Postoperative opioid-prescribing practices in otolaryngology: Evidence-based guideline outcomes.

Objectives: We previously reported that >50% of postoperative opioids prescribed at our institution went unused for common otolaryngologic procedures. Based on these findings, we instituted multimodal, evidence-based guidelines for postoperative pain management. In the second part of our multiphasic study, we evaluated the effects of these guidelines on (1) quantity of unused opioids, (2) patient satisfaction, and (3) institutional perceptions toward the opioid epidemic and prescribing guidelines. Methods: Standardized, procedure-specific opioid prescription guidelines were created using prospective data from the first phase of our study and evidence from current literature. Again, we examined sialendoscopy, parotidectomy, parathyroidectomy/thyroidectomy, and transoral robotic surgery (TORS). Patients were surveyed at their first postoperative appointment. Groups from Phases I and II were compared. Attending physicians were surveyed before the start of the multiphasic project and after prescribing guidelines were implemented. Results: Prescribing guidelines led to an average reduction in prescribed morphine milligram equivalents (MME) per patient by: 48% (sialendoscopy), 63% (parotidectomy), 60% (para/thyroidectomy), and 42% (TORS). Average used MME per patient for parotidectomy was significantly reduced (64%). The proportion of unused MME per patient and patient satisfaction scores did not significantly change after guidelines were implemented. Conclusion: Implementation of opioid-prescribing guidelines and the use of multimodal analgesia substantially reduced the amount of opioids prescribed across all procedures without impacting patient satisfaction. Level of Evidence: 2.

Head and Neck Reconstruction in Patients with Polycythemia Vera: Case Series and Literature Review.

Background Polycythemia vera (PV) is a myeloproliferative disease with overproduction of erythrocytes, leukocytes, and platelets causing an increased risk of both thrombosis and hemorrhage. There are limited reports and no established guidelines for managing such patients undergoing reconstructive surgery. Methods We present four patients with PV and head and neck cancer who required reconstruction after resection and provide a review of the current literature. Results Preoperatively, patients on cytoreductive therapy continued with their treatment throughout their hospital course and had hematologic parameters normalized with phlebotomy or transfusions if needed. Two patients who underwent free flap surgery (cases 1 and 2) had postoperative courses complicated by hematoma formation and persistent anemia, requiring multiple transfusions. Cases 3 and 4 (JAK2+ PV and JAK2- PV, respectively) underwent locoregional flap without postoperative complications. Conclusion Concomitant presentation of PV and head and neck cancer is uncommon and presents unique challenges for the reconstructive surgeon. Overall, we recommend that patients should have hematologic parameters optimized prior to surgery, continue ruxolitinib or hydroxyurea, and hold antiplatelet/anticoagulation per established department protocols. It is essential to engage a multidisciplinary team involving hematology, head and neck and reconstructive surgery, anesthesia, and critical care to develop a standardized approach for managing this unique subset of patients.

E-cigarette or Vaping Product Use Associated Lung Injury Among Three Young Adults: A Retrospective Case Series From Delaware.

BACKGROUND: E-cigarette or vaping associated lung injury (EVALI) is a lung disease associated with an inflammatory response to the vaping fluid. Currently, diagnosis remains elusive without definitive biomarkers. CASE PRESENTATION: Herein, we describe three cases of EVALI among 18- to 21-year-old patients ranging from mild to severe. All cases presented with a combination of respiratory, gastrointestinal, and constitutional symptoms. Oxygen support and level of medical care varied based on disease severity. Bilateral pulmonary opacities were observed on chest imaging in each case. Additionally, each case had markedly elevated inflammatory markers, specifically C-reactive protein (CRP). None of these patients improved with intravenous (IV) antibiotics and all required IV corticosteroid therapy to achieve clinical improvement. CONCLUSION: EVALI should be suspected among young, otherwise healthy patients who present with new-onset hypoxia, non-specific gastrointestinal symptoms, and endorse a history of vaping. Though considered a diagnosis of exclusion, diagnosing EVALI requires thorough history taking. Inflammatory studies, CRP, and erythrocyte sedimentation rate (ESR) should be considered adjunctive biomarkers to aid clinicians when the diagnosis remains unclear. Corticosteroids are the mainstay of treatment and patients should have close follow-up whether or not they require hospitalization.

Disseminated Tuberculosis Involving Lung, Peritoneum, and Endometrium in an Immunocompetent 17-Year-Old Patient.

