Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.

Light-Driven Water Oxidation with the Ir-blue Catalyst and the Ru(bpy)32+/S2O82- Cycle: Photogeneration of Active Dimers, Electron-Transfer Kinetics, and Light Synchronization for Oxygen Evolution with High Quantum Efficiency.

Light-driven water oxidation is achieved with the Ru(bpy)32+/S2O82- cycle employing the highly active Ir-blue water oxidation catalyst, namely, an IrIV,IV2(pyalc)2 µ-oxo-dimer [pyalc = 2-(2'-pyridyl)-2-propanoate]. Ir-blue is readily formed by stepwise oxidation of the monomeric Ir(III) precursor 1 by the photogenerated Ru(bpy)33+, with a quantum yield ϕ of up to 0.10. Transient absorption spectroscopy and kinetic evidence point to a stepwise mechanism, where the primary event occurs via a fast photoinduced electron transfer from 1 to Ru(bpy)33+, leading to the Ir(IV) monomer I1 (k1 ∼ 108 M-1 s-1). The competent Ir-blue catalyst is then obtained from I1 upon photooxidative loss of the Cp* ligand and dimerization. The Ir-blue catalyst is active in the Ru(bpy)32+/S2O82- light-driven water oxidation cycle, where it undergoes two fast photoinduced electron transfers to Ru(bpy)33+ [with kIr-blue = (3.00 ± 0.02) × 108 M-1 s-1 for the primary event, outperforming iridium oxide nanoparticles by ca. 2 orders of magnitude], leading to a IrV,V2 steady-state intermediate involved in O-O bond formation. The quantum yield for oxygen evolution depends on the photon flux, showing a saturation regime and reaching an impressive value of ϕ(O2) = 0.32 ± 0.01 (corresponding to a quantum efficiency of 64 ± 2%) at low irradiation intensity. This result highlights the key requirement of orchestrating the rate of the photochemical events with dark catalytic turnover.

Feeding tubes in children.

PURPOSE OF REVIEW: A practical guide to different feeding tubes available for nutritional support in children, focused on indications, placement methods and complications. RECENT FINDINGS: Enteral nutritional support refers to the delivery of nutrition into the gastrointestinal tract distal to the oesophagus. Different feeding tubes are available for exclusive or supplemental nutritional support in children who are unable to independently sustain their own growth, nutritional and hydration status. Gastric feeding is the first choice; however, jejunal feeding provides a good alternative route in the presence of contraindications or intolerance. Feeding tubes can be short or long term: nasogastric and nasojejunal tubes provide short-term nutrition support, gastrostomy and jejunostomy tubes, long-term enteral feeding. The latter are established surgically through the formation of a stoma, an artificial connection between gastric or jejunal lumen and the abdominal wall, performed either endoscopically (percutaneous endoscopic gastrostomy, percutaneous endoscopic gastrojejunostomy) or surgically (gastrostomy, direct jejunostomy). Awareness of different available options, technical considerations and potential risks will inform the decision-making process for an individual patient to ensure the correct balance between adequate enteral nutritional and unnecessary morbidity. SUMMARY: Successful administration of nutrition support requires knowledge of the correct indication, route and specific functional details of the appropriate feeding tube.

Anti-Glypican 3, a Novel Ancillary Maker in the Histological Assessment of Hirschsprung's Disease.

