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1.
Article in English | MEDLINE | ID: mdl-38853655

ABSTRACT

KEY POINTS: A convolutional neural network (CNN)-based model can accurately localize and segment turbinates in images obtained during nasal endoscopy (NE). This model represents a starting point for algorithms that comprehensively interpret NE findings.

2.
Insect Mol Biol ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38655882

ABSTRACT

Agricultural insect pests (AIPs) are widely successful in adapting to natural and anthropogenic stressors, repeatedly overcoming population bottlenecks and acquiring resistance to intensive management practices. Although they have been largely overlooked in evolutionary studies, AIPs are ideal systems for understanding rapid adaptation under novel environmental conditions. Researchers have identified several genomic mechanisms that likely contribute to adaptive stress responses, including positive selection on de novo mutations, polygenic selection on standing allelic variation and phenotypic plasticity (e.g., hormesis). However, new theory suggests that stress itself may induce epigenetic modifications, which may confer heritable physiological changes (i.e., stress-resistant phenotypes). In this perspective, we discuss how environmental stress from agricultural management generates the epigenetic and genetic modifications that are associated with rapid adaptation in AIPs. We summarise existing evidence for stress-induced evolutionary processes in the context of insecticide resistance. Ultimately, we propose that studying AIPs offers new opportunities and resources for advancing our knowledge of stress-induced evolution.

3.
Ophthalmic Genet ; 45(2): 207-209, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37722826

ABSTRACT

BACKGROUND: We present a case of a child with Floating-Harbor Syndrome (FHS) with bilateral chorioretinal coloboma (CC). To the best of our knowledge, this is the first case report of this association. Floating- Harbor syndrome is an extremely rare autosomal dominant genetic disorder with approximately 100 cases reported. It is characterized by a series of atypical features that include short stature with delayed bone age, low birth weight, skeletal anomalies, delayed speech development, and dysmorphic facial characteristics that typically portray a triangular face, deep-set eyes, long eyelashes, and prominent nose. MATERIALS AND METHODS: Our patient was examined by a pediatric ophthalmologist for the time at age of 7. Visual acuity, optical coherence tomography (OCT) and Optos imaging were collected on every visit. The patient had whole genome sequencing ordered by a pediatric geneticist to confirm Floating-Harbor syndrome. RESULTS: We present the patient's OCT and Optos images that illustrate the location of the patient's inferior chorioretinal coloboma in both eyes. The whole genome sequencing report collected revealed a heterozygous de novo pathogenic variant in the SRCAP gene, consistent with a Floating-Harbor syndrome diagnosis in the literature. DISCUSSION: Both genetic and systemic findings are consistent with the diagnosis of Floating-Harbor syndrome in our patient. Rubenstein-Taybi and Floating-Harbor syndrome share a similarity in molecular and physical manifestations, but because of the prevalence in Rubenstein-Taybi diagnoses, it is a syndromic condition that includes coloboma and frequently associated with each other. Therefore, a retinal exam should become part of the standard protocol for those with FHS, as proper diagnosis, examination and treatment can prevent irreversible retinal damage.


Subject(s)
Abnormalities, Multiple , Coloboma , Craniofacial Abnormalities , Heart Septal Defects, Ventricular , Humans , Child , Coloboma/diagnosis , Coloboma/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnosis , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/genetics , Growth Disorders/diagnosis , Growth Disorders/genetics
4.
Am J Cardiol ; 205: 298-301, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37633064

