Texture and color enhancement imaging versus high definition white-light endoscopy for detection of colorectal neoplasia: a randomized trial.

BACKGROUND: Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia. METHODS: Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated. RESULTS: We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20-1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16-1.73]) and 6-9 mm (RR 1.36 [1.01-1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17-1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05-1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05-1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18-1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25-1.88]). CONCLUSIONS: TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.

Orbital myositis induced by alendronate: A case report.

BACKGROUND AND PURPOSE: Bisphosphonates are widely used, notably for osteoporosis treatment. Their common side effects are well known. However, they can trigger less common effects such as orbital inflammation. Here, the case is reported of an orbital myositis triggered by alendronate. METHODS: This is a case report at an academic medical center. An orbital magnetic resonance imaging scan, a thoraco-abdominal computed tomography scan and blood sample analyses were performed. RESULTS: A 66-year-old woman treated by alendronate for her osteoporosis was investigated. She developed an orbital myositis after the first intake. Neurological examination revealed a painful diplopia with decreased downward and adduction movements of the right eye and edema of the upper eyelid. Orbital magnetic resonance imaging showed an orbital myositis of the right eye. No other cause of orbital myositis was found than the alendronate intake. After alendronate arrest and a short course of prednisone, the symptoms resolved. CONCLUSION: This case highlights that alendronate can cause an orbital myositis whose early diagnosis is of major importance because it is a treatable side effect.

From coins to cancer therapy: Gold, silver and copper complexes targeting human topoisomerases.

Cancer is a complex issue and, even though the prevention basics and therapy have been implemented, it is still the second leading death cause worldwide. With the hope to discover new powerful and safer molecules to fight cancer, many researchers focused their attention on metal-based compounds, starting from the most famous and successfully employed anticancer drug, i.e. cisplatin. The current article aims to report the most recent discoveries about the use of gold, silver and copper complexes as antitumor agents, highlighting their influences on important enzymes, namely human topoisomerases. The latter are fundamental for the cell life and, if overexpressed, strongly implicated in cancer onset and progression. The identification of lead complexes targeting human topoisomerases and gifted with the appropriate chemical and pharmacological properties represents a fecund starting point to obtain new and more effective anticancer molecules.

Synthesis, anticancer and antioxidant properties of new indole and pyranoindole derivatives.

The indole scaffold has been recognized, over the years, as a model for the synthesis of compounds with anticancer activity by dint of its substantiated ability to act via multiple mechanisms, which also involves the inhibition of enzymes engaged in DNA replication. In this regard, a new series of indole and pyranoindole derivatives have been prepared, some of which showed good antitumor activity and proved their inhibitory effects on the tubulin target. The anticancer activity of the newly synthesized compounds has been evaluated on breast cancer cell lines, as MCF-7 and MDA-MB231, cervical cancer cells line HeLa and Ishikawa endometrial cancer cell line. Among the compounds under study, 7 exhibited a good antitumor activity on HeLa cell line (IC50 = 3.6 ± 0.5), leading to cell death by apoptosis due to the inhibition of tubulin polymerization, which demonstrated that the compound can explicate its function in a similar way to Vinblastine, a well-known inhibitor of tubulin polymerization. The data were also confirmed by in silico assays. No cytotoxicity against normal cells has been detected. Furthermore, in order to investigate the antioxidant properties, DPPH and ABTS tests were performed, together with fluorescence assays on 3T3-L1 cells. All our findings taken together led us to consider compound 7 a favourable candidate for the battle against cancer.

The clinical significance of extraluminal air in Hinchey 1a diverticulitis: results from a retrospective cohort study with 10-year follow-up.

BACKGROUND: Some patients with uncomplicated diverticulitis have extraluminal air. Our objective was to determine if patients with Hinchey 1a diverticulitis and isolated extraluminal air present more severe episode than patients without extraluminal air. METHODS: The present study is a monocentric observational retrospective cohort study. Computed tomographies of patients with diagnosed uncomplicated diverticulitis were retrospectively reviewed from the 01 January 2005 to the 31 December 2009. The presence of extraluminal air was determined. Leukocyte count, CRP value, and length of hospitalization were extracted from the patients' files. The follow-up period was from the time of diagnosis to the 15th of March 2019, the latest. Follow-up was censored for death and sigmoidectomy. Recurrence and emergency sigmoidectomy were documented during the follow-up period. The study was performed according to the STROBE guideline. RESULTS: Three hundred and one patients with an episode of Hinchey 1a diverticulitis were included. Extraluminal air was present in 56 patients (18.60%). Leukocyte count (12.4 ± 4.1(G/l) versus 10.7 ± 3.5(G/l), p = 0.05), CRP value (156.9 ± 95.1(mg/l) versus 89.9 ± 74.8(mg/l), p < 0.001), and length of hospital stay (10.9 ± 5.5(days) versus 8.4 ± 3.6(days), p < 0.001) were significantly higher in patients with extraluminal air than in patients without extraluminal air. Seventy-two patients (23.92%) presented a recurrence during the follow-up period. Survival estimates did not differ between patients with or without extraluminal air (p = 0.717). Eleven patients (3.65%) required emergency surgery during the follow-up period. Patients with extraluminal air had shorter emergency surgery-free survival than patients without extraluminal air (p < 0.05). CONCLUSION: The presence of extraluminal air in Hinchey 1a diverticulitis indicates a more severe episode, with higher inflammation parameters at admission, longer length of stay, and an increased risk for emergency sigmoidectomy.

