The ATOM-Seq sequence capture panel can accurately predict microsatellite instability status in formalin-fixed tumour samples, alongside routine gene mutation testing.

Microsatellite instability (MSI) occurs across a number of cancers and is associated with different clinical characteristics when compared to microsatellite stable (MSS) cancers. As MSI cancers have different characteristics, routine MSI testing is now recommended for a number of cancer types including colorectal cancer (CRC). Using gene panels for sequencing of known cancer mutations is routinely performed to guide treatment decisions. By adding a number of MSI regions to a small gene panel, the efficacy of simultaneous MSI detection in a series of CRCs was tested. Tumour DNA from formalin-fixed, paraffin-embedded (FFPE) tumours was sequenced using a 23-gene panel kit (ATOM-Seq) provided by GeneFirst. The mismatch repair (MMR) status was obtained for each patient from their routine pathology reports, and compared to MSI predictions from the sequencing data. By testing 29 microsatellite regions in 335 samples the MSI status was correctly classified in 314/319 samples (98.4% concordance), with sixteen failures. By reducing the number of regions in silico, comparable performance could be reached with as few as eight MSI marker positions. This test represents a quick, and accurate means of determining MSI status in FFPE CRC samples, as part of a routine gene mutation assay, and can easily be incorporated into a research or diagnostic setting. This could replace separate mutation and MSI tests with no loss of accuracy, thus improving testing efficiency.

Fat Necrosis in Single Perforator Deep Inferior Epigastric Artery and Superficial Epigastric Artery Perforator Free Flaps: A Prospective Randomized Study.

Background: The deep inferior epigastric perforator (DIEP) flap is the standard of care in autologous breast reconstruction. The superficial inferior epigastric artery perforator flap (SIEA) is an alternative reconstructive option, with the compromise of less donor-site morbidity but variable perfusion to subscarpal fat zones. Fat necrosis is a known complication from marginal perfusion variability. Volumetric analysis of fat necrosis has not been performed between the two reconstructive options, nor has the amount of flap necrosis following radiation. Our objective was to compare rates and volume of fat necrosis between single-perforator DIEP and SIEA flap techniques. Methods: A single-center, blinded, prospective cohort study of patients randomized between SIEA and DIEP breast reconstruction was conducted over 2 years (June 2011-July 2013). Inclusion criteria were women undergoing immediate reconstruction following mastectomy. Randomization protocols were strictly followed. Fat necrosis volumetric analysis was determined by an ultrasound-trained attending surgeon at 12 months postoperatively. Patient demographics and adjuvant/neoadjuvant cancer treatment were analyzed. Statistical analyses included Mann-Whitney U tests, chi square, and/or Fisher exact tests. P values of 0.05 or less were considered significant. Results: Fat necrosis was detected in 11 of 46 flaps (23.9%), with a median area of 17.9 cm2. There was no significant difference in prevalence of fat necrosis between the two flap types (P = 0.19). Postoperative radiation did not increase the prevalence (P = 0.30) or extent (P = 0.92) of fat necrosis. Conclusion: Single-perforator DIEP and SIEA flaps have comparable rates of fat necrosis. Postoperative radiation did not result in increased prevalence or extent of fat necrosis.

Verrucous Carcinoma of the Foot: A Single Canadian Center Experience on Diagnosis, Management, and Outcomes.

INTRODUCTION: Verrucous carcinoma (VC) was first described in 1948 by Dr. Ackerman. It is a low-grade cutaneous squamous carcinoma that usually develops in the oral cavity, the anogenital region, and the plantar surface of the foot. Clinically, there is low suspicion for malignancy given the slow growth of VC lesions and their wart-like appearance. Diagnosis can be difficult because of the benign histological appearance with well-differentiated cells and absence of dysplasia. Surgical excision is the only satisfactory form of treatment for plantar VC; however, this becomes difficult given its benign clinical appearance and the pathologic misinterpretation of the lesion as a benign hyperplasia. While there are case reports and retrospective studies of patients with plantar VC in the literature, we present the largest case series of plantar VC within North America, with recurrence despite negative margins. METHODS: We report on all the plantar VC excised between 2014-2023. We report six cases of VC, their treatment, and their outcomes. RESULTS: Six patients obtained a diagnosis of plantar VC by incisional biopsy. All patients underwent excision of their lesions and had negative margins reported on the final pathology. All patients developed nonhealing wounds at the site of their lesion excision; therefore, biopsies were performed to confirm a recurrence. All patients had a recurrence of VC at the initial site. All patients underwent re-excision of the lesions. Despite negative margins again on final pathology, all patients had a subsequent second recurrence. Ultimately, all patients underwent an amputation as definitive management. Each patient had an average of 3 operations. There were 4 different surgeons and different pathologists reporting their findings. CONCLUSIONS: Our experience with plantar VC suggests that an aggressive approach to surgical management is needed. Furthermore, management is optimized with the combined expertise of an experienced dermatopathologist and surgeon. Despite negative margins and repeated excisions, VC lesions recur and invade local tissues to the extent that only amputation of the involved foot has resulted in cure.

Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.

Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

Xylosyltransferase Bump-and-hole Engineering to Chemically Manipulate Proteoglycans in Mammalian Cells.

Mammalian cells orchestrate signalling through interaction events on their surfaces. Proteoglycans are an intricate part of these interactions, carrying large glycosaminoglycan polysaccharides that recruit signalling molecules. Despite their importance in development, cancer and neurobiology, a relatively small number of proteoglycans have been identified. In addition to the complexity of glycan extension, biosynthetic redundancy in the first protein glycosylation step by two xylosyltransferase isoenzymes XT1 and XT2 complicates annotation of proteoglycans. Here, we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. By employing a tactic termed bump- and-hole engineering, we engineer the two isoenzymes XT1 and XT2 to specifically transfer a chemically modified xylose analogue to target proteins. The chemical modification contains a bioorthogonal tag, allowing the ability to visualise and profile target proteins modified by both transferases in mammalian cells. The versatility of our approach allows pinpointing glycosylation sites by tandem mass spectrometry, and exploiting the chemical handle to manufacture proteoglycans with defined GAG chains for cellular applications. Engineered XT enzymes permit a view into proteoglycan biology that is orthogonal to conventional techniques in biochemistry.

Synovial Lipomatosis With Extra-articular Extension in the Arthritic Wrist: An Unexpected Diagnosis.

ABSTRACT: Synovial lipomatosis is a rare condition characterized by adipocyte proliferation within joint synovial tissue. It most commonly affects the knee and is typically intra-articular. Only 5 published case reports describe extra-articular synovial lipomatosis of the wrist. We present a case of a sexagenarian patient seen for his wrist arthropathy. His x-ray revealed pan-wrist arthritis and inflammatory soft tissue swelling. The patient was slated for a wrist fusion and Darrach procedure. Following the dorsal skin incision in the operating room, an unusual adipose mass was identified infiltrating all extensor compartments: midcarpal, radiocarpal, and distal radioulnar joints. The mass was excised and sent to pathology prior to proceeding with the slated surgery. Synovial lipomatosis was diagnosed postoperatively based on histopathology. Six weeks postoperatively, the wrist fusion had healed clinically and radiographically, and his pain had improved. There was no evidence of recurrence. Synovial lipomatosis is a rare entity that may imitate multiple other pathologies. It is possible that synovial lipomatosis may represent a secondary occurrence following degenerative articular disease or trauma in older patients. This is the first case report to date describing synovial lipomatosis of the wrist with extra-articular extension in the setting of pan-carpal wrist arthritis.

Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection.

Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures.

The relationship between response style and symptom reporting in cancer patients.

PURPOSE: Patient-reported outcomes are considered the gold standard for documenting treatment-related toxicities and cancer-related symptoms in the management of oncology patients. Poor concordance between patients and health care professionals (HCPs) on patients' symptoms has been documented. The purpose of this study is to examine the association between social desirability, a response style, and symptom reporting in a colorectal cancer clinic. METHODS: Patients being treated for colorectal cancer completed a social desirability measure and a symptom measure before their appointment in the oncology clinic. The HCP who saw the patient completed a symptom measure for the patient after the clinic visit. RESULTS: One hundred sixty-nine patients consented to participate in the study. The majority of the patients had stage 4 disease. There was a statistically significant positive correlation between social desirability and overall reported symptom burden. There was a statistically significant negative correlation between social desirability and concordance between the patient and the HCP on the patient's symptoms. Social desirability scores were stable over the course of 1 year. CONCLUSION: Sensitivity to social desirability effects seems to play an important role in patient self-report of symptoms. As social desirability is a stable quality, patients sensitive to it may be persistently at risk for undertreatment of symptoms due to limited symptom reporting.

Identification of global inhibitors of cellular glycosylation.

Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation and selected the GalNAc-T11 isoenzyme that selectively glycosylates endocytic low-density lipoprotein receptor (LDLR)-related proteins as targets. Our screen of a limited small molecule compound library did not identify selective inhibitors of GalNAc-T11, however, we identify two compounds that broadly inhibited Golgi-localized glycosylation processes. These compounds mediate the reversible fragmentation of the Golgi system without affecting secretion. We demonstrate how these inhibitors can be used to manipulate glycosylation in cells to induce expression of truncated O-glycans and augment binding of cancer-specific Tn-glycoprotein antibodies and to inhibit expression of heparan sulfate and binding and infection of SARS-CoV-2.

Citation Analysis in Breast Reconstruction Publications Between 2000 and 2010.

Introduction and Purpose: Breast reconstruction is an active area of plastic surgery research. Citation analysis allows for quantitative analysis of publications, with more citations presumed to indicate greater influence. We performed citation analysis to evaluate the most cited papers on breast reconstruction between 2000 to 2010 to identify contemporary research trends. Methods: The SCI-EXPANDED database was used to identify the 50 most cited papers. Data points included authorship, publication year, publication journal, study design, level of evidence, number of surgeons/institutions, center of surgery, primary outcome assessed, implant/flap/acellular dermal matrix/fat graft, acellular dermal matrix brand and use with implants/flaps, fat graft use with implants/flaps, unilateral/bilateral, one-/two-stage, immediate/delayed, number of patients/procedures, complications. Descriptive analysis of trends was performed based on results. Results: 20% of papers were published in 2006, 16% in 2007 and 12% in both 2004/2009. 66% were published in Plastic and Reconstructive Surgery. The majority were retrospective or case series, and of Level III or IV evidence. The one Level I study was a prospective multicenter trial. 21 and 7 papers discussed procedures by single/multiple surgeons, respectively. Results from single/multiple centers were discussed in 18 and 6 papers, respectively. 30 papers discussed implant-based reconstruction, 22 papers flap-based (19 microsurgical), 15 papers acellular dermal matrix, and five papers fat grafting. The primary focus in the majority was complications or outcomes. Conclusion: Our analysis demonstrates continually evolving techniques in breast reconstruction. However, there is notable lack of high quality evidence to guide surgical decision-making in the face of increasing surgical options.

Introduction et objectif: La reconstruction mammaire est un secteur actif de la recherche en chirurgie plastique. L'analyse de citations permet de procéder à une analyse quantitative des publications, un plus grand nombre de citations étant réputé indiquer une plus grande influence. Les chercheurs ont effectué une analyse de citations pour évaluer les articles les plus cités sur la reconstruction mammaire entre 2000 et 2010 et établir les tendances contemporaines de la recherche. Méthodologie: Les chercheurs ont utilisé la base de données SCI-EXPANDED pour extraire les 50 articles les plus cités. Les éléments de données incluaient les auteurs; l'année de publication; la revue; la méthodologie; la qualité des preuves; le nombre de chirurgiens et d'établissements, le centre chirurgical, l'évaluation des résultats primaires; l'implant, le lambeau, la matrice dermique acellulaire, la greffe de graisse; le type de matrice dermique acellulaire et son utilisation avec les implants et les lambeaux; l'utilisation de greffe de graisse avec les implants et les lambeaux; les reconstructions unilatérales ou bilatérales, en une ou deux phases, immédiates ou tardives; le nombre de patientes et d'interventions et les complications. Les chercheurs ont procédé à une analyse descriptive des tendances en fonction des résultats. Résultats: L'analyse a démontré que 20 % des articles ont été publiés en 2006, 16 % en 2007 et 12 % à la fois en 2004 et 2009. De plus, 66 % ont paru dans la revue Plastic and Reconstructive Surgery. La plupart étaient des études rétrospectives ou des séries de cas et contenaient des données probantes de niveau III ou IV. La seule étude de niveau I était un essai multicentrique prospectif. Par ailleurs, 21 articles ont traité d'interventions réalisées par un seul chirurgien, et sept, par de multiples chirurgiens. Les résultats monocentriques ont été abordés dans 18 articles, et les résultats multicentriques, dans six articles. Enfin, 30 articles portaient sur les reconstructions par implant, 22, sur les reconstructions par lambeau (dont 19 microchirurgies), 15, sur la matrice dermique acellulaire et cinq, sur les greffes de graisse. Les complications ou les résultats cliniques étaient l'objectif principal de la majorité des études. Conclusion: L'analyse a démontré que les techniques de reconstruction mammaire sont en constante évolution. Cependant, les données de qualité font défaut pour orienter les décisions chirurgicales à la lumière des possibilités chirurgicales croissantes.

