Neurotrauma admissions and COVID-19: a National Centre experience.

BACKGROUND: To investigate the impact of COVID-19 on trauma admissions to a National Neurosurgical Centre in Ireland. METHODS: Retrospective analysis of a prospectively maintained database of all trauma admissions to the National Neurosurgical Centre at Beaumont Hospital, Dublin, during the period March 1 to May 31, 2019 and 2020. Primary outcome was 30-day mortality rate. Secondary outcomes included time transfer time, time from admission to time of surgery, and intensive care unit (ICU) admissions. Patients under the age of 16 were excluded. RESULTS: A total of 32 and 39 patients were admitted to the National Neurosurgical Centre following trauma over the 3-month period in 2020 and 2019 respectively, giving a 17.9% reduction in admissions. The 30-day mortality rate increased from 7.7% in 2019 to 15.6% on 2020 (p = 0.45). Mean transfer time was 4 h 58 min in 2019 and 3 h 55 min in 2020 (0.22). Mean time from admission to time of surgery was 9 h 10 min in 2019 and 5 h 37 min in 2020 respectively (p = 0.35). In 2019, 20 patients (51.3%) were admitted to ICU. This increased to 23 patients (69.7%) in 2020 (p = 0.08). CONCLUSIONS: Traumatic brain injury 30-day mortality rates increased during the first COVID-19 lockdown period. Trauma admission rates to ICU remained unchanged despite an overall reduction in trauma admissions. Transfer time, time to surgery, and length of stay were impacted by COVID-19. Despite the challenges COVID-19 has posed, it is important to maintain a fully functioning neurosurgical and neurocritical care service during the pandemic.

Acute respiratory distress syndrome in a case of diabetic ketoacidosis requiring ECMO support.

SUMMARY: Acute respiratory distress syndrome (ARDS) is a rare but life-threatening complication of diabetic ketoacidosis (DKA). We present the case of a young female, with no previous diagnosis of diabetes, presenting in DKA complicated by ARDS requiring extra corporeal membrane oxygenation (ECMO) ventilator support. This case report highlights the importance of early recognition of respiratory complications of severe DKA and their appropriate management. LEARNING POINTS: ARDS is a very rare but life-threatening complication in DKA. The incidence of ARDS remains unknown but less frequent than cerebral oedema in DKA. The mechanism of ARDS in DKA has multifactorial aetiology, including genetic predisposition. Early recognition and consideration of rare pulmonary complication of DKA can increase survival rate and provide very satisfactory outcomes. DKA patients who present with refractory ARDS can be successfully rescued by ECMO support.

Transgastric Drainage for Esophageal Injuries: A Dynamic Strategy for a Heterogenous Patient Cohort.

BACKGROUND: Esophageal injury is a rare but potentially lethal surgical emergency. It is associated with significant morbidity and mortality because of mediastinal contamination and difficulty of access. Surgery in such septic patients exacts a heavy physiological price, mandating consideration of more conservative measures. We review our experience with transgastric drainage for esophageal perforation and high-risk anastomotic dehiscence. PATIENTS AND METHODS: A select cohort of patients presenting with esophageal perforation, or complex anastomotic leaks, over 10 years were considered for transgastric drainage (TGD). A modified 36F chest drainage tube was inserted by percutaneous endoscopic gastrostomy technique, either endoscopically or at open surgery, and a negative pressure (-10 cmH2O) was applied until the leak had sealed. Endpoints include, length of stay, restoration of gastrointestinal tract continuity and mortality. RESULTS: Of 14 patients treated, 10 had perforations and 4 had complex anastomotic leaks. Ten patients had drainage alone, while 4 required concomitant operative intervention. The median duration of drain insertion for those treated with TGD alone was 19.5 days. Complete restoration of gastrointestinal tract continuity was achieved in all patients. There was no procedure-related morbidity or mortality. CONCLUSION: These results show that TGD is a safe and effective management strategy. We advocate its use alone or as an adjunct to operative treatment for esophageal perforation or anastomotic leaks. This is the first report of completely endoscopic TGD for esophageal perforation.

