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The article reports that the hypertonic saline/dextran (HSD) is known to provide a fast recovery of macro and microhemodynamics after resuscitation of hemorrhagic shock. Along with improved sinusoidal perfusion, an immediate significant decrease of the number of stagnant leukocytes in the liver microcirculation is also present, as compared to crystalloid solutions. Whether these effects last a long time is questionable. In addition, there is evidence that positive immunomodulatory effects are associated with less leukocyte accumulation in the liver. The aim of the study was to evaluate the effects of HSD 8 hours after hemorrhagic shock and resuscitation.

Background: Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management., Objectives: To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti-ADAMTS-13 autoantibodies (AAbs) in patients with iTTP., Methods: This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL)., Results: For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [-0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence ( P  < .001, Cohen's g  = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations., Conclusion: While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%., (© 2024 The Authors.)

Fournier's gangrene (FG) is a rare form of necrotizing fasciitis of the perineal, genital, or perianal region. It is characterized by an aggressive course and high mortality rate, over 20%. FG demands immediate treatment including resuscitation maneuvers, intravenous antibiotic therapy and early surgical debridement. Background/Objectives : The gold-standard treatment for FG is surgical reconstruction. However, up to date, no precise guidelines exist. Thus, we decided to systematically review the literature, focusing on FG contemporary approaches to reconstructive surgery, aiming to analyze the various reconstructive strategies and their specific indications. Methods : A systematic review was carried out according to the PRISMA statement by searching various databases from April 2014 to April 2024, using the terms ''Fournier Gangrene OR Fournier Gangrene Reconstruction OR Fournier Gangrene Treatment OR Fournier Gangrene Plastic Surgery OR Necrotizing Fasciitis OR Necrotizing Fasciitis AND Reconstruction". The eligibility criteria included original studies aimed at discussing FG reconstruction with at least three clinical cases. Results : The final synthesis included 38 articles, and 576 reconstructions were described. Of these, 77.6% were minimally invasive strategies (direct closure, secondary healing, grafts, and local random flaps), while more invasive reconstructions (loco-regional flaps based on known vascular anatomy) were adopted in 22.4%. No free flaps were reported. Conclusions : FG requires immediate medical interventions including broad-spectrum antibiotic therapy, surgical debridement, adjuvant therapies, and reconstructive surgeries. Taking into account the anatomical characteristics of the inguinal-crural region, skin grafts and local random flaps could offer versatile and effective reconstructions for most FG cases, while the more invasive strategies should be reserved for very few cases. Future research is warranted to define an FG dedicated reconstruction protocol.

Introduction: Experience accumulated over the last decades suggests nonoperative management (NOM) of civilian gunshot liver injuries can be safely applied in selected cases. This study aims to compare the outcomes of selective NOM versus operative management (OM) of patients sustaining gunshot wounds (GSW) to the liver., Methods: A registry-based retrospective cohort analysis was performed for the period of 2008 to 2016 in a Brazilian trauma referral. Patients aged 16-80 years sustaining civilian GSW to right-sided abdominal quadrants and liver injury were included. Baseline data, vital signs, grade of liver injury, associated injuries, injury severity scores, blood transfusion requirements, liver- and non-liver-related complications, length-of-stay (LOS), and mortality were retrieved from individual registries., Results: A total of 54 patients were eligible for analysis, of which 37 underwent NOM and 17 underwent OM. The median age was 25 years and all were male. No statistically significant differences were observed between groups regarding patients' demographics, injury scores, grade of liver injury and associated lesions. NOM patients tended to sustain higher-grade injuries (86.5% vs 64.7%; p = 0.08), and failure of conservative management was recorded in two (5.4%) cases. The rate of complications was 48% with no between-group statistically significant difference. Blood transfusion requirements were significantly higher in the OM group (58.8% vs 21.6%; p = 0.012). The median LOS was seven days. No deaths were recorded., Conclusion: Patients with liver GSW who are haemodynamically stable and without peritonitis are candidates for NOM. In this study, NOM was safe and effective even in high-grade injuries.

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien-Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m 2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.

