The Effect of JAK1/2 Inhibitors on HIV Reservoir Using Primary Lymphoid Cell Model of HIV Latency.

HIV eradication is hindered by the existence of latent HIV reservoirs in CD4+ T cells. Therapeutic strategies targeting latent cells are required to achieve a functional cure, however the study of latently infected cells from HIV infected persons is extremely challenging due to the lack of biomarkers that uniquely characterize them. In this study, the dual reporter virus HIVGKO was used to investigate latency establishment and maintenance in lymphoid-derived CD4+ T cells. Single cell technologies to evaluate protein expression, host gene expression, and HIV transcript expression were integrated to identify and analyze latently infected cells. FDA-approved, JAK1/2 inhibitors were tested in this system as a potential therapeutic strategy to target the latent reservoir. Latent and productively infected tonsillar CD4+ T cells displayed similar activation profiles as measured by expression of CD69, CD25, and HLADR, however latent cells showed higher CXCR5 expression 3 days post-infection. Single cell analysis revealed a small set of genes, including HIST1-related genes and the inflammatory cytokine, IL32, that were upregulated in latent compared to uninfected and productively infected cells suggesting a role for these molecular pathways in persistent HIV infection. In vitro treatment of HIV-infected CD4+ T cells with physiological concentrations of JAK1/2 inhibitors, ruxolitinib and baricitinib, used in clinical settings to target inflammation, reduced latent and productive infection events when added 24 hr after infection and blocked HIV reactivation from latent cells. Our methods using an established model of HIV latency and lymphoid-derived cells shed light on the biology of latency in a crucial anatomical site for HIV persistence and provides key insights about repurposing baricitinib or ruxolitinib to target the HIV reservoir.

First Locally Acquired Congenital Zika Syndrome Case in the United States: Neonatal Clinical Manifestations.

In the spring of 2017, a full-term infant with microcephaly was delivered in South Florida. During first trimester, the mother presented with fever, nausea, and vomiting. She reported no foreign travel for herself or her partner. The infant's neurologic, ophthalmologic, neuroradiologic, and audiologic findings were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM antibodies and plaque reduction neutralization test. New observations, including peripheral temporal retinal avascularity and peripapillary retinal nerve fiber layer thinning, are presented from this first known case of non-travel-associated CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93-e98.].

A pediatric carotid body tumor.

Carotid body tumors are rare childhood extra-adrenal paragangliomas. We present an 8-year old female with a neck mass mistaken as reactive lymphadenopathy. Computed tomography and magnetic resonance angiography, as well as preoperative embolization and balloon test occlusion, were utilized for planning and management. Surgical excision of the tumor was successful and pathological examination revealed a benign paraganglioma. Surgical treatment is curative for these benign lesions, however rare cases have presented years later with metastatic disease. Therefore, a child, like our patient, will require lifelong surveillance for the development of potential metastasis.

Zika Virus: An Emerging Global Health Threat.

Zika virus (ZIKV) is an emerging healthcare threat. The presence of the mosquito Aedes species across South and Central America in combination with complementary climates have incited an epidemic of locally transmitted cases of ZIKV infection in Brazil. As one of the most significant current public health concerns in the Americas, ZIKV epidemic has been a cause of alarm due to its known and unknown complications. At this point, there has been a clear association between ZIKV infection and severe clinical manifestations in both adults and neonates, including but not limited to neurological deficits such as Guillain-Barré syndrome (GBS) and microcephaly, respectively. The gravity of the fetal anomalies linked to ZIKV vertical transmission from the mother has prompted a discussion on whether to include ZIKV as a formal member of the TORCH [Toxoplasma gondii, other, rubella virus, cytomegalovirus (CMV), and herpes] family of pathogens known to breach placental barriers and cause congenital disease in the fetus. The mechanisms of these complex phenotypes have yet to be fully described. As such, diagnostic tools are limited and no effective modalities are available to treat ZIKV. This article will review the recent advancements in understanding the pathogenesis of ZIKV infection as well as diagnostic tests available to detect the infection. Due to the increase in incidence of ZIKV infections, there is an immediate need to develop new diagnostic tools and novel preventive as well as therapeutic modalities based on understanding the molecular mechanisms underlying the disease.

