Transpleural systemic artery-pulmonary artery communications in the absence of chronic inflammatory lung disease. A case series and review of the literature

AIM: To describe the causes and computed tomography (CT) and angiographic appearances of transpleural systemic artery-pulmonary artery shunts in patients without chronic inflammatory lung disease and determine their best management. MATERIALS AND METHODS: All patients referred to a tertiary referral unit between January 2013 and January 2020 in whom a diagnosis of a systemic-pulmonary artery communication without underlying chronic inflammatory lung disease was subsequently made have been included in this report. Medical records and imaging findings were reviewed retrospectively. RESULTS: Ten patients (male: female ratio = 7:3; median age 42 years [range 22-70 years]) with systemic artery-pulmonary artery shunts without chronic inflammatory lung disease were identified. Five were misdiagnosed as having a pulmonary arteriovenous malformation and had been referred for embolisation. In six patients, there was either a history of accidental or iatrogenic thoracic trauma or of inflammatory disease involving the pleura, and in two patients, in whom a previous medical history could not be obtained, there were CT features suggesting previous pleural inflammatory disease. Two shunts were thought to be congenital. All individuals were asymptomatic other than one with localised thoracic discomfort that dated from the time of surgery. All patients were managed conservatively and have remained well with a median follow-up of 4.5 years (range 1-11.3 years). CONCLUSIONS: Localised transpleural systemic artery-pulmonary artery shunts in the absence of chronic inflammatory lung disease are usually related to previous thoracic trauma/intervention or abdominal or pulmonary sepsis involving a pleural or diaphragmatic surface. Congenital shunts are rare. The present study and much of the literature supports conservative management

Prevalence of ‘pouch failure’ of the ileoanal pouch in ulcerative colitis: A systematic review and meta-analysis

Background and aims The ileoanal pouch (IPAA) provides patients with ulcerative colitis (UC) that have not responded to medical therapy an option to retain bowel continuity and defecate without the need for a long-term stoma. Despite good functional outcomes, some pouches fail, requiring permanent diversion, pouchectomy, or a redo pouch. The incidence of pouch failure ranges between 2 and 15% in the literature. We conducted a systematic review and meta-analysis aiming to define the prevalence of pouch failure in patients with UC who have undergone IPAA using population-based studies. Methods We searched Embase, Embase classic and PubMed from 1978 to 31st of May 2021 to identify cross-sectional studies that reported the prevalence of pouch failure in adults (≥ 18 years of age) who underwent IPAA for UC. Results Twenty-six studies comprising 23,389 patients were analysed. With < 5 years of follow-up, the prevalence of pouch failure was 5% (95%CI 3–10%). With ≥ 5 but < 10 years of follow-up, the prevalence was 5% (95%CI 4–7%). This increased to 9% (95%CI 7–16%) with ≥ 10 years of follow-up. The overall prevalence of pouch failure was 6% (95%CI 5–8%). Conclusions The overall prevalence of pouch failure in patients over the age of 18 who have undergone restorative proctocolectomy in UC is 6%. These data are important for counselling patients considering this operation. Importantly, for those patients with UC being considered for a pouch, their disease course has often resulted in both physical and psychological morbidity and hence providing accurate expectations for these patients is vital

Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response

First COVID-19 molecular docking with a chalcone-based compound: synthesis, single-crystal structure and Hirshfeld surface analysis study

The first example of molecular docking of the SARS-CoV-2 main protease for COVID-19 [Mpro, Protein Data Bank (PDB) code 7BQY] by a chalcone-based ligand, namely, (E)-1-(2,4-dichlorophenyl)-3-[4-(morpholin-4-yl)phenyl]prop-2-en-1-one, C19H17Cl2NO2, I, is presented. Two-dimensional (2D) LIGPLOT representations calculated for the inhibitor N3, viz. N-{[(5-methylisoxazol-3-yl)carbonyl]alanyl}-l-valyl-N 1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-l-leucinamide, and 7BQY are included for comparison with our chalcone-based complexes. The binding affinity of our chalcone ligand with 7BQY is-7.0 kcal mol-1, a high value which was attributed to the presence of a hydrogen bond, together with many hydrophobic interactions between the drug and the active amino acid residues of the receptor. Docking studies were also performed, employing rigid and flexible binding modes for the ligand. The superposition of N3 and the chalcone docked into the binding pocket of 7BQY is also presented. The synthesis, single-crystal structure, Hirshfeld surface analysis (HSA) and spectral characterization of heterocyclic chalcone-based compound I, are also presented. The molecules are stacked, with normal π-π interactions, in the crystal

