Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

Background: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear.

Methods: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021.

Safety and Predictors of 30-Day Adverse Events of Laryngeal Framework Surgery: An Analysis of ACS-NSQIP data.

Objectives/hypothesis: To characterize and identify predictors of 30-day adverse events in patients undergoing laryngeal framework surgery (LFS).

Study Design: This study is a retrospective analysis of the National Surgical Quality Improvement dataset.

Methods: LFS cases were identified from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database from 2008 to 2018.

A diverse collection of B cells responded to HIV infection in infant BG505.

Increasing evidence suggests infants develop unique neutralizing antibody (nAb) responses to HIV compared to adults. Here, we dissected the nAb response of an infant whose virus is in clinical trials as a vaccine immunogen, with a goal of characterizing the broad responses in the infant to this antigen. We isolated 73 nAbs from infant BG505 and identified a large number of clonal families.

A Guide to Creating a Gender-Affirming Environment Through a Community Lens Approach.

Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) communities continue to experience health care disparities and inequities due to a shortage of trained health care providers, despite increased attention to LGBTQI+ health care. Many settings are starting to integrate gender-affirming health care and focus training on the provision of hormonal therapy, medications to decrease the risk of human immunodeficiency acquisition, and referrals to surgeons for affirming surgical procedures. A vital component to providing inclusive and comprehensive care involves community input, engagement, and buy-in.

Assessing the Clinical Utility of the Early Postoperative Pharyngogram in Hypopharyngeal Surgery for Dysphagia.

Objectives/hypothesis: To evaluate the clinical utility of postoperative contrast x-ray pharyngograms (XRP) for detecting pharyngoesophageal leaks following hypopharyngeal dysphagia surgery.

Study Design: Retrospective cohort study.

Methods: Medical records were reviewed of patients undergoing endoscopic (E-) or open (O-) Zenker's diverticulectomy (-ZD) with cricopharyngeal myotomy (-CPM) and CPM alone from 2008 to 2020 at one academic institution.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

Background: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear.

Methods: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses.

Results: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS).

A Novel Curriculum for Medical Student Training in LGBTQ Healthcare: A Regional Pathway Experience.

Background: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals face considerable health disparities, often due to a lack of LGBTQ-competent care. Such disparities and lack of access to informed care are even more staggering in rural settings. As the state medical school for the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region, the University of Washington School of Medicine (UWSOM) is in a unique position to train future physicians to provide healthcare that meets the needs of LGBTQ patients both regionally and nationally.

Case of Esophageal Perforation and Repair with a Supraclavicular Artery Island Fascial Flap 15 Years After Anterior Spine Surgery.

Background: Esophageal perforation represents a rare but potentially life-threatening complication of an anterior cervical diskectomy and fusion (ACDF). Delayed presentations of esophageal perforation more than 10 years following surgery are exceedingly rare and difficult to diagnose. Here, we discuss the case of an 80-year-old man who presented to the emergency department with progressive dysphagia 15 years after his ACDF.

The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3.

Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication is not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such as IFITM3, have been identified largely using overexpression studies. Here, we tested whether diverse ZIKV strains differed in their susceptibility to IFN-I-mediated restriction and the contribution of IFITM3 to this restriction.

Zika Virus Circulates at Low Levels in Western and Coastal Kenya.

Background: Zika virus (ZIKV) was discovered over 70 years ago in East Africa, but little is known about its circulation and pathogenesis there.

Methods: We screened 327 plasma samples collected 2-12 months after febrile illness in Western and coastal Kenya (1993-2016) for binding and neutralizing antibodies to distinguish ZIKV and dengue virus (DENV) responses, which we found were common in coastal Kenya.

Results: Two cases had durable ZIKV-specific antibodies and 2 cases had ZIKV antibodies at similar levels as DENV antibodies.

Diversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical Transmission.

Infants of HIV-positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer.

Identification of HIV gp41-specific antibodies that mediate killing of infected cells.

Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity.

Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy.

Objective: To evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy.

Study Design: Retrospective cohort study.

Setting: Tertiary care medical center.

Genome sequencing in a case of Niemann-Pick type C.

Adult-onset Niemann-Pick disease type C (NPC) is an infrequent presentation of a rare neurovisceral lysosomal lipid storage disorder caused by autosomal recessive mutations in (∼95%) or (∼5%). Our patient was diagnosed at age 33 when he presented with a 10-yr history of difficulties in judgment, concentration, speech, and coordination. A history of transient neonatal jaundice and splenomegaly with bone marrow biopsy suggesting a lipid storage disorder pointed to NPC; biochemical ("variant" level cholesterol esterification) and ultrastructural studies in adulthood confirmed the diagnosis.

Structural and Functional Analysis of the Allosteric Inhibition of IRE1α with ATP-Competitive Ligands.

The accumulation of unfolded proteins under endoplasmic reticulum (ER) stress leads to the activation of the multidomain protein sensor IRE1α as part of the unfolded protein response (UPR). Clustering of IRE1α lumenal domains in the presence of unfolded proteins promotes kinase trans-autophosphorylation in the cytosol and subsequent RNase domain activation. Interestingly, there is an allosteric relationship between the kinase and RNase domains of IRE1α, which allows ATP-competitive inhibitors to modulate the activity of the RNase domain.

Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70.

Inducible Hsp70 (Hsp70i) is overexpressed in a wide spectrum of human tumors, and its expression correlates with metastasis, poor outcomes, and resistance to chemotherapy in patients. Identification of small-molecule inhibitors selective for Hsp70i could provide new therapeutic tools for cancer treatment. In this work, we used fluorescence-linked enzyme chemoproteomic strategy (FLECS) to identify HS-72, an allosteric inhibitor selective for Hsp70i.

Synthesis and structure–activity relationships of small molecule inhibitors of the simian virus 40 T antigen oncoprotein, an anti-polyomaviral target.

Polyomavirus infections are common and relatively benign in the general human population but can become pathogenic in immunosuppressed patients. Because most treatments for polyomavirusassociated diseases nonspecifically target DNA replication, existing treatments for polyomavirus infection possess undesirable side effects. However, all polyomaviruses express Large Tumor Antigen (T Ag), which is unique to this virus family and may serve as a therapeutic target.