ABSTRACT

Our study aimed to explore the national trends in the rates of perioperative complications, in-hospital mortality, and readmissions after pericardiectomy and the impact of center volume on these outcomes. Using the Nationwide Readmission Database, we identified patients who underwent isolated pericardiectomy from 2010 to 2019. In-hospital mortality and readmission rates were assessed using orthogonal polynomial contrasts, with the linear and nonlinear trends evaluated as needed. Multivariable logistic regression models were constructed to identify the independent predictors of mortality and readmission. All analyses accounted for the Nationwide Readmission Database sampling design and were performed using SAS version 9.4 (SAS Institute Inc. Cary, NC.) with p <0.05 used to indicate statistical significance. A total of 26,169 hospitalizations for pericardiectomy were identified during the study period. The median age was 59 years and 44% were female. In-hospital mortality was 5.2%, and the median length of stay was 7 days. Advanced age, higher co-morbidity index, and lower annual facility pericardiectomy volume were independent predictors of in-hospital mortality. The 30- and 90-day readmission rates after pericardiectomy were 18% and 28%, respectively. Previous cardiac surgery, diagnosis of constrictive pericarditis, and greater co-morbidity score were independent predictors of readmission. In conclusion, isolated pericardiectomy rates have remained mostly constant, with relatively small changes in in-hospital mortality and 30- and 90-day readmission rates over the last decade. Advanced age, lower facility pericardiectomy volume, and higher Elixhauser co-morbidity index are independent predictors of surgical mortality.


Subject(s)
Patient Readmission , Pericardiectomy , Humans , Female , United States/epidemiology , Middle Aged , Male , Hospital Mortality , Contrast Media , Databases, Factual
5.
JHEP Rep ; 5(5): 100714, 2023 May.
Article in English | MEDLINE | ID: mdl-37122689

ABSTRACT

Background & Aims: Although fat loss is observed in patients with cholestasis, how chronically elevated bile acids (BAs) impact white and brown fat depots remains obscure. Methods: To determine the direct effect of pathological levels of BAs on lipid accumulation and mitochondrial function, primary white and brown adipocyte cultures along with fat depots from two separate mouse models of cholestatic liver diseases, namely (i) genetic deletion of farnesoid X receptor (Fxr); small heterodimer (Shp) double knockout (DKO) and (ii) injury by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), were used. Results: As expected, cholestatic mice accumulate high systemic BA levels and exhibit fat loss. Here, we demonstrate that chronic exposure to pathological BA levels results in mitochondrial dysfunction and defective thermogenesis. Consistently, both DKO and DDC-fed mice exhibit lower body temperature. Importantly, thermoneutral (30 °C) housing of the cholestatic DKO mice rescues the decrease in brown fat mass, and the expression of genes responsible for lipogenesis and regulation of mitochondrial function. To overcome systemic effects, primary adipocyte cultures were treated with pathological BA concentrations. Mitochondrial permeability and respiration analysis revealed that BA overload is sufficient to reduce mitochondrial function in primary adipocytes, which is not as a result of cytotoxicity. Instead, we found robust reductions in uncoupling protein 1 (Ucp1), PR domain containing 16 (Prdm16), and deiodinase, iodothyronine, type II (Dio2) transcripts in brown adipocytes upon treatment with chenodeoxycholic acid, whereas taurocholic acid led to the suppression of Dio2 transcript. This BA-mediated decrease in transcripts was alleviated by pharmacological activation of UCP1. Conclusions: High concentrations of BAs cause defective thermogenesis by reducing the expression of crucial regulators of mitochondrial function, including UCP1, which may explain the clinical features of hypothermia and fat loss observed in patients with cholestatic liver diseases. Impact and Implications: We uncover a detrimental effect of chronic bile acid overload on adipose mitochondrial function. Pathological concentration of different BAs reduces the expression of distinct genes involved in energy expenditure, which can be mitigated with pharmacological UCP1 activation.

6.
Nature ; 613(7943): 345-354, 2023 01.
Article in English | MEDLINE | ID: mdl-36599983

ABSTRACT

Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine1,2. Here we reduced this complexity by focusing on cellular organization-a key readout and driver of cell behaviour3,4-at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the 'wiring' of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring.


