Evaluation of esophageal motility using multichannel intraluminal impedance in healthy children and children with gastroesophageal reflux: comments

Abstract OBJECTIVE: : Multichannel intraluminal impedance (MII) directly evaluates esophageal bolus transport. There is a good correlation between MII and manometry in healthy adults, but there are no reports concerning children.The aim of the present study was to determine normal values of esophageal motility using only impedance measurements in healthy children and in a pediatric population with gastroesophageal reflux (GER). PATIENTS AND METHODS: : We described in the present study 60 children submitted to pH-MII for 24 hours for suspected GER. Patients were divided into 2 different groups on the basis of their pH-MII report. Group 1 patients showed acid GER, whereas group 2 patients had negative pH-MII analysis for GER despite symptoms. We described impedance reflux and motility parameters on 10 standardized swallows: number of reflux, mean acid clearing time, median bolus clearing time, bolus presence time, total bolus transit time, segmental transit time, and total propagation velocity. RESULTS: : In group 1, the median mean acid clearing time was 151 seconds, whereas the median mean bolus clearing time was 25 seconds. In group 2 patients, all of the reflux parameters were normal. In group 1 the median bolus presence time at each measuring site, the median total bolus transit time, and the median segmental transit time were significantly greater and total propagation velocity lower than values reported in group 2 (P < 0.001), if compared with those described for adult patients. CONCLUSIONS: : The pH-MII is an ideal test in children because it studies GER with its characteristics and motility pattern. Our report summarizes for the first time impedance motility parameters in healthy children

An Update of Carbazole Treatment Strategies for COVID-19 Infection

The Coronavirus disease 2019 (COVID-19) outbreak was declared by the World Health Organization (WHO) in March 2020 to be a pandemic and many drugs used at the beginning proved useless in fighting the infection. Lately, there has been approval of some new generation drugs for the clinical treatment of severe or critical COVID-19 infections. Nevertheless, more drugs are required to reduce the pandemic’s impact. Several treatment approaches for COVID-19 were employed since the beginning of the pandemic, such as immunomodulatory, antiviral, anti-inflammatory, antimicrobial agents, and again corticosteroids, angiotensin II receptor blockers, and bradykinin B2 receptor antagonists, but many of them were proven ineffective in targeting the virus. So, the identification of drugs to be used effectively for treatment of COVID-19 is strongly needed. It is aimed in this review to collect the information so far known about the COVID-19 studies and treatments. Moreover, the observations reported in this review about carbazoles as a treatment can signify a potentially useful clinical application; various drugs that can be introduced into the therapeutic equipment to fight COVID-19 or their molecules can be used as the basis for designing new antivirals

Efficacy of periportal infiltration and intraperitoneal instillation of ropivacaine after laparoscopic surgery in children

Postoperative pain is less intense after laparoscopic than after open surgery. However, minimally invasive surgery is not a a pain-free procedure. Many trials have been done in adults using intraperitoneal and/or incisional local anesthetic, but similar studies have not yet been reported in the literature in children. Aim: The aim of this study was to evaluate the analgesic effect of periportal infiltration and intraperitoneal instillation of ropivacaine in children undergoing laparoscopic surgery. Materials and Methods: Thirty patients who underwent laparoscopic surgery were randomly allocated to one of three groups. Group A (n 10) received local infiltration of port sites with 10 mL of ropivacaine. Group B (n 10) received both an infiltration of port sites with 10 mL of ropivacaine and an intraperitoneal instillation of 10 mL of ropivacaine. Group C did not receive any analgesic treatment. The local anesthetic was always administered at the end of surgery. The degree of postoperative abdominal parietal pain, abdominal visceral pain, and shoulder pain was assessed by using a Wong-Baker pain scale and a Visual Analog Scale (VAS) at 3, 6 12, and 24 hours postoperatively. The following parameters were also evaluated: rescue analgesic treatment, length of hospital stay, and time of return to normal activities. Results: Three hours after operation, patients had low pain scores. Six and 12 hours postoperatively, the abdominal parietal pain was significantly higher (P 0.0005) in group C than in the other two groups, both treated with an infiltration at the trocar sites; mean intensity of abdominal visceral pain was significantly lower (P 0.0005) in group B than in groups A and C; the overall incidence of shoulder pain was significantly lower (P 0.0005) in group B patients than in patients of groups A and C. At 20 hours postoperatively, pain scores were significantly reduced of intensity in all groups. Rescue analgesic treatment was significantly higher in group C, if compared to groups A and B 12 hours after the operation. No statistically significant difference was found in length of hospital stay, but children who received analgesic treatment had a more rapid return to normal activities than untreated patients (P 0.0005). Conclusions: Our study demonstrates that the combination of local infiltration and intraperitoneal instillation of ropivacaine is more effective for pain relief in children after laparoscopic surgery than the administration of ropivacaine only at the trocar sites

