Continuous Intraoperative Nerve Monitoring of a Non-Recurrent Laryngeal Nerve: Real-Life Data of a High-Volume Thyroid Surgery Center.

Thyroid surgery is associated with a risk of injury to the recurrent laryngeal nerve, especially in the presence of anatomical variants such as a non-recurrent laryngeal nerve (NRLN). Injury to the nerve leads to transient or permanent vocal cord palsy (VCP). A novel method to prevent VCP is continuous intraoperative nerve monitoring (cIONM), but less is known about the applicability of this method in patients with NRLN. The aim of this study was to evaluate our own data regarding feasibility and detailed characteristics of cIONM in NRLN patients. We performed a monocentric retrospective cohort analysis including clinical data and intraoperative nerve monitoring data (measured by Inomed Medizintechnik GmbH, Emmendingen, 'C2' and 'C2 Xplore' device) of all thyroid surgery patients, showing NRLN between 2014 and 2022. Of 1406 patients who underwent thyroid surgery with cIONM between 2014 and 2022, 12 patients (0.9%) showed NRLN intraoperatively. Notably, cIONM was feasible in eight patients (67%). In all cases the onset latency of the right vagus nerve was shorter (<3.0 ms) than usually expected, suggesting that a short latency might be suitable to distinguish NRLN. None of the patients had a post-operative VCP. Overall, cIONM appears to be feasible and safe in NRLN patients and provides helpful information to prevent VCP.

Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.

RATIONALE: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. AIM: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. METHODS AND DESIGN: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. SAMPLE SIZE ESTIMATES: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. STUDY OUTCOME: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). DISCUSSION: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.

OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D ß-Lactamase From Escherichia coli.

OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative Enterobacterales worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical E. coli isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The bla OXA - 484 was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring bla OXA - 181. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10-7 to 2.1 × 10-6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as ß-lactamase activity of OXA-232.

Pathogenicity of Clinical OXA-48 Isolates and Impact of the OXA-48 IncL Plasmid on Virulence and Bacterial Fitness.

OXA-48 is the most common carbapenemase in Enterobacterales in Germany and one of the most frequent carbapenemases worldwide. Several reports have associated bla OXA - 48 with a virulent host phenotype. To challenge this hypothesis, 35 OXA-48-producing clinical isolates of Escherichia coli (n = 15) and Klebsiella pneumoniae (n = 20) were studied in vitro, in vivo employing the Galleria mellonella infection model and by whole-genome sequencing. Clinical isolates belonged to 7 different sequence types (STs) in E. coli and 12 different STs in K. pneumoniae. In 26/35 isolates bla OXA- 48 was located on a 63 kb IncL plasmid. Horizontal gene transfer (HGT) to E. coli J53 was high in isolates with the 63 kb IncL plasmid (transconjugation frequency: ∼103/donor) but low in isolates with non-IncL plasmids (<10-6/donor). Several clinical isolates were both highly cytotoxic against human cells and virulent in vivo. However, 63 kb IncL transconjugants generated from these highly virulent isolates were not more cytotoxic or virulent when compared to the recipient strain. Additionally, no genes associated with virulence were detected by in silico analysis of OXA-48 plasmids. The 63 kb plasmid was highly stable and did not impair growth or fitness in E. coli J53. In conclusion, OXA-48 clinical isolates in Germany are diverse but typically harbor the same 63 kb IncL plasmid which has been reported worldwide. We demonstrate that this 63 kb IncL plasmid has a low fitness burden, high plasmid stability and can be transferred by highly efficient HGT which is likely the cause of the rapid dissemination of OXA-48 rather than the expansion of a single clone or gain of virulence.

Attenuation of Severe Generalized Junctional Epidermolysis Bullosa by Systemic Treatment with Gentamicin.

Severe generalized junctional epidermolysis bullosa (JEB), a lethal genodermatosis, is mainly caused by premature termination codons (PTCs) in one of the three genes encoding the anchoring protein laminin-332. Only symptomatic treatment has been established; overcoming PTCs by aminoglycosides may represent an interesting alternative. This retrospective study aimed at assessing for the first time the clinical effects of systemic gentamicin application in infants with severe generalized JEB. Five patients, homozygous or compound-heterozygous for PTCs in the gene LAMB3, were treated with gentamicin which was administered intravenously or by intramuscular injection at doses of 7.5 mg/kg/d for three weeks. Skin biopsies were investigated by immunofluorescence analyses. Clinical effects of the medication were recorded with a parent questionnaire and by assessing weight-for-age charts. Gentamicin application was well tolerated, long hospitalization was not required. Low levels of laminin-332 could be detected in a skin sample obtained after treatment. Gentamicin had a positive impact on skin fragility and daily life in four patients but did not influence weight gain and failed to reverse the lethal course of the disease. Gentamicin injections should be considered regularly in cases of severe generalized JEB caused by PTCs as they may attenuate JEB symptoms without impeding quality of life.

Surgical Treatment of Spinal Ependymomas: Experience in 49 Patients.

