Community Health Worker Intervention for Newborns Not Passing Initial Universal Hearing Screening.

BACKGROUND: Universal newborn hearing screening (UNHS) is effective in identifying newborns with possible hearing loss (HL). Outpatient follow-up for newborns referred after hospital-based screening remains a potential area of improvement. In this study, we evaluate the efficacy of a community health worker (CHW) intervention in promoting adherence to outpatient rescreening for newborns referred after initial UNHS. METHODS: A mixed prospective-retrospective cohort study was performed to evaluate a CHW intervention at an academic medical center. Caregivers of referred newborns were contacted by CHWs prior to discharge and educated about HL and the importance of follow-up screening. The CHW outreach intervention was performed for 297 referred newborns between May 2020 and June 2021 and compared to a cohort of 238 newborns without the CHW intervention between March 2019 and June 2021. Statistical analyses were conducted using 2 × 2 Chi-square tests, two-tailed unpaired t-tests, multinomial logistic regression, and multiple linear regression. RESULTS: In the intervention group, 236 of 297 newborns (79.5%) completed their outpatient follow-up rescreening; in the comparison group, 170 of 238 newborns (71.4%) completed their follow-up rescreening (P = .031, OR = 1.55 with regression P = .04). In the intervention group, the average time to follow-up was 13.4 days versus 12.5 days for the comparison group (P = .449, multiple R2 = .02 with P = .78). CONCLUSIONS: CHW outreach intervention may increase adherence to outpatient follow-up rescreening for newborns referred after initial, hospital-based UNHS. Expansion of nursery teams to include CHWs may thus improve completion of recommended follow-up hearing screens.

Physiologic Effects of Microneedle-Mediated Intracochlear Dexamethasone Injection in the Guinea Pig.

OBJECTIVES: Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM). METHODS: In Hartley guinea pigs (n = 5), a post-auricular incision followed by bullostomy was made to access the round window membrane. Using 100 µm diameter hollow microneedles, 1.0 µl of 10 mg/ml dexamethasone was injected through the RWM over 1 min. Compound action potential (CAP) and distortion product otoacoustic action emissions (DPOAE) were measured before perforation, at 1 h, and at 5 h following injection. CAP hearing thresholds were measured from 0.5 to 40 kHz, and DPOAE f2 frequencies ranged from 1.0 and 32 kHz. Repeated measures ANOVA followed by pairwise t-tests were used for statistical analysis. RESULTS: ANOVA identified significant CAP threshold shifts at four frequencies (4, 16, 36, and 40 kHz) and differences in DPOAE at 1 frequency (6 kHz). Paired t-tests revealed differences between the pre-perforation and 1 h time point. By 5 h post injection, both CAP hearing thresholds and DPOAE recover and are not significantly different from baseline thresholds. CONCLUSION: Direct intracochlear delivery of dexamethasone via microneedles results in temporary shifts in hearing thresholds that resolve by 5 hours, thus supporting microneedle technology for the treatment of inner ear disorders. LEVEL OF EVIDENCE: NA Laryngoscope, 134:388-392, 2024.

Exploration and Analysis of Cochlear Implant Content on Social Media.

INTRODUCTION: Social media has an ever-growing presence in patients' lives, particularly with the dissemination of both useful and misleading information. We performed an exploration and analysis of content pertaining to cochlear implantation on a popular social media platform. METHODS: "Cochlear implant" (CI) was queried on TikTok in early October 2022 in a cross-sectional analysis. The 100 top videos were collected. Non-English and duplicate videos were excluded. Two independent researchers used the Global Quality Scale (GQS) and modified DISCERN tool to score videos; higher ratings indicate increased quality and reliability. Demographic data were also recorded. RESULTS: Of the 100 videos assessed, 95 met the inclusion criteria. The average video had 2.36 million views, 328 thousand likes, and a duration of 36.1 seconds. The mean GQS was 1.91 (standard deviation (SD) 0.85), and the modified DISCERN score was 1.48 (SD 1.20). Posters were predominantly laypersons (93.7%), including CI users or parents of pediatric CI users. No videos featured audiologists or otolaryngologists. Nearly half of the videos (48.4%) discussed the experience of a patient or parent of a pediatric patient with CIs, and 24.2% were aimed at directly educating the viewers about CIs or the deaf community. CONCLUSIONS: Most videos featured CI users or families of pediatric CI users and detailed specific patient experiences. The deaf and CI communities have strong social media presences. Most videos had limited quality and reliability, measured via the GQS and modified DISCERN tool, and no videos featured hearing healthcare professionals, highlighting opportunities for clinicians to use the platform as a patient resource.

Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs.

HYPOTHESIS: Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours. BACKGROUND: We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing. METHODS: Volumes of 1.0, 2.5, or 5.0 µL of artificial perilymph were injected into the cochlea at a rate of 1 µL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 µL of FM 1-43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy. RESULTS: Direct intracochlear injection of 1.0 µL of artificial perilymph in vivo , corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 µL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1-43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns. CONCLUSION: Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.

Anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the round window membrane.

BACKGROUND: We have developed 3D-printed microneedle technology for diagnostic aspiration of perilymph and intracochlear delivery of therapeutic agents. Single microneedle-mediated round window membrane (RWM) perforation does not cause hearing loss, heals within 48-72 h, and yields sufficient perilymph for proteomic analysis. In this study, we investigate the anatomic, physiologic, and proteomic consequences of repeated microneedle-mediated perforations of the same RWM at different timepoints. METHODS: 100-µm-diameter hollow microneedles were fabricated using two-photon polymerization (2PP) lithography. The tympanic bullae of Hartley guinea pigs (n = 8) were opened with adequate exposure of the RWM. Distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) were recorded to assess hearing. The hollow microneedle was introduced into the bulla and the RWM was perforated; 1 µL of perilymph was aspirated from the cochlea over the course of 45 s. 72 h later, the above procedure was repeated with aspiration of an additional 1 µL of perilymph. 72 h after the second perforation, RWMs were harvested for confocal imaging. Perilymph proteomic analysis was completed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Two perforations and aspirations were performed in 8 guinea pigs. In six, CAP, DPOAE, and proteomic analysis were obtained; in one, only CAP and DPOAE results were obtained; and in one, only proteomics results were obtained. Hearing tests demonstrated mild hearing loss at 1-4 kHz and 28 kHz, most consistent with conductive hearing loss. Confocal microscopy demonstrated complete healing of all perforations with full reconstitution of the RWM. Perilymph proteomic analysis identified 1855 proteins across 14 samples. The inner ear protein cochlin was observed in all samples, indicating successful aspiration of perilymph. Non-adjusted paired t-tests with p < 0.01 revealed significant changes in 13 of 1855 identified proteins (0.7%) between the first and second aspirations. CONCLUSIONS: We demonstrate that repeated microneedle perforation of the RWM is feasible, allows for complete healing of the RWM, and minimally changes the proteomic expression profile. Thus, microneedle-mediated repeated aspirations in a single animal can be used to monitor the response to inner ear treatments over time.

Characterization of otologic symptoms appearing after COVID-19 vaccination.

