Autoimmune disease of head and neck, imaging, and clinical review.

Autoimmune disease of the head and neck (H&N) could be primary or secondary to systemic diseases, medications, or malignancies. Immune-mediated diseases of the H&N are not common in daily practice of radiologists; the diagnosis is frequently delayed because of the non-specific initial presentation and lack of familiarity with some of the specific imaging and clinical features. In this review, we aim to provide a practical diagnostic approach based on the specific radiological findings for each disease. We hope that our review will help radiologists expand their understanding of the spectrum of the discussed disease entities, help them narrow the differential diagnosis, and avoid unnecessary tissue biopsy when appropriate based on the specific clinical scenarios.

Cholangiocarcinoma obscured by a large paraesophageal hernia causing traction compression of the common hepatic duct ultimately diagnosed with percutaneous cholangioscopy.

Video 1Case presentation including cross-sectional imaging, percutaneous cholangiogram, percutaneous cholangioscopy, and histopathology of cholangioscopy-directed biopsies.

Sellar, suprasellar, and parasellar masses: Imaging features and neurosurgical approaches.

The sellar, suprasellar, and parasellar space contain a vast array of pathologies, including neoplastic, congenital, vascular, inflammatory, and infectious etiologies. Symptoms, if present, include a combination of headache, eye pain, ophthalmoplegia, visual field deficits, cranial neuropathy, and endocrine manifestations. A special focus is paid to key features on CT and MRI that can help in differentiating different pathologies. While most lesions ultimately require histopathologic evaluation, expert knowledge of skull base anatomy in combination with awareness of key imaging features can be useful in limiting the differential diagnosis and guiding management. Surgical techniques, including endoscopic endonasal and transcranial neurosurgical approaches are described in detail.

Disposable digital percutaneous cholangioscope-aided retrieval of a plastic biliary stent after failed retrieval at ERCP.

Video 1Cholangioscopy, fluoroscopy, and endoscopy of the percutaneous retrieval of a biliary stent across an iatrogenic common hepatic duct stricture due to surgical staples.

Orbital and nasal meningoencephaloceles secondary to chronic hydrocephalus: A rare cause of bilateral proptosis.

Introduction Orbital meningoencephalocele formation is primarily a result of congenital defects in the pediatric population and trauma of the anterior cranial fossa in adults. We present a unique case of nontraumatic nasal and orbital meningoencephaloceles presenting as bilateral proptosis with exotropia secondary to chronic hydrocephalus. Clinical presentation A 20-year-old male with a history of tuberous sclerosis, X-linked intellectual disability, and epilepsy presented to the emergency department with two days of nausea, emesis, seizures, and two months of progressive proptosis. Initial radiographs of the skull showed a "copper beaten" appearance, indicating chronically elevated intracranial pressure. Computed tomography imaging of the head demonstrated bilateral defects in the cribriform plate and anterior cranial fossa. Magnetic resonance imaging of the brain revealed triventricular hydrocephalus with meningoencephalocele extension into the nasal cavity and frontal horn herniation into the extraconal space of the orbits. The hydrocephalus was managed with ventriculoperitoneal shunt placement with rapid and complete resolution of the proptosis. Conclusion No reports have described bilateral proptosis as the presenting finding of orbital and nasal meningoencephaloceles in the absence of trauma or congenital defect. This case study demonstrates the management of meningoencephalocele formation secondary to chronic hydrocephalus.

Morbidity Associated with Fetal Macrosomia among Women with Diabetes Mellitus.

OBJECTIVE: This article aims to compare the composite maternal and neonatal morbidities (CMM and CNM, respectively) between macrosomic (≥4,000 g) and nonmacrosomic (<4,000 g) newborns among women with diabetes mellitus (DM). METHODS: Maternal demographic and peripartum outcome data (N = 1,260) were collected from a retrospective cohort. CMM included chorioamnionitis/endometritis, wound infection, shoulder dystocia, eclampsia, pulmonary edema, admission for hypoglycemia, 3rd/4th degree perineal laceration, and death. CNM included 5-minute Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score of <4, neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, intraventricular hemorrhage grade III/IV, necrotizing enterocolitis stage II/III, hypoglycemia, hypocalcemia, bronchopulmonary dysplasia, sepsis, seizures, hyperbilirubinemia, and death. Multivariable Poisson regression models with robust error variance were used to calculate adjusted relative risk (aRR) and 95% confidence interval (CI). RESULTS: The study population consisted of 967 subjects, including 854 (88.3%) nonmacrosomic and 113 (11.7%) macrosomic infants. After adjustment, the risk of CMM was higher among macrosomic deliveries (aRR = 4.08, 95% CI = 2.45-6.80). The risk of CNM was also higher among macrosomic deliveries (aRR = 1.77, 95% CI = 1.39-2.24). Macrosomia was associated with an increased risk in NICU admission, hypoglycemia, and hyperbilirubinemia. CONCLUSION: Among DM deliveries, macrosomia was associated with a fourfold higher risk of CMM and almost twofold higher risk of CNM.

