A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders.

The incidence and prevalence of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC) are increasing ( 1 ). These conditions will inevitably become more widely recognized and better understood. There is currently no Food and Drug Administration (FDA)-approved treatment for EoE, but there are standard-of-care treatments that are well established and widely used. In contrast, there is a paucity of data regarding standard-of-care treatment for non-EoE eosinophilic gastrointestinal disorders (EGID). We identified 3 patients that all achieved clinical and histopathologic remission on dupilumab, a monoclonal antibody that blocks the downstream signaling of interleukin (IL)-4 and IL-13. These patients had extra-esophageal forms of EGID with two patients failing to achieve remission on standard-of-care therapies and one patient experiencing significant side effects on swallowed budesonide therapy. The reduction in mucosal eosinophilia in several GI tract segments in these 3 patients highlights a new potential clinical indication for dupilumab in the treatment of pediatric EGID patients.

Acceleration of the formation of biofilms on contact lens surfaces in the presence of neutrophil-derived cellular debris is conserved across multiple genera.

Purpose: We have previously shown that invasive strains of Pseudomonas aeruginosa exploit the robust neutrophil response to form biofilms on contact lens surfaces and invade the corneal epithelium. The present study investigated the ability of multiple bacterial genera, all commonly recovered during contact lens-related infectious events, to adhere to and form biofilms on contact lens surfaces in the presence of neutrophils. Methods: Five reference strains from the American Type Culture Collection were used: P. aeruginosa, Serratia marcescens, Stenotrophomonas maltophilia, Staphylococcus aureus, and Staphylococcus epidermidis. Each bacterial strain was incubated overnight with or without stimulated human neutrophils in the presence of an unworn contact lens. Standard colony counts and laser scanning confocal microscopy of BacLight-stained contact lenses were used to assess bacterial viability. Three-dimensional modeling of lens-associated biofilms with Imaris software was used to determine the biofilm volume. Lenses were further examined using scanning electron microscopy. Results: Less than 1% of the starting inoculum adhered to the contact lens surface incubated with bacteria alone. There were no differences in adhesion rates to contact lens surfaces between bacteria in the absence of neutrophils for either the Gram-negative or Gram-positive test strains. Bacterial adhesion to contact lens surfaces was accelerated in the presence of human neutrophils for all test strains. This effect was least evident with S. epidermidis. There was also an increase in the number of viable bacteria recovered from contact lens surfaces (p<0.001 for the Gram-negative and Gram-positive test strains, respectively) and in biofilm volume (p<0.001 for the Gram-negative test strains, p = 0.005 for S. aureus). Conclusions: These results show that in addition to P. aeruginosa, other bacteria commonly encountered during contact lens wear possess the capacity to utilize neutrophil-derived cellular debris to facilitate colonization of the lens surface. These data suggest that this phenomenon is conserved among multiple genera. Thus, during contact lens wear, the presence of inflammation and the accumulation of neutrophil debris under the posterior lens surface likely contribute to colonization of the lens. Further studies are needed to correlate these findings with risk for infection in an animal model.

Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb) to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

Disparity in Treatment Receipt by Race and Treatment Guideline Revision Years for Stage 1A Non-Small Cell Lung Cancer Patients in the US.

INTRODUCTION: Treatment guideline revision introduced by the National Comprehensive Cancer Network (NCCN) is referred to by about 95% of the United States (US) oncologists in treatment decision-making for stage 1A non-small cell lung cancer. It is vital to account for this factor that affects the standard treatment receipt among stage 1A patients, with about a 75% survival rate if treated on time. The first choice for medically fit patients is lobectomy; however, over the decades since the initial guidelines were published, several medical advances have introduced trends in treatment receipt along with other sociodemographic factors that could help identify survival outcomes associated with treatment receipt. Establishing the role of treatment guideline revision years is important to determine a close to true causal relationship in racial treatment disparities. METHODS: US national cancer registry data for all US counties and historical Area Health Resource Files for the study period 1988-2015 were utilized. Logistic regression analysis was adjusted for clustering of standard errors at the state level and for time-invariant unobserved factors for the year of diagnosis and county. The time-invariant unobservable for each year of diagnosis and county specificity were accounted for by including their dummy variables in the regression model with standard errors clustered at the state level. RESULTS: Black patients, Medicaid beneficiaries, large fringe metropolitan residents, and those diagnosed post-2007 treatment revisions years are less likely to receive lobectomy, which is the standard treatment guideline for medically fit patients. CONCLUSION: The study concludes that there exists a difference in treatment type received among stage 1A NSCLC patients in the US by race, socioeconomic status, and treatment guideline revisions.