The impact of COVID-19 on trauma referrals to a National Neurosurgical Centre.

BACKGROUND: To investigate the impact of COVID-19 on trauma referrals to a National Neurosurgical Centre during the first wave of COVID-19 in Ireland. METHODS: Retrospective analysis of a prospectively maintained database of all trauma referrals to the National Neurosurgical Centre at Beaumont Hospital, Dublin, during the period March 1-May 31, 2019 and 2020. Patient characteristics including age, sex, alcohol use, anticoagulant/antiplatelet use and initial Glasgow Coma Scale (GCS) were recorded. Patients were grouped based on trauma aetiology and diagnosis. RESULTS: There were 527 and 437 trauma referrals in 2019 and 2020 respectively. Overall, there was a 17.1% reduction in trauma referrals between 2019 and 2020. Traumatic brain injury, spinal injury and cranial fractures referrals reduced 25% (375 vs 283), 59% (32 vs 13) and 18% (39 vs 32) respectively from 2019 to 2020. Low-energy falls below 2 m was the most common mechanism of injury and accounted for 60 and 61% of referrals in 2019 and 2020. No reduction in road traffic collision (33 vs 34) and assault (40 vs 40) referrals were observed between years. CONCLUSIONS: COVID-19 has had a significant impact on both the volume and mechanism of trauma referrals to the National Neurosurgical Centre in Ireland, with falls below 2 m the most common mechanism of trauma referral across both years. The workload remains substantial and a fully resourced neurosurgical department is essential in any future COVID-19 waves.

The provision of neuro-oncology and glioma neurosurgery during the SARS-CoV-2 pandemic: a single national tertiary centre experience.

BACKGROUND: The COVID-19 pandemic has resulted in a significant disruption in the provision of healthcare globally. The aim of this study was to assess the implications of the COVID-19 pandemic on the provision of neuro-oncology surgery and comparison with a similar 3-month period in 2019. METHODS: Retrospective review of prospectively curated database of patients requiring neuro-oncology surgery at our tertiary referral centre between 1st March 2020 and 31st May 2020. We also analysed data for the same time period (1st March-31st May) in 2019 for comparison. Number and type of tumours operated on, postoperative morbidity and mortality, COVID-19-related complications and delays in treatment were recorded. RESULTS: During the 3-month periods studied in 2020 and 2019, there were 127 and 139 admissions for neuro-oncological surgery, respectively. Sixty patients underwent surgery for gliomas during the 2020 period vs 56 in the 2019 period. We observed no increase in mean length of time from referral to inter-hospital transfer (mean of 76 h in 2020 vs 93 h in 2019 (p = 0.10)) or in mean length of time from admission to surgery in the acute admissions (2.39 days in 2020 vs 2.89 days in 2019). The postoperative 30-day morbidity and mortality rates were lower in 2020; 8.7% (n = 11) compared with 10.1% (n = 14) in 2019. There was one COVID-19-related death which occurred in a patient with B cell lymphoma with negative preoperative COVID-19 test. CONCLUSION: The provision of neuro-oncological surgery can be safely continued during respiratory illness epidemic or pandemic if a rigorous testing and staffing framework is implemented.

Aminoethylglycine-functionalized Ru(bpy)3(2+) with pendant bipyridines self-assemble multimetallic complexes by copper and zinc coordination.