Subject(s)
Induced Pluripotent Stem Cells , Intracellular Space , Humans , Induced Pluripotent Stem Cells/cytology , Single-Cell Analysis , Datasets as Topic , Interphase , Cell Shape , Mitosis , Cell Polarity , Cell Survival
7.
Laryngoscope ; 133(10): 2597-2602, 2023 10.
Article in English | MEDLINE | ID: mdl-36651328

ABSTRACT

OBJECTIVES: Bone resorption of more conventional vascularized bone grafts have been well described showing minimal resorption over time. Few studies have evaluated osseous union and bone resorption in scapula tip free flaps (STFF) in the reconstruction of mandibulectomy defects. We aimed to describe our series on STFF with respect to osseous union and bone resorption over time. METHODS: Retrospective chart review of patients receiving STFF from January 2014-January 2017 (n = 25). A neuroradiologist analyzed follow-up CT scans to assess (1) STFF complete, partial, or no osseous union with native mandible and (2) STFF volume change over time in a subset with multiple follow-up scans (n = 18). RESULTS: Twenty-three of 25 patients (92%) showed complete or partial STFF osseous union with native mandible either distally or proximally. STFF volume change ranged from +4.8 to -54% (median -0.5%) over median follow-up interval of 23 months. History of chemoradiation therapy, bisphophonate use, sex, age, or smoking history did not correlate with bone resorption. CONCLUSIONS: STFFs shows high rates of osseous union and limited bone resorption that is equivalent to, or less than, vascularized fibular and iliac crest flaps. Clinically, this translates into both optimal healing and functional and cosmetic outcomes, especially in the setting of prior therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2597-2602, 2023.


Subject(s)
Bone Resorption , Free Tissue Flaps , Mandibular Neoplasms , Mandibular Reconstruction , Humans , Free Tissue Flaps/transplantation , Retrospective Studies , Mandibular Neoplasms/surgery , Mandibular Reconstruction/methods , Osseointegration , Mandible/surgery , Scapula/transplantation , Bone Resorption/etiology , Bone Resorption/surgery , Bone Transplantation/methods
8.
J Clin Neurophysiol ; 40(4): 331-338, 2023 May 01.
Article in English | MEDLINE | ID: mdl-34482314

ABSTRACT

PURPOSE: Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses-a superconditioning (SC) train-when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles. METHODS: We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalized to test input responses and were compared within and between subjects. RESULTS AND CONCLUSIONS: For inhibition, the minimum intensity of SC pulses needed to influence the follow-on MEP was found to be 60% of the target muscle's resting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse-often reported as 80% of the single-pulse threshold-typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.


Subject(s)
Evoked Potentials, Motor , Motor Cortex , Humans , Aged , Evoked Potentials, Motor/physiology , Electromyography/methods , Transcranial Magnetic Stimulation/methods , Motor Cortex/physiology , Muscle, Skeletal/physiology
9.
Poult Sci ; 102(2): 102300, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36502566

ABSTRACT

A 28-day battery cage study was conducted to test the efficacy of tannin-free grain sorghum varieties fed to Cobb 500 male broiler chickens (n = 512) and challenged with Eimeria maxima (EM) and Clostridium perfringens (CP). Birds were fed 1 of 8 treatments (corn, red/bronze, white/tan, or U.S. No. 2 sorghum) and were grouped by challenge method (challenged with EM/CP or unchallenged). On d 14, birds in the challenge group were orally inoculated with ∼5,000 oocysts of EM, and on d 19, 20, and 21, birds were given a broth culture of CP with ∼108 CFU/mL once daily. On d 21, three birds were scored for the degree/presence of necrotic enteritis (NE) lesions. Birds and feed were group weighed (d 0, 14, 21, and 28) to calculate average feed intake (FI), body weight gain (BWG), and adjusted feed conversion ratio (AdjFCR). Intestinal integrity was assessed through histological analysis of intestinal tissues, and change in transcriptome was determined using mRNA-sequencing on intestinal mucosa. Relative concentrations of secondary metabolites in grain sorghum were determined by LC-MS/MS analysis. Data were analyzed as a 2-way ANOVA with factors of treatment, challenge and their interaction. Regardless of challenge from 14 to 21 d, birds on the corn, white/tan, and U.S. No. 2 treatments were more efficient than those fed red/bronze treatment (P = 0.0026). From 14 to 28 d, BWG was significantly higher for the white/tan treatment (P = 0.024) compared to the red/bronze treatment. At 21 d, a significant interaction was observed for lesion score (P = 0.0001) in which, challenged birds fed red/bronze and white/tan treatments had reduced intestinal lesions compared to U.S. No. 2 and corn treatments. No differences among treatments were observed in jejunum morphology, but differential expression analysis showed an upregulation in defense response to bacteria and biotic stress in the challenged red/bronze treatment compared to the challenged corn. This study demonstrated improved gut health and minimal impact on growth and efficiency of broilers fed select grain sorghum varieties when challenged with EM/CP.