Clinical and Ultrasound Predictors of Placenta Accreta in Pregnant Women with Antepartum Diagnosis of Placenta Previa: A Multicenter Study.

BACKGROUND/AIMS: Abnormally invasive placenta (AIP) includes placenta accreta, increta, and percreta and represents major complications of pregnancy. This study was designed to assess the role of ultrasonography in the identification of AIP among pregnant women with antepartum diagnosis of placenta previa. METHODS: A cross-sectional study was performed between May 2015 and April 2016 in 11 centers, including 242 women with antepartum diagnosis of placenta previa. RESULTS: Ninety-eight out of 242 (40.49%) women had a histological diagnosis of placenta accreta. A higher number of caesarean deliveries (p = 0.001) and curettages (p = 0.027) and older age of the woman at the delivery (p = 0.031) were identified as risk factors for placenta accreta. The presence of irregularly shaped placental lacunae (vascular spaces) within the placenta (p = 0.008), protrusion of the placenta into the bladder (p < 0.0001), and turbulent blood flow through the lacunae on Doppler ultrasonography (p = 0.008) were predictors of placenta accreta. CONCLUSIONS: Women with a prior delivery by caesarean section have a high incidence of placenta accreta among women with antepartum diagnosis of placenta previa.

Carbazole Derivatives as Antiviral Agents: An Overview.

Keywords: carbazole; tetrahydrocarbazole; antiviral agents.

N-thioalkylcarbazoles derivatives as new anti-proliferative agents: synthesis, characterisation and molecular mechanism evaluation.

Synthetic or natural carbazole derivatives constitute an interesting class of heterocycles, which showed several pharmaceutical properties and occupied a promising place as antitumour tools in preclinical studies. They target several cellular key-points, e.g. DNA and Topoisomerases I and II. The most studied representative, i.e. Ellipticine, was introduced in the treatment of metastatic breast cancer. However, because of the onset of dramatic side effects, its use was almost dismissed. Many efforts were made in order to design and synthesise new carbazole derivatives with good activity and reduced side effects. The major goal of the present study was to synthesise a series of new N-thioalkylcarbazole derivatives with anti-proliferative effects. Two compounds, 5a and 5c, possess an interesting anti-proliferative activity against breast and uterine cancer cell lines without affecting non-tumoural cell lines viability. The most active compound (5c) induces cancer cells death triggering the intrinsic apoptotic pathway by inhibition of Topoisomerase II.

Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity.

BACKGROUND: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus) prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection. METHODS: Six chloro-1,4-dimethyl-9H-carbazoles (2a,b-4a,b) have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli ß-galactosidase expressing CD4⁺, CXCR4⁺, CCR5⁺ TZM-bl cells. RESULTS AND CONCLUSION: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9H-carbazoles has been carried out. Among all tested compounds, a nitro-derivative (3b) showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs.

Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes.

The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds having anticancer action. Among the many metal compounds synthesized and tested, those based on titanium have received considerable attention because of their cytotoxic activity against solid tumors. Particularly, new titanocene compounds containing aromatic groups linked to the Cp (cyclopentadienyl ring, C5H5) have been synthetized, such as the titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium dichloride) that displayed promising medium-high cytotoxic activity on breast cancer cell lines. Other titanocene complexes recently synthesized, obtained by replacing the substituent methoxy-aryl of cyclopentadienes of titanocene Y with ethenyl-methoxide or ethenyl-phenoxide, showed increased cytotoxic activity on breast cancer cell lines being more stable compounds. In this paper, we report that new titanocene complexes holding lipophilic groups, for instance a methyl group on benzyl carbon, exhibit improved antiproliferative effect on breast cancer cell line MCF-7. Similar results have been obtained introducing a 5-methoxy naphthyl group to further stabilize the titanocene complexes. These inhibitory effects on breast cancer cells have been ascribed to human topoisomerase I and II inhibition as demonstrated by specific enzymatic assays.