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction.

Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.

Olivine Crystal Structure-Directed Twinning in Iron Germanium Sulfide (Fe2GeS4) Nanoparticles.

Understanding the microstructure of complex crystal structures is critical for controlling material properties in next-generation devices. Synthetic reports of twinning in bulk and nanostructured crystals with detailed crystallographic characterization are integral for advancing systematic studies of twinning phenomena. Herein, we report a synthetic route to controllably twinned olivine nanoparticles. Microstructural characterization of Fe2GeS4 nanoparticles via electron microscopy (imaging, diffraction, and crystallographic analysis) demonstrates the formation of triplets of twins, or trillings. We establish synthetic control over the particle crystallinity and crystal growth. We describe the geometrical basis for twin formation, hexagonal pseudosymmetry of the orthorhombic lattice, and rank all of the reported olivine compounds according to this favorability to form twins. The work in this study highlights an area ripe for future exploration with respect to the advancement of solution-phase synthetic approaches that can control microstructure in compositionally complex, technologically relevant structures. Finally, we discuss the potential implications for olivine properties and performance in various applications.

Chondroitin Sulfate Disaccharides in the Gas Phase: Differentiation and Conformational Constraints.

Glycosaminoglycans (GAGs) are a family of complex carbohydrates vital to all mammalian organisms and involved in numerous biological processes. Chondroitin and dermatan sulfate, an important class of GAGs, are linear macromolecules consisting of disaccharide building blocks of N-acetylgalactosamine and two different uronic acids. The varying degree and the site of sulfation render their characterization challenging. Here, we combine mass spectrometry with cryogenic infrared spectroscopy in the wavenumber range from 1000 to 1800 cm-1. Fingerprint spectra were recorded for a comprehensive set of disaccharides bearing all known motifs of sulfation. In addition, state-of-the-art quantum chemical calculations were performed to aid the understanding of the differences in the experimental fingerprint spectra. The results show that the degree and position of charged sulfate groups define the size of the conformational landscape in the gas phase. The detailed understanding of cryogenic infrared spectroscopy for acidic and often highly sulfated glycans may pave the way to utilize the technique in fragment-based sequencing approaches.

Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Perioperative aspiration events in children: A report from the Wake Up Safe Collaborative.

BACKGROUND: Perioperative aspiration, while rare, is a serious complication of anesthetic care. Consequences of aspiration may include physical obstruction, wheezing, and pneumonia, resulting in mild to severe hypoxemia and even death. AIM: We used a multi-institutional registry of pediatric patients to identify factors that influence the rate and resulting harm of perioperative pulmonary aspiration. METHODS: The Wake Up Safe registry was queried for all severe adverse events reported from 29 institutions from 2010 to 2017. Aspiration events were identified through the "respiratory adverse event" data entry form or through free text search. Multivariable regression was used to predict aspiration events, and contributory factors were identified by reviewing free text case comments. RESULTS: Analysis included 2 440 810 anesthetics administered involving patients ≤18 years of age. There were 135 pulmonary aspiration events, for an incidence of 0.006%. Within these 135 cases, 110 cases (82%) resulted in escalation of care and 51 (38%) resulted in patient harm, including 2 deaths (1.5%). In multivariable analysis, patients undergoing emergency surgery (OR 2.0 [1.2-3.5]) or with higher ASA status were more likely to experience aspiration (ASA 3 (OR 5.0 [2.6-9.1]); ASA ≥ 4 (OR 5.5 [3.8-16.8])). Noted causes of aspiration included gastrointestinal comorbid conditions (19%), postcoughing event or laryngospasm (14%), nil per os (NPO) violation (11%), blood or secretions in the airway following or during the procedure (6%), and oral premedication reaction (3%). CONCLUSION: Although infrequent, death was reported as a consequence of perioperative aspiration in two patients. The frequency with which NPO violations were identified as a potential cause of aspiration highlights the struggles institutions face with adherence to NPO regulations, as these cases may be preventable. Furthermore, preventive measures may be needed to address other common causes of aspiration, such as gastrointestinal comorbid conditions.

Amide-Assisted Synthesis of Iron Germanium Sulfide (Fe2GeS4) Nanostars: The Effect of LiN(SiMe3)2 on Precursor Reactivity for Favoring Nanoparticle Nucleation or Growth.