OBJECTIVES: Hirschsprung's disease (HSCR) results from a malformation of the enteric nervous system. A congenital absence of intrinsic ganglion cells from the distal rectum and a variable length of the contiguous bowel is the required diagnostic feature of Hirschsprung's disease and total colonic aganglionosis (TCA). We evaluated the utility of a monoclonal antibody directed against glypican 3 (GPC-3), a membrane bound protein involved in regulation of the signaling of Wingless-types (WNTs), Hedgehogs (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), in the detection of ganglion cells in formalin-fixed, paraffin-embedded tissue sections. METHODS: The presence/absence of ganglion cells was evaluated retrospectively by immunohistochemical staining for calretinin and GPC-3 in tissue specimens; a total of 15 patients who underwent colectomy (total or sub-total) for histologically proven aganglionosis (14 HSCR, 1 TCA) and 5 rectal suction biopsies (4HSCR-B, 1 TCA-B) were considered. Of the 20 considered cases, a total of 60 tissue specimens (3 for each patient) were selected. A total of 30 additional normal (N) colonic mucosa biopsy samples were also included. RESULTS: GPC-3 constantly identified ganglion cell bodies in all but 2 normal biopsies (with normal presentation of ganglion cells on hematoxylin and eosin (H&E) stain), and was negative in all 60 aganglionotic biopsies; these results were reflective of calretinin staining pattern. CONCLUSIONS: The present study indicates that monoclonal anti-GPC-3 might prove to be useful immunohistochemical marker in the identification of ganglion cells in paraffin-embedded rectal tissue specimens and suction biopsies. Further studies in larger series will contribute to demonstrate its utility as an ancillary marker in the histological assessment of HSCR aganglionosis.

Simultaneous Electro-Optical Tracking for Nanoparticle Recognition and Counting.

We present the first detailed experimental observation and analysis of nanoparticle electrophoresis through a nanochannel obtained with synchronous high-bandwidth electrical and camera recordings. Optically determined particle diffusion coefficients agree with values extracted from fitting electrical transport measurements to distributions from 1D Fokker-Planck diffusion-drift theory. This combined tracking strategy enables optical recognition and electrical characterization of nanoparticles in solution, which can have a broad range of applications in biology and materials science.

Water oxidation catalysis upon evolution of molecular Co(III) cubanes in aqueous media.

The increasing global energy demand has stimulated great recent efforts in investigating new solutions for artificial photosynthesis, a potential source of clean and renewable solar fuel. In particular, according to the generally accepted modular approach aimed at optimising separately the different compartments of the entire process, many studies have focused on the development of catalytic systems for water oxidation to oxygen. While in recent years there have been many reports on new catalytic systems, the mechanism and the active intermediates operating the catalysis have been less investigated. Well-defined, molecular catalysts, constituted by transition metals stabilised by a suitable ligand pool, could help in solving this aspect. However, in some cases molecular species have been shown to evolve to active metal oxides that constitute the other side of this catalysis dichotomy. In this paper, we address the evolution of tetracobalt(III) cubanes, stabilised by a pyridine/acetate ligand pool, to active species that perform water oxidation to oxygen. Primary evolution of the cubane in aqueous solution is likely initiated by removal of an acetate bridge, opening the coordination sphere of the cobalt centres. This cobalt derivative, where the pristine ligands still impact on the reactivity, shows enhanced electron transfer rates to Ru(bpy)3(3+) (hole scavenging) within a photocatalytic cycle with Ru(bpy)3(2+) as the photosensitiser and S2O8(2-) as the electron sink. A more accentuated evolution occurs under continuous irradiation, where Electron Paramagnetic Resonance (EPR) spectroscopy reveals the formation of Co(ii) intermediates, likely contributing to the catalytic process that evolves oxygen. All together, these results confirm the relevant effect of molecular species, in particular in fostering the rate of the electron transfer processes involved in light activated cycles, pivotal in the design of a photoactive device.

Calretinin, ß-tubulin immunohistochemistry, and submucosal nerve trunks morphology in Hirschsprung disease: possible applications in clinical practice.

