To Operate or Not to Operate? Reconstructive Surgical Burden and Quality of Life of Pediatric Patients with Facial Differences.

OBJECTIVE: The Craniofacial Condition Quality of Life Scale (CFC-QoL) was used to evaluate the relationship between surgical burden and quality of life (QoL). DESIGN: Patient-parent dyads completed the CFC-QoL which queries the following QoL domains: Bullying, Peer Problems, Psychological Impact, Family Support, Appearance Satisfaction, and Desire for Appearance Change. Stepwise multivariate linear regressions were performed for each QoL domain. SETTING: Urban tertiary care center. PATIENTS, PARTICIPANTS: Pediatric patients with facial differences, and their parents. INTERVENTION: Survey study. MAIN OUTCOME MEASURE(S): Demographic, diagnostic, and surgical characteristics were collected. Surgical burden was calculated as the standard deviation from the mean number of surgeries per diagnostic cohort. RESULT: Patients (N = 168) were majority female (57.1%) and Hispanic (64.3%). Diagnoses were cleft lip and/or palate (CLP,n = 99) or other craniofacial conditions (CFC,n = 69). Average patient age was 2.3 ± 5.6 years at first reconstructive surgery and 12.3 ± 3.4 years at study enrollment. Patients received an average of 4.3 ± 4.1 reconstructive surgeries.Worse Bullying was associated with higher surgical burden. Worse Peer Problems was associated with higher surgical burden, but only for children with non-CLP CFCs. Worse Family Support was associated with CFC diagnosis, female sex, and higher surgical burden. Worse Psychological Impact was associated with higher surgical burden. Worse Appearance Satisfaction was associated with younger age and with lower surgical burden. Greater Desire for Appearance Change was associated with older age, higher surgical burden, CLP diagnosis, female sex, and non-Hispanic ethnicity. Socioeconomic status did not predict QoL per patient self- or parent-proxy report. CONCLUSIONS: Higher surgical burden was associated with worse QoL outcomes in multiple domains.

Perioperative Comparison Between Open Cranial Vault Remodeling and Distraction Osteogenesis for Unilateral Lambdoid Craniosynostosis.

There are multiple treatment options for unilateral lambdoid craniosynostosis (ULS) including open posterior cranial vault remodeling (OCVR) and distraction osteogenesis (DO). There is a paucity of data comparing these techniques in the treatment of ULS. This study compared the perioperative characteristics of these interventions for patients with ULS. An IRB-approved chart review was performed from January 1999 to November 2018 at a single institution. Inclusion criteria included the diagnosis of ULS, treatment with either OCVR or DO using a posterior rotational flap technique, and a minimum 1-year follow-up. Seventeen patients met the inclusion criteria (12 OCVR and 5 DO). Patients in each cohort were found to have a similar distribution in sex, age at the time of surgery, synostosis laterality, weight, and length of follow-up. There was no significant difference in mean estimated blood loss/kg, surgical time, or transfusion requirements between cohorts. Distraction osteogenesis patients had a longer mean hospital length of stay (3.4 +/- 0.6 d versus 2.0 +/- 0.6 d, P = 0.0004). All patients were admitted to the surgical ward postoperatively. In the OCVR cohort, complications included 1 dural tear, 1 surgical site infection, and 2 reoperations. In the DO cohort, 1 patient had a distraction site infection, treated with antibiotics. There was no significant difference in estimated blood loss, volume of blood transfusion, or surgical time between OCVR and DO. Patients who underwent OCVR had a higher incidence of postoperative complications and the need for reoperation. This data provides insight into the perioperative differences between OCVR and DO in patients with ULS.

Virtual and In-Person Day Camps for the Craniofacial Community.

ABSTRACT: Children with congenital craniofacial conditions (CFCs) and their families may stand to benefit from day camps offering tailored psychosocial support and resources. Nonprofit ConnectMed International has held virtual and in-person day camps in San Diego for this community since 2018. We administered surveys before and after a series of day camps to understand the needs of this community and benefits perceived programming offered. Although studies have reported the psychosocial benefits of camps for children with rare diseases, few have examined the specific benefit for children with CFCs and their parents. Herein, we present the findings of our survey study as the first article to report a needs assessments and psychosocial benefits of day camps for children with CFCs and their parents.

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis.