Mitotane is a chiral drug used to treat adrenocortical carcinoma, being metabolized to the o,p'-dichlorodiphenyl acetic acid (o,p'-DDA), also a chiral compound. Despite of its therapeutic significance, the overall ratios and enantiomers have not been known. In this study, we analyzed the enantiomers of mitotane and o,p'-DDA in the plasma of patients by a newly developed chiral-phase method employed in two-dimensional chromatography. Important differences were observed in the ratio of (S)/(R)-mitotane, which varied substantially from 1:1.2 to 1:10 whereas the (S)/(R)-o,p'-DDA ratio was relatively conserved, at approximately 2:1. These findings provide evidence for the enantioselective metabolism and provide a method for further analyses of mitotane and metabolites, which can explain the variation in the therapeutic response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) has been used with high effectiveness in early-stage non-small cell lung cancer (NSCLC) but has not been studied extensively in locally advanced NSCLC. We conducted a phase 2 study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node-positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques used on this trial and the subsequent phase 3 study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results., Methods and Materials: We initiated a phase 2 multicenter single arm study evaluating SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by conventionally fractionated chemoradiation to 60 Gy in 2 Gy fractions with doublet chemotherapy to the involved lymph nodes for patients with stage III or unresectable stage II NSCLC. Patients eligible for adjuvant immunotherapy received up to 12 months of durvalumab. We report a detailed guide for the entire treatment process from computed tomography simulation through treatment planning and delivery. The dosimetric outcomes from the 60 patients who completed therapy on study are reported both for target coverage and normal structure doses. We also report correlation between radiation-related toxicities and dosimetric parameters., Results: Sixty patients were enrolled between 2017 and 2022. Planning techniques used were primarily volumetric modulated arc therapy for SBRT to the primary tumor and conventionally fractionated radiation to the involved nodes, with a minority of cases using dynamic conformal arc technique or static dynamic multileaf collimator intensity modulated radiation therapy. Grade 2 or higher pneumonitis was associated with lung dose V5 Gy > 70% and grade 2 or higher pulmonary toxicity was associated with lung dose V10 Gy > 50%. Only 3 patients (5%) experienced grade 3 or higher pneumonitis. Grade 2 or higher esophagitis was associated with esophageal doses, including mean dose > 20 Gy, V60 Gy > 7%, and D1cc > 55 Gy. Only 1 patient (1.7%) experienced grade 3 esophagitis., Conclusions: SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes is feasible with planning techniques as described. Radiation-related toxicity on this phase 2 study was low. This manuscript serves as a guideline for the recently activated NRG Oncology LU-008 phase 3 trial evaluating this experimental regimen., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

We experimentally demonstrate how a concatenation of the standard and microstructure fiber segments permits adjusting the four-wave mixing sideband position over a large spectral range by varying the chirp of an input pulsed pump at a fixed wavelength in the presence of a self-phase modulation. The blue- and redshifted sidebands can stand aside over ∼200 nm and ∼450 nm from the pump, respectively, which agrees well with the numerical simulations. We validate our approach by showing the feasibility of CARS imaging.

Background: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost., Methods: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models., Results: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs., Conclusions: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH., Trial Registration: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018., (© 2023. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1-2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE.

Purpose: Non allergic rhinitis (NAR) comprises different clinical definitions and phenotypes, including non inflammatory non allergic (NINAR) and cellular inflammatory forms. Nasal cytology, usually performed by scraping the inferior turbinate, is a non invasive, cheap and point-of-care tool to distinguish among the different NAR phenotypes, but still a relevant proportion of patients evaluated by nasal cytology receive a non precise definition of NAR phenotype. We hypothesize that collecting nasal cytology samples from middle meatus could increase the diagnostic accuracy., Methods: Consecutive patients with chronic rhinitis without evidence of allergic sensitization were assessed for nasal cytology by means of scraping both the inferior turbinate and the middle meatus (lateral-inferior wall of the middle turbinate)., Results: 107 consecutive patients with NAR were enrolled in the study. According to inferior turbinate cytology, 42.1% were defined as affected by NINAR, 2.8% by bacterial rhinitis, 10.3% by non allergic rhinitis with eosinophils (NARES), 15.0% non allergic rhinitis with neutrophils (NARNE), 19.6% non allergic rhinitis with mast-cells (NARMA) and 10.3% non allergic rhinitis with eosinophils and mast-cells (NARESMA). Middle meatus cytology was in accordance with inferior turbinate cytology in only 37.6% of cases. Eosinophils and mast-cells were detectable more frequently in middle meatus samples (49.5% vs 19.6%, p < 0.01, 59.8% vs 29.9%, p < 0.01, respectively). 93.3% of NINAR patients received an inflammatory NAR phenotype at middle meatus cytology: 26.7% NARES, 24.4% NARNE, 31.1% NARMA and 11.1% NARESMA., Conclusion: Middle meatus cytology is more reliable than inferior turbinate cytology in phenotyping patients with NAR. Our study strengthen that nasal cytology should be implemented in clinical practice collecting samples at the middle meatus level., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Change in temperature of aquatic environment have impacts on the physiology of fish, especially in the brain, which is a vital organ and prone to oxidative damage. Astyanax lacustris is a freshwater fish that play an important role in the food market and has been increasingly used in fish farms, besides environmental monitoring studies. Therefore, this study aimed to evaluate the responses of antioxidant biomarkers and products of the oxidative process in the brains A. lacustris subjected to thermal shock. The specimens were obtained from artificial farming lakes and subjected to shock induced by exposure to high (31 °C ± 0.5) and low (15 °C ± 0.5) temperature for 2, 6, 12, 24, 48, 72 and 96 h; control group were maintained at 23 °C ± 0.5. At 31 °C, glutathione-related enzymes were more responsive, suggested by the change activity of GPx and G6PDH enzymes, in addition to GSH levels. At 15 °C, enzymes of the first line of defense were more active, evidenced by the change CAT activity. No significant changes were detected in the levels of ROS, LPO and PCO. These results indicate that the brains of A. lacustris have an efficient antioxidant defense system with the ability to acclimatize to the temperatures tested., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aim: Allergic rhinitis (AR) and non-allergic rhinitis (NAR) belong to field of vasomotor rhinitis, characterized by nasal hyper-reactivity. Since AR and NAR are two separate nosological entities, these rhinopaties can coexist in the same patient in up to 15-20% of cases. Overlapped rhinitis (ORs) are associated with intense and persistent symptoms and are often misdiagnosed. Typically, when medical treatment fails, patients undergo turbinate surgery. We evaluated which rhinopaties are most at risk of undergoing turbinate surgery and established the percentage of ORs.  Methods: The study included 120 patients undergoing turbinate surgery for turbinate hypertrophy. Anterior rhinoscopy, nasal endoscopy, nasal cytology, skin prick tests (SPT) and/or specific IgE serum assays (CAP-RAST) were performed preoperative on all patients., Results: Among patients with indication for turbinate surgery, 75% suffered from AR, whereas 25% of them had NAR. On closer analysis, only 7 (8%) of allergic patients presented a "pure" allergy.  NAR with eosinophils and mast cells (NARESMA) represented the most common type of superimposed rhinitis (62.5%), while NAR with mast cells (NARMA) and with eosinophils (NARES) represented 25% and 12.5% of the superimposed forms, respectively., Conclusion: Most of the patients undergoing turbinate surgery actually have complex forms of rhinitis. The non-allergic component of ORs often causes therapeutic failure. NARESMAs overlapping ARs are at most risk of undergoing turbinate surgery. Correctly framing a rhino-allergological patient is essential in order to guarantee the most adequate treatment. Hence the importance of introducing in clinical practice investigations, including allergy tests and nasal cytology.

Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders. Seizures apart, epileptic patients present a high risk to develop neuropsychological comorbidities such as cognitive deficits, emotional disturbance, and psychiatric disorders, which severely impair quality of life. Currently, the treatment for epilepsy includes the administration of drugs or surgery, but about 30% of the patients treated with antiepileptic drugs develop time-dependent pharmacoresistence. Therefore, further investigation about epilepsy and its causes is needed to find new pharmacological targets and innovative therapeutic strategies. Pharmacoresistance is associated to changes in neuronal plasticity and alterations of GABA A receptor-mediated neurotransmission. The downregulation of GABA inhibitory activity may arise from a positive shift in GABA A receptor reversal potential, due to an alteration in chloride homeostasis. In this paper, we review the contribution of K + -Cl - -cotransporter (KCC2) to the alterations in the Cl - gradient observed in epileptic condition, and how these alterations are coupled to the increase in the excitability., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study compared three severity measures for chronic rhinosinusitis with nasal polyps (CRSwNP). The outcome was to identify patients who are eligible for biological therapy., Methods: 330 adult patients with CRSwNP were examined. Nasal polyp score (NPS), sinonasal outcome test (SNOT-22) and clinical-cytological grading (CCG) were compared. Clinical history, past surgery and asthma control test were also considered., Results: Only 45 (13.6%) patients had a contextual positivity to the three severity measures. The concordance among tests was slight/fair. Patients with severe disease (all tests positive) had more impaired parameters. The mixed cytotype (OR = 4.07), nasal obstruction (OR = 10.06), post-nasal drip (OR = 1.98), embarrassment (OR = 2.53) and difficulty falling asleep (OR = 1.92) were significantly associated with severe CRSwNP., Conclusions: To identify candidates for biological therapy, the contextual use of NPS, SNOT-22 and CCG is preferable. In this way, global assessment of CRSwNP, including morphology, inflammation, comorbidity, symptoms and quality of life is possible., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background and Aims: Monitoring the immune response against SARS-CoV-2 is pivotal in the evaluation of long-term vaccine efficacy. Immunoglobulin G (IgG) antibodies represent an advisable tool to reach this goal, especially for the still poorly defined antibody trend induced by the new class of mRNA vaccines against SARS-CoV-2., Materials and Methods: Anti-Spike RBD IgG antibodies were monitored in a cohort of healthcare workers at CRO Aviano, National Cancer Institute, through MAGLUMI® chemiluminescence assay, at 1 and 4 months after full-schedule of BNT162b2 or mRNA-1273 vaccination., Results: At 1 month after vaccination, 99.9% of 767 healthcare workers showed a reactive antibody response, which was inversely correlated with age, and positively associated with a previous history of COVID-19, and mRNA-1273 vaccination. Serological response was maintained in 99.6% of the 516 subjects monitored also at follow-up. An antibody decay from 559.8 AU/mL (IQR 359.7-845.7) to 92.7 AU/mL (IQR 65.1-148.6; p < 0.001) was observed, independently from age and sex., Conclusion: Our data supported the ability of SARS-CoV-2 mRNA vaccines to induce at least a 4 months-lasting IgG response, even outside the rules of clinical trials. The antibody decay observed at follow-up suggested to deepen the immune response characterization to identify subjects with low anti-SARS-CoV-2 immunity possibly requiring a vaccination boost., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The systematic removal of death from social life in the West has exposed people living in areas affected by COVID-19 to the risk of being unable to adequately manage the anxiety caused by mortality salience. Death education is a type of intervention that helps people manage their fear of death by offering them effective strategies to deal with loss and anxiety. To that end, a path of death education has been carried out with University students of psychology. The main purpose of the research is to understand how students who participated in the death education course perceive the lockdown experience in light of course teachings. The research was carried out at a University in northern Italy in an area severely affected by COVID-19, during the first year of the pandemic. The group of participants included 38 students, 30 women and 8 men, with an average age of 25.45 years ( SD = 7). At the end of the course, the students could respond on an optional basis to the request to comment on the training experience according to what they experienced during the pandemic. A thematic analysis was subsequently carried out on the texts, which made it possible to identify the most relevant thematic areas for the students. The qualitative analyses permitted recognition of three main forms of discovery: the removal of death in contemporary culture; the importance of community, ritual and funeral, and spirituality; and the significance of death education for future health professionals. The texts have highlighted how the removal of these issues exposes people to the risk of being unable to handle extremely painful events such as those related to dying. The results show the positivity of death education pathways conducted at the University level to help students reflect on these issues and manage the related anguish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Testoni, Iacona, Corso, Pompele, Dal Corso, Orkibi and Wieser.)