OBJECTIVES: Anecdotal reports of sudden sensorineural hearing loss (SSNHL) following COVID-19 vaccination have emerged in the otolaryngology community. Studies have demonstrated no association between COVID-19 vaccination and SSNHL. We aim to characterize the spectrum of otologic symptoms following COVID-19 vaccination. METHODS: A cross-sectional study of patients seen in the otology clinic at an academic center was performed. Patients completed a questionnaire on the development of new otologic symptoms within 4 weeks of COVID-19 vaccination. Diagnostic and audiometric data was collected retrospectively for patients reporting otologic symptoms. RESULTS: Between May and July 2021, 500 patients were screened. Median age was 56.6 years old, with 59.4 % female and 40.2 % male. 420 patients (84.0 %) were vaccinated, with 58.4 % receiving Pfizer, 29.1 % receiving Moderna, and 3.8 % receiving Johnson & Johnson. 61 patients (14.5 %) reported one or more otologic symptoms within 4 weeks of vaccination, including 21 (5.0 %) with hearing loss, 26 (6.2 %) with tinnitus, 33 (7.9 %) with dizziness, and 19 (4.5 %) with vertigo. Of the 16 patients (3.2 %) reporting tinnitus with no associated hearing loss, 8 were diagnosed with subjective tinnitus and 4 were diagnosed with temporomandibular joint syndrome. Of the 18 patients reporting hearing loss, 11 had exacerbations of underlying pathologies (e.g. Meniere's disease, presbycusis) and 7 were newly diagnosed with SSNHL (1.4 %). CONCLUSIONS: Patients reporting otologic symptoms following COVID-19 vaccination received various diagnoses of uncertain etiology. The incidence of SSNHL in these patients is comparable to the general otology patient population. Additional studies are required to determine the incidence of specific diagnoses following vaccination.

A Phase 1B open-label study of gedatolisib (PF-05212384) in combination with other anti-tumour agents for patients with advanced solid tumours and triple-negative breast cancer.

BACKGROUND: This Phase 1b study (B2151002) evaluated the PI3K/mTOR inhibitor gedatolisib (PF-05212384) in combination with other anti-tumour agents in advanced solid tumours. METHODS: Patients with various malignancies were administered gedatolisib (90‒310 mg intravenously every week [QW]) plus docetaxel (arm A) or cisplatin (arm B) (each 75 mg/m2 intravenously Q3W) or dacomitinib (30 or 45 mg/day orally). The safety and tolerability of combination therapies were assessed during dose escalation; objective response (OR) and safety were assessed during dose expansion. RESULTS: Of 110 patients enrolled, 107 received gedatolisib combination treatment. Seven of 70 (10.0%) evaluable patients had dose-limiting toxicities; the most common was grade 3 oral mucositis (n = 3). Based upon reprioritisation of the sponsor's portfolio, dose expansion focused on arm B, gedatolisib (180 mg QW) plus cisplatin in patients (N = 22) with triple-negative breast cancer (TNBC). OR (95% CI) was achieved in four of ten patients in first-line (overall response rate 40.0% [12.2-73.8%]) and four of 12 in second/third-line (33.3% [9.9-65.1%]) settings. One patient in each TNBC arm (10%, first-line; 8.3%, second/third-line) achieved a complete response. CONCLUSIONS: Gedatolisib combination therapy showed an acceptable tolerability profile, with clinical activity at the recommended Phase 2 dose in patients with TNBC. CLINICAL TRIAL: ClinicalTrial.gov: NCT01920061.

Development of an optimized preoperative computed tomography imaging checklist for endoscopic sinus surgery utilizing a systematic review of the literature and the modified Delphi method.

BACKGROUND: Critical review of computed tomography (CT) imaging is essential in preoperative planning for endoscopic sinus surgery. In this study, we used a systematic review and a modified Delphi method to develop a comprehensive checklist that facilitates preoperative review of sinus CT imaging. METHODS: We performed a systematic review of PubMed, Embase, CINAHL, Cochrane, and Web of Science databases to identify existing checklists developed to evaluate sinus CT imaging. An inclusive list of items from these checklists was compiled and a modified Delphi methodology was used to assign ranked priority. The Delphi process involved 14 rhinologists and had three phases: an initial survey with Likert priority (scale of 1-9) and two rounds of live discussions followed by survey to confirm consensus. RESULTS: Ninety-seven possible checklist items were identified from a systematic review and panelist input. On initial survey, 63 items reached a consensus score of 7+, and 13 items had near consensus scores between 6 and 7; two of these 13 borderline items were retained after subsequent panelist discussion. The resulting items were consolidated into an 11-item disease checklist and a 24-item anatomical checklist; the anatomical checklist was further divided into six subsections: nasal cavity, maxillary, ethmoid, sphenoid, frontal, skull base, and orbit. Additionally, panelists identified six core aspects of patient history to consider prior to surgery. CONCLUSIONS: After establishing content validity through a systematic literature review and a modified Delphi method, we developed a comprehensive checklist for preoperative sinus CT imaging review; implementation and evaluation of validity among trainees will suggest overall utility.

