Citations

ABSTRACT The rpoB gene has been proposed as a promising phylogenetic marker for bacterial identification, providing theoretically improved species-level resolution compared to the 16S rRNA gene for a range of clinically important taxa. However, its utility in diagnostic microbiology has been limited by the lack of broad-range primers allowing for its amplification from most species with a single PCR assay. Here, we present an assay for broad-range partial amplification and Sanger sequencing of the rpoB gene. To reduce cross-reactivity and allow for rpoB amplification directly from patient samples, primers were based on the dual priming oligonucleotide principle. The resulting amplicon is ~550 base pairs in length and appropriate for species-level identification. Systematic in silico evaluation of a wide selection of taxa demonstrated improved resolution within multiple important genera, including Enterococcus, Fusobacterium , Mycobacterium , Streptococcus , and Staphylococcus species and several genera within the Enterobacteriaceae family. Broad-range rpoB amplification and Sanger sequencing of 115 bacterial isolates provided unambiguous species-level identification for 97 (84%) isolates, as compared to 57 (50%) using a clinical 16S rRNA gene assay. Several unresolved taxonomic matters disguised by the low resolution of the 16S rRNA gene were revealed using the rpoB gene. Using a collection of 33 clinical specimens harboring bacteria and assumed to contain high concentrations of human DNA, the rpoB assay identified the pathogen in 29 specimens (88%). Broad-range rpoB amplification and sequencing provides a promising tool for bacterial identification, improving discrimination between closely related species and making it amenable for use in culture-based and culture-independent diagnostic approaches.

Introduction: More than 90% of orthopaedic surgery residents in the United States complete a fellowship program. While there is significant oversight of the educational process and rights of residents during residency, there is little standardization in fellowships in the United States. Applicants to fellowship need to be aware that they may be required to sign restrictive covenants (“non-competes”) as part of the fellowship application or acceptance process. These restrictive covenants may be designed to protect the business interests of the host institution but may affect the fellow's ability to obtain employment in a geographic region. Methods: A review of society websites designed to education fellowship applicants was reviewed. Information was gathered on whether the society provided information on restrictive covenants in fellowship programs. Results: There is little standardization of restrictive covenants in orthopedic fellowships in the United States. Only accredited fellowships prohibit restrictive covenants in orthopedic fellowships. Pediatrics is the only sub-specialty society that provides information to applicants on restrictive covenants for fellowship applicants. Conclusion: The current lack of standardization in the fellowship process means applicants need to be well versed in these restrictive covenants before applying. In turn, fellowships themselves, as well as subspecialty societies, should seek to be transparent in providing information on restrictive covenant requirements of their respective fellowships.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a global health problem with a worldwide increase in incidence. While previously it was more prevalent in Western countries, especially in North America and Europe, there has been a recent sizeable increase in the incidence of IBD in Asia. This article is a brief overview of the causative factors that contribute to this rise in IBD cases in Asian countries. There is a notable disparity between the Asian IBD population and the Western one in terms of age distribution and gender predilection, and genetic studies reveal both shared and unique susceptibility loci. Changes in environmental factors, including alterations in diet, hygiene, and lifestyle, are thought to play a key role in the epidemiological transition observed in Asia. It is crucial to comprehend how genetic predisposition interacts with environmental factors in order to understand the causes of IBD in the Asian population and develop precise interventions to alleviate its impact.