A 17-year-old Guatemalan female with a recent history of spontaneous abortion requiring dilation and curettage at 16 weeks' gestation presented two weeks post-procedure to a pediatric hospital for three days of worsening generalized abdominal pain, diarrhea, fevers, and cough. The patient's vital signs showed hypoxia, tachypnea, tachycardia, and hypotension; she was alert and oriented with a thin body habitus and suprapubic abdominal tenderness without rebound, guarding, or hepatosplenomegaly. She had no crackles, rales, or wheezing on lung examination. Labs revealed neutrophilic leukocytosis, acute kidney injury, transaminitis, and coagulopathy. Pelvic ultrasound demonstrated a septated pelvic fluid collection with an endometrial thickening. CT abdomen and pelvis showed significant nodular omental thickening and ascites. CT angiogram of the chest demonstrated an apical lung cavity and bilateral micro-nodularity without lymphadenopathy. Due to concern for septic shock secondary to endometritis, the patient was started on broad-spectrum antibiotics and intubated for acute hypoxic respiratory failure. Repeat dilation and evacuation revealed degenerative first trimester products of conception and necrotizing granulomatous endometritis with Mycobacterium tuberculosis (M. tuberculosis) bacteria. Paracentesis indicated tuberculosis (TB) in ascites fluid, and bronchoalveolar lavage (BAL) showed pulmonary TB. Human immunodeficiency virus (HIV) screen and serum QuantiFERON®-TB Gold testing were negative. Rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy was initiated alongside piperacillin-tazobactam for the treatment of both disseminated TB and septic abortion. She was extubated with hemodynamic stability, but fevers persisted. Repeat fallopian tube fluid sampling after five weeks of RIPE indicated numerous acid-fast bacilli. The patient's septic clinical picture clouded her TB diagnosis as it appeared unusual that a healthy 17-year-old would concurrently have a septic abortion and disseminated TB; the lack of lymphadenopathy on CT scan also contributed to diagnostic uncertainty. Among patients from endemic regions, TB is a cause of spontaneous abortion. Conversely, during pregnancy, progesterone suppresses the T-helper 1 (Th1) proinflammatory response and increases susceptibility to TB. Peripartum women are at higher risk for disseminated TB, and postpartum women are twice as likely to experience reactivation of latent TB than nonpregnant women. Disseminated TB must be considered in pregnant adolescents presenting with appropriate clinical characteristics and imaging findings.

Empiric Treatment for Suspected Malaria in the United States: A Case Report.

Malaria in the United States is rare and most commonly presents among returning travelers from endemic areas. Diagnosis is classically dependent on a positive blood smear or polymerase chain reaction (PCR) test. The objective of this case report is to highlight a case of suspected malaria in a high-risk individual with negative diagnostic testing where a trial of empiric treatment was initiated based on clinical presentation after a thorough discussion of risks and benefits. However, empiric treatment based on a single case is limiting. We present a case of a 56-year-old man with extensive travel history throughout Asia, who presented after multiple episodes of unprovoked 24-hour fevers over the past seven years. A thorough rheumatologic and infectious inpatient workup was negative and oncology was consulted with low suspicion for malignancy. However, based on clinical presentation and history, malaria remained highly suspected and an empiric trial of anti-malarial treatment was initiated. One year after receiving treatment, the patient has not experienced any further febrile episodes. The efficacy of blood smears and PCR may be influenced by the malarial strain, as some species have low circulating biomass. Therefore, blood smears and PCR testing may not always be diagnostic. Clinical signs supportive of a malarial infection include fever, rigors, chills, hepato/splenomegaly, hyperbilirubinemia, and thrombocytopenia. Malaria is endemic to many regions outside of Africa, including Asia, and should be considered in any returning traveler with recurrent fevers.

Allergy and Lung Injury Among Rescue Workers Exposed to the World Trade Center Disaster Assessed 17 Years After Exposure to Ground Zero.