BACKGROUND: The optimal enoxaparin dosing strategy to achieve venous thromboembolism (VTE) prophylaxis in trauma patients remains unclear. Current dosing guidelines often include weight, age, and renal function but still fail to achieve appropriate prophylactic anti-Xa levels in many patients. We hypothesized that additional patient factors influence anti-Xa response to enoxaparin in trauma patients. METHODS: This is a retrospective review of patients admitted to a Level 1 trauma center for ≥4 days from July 2015 to September 2020, who received enoxaparin VTE prophylaxis per protocol (50-59 kg, 30 mg/dose; 60-99 kg, 40 mg/dose; ≥100 kg, 50 mg/dose; all doses every 12 hours) and had an appropriately timed peak anti-Xa level. Multivariate regression was performed to identify independent predictors of prophylactic anti-Xa levels (0.2-0.4 IU/mL) upon first measurement. RESULTS: The cohort (N = 1,435) was 76.4% male, with a mean ± SD age of 49.9 ± 20.0 years and a mean ± SD weight of 82.5 ± 20.2 kg (males, 85.2 kg; females, 73.7 kg; p <0.001). Overall, 68.6% of patients (n = 984) had a prophylactic anti-Xa level on first assessment (69.6% of males, 65.1% of females). Males were more likely to have a subprophylactic level than females (22.1% vs. 8.0%, p <0.001), whereas females were more likely to have supraprophylactic levels than males (26.9% vs. 8.3%, p < 0.001). When controlling for creatinine clearance, anti-Xa level was independently associated with dose-to-weight ratio (odds ratio, 0.191 for 0.5 mg/kg; p < 0.001; confidence interval, 0.151-0.230) and female sex (odds ratio, 0.060; p < 0.001; confidence interval, 0.047-0.072). Weight and age were not significant when controlling for the other factors. CONCLUSION: Male patients have a decreased anti-Xa response to enoxaparin when compared with female patients, leading to a greater incidence of subprophylactic anti-Xa levels in male patients at all dose-to-weight ratios. To improve the accuracy of VTE chemoprophylaxis, sex should be considered as a variable in enoxaparin dosing models. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Cephalic arch restenosis rates in hemodialysis patients with brachiocephalic fistulae: a retrospective multicenter analysis of 3301 patients.

BACKGROUND: We evaluated restenosis rates at the cephalic arch after percutaneous angioplasty and stenting procedures in patients with brachial artery to cephalic vein arteriovenous fistula (BCAVF) hemodialysis access. METHODS: We used data from adult hemodialysis patients treated at a national network of 44 outpatient interventional facilities during Oct 2011-2015. We included data from patients with BCAVF who received an exclusive angioplasty, or stent with angioplasty, for treatment of cephalic arch stenosis and had ≥1 subsequent evaluation of the cephalic arch. Median percent restenosis per month at cephalic arch and days between encounters was calculated from the 1st index to 2nd procedure, and for up to 4 subsequent encounters. Analyses were stratified by intervention and device types. RESULTS: We identified a cohort of 3301 patients (mean age 62.2 ± 13.9 years, 58.5% male, 33.2% white race) with a BCAVF who had an angioplasty, or stent, at the cephalic arch for an index and ≥ 1 follow-up procedure. Between the 1st index to 2nd procedure, patients who received an angioplasty (n = 2663) or stent (n = 933) showed a median decrease of 18.9 and 16.5% in luminal diameter per month and a median time of 93 and 91 days between encounters, respectively. Restenosis and day rates were similar for standard versus high-pressure angioplasties. Bare metal stents showed 10.1 percentage point higher restenosis rate compared to stent grafts. Restenosis rates and time to restenosis were relatively consistent across subsequent encounters. CONCLUSIONS: Findings suggest hemodialysis patients with a BCAVF who require an angioplasty or stent to treat a stenosis at the cephalic arch will have stenosis reformed at a rate of 18.9 and 16.5% per month after the first intervention, respectively. Findings suggest patients are at risk of having significant lesions at the cephalic arch within 3 months after the previous intervention.

Delayed Presentation of Sagittal Suture Craniosynostosis.