Using corticosteroids to treat sudden sensorineural hearing loss in pregnancy: A case report and literature review.

Sudden sensorineural hearing loss (SSNHL) can manifest in pregnancy, but very few cases of SSNHL in pregnancy have been reported and none has been reported in the United States. Additionally, there are no established guidelines for how to treat SSNHL in pregnancy. The purpose of this report is to describe how SSNHL presents in pregnancy, to evaluate other etiologies and discuss current treatment options. A 35-year-old parous woman at 22 weeks of gestation, with a 2-week history of left-sided hearing loss, was shown to have a speech recognition threshold of 70 dB in her left ear. Otolaryngology confirmed the diagnosis of SSNHL. The patient was prescribed an oral prednisone taper that helped alleviate the hearing loss. She had an uncomplicated delivery and treatment with corticosteroids had no adverse consequences for the patient. After ruling out etiologies of SSNHL, corticosteroids may be used safely and efficaciously to treat SSNHL during the second trimester of pregnancy.

Conservative Management of Placenta Accreta Using Helium Plasma Focused Radiofrequency Energy: A Surgical Technique.

The incidence of abnormal placentation has escalated due to the increase in cesarean sections. Adherent placentas are associated with significant maternal morbidity and mortality and often result in cesarean hysterectomy due to life-threatening hemorrhage. The purpose of these case reports is to describe conservative management of placenta accreta by utilizing a helium plasma device to fulgurate the placental bed. Placenta accreta is associated with a 7% mortality rate and 60% morbidity rate. Conservative treatment for uterine preservation include embolization, placenta left in-situ, uterine balloon tamponade, and methotrexate. Complications of these options include hemorrhage, endometritis, and morbidly adherent placentas (MAP) recurrence in subsequent pregnancies. The helium plasma device utilizes radiofrequency (RF) to ionize helium into a plasma beam capable of coagulating and fulgurating tissue with high precision and minimal thermal spread. This instrument is Food and Drug Administration (FDA) approved for surgical coagulation and fulguration, but has not been evaluated in the treatment of placenta accreta at the time of a cesarean section. The helium plasma device was used to fulgurate the placenta accreta at 40% power 4 L/min gas flow for 30 seconds, providing adequate hemostasis to the 12.76 cc of retained placental bed. Estimated blood loss was 560 cc. The patient remained hemodynamically stable and had no complications at follow up. The device provided efficient management of placenta accreta. This approach offers a safer alternative management of abnormal placentation and avoiding a cesarean hysterectomy. This novel surgical technique allows women with morbidly adherent placentas to maintain reproductive capability.

An unusual presentation of ACE inhibitor-induced visceral angioedema.

ACE inhibitors (ACEi) are common anti-hypertensive drugs that can cause angioedema. Though classic, or facial angioedema is rare, visceral angioedema is even less common. When angioedema occurs, it typically presents early, within 30 days of initiating therapy. Visceral angioedema most commonly presents with nausea, emesis, abdominal pain and diarrhoea, and thus is often mistaken for an episode of gastroenteritis. When a CT scan is obtained, it typically shows characteristic findings, including ascetic fluid, mild mesenteric oedema and thickening of the small bowel. In this case report, we present a patient who did not experience her first episode of visceral angioedema until after she had been on ACEi therapy for 5-7 years. In addition, she experienced recurrent episodes of visceral angioedema that were separated by approximately 4 years at a time. Both of these features make for a particularly unique presentation.