Olivine Fe2GeS4 has been identified as a promising photovoltaic absorber material introduced as an alternate candidate to iron pyrite, FeS2. The compounds share similar benefits in terms of elemental abundance and relative nontoxicity, but Fe2GeS4 was predicted to have higher stability with respect to decomposition to alternate phases and, therefore, more optimal device performance. Our initial report of the nanoparticle (NP) synthesis for Fe2GeS4 was not well understood and required an inefficient 24 h growth to dissolve an iron sulfide impurity. Here, we report an amide-assisted Fe2GeS4 NP synthesis that directly forms the phase-pure product in minutes. This significant advance was achieved by the replacement of the poorly understood hexamethyldisilazane (HMDS) additive and TMS2S by the conjugate base, lithium bis(trimethylsilyl)amide (LiN(SiMe3)2), and elemental S, respectively. We hypothesized that fragments of both TMS2S and HMDS had carried out the roles that Brønsted bases play in amide-assisted NP syntheses and were necessary for Ge incorporation. Convolution of this role with the supply of S in TMS2S caused the iron sulfide impurities. Separating these effects in the use of LiN(SiMe3)2 and elemental S resulted in synthetic control over the ternary phase. Herein we explore the Fe-Ge-S reaction landscape and the role of the base. Its concentration was found to increase the reactivities of the Fe, Ge, and S precursors, and we discuss possible metal-amide intermediates. This affords tunability in two areas: favorability of NP nucleation versus growth and phase formation. The phase-purity of Fe2GeS4 depends on the molar ratios of the cations, base, and amine as well as the Fe:Ge:S molar ratios. The resultant Fe2GeS4 NPs exhibit an interesting star anise-like morphology with stacks of nanoplates that intersect along a 6-fold rotation axis. The optical properties of the Fe2GeS4 NPs are consistent with previously published measurements showing a measured band gap of 1.48 eV.

The Incidence and Severity of Hypocarbia in Neonates Undergoing General Anesthesia.

BACKGROUND: Extended periods of hypocarbia in preterm infants may be associated with intraventricular hemorrhage, periventricular leukomalacia, and bronchopulmonary dysplasia. To evaluate the current anesthetic practice in preterm neonates, we retrospectively reviewed the intraoperative course with regard to [Formula: see text] and ventilation during non-cardiac surgical procedures in infants <60 weeks postmenstrual age. METHODS: This was a single-center, retrospective study during non-cardiac surgical procedures in neonates. Hyperventilation was defined as a [Formula: see text] ≤ 35  mm  Hg, significant hyperventilation as a [Formula: see text] ≤ 30 mm Hg, and extreme hyperventilation as a [Formula: see text] ≤ 25  mm  Hg. RESULTS: The study cohort included 112 neonates, with a median postnatal age of 40 weeks, median gestational age of 38 weeks, and median weight of 5 kg. Thirty-seven subjects (33%) had at least one arterial blood gas value that demonstrated hyperventilation. Thirteen (12%) were noted to have significant hyperventilation ([Formula: see text] ≤ 30  mm  Hg) and 2 had extreme hyperventilation ([Formula: see text] ≤ 25  mm  Hg). CONCLUSIONS: The incidence of at least one arterial blood gas that demonstrated inadvertent hyperventilation in neonates was high during intraoperative care. These data may provide the baseline for future studies that address more rigorous monitoring and control of [Formula: see text] during intraoperative care. Although the duration of the anesthetic care and surgical procedure is brief compared with the neonatal ICU length of stay because there is no demonstrated benefit of hypocapnia and, in fact, well-documented harm associated with hyperventilation in neonates, care should be directed at limiting inadvertent hyperventilation. (ClinicalTrials.gov registration NCT03823716.).

Indium-111 labelling of liposomal HEGF for radionuclide delivery via ultrasound-induced cavitation.

