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OBJECTIVE: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. METHODS: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE É4 status, and Area Deprivation Index. RESULTS: Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (ß = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (ß = 2.65, 95% CI = 0.38-4.91, p = 0.023). INTERPRETATION: Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.
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Enfermedad de Alzheimer , Trastornos del Conocimiento , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/complicaciones , Negro o Afroamericano , Trastornos del Conocimiento/etiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/complicaciones , Factores de Riesgo , BlancoRESUMEN
While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to SH TP53MT AML (p <0.001); whereas ASXL1 (p= <0.001), RAS (p<0.001), splicing factor (p= 0.003), IDH1/2 (p= 0.001), FLT3 ITD (p= <0.001) and NPM1 (p= 0.005) mutations significantly clustered with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between SH and MH (event free survival [EFS]: 3.0 vs 2.20 months, p= 0.22/ overall survival [OS]: 8.50 vs 7.53 months, respectively, p= 0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation (allo-HCT) as a time-dependent covariate were associated with superior EFS (HR; 0.44, 95% CI: 0.19-1.01, p= 0.05/ HR; 0.34, 95% CI: 0.18-0.62, p<0.001) and OS (HR; 0.24, 95% CI: 0.08-0.71, p= 0.01/ HR; 0.28, 95% CI: 0.16-0.47, p<0.001). While complex CG (HR; 1.56, 95% CI: 1.01-2.40, p= 0.04) retained unfavorable significance for OS. Our analysis suggests that unlike in MDS, multihit TP53MT is less relevant in independently predicting outcomes in patients with AML.
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BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. STUDY: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. RESULTS: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. CONCLUSIONS: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.
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Enfermedad de Crohn , Sistema Renina-Angiotensina , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Enfermedad de Crohn/tratamiento farmacológico , Estudios Retrospectivos , Progresión de la Enfermedad , Corticoesteroides/efectos adversosRESUMEN
INTRODUCTION: The scarcity of available organs for kidney transplantation has resulted in a substantial waiting time for patients with end-stage kidney disease. This prolonged wait contributes to an increased risk of cardiovascular mortality. Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, and it is common among candidates for kidney transplant. The aim of this study was to correlate abdominal arterial calcification (AAC) score value with mortality on the waitlist. METHODS: We modified the coronary calcium score and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were listed for kidney transplant, between 2005 and 2015, and had abdominal computed tomography scan. Patients were divided into two groups: those who died on the waiting list group and those who survived on the waiting list group. RESULTS: Each 1,000 increase in the AAC score value of the sum score of the abdominal aorta, bilateral common iliac, bilateral external iliac, and bilateral internal iliac was associated with increased risk of death (HR 1.034, 95% CI: 1.013, 1.055) (p = 0.001). This association remained significant even after adjusting for various patient characteristics, including age, tobacco use, diabetes, coronary artery disease, and dialysis status. CONCLUSION: The study highlights the potential value of the AAC score as a noninvasive imaging biomarker for kidney transplant waitlist patients. Incorporating the AAC scoring system into routine imaging reports could facilitate improved risk assessment and personalized care for kidney transplant candidates.
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Trasplante de Riñón , Calcificación Vascular , Listas de Espera , Humanos , Listas de Espera/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Calcificación Vascular/mortalidad , Calcificación Vascular/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Anciano , Tomografía Computarizada por Rayos X , Aorta Abdominal/diagnóstico por imagenRESUMEN
OBJECTIVE: The aim of this study was to highlight the safety of OnabotulinumtoxinA (BTA) injections, with or without concurrent pudendal nerve block, in treating women with myofascial pelvic pain (MFPP). DESIGN: This was a retrospective cohort study. SETTING: The review was conducted in a tertiary care academic center. Participants/Materials: We conducted a chart review of patients who were diagnosed with MFPP and treated with BTA with or without pudendal nerve block between January 2010 and February 2022. METHODS: BTA was injected transvaginally into the pelvic floor muscle group. The primary outcomes were adverse events after BTA injections, and the secondary outcome was the effect of concomitant pudendal nerve block at the time of BTA injections. RESULTS: The cohort included 182 patients; 103 (56.6%) received BTA injections with pudendal nerve block, and 79 (43.4%) received BTA alone. There were no significant demographic differences between the two groups. Post-treatment complications of BTA administration included worsening of pelvic pain (11.5%), constipation (6.6%), urinary tract infection (2.7%), urinary retention (3.8%), and fecal incontinence (2.7%). No statistical difference was noted in the number of phone calls, patient-initiated electronic messages, emergency room visits, or clinic visits for both groups within 30 days post-treatment. The mean number of total injections was 1.6 in the BTA-only group and 1.7 in the BTA with pudendal block group (p = 0.421). Median time to re-intervention with a second BTA injection was 6.0 months; 5.6 months in the BTA with pudendal block group; and 6.8 months in the BTA-only group, p = 0.46. There were 63 re-intervention events after BTA injections. LIMITATIONS: Limitations of our study include the retrospective design making it vulnerable to missing or incomplete data available for review. CONCLUSION: OnabotulinumtoxinA is beneficial in treating women with MFPP; with a duration of therapeutic effect of approximately 6 months. The use of a concurrent pudendal nerve block did not impact clinical outcomes.
