a mononuclear LCu II (OOH) species, which oxidizes the aromatic sp 2 C-H bonds via a concerted heterolytic O-O bond cleavage with concomitant electrophilic attack on the arene system.

Background: To design effective nutrition education interventions for college students, research is needed to determine the factors influencing food choices. The purpose of this study was to identify perceived barriers and enablers of healthy eating in college students ages 18-24 at the University of Hawai'i at Mānoa., Methods: Prior to conducting focus groups, an interview guide was developed based on a literature review of relevant studies. The interview guide was successfully tested in the first focus group and used in the rest of the focus groups. Eleven focus groups with group sizes of two to six were conducted ( n  = 44). Focus groups were audio-recorded and transcribed. Transcripts were coded in NVIVO11 using content analysis, and additional codes were added to the codebook based on emergent ideas from the transcripts. After completion of the final codebook, transcripts were recoded with the new codebook. Final code counts were used to identify overarching ideas based on the socio-ecological model of health, consisting of four levels of influence: individual (intrapersonal), social environmental (interpersonal), physical environmental (community settings), and macrosystem (societal)., Results: The largest barriers according to level of influence in the socio-ecological model were nutrition knowledge deficit (individual), peer pressure (social environmental), unsupportive institutional environment (physical environmental), and cost (macrosystem). The largest enablers were nutrition knowledge (individual), parental influence (social environmental), an institutional environment with consistent healthy offerings (physical environmental), and social media (macrosystem). Some factors served as barriers for some participants and enablers for others, such as parental influence., Conclusion: Factors such as individual knowledge and parental support were cited as having a positive influence in promoting healthy eating, while factors such as the cost of living and food availability at college serve as barriers even for motivated students. Results from this study identify potential areas of intervention, such as improving nutrition knowledge (individual), offering more healthy options (physical environmental), or reducing cost of food (macrosystem). However, more research is needed to identify which level of intervention may be most effective in changing food habits, and which barriers or enablers are deciding factors in determining this population's food choices., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Objective: To evaluate the reliability and validity of the Italian version of the VTD scale (I-VTD scale)., Study Design: Cross-sectional, nonrandomized, prospective study with controls., Methods: For the item generation, a cross-cultural adaptation and translation process was performed following the back translation process (phase 1). For reproducibility analysis (phase 2), 102 patients with dysphonia were recruited (internal consistency analysis); 57 of them completed the I-VTD scale twice (test-retest reliability analysis). Seventy-three vocally healthy participants completed the I-VTD scale for normative data generation (phase 3). For validity analysis (phase 4), the scores obtained by patients with dysphonia and by vocally healthy participants were compared (construct validity analysis); in addition, 45 patients with dysphonia completed both the I-VTD scale and the Italian version of the Voice Handicap Index for criterion validity analysis. Finally, for responsiveness analysis (phase 5), a cohort of 30 patients with muscle tension dysphonia was recruited, and scores of the I-VTD scale before and after voice therapy were compared., Results: Both the internal consistency and the test-retest reliability of the I-VTD scale were satisfactory. The scores obtained by patients with dysphonia and vocally healthy participants were significantly different. Moderate correlations between the Italian version of the Voice Handicap Index and the I-VTD scores were found. Finally, the scores of the I-VTD scale obtained in pretreatment conditions appeared to be significantly higher than those obtained after successful voice therapy., Conclusion: The I-VTD scale appears a reliable and valid instrument for the assessment of vocal tract discomfort in Italian-speaking patients., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We report the long-term (19 years) clinical and echocardiographic results of the quadrangular resection with annular plication and annuloplasty., Methods: Included were 145 consecutive patients (mean age, 58 ± 11.1 years; left ventricular ejection fraction, 0.59 ± 0.095) with severe degenerative mitral regurgitation due to posterior leaflet prolapse/flail who underwent quadrangular resection of the posterior leaflet combined with ring (127 patients [87.5%]) or pericardium (18 patients [12.5%]) annuloplasty., Results: No hospital deaths occurred. At hospital discharge, all patients but 1 had none or trivial mitral regurgitation. Follow-up was 97% complete (median, 19 years; interquartile range, 18 to 20 years). At 20 years, the overall survival was 74% ± 3.7%. At 19 years, cumulative incidence function of cardiac death with noncardiac death as a competing risk was 9.9% ± 2.5% (95% confidence interval [CI], 5.7% to 15.5%). Age was the only significant predictor of cardiac death (hazard ratio, 1.1; 95% CI, 1.0 to 1.1; p = 0.01) at multivariate analysis. Only 6 patients (4%) were reoperated on for recurrent severe mitral regurgitation. At 19 years, cumulative incidence function of reoperation and recurrence of mitral regurgitation 3+ or higher with death as a competing risk was 4.3% ± 1.7% (95% CI, 1.7% to 8.8%) and 8.8% ± 2.8% (95% CI, 4.3% to 15.5%), respectively. Indeed, only 11 patients (8%) had recurrent mitral insufficiency 3+ or higher. No predictor of reoperation and recurrence of mitral regurgitation 3+ or higher was identified. At the last follow-up, moderate mitral regurgitation (2+/4+) was detected in 14 patients (10%)., Conclusions: Quadrangular resection with annular plication for posterior leaflet prolapse, combined with annuloplasty, is associated with a very low probability of reoperation and recurrent mitral regurgitation for up to 2 decades after the operation. These results provide reference values to which all of the other more recently introduced surgical and transcatheter options need to be compared., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Central Mesh Failure (CMF) after abdominal wall repair (AWR) is uncommon but should be considered in case of recurrence. The mechanism is unclear and different theories are actually proposed, as the action of opposite forces acting in the abdominal wall on the prosthesis, and the characteristics of the device to be implanted. The use of lightweight meshes in some cases could be inadequate to withstand the bursting strenght of the abdominal wall. Three cases of incisional hernia recurrence due to central mesh failure are here reported. KEY WORDS: Abdominal wall repair (AWR), Central mesh failure (CMF), Hernia recurrence, Lightweight mesh.

