Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer.

Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy.

The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines CXCL10/CXCL11 and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens and found an association with beneficial response to PD-1 blockade. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcome. This hub is distinct from mature tertiary lymphoid structures and is enriched for stem-like TCF7+PD-1+CD8+ T cells, activated CCR7+LAMP3+ dendritic cells and CCL19+ fibroblasts as well as chemokines that organize these cells. Within the stem-immunity hub, we find preferential interactions between CXCL10+ macrophages and TCF7-CD8+ T cells as well as between mature regulatory dendritic cells and TCF7+CD4+ and regulatory T cells. These results provide a picture of the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes.

Spatially organized multicellular immune hubs in human colorectal cancer.

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

Spns1 is an iron transporter essential for megalin-dependent endocytosis.

Proximal tubule endocytosis is essential to produce protein-free urine as well as to regulate system-wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules. The endocytic defect was accompanied by changes in megalin phosphorylation as well as enlargement of lysosomes, confirming previous findings in Drosophila and Zebrafish. The endocytic defect was also accompanied by iron overload in proximal tubules. Remarkably, iron levels regulated the Spns1 phenotypes because feeding an iron-deficient diet or mating Spns1 knockout with divalent metal transporter1 knockout rescued the phenotypes. Conversely, iron-loading wild-type mice reproduced the endocytic defect. These data demonstrate a reversible, negative feedback for apical endocytosis and raise the possibility that regulation of endocytosis, pinocytosis, megalin activation, and organellar size and function is nutrient-responsive.NEW & NOTEWORTHY Spns1 mediates a novel iron conductance essential during embryogenesis. Spns1 knockout leads to endocytic and lysosomal defects, accompanied by iron overload in the kidney. Reversal of iron overload by restricting dietary iron or by concurrent knockout of the iron transporter, DMT1 rescued the endocytic and organellar defects and reverted markers of iron overload. These data suggest feedback between iron and proximal tubule endocytosis.

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients.

OBJECTIVES: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU. DESIGN: Observational cohort study and separate in vitro laboratory study. SETTING: Multicenter tertiary referral ICUs. PATIENTS: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: -0.52, p = 0.002; TEG r: -0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings. CONCLUSIONS: Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient's hemoglobin concentration.

Epidemiology and Management of Adult Laryngeal Trauma: An Analysis of the National Trauma Data Bank.

INTRODUCTION: Laryngeal injuries are rare but life-threatening airway emergencies. Increased understanding of the epidemiology of these injuries can inform treatment and improve outcomes. We aimed to characterize the demographics and management of adult laryngeal trauma. METHODS: The National Trauma Data Bank (NTDB) was queried from 2007 to 2015 for patients ≥18 years old with laryngeal trauma. Patient demographics, injury characteristics, and treatment course were collected. Outcomes were assessed via multivariate logistic regression. RESULTS: From 7.3 million patients, 6,890 (0.1%) patients with laryngeal trauma were identified. Eighty-five percent of patients were male, and the median age was 40. Of these patients, 343 (5.0%) were dead on arrival and of the remaining patients, 510 (7.8%) of patients were deceased at discharge. Common concomitant injuries included facial fractures (27%), intracranial injuries (21%), and rib and sternum fractures (19%). The most common cause of injury was motor vehicle accident (26%), followed by assault with firearms/explosives (12%) and assault with cutting instruments (8%). Forty-three percent of patients received mechanical ventilation and 15% received surgical repair. After correcting for gender, age, and injury severity, firearm injuries (odds ratio [OR] 3.46, 95% CI: [2.88-4.15]) and cutting/piercing injuries (OR 2.23, 95% CI: [1.89-2.64]) were positively associated with the need for mechanical ventilation. Motor vehicle trauma (OR 0.63, 95% CI: [0.46-0.84]) was negatively associated with surgical repair while striking injuries (OR 1.61, 95% CI: [1.25-2.06]) were positively associated. Lastly, shorter time to tracheostomy was significantly associated with shorter ICU stays (p < 0.0001). CONCLUSION: This study is the largest epidemiologic study of laryngeal trauma to date and identifies the risk of surgical intervention with firearm and cutting injuries as well as the importance of earlier time to tracheostomy for ICU management.

Epidemiology of Anterior and Lateral Basilar Skull Fractures With CSF Leak: A National Trauma Data Bank Analysis.