New titanocene derivatives with high antiproliferative activity against breast cancer cells.

The synthesis and characterization of some new titanocene-complexes, having a ethenyl-phenoxide or a benzyl group as substituents of the cyclopentadienyl rings, are reported. The synthesized compounds have been evaluated for their cytotoxic potential against two human breast cancer cell lines, that is: MCF7 and SkBr3. Most of these compounds have shown significant cytotoxic effects, compared to cisplatin, in MTT-based cell tests.

Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles.

Several new alkylguanidines derived from carbazole have been synthesized in a simple one-pot reaction starting from 3-aminocarbazole derivatives. The aminocarbazoles were reacted with ethoxycarbonylisothiocyanate, to give thiourea intermediates, followed by the addition of an alkylamine and HgCl2 to give ethoxycarbonylguanidine intermediates. The reaction mixture was then heated at 160 °C to give the N-(1,4-dimethyl-9H-carbazol-3-yl)-N'-alkylguanidines. The cytotoxic activity of all the synthesized guanidines was evaluated against different cell lines.

Acute inflammatory response in the subcutaneous versus periprosthethic space after incisional hernia repair: an original article.

BACKGROUND: The acute inflammatory response following mesh implantation has been often evaluated in vitro and in animal models. The aim of this study was to evaluate the acute inflammatory response near the prosthesis in human by analysing some inflammatory indicators. METHODS: We used a cohort of twelve male patients affected by midline incisional hernia, who were admitted for surgical mesh repair. A suction drain was placed between the mesh and rectal muscles whereas, the other one was placed between the subcutaneous tissue and the oblique external sheath. The acute inflammatory response was analyzed by measuring the production of interleukin [IL]-1, IL-10, IL-1ra, C-Reactive Protein (CRP), total proteins, albumin and pH in the drain fluids. RESULTS: The dynamics of CRP and ILs production resulted similar in both drainages. Comparing drain over mesh and subcutaneous drain at all times, IL-1 and CRP values always resulted significantly higher in the first one, whereas IL-1ra and IL-10 values were significantly higher in the last one. Total protein and albumin were similar in both drains at all time; only in the drain over mesh fluid, pH values resulted significantly reduced in the fourth post-operative day. CONCLUSIONS: Our data showed that an acute inflammatory reaction is present in both sites examined. However, it was significantly higher in the space after mesh implantation.

N-alkyl carbazole derivatives as new tools for Alzheimer's disease: preliminary studies.

Alzheimer's disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of "dementia", because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid ß-peptide (Aß) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aß aggregation. In this context, we evaluated the ability of two recently synthesized series of N-alkyl carbazole derivatives to increase the Aß soluble forms, through molecular docking simulations and in vitro experiments. Our data evidenced that two carbazole derivatives, the most active, adopt distinct binding modes involving key residues for Aß fibrillization. They exhibit a good interfering activity on Aß aggregation in mouse (N2a) cells, stably expressing wild-type human amyloid precursor protein (APP) 695. These preliminary results are promising and we are confident that the N-alkyl carbazole derivatives may encourage next future studies needed for enlarging the knowledge about the AD disease approach.

TMBcalc: a computational pipeline for identifying pan-cancer Tumor Mutational Burden gene signatures.

Background: In the precision medicine era, identifying predictive factors to select patients most likely to benefit from treatment with immunological agents is a crucial and open challenge in oncology. Methods: This paper presents a pan-cancer analysis of Tumor Mutational Burden (TMB). We developed a novel computational pipeline, TMBcalc, to calculate the TMB. Our methodology can identify small and reliable gene signatures to estimate TMB from custom targeted-sequencing panels. For this purpose, our pipeline has been trained on top of 17 cancer types data obtained from TCGA. Results: Our results show that TMB, computed through the identified signature, strongly correlates with TMB obtained from whole-exome sequencing (WES). Conclusion: We have rigorously analyzed the effectiveness of our methodology on top of several independent datasets. In particular we conducted a comprehensive testing on: (i) 126 samples sourced from the TCGA database; few independent whole-exome sequencing (WES) datasets linked to colon, breast, and liver cancers, all acquired from the EGA and the ICGC Data Portal. This rigorous evaluation clearly highlights the robustness and practicality of our approach, positioning it as a promising avenue for driving substantial progress within the realm of clinical practice.

Suicidal decapitation by hanging: A systematic review of the literature and comparison with case reports.