BACKGROUND: Sagittal craniosynostosis typically presents as dolichocephaly or less frequently as clinocephaly, a "saddle-shaped" phenotype. This project aimed to characterize clinically relevant differences between sagittal synostosis phenotypes and examine the etiology of the delay in presentation. METHODS: An institutional review board-approved retrospective review was performed from January 1999 to November 2018 at a single institution. Analyses examined correlations between subphenotype, time of presentation, minor suture fusion, developmental delay, and operative technique. RESULTS: One hundred sixty patients diagnosed with single-suture sagittal craniosynostosis were identified. A total of 30.6% had a saddle phenotype (n = 49) and 69.4% had dolichocephaly (n = 111). Patients with the saddle phenotype were more likely to present with a developmental delay and to have at least 1 minor suture fused than patients with dolichocephaly were. Patients with the saddle phenotype presented for surgery at an older age and were more likely to undergo open cranial vault repair, with increased blood loss, higher transfusion volume, and longer time. CONCLUSIONS: This study highlights clinical differences in sagittal craniosynostosis phenotypes and shows that developmental delay is an initial presentation of the saddle phenotype. The saddle phenotype also correlated with fusion of the minor squamous and sphenoid sutures. The link between developmental delay and minor suture fusion was notable and should be explored with a larger sample size. Patients with saddle synostosis present for surgery at an older age than patients with dolichocephaly and therefore are more likely to receive open cranial vault repair, with a taxing intraoperative experience characterized by increased blood loss, increased transfusions, and longer operation time.

Room-Temperature Mechanical Resonator with a Single Added or Subtracted Phonon.

A room-temperature mechanical oscillator undergoes thermal Brownian motion with an amplitude much larger than the amplitude associated with a single phonon of excitation. This motion can be read out and manipulated using laser light using a cavity-optomechanical approach. By performing a strong quantum measurement (i.e., counting single photons in the sidebands imparted on a laser), we herald the addition and subtraction of single phonons on the 300 K thermal motional state of a 4 GHz mechanical oscillator. To understand the resulting mechanical state, we implement a tomography scheme and observe highly non-Gaussian phase-space distributions. Using a maximum likelihood method, we infer the density matrix of the oscillator, and we confirm the counterintuitive doubling of the mean phonon number resulting from phonon addition and subtraction.

Multimodal small-molecule screening for human prion protein binders.

Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including 19F-observed and saturation transfer difference (STD) NMR spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, and in silico screening. A single benzimidazole compound was confirmed in concentration-response, but affinity was very weak (Kd > 1 mm), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. Whereas orthogonal binder discovery methods could yield high-affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.

Efficient bidirectional piezo-optomechanical transduction between microwave and optical frequency.

Efficient interconversion of both classical and quantum information between microwave and optical frequency is an important engineering challenge. The optomechanical approach with gigahertz-frequency mechanical devices has the potential to be extremely efficient due to the large optomechanical response of common materials, and the ability to localize mechanical energy into a micron-scale volume. However, existing demonstrations suffer from some combination of low optical quality factor, low electrical-to-mechanical transduction efficiency, and low optomechanical interaction rate. Here we demonstrate an on-chip piezo-optomechanical transducer that systematically addresses all these challenges to achieve nearly three orders of magnitude improvement in conversion efficiency over previous work. Our modulator demonstrates acousto-optic modulation with [Formula: see text] = 0.02 V. We show bidirectional conversion efficiency of [Formula: see text] with 3.3 µW  red-detuned optical pump, and [Formula: see text] with 323 µW blue-detuned pump. Further study of quantum transduction at millikelvin temperatures is required to understand how the efficiency and added noise are affected by reduced mechanical dissipation, thermal conductivity, and thermal capacity.

Post-operative emergence of acute brachial neuritis following posterior cervical laminectomy with fusion: A case report and review of the literature.

INTRODUCTION: Idiopathic brachial plexus neuritis or neuralgic amyotrophy is a rare neurological condition whose true etiology currently remains unknown. Epidemiologically, the incidence of this condition is exceptionally rare with only 1.6 cases for every 100,000 people (Turner and Parsonage, 1987). Symptoms present an initial acute and sudden pain to the shoulder girdle and upper arm which is followed by a sense of profound weakness and numbness to the upper arm (Parsonage and Turner, 1948). Localized neuropathy within the arm-pit region may also be presented. The pain often exacerbates upon movement of the shoulder. Due to the anatomic location affected and the nature of the clinical symptoms presented, accurate diagnosis of brachial plexus neuritis poses a challenging diagnostic task for physicians due to remarkably similar symptoms expressed by differential diagnoses. PRESENTATION OF CASE: Here, we report the case of a 55-year-old woman who underwent surgery entailing cervical laminectomy with instrumented fusion. She presented with postoperative symptoms of severe pain in the left arm with significant weakness within 24 h after surgery. A diagnosis of brachial plexus neuritis was made based on the symptoms presented and upon review of imaging scans. DISCUSSION: After a six-month follow-up visit, the patient recovered from the brachial neuritis but has residual numbness in the hand. The presentation of this case serves to transmit three fundamental purposes. First, this case serves to establish an intriguing possible association of the post-surgical period of cervical laminectomy with acute brachial neuritis and signifies the importance post-operative linkage with brachial neuritis in general. Second, this case also highlights the importance of close clinical monitoring of patients with unique symptoms within the postoperative follow-up period to ensure successful improvement and accurate diagnosis. CONCLUSION: As an underdiagnosed and relatively obscure condition, this case serves as an imperative reference for physicians to illuminate differential diagnosis of similar symptomatic conditions and also to promote knowledge of brachial plexus neuritis which can lead to an early and precise diagnosis.