OBJECTIVE: Cerebrospinal fluid (CSF) leaks are a complication from dural violations that can occur in the setting of skull base fractures. No prior study provides a nationwide epidemiological analysis of traumatic CSF leaks. The objective of this report is to characterize patient demographics, injury-related variables, and operative management. METHODS: The national trauma data bank was queried for both anterior and lateral skull base fracture cases between 2008 and 2016. Clinical data were extracted. RESULTS: A total of 242 skull base fractures with CSF leak were identified. Most patients were male (84.3%), and the median patient age was 39.7±17.6 years old. Glasgow Coma Scale was 14.0 [interquartile range (IQR): 6.5-10.6] for lateral fractures, 13.0 (IQR: 3.0-10.0) for anterior fractures, and severe range for combined fractures at 7.0 (IQR: 5.0-9.0) (analysis of variance, P =0.122). Common mechanisms of injury were motor vehicle accidents (107, 44.2%), followed by falls and firearms (65, 26.9% and 20, 8.3%, respectively). The median length of stay was 2 weeks, with a median of 14 days (IQR: 10-25) for the anterior fractures and 10 days (IQR 5-19) among the lateral fractures ( P =0.592). Patients were most commonly discharged home in both the anterior (43.8%) and lateral (49.2%) groups. CONCLUSIONS: The prototypical patient tends to be a young adult male presenting with moderate-to-severe range neurological dysfunction after a vehicular accident. The overall prognosis of skull base fractures with CSF leak remains encouraging, with nearly half of these patients being discharged home within 2 weeks.

Genomic Mismatch at LIMS1 Locus and Kidney Allograft Rejection.

BACKGROUND: In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. METHODS: We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses. RESULTS: In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval [CI], 1.35 to 2.50; P = 9.8×10-5). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor-recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10-5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10-8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses. CONCLUSIONS: We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.).

Longitudinal Outcomes of COVID-19-Associated Collapsing Glomerulopathy and Other Podocytopathies.

BACKGROUND: The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19-associated collapsing glomerulopathy were median age 57 years (range, 35-72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30-412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19-associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.

A systematic quality appraisal of clinical practice guidelines for Ménière's disease using the AGREE II instrument.

PURPOSE: To systematically appraise clinical practice guidelines for the diagnosis and treatment of Ménière's disease using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. MATERIALS AND METHODS: A systematic literature search was performed to identify guidelines pertaining to the diagnosis and treatment of Ménière's disease. Data were abstracted from guidelines that met inclusion criteria and appraised by four independent reviewers in the six domains of quality defined by the AGREE II. Domain scores reflecting quality in each domain were calculated. Intraclass correlation coefficients (ICC) were calculated across domains to qualify interrater reliability. RESULTS: Six guidelines were found to meet inclusion criteria after a systematic literature search. Of the six clinical practice guidelines appraised using the AGREE II, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline received the highest average score, with a mean of 90.7% spanning six quality domains. The guideline with the lowest average score across all domains was the European Position Statement on diagnosis and treatment of Ménière's disease, receiving an average score across domains of 34.6%. Overall quality scores of clinical practice guidelines for Ménière's disease had a standard deviation of 21.3%. Two guidelines met the quality threshold of > 60% in at least five domains, qualifying as 'high': AAO-HNS and National Institute for Health and Care Excellence. Average ICC across all six domains was 0.87, suggesting near total agreement between reviewers. CONCLUSION: Ménière's disease remains a challenging entity to diagnose and treat; few existing clinical guidelines meet the standards of quality established by the AGREE II appraisal instrument.

Clinical practice guidelines on management of infantile hemangioma: a systematic quality appraisal using the AGREE II instrument.

Infantile hemangiomas (IH) are the most common benign tumors of childhood. Timely diagnosis and management of higher-risk IH is key in avoiding permanent disfigurement, visual impairment, and life-threatening airway compromise. Here, we identify and critically appraise existing clinical practice guidelines (CPGs) for IH diagnosis and management. A systematic search of MEDLINE, SCOPUS, and EMBASE was conducted until August 2021. Four independent reviewers assessed each CPG utilizing the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). An scaled domain score of ≥60% demonstrated adequacy in a given domain. Intraclass correlation coefficients (ICC) assessed agreement and scoring consistency between the reviewers. Eight CPGs were eligible and included for critical appraisal. Only one CPG was classified as 'high quality', with the remaining seven guidelines being 'average' (n = 3) or 'low' (n = 4) quality. Six guidelines (75.0%) were conducted via nonsystematic literature searches. The 'Applicability' (40.4%±14.0) and 'Rigor of development' (46.9%±17.3) domains achieved the lowest scores, while the highest average scores were in 'Scope and purpose' (76.7%±11.3) and 'Editorial independence' (90.8%±13.0). We found high consistency between the four independent reviewers, with 'very good' (n = 5) or 'good' (n = 1) interrater reliability in all six AGREE II domains. Based on the AGREE II instrument, there is only one available high-quality consensus statement on the diagnosis and management of IH. Low scores in 'Rigor of development' and 'Applicability' suggest notable weaknesses in the development process and reporting quality of existing IH CPGs. Future guidelines should be backed by systematic literature searches and focus on guideline clinical translation.