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Toxinas Botulínicas Tipo A , Síndromes del Dolor Miofascial , Nervio Pudendo , Femenino , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Dolor Pélvico/tratamiento farmacológico , Dolor Pélvico/etiología , Estudios Retrospectivos , Atención Terciaria de Salud , Síndromes del Dolor Miofascial/tratamiento farmacológico , Bloqueo Nervioso , Inyecciones Intramusculares , Resultado del TratamientoRESUMEN
PURPOSE: Pelvic floor physical therapy (PFPT) is first-line therapy for treatment of pelvic floor tension myalgia (PFTM). Pelvic floor trigger point injections (PFTPI) are added if symptoms are refractive to conservative therapy or if patients experience a flare. The primary objective was to determine if a session of physical therapy with myofascial release immediately following PFTPI provides improved pain relief compared to trigger point injection alone. METHODS: This was a retrospective cohort analysis of 87 female patients with PFTM who underwent PFTPI alone or PFTPI immediately followed by PFPT. Visual analog scale (VAS) pain scores were recorded pre-treatment and 2 weeks post-treatment. The primary outcome was the change in VAS between patients who received PFTPI alone and those who received PFTPI followed by myofascial release. RESULTS: Of the 87 patients in this study, 22 received PFTPI alone and 65 patients received PFTPI followed by PFPT. The median pre-treatment VAS score was 8 for both groups. The median post-treatment score was 6 for the PFTPI only group and 4 for the PFTPI followed by PFPT group, showing a median change in VAS score of 2 and 4, respectively (p = 0.042). Seventy-seven percent of patients in the PFTPI followed by PFPT group had a VAS score improvement of 3 or more, while 45% of patients in the PFTPI only group had a VAS score improvement greater than 3 (p = 0.008). CONCLUSION: PFTPI immediately followed by PFPT offered more improvement in pain for patients with PFTM. This may be due to greater tolerance of myofascial release immediately following injections.
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Mialgia , Puntos Disparadores , Humanos , Femenino , Mialgia/terapia , Estudios Retrospectivos , Diafragma Pélvico , Terapia de Liberación Miofascial , Resultado del TratamientoRESUMEN
BACKGROUND: Preoperative breast MRI is indicated for staging but can lead to complex imaging workups. This study reviewed imaging recommendations made on preoperative MRI exams, to simplify management approaches for patients with newly diagnosed breast cancer. METHODS: This retrospective single-institution review was restricted to women with breast cancer who underwent staging MRI. Additional breast lesions, separate from index tumors, recommended for additional workup or surveillance were assessed to see which were detected and which characteristics predicted success in detection. Univariate mixed-effects logistic modeling predicted the likelihood of finding lesions using MRI-directed ultrasound (US), with odds ratios reported. Tests were two-sided, with a p value lower than 0.05 considered significant. RESULTS: In this study, 534 (39.6%) patients had recommendations for additional workup after preoperative MRI. MRI detected additional malignancy in 178 patients (33.3%). Half of the 66 patients who refused an additional workup and opted for mastectomy had additional malignancies at mastectomy. MRI-directed US was 14 times more likely to detect masses than nonmass enhancement (NME) (p < 0.001). NME was detected on US in only 16% of cases, with one third of subsequent biopsy results considered discordant. Probably benign assessments were given to 35 patients, with 23% not returning for follow-up evaluation and 7% returning at least 6 months later than recommended. CONCLUSION: Use of preoperative breast MRI has increased. Although it can add value, institutions should establish indications and expectations to prevent unnecessary workups. Limiting MRI-directed US to masses, avoiding probably benign assessments, and consulting with patients after MRI but prior to workups can prevent unnecessary exams and confusion.