Introduction: Echocardiography (ECHO) with color flow Doppler is considered as the gold standard to identify a hemodynamic patent ductus arteriosus (hs-PDA). However, the optimal diagnostic and therapeutic management for newborns with hs-PDA is still controversial. We aimed to investigate two clinical strategies: (1) targeted treatment based on ECHO criteria and (2) treatment based on ECHO criteria in addition to clinical signs and symptoms. Materials and Methods: This is a cohort study including all neonates consecutively admitted in the Neonatal Intensive Care Unit of University La Sapienza in Rome, with gestational age <32 weeks or body birth weight <1,500 g and with a diagnosis of hs-PDA as confirmed by ECHO evaluation performed within 72 h of life. We classified the babies in two cohorts: (A) pharmacological treatment immediately after ECHO screening and (B) pharmacological therapy for PDA was administered when the relevance of a hs-PDA was associated with clinical signs of hemodynamic instability. Results: We considered as primary outcome newborns who survived without any morbidities (A: 48.1% vs. B: 22.2%, p = 0.022). In particular, we found that the rate of intraventricular hemorrhage stage ≥2 was increased in cohort B (A: 3.7% vs. B 24.4%, p = 0.020). A multivariate analysis showed that assignment to cohort A independently influences the primary outcome. Conclusions: Adopting an hs-PDA management option based on ECHO-directed therapy regardless of symptoms may reduce the morbidity and improve the survival of very low birth weight infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Terrin, Di Chiara, Boscarino, Versacci, Di Donato, Giancotti, Pacelli, Faccioli, Onestà, Corso, Ticchiarelli and De Curtis.)

The coronavirus disease 19 (COVID-19) is caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected the global population despite socioeconomic status and amazed surveillance agencies for its incidence, mortality, and recovery rates. COVID-19 affects all age groups; however, it is suggested to progress into severe disease and cause mortality in over 10% of the confirmed cases, depending on the individual characteristics of the affected population. One of the biggest unanswered questions it is why only some individuals develop into the severe stages of the disease. Current data indicate that most of the critically ill are the elderly or those with comorbidities such as hypertension, diabetes, and asthma. However, it has been noted that, in some populations, severe disease is mostly observed in much younger individuals (<60-years old) with no reported underlying medical conditions. Certainly, many factors may contribute to disease severity including intrinsic host factors such as genetic variants, the expression levels of tissue proteins, among others. Considering all these aspects, this review aims to discuss how the expression levels of tissue proteases and the different profiles of immune responses influence the susceptibility to COVID-19 as well as disease severity and outcome.

Canine oral melanoma (COM) is the most frequent tumour with oral localization in dogs. Copy number gains and amplifications of CCND1, a gene coding for Cyclin D1, are the most frequent chromosomal aberrations described in human non-UV induced melanomas. Twenty-eight cases of COM were retrieved from paraffin-blocks archives. A total of 4 μm thick sections were immunostained with an antibody against human Cyclin D1 and Ki-67. Cyclin D1 and Ki-67 expressions were scored through two counting methods. DNA was extracted from 20 μm thick sections of formalin-fixed paraffin-embedded blocks. Pathological and surrounding healthy tissue was extracted independently. Cyclin D1 immunolabelling was detected in 69% (18/26) while Ki-67 was present in 88.5% (23/26) of cases. Statistical analysis revealed correlation between two counting methods for Cyclin D1 (r = 0.54; P = .004) and Ki-67 (r = 0.56; P = .003). The correlation found between Ki-67 and Cyclin D1 indexes in 16/26 cases labelled by both antibodies (r = 0.7947; P = .0002) suggests a possible use of Cyclin D1 index as prognostic marker. Polymerase chain reaction analysis on CCND1 coding sequence revealed the presence of nine somatic mutations in seven samples producing synonymous, missense and stop codons. Since none of the single-nucleotide polymorphisms was found to be recurrent, it is suggested that overexpression of Cyclin D1 may be the consequence of alterations of CCND1 upstream regions or other genetic aberrations not detectable with the methodology used in this study. Future studies are needed to verify the potential use of Cyclin D1 index as prognostic indicator and to highlight the molecular events responsible for Cyclin D1 overexpression in COMs., (© 2019 John Wiley & Sons Ltd.)

Introduction: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting., Methods: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS., Results: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV < 4, BMV 4-13, and BMV > 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p < 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p < 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p < 0.0001) remained predictive of BMV (adjusted R 2  = 0.06)., Conclusions: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF., (Copyright © 2019 Elsevier B.V. All rights reserved.)

