Sepsis-induced endothelial dysfunction drives acute-on-chronic liver failure through Angiopoietin-2-HGF-C/EBPß pathway.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patients with previously stable cirrhosis. A common cause of ACLF is sepsis secondary to bacterial infection. Sepsis-associated ACLF involves a loss of differentiated liver function in the absence of direct liver injury, and its mechanism is unknown. We aimed to study the mechanism of sepsis-associated ACLF using a novel mouse model. APPROACH AND RESULTS: Sepsis-associated ACLF was induced by cecal ligation and puncture procedure (CLP) in mice treated with thioacetamide (TAA). The combination of TAA and CLP resulted in a significant decrease in liver synthetic function and high mortality. These changes were associated with reduced metabolic gene expression and increased CCAAT enhancer binding protein beta (C/EBPß) transcriptional activity. We found that C/EBPß binding to its target gene promoters was increased. In humans, C/EBPß chromatin binding was similarly increased in the ACLF group compared with control cirrhosis. Hepatocyte-specific Cebpb knockout mice had reduced mortality and increased gene expression of hepatocyte differentiation markers in TAA/CLP mice, suggesting that C/EBPß promotes liver failure in these mice. C/EBPß activation was associated with endothelial dysfunction, characterized by reduced Angiopoietin-1/Angiopoietin-2 ratio and increased endothelial production of HGF. Angiopoietin-1 supplementation or Hgf knockdown reduced hepatocyte C/EBPß accumulation, restored liver function, and reduced mortality, suggesting that endothelial dysfunction induced by sepsis drives ACLF through HGF-C/EBPß pathway. CONCLUSIONS: The transcription factor C/EBPß is activated in both mouse and human ACLF and is a potential therapeutic target to prevent liver failure in patients with sepsis and cirrhosis.

Evaluating the clinical behavior of veneered zirconia in comparison with monolithic zirconia complete arch implant-supported prostheses: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Because the use of zirconia in dentistry is relatively new, the number of published studies on the subject is scarce, even though material selection is an important factor in clinical performance. Therefore, a systematic assessment of the impact of the prosthetic material, framework design, veneering material, and manufacturing process is required. PURPOSE: The purpose of this systematic review and meta-analysis was to investigate the survival and success rates of feldspathic porcelain veneered zirconia (VZir) in comparison with monolithic zirconia (MZir) complete arch implant-supported prostheses (CAISPs). A secondary objective was to assess the influence of the type of loading, the presence or absence of a cantilever, the type of zirconia used, the location, and the opposing arch on complications rates and patient satisfaction. MATERIAL AND METHODS: An electronic search of the MEDLINE database (via PubMed), Scopus, Science Direct, Cochrane Library, and OpenGrey was carried out. The criteria described in the preferred reporting items for systematic reviews and meta-analyses statement were used. The search was restricted from January 2000 to January 2022. RESULTS: The systematic search resulted in 20 articles that met the established criteria. In total, 751 patients (VZir=302; MZir=449) with 3038 CAISPs (VZir=368; MZir=2670) were analyzed. Higher prosthetic survival and success rates were found in MZir compared with VZir CAISPs (100% and 95.45%, respectively). The meta-analysis found significantly fewer complications related to MZir (9.4% [4.8%-14.1%]) compared with VZir (33.7% [17.5%-49.9%]). CONCLUSIONS: Based on the findings of this systematic review, MZir CAISPs had higher survival and success rates than VZir CAISPs, with significantly fewer prosthetic complications. The influence of factors such as the type of functional loading, the presence of a cantilever, the material used in the prosthodontic workflow, the location of the CAISP, and the type of antagonist arch on the performance of Zir CAISPs remains unclear.

Targeted Proteomics for Studying Pathogenic Bacteria.

Mass spectrometry-based proteomics has been extensively used to map bacterial proteomes, which has led to a better understanding of the molecular mechanisms underlying bacterial infection and bacteria-host interactions. Quantitative proteomics using selected or parallel reaction monitoring is considered one of the most sensitive and specific quantitative MS-based approaches and has significantly advanced proteome studies of pathogenic bacteria. Here, recent applications of targeted proteomics for bacteria identification, biomarker discovery, and the characterization of bacterial virulence and antimicrobial resistance are reviewed among others. Results of such studies are expected to further contribute to improve the fight against the most common human pathogenic bacteria.

