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Sialadenoma papilliferum (SP) is a rare salivary gland tumor mostly reported in the oral cavity. Here we describe a bronchial SP in the left upper lobe bronchus of a 10-year-old boy. At bronchoscopy, a well-circumscribed polypoid lesion protruding into the bronchial lumen was identified. The tumor was excised, but eventually, the patient had to undergo a sleeve resection after 2 recurrences. Pathology revealed a papillocystic lesion with exophytic and endophytic components. The cells lining the exophytic surface and papillary structures were columnar and squamous, and the cells lining endophytic cystic and papillary structures were cuboidal to columnar, all of which were diffusely reactive with antibodies to SOX10 protein. The presence of basal cells was demonstrated by p63 immunoreactivity. The cells failed to immunohistochemically express BRAF V600E. Fluorescence in situ hybridization analysis revealed no MAML2 or RET gene rearrangement. The patient is alive 24 years after resection with no additional recurrences. Bronchial SP needs to be recognized and distinguished from other benign and malignant salivary gland and pulmonary neoplasms so that patients can receive appropriate treatment and follow-up.
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Stemming from early seminal notions of molecular recognition and encapsulation, three-dimensional, cavity-containing capsular compounds and assemblies have attracted intense interest due to the ability to modulate chemical and physical properties of species encapsulated within these confined spaces compared to bulk environments. With such a diverse range of covalent motifs and non-covalent (supramolecular) interactions available to assemble building blocks, an incredibly wide-range of capsular-type architectures have been developed. Furthermore, synthetic tunability of the internal environments gives chemists the opportunity to engineer systems for uses in sensing, sequestration, catalysis and transport of molecules, just to name a few. In this tutorial review, an overview is provided into the design principles, synthesis, characterisation, structural facets and properties of coordination cages, porous organic cages, supramolecular capsules, foldamers and mechanically interlocked molecules. Using seminal and recent examples, the advantages and limitations of each system are explored, highlighting their application in various tasks and functions.
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Purpose: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. Methods: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Results: Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Conclusion: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.
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BACKGROUND: Drug-induced liver injury (DILI) is a major concern for oncology drugs in clinical practice and under development. Monitoring cancer patients for hepatotoxicity is challenging as these patients may have abnormal liver tests pre-treatment or on-study for many reasons including liver injury due to past oncology treatments, hepatic metastases, medical co-morbidities such as heart failure, and concomitant medications. At present, there are no regulatory guidelines or position papers that systematically address best practices pertaining to DILI detection, assessment and management in oncology patients. AIMS: The goals of this review are (1) to examine and interpret the available evidence and (2) to make recommendations for detection, monitoring, adjudication, and management of suspected hepatocellular DILI during oncology clinical trials. METHODS: This manuscript was developed by the IQ Consortium (International Consortium for Innovation and Quality in pharmaceutical development) DILI Initiative that consists of members from 17 pharmaceutical companies, in collaboration with academic and regulatory DILI experts. The manuscript is based on extensive literature review, expert interpretation of the literature, and several rounds of consensus discussions. RESULTS: This review highlights recommendations for patient eligibility for clinical trials with or without primary/metastatic liver involvement, as well as changes in liver tests that should trigger increased monitoring and/or discontinuation of study drug. Guidance regarding causality assessment for suspected DILI events, rechallenge and dose-modification is provided. CONCLUSIONS: This review brings together evidence-based recommendations and expert opinion to provide the first dedicated consensus for best practices in detection, assessment, and management of DILI in oncology clinical trials.