MRI guided Focused Ultrasound (MRgFUS) has shown to be effective therapeutic modality for non-invasive clinical interventions in ablating of uterine fibroids, in bone metastasis palliative treatments, and in breast, liver, and prostate cancer ablation. MRgFUS combines high intensity focused ultrasound (HIFU) with MRI images for treatment planning and real time thermometry monitoring, thus enabling non-invasive ablation of tumor tissue. Although in the literature there are several studies on the Ultrasound (US) effects on cell in culture, there is no systematic evidence of the biological effect of Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) treatment on osteosarcoma cells, especially in lower dose regions, where tissues receive sub-lethal acoustic power. The effect of MRgFUS treatment at different levels of acoustic intensity (15.5-49 W/cm 2 ) was investigated on Mg-63 and Saos-2 cell lines to evaluate the impact of the dissipation of acoustic energy delivered outside the focal area, in terms of cell viability and osteogenic differentiation at 24 h, 7 days, and 14 days after treatment. Results suggested that the attenuation of FUS acoustic intensities from the focal area (higher intensities) to the "far field" (lower intensities) zones might determine different osteosarcoma cell responses, which range from decrease of cell proliferation rates (from 49 W/cm 2 to 38.9 W/cm 2 ) to the selection of a subpopulation of heterogeneous and immature living cells (from 31.1 W/cm 2 to 15.5 W/cm 2 ), which can clearly preserve bone tumor cells.

A residual liquid inoculum (RLI) was used to decolourise solutions of Acid Yellow 25 (AY25) and Direct Violet 51 (DV51) azo dyes. The RLI was obtained through anaerobic digestion of food waste from a university restaurant. The concentration of bacteria in the RLI was 8.45 × 10 7 CFU mL -1 . Dye solutions (50 μg mL -1 ) were inoculated with the RLI (20% v/v) and incubated at room temperature. The decolourisation studies took place at microaerophilic and in-batch conditions and at pH = 2.50. Initially, the dyes were taken up from solution by biosorption; maximum colour removal was achieved after 3 hours of incubation, with 88.66% for AY25 and 77.65% of DV51. At prolonged incubation times (3-96 hours) decolourisation was mainly attributed to biodegradation of the azo solutions, with breakage of the azo bond, as detected by UV-VIS spectroscopy and Fourier transform infrared (FT-IR) analysis. Analysis of UV-VIS absorption rates of dyes showed, however, that AY25 was more readily biodegradable whereas DV51 was more recalcitrant to the action of the RLI.

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

Background: This study aimed to evaluate the prevalence of sedentarism, and to assess physical capacity and nutritional status in a cohort of older patients on peritoneal dialysis (PD), with respect to age-matched non-dialysis CKD population, using highly accessible, simple methods, namely the Rapid Assessment of Physical activity (RAPA) test and the 30″ Sit-to-stand (STS) test., Methods: This cross-sectional multicenter study included 151 renal patients older than 60 years; 71 pts. (44 m, age 72 ± 7 yrs) were on PD and 80 pts. (63 m, age 74 ± 7 yrs) were affected by 3-4 stage CKD., Results: The prevalence of sedentary/underactive patients was double of that of the active patients as assessed by RAPA test, both in the PD (65.3%) and in the CKD (67.5%) cohort. The 30"STS test showed a reduced physical performance in both groups: 84.5% of PD patients and 87.5% of CKD patients did not reach the expected number of stands by age and gender. A malnutrition-inflammation score (MIS) ≥ 6 occurred in 37 % of PD patients and in 2.5 % of CKD patients. In PD patients, an independent significant association was observed between 30"STS test and MIS (beta -0.510, p = 0.013), as well as between RAPA and MIS (beta -0.544, p = 003) and phase angle (beta -0.506, p = 0.028)., Conclusions: A high prevalence of low- performance capacity and sedentarism has been detected among elderly patients on PD or with CKD stage 3-4. Apart from age, a condition of malnutrition-inflammation was the major determinant of poor physical activity and capacity in PD patients. Better body composition seems to be positively associated with physical activity in PD and with physical capacity in CKD patients. Routine clinical management should include a close evaluation of nutritional status and evaluation of physical activity and capacity which can be easily assessed by RAPA and 30″STS tests.

Introduction: Resection is the primary treatment for retroperitoneal (RP) soft tissue sarcomas (STS). Whether obtaining microscopically negative margins (R0) improves overall survival (OS) over microscopically positive margins (R1) remains unclear., Methods: Using the National Cancer Data Base, we identified adult patients diagnosed with RP STS after R0 or R1 resection from 1998 to 2011. We used a multivariable logistic regression model to identify clinicopathologic factors associated with margin status, including radiotherapy receipt. To assess differences in OS, the log-rank test, Cox proportional hazards regression, and propensity score matching were used., Results: We identified 4015 patients; 2593 (64.6%) underwent R0 resection and 1422 (35.4%) underwent R1 resection. The most common histology was liposarcoma (2,371, 59.1%), median age was 60 years, and median follow up was 67 months. Median OS for R0 vs. R1 patients was 92 and 70 months, respectively (log-rank p < .001). Pre-operative RT was associated with increased probability of R0 resection (68.0% vs. 57.2%, p = .012). Multivariable regression showed R0 vs. R1 resection (HR 0.70, 95% CI 0.60-0.81, p < .001) was associated with improved survival, a finding confirmed on propensity score matching. Other significant predictors of OS included low tumor grade, younger age, smaller tumor size, liposarcoma histology, and receipt of RT (HR 0.81, 95% CI 0.70-0.93, p = .016)., Conclusions: Patients who undergo R0 resection for RP STS appear to experience superior OS compared with patients who had R1 resections., (Copyright © 2016 Elsevier Ltd and British Association of Surgical Oncology/European Society of Surgical Oncology. All rights reserved.)

