Characterization of the intracellular neurexin interactome by in vivo proximity ligation suggests its involvement in presynaptic actin assembly.

Neurexins are highly spliced transmembrane cell adhesion molecules that bind an array of partners via their extracellular domains. However, much less is known about the signaling pathways downstream of neurexin's largely invariant intracellular domain (ICD). Caenorhabditis elegans contains a single neurexin gene that we have previously shown is required for presynaptic assembly and stabilization. To gain insight into the signaling pathways mediating neurexin's presynaptic functions, we employed a proximity ligation method, endogenously tagging neurexin's intracellular domain with the promiscuous biotin ligase TurboID, allowing us to isolate adjacent biotinylated proteins by streptavidin pull-down and mass spectrometry. We compared our experimental strain to a control strain in which neurexin, endogenously tagged with TurboID, was dispersed from presynaptic active zones by the deletion of its C-terminal PDZ-binding motif. Selection of this control strain, which differs from the experimental strain only in its synaptic localization, was critical to identifying interactions specifically occurring at synapses. Using this approach, we identified both known and novel intracellular interactors of neurexin, including active zone scaffolds, actin-binding proteins (including almost every member of the Arp2/3 complex), signaling molecules, and mediators of RNA trafficking, protein synthesis and degradation, among others. Characterization of mutants for candidate neurexin interactors revealed that they recapitulate aspects of the nrx-1(-) mutant phenotype, suggesting they may be involved in neurexin signaling. Finally, to investigate a possible role for neurexin in local actin assembly, we endogenously tagged its intracellular domain with actin depolymerizing and sequestering peptides (DeActs) and found that this led to defects in active zone assembly. Together, these results suggest neurexin's intracellular domain may be involved in presynaptic actin-assembly, and furthermore highlight a novel approach to achieving high specificity for in vivo proteomics experiments.

Myocardial Infarction in Chronic Myeloid Leukemia: Results from the Nationwide Readmission Database.

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After the advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKIs), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts. METHOD: This is a retrospective cohort study using the Nationwide Readmission Database from January 2016 to December 2020. Adults with or without CML hospitalized for acute myocardial infarction and underwent PCI were included. The patients were identified using ICD-10 codes. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were PCI complications rates. RESULTS: Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. CML patients were significantly older (mean age: 68.34 ± 11.14 vs. 64.40 ± 12.61 years, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% vs. 78.64%), diabetes (45.48% vs. 37.29), stroke (11.84% vs. 7.78) at baseline were significantly higher in the CML group. Prior myocardial infarction events (20.51% vs. 15.17%) and prior PCI procedure (24.47% vs. 16.89%) were significantly higher in the CML group. CML patients had a significantly longer hospital stay (4.66 ± 4.40 vs. 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. The risk of post-PCI complications did not differ between the comparison groups in the propensity matched analysis except for coronary artery dissection (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.02-0.65, p = 0.016) and ischemic stroke (OR: 0.35; 95% CI: 0.14-0.93, p = 0.034) which were lower in the CML group. CONCLUSION: This analysis showed no statistically significant difference in mortality, 30-day readmission, and post PCI complications rates between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke events than those without CML diagnosis.

Neoadjuvant PD-1 Inhibitors: A Tale of Two Cases.

Treatment responses for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC) are often short lived and are marred with recurrences. The introduction of adjuvant PD-1 inhibitors has demonstrated significant improvement in both, response rates, and duration of response. For patients with high-risk resectable disease, adjuvant treatments have not demonstrated an ability to reduce recurrence risk. However, there is an opportunity in the neoadjuvant setting to alter recurrence risk. Here we dem-onstrate two cases of neoadjuvant treatment of cSCC and MCC with impressive results.  J Drugs Dermatol. 2024;23(2):     doi:10.36849/JDD.7043e.

Phosphaturic mesenchymal tumor: management and outcomes of ten patients treated at a single institution.