Instrumented insoles for assessment of gait in patients with vestibular schwannoma.

Background: Imbalance and gait disturbances are common in patients with vestibular schwannoma (VS) and can result in significant morbidity. Current methods for quantitative gait analysis are cumbersome and difficult to implement. Here, we use custom-engineered instrumented insoles to evaluate the gait of patients diagnosed with VS. Methods: Twenty patients with VS were recruited from otology, neurosurgery, and radiation oncology clinics at a tertiary referral center. Functional gait assessment (FGA), 2-minute walk test (2MWT), and uneven surface walk test (USWT) were performed. Custom-engineered instrumented insoles, equipped with an 8-cell force sensitive resistor (FSR) and a 9-degree-of-freedom inertial measurement unit (IMU), were used to collect stride-by-stride spatiotemporal gait parameters, from which mean values and coefficients of variation (CV) were determined for each patient. Results: FGA scores were significantly correlated with gait metrics obtained from the 2MWT and USWT, including stride length, stride velocity, normalized stride length, normalized stride velocity, stride length CV, and stride velocity CV. Tumor diameter was negatively associated with stride time and swing time on the 2MWT; no such association existed between tumor diameter and FGA or DHI. Conclusions: Instrumented insoles may unveil associations between VS tumor size and gait dysfunction that cannot be captured by standardized clinical assessments and self-reported questionnaires.

Integrated Pest Management Strategies for Asian Citrus Psyllid Diaphorina citri Kuwayama (Hemiptera: Psyllidae) and Huanglongbing in Citrus for Sarawak, East Malaysia, Borneo.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, transmits 'Candidatus Liberibacter asiaticus' (CLas), a phloem-limited bacterium associated with the severe Asian form of huanglongbing (HLB), and the most destructive disease of citrus. The pathogen and the psyllid, both of South Asian origin, are now widespread in citrus regions of Asia and the Americas. There is no cure for the disease. Application of synthetic pesticides, in some instances more frequently than fortnightly, to minimise incidence of ACP in citrus orchards, has not prevented inevitable impacts of the disease in regions of Asia where CLas is present. Despite the inevitable spread of the disease, significant progress has been made in Sarawak since the mid-1990s towards effectively implementing integrated pest management (IPM) programs for stemming the impact of the disease and detrimental consequences of over-reliance on synthetic pesticides. Growers are encouraged to plant pathogen-free trees, remove diseased trees, monitor incidence of the psyllid, and to use pesticides judiciously to reduce their detrimental impacts on natural enemies. Knowledge has been enhanced through research on seasonal incidence of the psyllid, use of mineral oils, development of protocols and iodine−starch test kits for detecting infected trees, PCR for confirming the presence of CLas in symptomatic leaves, methods for monitoring incidence the psyllid, and training extension staff and growers. However, major impediments to increasing the average longevity of trees beyond <5 years in poorly managed orchards, based on marcotting (air layering), and >12 years in well-managed orchards, based on pathogen-free trees, still need to be addressed. These include grower knowledge, marcotting, aggressive marketing of synthetic pesticides, high prices of mineral oils, spray application procedures, and better reliance on natural enemies of the psyllid.

Inner Ear Diagnostics and Drug Delivery via Microneedles.

OBJECTIVES: Precision medicine for inner ear disorders has seen significant advances in recent years. However, unreliable access to the inner ear has impeded diagnostics and therapeutic delivery. The purpose of this review is to describe the development, production, and utility of novel microneedles for intracochlear access. METHODS: We summarize the current work on microneedles developed using two-photon polymerization (2PP) lithography for perforation of the round window membrane (RWM). We contextualize our findings with the existing literature in intracochlear diagnostics and delivery. RESULTS: Two-photon polymerization lithography produces microneedles capable of perforating human and guinea pig RWMs without structural or functional damage. Solid microneedles may be used to perforate guinea pig RWMs in vivo with full reconstitution of the membrane in 48-72 h, and hollow microneedles may be used to aspirate perilymph or inject therapeutics into the inner ear. Microneedles produced with two-photon templated electrodeposition (2PTE) have greater strength and biocompatibility and may be used to perforate human RWMs. CONCLUSIONS: Microneedles produced with 2PP lithography and 2PTE can safely and reliably perforate the RWM for intracochlear access. This technology is groundbreaking and enabling in the field of inner ear precision medicine.