AbstractINTRODUCTIONCorticobasal syndrome (CBS) can result from underlying Alzheimer's disease (AD) pathologies. Little is known about the utility of blood plasma metrics to predict positron emission tomography (PET) biomarker‐confirmed AD in CBS.METHODSA cohort of eighteen CBS patients (8 amyloid beta [Aβ]+; 10 Aβ−) and 8 cognitively unimpaired (CU) individuals underwent PET imaging and plasma analysis. Plasma concentrations were compared using a Kruskal–Wallis test. Spearman correlations assessed relationships between plasma concentrations and PET uptake.RESULTSCBS Aβ+ group showed a reduced Aβ42/40 ratio, with elevated phosphorylated tau (p‐tau)181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentrations, while CBS Aβ− group only showed elevated NfL concentration compared to CU. Both p‐tau181 and GFAP were able to differentiate CBS Aβ− from CBS Aβ+ and showed positive associations with Aβ and tau PET uptake.DISCUSSIONThis study supports use of plasma p‐tau181 and GFAP to detect AD in CBS. NfL shows potential as a non‐specific disease biomarker of CBS regardless of underlying pathology.Highlights Plasma phosphorylated tau (p‐tau)181 and glial fibrillary acidic protein (GFAP) concentrations differentiate corticobasal syndrome (CBS) amyloid beta (Aβ)− from CBS Aβ+. Plasma neurofilament light concentrations are elevated in CBS Aβ− and Aβ+ compared to controls. Plasma p‐tau181 and GFAP concentrations were associated with Aβ and tau positron emission tomography (PET) uptake. Aβ42/40 ratio showed a negative correlation with Aβ PET uptake.

AbstractBackgroundGastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades.PurposeThe objectives of this review are to develop an understanding of the goals of treatment, the evidence‐based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence‐based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof‐of‐efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof‐of‐efficacy, placebo‐controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.

Summary: Lymphedema following oncologic intervention can cause significant lifelong morbidity for patients in whom conservative management fails. The associated swelling, discomfort, pain, and recurrent cellulitis greatly diminish quality of life. Surgical procedures, including suction-assisted lipectomy, lymphovenous anastomosis (LVA), and vascularized lymph node transfers, show effectiveness in both volume reduction in affected extremities and symptom relief. However, the success of procedures like LVA is dependent on effective preoperative lymphatic mapping to identify suitable vessels for anastomosis. Traditional superficial lymphatic mapping uses near infrared fluorescence indocyanine green (ICG) imaging. Moreover, recent advances in contrast-enhanced ultrasound (CEUS) lymphography increased lymphovenous bypass target identification for LVA in the extremities.7 CEUS lymphography uses microbubbles as a contrast-enhancing agent injected intradermally into the affected extremity with subsequent identification of superficial collecting lymphatic vessels using ultrasound. Although a recent report noted an uptick in severe and critical adverse drug reactions to an ultrasound contrast agent injected intravenously in stress echocardiography, adverse drug reactions associated with ultrasound contrast-enhancing agents in body ultrasound are rare. The safety profile and potential complications from CEUS lymphography in the lymphedema population have yet to be fully characterized. In this case report, the authors present the first cutaneous adverse drug event following a secondary exposure to the contrast used for CEUS imaging. Mechanisms and justifications for an immune-mediated process are explored, and a review of similar manifestations in other related contrast applications is discussed.

AbstractPurposeSinonasal malignancies (SNMs) adversely impact patients’ quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients.MethodsIn this prospective, multi‐institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease‐related factors that influence each of the 12 UWQOL subdomains from baseline to 5 ‐years post‐treatment.ResultsMultivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI −10.8, −2.4, p = 0.01) and pain (CI −17.0, −4.0, p < 0.001). Neck dissection predicted worse swallow (CI −14.8, −2.8, p < 0.001), taste (CI −31.7, −1.5, p = 0.02), and salivary symptoms (CI −28.4, −8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI −21.8, −5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI −13.0, −2.0, p = 0.03).ConclusionsSurgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course.

AbstractIntroductionSurgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi‐center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques.MethodsA retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Comparisons of postoperative complications, SNOT‐22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test.ResultsFive hundred and one patients were identified. The median tumor size was 2.1 cm, and 64% were non‐functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3 cm), medial cavernous sinus wall resection, and high‐flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p < 0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication.ConclusionThe effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high‐flow intraoperative CSF leaks.