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PURPOSE: DEK::AFF2 fusion-associated squamous cell carcinoma (DEK::AFF2 SCC), also reported in the literature as low-grade papillary sinonasal (Schneiderian) carcinoma (LGPSC), is a rare, primarily bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), especially on small or limited biopsy, often leading to misdiagnosis. DEK::AFF2 SCC is devoid of the underlying mutually exclusive EGFR or KRAS driver mutations of SP, suggesting it may represent a distinct unique entity. METHODS: In this study, we conducted a retrospective search of "unusual" SP reported either as atypical, dysplastic, or suspicious for malignant transformation at our institution in the last 13 years (2010-2023), to identify potential cases of DEK::AFF2 SCC. RESULTS: Of the 201 SP cases during this time period, 30 "unusual" SP cases were identified. On morphologic review of these 30 cases, 6 were worrisome for DEK::AFF2 SCC and were selected for AFF2 immunohistochemical stain (IHC), of which 3 cases were positive. All 3 AFF2 IHC positive cases were also positive for DEK::AFF2 fusion by fluorescence in situ hybridization (FISH), thereby, confirming IHC results. CONCLUSIONS: This study highlights that AFF2 IHC can be an invaluable surrogate marker to FISH in identifying DEK::AFF2 SCC in challenging cases to avoid misdiagnosis. Detailed clinical and pathologic data were collected to gain a better understanding of this emerging challenging entity. A literature review was performed to enrich our knowledge of DEK::AFF2 SCC.
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Proteínas Cromossômicas não Histona , Proteínas Oncogênicas , Proteínas de Ligação a Poli-ADP-Ribose , Humanos , Masculino , Proteínas de Ligação a Poli-ADP-Ribose/genética , Pessoa de Meia-Idade , Feminino , Proteínas Oncogênicas/genética , Proteínas Cromossômicas não Histona/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Idoso , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/genética , Adulto , Estudos Retrospectivos , Proteínas de Fusão Oncogênica/genéticaRESUMO
Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54-66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02-1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34-1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02-1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08-1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management.
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Terapia de Imunossupressão , Imunossupressores , Transplante de Fígado , Neoplasias Cutâneas , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Retrospectivos , Idoso , Estados Unidos/epidemiologia , Imunossupressores/efeitos adversos , Neoplasias Cutâneas/epidemiologia , Terapia de Imunossupressão/efeitos adversos , Fatores de Risco , Incidência , Queratinócitos/imunologia , Inibidores de Calcineurina/efeitos adversos , Carcinoma Basocelular/epidemiologiaRESUMO
The concept of using diet as therapy in inflammatory bowel disease (IBD) is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to affect not only disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review is to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.
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BACKGROUND & AIMS: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD. METHODS: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 United States sites from 2019 to 2022. Parents/guardians reported race, ethnicity, time between symptom onset and diagnosis, and other social determinants of health. Through bivariate and multivariable analyses using generalized estimating equations, we evaluated associations between these factors and diagnosis time defined as ≤60 days, 61 to 180 days, 181 to 365 days, and >365 days. RESULTS: We enrolled 869 participants (mean age at diagnosis, 13.1 years; 52% male; 57% Crohn's disease [CD]; 34% ulcerative colitis [UC]; 8% Hispanic; 30% non-White). Overall, the mean time to diagnosis was 265.9 days. After adjustment, factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.9-3.5), 2 or more other health conditions (OR, 1.7; 95% CI, 1.1-2.7), and longer travel time to clinic (>1 hour [OR, 1.7; 95% CI, 1.2-2.4], >2 hours (OR, 1.8; 95% CI, 1.2-2.9] each vs <30 minutes). There was no association with race, ethnicity, birth country, sex, parent education, household income, insurance type, health literacy, and health system distrust. CONCLUSIONS: Consistent with prior literature, diagnostic delay is longer for CD than UC. Reassuringly, time to diagnosis is equitable across racioethnic groups. New models of diagnostic care are needed for communities affected by longer travel times.
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Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission.