Predicting revision sinus surgery in allergic fungal and eosinophilic mucin chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis consists of several disease processes. Eosinophilic mucin is found in the subtypes of allergic fungal sinusitis (AFS) and eosinophilic mucin chronic rhinosinusitis (EMCRS). These entities frequently require surgical intervention and have high recurrence rates. OBJECTIVE: We aimed to determine factors in patients with AFS and EMCRS that may be associated with a higher rate of revision surgeries. Our hypothesis is that patients who have polyps, high Lund-Mackay score (LMS), and fungus may have higher revision rates. STUDY DESIGN: Retrospective cohort study. METHODS: This is a retrospective analysis of 117 patients identified over a 5-year period (2005-2009) with the diagnosis of AFS or EMCRS. Contingency tables were created to obtain the odds ratios estimates, and 95% confidence intervals were used to access the association between the outcome (having revision surgery or not) and other clinical binary predictors. RESULTS: Twenty-six of 117 (22%) of the study patients underwent revision surgery. Within the 2-year follow-up period, an additional five of 26 (19%) required another revision surgery. Average LMS was slightly higher in those who underwent revision surgery (16 vs. 13) on a scale of 0 to 24, with an overall mean score of 18 and standard deviation of 6.82 for the whole sample (117). Other factors evaluated were the presence of fungus, polyps, eosinophilic mucin, and the eosinophilic count and medical therapy received. CONCLUSION: The presence of eosinophilic mucin was significantly associated a higher rate of revision surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:59-63, 2017.

Single-stage total endoscopic resection of a plexiform neurofibroma of the maxillary sinus in a child with type 1 neurofibromatosis.

Plexiform neurofibromas are peripheral nerve sheath tumors associated with neurofibromatosis type 1. The maxillary sinus is an extremely rare location of the plexiform neurofibroma and only two adult cases have been previously reported. We report the first case of plexiform neurofibroma of the maxillary sinus occurring in a child with neurofibromatosis type 1. This unusual location presents a management challenge considering the infiltrative nature and the potential malignant degeneration of this type of tumor. MRI is highly valuable to diagnose and plan the surgical approach of the plexiform neurofibroma of the maxillary sinus. Due to the location of the tumor and the patient's age, conservative surgery is highly recommended. We performed an endoscopic total en-bloc resection of the tumor with no recurrence after nine months of follow-up.

Improving the penetration of ototopicals through tympanostomy tubes: role of surfactants.

OBJECTIVE: To evaluate the ability of surfactants to increase the penetration of ototopicals through tympanostomy tubes (TT). METHODS: An in vitro model was used to test the penetration of ototopicals with and without two surfactants (docusate sodium and beractant) through fluoroplastic and titanium TTs. The model was created by placing a TT through a perforation (myringotomy) in a model of the tympanic membrane (silastic sheet) fixed between the ends of two 1 mL syringes. Measurements were recorded of the maximum height various solutions (distilled water, soapy water, ofloxacin otic, ciprofloxacin/dexamethasone otic) achieved before penetrating the TTs (1.27 mm Reuter Bobbin titanium, 1.27 mm fluoroplastic). These same measurements were then performed with the addition of docusate sodium or beractant to the distilled water and each of the ototopical solutions. RESULTS: The addition of docusate sodium significantly increased the penetration of water and ofloxacin otic through both types of TTs. It significantly increased penetration of ciprofloxacin/dexamethasone otic through fluoroplastic tubes with a trend towards increased penetration through titanium tubes. Adding beractant showed a modest trend toward increasing the penetration of both ototopicals in fluoroplastic tubes which did not reach statistical significance. CONCLUSIONS: These results demonstrate that the penetration of ototopicals through TTs can be improved by the addition of surfactants. Increasing the penetration of ototopicals may make them more effective in treating TT otorrhea. However, we strongly discourage clinicians from using these compounds clinically until their safety has been established.

Tonsillectomy and adenoidectomy techniques: past, present and future.