Subject(s)
Clostridium Infections , Coccidiosis , Eimeria , Enteritis , Poultry Diseases , Sorghum , Animals , Male , Clostridium perfringens/physiology , Chickens , Clostridium Infections/microbiology , Clostridium Infections/veterinary , Enteritis/microbiology , Enteritis/veterinary , Tannins , Chromatography, Liquid/veterinary , Coccidiosis/veterinary , Tandem Mass Spectrometry/veterinary , Eimeria/physiology , Poultry Diseases/microbiology , Animal Feed/analysis , Diet/veterinary
10.
Curr Opin Insect Sci ; 55: 101000, 2023 02.
Article in English | MEDLINE | ID: mdl-36521782

ABSTRACT

Despite considerable research, efforts to manage insecticide resistance continue to fail. The Colorado potato beetle (CPB), Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae), epitomizes this problem, as it has repeatedly and rapidly evolved resistance to>50 insecticides. The patterns of resistance evolution are intriguing, as they defy models where resistance evolves from rare mutations. Here, we synthesize recent research on insecticide resistance in CPB showing that polygenic resistance drawn from standing genetic diversity explains genomic patterns of insecticide resistance evolution. However, rapid gene regulatory evolution suggests that other mechanisms might also facilitate adaptive change. We explore the hypothesis that sublethal stress from insecticide exposure could alter heritable epigenetic modifications, and discuss the range of experimental approaches needed to fully understand insecticide resistance evolution in this super pest.


Subject(s)
Coleoptera , Insecticides , Solanum tuberosum , Animals , Coleoptera/genetics , Insecticide Resistance/genetics , Insecticides/pharmacology , Gene Expression Regulation
11.
Laryngoscope ; 133(8): 1818-1823, 2023 08.
Article in English | MEDLINE | ID: mdl-36222454

ABSTRACT

OBJECTIVE: To evaluate the predictive ability of symptom self-localization to distinguish obstructive eustachian tube dysfunction from non-obstructive salpingitis. METHODS: Adult (age ≥18 years) patients with a primary complaint of aural discomfort who underwent diagnostic nasal endoscopy and tympanometry at a tertiary academic center were enrolled. Symptoms were self-localized by using a single finger on the affected side. All patients completed the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and underwent scoring of eustachian tube inflammation using the Endoscopic Evaluation of the Eustachian Tube (3ET) system. RESULTS: Seventy-three patients were included in the study. Symptoms were localized to the external auditory canal (EAC) in 28 (38.4%), to the infratemporal fossa (ITF) below the lobule in 37 (50.7%), and to the preauricular region in 8 (11.0%). Demographics and medical history were similar between groups. The EAC group had significantly more negative tympanometric peak pressure (TPP) (median, -92.0 daPa; IQR, 95.5) and higher 3ET scores. In contrast, the ITF group had normal TPP (median, -2.0 daPa; IQR, 7.0) and higher 3ET scores. The preauricular group was more likely to have temporomandibular joint or pterygoid muscle pain. ETDQ-7 scores did not differ significantly between groups. CONCLUSION: Symptom localization is associated with specific objective findings in the evaluation of aural discomfort. Patients with pain localizing to the ITF are more likely to have findings of eustachian tube salpingitis without obstruction whereas patients with symptoms deep in the EAC are more likely to have findings consistent with obstructive eustachian tube dysfunction. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1818-1823, 2023.