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INTRODUCTION: Many of the first line medications for the treatment of active and latent M. tuberculosis are hepatoxic and cause a spectrum of anti-tuberculosis drug induced liver injury (ATLI), including acute liver failure (ALF). Despite advances in recognition of and prevention of ATLI, isoniazid remains one of the leading causes of DILI as well as drug-induced ALF. AREAS COVERED: A literature search of the incidence, risk factors, current societal guidelines, monitoring, and prophylactic medication usage in ATLI was performed using PubMed and institutional websites. Relevant articles from 1972 to 2024 were included in this review. EXPERT OPINION: Current societal guidelines regarding ATLI monitoring are mixed, but many recommend liver enzyme testing of high-risk populations. We recommend liver test monitoring for all patients on multi-drug therapy as well as those on isoniazid therapy. Precision medicine practices, such as N-acetyltransferase-2 polymorphism genotyping, are thought to be beneficial in reducing the incidence of ATLI in high-risk populations. However, broader implementation is currently cost prohibitive. Hepatoprotective drugs are not currently recommended, although we do recognize their potential. In patients who develop ATLI but require ongoing anti-TB treatment, strategies to restart the same or less hepatotoxic regimens are currently being followed.
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Antituberculosos , Doença Hepática Induzida por Substâncias e Drogas , Isoniazida , Gestão de Riscos , Tuberculose , Humanos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Antituberculosos/efeitos adversos , Antituberculosos/administração & dosagem , Fatores de Risco , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Isoniazida/efeitos adversos , Isoniazida/administração & dosagem , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/prevenção & controle , Falência Hepática Aguda/tratamento farmacológico , Guias de Prática Clínica como Assunto , Incidência , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Testes de Função Hepática , Medicina de PrecisãoRESUMO
Vancomycin and daptomycin are frequently used in outpatient parenteral antimicrobial therapy (OPAT). We analyze health care utilization and cost to the health care system for vancomycin vs daptomycin in the outpatient setting and find that vancomycin results in significantly higher health care utilization and similar cost per course compared with daptomycin in OPAT.
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Due to the anatomic complexity of the head and neck and variable proximity between laboratory and operating room (OR), effective communication during frozen section analysis (FSA) between surgeons and pathologists is challenging. This proof-of-concept study investigates an augmented reality (AR) protocol that allows pathologists to virtually join the OR from the laboratory. Head and neck cancer specimens were scanned ex vivo using a 3-dimensional scanner and uploaded into an AR platform. Eight head and neck specimens were discussed by surgeons and pathologists in an AR environment. AR-guided intraoperative consultation was used for specimen orientation and discussion of FSA margin sampling sites. One patient had positive initial margins on FSA and was re-resected to negative final margins. AR-guided FSA is possible and allows pathologists to join the operating from any location for intraoperative discussion.
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PURPOSE: Multidisciplinary tumor boards (TB) are the standard for discussing complex head and neck cancer cases. During TB, imaging and microscopic pathology is reviewed, but there is typically no visualization of the resected cancer. METHODS: A pilot study was conducted to investigate the utility of visual pathology reports at weekly TB for 10 consecutive weeks. Faculty-level participants completed a pre-survey and post-survey to assess understanding of resected cancer specimens. RESULTS: Providers (n = 25) across seven medical specialties completed pre-survey and post-survey. Following intervention, providers reported significant improvement in understanding of anatomic orientation of the specimen and sites of margin sampling (mean 47.4-96.1, p < 0.001), ability to locate the site of a positive margin (mean 69.5-91.1, p < 0.001), and confidence in treatment plans created (mean 69.5-89.2, p < 0.001) with the addition of visual pathology reports. CONCLUSIONS: Visual pathology reports improve provider understanding of resected cancer specimens at multidisciplinary TB.