Nutritional abnormalities and physical inactivity are risk factors of increased morbidity and mortality in patients with ESRD. Identify and define malnutrition, in particular protein-energy depletion (PEW), is an important task in the management of renal patients. The aim of this multicenter observational study was to implement the assessment of nutritional status and functional capacity in patients on peritoneal dialysis, including tests and validated methods which are relatively easy to apply in daily clinical practice. The study includes all the 133 prevalent patients (80 m, 53 f, age 65 14 years), in peritoneal dialysis treatment (vintage 26 19 months) in 9 centers in Tuscany. We performed anthropometry, bioimpedance (BIA), clinical biochemistry, evaluation of habitual physical activity (RAPA tests) and performance (Sit-To-Stand test), appetite-evaluation questionnaire, and indices including the Malnutrition Inflammation Score (MIS), Geriatric Nutrition Risk Index (GNRI), Charlson comorbidity index, Barthel and Karnowsky index. The latter showed a condition of dependence in 7.2% and 19.7% of cases, respectively. Poor appetite was recorded in 48.2%. The majority of patients fell within the overweight / obesity range (51%) with waist circumference values associated with increased cardiovascular risk in 51% of males and 60% of females. At the BIA analysis, a BCMI <8 kg/m2 was detected in 39% of patients; an estimated protein intake <1.0 g / kg/d was found in 59% of cases; 34% of patients had serum albumin <3.5 g / dl; control of acidosis was good (bicarbonate 25.4 3.8 mM) but hyperphosphatemia was present in 64.6% of patients. A condition of sedentary or light physical activity was reported by 65.1% of patients, vigorous activity only by 11.9%. The 86.5% of patients able to perform the Sit-to-stand test reported a lower than the reference values for age and sex. A diagnosis of PEW was possible in 8% of our series, while a MIS score> 11, indicative of PEW, took place in 12.7% of cases. The values of the MIS correlated directly with age and the degree of comorbidity and inversely with the sit-to-stand test, RAPA tests and appetite level. The data in this study show that single tests indicative of malnutrition disorders are frequent to be found in our series of peritoneal dialysis patients. However, a diagnosis of PEW is quite infrequent. A large percentage of patients are overweight with increased abdominal adiposity, and reduced cell mass and protein intake below recommended levels; the level of habitual physical activity is low, and the level of physical capability is scarce. Therefore it is conceivable a nutritional counseling intervention to increase the intake of proteins, limiting the phosphorus and (when indicated) energy intake and to stimulating spontaneous physical activity or arranging assisted programs for functional rehabilitation. Close monitoring of the nutritional status and implementation of programs of adapted physical activity should have a prominent role in the clinical management of patients on peritoneal dialysis.

Introduction: The Facultad de Medicina of the Universidad de La Sabana routinely uses lectures as the major educational strategy in clinical areas. Since 2012, a curriculum in context and a flipped classroom were introduced in the surgery course., Objective: To compare the impact of lectures versus the flipped classroom model in the learning environment in surgery., Materials and Methods: The Dundee Ready Education Environment Measure (DREEM) questionnaire was administered to four cohorts of students. The five domains and the overall scores for both strategies were analyzed, and ANOVA was used to determine the differences among the domains (p<0.05). The internal consistency was assessed using Cronbach´s alpha coefficient., Results: There were 207 participants (men: 36%) that completed the questionnaire (age: 21.9 ± 1.49 years old). The overall DREEM score and the subscales were higher with the flipped classroom, which suggests that this environment had a higher level of excellence. The ANOVA for each domain and the overall scores showed no differences with a flipped classroom. However, significant differences were identified in all domains and the overall scores with lectures (p<0.01). There were high levels of reliability (Cronbach>0.90) for all measurements in both environments, and there was consistency across all cohorts., Conclusions: The flipped classroom strategy showed a higher score than the lecture-based approach according to the DREEM questionnaire. Identifying factors with a negative score is crucial to improving the learning environment. It is necessary to conduct further measurements over time to ensure the quality and success of the strategy.

Objectives: PEComas (perivascular epithelioid cell tumors) are a family of neoplastic lesions that share overlapping ultrastructure and morphological and immunohistochemical appearance and include angiomyolipoma, lymphangioleiomyomatosis, and clear cell "sugar" tumor of the lung, as well as similar tumors that occur in a variety of visceral, cutaneous, and soft tissue sites throughout the body., Methods: A 40-year-old woman came to medical attention because of epistaxis and because of unilateral nasal obstruction of 3 months' duration. Endoscopic examination revealed a well-demarcated exophytic lesion attached to the anterior portion of the middle turbinate., Results: The lesion was superficially located, and therefore amenable to complete surgical excision. Seven years after surgery, the patient is alive and well, without evidence of local recurrence or metastastic disease. Based on morphological and immunohistochemical appearance, a diagnosis of PEComa with worrisome histologic features was rendered., Conclusions: In the present study, we describe a PEComa that occurred in the nasal cavity and discuss the behavior of this entity. The importance of recognizing this disease will ensure its consideration in the differential diagnosis of tumors of the head that have similar morphological features. The histogenesis of PEComa still remains elusive, and collection of additional cases with a prolonged follow-up will be important in accurately determining the behavior of these distinctive tumors.