Subject(s)
Ear Diseases , Eustachian Tube , Salpingitis , Adult , Female , Humans , Adolescent , Surveys and Questionnaires , Endoscopy , Ear Diseases/diagnosis
12.
Laryngoscope Investig Otolaryngol ; 7(4): 955-962, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36000052

ABSTRACT

Background: Oral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation. We aimed to determine outcomes of oral cavity defect reconstruction using scapular tip free flaps with a myogenous intraoral component. Methods: All patients with a mandibular or maxillary bony defect that included a disruption of the intraoral mucosa component between 07/1/14 and 07/31/17. Patients were reconstructed with a scapular tip free flap, which included a muscular component that was used to recreate the oral mucosa. The primary study outcomes were flap success rates, development of orocutaneous or oronasal fistula, rate of resuming oral diet as well as the occurrence of medical and surgical complications in the first month following surgery. The tested hypothesis was formulated before data collection began. Results: Twenty-five patients were identified by the study criteria. There was one (4%) flap that failed, while orocutaneous fistula occurred in two patients (8%). Prior history of osteoradionecrosis was a statistically significant predictor of overall complication (p < .05). Conclusions: Intraoral myogenous reconstruction allows for re-mucosalization of the oral cavity defect and is associated with high viability and low-complication rates. In patients with amenable oral mucosal defects, a myogenous scapular tip free flap is a suitable reconstructive option.

13.
Anim Biosci ; 35(12): 1911-1920, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35798046

ABSTRACT

OBJECTIVE: This study was performed to determine the apparent metabolizable energy (AMEn) content of tannin-free red/bronze, white/tan and U.S. No. 2 varieties of grain sorghum for feeding Japanese quail and validate their nutrient profile by evaluating effects on performance and carcass traits with full-substitution of corn. METHODS: Experiment 1 determined the AMEn content of red/bronze, white/tan, and U.S. No. 2 grain sorghum varieties fed to mixed-sex Japanese quail (Coturnix japonica) (n = 314) at 3 and 6-weeks of age. Analyses were based on a 2×4 factorial treatment design with age and grain types defining the treatments, and a randomized complete block experiment design with cage and trials defining the block. AMEn values were validated by evaluating the performance and carcass traits of Japanese quail (n = 644) from 1 to 40 days of age in Experiment 2 with birds were fed 1 of 4 complete diets. Statistical analyses were conducted on performance data and select individual carcass trait measurements. RESULTS: Determined AMEn values at 3-weeks of age were 3,524±122.03 (red/bronze), 3,252±122.03 (white/tan), and 3,039±123.44 (U.S. No. 2) kcal/kg. At 6-weeks of age, determined AMEn were 3,373±297.35 (red/bronze), 3,279±297.35 (white/tan), and 2,966±298.64 (U.S. No. 2) kcal/kg. Carcass traits showed live body weight (p = 0.0409) and hot carcass weight (p = 0.0234) were greatest in U.S. No. 2; however, carcass yield (p<0.0001) was lowest. No significant differences were observed among treatments for feed intake, feed conversion ratio, breast weight and breast yield (p>0.05). CONCLUSION: These studies demonstrated that tannin-free grain sorghum varieties may be a potential alternative to corn in quail diets while maintaining growth performance and carcass parameters.