BACKGROUND: Phosphaturic mesenchymal tumor (PMT) is a rare tumor that causes tumor-induced osteomalacia. Patients present with non-specific symptoms secondary to renal phosphate wasting and decreased bone mineralization. We sought to assess: (1) What are the common presenting features, laboratory and imaging findings, histologic findings of phosphaturic mesenchymal tumors? (2) What are the available treatment strategies for phosphaturic mesenchymal tumors and their long-term outcomes in terms of local recurrence and symptom control after treatment? METHODS: We retrospectively identified patients with a histologic diagnosis of PMT located in the axial or appendicular skeleton, or surrounding soft tissues. A total of 10 patients were finally included in our study. RESULTS: Median tumor size was 1.9 cm (range, 1.1 to 6.1) and median time from symptom onset to diagnosis was 3 years (range, 0.5 to 15 years). All patients but one presented with hypophosphatemia (median 1.9 mg/dL, range 1.2 to 3.2). Pre-operative FGF-23 was elevated in all cases (median 423.5 RU/mL, range 235 to 8950). Six patients underwent surgical resection, three were treated percutaneously (radiofrequency ablation or cryoablation), and one refused treatment. Only one patient developed local recurrence and no patients developed metastatic disease. At last follow-up, nine patients showed no evidence of disease and one was alive with disease. CONCLUSION: Phosphaturic mesenchymal tumor is a rare tumor presenting with non-specific symptoms. Surgery is the standard treatment when negative margins can be achieved without significant morbidity. In patients with small tumors in surgically-inaccessible areas, radiofrequency ablation or cryoablation can be performed successfully.

Margin convergence vs. superior capsular reconstruction for massive irreparable rotator cuff tears: outcomes are equivalent unless there is preoperative pseudoparesis.

BACKGROUND: Margin convergence (MC) and superior capsular reconstruction (SCR) are common treatment options for irreparable rotator cuff tears in younger patients, although they differ in associated costs and operative times. The purpose of this study was to compare range of motion, patient-reported outcomes (PROs), and reoperation rates following MC and SCR. We hypothesized superior outcomes after SCR relative to MC regarding functional outcomes, subjective measures, and reoperation rates. METHODS: This was a multicenter retrospective review of 59 patients from 3 surgeons treating irreparable rotator cuff tears with either MC (n = 28) or SCR (n = 31) and minimum 1-year follow-up from 2014-2019. Visual analog scale (VAS) for pain, Subjective Shoulder Value (SSV), active forward flexion (FF), external rotation (ER), retear rate, and conversion rate to reverse shoulder arthroplasty were evaluated. t tests and χ2 tests were used for continuous and categorical variables, respectively (P < .05). RESULTS: Baseline demographics, range of motion, and magnetic resonance imaging findings were similar between groups. Average follow-up was 31.5 months and 17.8 months for the MC and SCR groups, respectively (P < .001). The MC and SCR groups had similar postoperative FF (151° ± 26° vs. 142° ± 38°; P = .325) and ER (48° ± 12° vs. 46° ± 11°; P = .284), with both groups not improving significantly from their preoperative baselines. However, both cohorts demonstrated significant improvements in VAS score (MC: 7.3 to 2.5; SCR: 6.4 to 1.0) and SSV (MC: 54% to 82%; SCR: 38% to 87%). There were no significant differences in postoperative VAS scores, SSV, and rates of retear or rates of conversion to arthroplasty between the MC and SCR groups. In patients with preoperative pseudoparesis (FF < 90°), SCR (n = 9) resulted in greater postoperative FF than MC (n = 5) (141° ± 38° vs. 67° ± 24°; P = .002). CONCLUSION: Both MC and SCR demonstrated excellent postoperative outcomes in the setting of massive irreparable rotator cuff tear, with significant improvements in PROs and no significant differences in range of motion. Specifically for patients with preoperative pseudoparesis, SCR was more effective in restoring forward elevation. Further long-term studies are needed to compare outcomes and establish appropriate indications.

Evaluation of lead-based echodensities on transesophageal echocardiogram in patients with cardiac implantable electronic devices.