INTRODUCTION: Suicidal hanging resulting in decapitation is rarely documented. This discussion involves a case of a 35-year-old man found decapitated in his residence's garden. A systematic literature review on hanging-induced decapitation was conducted to comprehensively investigate and compare the case to existing literature. The study aims to identify frequently described post-mortem findings in cases of suicidal hanging leading to decapitation. CASE REPORT: A 35-year-old man was found decapitated in his garden, with a jute strap and chimney debris nearby. The cervical region was completely severed along the dorsoventral and craniocaudal plane, exposing internal structures. A ligature mark was present, along with Amussat's sign and Simon's bleeding. METHODS: The systematic review of the literature followed PRISMA standards, analyzing 3622 publications from Google Scholar, PubMed, and Scopus databases up to 2023. Inclusion criteria comprised cases of complete or incomplete decapitation resulting from hanging, available in full-text and written in English. RESULTS: 16 articles on hanging-induced decapitation met the selection criteria; 22 cases were analyzed. Studies, mostly from Europe, showed a mean victim age of 44.3, all male. Fall height ranged from 1 m to 18 m, with various suspension media. Most cases displayed complete decapitation, primarily between cervical vertebrae C1 and C3. Some cases noted collateral findings. CONCLUSIONS: Complete crime scene investigation and thorough post-mortem examination are crucial for reconstructing events, especially with confounding elements. Precise evidence collection and literature comparison are essential to understand the case and substantiate the forensic pathologist's hypothesis in court.

Synthesis, characterization and cytotoxic activity on breast cancer cells of new half-titanocene derivatives.

A series of novel titanocene-complexes has been prepared and evaluated for their growth regulatory effects in MCF7 and SkBr3 breast cancer cells. The capability of some of these compound to elicit relevant repressive effects on cancer cell growth could be taken into account towards novel pharmacological approaches in cancer therapy.

Synthesis and cytotoxic activity evaluation of 2,3-thiazolidin-4-one derivatives on human breast cancer cell lines.

It is well known that resveratrol (RSV) displayed cancer-preventing and anticancer properties but its clinical application is limited because of a low bioavailability and a rapid clearance from the circulation. Aim of this work was to synthesize pharmacologically active resveratrol analogs with an enhanced structural rigidity and bioavailability. In particular, we have synthesized a library of 2,3-thiazolidin-4-one derivatives in which a thiazolidinone nucleus connects two aromatic rings. Some of these compounds showed strong inhibitory effects on breast cancer cell growth. Our results indicate that some of thiazolidin-based resveratrol derivatives may become a new potent alternative tool for the treatment of human breast cancer.

Biological activity of 3-chloro-azetidin-2-one derivatives having interesting antiproliferative activity on human breast cancer cell lines.

Resveratrol (3,4',5 tri-hydroxystilbene), a natural plant polyphenol, has gained interest as a non-toxic agent capable of inducing tumor cell death in a variety of cancer types. However, therapeutic application of these beneficial effects remains very limited due to its short biological half-life, labile properties, rapid metabolism and elimination. Different studies were undertaken to obtain synthetic analogs of resveratrol with major bioavailability and anticancer activity. We have synthesized a series 3-chloro-azetidin-2-one derivatives, in which an azetidinone nucleus connects two aromatic rings. Aim of the present study was to investigate the effects of these new 3-chloro-azetidin-2-one resveratrol derivatives on human breast cancer cell lines proliferation. Our results indicate that some azetidin-based resveratrol derivatives may become new potent alternative tools for the treatment of human breast cancer.

Gastroesophageal reflux in patients treated for congenital diaphragmatic hernia: short- and long-term evaluation with multichannel intraluminal impedance.

PURPOSE: The incidence of GER, related symptoms and complications in patients treated for congenital diaphragmatic hernia (CDH) are poorly defined. The aim was to evaluate incidence and development of GER in children treated for CDH in a short- and long-term follow-up period, identifying potential risk factors of morbidity. METHODS: Thirty-six patients were evaluated with pH-MII at a median age of 6 months (T1) and re-evaluated with pH-MII and endoscopy at a median age of 5 years (T2). RESULTS: The incidence of reflux was 83 % in T1 and 61 % in T2; the incidence of symptoms was 62 % in T1 and 38 % in T2. In both groups the reflux was mainly non-acidic. Patch, intrathoracic stomach and esophageal dysmotility were risk factors for GER. CONCLUSIONS: The incidence of GER and symptoms decrease over the time but it was higher than in the literature, probably because it is mainly non-acidic and evaluable only with MII. The esophageal dysmotility was found to be the main risk factor. An high incidence of reflux and esophagitis was found also in asymptomatic patients, and so a close follow-up is recommended in all patients even if it is asymptomatic.