14.
Microsurgery ; 42(1): 80-83, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34403154

ABSTRACT

Near-total mandibular reconstruction poses many challenges to reconstructive surgeons. The purpose of this article is to present a challenging case in a patient with osteoradionecrosis of the mandible requiring a near-total mandibular reconstruction using bilateral scapula tip free tissue reconstruction. A 68-year-old African-American male with a history of T2N0M0 squamous cell carcinoma of the tonsil presented with advanced stage osteoradionecrosis of the mandible. Reconstruction was planned using 3D Systems (Denver, CO), mandibular osteotomies were planned inferior to the sigmoid notch on the ascending rami. Neither fibula flap was amenable for harvesting due to poor vasculature of the patient's lower extremities, and bilateral scapula tip free flaps were subsequently planned. The post-operative course was complicated by venous congestion in the right scapula flap which required revision to the venous anastomosis on POD 1. The patient had intraoral breakdown that required debridement in the operating room and application of a cellular matrix. The patient fully recovered from the acute surgery and was discharged home without a tracheostomy. At the last follow up visit, the patient was taking 100% of diet peroral and had no signs of oral incompetence, mental projection was satisfactory, and the ability to verbally communicate was unimpaired. We report a complex case of near-total mandibular reconstruction using simultaneous bilateral scapula tip free flaps. While we do not advocate simultaneous bilateral scapula tip free flaps as the standard of care for large mandibulectomy defects, it may be considered for patients in which traditional osseous free flaps are not available.


Subject(s)
Free Tissue Flaps , Mandibular Reconstruction , Osteoradionecrosis , Plastic Surgery Procedures , Aged , Fibula , Humans , Male , Mandible/surgery , Osteoradionecrosis/etiology , Osteoradionecrosis/surgery , Scapula/surgery
15.
BMC Psychiatry ; 21(1): 331, 2021 07 03.
Article in English | MEDLINE | ID: mdl-34217252

ABSTRACT

BACKGROUND: Frontal variant frontotemporal dementia is a common cause of presenile dementia. A hexanucleotide expansion on chromosome 9 has recently been recognized as the most common genetic mutation cause of this illness. This sub-type tends to present psychiatrically with psychosis being a common presenting symptom before the onset of cognitive changes or brain atrophy. A few case series have been published describing the prominence of early psychotic symptoms, and lack of clear brain atrophy on clinical brain imaging imposing a challenge in reaching early accurate diagnosis. In this report, we present a case whereby the diagnosis of Schizophrenia syndrome was made and the patient was treated for years with multiple interventions for that syndrome before reaching the accurate diagnosis of Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9. This diagnosis was confirmed after genetic testing and findings on a hybrid Positron Emission Tomography/Magnetic Resonance Imaging scanning. A 60-year-old female diagnosed with schizophrenia at age 50 after presenting with delusions and hallucinations, which proved to be refractor to several lines of pharmacological and non-pharmacological interventions including electroconvulsive therapy. Patient had a history of post-partum psychosis in her 20s. She was referred to cognitive neurology due to progressive decline in function. While clinical structural brain imaging data were not adequate to support an alternative neurological diagnosis, careful inquiry elicited a history of psychotic illness followed by progressive decline in a sister. Genetic testing confirmed hexanucleotide expansion on chromosome 9 mutation. The patient was offered a state-of-the-art FD-Glucose Positron Emission Tomography/Magnetic Resonance Imaging scan available at our centre. While volumetric Magnetic Resonance Imaging scan did not show volume loss in frontotemporal areas, the hybrid scan showed regionally specific deficit in FD-Glucose Positron Emission Tomography affecting medial superior frontal, insula, inferior temporal, thalamus, and anterior cingulate cortex consistent with behavioral variant frontotemporal dementia. CONCLUSIONS: This case highlights the importance of considering Frontal variant frontotemporal dementia due to hexanucleotide expansion on chromosome 9 when facing relatively late-onset, refractory schizophrenia-like syndrome. Careful history from all available sources to elicit family history of similar presentation is very important. Genetic testing and functional brain imaging can aid in confirming the diagnosis and potentially streamlining the management of these cases.