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BACKGROUND: With the increasing legalization of medical and recreational cannabis, patients and providers have growing interest in the role of cannabinoids in treating inflammatory bowel disease. Prior meta-analysis has shown inconclusive evidence for efficacy of cannabinoids. We sought to produce an up-to-date meta-analysis that pools new data to evaluate the therapeutic effects of cannabinoids in both Crohn's disease (CD) and ulcerative colitis (UC). METHODS: PubMed, Embase, CENTRAL and CINAHL were queried for randomized-controlled trials evaluating the impact cannabinoids in CD or UC. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. RESULTS: Eight studies, including 4 studies of CD, 3 studies of UC, and 1 study of both diseases met inclusion criteria. Among 5 studies of CD, a statistically significant decrease in clinical disease activity following intervention was observed (risk ratios [RR],â -0.91; 95% CI, CI:1.54 to CI:0.28, I2â =â 71.9%). Clinical disease activity in UC was not significantly lower in the pooled analysis (RR, -2.13; 95% CI, -4.80 to 0.55; I2â =â 90.3%). Improvement in quality of life (QoL) was observed in both CD and UC combined (RR, 1.79; 95% CI, 0.92-0.2.66; I2â =â 82.8%), as well as individually. No differences were observed in the analysis on endoscopic disease activity and inflammatory markers. CONCLUSIONS: This meta-analysis of clinical trials suggests that cannabinoids are associated with improved quality of life in both CD and UC, as well as improved disease activity but not inflammation.
This updated systematic review and meta-analysis suggests that cannabis for inflammatory bowel disease may improve quality of life and disease activity but not inflammation.
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End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1 y) or late (≥1 y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10 mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction.
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BACKGROUND: Fatigue imposes a socioeconomic burden on patients with Crohn's disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue. METHODS: Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician's Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue. RESULTS: The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician's global assessment, and night-time bowel movements were significantly associated with fatigue. CONCLUSIONS: Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can lead to fatigue in many patients regardless of their disease severity. Fatigue not only affects patients' quality-of-life but also their ability to work and their mental health. However, research specific to the IBD related symptoms that contribute to fatigue in these patients is not currently available, especially in the United States (US). To address this gap, real-world data was analyzed to understand how common fatigue is among patients with CD and UC in the US and clinical symptoms that co-occur with fatigue. We found that fatigue affects more than 40% of the patients. Our results suggest that fatigue is correlated with more severe disease symptoms and overall lower well-being among patients with CD and UC.
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Colite Ulcerativa , Doença de Crohn , Fadiga , Humanos , Doença de Crohn/epidemiologia , Doença de Crohn/complicações , Masculino , Feminino , Fadiga/epidemiologia , Fadiga/etiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/complicações , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Prevalência , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Ibrexafungerp is a new triterpenoid antifungal agent with activity against a variety of fungal species, including Aspergillus spp. and echinocandin-resistant Candida spp. AREAS COVERED: This evaluation will summarize currently available clinical evidence on the use of ibrexafungerp in the treatment/prevention of vulvovaginal candidiasis (VVC) and detail the mechanism of action, pharmacokinetic/pharmacodynamic parameters, and ongoing/latest research involving ibrexafungerp. EXPERT OPINION: The evidence involving the utilization of ibrexafungerp for the treatment of VVC shows that it is superior when compared to placebo and has comparable clinical cure rates when compared with fluconazole. Ibrexafungerp demonstrates reliable coverage against several Candida spp. including echinocandin-resistant strains, Candida auris, and Aspergillus spp. For VVC, a dose of 300 mg (two 150 mg tablets) twice daily is recommended and does not require dose adjustments based on renal or hepatic function. The use of ibrexafungerp outside of VVC is currently under study with several ongoing trials showing promising interim data.