Postmortem Kidney Pathology Findings in Patients with COVID-19.

BACKGROUND: AKI is common among hospitalized patients with coronavirus disease 2019 (COVID-19) and is an independent risk factor for mortality. Although there are numerous potential mechanisms underlying COVID-19-associated AKI, our current knowledge of kidney pathologic findings in COVID-19 is limited. METHODS: We examined the postmortem kidneys from 42 patients who died of COVID-19. We reviewed light microscopy findings in all autopsies and performed immunofluorescence, electron microscopy, and in situ hybridization studies for SARS-CoV-2 on a subset of samples. RESULTS: The cohort had a median age of 71.5 years (range, 38-97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension. Among patients with available data, AKI developed in 31 of 33 patients (94%), including 6 with AKI stage 1, 9 with stage 2, and 16 with stage 3. The predominant finding correlating with AKI was acute tubular injury. However, the degree of acute tubular injury was often less severe than predicted for the degree of AKI, suggesting a role for hemodynamic factors, such as aggressive fluid management. Background changes of hypertensive arterionephrosclerosis and diabetic glomerulosclerosis were frequent but typically mild. We identified focal kidney fibrin thrombi in 6 of 42 (14%) autopsies. A single Black patient had collapsing FSGS. Immunofluorescence and electron microscopy were largely unrevealing, and in situ hybridization for SARS-CoV-2 showed no definitive positivity. CONCLUSIONS: Among a cohort of 42 patients dying with COVID-19, autopsy histologic evaluation revealed acute tubular injury, which was typically mild relative to the degree of creatinine elevation. These findings suggest potential for reversibility upon resolution of SARS-CoV-2 infection.

Kidney Biopsy Findings in Patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. METHODS: We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. CONCLUSIONS: Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.

Unique Transcriptional Programs Identify Subtypes of AKI.

Two metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to the injury of the kidney tubule and the epithelial cells thereof (AKI). Yet neither criterion emphasizes the etiology or the pathogenetic heterogeneity of acute decreases in kidney excretory function. In fact, whether decreased excretory function due to contraction of the extracellular fluid volume (vAKI) or due to intrinsic kidney injury (iAKI) actually share pathogenesis and should be aggregated in the same diagnostic group remains an open question. To examine this possibility, we created mouse models of iAKI and vAKI that induced a similar increase in serum creatinine concentration. Using laser microdissection to isolate specific domains of the kidney, followed by RNA sequencing, we found that thousands of genes responded specifically to iAKI or to vAKI, but very few responded to both stimuli. In fact, the activated gene sets comprised different, functionally unrelated signal transduction pathways and were expressed in different regions of the kidney. Moreover, we identified distinctive gene expression patterns in human urine as potential biomarkers of either iAKI or vAKI, but not both. Hence, iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify our current definitions of acute changes in kidney excretory function.

Is Postoperative Voice Rest Unnecessary? A Systematic Review and Meta-analysis of Voice Rest Recommendation Outcomes.

BACKGROUND: Voice rest (VR) is widely recommended after microlaryngeal surgery to facilitate recovery and improve voice outcomes. Our study is the first systematic review and meta-analysis summarizing the impact of postoperative absolute voice rest (AVR) and no voice rest (NVR) instructions on voice outcomes. METHODS: PubMed, Embase, and Cochrane Library databases were searched using "voice rest laryngeal surgery" and "postoperative voice rest" for articles published before December 2022. Risk of bias was assessed using ROBINS-I and RoB2 tools. Meta-analysis using a random effects model was performed for studies comparing Voice Handicap Index (VHI-10) outcomes between NVR and AVR. Analysis was performed in R Studio. RESULTS: In total, 255 articles were reviewed, 24 underwent full-text screening, and nine met inclusion criteria. Four randomized control trials (RCT) and one retrospective review compared AVR durations (range: 2-10days). Four studies (two cohort, one cross-sectional, and one RCT) compared AVR to NVR. All studies had risk of bias (ROBINS-I: two moderate, two serious; RoB2: five with concerns). Comparing AVR durations, two found no difference between short and long duration, while two reported improved outcomes for the short cohort. In studies comparing AVR to NVR, all concluded no significant difference in outcomes. Pooled analysis of three studies (355 patients) comparing NVR and AVR demonstrated no significant differences in pre- and postoperative VHI-10 change (mean difference=-0.87; 95% CI, -2.51 to 0.77; P = 0.27). CONCLUSION: Systematic review findings indicate postoperative VR may not lead to improved voice outcomes, and a meta-analysis demonstrated no difference in VHI-10 outcomes between AVR and NVR.