The purpose of this exploratory study was to investigate the combination of a radiopharmaceutical, nanoparticles and ultrasound (US) enhanced delivery to develop a clinically viable therapeutic strategy for tumours overexpressing the epidermal growth factor receptor (EGFR). Molecularly targeted radionuclides have great potential for cancer therapy but are sometimes associated with insufficient delivery resulting in sub-cytotoxic amounts of radioactivity being delivered to the tumour. Liposome formulations are currently used in the clinic to reduce the side effects and improve the pharmacokinetic profile of chemotherapeutic drugs. However, in contrast to non-radioactive agents, loading and release of radiotherapeutics from liposomes can be challenging in the clinical setting. US-activated cavitation agents such as microbubbles (MBs) have been used to release therapeutics from liposomes to enhance the distribution/delivery in a target area. In an effort to harness the benefits of these techniques, the development of a liposome loaded radiopharmaceutical construct for enhanced delivery via acoustic cavitation was studied. The liposomal formulation was loaded with peptide, human epidermal growth factor (HEGF), coupled to a chelator for subsequent radiolabelling with 111Indium ([111In]In3+), in a manner designed to be compatible with preparation in a radiopharmacy. Liposomes were efficiently radiolabelled (57%) within 1 h, with release of ~12% of the radiopeptide following a 20 s exposure to US-mediated cavitation in vitro. In clonogenic studies this level of release resulted in cytotoxicity specifically in cells over-expressing the epidermal growth factor receptor (EGFR), with over 99% reduction in colony survival compared to controls. The formulation extended the circulation time and changed the biodistribution compared to the non-liposomal radiopeptide in vivo, although interestingly the biodistribution did not resemble that of liposome constructs currently used in the clinic. Cavitation of MBs co-injected with liposomes into tumours expressing high levels of EGFR resulted in a 2-fold enhancement in tumour uptake within 20 min. However, owing to the poor vascularisation of the tumour model used the same level of uptake was achieved without US after 24 h. By combining acoustic-cavitation-sensitive liposomes with radiopharmaceuticals this research represents a new concept in achieving targeted delivery of radiopharmaceuticals.

The Interaction of Race and Gender as a Significant Driver of Racial Arrest Disparities for African American Men.

The mass incarceration of African Americans is both a driver of racial health inequalities in the USA. Systemic social biases which associate African American men with criminality, violence, and as a particular threat to white women may partially explain their over-representation in the criminal justice system. We combined data from the Washington, DC Metro Police Department (MPD) and the American Community Survey to test whether neighborhood-level gender, race, and economic makeup were associated with elevated drug-related arrest disproportions for African American men. We found that African American men were significantly overrepresented in all drug-related arrests across the District, and that this arrest disproportion was significantly higher in neighborhoods that had a higher percentage of white female residents. The association between race and gender was somewhat attenuated, but not completely eliminated, when we introduced socio-economic variables to our model. Addressing the social determinants of criminal justice disparities must account for the intersection of race, gender, and economics, rather than considering race in isolation.

Pediatric obstructive sleep apnea screening questionnaire and post-operative outcomes: A prospective observational study.

INTRODUCTION: Obstructive Sleep Apnea (OSA) and Sleep Disordered Breathing (SDB) in children tend to be a more complex and multifactorial disease than in adults. Although adult screening tools, such as the STOP-BANG questionnaire, their application limited in pediatrics. We used our previously described 6-point questionnaire to identify OSA in children and evaluated its use for predicting post-operative respiratory events. METHODS: Children from 3 to 18 years of age presenting for surgery were eligible. Exclusion criteria were emergency surgery or refusal to participate. A 6-question survey regarding symptoms of OSA/SDB was administered preoperatively. Neck circumference was measured. Height and weight were recorded from preoperative data and the body mass index (BMI) percentile obtained. RESULTS: 749 patients were enrolled in the study. 707 patients were in the final analysis (359 boys and 348 girls, mean age 12 ±â€¯4 years). The median 6-item questionnaire score was 1 (interquartile range: 0, 2) and 186 (26%) scored ≥ 2 of 6 points. Children with predicted OSA (yes on ≥ 2 questions) were more likely than without predicted OSA to require supplemental oxygen in the PACU (24% vs. 17%; 95% confidence interval [CI] of difference: -0.3%, 13%; p = 0.049). Amongst 681 patients with available data on Post Anesthesia Care Unit (PACU) length of stay (LOS), prolonged LOS (>1 h) was not more likely among children with predicted OSA (42%) compared to those without predicted OSA (39%; 95% CI of difference: -5%, 11%; p = 0.479). Outcomes assessed after PACU discharge noted no differences. Specifically, overnight hospital stay was required in 33% of patients with predicted OSA as compared to 29% of those without (95% CI of difference: -4%, 11%; p = 0.399). On POD 0, supplemental oxygen was used on the inpatient ward for 6% of patients with predicted OSA compared to 4% of patients without predicted OSA (95% CI of difference: -2%, 6%; p = 0.272). CONCLUSION: The incidence of OSA/SDB is under-appreciated in children presenting for non-otolaryngological surgical procedures. Although patients judged to have OSA on the 6-item question may need for supplemental oxygen longer in the PACU, no other outcomes differences were noted.