Introduction: Meshes are commonly employed in abdominal hernia repair to reduce recurrence rates. Prosthetic repair, however, increases the risk of mesh related complications, including migration into adjacent viscera and erosion which can occur as uncommon and can be difficult to be diagnose., Presentation of Case: This is a case of transmural migration of composite mesh into the bowel, presenting as chronic abdominal pain and anemia 14 years after incisional hernia repair., Discussion: Mesh implantation in hernia repair has increased the incidence of complications, such as seroma, hematoma and infection. Migration into adjacent viscera and erosion may present as complications related to the use of meshes. Their precise frequency after abdominal wall hernia repair is not well known and their late occurrence can make the diagnosis difficult., Conclusion: Transmural migration of composite mesh is an uncommon complication of incisional hernia repair. Its pathogenesis is still not completely clear but it has been reported many years after implant surgery. It should be considered in a typical presentation of patients with history of previous prosthetic ventral hernia repair., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In ventral hernia repair, when prosthetic material is placed intraperitoneally, it may lead to an inflammatory reaction resulting in adhesions between the mesh and abdominal viscera. Several meshes have been developed to minimize this process. In this experimental study, the ability of different combined meshes to attenuate the adhesion formation was examined., Methods: Three commercially available lightweight porous combined meshes were placed intraperitoneally to repair an abdominal wall defect in rats: DynaMesh-IPOM (PVDF + PP), TiMesh (titanium-coated filament PP) and C-QUR/FX (omega-3 fatty acid-coated filament PP). The DynaMesh-CICAT (PVDF) was implanted in the control group. Adhesion formation was macroscopically evaluated and scored after 7 and 21 days., Results: All animals except two presented intra-abdominal adhesions. None of the meshes examined in the study demonstrated to prevent adhesions. C-QUR/FX reduced adhesion formation at 7 days' follow-up compared with all other meshes but by 21 days this effect was diminished. Between 7 and 21 days adhesion extension significantly decreased for TiMesh. TAS did not show significant modifications between 7 and 21 days' follow-up for each mesh., Conclusions: The combined porous meshes tested in the present study demonstrated to reduce but not to prevent the adhesion formation, even if with some differences. Combined porous meshes could be chosen instead of simple meshes for retro-rectus preperitoneal prosthetic ventral hernia repair.