Isolated traumatic orbital floor fracture: An analysis of the National Trauma Data Bank.

Objectives: To date, no study provides a comprehensive analysis of traumatic orbital floor fractures across the United States. We aimed to characterize patient demographics, injury-related variables, and operative management in this population. Method: The National Trauma Data Bank was queried for open or closed orbital floor fractures from 2008 to 2016. Clinical data were extracted. Results: Overall, 148,592 orbital floor fractures were identified, with 142,577 (95.9%) closed- and 6158 (4.1%) open-type fractures. A total of 106,243 (71.5%) patients were male and the median patient age was 41 years. The majority of patients (79.2%) had abbreviated injury scale scores of ≤2, indicating minor/moderate injury. Fracture mechanism of injury (MOI) differed by gender, with the most frequent being unarmed fights in men (34.3%) and falls in women (14.0%). There were 29,600 patients (19.9%) with isolated orbital floor (I-OF) fractures. The MOI most strongly associated with operative intervention of with I-OF fractures were penetrating injuries caused by a firearm (odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.62-5.20) and cuttings/piercings (OR: 2.17; 95% CI: 1.29-3.65). Conclusion: This large epidemiological study reveals that orbital floor fractures tend to present with minor or moderate injuries and are more likely to require operative intervention in setting of firearm or cut/pierce injuries.

The efficacy of the National Surgical Quality Improvement Program surgical risk calculator in head and neck surgery: A meta-analysis.

BACKGROUND: The National Surgical Quality Improvement Program surgical risk calculator (SRC) estimates the risk for postoperative complications. This meta-analysis assesses the efficacy of the SRC in the field of head and neck surgery. METHODS: A systematic review identified studies comparing the SRC's predictions to observed outcomes following head and neck surgeries. Predictive accuracy was assessed using receiver operating characteristic curves (AUCs) and Brier scoring. RESULTS: Nine studies totaling 1774 patients were included. The SRC underpredicted the risk of all outcomes (including any complication [observed (ob) = 35.9%, predicted (pr) = 21.8%] and serious complication [ob = 28.7%, pr = 17.0%]) except mortality (ob = 0.37%, pr = 1.55%). The observed length of stay was more than twice the predicted length (p < 0.02). Discrimination was acceptable for postoperative pneumonia (AUC = 0.778) and urinary tract infection (AUC = 0.782) only. Predictive accuracy was low for all outcomes (Brier scores ≥0.01) and comparable for patients with and without free-flap reconstructions. CONCLUSION: The SRC is an ineffective instrument for predicting outcomes in head and neck surgery.

Management of the Difficult Airway: An Appraisal of Clinical Practice Guidelines.

OBJECTIVE: Management of the difficult airway can be a challenging process, which necessitates actionable recommendations from well-established guidelines. Herein, clinical practice guideline (CPG) quality is evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. STUDY DESIGN: A systematic literature search was performed using Scopus, EMBASE, and MEDLINE via PubMed. SETTING: Literature database. METHODS: Data were abstracted from relevant guidelines and appraised by 4 expert reviewers in the 6 domains of quality defined by AGREE II. Intraclass correlation coefficients (ICC) were calculated across domains to quantify interrater reliability. RESULTS: Twelve guidelines met the inclusion criteria. With a mean quality score of 83.1%, the highest quality guideline was authored by the American Society of Anesthesiologists (ASA). Low-quality content was observed in CPGs authored by the Japanese Society of Anesthesiologists (JSA) and the Chinese Collaboration Group for Emergency Airway Management (CCGEAM). Overall, deficits were most pronounced in domains describing the involvement of stakeholders, developmental rigor, and editorial independence. These findings were consistent among the panel of independent reviewers, with high ICC inter-rater reliability scores of 58.0% to 70.0% for the referenced domains. CONCLUSION: By providing a comprehensive appraisal of guidelines, this report may serve as a reference for clinicians seeking to understand and improve upon the developmental quality of difficult airway management resources. According to AGREE II criteria for the quality of the guideline creation process, the 2022 ASA guideline outperforms its predecessors.