BACKGROUND: Ependymomas are rare central nervous system tumors. Local tumor distribution in the central nervous system depends on age: among adults, ependymomas occur mostly in the spinal cord, whereas among children, intracranial manifestations are more common. To date, there are no prospective studies about treatment strategies for ependymomas. In most cases, complete tumor resection is recommended. The role of radiation therapy in low-grade ependymomas is unclear. METHODS: We report the results of 49 patients over an 18-year-period. Patients' clinical and radiologic data were analyzed retrospectively. RESULTS: Mean age of patients at time of surgery was 46.4 years. There were 29 women (59%) and 20 men (41%). Gross total resection was achieved in 72% of patients. Tumors affected cervical spinal cord in 14 patients (29%), cauda equina and filum terminale in 10 (21%), conus medullaris in 8 (16%), thoracic spinal cord in 7 (14%), and cervicolumbar or thoracolumbar junction in 10 (20%). Postoperative radiation therapy was performed in 6 cases. Long-term follow-up was available for 39 patients (mean 50.7 months). High preoperative McCormick grade correlated with high risk for clinical deterioration postoperatively. On long-term follow-up, clinical status was the same as preoperatively in 51% of patients, worse in 21%, and improved in 28%. We found no differences in progression-free survival with regard to histology. Four tumors relapsed after progression-free survival of a mean of 21 months. CONCLUSIONS: Gross total resection is considered the first choice in treatment of spinal ependymomas. The most important predictor of clinical outcome is preoperative neurologic functioning. The role of postoperative radiation needs further clarification.

Ligamentum flavum hematomas of the cervical and thoracic spine.

OBJECTIVE: To report extremely rare cases of ligamentum flavum hematomas in the cervical and thoracic spine. Only six cases of thoracic ligamentum flavum hematomas and three cases of cervical ligamentum flavum hematomas have been reported so far. METHODS: Two patients presented with tetraparesis and one patient presented with radicular pain and paresthesias in the T3 dermatome. MRI was performed in two patients, which showed a posterior intraspinal mass, continuous with the ligamentum flavum. The mass was moderately hypointense on T2-weighted images and hyperintense on T1-weighted images with no contrast enhancement. The third patient underwent cervical myelography because of a cardiac pacemaker. The myelography showed an intraspinal posterior mass with compression of the dural sac at C3/C4. RESULTS: All patients underwent a hemilaminectomy to resect the ligamentum flavum hematoma and recovered completely afterwords, and did not experience a recurrence during follow-up of at least 2 years. CONCLUSION: This case series shows rare cases of ligamentum flavum hematomas in the cervical and thoracic spine. Surgery achieved complete recovery of the preoperative symptoms in all patients within days.

Common and disease-specific dysfunctions of brain systems underlying attentional and executive control in schizophrenia and bipolar disorder.

Schizophrenia and bipolar disorder broadly overlap in multiple areas involving clinical phenomenology, genetics, and neurobiology. Still, the investigation into specific elementary (sub-)processes of executive functioning may help to define clear points of distinction between these categorical diagnoses to validate the nosological dichotomy and, indirectly, to further elucidate their pathophysiological underpinnings. In the present behavioral study, we sought to separate common from diagnosis-specific deficits in a series of specific elementary sub-functions of executive processing in patients with schizophrenia and bipolar disorder. For our purpose, we administered a modern and multi-purpose neuropsychological task paradigm to equal-sized and matched groups of schizophrenia patients, patients with bipolar disorder, and healthy control subjects. First, schizophrenia patients compared to the bipolar group exhibited a more pronounced deficit in general measures of task performance comprising both response speed and accuracy. Additionally, bipolar patients showed increased advance task preparation, i.e., were better able to compensate for response speed deficits when longer preparation intervals were provided. Set-shifting, on the other hand, was impaired to a similar degree in both patient groups. Finally, schizophrenia patients exhibited a specific deficit in conflict processing (inhibitory control) and the shielding of task-relevant processing from distraction (i.e., attentional maintenance). The present investigation suggests that specific neuropsychological measures of elementary executive functions may represent important points of dissociation between schizophrenia and bipolar disorder, which may help to differentiate the pathophysiological underpinnings of these major psychiatric disorders. In this context, the present findings highlight the measures of inhibitory control and attentional maintenance as promising candidates.

Effects of Hydrolysed Whey Proteins on the Techno-Functional Characteristics of Whey Protein-Based Films.

Pure whey protein isolate (WPI)-based cast films are very brittle due to its strong formation of protein cross-linking of disulphide bonding, hydrogen bonding as well as hydrophobic and electrostatic interactions. However, this strong cross-linking is the reason for its final barrier performance. To overcome film brittleness of whey protein layers, plasticisers like glycerol are used. It reduces intermolecular interactions, increases the mobility of polymer chains and thus film flexibility can be achieved. The objective of this study was to investigate the influence of hydrolysed whey protein isolate (WPI) in whey protein isolate-based cast films on their techno-functional properties. Due to the fact, that the addition of glycerol is necessary but at the same time increases the free volume in the film leading to higher oxygen and water vapour permeability, the glycerol concentration was kept constant. Cast films with different ratios of hydrolysed and not hydrolysed WPI were produced. They were characterised in order to determine the influence of the lower molecular weight caused by the addition of hydrolysed WPI on the techno-functional properties. This study showed that increasing hydrolysed WPI concentrations significantly change the mechanical properties while maintaining the oxygen and water vapour permeability. The tensile and elastic film properties decreased significantly by reducing the average molecular weight whereas the yellowish coloration and the surface tension considerably increased. This study provided new data which put researchers and material developers in a position to tailor the characteristics of whey protein based films according to their intended application and further processing.

Resolution of persistent late postoperative chylothorax after coil occlusion of aortopulmonary collaterals.

We report on successful treatment of persistent late postoperative chylothorax with coil occlusion of significant aortopulmonary collaterals in a young infant with functionally univentricular heart after bidirectional cavopulmonary connection.