Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma

Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0.01). Furthermore, microbial populations can separate tumors by tobacco status (P < 0.008), but not by alcohol status (P = 0.41). If our subhypothesis regarding a mechanistic link from microorganism to carcinogenesis via inflammation and consequent aberrant DNA methylation is correct, then we should see hypermethylation of relevant genes associate with specific microbiomic profiles. Methylation analysis in four genes (MDR1, IL8, RARB, TGFBR2) previously linked to HNSCC or inflammation shows significantly increased methylation in tumor samples compared with normal oral mucosa. Of these, MDR1 promoter methylation associates with specific microbiomic profiles in tumor over normal mucosa. Additionally, we report that MDR1 methylation correlates with regional nodal metastases in the context of two specific bacterial subpopulations, Enterobacteriaceae and Tenericutes (P < 0.001 for each). These associations may lead to a different, and potentially more comprehensive, perspective on the pathogenesis of HNSCC, and support further exploration of mechanistic linkage and, if so, novel therapeutic strategies such as demethylating agents and probiotic adjuncts, particularly for patients with advanced or refractory disease

Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophthalmology, nuclear medicine and endocrinology

BackgroundPostoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement.MethodsA multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations.ResultsConsensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management.ConclusionSalivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163491/2/hed26417.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163491/1/hed26417_am.pd

An Experimental Analysis Of the Demand For Payday Loans

The payday loan industry is one of the fastest growing segments of the consumer financial services market in the United States. We design an environment similar to the one that payday loan customers face and then conduct a laboratory experiment to examine what effect, if any, the existence of payday loans has on individuals\u27 abilities to manage and to survive financial setbacks. Our primary objective is to examine whether access to payday loans improves or worsens the likelihood of financial survival in our experiment. We also test the degree to which people\u27s use of payday loans affects their ability to survive financially. We find that payday loans help the subjects to absorb expenditure shocks and therefore survive financially. However, subjects whose demand for payday loans exceeds a certain threshold level are at a greater risk than a corresponding subject in the treatment in which payday loans do not exist

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The use of biopsy in the evaluation of pediatric nasopharyngeal masses

Pediatric nasopharyngeal tumors are rare, and few clinicians possess more than anecdotal experience. The differential diagnosis includes a diverse group of benign and malignant tumors, but can be narrowed further based on the clinical and radiographic appearance of the mass. Nasopharyngeal angiofibroma has such characteristic angiographic and CT imaging that many authors suggest biopsy is not essential in the evaluation of this lesion. We present a case of a pediatric nasopharyngeal neoplasm with angiographic, CT, and clinical findings consistent with angiofibroma. We then discuss the preoperative evaluation of, operative approach to, and postoperative staging and treatment of the biopsy-proven embryonal rhabdomyosarcoma. A review of the literature pertinent to this case is presented, and recommendations made concerning biopsy of lesions resembling juvenile nasopharyngeal angiofibroma. We believe this report reaffirms the use of histologic study whenever possible, in addition to radiographic imaging, in the diagnosis of pediatric nasopharyngeal masses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28324/1/0000080.pd

Lateral Arm Microvascular Flap in Head and Neck Reconstruction

OBJECTIVES: To report our results of a study of 28 patients who underwent sequential reconstructions of the head and neck using the lateral arm flap. To discuss the situations where we have found the procedure useful, report the complication rates, and delineate the advantages and disadvantages of using this flap. DESIGN: A clinical series of patients was followed up prospectively. The swallowing function of a subgroup that underwent oropharyngeal reconstruction was compared with that of a simultaneous control group that underwent reconstruction with the pectoralis major flap. SETTING: University medical center. PARTICIPANTS: Patients with malignant neoplasms of the head and neck who underwent resections and reconstruction with the lateral arm flap. INTERVENTIONS: Twenty-eight patients underwent head and neck reconstruction using lateral arm flaps. In 17 patients, the lateral arm flaps were used for pharyngeal and posterior oral cavity defects. Thirteen of these patients underwent reinnervation. Nine combined palatal and midfacial defects were reconstructed, and 1 lateral facial defect was reconstructed. Most cases were advanced malignant neoplasms and represented a selected minority of similar resections performed at our institutions. Three maxillary reconstructions were performed secondarily. All other reconstructions were performed at the time of tumor ablation. MAIN OUTCOME MEASURES: Data were collected regarding flap survival, return of sensation in flaps, complication rates, and the ability to feed orally. RESULTS: All flaps survived in their entirety. Of 7,5 tested flaps acquired sensation. Of 14 patients with large oropharyngeal defects, 8 resumed early oral feeding and all survivors eventually obtained nutrition orally. The ability to swallow was superior to the results obtained in a retrospective analysis of a group reconstructed using pectoralis major flaps. CONCLUSIONS: A unique feature of this flap is that it incorporates both thin skin from the proximal forearm and thicker skin from the upper arm. This is ideal for an oropharyngeal defect, where the thin malleable portion can be used in the posterior oral cavity or pharyngeal wall and the thicker portion in the tongue base. Either portion can be used alone as well. The availability of intermediate tissue bulk can also be advantageous for midfacial reconstruction. Sensation can be reliably reconstituted with this flap. We think that the lateral arm flap is versatile and has particularly low donor-site morbidity.Arch Otolaryngol Head Neck Surg. 1997;123:830-83