INTRODUCTION: Transesophageal echocardiography (TEE) is recommended to rule out endocarditis in patients with cardiac implantable electronic devices (CIED). A lead-based echodensity (LBE), however, is often found on TEE in patients with a CIED and may not represent an infection. We sought to evaluate the predictors, characteristics, and clinical significance of LBEs seen on TEE in patients with a CIED. METHODS: Patients with a CIED were retrospectively identified from a database using International Classification of Diseases (ICD)-9/ICD-10 codes and were cross-matched with Current Procedural Terminology codes for a TEE. Clinical and follow-up data were collected. A blinded echo board-certified cardiologist reviewed all TEEs. RESULTS: Out of the 231 patients in the cohort, 191 had TEE performed for a noninfection-related indication while 40 TEEs were part of an endocarditis workup. A total of 50 LBEs were identified, and a majority were in the noninfection cohort. Systemic anticoagulant use in the noninfection cohort was associated with a decreased odds of having LBE on TEE (odds ratio [OR] of 0.23 [95% confidence interval [CI]: 0.06-0.60, p = .003]). Lead dwell time in the noninfection cohort was associated with an increased odds of having LBE on TEE (OR 1.21 (95% CI: 1.04-1.39, p = .009]). CONCLUSION: In our cohort of patients who had TEE for noninfection indications we found that systemic anticoagulant use is associated with fewer LBEs on TEEs, suggesting possible thrombin fibrin composition of LBE.

Endoscopic management of gastrointestinal wall defects, fistula closure, and stent fixation using through-the-scope tack and suture system.

BACKGROUND : Multiple devices are available for tissue approximation. A new through-the-scope suturing (TTSS) device has recently been introduced; however, data on its scope of use and clinical effectiveness are limited. We aimed to assess the clinical course and effectiveness of this TTSS device. METHODS : A retrospective review was performed for consecutive patients who underwent TTSS application. Primary outcomes were technical and clinical success, and secondary outcomes included adverse events and long-term clinical success. RESULTS : 53 patients (mean age 67.8 years; 69.8 % females) were included, with a mean defect size of 32.6 mm (SD 11.9). Technical success was achieved in 51 patients (96.2 %). Clinical success was achieved in 49 patients (92.4 %). Two patients (3.8 %) experienced failed fistula closure after technical success. Long-term follow-up (> 30 days) was available for 45 patients (84.9 %), with a mean follow-up of 7.2 months. One patient (1.9 %) had self-reported bleeding that did not require further intervention. CONCLUSIONS : TTTS was an effective and safe method for the closure of large gastrointestinal defects and could be used for fistula closure and stent fixation, making it a valuable addition to the armamentarium of endoscopic closure devices.

Knotted and knotless double row transosseous equivalent repair techniques for arthroscopic rotator cuff repair demonstrate comparable post-operative outcomes.

PURPOSE: To compare failure rates and outcomes after transosseous equivalent (TOE) double row (DR) knotted suture bridge versus knotless suture tape bridge repair techniques for rotator cuff tears. METHODS: A consecutive series of 272 shoulders in 256 patients who underwent arthroscopic, double row, TOE repair for full-thickness tears of the supraspinatus tendon were reviewed. Eighty-four shoulders were repaired using knotted suture bridge (KSB) technique, and 188 shoulders were repaired using all knotless suture tape bridge (KTB) technique. Revision procedures and concomitant subscapularis tendon repairs were excluded from analysis. The minimum follow-up was 12 months. Primary outcome was failure of surgical repair, defined as either confirmed retear on MRI and/or need for revision surgery. Secondary clinical outcome measures were assessed including range of motion, strength, visual analog scale (VAS), operative time, subjective shoulder value (SSV), Patient-Reported Outcomes Measurement Information System (PROMIS) mental and physical health, American Shoulder and Elbow Surgeons Shoulder Score (ASES), Brophy shoulder activity scores, and need for manipulation under anesthesia (MUA). RESULTS: A total of 127 shoulders (38 KSB and 89 KTB) met inclusion criteria for the study. No significant difference in demographic variables were present between the groups at baseline. Supraspinatus tear size and average follow-up time did not differ significantly between groups. Failure rates were similar between the KSB and KTB repairs (13.1 vs 7.9%, n.s.). There was no significant difference in functional outcomes including strength, range of motion in forward flexion and external rotation, as well as patient reported outcomes including VAS, SSV, PROMIS, ASES, and Brophy scores between the groups. There was also no difference in post-operative stiffness requiring MUA. CONCLUSION: Both KSB and KTB repair techniques demonstrate low retear rates with excellent functional outcomes when compared to pre-operative examination. Both KSB and KTB techniques are viable options for achieving a successful rotator cuff repair. LEVEL OF EVIDENCE: Level III.