Awake Neurophysiologically Guided versus Asleep MRI-Guided STN DBS for Parkinson Disease: A Comparison of Outcomes Using Levodopa Equivalents.

BACKGROUND: Deep brain stimulation (DBS) for Parkinson's disease (PD) has traditionally been performed in awake patients. Some patients are unable to tolerate awake surgery or extensive time off their medication to allow for neurophysiological testing during traditional DBS implantation, which has previously limited surgical options for these patients. Recently, asleep image-guided lead placement using intraoperative MRI or CT for verification has been proposed as an alternative for patients unable or unwilling to undergo awake DBS surgery. METHODS: We conducted a retrospective chart review comparing PD patients who underwent asleep MRI-guided subthalamic nucleus (STN) DBS lead placement (n = 14) and awake neurophysiologically guided STN DBS lead placement (n = 23) at our institution. Both groups' levodopa equivalent daily doses (LEDDs) and complications at approximately 6 months of follow-up were compared, along with operative times. RESULTS: Both groups showed statistically similar reductions in LEDD at 6 months of therapy (38.27% for awake, 49.27% for asleep; p = 0.4447), and similar complications. Operative times were initially longer for MRI-guided DBS but improved with surgical experience. CONCLUSION: Asleep MRI-guided DBS is a viable option for PD patients unable or unwilling to undergo awake placement, with similar results in terms of LEDD reduction and complications.

Vertebral and Basilar Artery Dissection in a Patient With Alport Syndrome.

Basilar artery occlusion (BAO) is a rare cause of stroke associated with significant morbidity and mortality. It is most frequently thromboembolic in nature, but may be caused by vertebral artery dissection. We present a case of BAO in a 36-year-old woman with Alport syndrome. She was treated with emergent thrombectomy via the right vertebral artery with return to baseline neurological status. Her clinical status deteriorated later the same day and she was found to have re-occlusion. Repeat thrombectomy was complicated by persistent re-occlusion requiring 7 passes to achieve reperfusion. Unfortunately, her neurological exam remained poor and she was transitioned to comfort care, expiring on admission day 3. An autopsy demonstrated acute dissection of the left vertebral artery, basilar artery, and bilateral posterior cerebral arteries. Alport syndrome is a type IV collagenopathy most known for causing kidney disease. It may also be associated with vascular fragility as type IV collagen forms a significant component of the vascular basement membrane. There are reports of aortic, coronary, and cervical dissections, but few reports of intracranial dissections in patients with Alport syndrome. While iatrogenic dissection cannot be ruled out, the histological findings in this case are most consistent with spontaneous arterial dissection as the cause of her initial neurologic presentation. This highlights the need for further investigation into the relationship between Alport syndrome and vascular fragility and should alert clinicians to the possibility of intracranial dissection in patients with AS.

Elizabeth Crosby: Titan of Neuroanatomy and Friend of Neurosurgery.

Elizabeth Crosby (1888-1983) is a beloved and well-respected titan of neuroanatomy. Her contributions to our understanding of neuroanatomy are rooted in her seminal text, The Comparative Anatomy of the Nervous System of Vertebrates, Including Man, published in 1936, which is a masterful and comprehensive account of comparative neuroanatomy. Her later texts, Correlative Neurosurgery and Correlative Anatomy of the Nervous System, are standard reference texts to this day. Her mentorship of graduate students, close work with the University of Michigan neurosurgery department, and the quality of her research and scientific publications were recognized with many awards, culminating in the National Medal of Science presented by President Carter in 1980.

Conservative management of intraventricular migration of a gelatin sponge: illustrative case.

BACKGROUND: Gelatin sponges, such as Gelfoam, are used as hemostatic agents during surgery and are generally absorbed over the course of 4-6 weeks in most body cavities. The time course of the dissolution of Gelfoam sponges within the cerebral ventricles has not been described. OBSERVATIONS: The authors present a case of intraventricular migration of Gelfoam after ventriculoperitoneal shunt placement in a 6-week-old infant. The infant was imaged regularly after ventriculoperitoneal shunt placement, and the Gelfoam sponge persisted within the ventricles on all images until 11 months after surgery. At no time during follow-up did the patient have any symptoms of hydrocephalus requiring retrieval of the sponge or shunt revision. LESSONS: This is the first case describing time until absorption of a gelatin sponge within the ventricle and successful conservative management.