Histopathology of Labyrinthitis Ossificans From an Intralabyrinthine Surgical Specimen.

OBJECTIVE: Histologic characterization of labyrinthitis ossificans (LO) has mostly been limited to postmortem samples. In this report, we describe the histology of LO from a surgical specimen obtained from a patient undergoing labyrinthectomy with simultaneous cochlear implantation. PATIENT: A 38-year-old woman initially presenting to the emergency room with acute vertigo, left-sided hearing loss, tinnitus, and aural fullness. INTERVENTIONS: Contrast-enhanced magnetic resonance imaging (MRI) and computerized tomography (CT) were performed for the patient before labyrinthectomy and cochlear implantation. Audiometric testing was performed before and after surgical intervention. Histologic analysis was performed on a specimen obtained from the left lateral semicircular canal (SCC) during surgery. MAIN OUTCOME MEASURES: Preoperative CT and MRI findings, preoperative and postoperative hearing thresholds via air conduction and bone conduction, hematoxylin and eosin (H&E) stain of the surgical sample, and CD45 immunostain of the surgical sample. RESULTS: Preoperative CT and MRI confirmed the diagnosis of isolated LO of the left lateral SCC. Audiometric testing revealed significant improvement in hearing after labyrinthectomy and cochlear implantation. H&E stain demonstrated fibrosis and ossification in the left lateral SCC, and CD45 immunostain was negative. CONCLUSIONS: Histopathology of LO based on a surgical sample is comparable to heterotopic ossification (HO) seen in other human tissue. Given the similarities between LO and HO, agents effective in preventing HO may have utility in preventing LO.

Evolution of predictive and prognostic biomarkers in the treatment of advanced gastric cancer.

Despite new therapeutic options, advanced gastric cancer remains associated with a poor prognosis compared with other cancers. Recent gains in the treatment of gastric cancer were accompanied by the identification of novel biomarkers associated with various cellular pathways and corresponding diagnostic technologies. It is expected that the standardization of clinical workflow and technological refinements in biomarker assessment will support greater personalization and further improve treatment outcomes. In this article, we review the current state of prognostic and predictive biomarkers in gastric cancer.

Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients.

OBJECTIVES: Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reducing CRS symptom burden. This study seeks to evaluate the role of patient-reported quality-of-life measures in guiding interventions for CF-related sinus disease. METHODS: We performed a prospective, cross-sectional study of 105 patients presenting to a CF-accredited clinic between July and September 2018. Demographic data and sinus surgery history were collected, in addition to Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Disorders (QOD-NS) scores. Statistical analysis was conducted using correlation and non-parametric Mann-Whitney U tests. RESULTS: Baseline well-care visits accounted for 71.4% of all clinical evaluations. Prior otolaryngology intervention was noted in 69 (66%) patients, where the majority of these patients (63/69; 91%) underwent endoscopic sinus surgery (ESS). Patients with a history of otolaryngology intervention had an average SNOT-22 score of 33.2 (SD = 20.6) compared to 24.9 (SD = 18.5) for patients without prior intervention (P = .048). The average QOD-NS score was 5.5 (SD = 6.4) among patients referred to otolaryngologists and 3.1 (SD = 5.7) for non-referred patients (P = .012). SNOT-22 and QOD-NS scores were modestly correlated (R of .43). CONCLUSION: CF patients with symptoms resulting in worse quality-of-life assessments were more likely to have established coordinated care with an otolaryngologist. Further validation of the utility of SNOT-22 and QOD-NS questionnaires as care coordination metrics is necessary in the CF population.