Although the number of procedures has significantly decreased over the past century, tonsillectomy and adenoidectomy are commonly performed surgeries in the pediatric group, with obstructive sleep apnea being the most common indication. Despite the availability of newer technologies, tonsillectomy is still associated with a relatively high risk of postoperative morbidity. Pain and postoperative bleeding can have a significant impact on the child's health and quality of life. This article reviews the currently available techniques for tonsillectomy and adenoidectomy, with their characteristics and potential benefits. No gold standard exists at this point, and further prospective clinical trials are needed in this perspective.

Pediatric obstructive sleep apnea: current management.

Obstructive sleep apnea syndrome (OSAS) is a condition frequently encountered in children, and belongs to a spectrum of diseases called sleep-disordered breathing. Its pathophysiology is related to decreased ventilation despite respiratory effort, leading to episodes of hypopnea and apnea. Left untreated, this condition could have a significant impact on both physical and mental health. Primary snoring is often the presenting symptom reported by parents, and should warrant careful screening for OSAS. Although overnight polysomnography remains the gold standard diagnostic test for OSAS, its feasibility in clinical practice is less obvious, and furthermore, interpretation of its results is not unanimously agreed on. This is why in clinical practice history and physical examination remain among the most useful diagnostic tools. Management of OSAS traditionally includes tonsillectomy and/or adenoidectomy to which most of the cases respond. However, other risk factors and coexisting conditions should be carefully investigated and treated prior to considering surgical treatment.

Management of pediatric airway granular cell tumor: role of laryngotracheal reconstruction.

OBJECTIVE: To discuss the role of laryngotracheal reconstruction (LTR) in granular cell tumor (GCT) and to highlight the importance and seriousness of GCT in pediatric airway cases. METHODS: A historical literature review was performed and a GCT case from the University of Miami Pediatric Otolaryngology Clinic is presented to highlight the role of LTR in the treatment of GCT. RESULTS: A case of a GCT of the laryngotracheal airway is reported and the management is discussed. Histological discussion and a review of the literature are included regarding GCT. This case is the third reported in the English literature of two synchronous GCT lesions of the upper airway repaired with a laryngotracheal reconstruction. CONCLUSIONS: In the authors' experience once conservative management consisting of endoscopic debulking has failed the treatment of choice for GCTs of the pediatric airway that are unresectable is a single stage laryngotracheal reconstruction with negative frozen section pathology to assure total wide local excision.

Differential penetration of ototopicals and water through tympanostomy tubes.

OBJECTIVE: To evaluate the penetration of ototopicals and water through tympanostomy tubes (TT) using a physical model. STUDY DESIGN: An in vitro model was created to measure the ability of various solutions to penetrate a variety of TT. METHODS: A TT was placed through a perforation (myringotomy) in a silastic sheet (tympanic membrane) fixed between the ends of two 1 mL syringes. Measurements were obtained of the maximum height various liquids (tap water, 2% soapy water, ocean water, ofloxacin otic, corticosporin otic, and ciprofloxacin/dexamethasone otic) achieved before penetrating different TTs (1.0 mm or 1.27 mm Paparella silicone, 1.14 mm or 1.27 mm Reuter Bobbin titanium, 1.27 mm Collar Button fluoroplastic or 1.14 mm T-type silicone). RESULTS: Two percent soapy water was significantly more permeable than water and ocean water in all tubes studied. Ciprofloxacin/dexamethasone otic was significantly more permeable than tap water, ocean water, and ofloxacin otic in only the Collar Button fluoroplastic TT. Our results suggest that titanium TTs are more permeable than other TT. Otherwise, ototopicals, tap water, and ocean water behaved similarly across all TT studied. CONCLUSIONS: Our results demonstrate that ototopicals, tap water, and ocean water behave similarly with regard to TT penetration. Ciprofloxacin/dexamethasone otic may have better penetration than other ototopicals. Titanium TT may be easier to penetrate than other TT.

Revision single-stage laryngotracheal reconstruction in children.