OBJECTIVES: The aim of this study was to investigate calretinin and ß-tubulin immunohistochemical expression together with submucosal nerve trunks morphology in differently innervated segments of Hirschsprung disease (HD) and total colonic aganglionosis (TCA). METHODS: A total of 25 cases (22 HD, 3 TCA) and 18 controls were processed for calretinin and ß-tubulin immunohistochemistry. Sections representative of distal aganglionic, transition, and proximal ganglionic segments were evaluated by a visual grading score; ß-tubulin was evaluated also by image analysis. Submucosal nerve trunks hypertrophy and hyperplasia were measured by citomorphology. The length of proximal segment was correlated to postoperative bowel function. RESULTS: Controls showed intense calretinin and ß-tubulin staining. In HD and TCA, calretinin staining was related to the presence of ganglion cells: negative in distal, faint in transition, intense in proximal segment. ß-Tubulin staining was weak in all of the segments of HD and negative in TCA. Hypertrophic and hyperplastic nerve trunks characterized aganglionic segment, and progressively decreasing nerve size was observed in transition and ganglionic segments. Transient postoperative constipation, soiling, or enterocolitis was present in 59% of patients with HD without clear relation to proximal segment length or presence of hypertrophic nerve trunks. CONCLUSIONS: Calretinin is a reliable marker of the presence of ganglion cells, and, together with nerve hypertrophy, it helps to identify the transition zone. Length and nerve size of proximal segment in resected specimen did not affect the postsurgical intestinal function. Reduced ß-tubulin expression along the entire colonic tract, included proximal ganglionic segments, may represent a potential impairing factor for the enteric neural transmission.

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients.

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response.

Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant. Furthermore, non-responder patients are candidate to radical cystectomy in the absence of valuable alternative options. These aspects have prompted the search for newer biological response modifiers (BRM) with a better benefit/side effects ratio. The toll-like receptor (TLR) 2 ligand, Helicobacter pylori protein HP-NAP, has been shown to deserve a potential role as BRM. HP-NAP is capable of driving the differentiation of T helper (Th) 1 cells, both in vitro and in vivo, because of its ability to create an IL-12-enriched milieu. Herein, we report that local administration of HP-NAP decreases tumour growth by triggering tumour necrosis in a mouse model of bladder cancer implant. The effect is accompanied by a significant accumulation of both CD4+ and CD8+ IFN-γ-secreting cells, within tumour and regional lymph nodes. Noteworthy, HP-NAP-treated tumours show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Our findings strongly indicate that HP-NAP might become a novel therapeutic "bullet" for the cure of bladder tumours.

Digi-Care: Exploring the Impacts of Digitization on Nursing Work in Switzerland.

In this paper we present first findings of the Digi-Care project, a multidisciplinary, multi-stakeholder research project investigating the impacts of digitization on nursing work practices and in particular the transmission of patient care information within and beyond nursing work practices. We completed the initial data collection of the funded 3-year research project and report on a plethora of significant and critical IT-related events. Some of them can be attributed to usability issues.

Rapid spread of a new West Nile virus lineage 1 associated with increased risk of neuroinvasive disease during a large outbreak in northern Italy, 2022: One Health analysis.

BACKGROUND: A new strain of WNV lineage 1 (WNV - 1) emerged in the Veneto Region, northern Italy, in 2021, eight years after the last outbreak of WNV - 1 in Italy. The virus, which co-circulates with WNV-2, has become endemic in the Region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred. METHODS: Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from May 16th to August 21st, 2022, to determine if the high number of WNND cases was associated with WNV-1. RESULTS: As of August 21st, 2022, 222 human cases of WNV infection were confirmed by molecular testing, including 103 with fever (WNF) and 119 with WNND. WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. During the same period, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that patients with WNND were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% CI 95% 1.54 to 8.24; p = 0.0043). As observed in humans, in wild birds WNV-1 had higher infectious rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2. CONCLUSIONS: Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds, and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1 infected patients might have an increased risk to develop severe disease.

Imaging in prostate cancer diagnosis: present role and future perspectives.

Prostate cancer (PCa) remains a major health concern for the male population. Detection and primary diagnosis of PCa are based on digital rectal examination, serum prostate-specific antigen levels, and transrectal ultrasound (TRUS)-guided random biopsy. Moreover, the gold standard for detecting PCa, systematic biopsy, lacks sensitivity as well as grading accuracy. This review summarizes recent developments of ultrasonography modalities and functional magnetic resonance imaging (MRI) in the diagnosis of PCa. A comparison between the different methods is presented, including their clinical value and usefulness. It is concluded that innovative ultrasound techniques (including ultrasound contrast agents, 3-D and 4-D sonography, elastography and harmonic sonography) promise benefits in comparison to standard TRUS to accurately diagnose PCa. Promising advances have been made in the detection of PCa with multiparametric MRI. The combination of conventional and functional MRI techniques (including diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy) can provide information for differentiating PCa from noncancerous tissue and can be used for MRI-guided biopsies, especially in patients with persistent elevation of serum prostate-specific antigen and previous negative TRUS-guided biopsies. However, functional MRI technique and MRI-guided biopsy remain expensive and complex tools presenting inherent challenges.