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Antifúngicos , Candida , Candidíase Vulvovaginal , Farmacorresistência Fúngica , Triterpenos , Humanos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Feminino , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Triterpenos/administração & dosagem , Triterpenos/farmacocinética , Triterpenos/farmacologia , Fluconazol/administração & dosagem , Fluconazol/farmacocinética , Fluconazol/farmacologia , Animais , Aspergillus/efeitos dos fármacos , Glicosídeos/administração & dosagem , Glicosídeos/farmacocinética , Glicosídeos/farmacologia , Relação Dose-Resposta a DrogaRESUMO
PURPOSE: To report the indications and outcomes of emergency keratoplasty over a 21-year period in Greenlane Clinical Centre, the major tertiary eye referral center in Auckland, New Zealand (Aotearoa). METHODS: A retrospective review of medical records of all emergency keratoplasties performed in Greenlane Clinical Centre from January 2000 to September 2021 was conducted. Demographic, preoperative, intraoperative, and 1-year postoperative data were collected. RESULTS: Emergency keratoplasty was performed in 102 eyes of 97 patients (54 men), comprising 5.6% of transplants performed (N = 1830) in this period. The mean age was 53 years (range = 4-95 years, SD = 20). Patients of Maori ethnicity were overrepresented (31%). Corneal perforation was present in 90% of eyes, and microbial keratitis was the most common indication. Bacteria were the most commonly isolated organisms (38%). The mean preoperative and 12-month postoperative best potential corrected distance visual acuity was 1.6 and 1.2 (logMAR), respectively. All cases of therapeutic keratoplasty achieved initial therapeutic success, with no eyes lost or requiring repeat emergency keratoplasty. Complications included nonhealing epithelial defects (19%), cataract (19%), glaucoma (15%), allograft rejection (13%), and corneal melting (5%). Fifteen cases (15%) had documented graft failure at 12 months. Multivariate analysis revealed that younger age was the only statistically significant factor associated with failure at 12 months. CONCLUSIONS: Emergency keratoplasty was the indication for 5.6% of keratoplasties performed. Our results compare favorably with those in the literature, possibly because of early intervention and lower incidence of fungal keratitis. The reported overrepresentation of Maori has important implications for health access and delivery in New Zealand.
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The current work investigated the effects of mass-loading the eardrum on wideband absorbance in humans. A non-invasive approach to mass-loading the eardrum was utilized in which water was placed on the eardrum via ear canal access. The mass-loaded absorbance was compared to absorbance measured for two alternative middle ear states: normal and stiffened. To stiffen the ear, subjects pressurized the middle ear through either exsufflation or insufflation concurrent with Eustachian tube opening. Mass-loading the eardrum was hypothesized to reduce high-frequency absorbance, whereas pressurizing the middle ear was hypothesized to reduce low- to mid-frequency absorbance. Discriminant linear analysis classification was performed to evaluate the utility of absorbance in differentiating between conditions. Water on the eardrum reduced absorbance over the 0.7- to 6-kHz frequency range and increased absorbance at frequencies below approximately 0.5 kHz; these changes approximated the pattern of changes reported in both hearing thresholds and stapes motion upon mass-loading the eardrum. Pressurizing the middle ear reduced the absorbance over the 0.125- to 4-kHz frequency range. Several classification models based on the absorbance in two- or three-frequency bands had accuracy exceeding 88%.
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Orelha Média , Pressão , Membrana Timpânica , Humanos , Masculino , Feminino , Membrana Timpânica/fisiologia , Membrana Timpânica/anatomia & histologia , Orelha Média/fisiologia , Orelha Média/anatomia & histologia , Adulto , Adulto Jovem , Elasticidade , Estimulação Acústica , Tuba Auditiva/fisiologia , Tuba Auditiva/anatomia & histologia , Estribo/fisiologia , Água , Análise DiscriminanteRESUMO
Articulating clear and achievable expectations is fundamental to both education and organizational management. In this article, we provide a simple intervention for clarifying expectations-and establishing that these expectations have been understood-which proved beneficial both to community college interns and to their internship mentors in biotech-related undergraduate research experiences. Internship mentors were asked to utilize a simple Expectation Clarity Tool to outline the expectations, success metrics, baseline assessments, and training strategy and support that would be foundational to their intern's project. These included expectations around conceptual, technical, performance, and professional skills and behaviors. Concurrently, but independently, community college interns were asked to complete the same type of exercise as a way of identifying gaps in their knowledge and understanding of their mentor's expectations and their internship project. The mentor's completed Expectation Clarity Tool was then shared with their intern. As a result of completing this relatively simple intervention, the majority of mentors reported that it increased their confidence as a mentor, taught them a new mentoring skill, changed how they will mentor trainees moving forward, and positively impacted their relationship with their trainee. On the intern side, the majority of interns reported that engaging in this intervention, both as an independent exercise and in obtaining their mentor's completed Expectation Clarity Tool, increased their confidence as an intern and positively impacted the success of their internship.