Regulation of Diseases-Associated Microglia in the Optic Nerve by Lipoxin B4 and Ocular Hypertension.

Background: The resident astrocyte-retinal ganglion cell (RGC) lipoxin circuit is impaired during retinal stress, which includes ocular hypertension-induced neuropathy. Lipoxin B4 produced by homeostatic astrocytes directly acts on RGCs to increase survival and function in ocular hypertension-induced neuropathy. RGC death in the retina and axonal degeneration in the optic nerve are driven by the complex interactions between microglia and macroglia. Whether LXB4 neuroprotective actions include regulation of other cell types in the retina and/or optic nerve is an important knowledge gap. Methods: Cellular targets and signaling of LXB4 in the retina were defined by single-cell RNA sequencing. Retinal neurodegeneration was induced by injecting silicone oil into the anterior chamber of the mouse eyes, which induced sustained and stable ocular hypertension. Morphological characterization of microglia populations in the retina and optic nerve was established by MorphOMICs and pseudotime trajectory analyses. The pathways and mechanisms of action of LXB4 in the optic nerve were investigated using bulk RNA sequencing. Transcriptomics data was validated by qPCR and immunohistochemistry. Differences between experimental groups was assessed by Student's t-test and one-way ANOVA. Results: Single-cell transcriptomics identified microglia as a primary target for LXB4 in the healthy retina. LXB4 downregulated genes that drive microglia environmental sensing and reactivity responses. Analysis of microglial function revealed that ocular hypertension induced distinct, temporally defined, and dynamic phenotypes in the retina and, unexpectedly, in the distal myelinated optic nerve. Microglial expression of CD74, a marker of disease-associated microglia in the brain, was only induced in a unique population of optic nerve microglia, but not in the retina. Genetic deletion of lipoxin formation correlated with the presence of a CD74 optic nerve microglia population in normotensive eyes, while LXB4 treatment during ocular hypertension shifted optic nerve microglia toward a homeostatic morphology and non-reactive state and downregulated the expression of CD74. Furthermore, we identified a correlation between CD74 and phospho-phosphoinositide 3-kinases (p-PI3K) expression levels in the optic nerve, which was reduced by LXB4 treatment. Conclusion: We identified early and dynamic changes in the microglia functional phenotype, reactivity, and induction of a unique CD74 microglia population in the distal optic nerve as key features of ocular hypertension-induced neurodegeneration. Our findings establish microglia regulation as a novel LXB4 target in the retina and optic nerve. LXB4 maintenance of a homeostatic optic nerve microglia phenotype and inhibition of a disease-associated phenotype are potential neuroprotective mechanisms for the resident LXB4 pathway.

Effectiveness of hospital-based strategies for improving childhood immunization coverage: A systematic review.

BACKGROUND: Hospital settings represent an opportunity to offer and/or promote childhood vaccination. The purpose of the systematic review was to assess the effectiveness of different hospital-based strategies for improving childhood vaccination coverage. METHODS: A systematic search of multiple bibliographic databases, thesis databases, and relevant websites was conducted to identify peer-reviewed articles published up to September 20, 2021. Articles were included if they evaluated the impact of a hospital (inpatient or emergency department)-based intervention on childhood vaccination coverage, were published in English or French, and were conducted in high-income countries. High quality studies were included in a narrative synthesis. RESULTS: We included 25 high quality studies out of 7,845 unique citations. Studies focused on routine, outbreak, and influenza vaccines, and interventions included opportunistic vaccination (i.e. vaccination during hospital visit) (n = 7), patient education (n = 2), community connection (n = 2), patient reminders (n = 2), and opportunistic vaccination combined with patient education and/or reminders (n = 12). Opportunistic vaccination interventions were generally successful at improving vaccine coverage, though results ranged from no impact to vaccinating 71 % of eligible children with routine vaccines and 9-61 % of eligible children with influenza vaccines. Interventions that aimed to increase vaccination after hospital discharge (community connection, patient education, reminders) were less successful. CONCLUSIONS: Some interventions that provide vaccination to children accessing hospitals improved vaccine coverage; however, the baseline coverage level of the population, as well as implementation strategies used impact success. There is limited evidence that interventions promoting vaccination after hospital discharge are more successful if they are tailored to the individual.