Gender-specific outcomes after percutaneous left atrial appendage closure: A nationwide readmission database analysis.

INTRODUCTION: Thromboembolism-associated stroke is the most feared complication of atrial fibrillation (AF). Percutaneous left atrial appendage closure (pLAAC) is indicated for stroke prevention in patients with AF who can not tolerate long-term anticoagulation. We aim to study gender differences in peri-procedural and readmissions outcomes in pLAAC patients. METHODS: Using the national readmission database from January 2016 to December 2018, AF patients undergoing the pLAAC procedure were identified. We used multivariate logistic regression analyses and time-to-event Cox regression analyses to conduct the study. Propensity matching with the Greedy method was done for the accuracy of results. RESULT: A total of 28 819 patients were included in our study. Among them 11 946 (41.5%) were women and 16 873 (58.6%) were men. The mean age of overall population was 76.1 ± 8.5 years, with women ~1 year older than men. The overall rate of complications was higher in women (8.6% vs. 6.6%, p < .001), primarily driven by bleeding-related complications, that is, major bleed (odds ratio [OR]: 1.32 95% confidence interval [CI]: 1.03-1.69, p = .029), blood transfusion (OR: 1.45, 95% CI: 1.06-1.97, p = .019), and cardiac tamponade (OR: 1.80, 95% CI: 1.13-2.89, p = .014). Women had two times higher peri-procedural ischemic stroke. There was no difference in peri-procedural mortality. Women remained at 20% and 13% higher risk for readmission at 30 days and 6 months of discharge. CONCLUSION: Women had higher peri-procedural complications and were at higher risk of readmissions at 30 days and 6 months. However, there was no difference in mortality during the index hospitalization. Further studies are necessary to determine causality.

Multimodality Imaging of Cholecystectomy Complications.

Cholecystectomy is one of the most common surgeries performed in the United States. Although complications are uncommon, the high incidence of this surgery means that a radiologist will likely encounter these complications in practice. Complications may arise in the immediate postoperative period or can be delayed for weeks, months, or years after surgery. Vague and nonspecific symptoms make clinical diagnosis challenging. As a result, multimodality imaging is important in postoperative evaluation. US and multidetector CT are the usual first-line imaging modalities. Hepatobiliary scintigraphy, SPECT/CT, and MRI with conventional or gadoxetate hepatobiliary contrast material are important and complementary modalities that are used for workup. The authors begin with a brief discussion of surgical technique and expected postoperative findings and then describe complications organized into four groups: (a) biliary complications, (b) stone-related complications, (c) iatrogenic complications, and (d) gallbladder complications. Biliary complications include bile leaks and bilomas, acute biliary obstruction, and biliary stricture. Stone-related complications include retained and recurrent stones and spillage of stones into the peritoneum. Iatrogenic complications include hemorrhage, vasculobiliary injury, arterial pseudoaneurysms, duodenal injury, and migration of clips. Gallbladder complications include recurrent cholecystitis after subtotal reconstituting cholecystectomy and unexpected gallbladder cancer. An invited commentary by Mullens and Ibrahim is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Thirty-day unplanned readmission in hospitalised asthma patients in the USA.