Subdural hematoma prevalence and long-term developmental outcomes in patients with benign expansion of the subarachnoid spaces.

OBJECTIVE: Benign expansion of the subarachnoid spaces (BESS) is a condition seen in macrocephalic infants. BESS is associated with mild developmental delays which tend to resolve within a few years. It is accepted that patients with BESS are at increased risk of spontaneous subdural hematomas (SDHs), although the exact pathophysiology is not well understood. The prevalence of spontaneous SDH in BESS patients is poorly defined, with only a few large single-center series published. In this study the authors aimed to better define BESS prevalence and developmental outcomes through the longitudinal review of a large cohort of BESS patients. METHODS: A large retrospective review was performed at a single institution from 1995 to 2020 for patients 2 years of age or younger with a diagnosis of BESS by neurology or neurosurgery and head circumference > 85th percentile. Demographic data, head circumference, presence of developmental delay, occurrence of SDH, and need for surgery were extracted from patient charts. The subarachnoid space (SAS) size was measured from the available MR images, and the sizes of those who did and did not develop SDH were compared. RESULTS: Free text search revealed BESS mentioned within the medical records of 1410 of 2.6 million patients. After exclusion criteria, 480 patients remained eligible for the study. Thirty-two percent (n = 154) of patients were diagnosed with developmental delay, most commonly gross motor delay (53%). Gross motor delay resolved in 86% of patients at a mean age of 22.2 months. The prevalence of spontaneous SDH in this BESS population over a period of 25 years was 8.1%. There was no significant association between SAS size and SDH formation. CONCLUSIONS: This study represents results for one of the largest cohorts of patients with BESS at a single institution. Gross motor delay was the most common developmental delay diagnosed, and a majority of patients had resolution of their delay. These data support that children with BESS have a higher prevalence of SDH than the general pediatric population, although SAS size was not significantly associated with SDH development.

Skull Base Registries: A Roadmap.

Hospitals, payors, and patients increasingly expect us to report our outcomes in more detail and to justify our treatment decisions and costs. Although there are many stakeholders in surgical outcomes, physicians must take the lead role in defining how outcomes are assessed. Skull base lesions interact with surrounding anatomy to produce a complex spectrum of presentations and surgical challenges, requiring a wide variety of surgical approaches. Moreover, many skull base lesions are relatively rare. These factors and others often preclude the use of prospective randomized clinical trials, thus necessitating alternate methods of scientific inquiry. In this paper, we propose a roadmap for implementing a skull base registry, along with expected benefits and challenges.

Erratum: Skull Base Registries: A Roadmap.

[This corrects the article DOI: 10.1055/a-1934-9191.].

Retrospective Review of Surgical Site Infections after Endoscopic Endonasal Sellar and Parasellar Surgery: Multicenter Quality Data from the North American Skull Base Society.

Introduction Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes. Methods We conducted a multicenter retrospective analysis of shared quality data points for the endoscopic endonasal approach (EEA) for pituitary adenomas, along with other sellar and parasellar region masses that were included by participating institutions. Patient and operative characteristics, perioperative and postoperative antibiotic regimens and their durations, intraoperative and postoperative cerebrospinal fluid leak, and onset of postoperative meningitis and sinusitis were compared. Results Fifteen institutions participated and provided 6 consecutive months' worth of case data. Five hundred ninety-three cases were included in the study, of which 564 were pituitary adenomectomies. The incidences of postoperative meningitis and sinusitis were low (0.67 and 2.87% for all pathologies, respectively; 0.35% meningitis for pituitary adenomas) and did not correlate with any specific antibiotic regimen. Immunocompromised status posed an increased odds of meningitis in pituitary adenomectomies (28.6, 95% confidence interval [1.72-474.4]). Conclusions The results show no clear benefit to postoperative antimicrobial use in EEA, with further larger studies needed.

Analysis of the effect of intraoperative neuromonitoring during resection of benign nerve sheath tumors on gross-total resection and neurological complications.