A simple technique of oblique anastomosis can prevent stricture formation in primary repair of esophageal atresia

Background: Anastomotic stricture is an important problem after esophageal atresia (EA) repair. This study evaluates a technique of oblique esophageal anastomosis without use of a flap in order to prevent stricture formation. Methods: Medical records of 16 patients (14 with EA type III and 2 with EA type IV Ladd-Gross classification) who underwent primary repair of EA at birth without anastomotic tension were reviewed, evaluating long-term follow-up results. All patients were studied with esophageal contrast study, pH-multichannel intraluminal impedance, and endoscopy. The incidence of complications and their management were analysed. Results: Contrast esophagogram and esophagoscopy always showed regular patency of the suture line. Conclusions: Our technique of oblique anastomosis is simple, safe, and effective in preventing stricture formation even in the long-term follow-up

SIRT1 Mediates Melatonin’s Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence

Melatonin exerts direct neuroprotection against cerebral hypoxic damage, but the mechanisms of its action on microglia have been less characterized. Using both in vitro and in vivo models of hypoxia, we here focused on the role played by silent mating type information regulation 2 homolog 1 (SIRT1) in melatonin’s effects on microglia. Viability of rat primary microglia or microglial BV2 cells and SH-SY5Y neurons was significantly reduced after chemical hypoxia with CoCl2 (250 µM for 24 h). Melatonin (1 µM) significantly attenuated CoCl2 toxicity on microglia, an effect prevented by selective SIRT1 inhibitor EX527 (5 µM) and AMP-activated protein kinase (AMPK) inhibitor BML-275 (2 µM). CoCl2 did not modify SIRT1 expression, but prevented nuclear localization, while melatonin appeared to restore it. CoCl2 induced nuclear localization of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-kB), an effect contrasted by melatonin in an EX527-dependent fashion. Treatment of microglia with melatonin attenuated potentiation of neurotoxicity. Common carotid occlusion was performed in p7 rats, followed by intraperitoneal injection of melatonin (10 mg/kg). After 24 h, the number of Iba1+ microglia in the hippocampus of hypoxic rats was significantly increased, an effect not prevented by melatonin. At this time, SIRT1 was only detectable in the amoeboid, Iba1+ microglial population selectively localized in the corpus callosum. In these cells, nuclear localization of SIRT1 was significantly lower in hypoxic animals, an effect prevented by melatonin. NF-kB showed an opposite expression pattern, where nuclear localization in Iba1+ cells was significantly higher in hypoxic, but not in melatonin-treated animals. Our findings provide new evidence for a direct effect of melatonin on hypoxic microglia through SIRT1, which appears as a potential pharmacological target against hypoxic-derived neuronal damage.Fil: Merlo, Sara. Universidad de Catania; ItaliaFil: Luaces, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Spampinato, Simona Federica. Universidad de Catania; ItaliaFil: Toro Urrego, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Caruso, Grazia Ilaria. Universidad de Catania; ItaliaFil: D´Amico, Fabio. Universidad de Catania; ItaliaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Sortino, Maria Angela. Universidad de Catania; Itali

Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion

Dendritic cells (DCs) are professional antigen presenting cells (APCs) that in response to microbial infections generate long-lasting adaptive immune response. Following microbial uptake, DCs undergo a cascade of cellular differentiation that ultimately leads to “mature” DCs. Mature DCs produce a variety of inflammatory cytokines, including tumor necrosis factor-α (TNFα) a key cytokine for the inflammatory cascade. In numerous studies, polyphenols, including quercetin, demonstrated their ability to suppress TNFα secretion and protect from the onset of chronic inflammatory disorders. We show that murine bone marrow derived DCs express Slpi following quercetin exposure. Slpi is known to suppress LPS mediated NFκB activation, thus, it was hypothesized that its expression could be the key step for polyphenol induced inflammatory suppression. Slpi-KO DCs poorly respond to quercetin administration failing to reduce TNFα secretion in response to quercetin exposure. Supernatant from quercetin exposed DCs could also reduce LPS-mediated TNFα secretion by unrelated DCs, but this property is lost using an anti-Slpi antibody. In vivo, oral administration of quercetin is able to induce Slpi expression. Human biopsies from inflamed tract of the intestine reveal the presence of numerous SLPI(+) cells and the expression level could be further increased by quercetin administration. We propose that quercetin induces Slpi expression that in turn reduces the inflammatory response. Our data encourages the development of nutritional strategies to improve the efficiency of current therapies for intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively.In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatini

A: Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica 2011; 96

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine. Key words: thalassemia, iron chelation therapy, cardiac magnetic resonance imaging. Citation: Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti L, Malaventura C, Putti MC, Lippi A, Romeo MA, Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo L, Missere M, Midiri M, Rossi G, Positano V, Lombardi M, and Maggio A. Deferasirox, deferipron