In this report, we discuss indications, technique, outcome, and complications of revision single-stage laryngotracheal reconstruction (SSLTR), formulate guidelines to avoid or prevent procedure failure, and establish a protocol for the management of procedure failure. We retrospectively reviewed the charts of 122 patients between the ages of 8 months and 9 years who underwent SSLTR between January 1992 and September 2001 in 2 tertiary care children's medical centers in different cities and assessed the outcomes of patients who underwent revision SSLTR. A total of 122 patients underwent SSLTR, of whom 48 patients underwent anterior and posterior grafting. Of the 122 patients, 13 had revision SSLTR; 8 of these 13 underwent the initial laryngotracheal reconstruction at another institution. Five patients had anterior grafting laryngotracheal reconstruction without stenting, 7 had anterior and posterior grafting with 1 to 21 days of endotracheal intubation, and I had cricotracheal resection and anastomosis. Of the 13 patients, 5 had anterior wall or graft collapse (grade IV stenosis), 4 had subglottic stenosis (grade IV), 2 had circumferential subglottic stenosis (grade III), and 2 had subglottic and glottic stenosis (grade IV). The overall success rate for all patients was 86% (105 of 122). The success rates for the 122 patients were as follows: anterior grafting, 100%; anterior and posterior grafting, 83% (40 of 48); and revision cases, 70% (9 of 13). We conclude that laryngotracheal reconstruction with a costal cartilage rib graft should be considered the procedure of choice for the management of subglottic stenosis. We believe that patients in whom the first procedure fails should have a high chance of success with revision SSLTR if strict guidelines and protocols are followed.

Posterior cartilage graft in single-stage laryngotracheal reconstruction.

PURPOSE: Single-stage laryngotracheal reconstruction (LTR) has gained popularity during the past decade, but few reports discuss posterior grafting. We assessed the indications, treatment, complications, and outcomes for patients who underwent this procedure. METHODS: We reviewed the charts of 120 pediatric patients who underwent LTR at LeBonheur Children's Medical Center or the University of Mississippi Medical Center between January 1992 and September 2000. We identified and evaluated those who had undergone single-stage anterior plus posterior cartilage rib graft reconstruction during this period. RESULTS: Of 120 patients, 56 had anterior graft procedures, and 46 had anterior plus posterior cartilage rib graft reconstruction. The 46 patients included 26 boys and 20 girls (age range, 18 months to 9 years; follow-up periods, 3 months to 6 years). Twenty-one of 46 had circumferential grade III stenosis, 14 had grade IV stenosis, 4 had bilateral vocal cord paralysis, 4 had posterior glottic and subglottic stenosis, and 3 had laryngeal cleft. Eleven of 46 patients had previous procedures and required revision LTR. All 46 patients underwent single-stage reconstruction with temporary stenting using an endotracheal tube for 10 to 24 days; 4 failed required replacement of the tracheotomy tube, and 8 required reintubation after the first extubation. The overall decannulation success rate was 83% (38 of 46). CONCLUSIONS: LTR is the procedure of choice for the surgical management of subglottic stenosis. Although use of a posterior rib graft is technically demanding and requires extensive experience, good results can be obtained when the guidelines are followed.

Orbital infection as a complication of sinusitis: are diagnostic and treatment trends changing?

Orbital infection has long been the most common complication of sinusitis. In light of our increased knowledge of sinusitis, improved diagnostic tools, and new pharmacologic and surgical treatments, we investigated whether trends in diagnosis and treatment are changing. We reviewed the charts of all 43 patients who had been referred to our institution with orbital complications of sinusitis between Jan. 1, 1985, and Dec. 31, 1999. Nine of the 43 patients had been diagnosed between Jan. 1, 1985, and Dec. 31, 1990 (mean: 1.5 patients/yr) and 34 had been diagnosed between Jan. 1, 1991, and Dec. 31, 1999 (mean: 3.8 patients/yr). Of the 43 patients, 27 had cellulitis and 16 had an abscess (one of the 16 had two abscesses--one subperiosteal and one supraorbital). All 17 abscesses were treated surgically. Five of the 7 abscesses operated on from 1985 through 1990 were treated via an open external approach, whereas 7 of the 10 abscesses that were operated on later were treated via an endoscopic approach. We conclude that orbital complications of sinonasal origin are being recognized more frequently than they were in the past and that endoscopy has supplanted the open external approach as the preferred method of drainage.