Carotid-Axillary Bypass and Debridement for a Mycotic Aneurysm of the Left Subclavian Artery.

Mycotic subclavian aneurysms are rare, and their presence typically mandates urgent repair due to the associated high risk of rupture and mortality. A multi-disciplinary team effort is of utmost importance in ensuring favorable results. In this case report, we present a 79-year-old male with a rapidly enlarging mycotic left subclavian artery aneurysm secondary to a retrosternal abscess and left sternoclavicular septic arthritis, who underwent aneurysmal exclusion, a left carotid-left axillary bypass and pectoralis muscle flap coverage with a good outcome.

Impact of thoracic endovascular aortic repair timing on aortic remodeling in acute type B aortic intramural hematoma.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is increasingly utilized in the management of acute type B aortic intramural hematoma (TBIMH). Optimal timing for intervention has not been described. The aim of this study was to evaluate TEVAR timing on postoperative aortic remodeling. METHODS: A retrospective chart review was performed on patients who underwent TEVAR for TBIMH from January 2008 to September 2018. Imaging was reviewed pre- and postoperatively. Primary data points included true lumen diameter (TLD) and total aortic diameter (TAD) at the site of maximal pathology. Primary endpoint was aortic remodeling evidenced by a TAD/TLD ratio closest to 1.0. Secondary outcome was occurrence of aortic-related adverse events and mortality (AREM): aortic rupture, aortic-related death, progression to dissection, or need for aortic reintervention within 12 months. Patients undergoing emergent TEVAR (within 24 hours, 'eTEVAR') were compared with the remainder - delayed TEVAR ('dTEVAR'). RESULTS: We analyzed 71 patients that underwent TEVAR for TBIMH; 25 underwent emergent TEVAR and 46 patients underwent dTEVAR (median, 5.5 days; range, 2-120 days). There were no differences in demographics and comorbidities, and patients did not differ in presenting IMH thickness (12.6 ± 3.1 vs 11.3 ± 4.1 mm; P = .186) nor presenting TAD/TLD ratio (1.535 ± 0.471 vs 1.525 ± 0.397; P = .928) for eTEVAR and dTEVAR groups, respectively. eTEVAR patients had larger average presenting maximal descending aortic diameter (45.8 ± 14.3 vs 38.2 ± 7.5 mm; P = .018) and higher incidence of penetrating aortic ulcer on presenting computed tomography angiography (52.0% vs 21.7%; P = .033). Thirty-day mortality was 2 of 25 (8.0%) for eTEVAR and 2 of 45 (4.4%) for dTEVAR (P = .602). Postoperative aortic remodeling was more complete in the dTEVAR group (1.23 ± 0.12 vs 1.33 ± 0.15; P = .004). Case-control matching (controlling for presenting descending aortic diameter and penetrating aortic ulcer) on 30 patients still showed better aortic remodeling in the dTEVAR group (1.125 ± 0.100 vs 1.348 ± 0.42; P < .001). The incidence of AREM was higher in the eTEVAR (6/25; 24.0%) group compared with the dTEVAR group (2/46; 4.3%). At 12 months, freedom from AREM was higher in the dTEVAR group (95.7% vs 76.0%; P = .011). Postoperative TAD/TLD ratio was the best predictor for late aortic-related adverse events (area under the receiver operator characteristic = 0.825; P = .003). CONCLUSIONS: TEVAR for acute TBIMH within 24 hours of admission is associated with lower aortic remodeling and higher occurrence of late AREM. Delaying TEVAR when clinically possible could improve aortic remodeling and aortic-related outcomes.

Helicobacter monodelphidis sp. nov. and Helicobacter didelphidarum sp. nov., isolated from grey short-tailed opossums (Monodelphis domestica) with endemic cloacal prolapses.