Diabetes during Pregnancy: Influence of Body Mass Index on Composite Morbidity.

Objective This study aims to compare composite maternal and neonatal morbidities (MM, NM) among pregnant women with diabetes mellitus whose body mass index (BMI) at delivery was < 30 (group 1), 30.0 to 39.9 (group 2), and ≥ 40 kg/m 2 (group 3). We hypothesized that increased BMI class at delivery would be associated with worsening maternal and neonatal outcomes. Methods This is a retrospective cohort study. MM was defined as: chorioamnionitis, wound infection, eclampsia, diabetic ketoacidosis, hypoglycemia admission, third/fourth degree laceration, and/or death. NM was defined as umbilical arterial pH < 7.0, 5 minute Apgar < 4, respiratory distress syndrome, mechanical ventilation, neonatal sepsis, stillbirth, and/or death. Odds ratios were adjusted for possible confounders. Results MM was noted in 8, 13, and 24% of groups 1, 2, and 3, respectively, and significantly more common in group 2 versus 1 (adjusted odds ratio [aOR]: 1.66) and group 3 versus 1 (aOR: 3.06). NM was noted in 7, 8, and 15% of each BMI group, respectively, and differed significantly between group 3 vs. 2 (aOR: 1.77). Conclusions The increased rate of morbidities between the BMI groups is useful to inform diabetic women and highlights the need for further investigation of diabetes and obesity as comorbidities in pregnancy.

Hydrocarbon-stapled lipopeptides exhibit selective antimicrobial activity.

Antimicrobial peptides (AMPs) occur widely in nature and have been studied for their therapeutic potential. AMPs are of interest due to the large number of possible chemical structural combinations using natural and unnatural amino acids, with varying effects on their biological activities. Using physicochemical properties from known naturally occurring amphipathic cationic AMPs, several hydrocarbon-stapled lipopeptides (HSLPs) were designed, synthesized, and tested for antimicrobial properties. Peptides were chemically modified by N-terminal acylation, C-terminal amidation, and some were hydrocarbon stapled by intramolecular olefin metathesis. The effects of peptide length, amphipathic character, and stapling on antimicrobial activity were tested against Escherichia coli, three species of Gram-positive bacteria (Staphylococcus aureus, Bacillus megaterium, and Enterococcus faecalis), and two strains of Candida albicans. Peptides were shown to disrupt liposomes of different phospholipid composition, as measured by leakage of a fluorescent compound from vesicles. Peptides with (S)-2-(4'-pentenyl)-alanine substituted for l-alanine in a reference peptide showed a marked increase in antimicrobial activity, hemolysis, and membrane disruption. Stapled peptides exhibited slightly higher antimicrobial potency; those with greatest hydrophobic character showed the greatest hemolysis and liposome leakage, but lower antimicrobial activity. The results support a model of HSLPs as membrane-disruptive AMPs with potent antimicrobial activity and relatively low hemolytic potential at biologically active peptide concentrations.

Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.

Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy. Comparable to rucaparib development, other PARP inhibitors, such as olaparib, niraparib, veliparib and talazoparib, are developing CDx tests for targeted therapy. PARP inhibitor clinical trials and CDx assays are discussed in this review, as are potential PARP inhibitor combination therapies and likely resistance mechanisms.

Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides.

A method to facilitate the characterization of stapled or cyclic peptides is reported via an arginine-selective derivatization strategy coupled with MS/MS analysis. Arginine residues are converted to ornithine residues through a deguanidination reaction that installs a highly selectively cleavable site in peptides. Upon activation by CID or UVPD, the ornithine residue cyclizes to promote cleavage of the adjacent amide bond. This Arg-specific process offers a unique strategy for site-selective ring opening of stapled and cyclic peptides. Upon activation of each derivatized peptide, site-specific backbone cleavage at the ornithine residue results in two complementary products: the lactam ring-containing portion of the peptide and the amine-containing portion. The deguanidination process not only provides a specific marker site that initiates fragmentation of the peptide but also offers a means to unlock the staple and differentiate isobaric stapled peptides.