Directed self-assembly using inorganic coordination chemistry is an attractive approach for making functional supramolecular structures. In this article, the synthesis and characterization of Ru(bpy) 3 (2+) compounds derivatized with aminoethylglycine (aeg) substituents containing pendant bipyridine (bpy) ligands is presented. The free bpy ligands in these complexes are available for metal chelation to form coordinative cross-links; addition of Cu (2+) or Zn (2+) assembles heterometallic structures containing two or three transition-metal complexes. Control over relative placement of metal complexes is accomplished using two strategies: two bipyridine-containing aeg strands tethered to Ru(bpy) 3 (2+) allow intramolecular coordination and result in a dimetallic hairpin motif. Ru(bpy) 3 (2+) modified with a single strand forms intermolecular cross-links forming the trimetallic complex. Each of these is characterized by a range of methods, and their photophysical properties are compared. These data, and comparison to an acetyl aeg- modified Ru(bpy) 3 (2+) complex, confirm that the metal ions cross-link bpy-containing aeg strands. Heterometallic complexes containing bound Cu (2+) cause a dramatic reduction in the Ru(bpy) 3 (2+) quantum yields and lifetimes. In contrast, the Ru(bpy) 3 (2+) hairpin with coordinated Zn (2+) has only a slight decrease in quantum yield but no change in lifetime, which could be a result of steric impacts on structure in the dimetallic species. Analogous effects are not observed in the trimetallic Ru-Zn-Ru structures in which this constraint is absent. Each of these heterometallic structures represents a facile and reconfigurable means to construct multimetallic structures by metal-coordination-based self-assembly of modular artificial peptide units.

Expression profiling of the Leishmania life cycle: cDNA arrays identify developmentally regulated genes present but not annotated in the genome.

As genomic sequencing of Leishmania nears completion, functional analyses that provide a global genetic perspective on biological processes are important. Despite polycistronic transcription, RNA transcript abundance can be measured using microarrays. To provide a resource to evaluate cDNA arrays, we undertook 5' expressed sequence tag analysis of 2183 full-length randomly selected cDNAs from Leishmania major promastigote (days 3, 7, 10 of culture in vitro), and lesion-derived amastigote libraries. PCR-amplified inserts from 1830 of these cDNA representing 1001 unique genes were spotted onto microarrays, and compared internally with PCR-amplified open reading frames (ORFs) from 904 genes representing 842 unique genes annotated in the L. major genome. Microarrays were screened with RNA from procyclic, metacyclic and amastigote populations of L. major. Redundant clones on the array gave highly reproducible results, providing confidence in identification of stage-specific gene expression. Four hundred and thirty unique (i.e. non-redundant) stage-specific genes were identified. A higher percentage of stage-specific gene expression was observed in amastigotes ( approximately 35%) compared to metacyclics ( approximately 12%) for both cDNAs and ORFs, but cDNAs provided a richer source of regulated genes than currently annotated ORFs from the Leishmania genome. In mapping cDNAs onto the Leishmania genome, we noted that approximately 42% aligned to regions not recognised as genes using current predictive annotation tools. These genes are highly represented in our stage-specific genes, and therefore represent important drug targets and vaccine candidates. Careful annotation of cDNAs onto the Leishmania genome will be important before producing the next generation of oligonucleotide arrays based on annotated genes of the genomic sequencing project.

Comparative analysis of two slc11 (Nramp) loci in Takifugu rubripes.

To study the evolution of the solute carrier family 11 (slc11; formerly Nramp) protein, we isolated and characterized two paralogs from the pufferfish Takifugu rubripes (Fugu). These teleost genes, designated Fugu slc11a-a and Fugu slc11a-b, comprise open reading frames of 1743 nucleotides (581 amino acids) and 1662 nt (554 aa), respectively. The proteins are 81% similar, and both exhibit signature features of the slc11 family of proteins including 12 transmembrane domains, a conserved transport motif and a glycosylated loop. Both Fugu paralogs are more Slc11a2-like based on sequence homology and phylogenetic studies. Analysis of gene environment placed both in the proximity of multiple loci syntenic to human chromosome 12q13, that is, within a SLC11A2 gene environment. However, Fugu slc11a-a also gave one match with chromosome 2q35, where human SLC11A1 resides. Functional diversification was suggested by differences in tissue distribution and subcellular localization. Fugu slc11a-a exhibits a restricted expression profile and a complex subcellular localization, including LAMP1 positive late endosomes/lysosomes in transiently transfected mouse macrophages. Fugu slc11a-b is expressed ubiquitously and localizes solely to late endosomes/lysosomes. This comparative analysis extends our understanding of the evolution and function of this important family of divalent cation transporters. [Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AJ496547/8/9 and AJ496550.]