Objectives: The study was performed to evaluate the prognostic relevance of cell proliferation associated with Ki-67/ Mib-1 immunostaining in malignant tumors of the major salivary glands., Methods: Cell proliferation was evaluated by Mib-1 antibody against Ki-67 antigen in 41 patients with cancer of the parotid or submandibular glands, including 14 acinic cell carcinomas, 12 ductal carcinomas, 7 mucoepidermoid carcinomas, 5 carcinomas ex pleomorphic adenoma, 1 adenoid cystic carcinoma, 1 undifferentiated carcinoma, and 1 polymorphous low-grade adenocarcinoma., Results: Patients with Ki-67 values of more than 15% and those with Ki-67 values of 15% or less differed both in disease-free survival (p < 0.001) and in overall survival (p < 0.001). We evaluated the association between Ki-67 and time to recurrence in correlation to age, sex, ductal histotype, and N stage; the Cox regression model was significant (p = 0.013). In the group of patients with T1 and T2 cancers, those with Ki-67 values of 15% or less had better survival rates than did those with Ki-67 values of more than 15% (p = 0.004). In the group of patients with N0 cancers, those with Ki-67 values of 15% or less had a better survival than did those with Ki-67 values of more than 15% (p < 0.001)., Conclusions: To our knowledge, this is the first study to stratify different risk classes in early T1-T2 or N0 malignant tumors of the major salivary glands that identified aggressive lesions with elevated Ki-67 expression at an initial stage.

Drug-induced thrombocytopenia is a challenging diagnosis in the clinical practice because of the many drugs or alternative causes that may be implicated. Exact identification of such drug(s) is required to guide future management and avoid re-exposure. We describe two cases of isolated thrombocytopenia in which cytometric analysis, a readily available technique, allowed the identification of the causative drug in the context of complex therapies (rifampicin and abciximab causing late onset thrombocytopenia)., ((c) 2007 Wiley-Liss, Inc.)

Living with a chronic disease is for the patient a ''disease experience'' that also affects the psychosocial sphere and has a negative impact on perceived quality of life. To estimate the effect of dialysis on the perceived quality of life and to identify by means of a specific questionnaire the aspects that are compromised most. From our results it emerged that the examined patients had a sufficiently good total perception of quality of life, even though about 30% of the patients reported critical aspects related to daily life and, in some age groups, also related to dialysis method. This study confirms the importance of developing educational and supportive predialysis programs in order to identify and reduce the critical aspects.

Summary: Anastomotic fistula represents one of the frequent causes of postoperative morbidity and mortality following transhiatal esophageal resections. The main etiological factor is the ischemia of the gastric tube created for digestive transit reconstruction. Evidence suggests that per operative hypoperfusion can be maintained or even impaired after the surgery. Several methods have been employed in an attempt to assess the blood perfusion of the gastric flap, but they all pose limitations. However, there is a chronological relationship between perfusion assessments, which are almost exclusively performed per operatively, and the occurrence of a leak, which commonly appears several days after the surgery. The authors have developed a method of gastric perfusion evaluation by single photon emission computed tomography scintigraphy, which corrects that temporal matter, allowing the estimation of postoperative gastric perfusion. It is noninvasive, low cost, and may be applied by the time frame when most fistulas occur. High correlation between the event fistula and the low radiotracer uptake in the group of studied patients could be demonstrated. A role in the research of perfusion evaluation of different types of esophageal reconstruction is suggested.

Background: Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity., Methods: Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy., Results: Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran., Conclusion: After resuscitation with rHb1.1, arteriolar vasoconstriction quickly restored MAP, but this was achieved at the expense of FCD. In contrast, after resuscitation with rHb2.0, the recovery of MAP could be translated into a significantly improved FCD.

Conclusions: Our results confirm that supracricoid laryngectomies (SL) are reliable techniques for glottosupraglottic tumors, even for selected T3 and T4 cases, if the indications are correct. These surgical techniques allow a good quality of life with the preservation of the larynx., Objective: SL with cricohyoidoepiglottopexy (CHEP) and cricohyoidopexy (CHP) have been popular over the last 20 years for the treatment of the glottic and/or supraglottic squamous cell carcinoma due to demonstrated good oncological and functional results. We report our experience with these techniques, with special focus on long-term oncological and functional results., Patients and Methods: We retrospectively reviewed 206 patients who had undergone SL with CHEP or CHP technique between 1987 and 1998 for glottosupraglottic squamous cell carcinoma in our department. The long-term results for 206 patients with T1-T4 laryngeal carcinomas treated with SL are reported: 90.8% CHEP and 9.2% CHP. The mean follow-up was 62 months., Results: Oncological results: the 5-year actuarial disease-free survival was 85%; the 5-year determinate actuarial survival was 88.3%. Functional results: organ preservation rate was 97%. Phonation was assessed according to the GRBAS scale.