INTRODUCTION: Hospital quality improvement and hospital performance are commonly evaluated using parameters such as average length of stay (LOS), patient safety measures and rates of hospital readmission. Thirty-day readmission (30-DR) rates are widely used as a quality indicator and a quantifiable metric for hospitals since patients are often readmitted for the exacerbation of conditions from index admission. The quality of patient education and postdischarge care can influence readmission rates. We report the 30-DR rates of patients with asthma using a national dataset for the year 2013. OBJECTIVES: The aim of our study was to assess the 30- day readmission (30-DR) rate as well as, the causes and predictors of readmissions. STUDY DESIGNS/METHODS: Using the Nationwide Readmission Database (NRD) (2013), we identified primary discharge diagnoses of asthma by using International Classification of Diseases, Ninth Revision, Clinical Modification code '493'. Categorical and continuous variables were assessed by a χ2 test and a Student's t-test, respectively. The independent predictors of unplanned 30-DR were detected by multivariate analysis. We used sampling weights, which are provided in the NRD, to generate the national estimates. RESULTS: There were 130 490 (weighted N=311 173) inpatient asthma admissions during 2013. The overall 30-DR for asthma was 11.9%. The associated factors for 30-DR were age 45-84 years (40.32% vs 29.05%; p<0.001), enrolment in Medicare (49.33% vs 30.61% p<0.001), extended LOS (mean, 4.40±0.06 vs 3.25±0.04 days; p<0.001), higher mean cost (US$8593.91 vs US$6741.31; p<0.001) and higher disposition against medical advice (DAMA) (4.14% vs 1.51%; p<0.001). The factors that increased the chance of 30-DR were advanced age (≥45-64 vs ≤17 years; OR 4.61, 95% CI 4.04 to 5.27, p<0.0001), male sex (OR 1.19, 95% CI 1.13 to 1.26, p<0.0001), a higher Charlson Comorbidity Index (CCI) (OR 1.16, 95% CI 1.14 to 1.18, p<0.0001), DAMA (OR 2.32, 95% CI 2.08 to 2.59, p<0.0001), non-compliance with medication (OR 1.34, 95% CI 1.24 to 1.46, p<0.0001), post-traumatic stress disorder (OR 1.48, 95% CI 1.22 to 1.79, p<0.0001), alcohol use (OR 1.45, 95% CI 1.27 to 1.65, p<0.0001), gastro-oesophageal reflux disease (OR 1.20, 95% CI 1.14 to 1.27, p<0.0001), obstructive sleep apnoea (OR 1.11, 95% CI 1.03 to 1.18, p<0.0042) and hypertension (OR 1.11, 95% CI 1.06 to 1.17, p<0.0001). CONCLUSIONS: We found that the overall 30-DR rate for asthma was 11.9% all-cause readmission. Major causes of 30-DR were asthma exacerbation (36.74%), chronic obstructive pulmonary disease (11.47%), respiratory failure (6.46%), non-specific pneumonia (6.19%), septicaemia (3.61%) and congestive heart failure (3.32%). One-fourth of the revisits occurred in the first week, while half of the revisits took place in the first 2 weeks. Education regarding illness and the importance of medicine compliance could play a significant role in preventing asthma-related readmission.

Minimally Invasive Cervical Access in Head and Neck Microvascular Surgery.

Free flap reconstruction often involves extensive cervical access for microvascular anastomosis where management of pathology would otherwise not require cervical approach. This study reports a minimally invasive alternative technique. Investigators designed a prospective case series with subjects who underwent microvascular reconstruction between 2015 and 2020, using a small 2 cm incision for vessel access, just below the mandible where facial artery/vein cross. Study variables were subject demographic characteristics, type and location of pathology/defect, and free flap types. Outcomes examined were flap success, postoperative facial weakness using House-Brackmann scale, and esthetic result with Visual Analog Scale. Descriptive statistics computed for study variables. Study sample was 43 subjects, mean age of 48 years with 20 males and 23 females. There were a total of 43 flaps with 100% success using our technique. One subject had House-Brackmann level 2 postoperative facial weakness that resolved within 1 week. Mean Visual Analog Scale score for scar satisfaction was 9.23/10, standard deviation 0.83. This minimally invasive approach represents an alternative to extensive open cervical access for microvascular anastomosis, offering minimal morbidity and excellent esthetic results.