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Neoplasias de la Mama , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Mastectomía , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
OBJECTIVE: Endosalpingiosis is a poorly understood condition of ectopic epithelium resembling the fallopian tubes. It has been described as an incidental pathology finding, a disease similar to endometriosis, and in association with malignancy. The objective of this study is to determine if endosalpingiosis (ES) has an increased association with gynecologic malignancy when compared to endometriosis (EM). METHODS: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable cohort of EM patients. Demographic and clinical data were obtained, and statistical analysis was performed. RESULTS: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs 48 years, p < 0.001). The ES group had significantly more cancer diagnoses at surgery than the EM group (40.1% vs 18.1%, p < 0.001); this difference persisted in a sub-analysis excluding patients with known or suspected malignancy (20.9% vs 5.6%, p < 0.001). ES patients had lower overall survival (10-year freedom from death: 77.0% vs 90.5%, p < 0.001). After adjusting for confounders, multivariable analysis showed that ES patients had increased cancer diagnosed at surgery (OR = 2.48, p < 0.001) and greater risk of death (OR = 1.69, p = 0.017). CONCLUSIONS: Endosalpingiosis was found concurrently with malignancy in 40% of cases, and this effect was preserved in multi-variable and sub-group analyses. Further research consisting of longer follow-up and exploration of molecular relationships between ES and cancer are forthcoming.
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Endometriosis , Enfermedades de las Trompas Uterinas , Neoplasias de los Genitales Femeninos , Enfermedades Urogenitales , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/epidemiología , Enfermedades de las Trompas Uterinas/diagnóstico , Enfermedades de las Trompas Uterinas/epidemiología , Trompas Uterinas/patología , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/epidemiología , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Procalcitonin (PCT) levels rise in systemic inflammation, especially if bacterial in origin. COVID-19, caused by the novel coronavirus SARS-CoV-2, presents with acute respiratory distress syndrome. Elevated procalcitonin in COVID-19 is considered as a marker for severity of disease. There is no study available that indicates whether elevated PCT in COVID-19 is associated with inflammation or superimposed bacterial infection. The objective of this study is to evaluate the association between PCT levels and superadded bacterial infection, and the effect of discontinuation of antibiotic in the low PCT (<0.25 ng/ml) group on patients' outcomes. METHODS: A retrospective chart review of patients admitted with COVID-19 pneumonia at a single tertiary care centre. We collected information on demographics, co-morbidities, PCT level, antibiotic use, culture results for bacterial infection, hospital length of stay (LOS) and mortality. STATISTICAL ANALYSIS: Continuous variables were summarized with the sample median, interquartile range, mean and range. Categorical variables were summarized with number and percentage of patients. RESULTS AND DISCUSSION: We studied a total of 147 patients with COVID-19 pneumonia. 101 (69%) patients had a low PCT level (< 0.25 ng/ml). Bacterial culture results were negative for all patients, except 1 who had a markedly elevated PCT level (141.ng/ml). In patients with low PCT, 42% received no antibiotics, 59% received antibiotics initially, 32 (57%) patients antibiotic discontinued early (within 24 hours) and their culture remained negative for bacterial infections during hospitalizations. LOS was shorter (6 days in low PCT group compared to 9 days) in high PCT group. LOS was 1 day shorter (5 days vs 6 days) in no antibiotic group compared to antibiotic group. Our study examines the association between PCT level and superadded bacterial infection in COVID-19 pneumonia. Our results demonstrate that most patients admitted with COVID-19 have a low PCT (<0.25 ng/ml), which suggests no superadded bacterial infection and supports the previously published literature regarding low PCT in viral pneumonia. WHAT IS NEW AND CONCLUSION: Procalcitonin level remains low in the absence of bacterial infection. Early de-escalation/discontinuation of antibiotics is safe without adverse outcomes in COVID-19 pneumonia. Early de-escalation/discontinuation of antibiotics is associated with lower LOS.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Tratamiento Farmacológico de COVID-19 , COVID-19/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Privación de Tratamiento , Anciano , Biomarcadores/sangre , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2RESUMEN