Gene expression of TMEM178, which encodes a negative regulator of NFATc1, decreases with the progression of asthma severity.

In two independent microarray studies involving primary airway epithelial cells, the relative gene expression of TMEM178 decreases with the progression of asthma severity. Our manuscript creates a paradigm for future studies dissecting the role of Tmem178 in the pathogenesis of severe asthma.

Association between Knowledge of Zika Transmission and Preventative Measures among Latinas of Childbearing Age in Farm-Working Communities in South Florida.

Zika infection, an otherwise usually mild disease, is of serious public health concern due to the potential teratogenic effects of the virus. The incidence of Zika infection is difficult to document since it is mostly asymptomatic and detection of those carrying Zika is usually not possible. Currently, there is no vaccine for Zika; therefore, use of personal preventative measures is the only method of avoiding transmission. The aim of this study was to evaluate the association between knowledge of Zika transmission and the use of preventive measures among Latinas of childbearing age who lived in or near farm-working communities in South Florida. A secondary data analysis was performed on a cross-sectional study, sampling 100 Latina women aged 18⁻50 years. Sixty-nine percent demonstrated a high degree of knowledge of Zika transmission, and 68% were categorized as taking good preventative measures. Women with high knowledge were 5.86 times more likely to take good preventative measures than those with no knowledge (p-value = 0.05). Knowledge was associated with more preventative measures. Therefore, it is essential to further investigate this relationship in order to develop effective public health interventions for this population.

Antimicrobial Efficacy of Contact Lens Care Solutions Against Neutrophil-Enhanced Bacterial Biofilms.

PURPOSE: Neutrophil-derived extracellular debris has been shown to accelerate bacterial biofilm formation on hydrogel and silicone hydrogel contact lens surfaces compared to lenses inoculated with bacteria alone. The purpose of this study was to evaluate the disinfection efficacy of four standard commercial contact lens cleaning regimens against neutrophil-enhanced bacterial biofilms formed on silicone hydrogel contact lenses. METHODS: Four reference strains were used: Pseudomonas aeruginosa, Serratia marcescens, Stenotrophomonas maltophilia, and Staphylococcus aureus. Human neutrophils were isolated from peripheral blood by venipuncture. Unworn Lotrafilcon B lenses were incubated overnight in each respective strain with stimulated neutrophils. Contact lenses were then cleaned using one of four contact lens care solutions according to manufacturer instructions. Bacterial viability was assessed by colony counts and confocal microscopy. Volume of residual debris on lens surfaces after cleaning was quantified using IMARIS software. RESULTS: All four solutions tested showed effective antimicrobial activity against each bacterial strain; however, substantial amounts of nonviable bacteria and cellular debris remained on the lens surface despite concomitant digital cleaning. CONCLUSIONS: Necrotic cellular debris that accumulates under the posterior lens surface during wear of an inoculated contact lens is not fully removed during routine cleaning and disinfection. TRANSLATIONAL RELEVANCE: The accumulation of residual cellular debris on the contact lens surface may contribute to new colonization of the lens and represents a significant risk factor for a contact lens-related adverse event. Additional studies are needed to correlate these findings with risk for corneal infiltrative and/or infectious events in a standard animal model.

Dental, Dental Hygiene, and Advanced Dental Students' Use, Knowledge, and Beliefs Regarding Tobacco Products.