Imaging of renal cell carcinoma: state of the art and recent advances.

BACKGROUND AND AIM: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. METHODS: Literature search of peer-reviewed papers published by October 2010. RESULTS: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. CONCLUSIONS: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools.

Thoracoscopy versus thoracotomy for congenital lung malformations treatment: A single center experience.

INTRODUCTION: Our aim is to compare thoracoscopy to thoracotomy in the treatment of congenital lung malformations (CLM) in children. MATERIALS AND METHODS: We report a retrospective monocentric cohort study. Patients treated at our Center for CLM (1991-2020) were divided in two groups: patients treated with video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT). Characteristics of the two groups were compared through statistical analysis (GraphPad Prism7). A p value less than .05 was considered statistically significant. RESULTS: One hundred six patients were included: 58 in VATS group, 48 in OT group. Prenatal diagnosis was possible in 73.6%. The most frequent surgical procedures were lobectomy (43.4%) and sequestrectomy (22.6%). All VATS patients underwent lung exclusion, mostly by endobronchial blocker (69%). Mean operative time was 146.1 min (±52.04 SD) in VATS and 159.2 (±46.53 SD) in OT (p = .1973). Conversion to OT was necessary in 20.6% of VATS patients, but decreased in the last 5 years (6.2%). There were not any intraoperative complication. Respectively in VATS and OT group, length of stay (LOS) was 4.5 days ± 3.6 SD versus 7.7 ± 3.4 SD (p < .0001), chest tube duration 2.8 days ± 3.4 SD versus 3.7 ± 2.4 SD (p < .0001), antibiotic treatment duration 3.7 days ± 4.7 SD versus 5 ± 2.6 SD (p = .1196). Postoperative complications were described in 22.6%. The commonest histological diagnosis (40.6%) was congenital pulmonary airway malformation. CONCLUSION: VATS resulted a feasible, effective and safe technique. Operative time and postoperative complications were similar in VATS and OT groups. VATS conversion rate decreased in time. VATS had a statistically significant shorter LOS and chest tube duration.

Anesthesia in Children with Neuroblastoma, Perioperative and Operative Management.

Neuroblastoma (NB) is the most common extracranial, solid, pediatric malignancy and, despite the constant progress of treatment and development of innovative therapies, remains a complex, challenging disease causing major morbidity and mortality in children. There is significant variability in the management of neuroblastoma, partially due to the heterogeneity of the clinical and biological behavior, and partially secondary to the different approaches between treating institutions. Anesthesia takes an integral part in the multidisciplinary care of patients with NB, from diagnosis to surgery and pain control. This paper aims to review and discuss the critical steps of the perioperative and operative management of children undergoing surgery for neuroblastoma. Anesthesia and analgesia largely depend on tumor location, surgical approach, and extension of the surgical dissection. Attention should be paid to the physio-pathological changes on cardiovascular, gastrointestinal, and immune systems induced by the tumor or by chemotherapy. At the time of surgery meticulous patient preparation needs to be carried out to optimize intraoperative monitoring and minimize the risk of complications. The cross-sectional role of anesthesia in cancer care requires effective communication between all members of the multidisciplinary team.

Intensive intravesical mitomycin C therapy in non-muscle-invasive bladder cancer: a dose intensity approach.