Integrating community health workers into a community hearing health collaborative to understand the social determinants of health in children with hearing loss.

BACKGROUND: Children with hearing loss (HL) require coordination of care to navigate medical and social services. Strong evidence supports the role of community health workers (CHWs) to identify and address social barriers. OBJECTIVE: The goal of this study was to evaluate the impact of integrating CHWs into the medical teams of children with HL and identify the social needs associated with their caregivers at a large urban hospital center. METHODS: A retrospective chart review was conducted for 30 children with HL whose caregivers enrolled in a CHW program between August 1, 2017 and December 31, 2019. Baseline demographic data were collected, including social circumstances such as food and housing insecurity, status of social security supplemental income (SSI), and need for referral to early intervention (EI) or preschool/school services. Caregivers were assessed for confidence in self-management; baseline distress level was measured via a distress thermometer. RESULTS: Of the 30 charts reviewed, 93% demonstrated social needs including food insecurity (24%) and educational service needs (45%). Eighty-seven percent of caregivers reported a sense of control over the child's condition, yet 73% reported a stress level of four or greater on the distress thermometer scale. At 3 months follow-up, 70% of patients completed referrals; a significant number of patients had obtained hearing aids and cochlear implants compared to baseline (p = 0.017). CONCLUSIONS: Caregivers of children with HL face multiple social obstacles, including difficulties connecting to educational and financial resources. CHWs are instrumental in identifying social needs and connecting caregivers to services.

Effect of Horticultural Mineral Oil on Huanglongbing Transmission by Diaphorina citri Kuwayama (Hemiptera: Psyllidae) Population in a Commercial Citrus Orchard in Sarawak, Malaysia, Northern Borneo.

Diaphorina citri Kuwayama transmits a destructive citrus disease caused by a fastidious bacterium 'Candidatus Liberibacter asiaticus' (CLas) designated as Huanglongbing (HLB) which posed a risk of detrimental threat to the Malaysian citrus industry. All D. citri life stages show a lumped habit on young flushes and its population fluctuations was closely related to accessibility of young flushes. The study aimed to investigate if the appearance of young flush shoots on citrus influences ACP population fluctuation and if horticultural mineral oil (HMO) could reduce spread of HLB transmission by ACP in a commercial healthy orchard. Field research was carried out from 1 April 2011 to 1 December 2014 in a 2-year-old 1 ha citrus farm that consisted of 200 PCR-certified disease-free grafted non-bearing honey tangerine (Citrus reticulata L.) in southwestern Sarawak, Malaysia. The experiment had two treatments namely control (unsprayed) and nC24 HMO with four replications arranged in a simple randomized block design. ACP eggs, nymphs, and adults per flush shoot was assessed and HLB incidence was monitored for visual inspection of the citrus trees for the current existence of usual signs of characteristic symptoms of HLB such as yellowing shoots, leaf mottling, and corky or enlarged veins on leaves. HLB-specific primer was employed in 16S rDNA polymerase chain reaction to detect the CLas gene in diseased trees. Increase in abundance of D. citri is mainly affected by the citrus flushing cycles and their life stages are completed on these flush shoots. Relative degree of aggregation index for D. citri adults increased during periods of cyclic production of new flush. HMO-treated plots produced a significantly lower percentage up to 11.43% of diseased trees against 42.20% in untreated control plots. HMO is effective against D. citri and recommended to be incorporated in the IPM program to prevent infection and reduce the spread of HLB.

Targeted genomic analysis of 364 adrenocortical carcinomas.