From genome to vaccines for leishmaniasis: screening 100 novel vaccine candidates against murine Leishmania major infection.

The genomic sequence of Leishmania major provides a rich source of vaccine candidates. One hundred randomly selected amastigote-expressed genes were screened as DNA vaccines, and efficacy determined following high-dose L. major footpad challenge in BALB/c mice. Fourteen protective novel vaccine candidates were identified; seven vaccines exacerbated disease. There were no differences in the number of predicted MHC H-2d class I or II epitopes mapping to protective versus exacerbatory antigens. A proportion of both protective (7/14; 50%) and exacerbatory (4/7; 57%) proteins showed short (8- to 18-mer) 100% amino acid sequence identities to human, mouse or gut flora proteins. A high proportion of these (4/7 protective; 3/4 exacerbatory) showed full or partial overlap with RANKPEP-predicted H-2d classes I and II epitopes. Our data suggest, therefore, that there may be little difference between antigens/epitopes that drive regulatory versus effector CD4 T cell populations. The best novel protective antigen was an amastin-like gene that maps to a 17-gene tandem array on Leishmania chromosome 8 and is closely related to 37 other amastin-like genes. Two ribosomal proteins, a V-ATPase subunit, and a dynein light chain orthologue were the only other protective genes with putative functions.

Pyridine-substituted oligopeptides as scaffolds for the assembly of multimetallic complexes: variation of chain length.

This paper presents the synthesis and characterization of pyridine-substituted artificial oligopeptides with an aminoethylglycine backbone of varying length, which are designed to act as scaffolds for the self-assembly of multimetallic structures. The identities and purities of the oligopeptides are confirmed with mass spectrometry, (1)H NMR, HPLC, and pH titrations. The acid dissociation constants for the oligopeptides were determined and were found to decrease with increasing pyridine units. Titrations of the oligopeptides with Cu(II) and Pt(II) complexes containing the tridentate ligands 2,2':6',2''-terpyridine and pyridine 2,6-dicarboxylic acid were monitored using UV-visible absorption spectroscopy and showed stoichiometric binding based on the number of pyridines on the peptide strand. Metal titrations performed using an analogous oligopeptide with methyl substituents (in place of the pyridine ligands) showed very weak or no binding. In the case of the oligopeptides containing bound Pt(terpyridine)(2+) complexes, cyclic voltammetry reveals two sequential one-electron reductions at formal potentials that do not vary as a function of oligopeptide length. The measured diffusion coefficients were measured with chronoamperometry and were found to decrease with increasing oliopeptide length.

Artificial oligopeptide scaffolds for stoichiometric metal binding.

Two artificial peptides with pendant pyridine or bipyridine ligands have been synthesized and incorporated into oligomeric strands that are analogous to peptide nucleic acid. Spectrophotometric titrations with Cu(2+) and Fe(2+) show that the oligomers bind stoichiometric quantities of transition metals based on the number of pendant ligands. The identities of the titration products are confirmed by high resolution mass spectrometry. In the case of the bipyridine tripeptides, the titration stoichiometry and mass spectra indicate that the metal ions form interstrand cross-links between two oligopeptides, creating duplex structures linked exclusively by metal ions. Calculated molecular structures of the metalated oligopeptides and duplexes indicate that the peptide backbone acts as a scaffold for the directed assembly of metal ions. Electron paramagnetic resonance spectroscopy of the Cu-containing molecules have varying degrees of electronic interaction based on their charge and supramolecular structure. Cyclic voltammetry of the Fe(2+)- and Cu(2+)-linked bpy oligopeptide duplexes shows that they possess unique electrochemical signatures based on the redox reactivity of the metal complex.