OBJECTIVE: Investigate the following in rescue and cleanup workers exposed to the World Trade Center (WTC) disaster 17 years post-fallout: (1) allergic hypersensitivity; (2) spirometry; (3) impulse oscillometry; and (4) the reversibility of airway hyperresponsiveness and distal airways narrowing pre- and post-bronchodilator. METHODS: In subjects (n = 54) referred to our clinic from the WTC Health Program for management of allergy-immunology services, environmental allergy testing, impulse oscillometry (IOS), and spirometry results were retrospectively reviewed to determine the long-term impact of exposure to the WTC fallout. RESULTS: Rescue and cleanup workers exposed to the WTC fallout had a high incidence of allergic hypersensitivity and had evidence of permanent small airways dysfunction characterized by distal airways narrowing and airway hyperresponsiveness. CONCLUSION: Following exposure to the WTC disaster, the patients in our cohort developed allergic hypersensitivity and severe lung injury with only partial reversibility.

Postoperative opioid-prescribing practices in otolaryngology: A multiphasic study.

OBJECTIVES: In otolaryngology, postoperative pain management lacks evidence-based guidelines. We designed a prospective, multiphasic study aimed to develop evidence-based guidelines for postoperative pain management within our institution. In this first phase of our project, we investigated opioid prescription and consumption as well as pain trends for common otolaryngologic procedures. METHODS: Patients (n = 161) who underwent procedures between July 2018 and February 2019 were surveyed on their postoperative opioid usage and pain from day of discharge to first clinic visit. Opioid prescriptions were converted to standardized units of morphine milligram equivalents (MME). The procedures selected for analysis were parathyroidectomy/thyroidectomy, parotidectomy, sialendoscopy, and transoral robotic surgery resection (TORS). RESULTS: In total, 19,748 MME were prescribed: 8,588 MME (43.5%) were used, leaving 11,159 MME (56.5%) unused. TORS average MME used: 221 ± 227; total MME unused: 38%. Sialendoscopy average MME used: 31 ± 46; total MME unused: 67%. Parathyroidectomy/thyroidectomy average MME used: 30 ± 37; total MME unused: 66%. Parotidectomy average MME used: 43 ± 53; total MME unused: 65%. Male gender, smoking (current and former), and psychiatric medication use were positive predictors of opioid consumption in postoperative patients (P < 0.001). CONCLUSION: At our institution, over 50% of prescribed postoperative opioids went unused. This was most pronounced for nonmucosal surgeries. Postoperative pain management should account for this to minimize unnecessary opioid prescriptions. Based on our findings and review of current literature, we are in the process of developing prescribing recommendations to be implemented within our institution. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:659-665, 2020.

No Stones, Some Groans, and Psychiatric Overtones with "Non-specific" Splenomegaly.

Hypercalcemia is a potentially life-threatening electrolyte imbalance that is commonly caused by hyperparathyroidism, supplement or medication use, and/or malignancy. Splenomegaly is commonly a non-specific finding, but in the setting of hypercalcemia, may provide diagnostic insight into the underlying pathology and warrant further evaluation. A 70-year-old man presented from his outpatient provider with serum calcium > 15 mg/dL with complaints of one-month fatigue, weakness, poor oral intake, 10 lbs. unintentional weight loss, and periodic confusion noted by his wife. He received an extensive inpatient workup which was non-diagnostic. Splenomegaly was observed on radiographic imaging and reported as "nonspecific". Following discharge, denosumab was required to manage the hypercalcemia. Eventually, a diagnosis of primary splenic lymphoma was made months later. Laparoscopic splenectomy was planned but was advanced to an open laparotomy intraoperatively due to the rapid growth of the neoplasm. Early and close investigation of the spleen is warranted when splenomegaly presents in the setting of hypercalcemia and, as in this case, may prevent significant therapeutic burden.

PANCYTOPENIA AND LYMPHOID ORGAN HYPERPLASIA IN A PATIENT WITH GRAVES DISEASE: RESPONSE TO ANTITHYROID DRUG THERAPY.