Subject(s)
Schizophrenia , Brain/diagnostic imaging , C9orf72 Protein/genetics , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Mutation , Neuroimaging , Schizophrenia/diagnostic imaging , Schizophrenia/genetics
16.
Breast Cancer Res Treat ; 189(1): 103-110, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34120223

ABSTRACT

PURPOSE: Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). METHODS: Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. RESULTS: Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). CONCLUSION: Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.


Subject(s)
Breast Neoplasms , Maytansine , Ado-Trastuzumab Emtansine/adverse effects , Adult , Amenorrhea/chemically induced , Amenorrhea/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Female , Humans , Maytansine/adverse effects , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/therapeutic use , Receptor, ErbB-2/genetics , Trastuzumab/adverse effects , Young Adult
17.
Ann Otol Rhinol Laryngol ; 129(10): 988-995, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32456500

ABSTRACT

OBJECTIVE: To examine the use of intramuscular corticosteroid (IMCS) injections for treatment of acute upper respiratory infections (URI) and the influence on healthcare utilization. METHODS: This retrospective cohort study used patient encounter data from a large multicenter regional health care system between 2013 and 2017. Adult patients diagnosed with acute URI (acute pharyngitis, acute sinusitis, acute otitis media, and URI not otherwise specified) during ambulatory encounters were included. Follow-up encounters for a diagnosis of acute URI within 60 days were identified and patient characteristics, encounter details, and procedure codes were retrieved. Frequency data was used to calculate IMCS injection administration prevalence, utilization trends, and associations with covariates. Follow-up data for return encounters within 60 days for the same diagnosis was examined. RESULTS: Of the 153 848 initial encounters, 34 600 (22.5%) patients received IMCS injection for acute URI. Injection rates varied from 0.85% to 49.1% depending on specialty and practitioner type. Internal medicine, family medicine, urgent care, and otorhinolaryngology clinics most commonly administered IMCS. 3788 patients returned for a second encounter of which 751 (19.8%) received an injection. IMCS injection during the first encounter was associated with increased odds of repeat visit within 60 days (OR: 1.74; 95% CI: 1.61-1.88). CONCLUSION: IMCS use in the treatment of acute URI is highly prevalent despite lack of evidence for impact and safety. Prevalence is variable across multiple medical and surgical specialties including otorhinolaryngology. Administration of IMCS injection may contribute to the likelihood of a subsequent healthcare visit for the same indication.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Ambulatory Care/statistics & numerical data , Otitis Media/drug therapy , Pharyngitis/drug therapy , Practice Patterns, Physicians' , Respiratory Tract Infections/drug therapy , Sinusitis/drug therapy , Acute Disease , Adult , Aged , Family Practice , Female , Humans , Injections, Intramuscular , Internal Medicine , Male , Middle Aged , Otolaryngology , Patient Acceptance of Health Care , Retrospective Studies
18.
Otolaryngol Head Neck Surg ; 162(5): 612-621, 2020 May.
Article in English | MEDLINE | ID: mdl-32122242

ABSTRACT

OBJECTIVE: To describe the level of knowledge of human papillomavirus (HPV) and HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) among the general population and health care providers. DATA SOURCES: Systematic search was performed on December 20, 2018, using MEDLINE (1966 to December 2018), EMBASE (1975 to December 2018), Web of Science (1900 to December 2018), and CENTRAL (1996 to December 2018) databases. English-language literature involving human subjects was used, and studies were limited to case series, case-control, cohort, and randomized controlled trial designs. REVIEW METHODS: Studies were included if they assessed knowledge of HPV and HPV-associated OPSCC. The primary outcome measure was the knowledge of HPV-associated OPSCC among the general population and with health care providers. Meta-analysis of proportions was attempted using random-effects model. The PRISMA guidelines were used for accuracy of reporting. RESULTS: Thirty-two studies were included with 17,288 participants. There was a high degree of heterogeneity preventing completion of a meta-analysis. Knowledge of HPV and HPV-associated OPSCC varied between the general population and health care providers. The proportion of the general population and health care providers with knowledge of HPV ranged from 16% to 75% and 21% to 84%, respectively. Knowledge of HPV-associated OPSCC was greater in health care providers and ranged from 22% to 100% compared with the general population, which ranged from 7% to 57%. CONCLUSION: There is a knowledge gap of HPV-associated OPSCC for both the general population and health care providers. Additional education may not only increase awareness but may also result in prevention and earlier detection.