Editorial Commentary: Restoring Native Meniscal Anatomy With Medial Meniscus Allograft Transplantation and Augmentation of the Meniscotibial Ligament May Decrease Meniscal Graft Extrusion.

While studies have shown significant clinical improvement after medial meniscus allograft transplantation (MMAT) with good long-term graft survivorship, progression to osteoarthritis still occurs, even in the presence of intact grafts. Several factors can potentially explain the lack of chondroprotection despite graft survivorship, including meniscal degeneration, tearing, and remodeling after the initial procedure. A major factor contributing to progression of osteoarthritis is meniscal extrusion, which is seen in up to 60% of patients and seems to be more of an issue in medial meniscus transplantation compared to lateral and is present even immediately postoperatively. Grafts without extrusion provide protective effects similar to the native meniscus, while greater than 3 mm of extrusion leads to nearly complete loss of the protective effects. A reconstruction of the meniscotibial ligament, in addition to standard MMAT, may significantly decrease meniscal extrusion. Optimization of graft size, quality, and meniscal root positioning is best to prevent extrusion and restore native biomechanics.

Sarcopenia is Associated with Reduced Survival following Surgery for Adrenocortical Carcinoma.

AIM: Adrenocortical cancer (ACC) is an aggressive malignancy and robust prognostic factors remain unclear. The presence of sarcopenia has been shown to negatively impact survival for other malignancies, but has not been extensively analyzed in ACC. METHODS: Patients who underwent resection of their ACC between 2010 and 2020 were identified; therapeutic, operative, and outcome data were analyzed. Sarcopenia was assessed by calculation of the skeletal muscle index (SMI) and was defined as an SMI <52.4cm2/m2 for males and <38.5cm2/m2 for females. RESULTS: Data on 35 patients (18 F: 17 M; median age 54 [range: 18-86]) who had primary surgical treatment were analyzed. Median tumor size was 10 cm [range:3-15]. In eleven patients (31%), the tumor was hormonally active (cortisol = 8;23%). Seventeen patients (49%) were classified as having sarcopenia on their pre-operative CT scan. The Intraclass Correlation Coefficient (ICC) for intra- and inter-observer variability showed very good agreement (0.99 and 0.98). There was no difference in incidence of sarcopenia stratifying for sex, BMI, or tumor-size, but incidence was higher with increasing age (p < .05). Overall median survival was 36 months, with 1- and 3-year survival rates of 77% and 52%. The presence of sarcopenia was strongly associated with a shorter overall survival (HR = 3.21; [95%CI: 1.06-9.69];p = .03) on unadjusted analyses. Moreover, age, higher T-stage, and presence of capsular invasion were also associated with poorer survival on univariable analyses. CONCLUSION: The presence of sarcopenia in patients undergoing surgery for ACC could be a predictor of reduced overall survival, although replications of these analyses should be performed in similar, larger cohorts. Specifically, the influence of a patient's hormonal status on the manifestation of sarcopenia should be further defined.

Outcomes among patients with primary angiitis of the CNS: A Nationwide United States analysis.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified. METHODS: Analysis of the United States Nationwide Readmissions Database (2016-2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes. RESULTS: During the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0-66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03-1.04]]), male sex (OR, 1.22 [1.04-1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08-1.84]), ischemic stroke (OR, 2.79 [2.38-3.28]), and seizure disorder (OR, 1.57 [1.31-1.89]). CONCLUSION: Our study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

Patterns of craniomaxillofacial trauma among helmeted cyclists.