OBJECTIVE: The aim of this study was to examine the role of intraoperative neuromonitoring (IONM) during resection of benign peripheral nerve sheath tumors in achieving gross-total resection (GTR) and in reducing postoperative neurological complications. METHODS: Data from consecutive adult patients who underwent resection of a benign peripheral nerve sheath tumor at 7 participating institutions were combined. Propensity score matching was used to balance covariates. The primary outcomes of interest were the association between IONM and GTR and the association of IONM and the development of a permanent postoperative neurological complication. The secondary outcomes of interest were the association between IONM and GTR and the association between IONM and the development of a permanent postoperative neurological complication in the subgroup of patients with tumors involving a motor or mixed nerve. Univariate and multivariate logistic regression were then performed on the propensity score-matched samples to assess the ability of the independent variables to predict the outcomes of interest. RESULTS: A total of 337 patients who underwent resection of benign nerve sheath tumors were included. In multivariate analysis, the use of IONM (OR 0.460, 95% CI 0.199-0.978; p = 0.047) was a significant negative predictor of GTR, whereas none of the variables, including IONM, were associated with the occurrence of a permanent postoperative neurological complication. Within the subgroup of motor/mixed nerve tumors, in the multivariate analysis, IONM (OR 0.263, 95% CI 0.096-0.723; p = 0.010) was a significant negative predictor of a GTR, whereas IONM (OR 3.800, 95% CI 1.925-7.502; p < 0.001) was a significant positive predictor of a permanent postoperative motor deficit. CONCLUSIONS: Overall, 12% of the cohort had a permanent neurological complication, with new or worsened paresthesias most common, followed by pain and then weakness. The authors found that formal IONM was associated with a reduced likelihood of GTR and had no association with neurological complications. The authors believe that these data argue against IONM being considered standard of care but do not believe that these data should be used to universally argue against IONM during resection of benign nerve sheath tumors.

High day-to-day repeatability of lower extremity muscle activation patterns and joint biomechanics of dual-belt treadmill gait: A reliability study in healthy young adults.

PURPOSE: The reliability of lower extremity muscle activation patterns has not been clearly studied in a dual-belt instrumented treadmill environment. The primary study objective was to quantify the day-to-day reliability of quadriceps, hamstrings, gastrocnemius and gluteus medius activation patterns in healthy young adult gait. Secondarily, the reliability of spatiotemporal, and knee/hip motion and moment-based gait outcomes was assessed. SCOPE: 20 young adults were recruited and tested on two separate days. Using standardized procedures, participants were prepared for surface electromyography and lower extremity motion capture. All individuals walked on a dual-belt instrumented treadmill while muscle activation, segment motions and ground reaction forces were recorded. Sagittal plane motion and net external sagittal and frontal plane moments were calculated. Discrete biomechanical and muscle activation measures were calculated, and non-negative matrix factorization extracted amplitude and temporal muscle activation features. Intraclass Correlation Coefficients, Standard Error of Measurement and Minimum Detectable Change were calculated. CONCLUSIONS: High to excellent Intraclass correlation coefficients were found between visits for most primary and secondary outcomes. The absolute and relative reliability, including Minimum Detectable Change values, provided in this study support the use of dual-belt instrumented treadmill walking as an acceptable medium to collect biomechanical and lower extremity EMG outcomes for future studies.

Salmonella Typhi, Paratyphi A, Enteritidis and Typhimurium core proteomes reveal differentially expressed proteins linked to the cell surface and pathogenicity.

BACKGROUND: Salmonella enterica subsp. enterica contains more than 2,600 serovars of which four are of major medical relevance for humans. While the typhoidal serovars (Typhi and Paratyphi A) are human-restricted and cause enteric fever, non-typhoidal Salmonella serovars (Typhimurium and Enteritidis) have a broad host range and predominantly cause gastroenteritis. METHODOLOGY/PRINCIPLE FINDINGS: We compared the core proteomes of Salmonella Typhi, Paratyphi A, Typhimurium and Enteritidis using contemporary proteomics. For each serovar, five clinical isolates (covering different geographical origins) and one reference strain were grown in vitro to the exponential phase. Levels of orthologous proteins quantified in all four serovars and within the typhoidal and non-typhoidal groups were compared and subjected to gene ontology term enrichment and inferred regulatory interactions. Differential expression of the core proteomes of the typhoidal serovars appears mainly related to cell surface components and, for the non-typhoidal serovars, to pathogenicity. CONCLUSIONS/SIGNIFICANCE: Our comparative proteome analysis indicated differences in the expression of surface proteins between Salmonella Typhi and Paratyphi A, and in pathogenesis-related proteins between Salmonella Typhimurium and Enteritidis. Our findings may guide future development of novel diagnostics and vaccines, as well as understanding of disease progression.