In a search for potential causes of increased prolapse incidence in grey short-tailed opossum colonies, samples from the gastrointestinal tracts of 94 clinically normal opossums with rectal prolapses were screened for Helicobacter species by culture and PCR. Forty strains of two novel Helicobacter species which differed from the established Helicobacter taxa were isolated from opossums with and without prolapses. One of the Helicobacter species was spiral-shaped and urease-negative whereas the other Helicobacter strain had fusiform morphology with periplasmic fibres and was urease-positive. 16S rRNA gene sequence analysis revealed that all the isolates had over 99 % sequence identity with each other, and were most closely related to Helicobacter canadensis. Strains from the two novel Helicobacter species were subjected to gyrB and hsp60 gene and whole genome sequence analyses. These two novel Helicobacter species formed separate phylogenetic clades, divergent from other known Helicobacter species. The bacteria were confirmed as novel Helicobacter species based on digital DNA-DNA hybridization and average nucleotide identity analysis of their genomes, for which we propose the names Helicobacter monodelphidis sp. nov. with the type strain MIT 15-1451T (=LMG 29780T=NCTC 14189T) and Helicobacter didelphidarum sp. nov with type strain MIT 17-337T (=LMG 31024T=NCTC 14188T).

Medical therapy in type B aortic intramural hematoma is associated with a high failure rate.

OBJECTIVE: Intramural hematoma (IMH) is on the spectrum of acute aortic syndrome, but optimal management is poorly understood. The aim of this study was to evaluate outcomes of patients with type B IMH (TBIMH) after best medical therapy (BMT) and to assess for risk factors associated with failure of BMT. METHODS: This is a single-institution retrospective chart review of all patients with TBIMH between January 2008 and December 2017. Failure of BMT was defined as any of the following end points: aortic rupture, aorta-related death, aortic enlargement to at least 55 mm or growth of >10 mm within 12 months, or need for surgical aortic intervention for failed BMT. RESULTS: We identified 92 patients, of whom 25 received emergent thoracic endovascular aortic repair; 67 patients were initially managed with BMT, and of these, 32 underwent thoracic endovascular aortic repair within 14 days for early BMT failure. Two additional patients had early BMT failure; one died of aortic rupture due to retrograde type A dissection, and one patient was advised to undergo repair but did not comply and was lost to follow-up. Fourteen patients (20.9%) received endovascular therapy for late failure of BMT after the initial hospitalization. Medical management was successful in 19 patients (28.4%), although 5 patients had aortic enlargement but below the threshold for elective repair (maximal aortic diameter of 55 mm). On univariate analysis, presenting IMH thickness and growth of IMH thickness were risk factors for BMT failure. On multivariate analysis, presenting IMH thickness was the sole predictive risk factor for medical therapy failure (odds ratio, 1.083; 95% confidence interval, 1.021-1.149; P = .008), with an odds ratio of 6.810 (95% confidence interval, 1.921-24.146; P = .002) with a presenting IMH thickness of ≥8.0 mm, which was the calculated IMH thickness cutoff value with highest sensitivity and specificity to predict failure of BMT (area under the receiver operating characteristic curve = 0.795; P = .001; J = 0.62). CONCLUSIONS: BMT for TBIMH is associated with a high failure rate and need for interventions. IMH thickness on admission is the most reliable factor to predict failure of BMT.

Traditional autopsy versus computed tomography imaging autopsy in trauma: A case of "synergistic disagreement".