BACKGROUND/AIM: The head and face are prone to injury in bicycle accidents and helmets are proven to be helpful in decreasing injuries to some extent. The aim of this study was to determine whether certain craniomaxillofacial regions are at increased risk of injury (fracture) during bicycle accidents among helmeted cyclists. MATERIALS AND METHODS: This retrospective cohort study was conducted using data from the National Electronic Injury Surveillance System (NEISS). Data concerning craniomaxillofacial injuries as a result of cycling accidents between 2019 and 2020 were reviewed. The primary predictor variables were the craniomaxillofacial region and a craniofacial bone. The co-variates included patient characteristics (age, gender, race) and injury characteristics (location, season). The primary outcome variable was a fracture. Logistic regression was used to determine any independent risk factors for a fracture. RESULTS: Five hundred patients reported helmet use at the time of injury. Fractures of the face region were 75 times (p < .01) more likely than the head region. No particular craniofacial bone was at greater risk of fracture relative to the maxilla. Adults (OR 24.0, p < .01) and seniors (OR 38.6, p < .01) were each at greater risk for fracture relative to children. CONCLUSIONS: The facial region was at increased risk of fracture relative to the head during a bicycle accident. Adults and seniors were at increased risk of suffering craniofacial fractures relative to children.

Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources.

BACKGROUND: Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. RESULTS: We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. CONCLUSIONS: Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

Exploring the link between vitamin D and clinical outcomes in COVID-19.

The immunomodulating role of vitamin D might play a role in COVID-19 disease. We studied the association between vitamin D and clinical outcomes in COVID-19 patients. This is a retrospective cohort study on COVID-19 patients with documented vitamin D levels within the last year. Vitamin D levels were grouped as ≥ 20 ng/mL or < 20 ng/mL. Main outcomes were mortality, need for mechanical ventilation, new DVT or pulmonary embolism, and ICU admission. A total of 270 patients (mean ± SD) age, 63.81 (14.69) years); 117 (43.3%) males; 216 (80%) Blacks; 139 (51.5%) in 65 and older age group were included. Vitamin D levels were less than 20 ng/mL in 95 (35.2%) patients. During admission, 72 patients (26.7%) died, 59 (21.9%) needed mechanical ventilation, and 87 (32.2%) required ICU. Vitamin D levels showed no significant association with mortality (OR = 0.69; 95% CI, 0.39-1.24; P = 0.21), need for mechanical ventilation (OR = 1.23; 95% CI, 0.68-2.24; P = 0.49), new DVT or PE(OR= 0.92; 95% CI, 0.16-5.11; P = 1.00) or ICU admission (OR = 1.38; 95% CI, 0.81-2.34; P = 0.23). We did not find any significant association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission and the development of thromboembolism in COVID-19 patients.NEW & NOTEWORTHY Low vitamin D has been associated with increased frequency and severity of respiratory tract infections in the past. Current literature linking clinical outcomes in COVID-19 with low vitamin D is debatable. This study evaluated the role of vitamin D in severe disease outcomes among COVID-19 patients and found no association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission, and thromboembolism in COVID-19.

Advanced imaging for quantification of abnormalities in the salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVES: To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes. METHODS: In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored. RESULTS: Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration. CONCLUSION: Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS.

Osteoradionecrosis and microvascular free flap failure managed with negative pressure wound therapy: A case report.

A 56-year-old female with a history of meningioma status post subtotal resection (Simpson grade IV) and extensive radiation therapy presented with osteoradionecrosis (O.R.N.) managed previously with a microvascular free flap (MVFF). The evaluation revealed worsening O.R.N. and a scalp defect of 15 × 10 cm. The patient underwent MVFF reconstruction utilizing a free latissimus muscle flap covered by meshed split-thickness skin graft (STSG). Her surgery was complicated by delayed free flap failure and Serratia marcescens growth, which occurred sometime after discharge from the hospital. This was managed with removal of the free muscle flap and skin graft, serial debridement's, antibiotics, and replacements of a synthetic dural matrix and negative pressure wound therapy (NPWT). Once a clean wound bed was again obtained, the patient underwent fasciocutaneous anterolateral thigh (A.L.T.) MVFF reconstruction, which was complicated by left hypoglossal nerve injury, dehiscence of the flap inset, and dehiscence of the neck access incision requiring revision surgery. On the last follow-up 2 weeks after her surgery, the patient had 100% flap viability and a 2 × 1.5 cm on the left parietal aspect of the flap healing be secondary intent. We demonstrate that NPWT is successful in managing open calvarial wounds due to O.R.N.