Subject(s)
Awareness , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/virology , Squamous Cell Carcinoma of Head and Neck/virology , Humans
19.
Public Health ; 182: 39-44, 2020 May.
Article in English | MEDLINE | ID: mdl-32163761

ABSTRACT

OBJECTIVES: Recent trends of 'vaccine hesitancy' have resulted in calls for public health campaigns to improve immunisation uptake to World Health Organisation (WHO) targets. One potential strategy to improve uptake is to offer opportunistic vaccination to those hospital in-patients who have missed them. We aimed to evaluate parental and staff attitudes about introducing such a service for hospitalised children. STUDY DESIGN: Cross sectional questionnaire-based design. METHODS: We developed and distributed a questionnaire for parents/guardians of paediatric inpatients aged 5 years and under, and a questionnaire for frontline paediatric staff (including medical, nursing and allied health professionals). Vaccination rates were assessed through discussion with parents and by reviewing the personal child health record. RESULTS: One-hundred families and 100 paediatric staff participated. Local vaccination rates were significantly below the WHO target (P < 0.001), particularly for the Bacille Calmette-Guerine (BCG) vaccination (P = 0.001). Both parents (89/100, 89%) and staff (87/100, 87%) regarded inpatient opportunistic vaccination acceptable. Parents of children with chronic disease reported a potentially higher rate of missed vaccinations, stating reasons of frequent illness and inpatient stays. The majority of staff (81/95, 85.3%) would be willing to support inpatient vaccination if appropriately trained. A significant minority had reservations. CONCLUSIONS: Opportunistic vaccination is a strategy deemed acceptable by the majority of parents and staff. Children with chronic disease would especially benefit from opportunistic inpatient immunisation. In order to facilitate this, improved digital access to primary care vaccination records and investment in staff training, education and support would be required.


Subject(s)
Attitude of Health Personnel , Hospitals , Parents/psychology , Vaccination/methods , Child, Preschool , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Health Personnel/education , Health Personnel/psychology , Health Promotion , Humans , Immunization/methods , Infant , Infant, Newborn , Inpatients , Male , Parents/education , Surveys and Questionnaires , Vaccines/administration & dosage
20.
Ochsner J ; 19(2): 181-183, 2019.
Article in English | MEDLINE | ID: mdl-31258433

ABSTRACT

Background: Metastatic melanoma to the mucosa of the upper aerodigestive tract is extremely rare, accounting for <0.6% of known metastasis to the head and neck region. We present a case of delayed metastatic melanoma to the pharyngeal tonsil. Case Report: A 57-year-old African American female presented for evaluation of a rapidly enlarging unilateral tonsil mass. Three years prior to presentation, she had undergone primary resection of and systemic therapy for cutaneous melanoma on the sole of her right foot. Tonsillectomy confirmed the diagnosis of metastatic melanoma. Because of the poor prognosis of the disease, the patient was referred for palliative chemotherapy but died shortly after beginning treatment. Conclusion: Metastatic melanoma is a rare disease in African Americans, and the presence of metastatic lesions is a significant prognostic indicator for long-term patient survival. Meticulous head and neck examinations should be performed during the follow-up period, and any pigmented lesion should have a high suspicion for metastasis in any patient with a history of cutaneous melanoma.

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