BACKGROUND: Decreases in the rates of traditional autopsy (TA) negatively impact traumatology, especially in the areas of quality improvement and medical education. To help enhance the understanding of trauma-related mortality, a number of initiatives in imaging autopsy (IA) were conceived, including the postmortem computed tomography ("CATopsy") project at our institution. Though IA is a promising concept, few studies directly correlate TA and IA findings quantitatively. Here, we set out to increase our understanding of the similarities and differences between key findings on TA and IA in a prospective fashion with blinding of pathologist and radiologist evaluations. METHODS: A prospective study of TA versus IA was conducted at an Academic Level I Trauma Center (June 2001-May 2010). All decedents underwent a postmortem, whole-body, noncontrast computed tomography that was interpreted by an independent, blinded, board-certified radiologist. A blinded, board-certified pathologist then performed a TA. Autopsy results were grouped into predefined categories of pathologic findings. Categorized findings from TA and IA were compared by determining the degree of agreement (kappa). The χ(2) test was used to detect quantitative differences in "potentially fatal" findings (eg, aortic trauma, splenic injury, intracranial bleeding, etc) between TA and IA. RESULTS: Twenty-five trauma victims (19 blunt; 9 female; median age 33 years) had a total of 435 unique findings on either IA or TA grouped into 34 categories. The agreement between IA and TA was worse than what chance would predict (kappa = -0.58). The greatest agreement was seen in injuries involving axial skeleton and intracranial/cranio-facial trauma. Most discrepancies were seen in soft tissue, ectopic air, and "incidental" categories. Findings determined to be "potentially fatal" were seen on both TA/IA in 48/435 (11%) instances with 79 (18%) on TA only and 53 (12%) on IA only. TA identified more "potentially fatal" solid organ and heart/great vessel injuries, while IA revealed more spine injuries, "potentially fatal" procedure-related findings, and the presence of ectopic air/fluid. CONCLUSION: This limited study does not support substitution of noncontrast, computed tomography-based IA for TA. Our quantitative analyses suggest that TA and IA evaluations may be complementary and synergistic when performed concurrently. There are potential benefits to using IA in trauma process/quality improvement and in educational settings. Further research should focus on the value (and limitations) of the information provided by IA in the absence of TA.

Laparoscopy in trauma: An overview of complications and related topics.

The introduction of laparoscopy has provided trauma surgeons with a valuable diagnostic and, at times, therapeutic option. The minimally invasive nature of laparoscopic surgery, combined with potentially quicker postoperative recovery, simplified wound care, as well as a growing number of viable intraoperative therapeutic modalities, presents an attractive alternative for many traumatologists when managing hemodynamically stable patients with selected penetrating and blunt traumatic abdominal injuries. At the same time, laparoscopy has its own unique complication profile. This article provides an overview of potential complications associated with diagnostic and therapeutic laparoscopy in trauma, focusing on practical aspects of identification and management of laparoscopy-related adverse events.

Complications of pericardiocentesis: A clinical synopsis.

Pericardiocentesis (PC) is both a diagnostic and a potentially life-saving therapeutic procedure. Currently echocardiography-guided pericardiocentesis is considered the standard clinical practice in the treatment of large pericardial effusions and cardiac tamponade. Although considered relatively safe, this invasive procedure may be associated with certain risks and potentially serious complications. This review provides a summary of pericardiocentesis and a focused overview of the potential complications of this procedure.

Pregnancy among women surgeons: trends over time.

BACKGROUND: Women compose half of all medical students but are underrepresented in the field of general surgery. Concerns about childbirth and pregnancy during training and practice are factors that may dissuade women from electing a career in surgery. OBJECTIVE: To assess experiences related to childbirth and pregnancy among women general surgeons. DESIGN: Survey questionnaire. SETTING: Self-administered survey sent individually to women surgeons in training and practice. PARTICIPANTS: Women members of the Association for Women Surgeons or the American College of Surgeons who graduated from medical school and practice general surgery or a general surgery subspecialty. MAIN OUTCOME MEASURES: Descriptive data on the timing of pregnancy and perception of stigma attending childbirth and pregnancy as experienced by women surgeons, according to date of medical school graduation (0-9 years since graduation, 10-19 years, 20-29 years, and ≥ 30 years). The survey response rate was 49.6%. Trends over time were evaluated using comparisons of proportions and the Cochrane-Armitage trend tests across age cohorts. RESULTS: The perception of stigma associated with pregnancy during training remained large but decreased from 76% in the most remote cohort to 67% in the most recent graduation cohort (P<.001). External influences, even women resident colleagues, were perceived as evincing negative instead of encouraging attitudes toward childbearing during residency, though less so than men, both resident colleagues and faculty. Frequency of pregnancy and pregnancies earlier in training increased over the time cohorts. CONCLUSIONS: The number of women general surgeons becoming pregnant during training has increased in recent years; however, substantial negative bias persists. Although the overall magnitude of perceived negative attitudes is greater among male peers than female peers and among faculty than peers, even women residents hold negative views of pregnancy among their colleagues during training. More than half of all women surgeons delay childbearing until they are in independent practice, post-training. Surgical residents and faculty of both sexes exerted negative influences with regard to consideration of childbearing. There was also a trend toward increased childbearing in more recent graduates.