PURPOSE: To define the risk of curve progression of idiopathic scoliosis (IS) to 35°, 40°, 45°, and 50° based on current curve magnitude and Sanders stage for boys and girls, using a large cohort of patients and encounters, to improve granularity and allow more accurate estimations to guide treatment. METHODS: Retrospective analysis of a prospectively collected scoliosis database. Generalized estimation equation logistic regression models estimated probabilities of curve progression to 35°, 40°, 45°, and 50° based on starting curve size and Sanders stage. Probabilities and their 95% confidence intervals were calculated for each combination of variables to each endpoint separately for boys and girls. RESULTS: A total of 309 patients (80% girls) were included. Starting curve size and Sanders stage were significant predictors for progression in both sexes (all P ≤ 0.04). Higher starting curve sizes and lower Sanders stages were associated with greater odds of progression. Risk of progression was still present even at higher Sanders stages. CONCLUSION: IS curves follow a predictable pattern, having more risk for progression when curves are larger and Sanders stages are smaller. Risk of curve progression is a spectrum based on these factors, indicating some risk of progression exists even for many smaller curves with higher Sanders stages. The improved granularity of this analysis compared to prior efforts may be useful for counseling patients about the risks of curve progression to various curve size endpoints and may aid shared decision-making regarding treatments. LEVEL OF EVIDENCE OR CLINICAL RELEVANCE: Level III: retrospective cohort study.
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BACKGROUND: Endosalpingiosis is a pathologic diagnosis of ectopic epithelium resembling the fallopian tubes. It has been described with clinical characteristics that are similar to endometriosis. The primary objective is to determine if endosalpingiosis (ES) has a similar association with chronic pelvic pain when compared to endometriosis (EM). METHODS: This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable EM cohort. Demographic and clinical data were obtained, and statistical analysis was performed. RESULTS: A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs. 48 years, P<0.001), but other demographic variables were similar. Fewer ES patients had baseline chronic pelvic pain than EM patients (25.3% vs. 47%, P<0.001), and patients with ES were less likely to undergo surgery for the primary indication of pelvic pain (16.1% vs. 35.4%, P<0.001). Pelvic pain as the surgical indication remained lower in the ES group in multivariable analysis (OR=0.49, P<0.001). There were similar rates of persistent postoperative pain between ES and EM groups (10.1% vs. 13.5%, P=0.109). CONCLUSIONS: Although endosalpingiosis can be associated with chronic pelvic pain, the incidence of pain is significantly lower than in patients who have endometriosis. These findings suggest that ES is a unique condition that differs from EM. Further research including long-term follow-up and patient-reported outcomes is imperative.
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Dolor Crónico , Endometriosis , Enfermedades de las Trompas Uterinas , Femenino , Humanos , Persona de Mediana Edad , Endometriosis/complicaciones , Endometriosis/epidemiología , Endometriosis/cirugía , Estudios Retrospectivos , Enfermedades de las Trompas Uterinas/complicaciones , Enfermedades de las Trompas Uterinas/cirugía , Enfermedades de las Trompas Uterinas/diagnóstico , Dolor Pélvico/etiología , Dolor Pélvico/complicaciones , Dolor Crónico/etiología , Dolor Crónico/complicacionesRESUMEN
INTRODUCTION: Persistence of embryonic urachal structures due to a failure of the urachus to involute into the median umbilical ligament is known as a urachal anomaly (UA). UAs may remain asymptomatic or lead to abdominal pain and recurrent infections. Management of UAs in pediatric patients has historically lacked a clear consensus between conservative and surgical management. While both urologists and general surgeons manage this pathology, a comparison of management style and outcomes between these specialties has not been published to our knowledge. OBJECTIVE: To (1) evaluate trends in management of UAs among pediatric urologists and general surgeons across three tertiary care children's hospitals and (2) identify factors that place patients at higher risk for requiring surgery. STUDY DESIGN: All patients diagnosed with a UA from 2016 to 2020 at our multi-site institution were identified by ICD-10 code Q64.4 "malformation of the urachus" and retrospectively reviewed. Patient demographics, treatment specialty, remnant subtype, and management strategy were recorded. Data was dichotomized between both urology and general surgery as well as between surgical and nonsurgical intervention to identify and compare management strategies. RESULTS: Overall, 143 patients diagnosed with UAs were identified. Of these patients, 74 were treated by urology and 69 were treated by general surgery. Patients who were treated by urology were significantly more likely to receive conservative treatment (66.2% treated conservatively vs. 33.8% treated surgically), while patients treated by general surgery were significantly more likely to undergo surgery (84.1% treated surgically vs. 15.9% treated conservatively, p < .0001). Though, urology was more likely to treat patients who presented incidentally (p < .01), and general surgery was more likely to treat patients who presented with an infected remnant (p < .01). Patients of male sex were more likely overall to receive surgery compared to female patients (p < .01). DISCUSSION: Management of UAs by urologists was more conservative than general surgeons. However, both specialties treat distinctly different patient presentations, with urology managing more incidental remnants and general surgery operating on more emergent, infected urachi. Limitations of the study included its retrospective nature and the insufficient reporting of urachal remnant subtypes and presence of infection among patients. CONCLUSIONS: Management strategies of UAs differ among urology and general surgery, but surgical and conservative treatments are necessary to appropriately treat their distinct patient populations. This study provides valuable insight into current practices of UA management and may help to inform future treatment.