Introduction: Entero-atmospheric fistula (EAF) is an uncommon complication. Its timing and surgical management could be extremely challenging because extensive adhesions may heavily affect the approach to the abdominal cavity., Presentation of Case: We hereby report a case of EAF in a 70 year-old man. In order to control the fistula output and the surrounding tissue damage from enteric content, the patient was managed conservatively using different technical solutions. Finally, the patient underwent surgery that started with a laparoscopic approach in order to avoid the hostile abdomen., Discussion: Due to the lack of guidelines, treatment of EAF requires a multidisciplinary approach and different technical options based on the experience and inventiveness of the surgeon. Among others, the vacuum assisted wound management proved to be a useful support andlaparoscopy demonstrated to be valuable in approaching the abdominal cavity., Conclusion: According to our experience the success of the treatment of EAF may be improved adopting a multidisciplinary approach and well-planned surgery in referral centers., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Aim of the present study is to propose a clinic-therapeutic course for the treatment of hemorrhoidal disease able to combine radical anatomic surgery with a painless postoperative path., Material of Study: The present study is based on the evaluation of 20 selected patients who underwent radical hemorrhoidectomy for very high grade hemorrhoidal disease. The clinical course was characterized by careful bowel cleansing, hemorrhoidectomy according to Milligan-Morgan using LigaSure, intraoperative perianal infiltration of Ropivacaine and postoperative use of analgesic drugs., Discussion: A low postoperative pain may descend from a scheduled timing of clinical procedures. Preoperative bowel cleansing delays the first postoperative evacuation, thus avoiding the perianal nerve stimulation. The use of LigaSure allows to perform surgical excision in a perfect way: lack of hemostatic stitches, less tissue trauma, very low early morbidity. A rational and scheduled intra and postoperative drug administration offers a highly significant contribution to the pain control. The intra and postoperative use of drugs makes it possible to perform the so-called "preventive anesthesia with activation of the pain memory" and postoperative evacuations with low pain perception. All patients, in fact, reported low and well tolerated pain, satisfaction and return to normal activities in a short period., Conclusions: Radical hemorrhoidectomy with LigaSure and attention to pre, intra and postoperative protocol makes the procedure painless, safe and with low morbidity., Key Words: Hemorrhoidectomy, LigaSure, Painless procedure.

Unlabelled: The history of groin hernia surgery is as long as the history of surgery. For many centuries doctors, anatomists and surgeons have been devoted to this pathology, afflicting the mankind throughout its evolution. Since ancient times the Italian contribution has been very important with many representative personalities. Authors, investigators and pioneers are really well represented. Every period (the classic period, the Middle Age, the Renaissance and the post-Renaissance) opened new perspectives for a better understanding. During the 18th century, more information about groin anatomy, mainly due to Antonio Scarpa, prepared the Bassini revolution. Edoardo Bassini developed the first modern anatomically based hernia repair. This procedure spread worldwide becoming the most performed surgical technique. After World War II synthetic meshes were introduced and a new era has begun for hernia repair, once again with the support of Italian surgeons, first of all Ermanno Trabucco. But Italian contribution extends also to educational, with the first national school for abdominal wall surgery starting in Rome, and to Italian participation and support in international scientific societies. Authors hereby wish to resume this long history highlighting the "made in Italy" for groin hernia surgery., Key Words: Bassini, Groin hernia, History, Prosthetic repair.

Unlabelled: Although Mesh Plug Repair (MPR) represents an effective method for the treatment of groin hernia, some criticisms still concern adverse effects related to the plug (shrinkage, chronic pain, migration and erosion). Different mesh and plug devices have been proposed in the past mostly to prevent migration but none of these achieved the same popularity as the cone or flower-shaped plug. Authors hereby present a pilot study with a new tridimensional device, denominated NeT Plug and Patch, that avoids any risk of migration. Results after 12 months follow-up have demonstrated low incidence of postoperative and chronic pain, with both patients and surgeons greatly satisfied. NeT Plug and Patch has proven to achieve a simple and effective repair for primary inguinal hernias., Key Words: Mesh-plug, Plug migration, Trabucco repair.

Plug repair actually represents one of most recommended procedures in open groin hernia repair. It is generally recognized that Lichtenstein in 1968 first introduced the plug technique for femoral and recurrent inguinal hernia. The present paper backdates more than 50 years the first application of a plug due to an ingenious Italian surgeon named Davide Fieschi.

In this paper, we consider nonlinear partial differential equations (PDEs) of diffusion/advection type underlying most problems in image analysis. As case study, we address the segmentation of medical structures. We perform a comparative study of numerical algorithms arising from using the semi-implicit and the fully implicit discretization schemes. Comparison criteria take into account both the accuracy and the efficiency of the algorithms. As measure of accuracy, we consider the Hausdorff distance and the residuals of numerical solvers, while as measure of efficiency we consider convergence history, execution time, speedup, and parallel efficiency. This analysis is carried out in a multicore-based parallel computing environment.