Bronchogenic cysts are rare congenital malformations of ventral foregut development. They are usually located in the mediastinum and intrapulmonary regions. Localization in the cervical area is unusual and the majority of cases reported have been found in the pediatric population: the literature reports few cases in adults. We describe a 57-year-old male who presented an asymptomatic right lateral neck mass. Diagnostic studies included chest X-ray, pharyngo-esophagus double-contrast X-ray, computed tomography (CT), and bronchoscopy. The mass was excised through a transverse right cervical skin incision. The right lateral neck mass of the patient was identified as a bronchogenic cyst. The embryology, the presentation, the pathological and radiological evaluation, treatment of the cyst and a review of the English literature are reported in this paper. Cervical bronchogenic cysts are usually diagnosed in the pediatric population; these lesions are rare in adults. We suggest that the clinical observation of an asymptomatic lateral neck mass in an adult should include the possibility of a bronchogenic cyst in the differential diagnosis. Surgical excision is the elective treatment for this tumor, in order to prevent complications including infection, compression symptoms, malignant transformation, and the rare but fatal air embolism.

Objective: Among detractors of elective neck (N0) treatments, most suggest that lymphadenectomy removes a barrier to the spread of disease with deleterious immunologic consequences. To test this hypothesis we performed a retrospective comparison of the survival results of N0 laryngeal cancer patients who received unnecessary elective neck treatments (N0-) and those of N0 patients subjected to close and regular follow-up., Material and Methods: A retrospective chart review of 749 N0 laryngeal cancer patients treated at the Institute of Otolaryngology-Head and Neck Surgery, University of Florence between January 1980 and January 1993 was performed. Of these, 245 (33%) received elective neck dissection (ED), while the remaining 504 (67%) N0 patients were subjected to close and regular follow-up (wait-and-see policy; WS)., Results: Of the 245 ED patients, 43 (17.5%) showed an occult neck disease, while of the 504 WS subjects, 83 (17%) developed neck metastases during follow-up. Moreover, 15 ED patients subsequently experienced a contralateral occult failure despite a unilateral negative neck specimen (N0-). Thus, ultimately 187 ED (164 of whom were treated unilaterally and 23 bilaterally) and 421 WS patients were used for survival analysis. No differences in terms of postoperative complications, local or distant failure or disease-free or overall actuarial survival were found between the two groups analyzed., Conclusions: These data indicate that unilateral or bilateral removal of cervical lymphatics in the absence of histologically proven lymph node metastases does not negatively affect the prognosis of N0 laryngeal cancer patients who were overtreated to the neck.

Background: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation., Methods: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days., Results: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT., Conclusion: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

Exposure to N-nitroso compounds is thought to play a key role in the development of gastric cancer in humans. The alkylating agent N-methyl-N'-nitrosoguanidine (MNNG) is carcinogenic in a number of animal models and its preferential target tissue is the gastrointestinal (GI) tract. The genetic synteny among rats and humans makes the rat a useful model for induced tumorigenesis. However, because of the limited availability of genetic information, cytogenetic and molecular studies are rarely performed in the rat. We report an investigation of eight MNNG-induced rat gastric tumors by comparative genomic hybridization (CGH). The tumors were from forestomach (induced by a single dose of MNNG) and from pylorus (induced by chronic exposure). CGH identified a genetic fingerprint of chromosomal imbalances common to the two types of the tumors. Frequent gains were observed at 9q11-q12, 15q22-25, and Xq11-q12. Forestomach carcinomas were also characterized by gains in 7q11-q12, 20q13, and Yq12. Homology studies between the rat and human genomes indicate the presence of genes within these regions with potential relevance to tumorigenesis in the GI tract. Our findings provide new insights into the location of genes involved in MNNG-induced gastric cancer initiation and/or progression in the rat., (Copyright 2004 Wiley-Liss, Inc.)

Objective: We surveyed retrospectively the expression of epidermal growth factor receptor (EGFR) and p53 in cases of T1-T2 glottis cancer involving the anterior (AC) or posterior commissure (PC) subsites to check for differences possibly explaining the different prognoses of cancer at these subsites., Material and Methods: Between 1970 and 1995, 15 patients with T1-T2 primary glottis cancer involving the PC, either partly or entirely, were treated. Thirty more cases were selected among 184 patients treated during the same time period for AC glottis cancer, to match the former cases with regard to age, sex, tumor stage, smoking habits and alcohol consumption., Results: A significantly higher frequency of EGFR expression occurred in PC than in AC cancer., Conclusion: These results, and the anatomy of the PC subsite, may explain the more frequent recurrence of T1-T2 PC compared to T1-T2 AC cancer and why radiotherapy achieves worse results in T1-T2 PC cancer than in AC cancer of comparable T grade.

For better understanding of the causation and behavior of T1-T2 commissural glottic laryngeal tumors, we retrospectively analyzed risk factors and outcome related to T class and type of therapy for tumors involving the anterior (184 cases) or the posterior (60 cases) commissure. The patients' smoking habits and alcohol consumption were similar, regardless of involved subsite. The disease-free interval was longer after surgery than after radiotherapy. The survival rates after recovery upon relapse were similar among subsites, T classes, and types of therapy. In anterior commissure tumors, the larynx remained preserved more frequently after partial laryngeal resection than after radiotherapy, and was more frequently preserved the lower the T class. In posterior commissure tumors, larynx preservation was less frequent and apparently independent of type of therapy or T class. In conclusion, smoking and alcohol consumption play similar pathogenetic roles in either subsite; partial laryngeal resection gave a higher rate of laryngeal preservation than did radiotherapy; and anatomic peculiarities of the subsites influence tumor behavior.