Cryogenic packaging of an optomechanical crystal.

There is an increasing need to simplify optical coupling techniques for low-temperature integrated photonics experiments. Various promising and scalable photonic packaging techniques have been under development, but few methods compatible with low-temperature operation have been reported. Here, we demonstrate 25% coupling efficiency from an optical fiber to a silicon optomechanical crystal at 7 mK in a dilution refrigerator without in-situ optical alignment at cryogenic temperatures. Our coupling scheme uses angle-polished fibers glued to the surface of the chip. The technique paves the way for scalable integration of optical technologies at low temperatures, circumventing the need for optical alignment in a highly constrained cryogenic environment. The technique is broadly applicable to studies of low-temperature optical physics and to emerging quantum photonic technologies.

3D collagen architecture regulates cell adhesion through degradability, thereby controlling metabolic and oxidative stress.

The collagen-rich tumor microenvironment plays a critical role in directing the migration behavior of cancer cells. 3D collagen architectures with small pores have been shown to confine cells and induce aggressive collective migration, irrespective of matrix stiffness and density. However, it remains unclear how cells sense collagen architecture and transduce this information to initiate collective migration. Here, we tune collagen architecture and analyze its effect on four core cell-ECM interactions: cytoskeletal polymerization, adhesion, contractility, and matrix degradation. From this comprehensive analysis, we deduce that matrix architecture initially modulates cancer cell adhesion strength, and that this results from architecture-induced changes to matrix degradability. That is, architectures with smaller pores are less degradable, and degradability is required for cancer cell adhesion to 3D fibrilar collagen. The biochemical consequences of this 3D low-attachment state are similar to those induced by suspension culture, including metabolic and oxidative stress. One distinction from suspension culture is the induction of collagen catabolism that occurs in 3D low-attachment conditions. Cells also upregulate Snail1 and Notch signaling in response to 3D low-attachment, which suggests a mechanism for the emergence of collective behaviors.

Single-Mode Phononic Wire.

Photons and electrons transmit information to form complex systems and networks. Phonons on the other hand, the quanta of mechanical motion, are often considered only as carriers of thermal energy. Nonetheless, their flow can also be molded in fabricated nanoscale circuits. We design and experimentally demonstrate wires for phonons by patterning the surface of a silicon chip. Our device eliminates all but one channel of phonon conduction, allowing coherent phonon transport over millimeter length scales. We characterize the phononic wire optically, by coupling it strongly to an optomechanical transducer. The phononic wire enables new ways to manipulate information and energy on a chip. In particular, our result is an important step towards realizing on-chip phonon networks, in which quantum information is transmitted between nodes via phonons.

An isothermal based recombinase polymerase amplification assay for rapid, sensitive and robust indexing of citrus yellow mosaic virus.

Management of viral diseases relies on definite and sensitive detection methods. Citrus yellow mosaic virus (CYMV), a double stranded DNA virus of the genus Badnavirus, causes yellow mosaic disease in citrus plants. CYMV is transmitted through budwood and requires a robust and simplified indexing protocol for budwood certification programme. The present study reports development and standardization of an isothermal based recombinase polymerase amplification (RPA) assay for a sensitive, rapid, easy, and cost-effective method for detection and diagnosis of CYMV. Two different oligonucleotide primer sets were designed from ORF III (coding for polyprotein) and ORF II (coding for virion associated protein) regions of CYMV to perform amplification assays. Comparative evaluation of RPA, PCR and immuno-capture recombinase polymerase amplification (IC-RPA) based assays were done using purified DNA and plant crude sap. CYMV infection was efficiently detected from the crude sap in RPA and IC-RPA assays. The primer set used in RPA was specific and did not show any cross-amplification with banana streak MY virus (BSMYV), another Badnavirus species. The results from the present study indicated that RPA assay can be used easily in routine indexing of citrus planting material. To the best of our knowledge, this is the first report on development of a rapid and simplified isothermal detection assay for CYMV and can be utilized as an effective technique in quarantine and budwood certification process.