Endovascular treatment of a huge cervical carotid artery pseudoaneurysm with Wallgraft prosthesis.

Traumatic pseudoaneurysm of the internal carotid artery (ICA) is a rare cause of epistaxis, which may be life-threatening if left untreated. We report the case of a massive epistaxis from left ICA pseudoaneurysm. Our patient was a 38 year-old man with the history of a severe traffic accident 13 years ago. The pseudoaneurysm was treated with the placement of a Wallgraft prosthesis inside the carotid artery. After the endovascular treatment, the left ICA remained patent and no recurrent hemorrhage was noted in the 1 year follow up after the procedure.

Encephalization, expensive tissues, and energetics: An examination of the relative costs of brain size in strepsirrhines.

The evolution of encephalization requires that energetic challenges be met. Several hypotheses, such as the maternal energy and expensive tissue hypotheses, have been proposed to explain how some species are able to provide adequate energetic resources for large brains. The former incorporates maternal investment strategies, such as extended life history and elevated resting metabolic rate, which contribute to the growth of a large brain. The latter incorporates the reduction of gut size, which increases available energy for the maintenance of adult brain size. This study examines a sample of strepsirrhines, testing the hypothesis that encephalized species utilize some combination of the above-mentioned strategies. Infants and juveniles from three species at the Duke Lemur Center (DLC) were measured periodically to arrive at head and body growth trajectories. These data were used to determine the energetic tradeoff among the offspring. The examination of gestation length, weaning age, intestinal size and resting metabolic rate was used to assess adult brain maintenance and maternal energetic contribution. The results reveal that Daubentonia, the most encephalized and thus human-like of the lemurs, does not experience an energetic trade-off between brain and body during ontogeny, but does exhibit a trade-off between extensive brain growth and possibly reduced intestinal growth. Also, maternal energy is utilized. Encephalized lemurs, such as Daubentonia, have higher resting metabolic rate, while encephalized lorisiforms have a longer period of gestation. These results demonstrate that there are several strategies for meeting the energetic demands of encephalization, and they can be manifested differentially across taxa.

Intracranial brain abscess preceded by orbital cellulitis and sinusitis.

A 17-year-old boy with pyrexia, headache, and frequent drop attacks reported an acute onset of periorbital pain and swelling 1 month previously. Coronal computed tomography (CT) identified an ethmoid sinusitis, which was treated with functional endoscopic sinus surgery and intravenous gentamicin, prostaphylline, and metronidazone. Because of persistent symptoms, the patient returned 1 month later. The CT identified accumulation of debris in both frontal sinuses and a multilobulated lesion over the right frontal lobe. Bicoronal craniotomy was performed, and a mass located in the right frontal lobe was excised; the mass comprised chronic inflammatory tissues without evidence of malignancy. A postoperative brain CT confirmed the absence of a residual mass, and no recurrence or neurologic deficits were noted during the 3-month follow-up period. Intracranial complications cannot be prevented entirely even with the judicious use of antibiotics. Early application of the appropriate imaging modality and institution of aggressive therapy in any patient, not just pediatric patients, to prevent potential long-term disabilities and death are essential.