Intracranial complications of sinusitis: a 15-year review of 39 cases.

Despite improvements in antibiotic therapies and surgical techniques, sinusitis still carries a risk of serious and potentially fatal complications. We examined the charts of 82 patients who had been admitted to the University of Mississippi Medical Center between Jan. 1, 1985, and Dec. 31, 1999, for treatment of complications of sinusitis. Of these 82 patients, 43 had orbital complications and 39 had intracranial complications. In this article, we describe our findings in those patients who had intracranial complications (our findings in patients with orbital complications will be reported in a future article). The most common intracranial complication was meningitis; others were epidural abscess, subdural abscess, intracerebral abscess, Pott's puffy tumor, and superior sagittal sinus thrombosis. Most patients with meningitis were treated with drug therapy only; patients with abscesses were generally treated with intravenous antibiotics and drainage of the affected sinus and the abscess. Advancements in antibiotic therapy, endoscopic surgery, imaging studies, and computer-assisted surgery have helped improve outcomes. Management of these patients should be undertaken immediately and is best achieved via a multidisciplinary approach, involving the otolaryngologist, neurosurgeon, radiologist, anesthesiologist, infection disease specialist, pediatrician, internist, and others.

History and current practice of tonsillectomy.

OBJECTIVE: To review important developments in the history of adenotonsillectomy and describe current methods and results for the operation. STUDY DESIGN: Review. METHODS: Tonsillectomy practices since antiquity were reviewed, with emphasis on introductions of new surgical tools and procedures, anesthesia methods, and patient care practices. Past and current indications for and complications associated with tonsillectomy were also reviewed. RESULTS: Devices used for adenotonsillectomy have included snares, forceps, guillotines, various kinds of scalpels, lasers, ultrasonic scalpels, powered microdebriders, and bipolar scissors. General anesthesia, the Crowe-Davis mouth gag, and methods for controlling bleeding have contributed greatly to success with the operation. Past and current indications for adenotonsillectomy are similar, although the relative importance of some indications has changed. The complication rate has declined, but the problems that do occur remain the same. Currently, cost-effectiveness is a principal concern. CONCLUSION: The instruments and procedures used for adenotonsillectomy have evolved to render it a precise operation. Today, the procedure is a safe, effective method for treating breathing obstruction, throat infections, and recurrent childhood ear disease.

The role of computed tomography and magnetic resonance imaging in patients with sinusitis with complications.

OBJECTIVES: This study compares the use of computed tomography (CT) with magnetic resonance imaging (MRI) and clinical assessment in the diagnosis and surgical management of patients with sinusitis with complications. The common CT findings of patients with intracranial or orbital infection of sinusitis are reviewed. STUDY DESIGN: We reviewed the charts of 82 adult and pediatric patients with the diagnosis of sinusitis with intracranial or orbital infection who were seen at the University of Mississippi Medical Center from January 1985 through December 1999. We assessed the diagnoses and outcomes to determine the most effective use of CT, with or without MRI, in the treatment of these patients. METHODS: Clinical presentations were reviewed, along with the CT and MRI findings, for patients who had sinusitis with complications. Clinical, CT, and MRI findings were compared for accuracy in diagnosing 43 patients with orbital infections and 39 patients with intracranial infections. RESULTS: For patients with orbital complications, most of whom had unilateral ethmoiditis, the diagnostic accuracy was 82% for clinical assessment compared with 91% for CT. For patients with intracranial complications, meningitis was the most common diagnosis, and MRI was more accurate (97%) in determining the diagnosis than CT (87%) or clinical findings (82%). CONCLUSION: CT remains the standard modality for diagnosing sinusitis, but MRI frequently is necessary, especially for patients with intracranial complications. Both diagnostic methods have improved the management and outcomes of patients who have sinusitis with complications.