T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load.

Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and L. infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present was focused on parasite load with T cell function in bone marrow of 26 VL patients. We observed significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0·0003) and interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg ) (P = 0·004) in the bone marrow (BM) of patients with high parasite load (HPL) compared with low parasite load (LPL). Concordantly, T effector cells producing interferon (IFN)-γ (P = 0·005) and IL-17A (P = 0·002) were reduced in the BM of HPL. Blocking of Treg -cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)-ß] rescued the effector T cells and their functions. However, it was observed that TGF-ß levels were dominant, favouring Treg cell differentiation. Furthermore, the low ratio of IL-6/TGF-ß favours the suppressive milieu in HPL patients. Here we show the change in levels of various cytokines with the parasitic load during active VL, which could be helpful in devising newer immunotherapeutic strategies against this disease.

Efficient photon coupling from a diamond nitrogen vacancy center by integration with silica fiber.

A central goal in quantum information science is to efficiently interface photons with single optical modes for quantum networking and distributed quantum computing. Here, we introduce and experimentally demonstrate a compact and efficient method for the low-loss coupling of a solid-state qubit, the nitrogen vacancy (NV) center in diamond, with a single-mode optical fiber. In this approach, single-mode tapered diamond waveguides containing exactly one high quality NV memory are selected and integrated on tapered silica fibers. Numerical optimization of an adiabatic coupler indicates that near-unity-efficiency photon transfer is possible between the two modes. Experimentally, we find an overall collection efficiency between 16% and 37% and estimate a single photon count rate at saturation above 700 kHz. This integrated system enables robust, alignment-free, and efficient interfacing of single-mode optical fibers with single photon emitters and quantum memories in solids.

Intracranial and spinal metastases from eccrine mucinous carcinoma: case report.

BACKGROUND AND IMPORTANCE: Mucinous eccrine carcinoma (MEC) is a rare but distinct type of sweat gland tumor. MECs tend to recur locally, and their spread to distant organs is very uncommon. This article describes the first case of MEC metastasizing to the brain and the spine. CLINICAL PRESENTATION: A 45-year-old female presented with a 2-year history of a scalp mass in the occipital area with lymph node spread. She underwent excision of the mass and neck lymph node dissection. Pathology confirmed the diagnosis of MEC. Postoperatively, she received radiation to the involved areas. Four years later the patient presented with left hemiparesis and underwent craniotomy for gross total resection of the metastasis. This recurred after 2.5 years and she underwent another craniotomy for gross total resection followed by whole brain radiation. In addition, the patient had metastases to T11 vertebral body and the left C6 to 7 neural foramen. Moreover, the patient developed leptomeningeal disease in the spine. The metastases to the spine were treated with radiation therapy. The patient died 1.5 years later. CONCLUSION: Even though it is rare for MEC to spread to distant organs, physicians should be aware of the risk of metastatic invasion of the brain and spine and be vigilant about surveillance of these sites. MEC metastases to the brain should be treated aggressively with surgical resection followed by stereotactic radiosurgery to the tumor bed. Spine metastases should be treated with a combination of surgery and image-guided radiation therapy, depending on the degree of cord compression from epidural metastatic disease.

Intramedullary Cervical Sarcoidosis as the Initial Presentation of Systemic Sarcoidosis.

We present a case of a 57-year-old African American man with systemic sarcoidosis, who initially presented with cervical spinal cord disease. Initial MRI showed an elongated intramedullary area of increased signal intensity on T2 and inversion recovery sequences within the cervical spinal cord with minimal contrast enhancement after gadolinium administration. Further radiologic evaluation led to a chest CT, which showed bilateral hilar lymphadenopathy. Thoracic lymph node biopsy revealed systemic sarcoidosis. Post treatment MRI showed improvement of the cervical spinal cord lesion, further supporting the diagnosis of systemic sarcoidosis.