Despite recent advances in elucidating molecular pathways underlying adrenocortical carcinoma (ACC), this orphan malignancy is associated with poor survival. Identification of targetable genomic alterations is critical to improve outcomes. The objective of this study was to characterize the genomic profile of a large cohort of patient ACC samples to identify actionable genomic alterations. Three hundred sixty-four individual patient ACC tumors were analyzed. The median age of the cohort was 52 years and 60.9% (n = 222) were female. ACC samples had common alterations in epigenetic pathways with 38% of tumors carrying alterations in genes involved in histone modification, 21% in telomere lengthening, and 21% in SWI/SNF complex. Tumor suppressor genes and WNT signaling pathway were each mutated in 51% of tumors. Fifty (13.7%) ACC tumors had a genomic alteration in genes involved in the DNA mismatch repair (MMR) pathway with many tumors also displaying an unusually high number of mutations and a corresponding MMR mutation signature. In addition, genomic alterations in several genes not previously associated with ACC were observed, including IL7R, LRP1B, FRS2 mutated in 6, 8 and 4% of tumors, respectively. In total, 58.5% of ACC (n = 213) had at least one potentially actionable genomic alteration in 46 different genes. As more than half of ACC have one or more potentially actionable genomic alterations, this highlights the value of targeted sequencing for this orphan cancer with a poor prognosis. In addition, significant incidence of MMR gene alterations suggests that immunotherapy is a promising therapeutic for a considerable subset of ACC patients.

Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy with concurrent radiotherapy (nCRT) is an accepted treatment regimen for patients with potentially curable esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The purpose of this study is to evaluate whether induction chemotherapy (IC) before nCRT is associated with improved pathologic complete response (pCR) and overall survival (OS) when compared with patients who received nCRT alone for esophageal and GEJ adenocarcinoma. METHODS: Using the National Cancer Database (NCDB), patients who received nCRT and curative-intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006 to 2015 were included. Chemotherapy and radiation therapy start dates were used to define cohorts who received IC before nCRT (IC + nCRT) versus those who only received concurrent nCRT before surgery. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups. RESULTS: 12,460 patients met inclusion criteria, of whom 11,880 (95%) received nCRT and 580 (5%) received IC + nCRT. Following propensity weighting, OS was significantly improved among patients who received IC + nCRT versus nCRT (HR 0.82; 95% CI 0.74-0.92; p < 0.001) with median OS for the IC + nCRT cohort of 3.38 years versus 2.45 years for nCRT. For patients diagnosed from 2013 to 2015, IC + nCRT was also associated with higher odds of pCR compared with nCRT (OR 1.59; 95% CI 1.14-2.21; p = 0.007). CONCLUSION: IC + nCRT was associated with a significant OS benefit as well as higher pCR rate in the more modern patient cohort. These results merit consideration of a sufficiently powered prospective multiinstitutional trial to further evaluate these observed differences.

Molecular Profiling-Based Assignment of Cancer Therapy (NCI-MPACT): A Randomized Multicenter Phase II Trial.

This trial assessed the utility of applying tumor DNA sequencing to treatment selection for patients with advanced, refractory cancer and somatic mutations in one of four signaling pathways by comparing the efficacy of four study regimens that were either matched to the patient's aberrant pathway (experimental arm) or not matched to that pathway (control arm). MATERIALS AND METHODS: Adult patients with an actionable mutation of interest were randomly assigned 2:1 to receive either (1) a study regimen identified to target the aberrant pathway found in their tumor (veliparib with temozolomide or adavosertib with carboplatin [DNA repair pathway], everolimus [PI3K pathway], or trametinib [RAS/RAF/MEK pathway]), or (2) one of the same four regimens, but chosen from among those not targeting that pathway. RESULTS: Among 49 patients treated in the experimental arm, the objective response rate was 2% (95% CI, 0% to 10.9%). One of 20 patients (5%) in the experimental trametinib cohort had a partial response. There were no responses in the other cohorts. Although patients and physicians were blinded to the sequencing and random assignment results, a higher pretreatment dropout rate was observed in the control arm (22%) compared with the experimental arm (6%; P = .038), suggesting that some patients may have had prior tumor mutation profiling performed that led to a lack of participation in the control arm. CONCLUSION: Further investigation, better annotation of predictive biomarkers, and the development of more effective agents are necessary to inform treatment decisions in an era of precision cancer medicine. Increasing prevalence of tumor mutation profiling and preference for targeted therapy make it difficult to use a randomized phase II design to evaluate targeted therapy efficacy in an advanced disease setting.