OBJECTIVE: The aim of this work was to verify the tolerability and the preliminary clinical results of intensive intravesical instillations of a mitomycin C (MMC) regimen. PATIENTS AND METHODS: From September 2007 to November 2009, 40 consecutive evaluable patients with pathologically confirmed intermediate-risk non-muscle-invasive bladder cancer (NMIBC) were enrolled after complete transurethral resection of all visible tumors. The mean age of the patients was 64.5 years. 40 mg MMC diluted in 50 ml of saline was instilled in the bladder three times a week for 2 weeks. The median follow-up was 9 months. RESULTS: All patients fulfilled the scheduled treatment. The local adverse events seen were negligible, while no significant deviation from normal values was observed in blood counts for each patient. Twenty-three of 40 patients (57.5%) showed negative at the cystoscopic control which was performed every 3 months with normal spontaneous and washing cytological exams. CONCLUSION: MMC is a well-known chemotherapeutic agent for the intravesical therapy of NMIBC. With a view to improving its results, we changed the frequency and intensity of the instillations. No significant local or systemic toxicity was reported. Intensive intravesical instillations of MMC might become a tool in the management of NMIBC.

Imaging in bladder cancer: present role and future perspectives.

Advances in imaging have an increasingly significant role in the diagnosis, staging and restaging of patients with bladder cancer. This paper reviews the current use of imaging in bladder neoplasms, comparing the different radiologic investigations, and discusses the potential applications of novel imaging techniques in the management of patients with bladder cancer.

Metastasis to the renal hilum from malignant melanoma of the anterior trunk: an unusual finding.

A retroperitoneal metastasis from malignant melanoma is an uncommon event and mostly secondary to a primary lesion of the posterior trunk. We report on a 38-year-old patient with malignant melanoma of the anterior trunk who presented a symptomatic metastatic mass of the left renal hilum not originating from the retroperitoneal lymph nodes of the renal hilum, surrounding and infiltrating the renal pelvis, treated with left nephrectomy, complete mass excision and regional lymph node dissection. The patient later developed also brain metastases and is now undergoing immunotherapy.

Novel iridium complexes with N-heterocyclic dicarbene ligands in light-driven water oxidation catalysis: photon management, ligand effect and catalyst evolution.

Iridium complexes [IrClCp*diNHC]PF6, with N-heterocyclic dicarbene (diNHC) and pentamethylcyclopentadienyl (Cp*) ligands, have been investigated in light driven water oxidation catalysis within the Ru(bpy)32+/S2O82- cycle (bpy = 2,2'-bipyridine). In particular, the effect of different diNHC ligands was evaluated by employing the complex 1a (diNHC = 1,1'-dimethyl-3,3'-ethylenediimidazol-2,2'-diylidene) and the novel and structurally characterised 2 (diNHC = 1,1'-dimethyl-3,3'-ethylene-5,5'-dibromodiimidazol-2,2'-diylidene) and 3 (diNHC = 1,1'-dimethyl-3,3'-ethylene-dibenzimidazol-2,2'-diylidene). The presented results include: (i) a photon management analysis of the 1a/Ru(bpy)32+/S2O82- system, revealing two regimes of O2 evolution rate, being dependent on the light intensity at low photon flux, where the system reaches an overall quantum yield up to 0.17 ± 0.01 (quantum efficiency 34 ± 2%), while being independent of light intensity at high photon flux thus indicating a change of limiting step; (ii) a trend of O2 evolution activity that follows the order 1a > 2 > 3 both under low and high photon flux conditions, with the reactivity that is favoured by the electron donating nature of the diNHC ligand, quantified on the basis of the carbene carbon chemical shift; (iii) an analogous trend also in the bimolecular rate constants of electron transfer kET from the iridium species to photogenerated Ru(bpy)33+, with kET values in the range 4.2-6.1 × 104 M-1 s-1, thus implying a significant reorganisation energy to the iridium sphere; (iv) the evolution of 1a, as the most active Ir species in the series, to mononuclear iridium species with lower molecular weight and originating from oxidative transformation of the organic ligand scaffold, as proven by converging UV-Vis, MALDI-MS and 1H-NMR evidences. These results can be used for the further design and engineering of novel catalysts.