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Quiste del Uraco , Uraco , Urología , Niño , Humanos , Masculino , Femenino , Estudios Retrospectivos , Uraco/cirugía , Uraco/anomalías , Tratamiento Conservador , Urólogos , Quiste del Uraco/diagnóstico , Quiste del Uraco/cirugíaRESUMEN
OBJECTIVE: The aim was to evaluate representation of women in otolaryngology by examining authorship of research publications and presentations, awards, research grants, leadership, and membership in related organizations. METHODS: Authorship was reviewed from articles published in three otolaryngology journals from 2000 through 2021 to assess the frequency and percentages of female and combination of male and female gender authorship. Gender was evaluated for poster and scientific abstract presentations from 2007 to 2021. Gender representation was reviewed for institutional and society leadership positions, award, and grant recipients in the American Laryngological Society (ALA). Changes in the frequency of female and combination of male and female gender authorship over time were examined with Cochran-Armitage test for trend. RESULTS: A total of 16,921 articles, 1,017 presentations, 480 leadership positions, 129 president positions, and 1,137 awards and grants were studied. Women were first authors in 4,153 (24.9%) and last authors in 2,935 (17.8%) published articles for which gender could be determined. Women were first authors in 372 (37.4%) presentations and last authors in 199 (20.2%). Most presentations had a combination of male and female presentation authorship (630, 68%). Women held 69 (14.4%) leadership positions. Of the award and grant recipients, 327 (28.8%) were female. Significant trends were observed for increasing female representation (first authorship publications increased 69.9% from 2000 to 2020, first authorship presentations increased 73.9% from 2007 to 2013, p < 0.001; leadership and awards from 3% to 18% representation, p = 0.02). CONCLUSION: The proportion of women receiving awards and holding leadership positions is increasing. Efforts that promote gender diversity may further increase representation of women in otolaryngology literature and among the grant and award winners. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2144-2152, 2024.
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Otolaringología , Publicaciones , Humanos , Masculino , Femenino , Autoria , LiderazgoRESUMEN
Background: Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. This UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet. Methods: Here we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9. Results: Compared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling. Conclusions: There are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.
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Alzheimer's disease (AD), characterized by the deposition of amyloid-ß (Aß) in senile plaques and neurofibrillary tangles of phosphorylated tau (pTau), is increasingly recognized as a complex disease with multiple pathologies. AD sometimes pathologically overlaps with age-related tauopathies such as four repeat (4R)-tau predominant argyrophilic grain disease (AGD). While AGD is often detected with AD pathology, the contribution of APOE4 to AGD risk is not clear despite its robust effects on AD pathogenesis. Specifically, how APOE genotype influences Aß and tau pathology in co-occurring AGD and AD has not been fully understood. Using postmortem brain samples (N = 353) from a neuropathologically defined cohort comprising of cases with AD and/or AGD pathology built to best represent different APOE genotypes, we measured the amounts of major AD-related molecules, including Aß40, Aß42, apolipoprotein E (apoE), total tau (tTau), and pTau181, in the temporal cortex. The presence of tau lesions characteristic of AD (AD-tau) was correlated with cognitive decline based on Mini-Mental State Examination (MMSE) scores, while the presence of AGD tau lesions (AGD-tau) was not. Interestingly, while APOE4 increased the risk of AD-tau pathology, it did not increase the risk of AGD-tau pathology. Although APOE4 was significantly associated with higher levels of insoluble Aß40, Aß42, apoE, and pTau181, the APOE4 effect was no longer detected in the presence of AGD-tau. We also found that co-occurrence of AGD with AD was associated with lower insoluble Aß42 and pTau181 levels. Overall, our findings suggest that different patterns of Aß, tau, and apoE accumulation mediate the development of AD-tau and AGD-tau pathology, which is affected by APOE genotype.