OBJECTIVE: In rare instances, cytopenias manifest as a complication of thyrotoxicosis. Here, we report a case of Graves disease (GD) thyrotoxicosis presenting as pancytopenia that resolved with antithyroid therapy. METHODS: A 35-year-old male presented with fever and chills following an outpatient colonoscopy. Initial blood work revealed pancytopenia. Workup included viral antigen titers, blood cultures, rheumatologic antibodies, inflammatory markers, immunocompetency, nutrient deficiency, metal toxicity, and malignancy. Bone marrow aspirate was analyzed by microscope, flow cytometry, fluorescence in situ hybridization, and genetic analysis. Computed tomography scan of the chest, abdomen, and pelvis was obtained. Thyroid labs included thyroid-stimulating hormone, total triiodothyronine, free thyroxine, thyroid-stimulating immunoglobulin, anti-thyroid peroxidase antibody, and radioiodine uptake scan. RESULTS: All workup above was non-revelatory except as follows. Imaging revealed thymic hyperplasia and splenomegaly. Thyroid labs revealed thyroid-stimulating hormone <0.02 µIU/mL (reference range is 0.30 to 5.00 µIU/mL), free thyroxine of 4.7 ng/dL (reference range is 0.7 to 1.7 ng/dL), total triiodothyronine of 191 pg/mL (reference range is 90 to 180 pg/mL), thyroid-stimulating immunoglobulin of 522% (reference range is <140%). Bone marrow biopsy was consistent with a reactive process suggesting an infectious or autoimmune process. Radioiodine uptake scan confirmed GD. He was discharged on antithyroid medication. Two-month follow-up labs revealed improved cell counts; his absolute neutrophil count was 1.94 × 109 cells/L (reference range is 1.50 to 8.00 × 109 cells/L), hemoglobin was 12.9 g/dL (reference range is 14.0 to 17.0 g/dL), and platelets were 153 × 109 cells/L (reference range is 140 to 400 × 109 cells/L). Definitive treatment was obtained with 12 mCi of 131-iodine. CONCLUSION: Pancytopenia and lymphoid organ hyperplasia (splenomegaly, thymic hyperplasia, and lymphadenopathy) have been previously reported to be associated with thyrotoxicosis secondary to GD, rarely simultaneously, and manifest from both thyrotoxic and immunologic mechanisms. After excluding alternative life-threatening pathologies, in such presentations, GD should be considered and treated if confirmed.

Development of an electronic health message system to support recovery after stroke: Inspiring Virtual Enabled Resources following Vascular Events (iVERVE).

PURPOSE: Worldwide, stroke is a leading cause of disease burden. Many survivors have unmet needs after discharge from hospital. Electronic communication technology to support post-discharge care has not been used for patients with stroke. In this paper, we describe the development of a novel electronic messaging system designed for survivors of stroke to support their goals of recovery and secondary prevention after hospital discharge. PARTICIPANTS AND METHODS: This was a formative evaluation study. The design was informed by a literature search, existing data from survivors of stroke, and behavior change theories. We established two working groups; one for developing the electronic infrastructure and the other (comprising researchers, clinical experts and consumer representatives) for establishing the patient-centered program. Following agreement on the categories for the goal-setting menu, we drafted relevant messages to support and educate patients. These messages were then independently reviewed by multiple topic experts. Concurrently, we established an online database to capture participant characteristics and then integrated this database with a purpose-built messaging system. We conducted alpha testing of the approach using the first 60 messages. RESULTS: The initial goal-setting menu comprised 26 subcategories. Following expert review, another 8 goal subcategories were added to the secondary prevention category: managing cholesterol; smoking; physical activity; alcohol consumption; weight management; medication management; access to health professionals, and self-care. Initially, 455 health messages were created by members of working group 2. Following refinement and mapping to different goals by the project team, 980 health messages across the health goals and 69 general motivational messages were formulated. Seventeen independent reviewers assessed the messages and suggested adding 73 messages and removing 16 (2%). Overall, 1,233 messages (18 administrative, 69 general motivation and 1,146 health-related) were created. CONCLUSION: This novel electronic self-management support system is ready to be pilot tested in a randomized controlled trial in patients with stroke.

Development of MGD007, a gpA33 x CD3-Bispecific DART Protein for T-Cell Immunotherapy of Metastatic Colorectal Cancer.

We have developed MGD007 (anti-glycoprotein A33 x anti-CD3), a DART protein designed to redirect T cells to target gpA33 expressing colon cancer. The gpA33 target was selected on the basis of an antibody-based screen to identify cancer antigens universally expressed in both primary and metastatic colorectal cancer specimens, including putative cancer stem cell populations. MGD007 displays the anticipated-bispecific binding properties and mediates potent lysis of gpA33-positive cancer cell lines, including models of colorectal cancer stem cells, through recruitment of T cells. Xenograft studies showed tumor growth inhibition at doses as low as 4 µg/kg. Both CD8 and CD4 T cells mediated lysis of gpA33-expressing tumor cells, with activity accompanied by increases in granzyme and perforin. Notably, suppressive T-cell populations could also be leveraged to mediate lysis of gpA33-expressing tumor cells. Concomitant with CTL activity, both T-cell activation and expansion are observed in a gpA33-dependent manner. No cytokine activation was observed with human PBMC alone, consistent with the absence of gpA33 expression on peripheral blood cell populations. Following prolonged exposure to MGD007 and gpA33 positive tumor cells, T cells express PD-1 and LAG-3 and acquire a memory phenotype but retain ability to support potent cell killing. In cynomolgus monkeys, 4 weekly doses of 100 µg/kg were well tolerated, with prolonged PK consistent with that of an Fc-containing molecule. Taken together, MGD007 displays potent activity against colorectal cancer cells consistent with a mechanism of action endowed in its design and support further investigation of MGD007 as a potential novel therapeutic treatment for colorectal cancer. Mol Cancer Ther; 17(8); 1761-72. ©2018 AACR.

Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance.

Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered. Nonsequestered MCGA (NS-MGCA) egressed from normal tubules, as evidenced by their ability to interact with systemically injected antibodies and form localized immune complexes outside the Sertoli cell barrier. NS-MGCA derived from cell fragments that were discarded by spermatids during spermiation. They egressed as cargo in residual bodies and maintained Treg-dependent physiological tolerance. In contrast, sequestered MGCA (S-MGCA) were undetectable in residual bodies and were nontolerogenic. Unlike postvasectomy autoantibodies, which have been shown to mainly target S-MGCA, autoantibodies produced by normal mice with transient Treg depletion that developed autoimmune orchitis exclusively targeted NS-MGCA. We conclude that spermiation, a physiological checkpoint in spermatogenesis, determines the egress and tolerogenicity of MGCA. Our findings will affect target antigen selection in testis and sperm autoimmunity and the immune responses to CTA in male cancer patients.

NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In addition, we found that VIP inhibits NFAT nuclear translocation in primary human pulmonary artery smooth muscle cells (PASMC). Early activation of NFATc3 in IPF patients may contribute to disease progression and the increase in VIP expression could be a protective compensatory mechanism.

Surgical treatment of far lateral lumbar disc herniation: a safe and simple approach.

Lumbar discectomy is one of the most commonly performed neurosurgical procedure. Far lateral disc herniations (FLDH) make up a minor portion of the total discectomy workload for spine surgeons. Due to their lower incidence, as well as their different anatomical positioning compared to the more common para-median disc herniation, the surgical procedures involved in releasing the neural compression caused by FLDHs are often challenging and at times frustrating to most spine surgeons, resulting in suboptimal outcomes for the patient related to the higher risk of spinal instability from facet joint disruption and may even be associated with nerve root injury. We discuss here a safe and simple approach to tackle FLDH.

Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent antitumor activity.

PURPOSE: The goal of this research was to harness a monoclonal antibody (mAb) discovery platform to identify cell-surface antigens highly expressed on cancer and develop, through Fc optimization, potent mAb therapies toward these tumor-specific antigens. EXPERIMENTAL DESIGN: Fifty independent mAbs targeting the cell-surface immunoregulatory B7-H3 protein were obtained through independent intact cell-based immunizations using human tissue progenitor cells, cancer cell lines, or cell lines displaying cancer stem cell properties. Binding studies revealed this natively reactive B7-H3 mAb panel to bind a range of independent B7-H3 epitopes. Immunohistochemical analyses showed that a subset displayed strong reactivity to a broad range of human cancers while exhibiting limited binding to normal human tissues. A B7-H3 mAb displaying exquisite tumor/normal differential binding was selected for humanization and incorporation of an Fc domain modified to enhance effector-mediated antitumor function via increased affinity for the activating receptor CD16A and decreased binding to the inhibitory receptor CD32B. RESULTS: MGA271, the resulting engineered anti-B7-H3 mAb, mediates potent antibody-dependent cellular cytotoxicity against a broad range of tumor cell types. Furthermore, in human CD16A-bearing transgenic mice, MGA271 exhibited potent antitumor activity in B7-H3-expressing xenograft models of renal cell and bladder carcinoma. Toxicology studies carried out in cynomolgus monkeys revealed no significant test article-related safety findings. CONCLUSIONS: This data supports evaluation of MGA271 clinical utility in B7-H3-expressing cancer, while validating a combination of a nontarget biased approach of intact cell immunizations and immunohistochemistry to identify novel cancer antigens with Fc-based mAb engineering to enable potent antitumor activity.