Efficacy of Resin Infiltrate in Noncavitated Proximal Carious Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVES: Resin infiltration is a minimally invasive technique for treating noncavitated proximal caries. It slows/stops the carious lesion progression rate by creating a diffusion barrier inside the porous enamel lesion body. The aim was to evaluate the efficacy of resin infiltration on noncavitated proximal carious lesions in primary and permanent teeth. MATERIALS AND METHODS: The records were obtained using electronic and other sources. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to ensure transparent reporting. Eligible studies were randomized controlled trials evaluating the efficacy of resin infiltration for noncavitated proximal carious lesions by comparing it with control/placebo. Each included study was assessed concerning the "risk of bias" using the Cochrane Collaboration's "risk-of-bias" assessment tool. High risk-of-bias studies were excluded from the meta-analyses due to selective reporting matters. The statistics were performed by RevMan software (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) utilizing the random effect model. The GRADE approach was implemented for assessing the quality of evidence. RESULTS: From 106 studies identified, 17 were assessed for eligibility. After "risk-of-bias" assessment, two meta-analyses were conducted to eliminate the limitation of the significant heterogeneity between trials inspecting primary teeth (n = 2) and permanent teeth (n = 3). I 2 = 0% indicates the absence of statistical heterogeneity. The risk of carious lesions' progression with resin infiltration was significantly lower in primary (risk ratio [RR]; 95% confidence interval [CI]: 0.48; 0.30-0.75, P = 0.001) and in permanent teeth (RR; 95% CI: 0.19; 0.11-0.33, P < 0.00001) compared to that of control/placebo. The GRADE approach revealed high quality of evidence. CONCLUSION: The available evidence conveys high confidence that proximal resin infiltration has superior efficacy in slowing/arresting the carious lesions' progression rate in comparison to conventional management modalities.

Successful surgical repair and recovery in a 2-week-old infant after birth-related cervical fracture dislocation.

Cervical spine injuries are the most common spine injuries in the pediatric population. The authors present the youngest known patient who underwent cervical spine fusion to repair birth trauma-induced cervical fracture dislocation, resulting in spondyloptosis and spinal cord injury. A 2-week-old boy was found to have spondyloptosis and spinal cord injury after concerns arose from reduced movement of the extremities. The patient's birth was complicated by undiagnosed abdominal dystocia, which led to cervical distraction injury. At 15 days of age, the boy underwent successful C-5 corpectomy, with anterior C4-6 and posterior C2-7 arthrodesis, using an autologous rib graft for a C-5 fracture dislocation. MRI performed 2 weeks postoperatively revealed significant improvement in the alignment of the spinal canal. The patient was discharged from the hospital in a custom Minerva brace and underwent close follow-up in addition to occupational therapy and physical therapy. At the latest follow-up 4.5 years later, the patient was able to walk and ride a tricycle by himself. The authors describe the patient's surgery and the challenges faced in achieving successful repair and cervical spine stabilization in such a young patient. The authors suggest that significant neurological recovery after spinal cord injury in infants is possible with appropriate, timely, and interdisciplinary management.

Overdrainage-related ependymal bands: a postulated cause of proximal shunt obstruction.

OBJECTIVEVentricular shunts have an unacceptably high failure rate, which approaches 50% of patients at 2 years. Most shunt failures are related to ventricular catheter obstruction. The literature suggests that obstructions are caused by in-growth of choroid plexus and/or reactive cellular aggregation. The authors report endoscopic evidence of overdrainage-related ventricular tissue protrusions ("ependymal bands") that cause partial or complete obstruction of the ventricular catheter.METHODSA retrospective review was completed on patients undergoing shunt revision surgery between 2008 and 2015, identifying all cases in which the senior author reported endoscopic evidence of ependymal tissue in-growth into ventricular catheters. Detailed clinical, radiological, and surgical findings are described.RESULTSFifty patients underwent 83 endoscopic shunt revision procedures that revealed in-growth of ventricular wall tissue into the catheter tip orifices (ependymal bands), producing partial, complete, or intermittent shunt obstructions. Endoscopic ventricular explorations revealed ependymal bands at various stages of development, which appear to form secondarily to siphoning. Ependymal bands are associated with small ventricles when the shunt is functional, but may dilate at the time of obstruction.CONCLUSIONSVentricular wall protrusions are a significant cause of proximal shunt obstruction, and they appear to be caused by siphoning of surrounding tissue into the ventricular catheter orifices.