Using cigarettes and alternative tobacco products (ATPs) is associated with negative oral health outcomes, and dental health professionals are poised to help patients quit. The aim of this study was to determine dental, dental hygiene, and advanced dental students' use, knowledge, and beliefs about cigarettes and ATPs, including perceptions about their education in tobacco dependence treatment and counseling experience. All 1,783 students enrolled in the dental, dental hygiene, and postdoctoral dental programs at the New York University College of Dentistry were invited to participate in the survey in 2016. A total of 708 students at least partially completed the survey, for a response rate of 39.7%. In the results, 146 of the students (20.1%) reported ever using cigarettes, while 253 (35.7%) reported ever using any ATP. Regarding tobacco use intervention, the students reported they had not received enough training on ATPs, were neutral about cigarettes, and were somewhat confident and not so confident counseling a cigarette smoker or ATP user, respectively. By their fourth year, 77.8% of the dental students reported they had counseled someone to stop smoking cigarettes, but only 40.7% had counseled someone to stop using ATPs. Overall, all groups of students reported feeling more confident and had received more education on interventions for cigarettes than for ATPs (p<0.001). These students reported low confidence in helping people quit tobacco and did not perceive they had received enough training on intervening with patients on use of cigarettes and ATPs. These findings call for a revised tobacco education curriculum for dental, dental hygiene, and advanced dental students, focused on building knowledge and confidence for promoting tobacco dependence treatment.

Effects of denture cleansers on denture material properties ­an observational case­control study / Efectos de los limpiadores de prótesis dentales sobre las propiedades del material: un estudio observacional de casos y controles

Everyday use of denture cleansers to prevent microbial colonization on dentures can affect the properties of the denture base material. Limited literature is available on the effects of denture cleanser on reinforced resins. This study aimed to evaluate and compare the effect of denture cleanser on the flexural and impact strength of conventional and reinforced heat cure acrylic resins. Materials and Methods: Rectangular shaped specimens were prepared for flexural and impact strength as per ISO 1567. The denture base resins used included conventional, high impact, nylon fiber reinforced and glass fiber reinforced heat cure acrylic resins. They were further categorized into subgroups A and B depending on immersion in distilled water or denture cleanser (3.8% sodium perborate based). The flexural strength and impact strength of specimens were measured. The study design is a observational case-control study. SPSS version 25 statistical analysis software was used, and the STROBE statement checklist was followed. Results: The mean flexural strength was highest for glass fiber reinforced heat cure resin followed by conventional heat cure resin, high impact heat cure resin and nylon reinforced heat cure resin, respectively. The mean impact strength was highest for high impact heat cure resin followed by glass fiber reinforced heat cure resin, conventional heat cure resin, and nylon fiber-reinforced resin respectively.Conclusion: All the denture base resins tested exhibited a decrease in flexural and impact strength following use of a denture cleanser.

El uso diario de limpiadores para prótesis dentales para prevenir la colonización microbiana en las prótesis puede afectar las propiedades del material base de estas. Existe literatura limitada sobre los efectos de los limpiadores de prótesis sobre resinas reforzadas. Este estudio tuvo como objetivo evaluar y comparar el efecto de un limpiador de prótesis sobre la resistencia a la flexión y al impacto de las resinas acrílicas de curado con calor convencionales y reforzadas. Material y Métodos: Muestras de forma rectangular se prepararon para testear la resistencia a la flexión y al impacto según ISO 1567. Las resinas de base de prótesis utilizadas fueron resinas acrílicas convencionales, de alto impacto, y de curado térmico reforzadas con fibra de vidrio o nylon. Posteriormente se clasificaron en los subgrupos A y B según la inmersión en agua destilada o limpiador de prótesis (3,8% de perborato de sodio). Se midieron la resistencia a la flexión y la resistencia al impacto de las muestras. El diseño del estudio fue de un estudio observacional de casos y controles. Se utilizó el software de análisis estadístico SPSS versión 25, y se siguió la guía de la declaración STROBE. Resultado: La resistencia a la flexión fue más alta para la resina de curado por calor reforzada con fibra de vidrio seguida de la resina de curado por calor convencional, la resina de curado por calor de alto impacto y la resina de curado por calor reforzada con nylon, respectivamente. La resistencia al impacto fue más alta para la resina de curado por calor de alto impacto seguida de la resina de curado por calor reforzada con fibra de vidrio, la resina de curado por calor convencional y la resina reforzada con fibra de nylon, respectivamente. Conclusión: Todas las resinas de base de prótesis probadas exhibieron una disminución en la resistencia a la flexión y al impacto después del uso de un limpiador de prótesis.