A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms

Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were SBNEN, G1/G2 NEN, initial tumour diagnosis, stage IV NEN, positivity on 68Ga somatostatin analogue PET/CT, eligible for surgery, and 177Lu peptide receptor radionuclide therapy (PRRT). Blood samples for NETest were collected longitudinally. Progression-free survival (PFS) and overall survival (OS) were calculated. NETest results were assessed prior to surgery and during clinical follow-up. Results: A surgical cohort of 39 SBNEN patients met eligibility criteria. Thirty-two patients underwent ileal resection and 7 right hemicolectomy. The mean number of 177Lu PRRT cycles was 4. Mortality was nil. Surgical morbidity was 10.3%. Transient grade 1/2 toxicity occurred in 41% (PRRT). NETest scores (n=9 patients) decreased in 100% following treatment and correlated with diminished tumour volume and disease stabilization following surgery and PRRT. Median follow-up: 78 months. Median PFS and OS: 42.7 and 110 months, respectively. Progression-free survival at 1-, 3-, and 5-years was 79.4%, 57.1% and 40.5%, respectively. Overall survival at 1-, 3-, and 5-years was 97.4%, 97.4%, and 94.1%, respectively. Conclusions: Surgery combined with 177Lu PRRT is safe and provides favourable PFS and OS in selected patients with advanced SBNEN. Liquid biopsy (NETest) has the potential to accurately delineate disease status

Patients with in-situ metallic coils and amplatzer vascular plugs used to treat pulmonary arteriovenous malformations since 1984 can safely undergo magnetic resonance imaging

OBJECTIVES: To examine the magnetic resonance imaging (MRI) safety of metallic coils and Amplatzer vascular plugs. Currently, concern regarding MR-safety of devices used to treat pulmonary arteriovenous malformations (PAVMs) causes delays in performing emergency MRI in patients presenting with acute neurological symptoms. METHODS: A retrospective audit was performed on all patients who underwent PAVM embolization at our institution between 1984 – 2017. Outcomes of all MRI studies performed at our institution were recorded. In addition, known outcomes of all known MRI studies performed on patients treated with the earliest steel coils (1984 – 1995) were recorded. RESULTS: At our institution, 20 patients underwent 1.5 T MRI after the insertion of 100 steel coils (15.5 – 28.6, median 22 years later), 140 coils designated MR-conditional (0.42 – 12.7, median 9.3 years later), and 54 MRI-conditional Amplatzer vascular plugs (0.17 – 8.0, median 0.75 years later), many in combination. The majority of scans were for cerebral indications, but other body regions scanned included spinal, thoracic, and pelvic regions. No adverse events were reported. Similarly, there were no adverse events in any MR scan known to have been performed in other institutions in seven further patients treated with the earliest steel coils (1984 – 1995). Again, the majority of scans were for cerebral indications. CONCLUSIONS: The findings demonstrate MR safety at 1.5 T of all PAVM embolization devices inserted in a main UK centre since inception in 1984. ADVANCES IN KNOWLEDGE: Magnetic resonance imaging of patients who have had pulmonary AVMs treated by embolization can be implemented without contacting specialist pulmonary arteriovenous malformation treatment centres for approval

The Spectral Measurement of Scattered Radiation From a Clinical Linear Accelerator Using a CZT Detector

The study of the induced radioactivity following radiotherapy with high energy X-rays from medical linear accelerator. Patient equivalent phantom made of Polymethyl methacrylate (PMMA) of 30x30x27 cm size irradiated with 15 MV X-rays from Versa HD medical linear accelerator form Elekta. Induced radioactive and ambient dose rates were measured at 0.25, 0.5 and 1 m from beam center using GR1® spectrometry with Cadmium Zinc Telluride (CZT) detectors having energy resolution less than 2%. Spectrum analysis was performed using MultiSpect software. The measured spectrum showed 511 keV annihilation photons possibly as a result of positron emitter of which most likely candidates are 62Cu(T1/2: 9.7 min), 64Cu (T1/2: 12.7 h )  and 57Ni  (T1/2:  35.6 h) and a  peak at ≈ 1780 keV that could be attributed 28Al and 214Bi radioisotope. Ambient photon dose rates post radiotherapy treatment ranged 660 µGyh-1at o.5 m to 41 µGyh-1at 1 m. These values agree well with the results presented in the literature. Keywords: Radiotherapy; Activation Products; Gamma spectrometry; Occupational exposure; Medical Linear Accelerator. DOI: 10.7176/ALST/83-05 Publication date: November 30th 2020

The Influence of Titanium Dioxide on Silicate-Based Glasses: An Evaluation of the Mechanical and Radiation Shielding Properties

The mechanical and radiation shielding features were reported for a quaternary Na2 O-CaO-SiO2-TiO2 glass system used in radiation protection. The fundamentals of the Makishima– Mazinize model were applied to evaluate the elastic moduli of the glass samples. The elastic moduli, dissociation energy, and packing density increased as TiO2 increased. The glasses’ dissociation energy increased from 62.82 to 65.33 kJ/cm3, while the packing factor slightly increased between 12.97 and 13.00 as the TiO2 content increased. The MCNP-5 code was used to evaluate the gamma-ray shielding properties. The best linear attenuation coefficient was achieved for glass samples with a TiO2 content of 9 mol%: the coefficient decreased from 5.20 to 0.14 cm−1 as the photon energy increased from 0.015 to 15 MeV. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-Track Research Funding Program