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Enfermedad de Alzheimer , Apolipoproteínas E , Tauopatías , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Amiloide , Péptidos beta-Amiloides , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Proteínas tau , Tauopatías/patologíaRESUMEN
OBJECTIVE: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. METHODS: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. RESULTS: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. CONCLUSION: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.
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Antibacterianos , COVID-19 , Polipéptido alfa Relacionado con Calcitonina , Humanos , Masculino , Femenino , Antibacterianos/uso terapéutico , Polipéptido alfa Relacionado con Calcitonina/sangre , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , COVID-19/mortalidad , COVID-19/complicaciones , Tratamiento Farmacológico de COVID-19 , Tiempo de Internación , Resultado del Tratamiento , SARS-CoV-2 , Hospitalización/estadística & datos numéricosRESUMEN
OBJECTIVES: To present a normal range of cerebrospinal fluid (CSF) protein levels in a community-based population and to evaluate factors that contribute to CSF protein level variability. PATIENTS AND METHODS: Samples of CSF protein were obtained from participants aged 32 to 95 years who underwent lumbar puncture (LP) between November 1, 2007, and October 1, 2017, as part of the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. RESULTS: A total of 633 participants (58.1% male; 99.1% White; mean ± SD age, 70.9±11.6 years) underwent LP with recorded CSF protein level. Mean ± SD CSF protein level was 52.2±18.4 mg/dL (to convert to mg/L, multiply by 10), with a 95% reference interval of 24.0 to 93.4 mg/dL (range, 14.0-148.0 mg/dL). Spinal stenosis and arterial hypertension were associated with higher CSF protein levels on univariable analysis (P<.001). Increasing age, male sex, and diabetes were all independently associated with higher CSF protein levels on multivariable analysis (P<.001). In the 66 participants with repeated LPs within 2.5 years, the coefficient of repeatability was 26.1 mg/dL. Eleven participants (16.7%) had a CSF protein level difference of 20 mg/dL or more between serial LPs, and 4 (6.1%) had a difference of 25 mg/dL or more. There was a trend toward greater CSF protein level variability in patients with spinal stenosis (P=.054). CONCLUSION: This large population-based study showed that CSF protein level can vary significantly among individuals. Elevated CSF protein level was independently associated with older age, male sex, and diabetes and is higher than listed in many laboratories. These findings emphasize the necessity of evidence-based reevaluation and standardization of CSF protein metrics.
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Estenosis Espinal , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Estenosis Espinal/metabolismo , Lipopolisacáridos/metabolismo , Proteínas del Líquido Cefalorraquídeo/análisis , Proteínas del Líquido Cefalorraquídeo/metabolismo , Punción Espinal , Envejecimiento , Líquido CefalorraquídeoRESUMEN
Background: The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Methods: Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates. Results: Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab. Conclusions: TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.
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INTRODUCTION: Urinary tract infections (UTI) are one of the most common infections encountered in the emergency department (ED) with an estimated 2-3 million annual visits. Commonly prescribed antibiotics for UTIs have shown growing rates of resistance. Previous studies lack direction on improving UTI treatment based on the labs available to the bedside clinician. METHODS: We sought to determine if antibiotic resistance in UTIs was related to demographics, urinalysis, and history of renal failure or kidney stones. We conducted an analysis of 892 women ≥18 years of age discharged from the ED with a UTI diagnosis. We assessed predictors of nitrofurantoin resistance, cefazolin resistance, ciprofloxacin resistance, and trimethoprim-sulfamethoxazole resistance using unadjusted and multivariable logistic regression models. RESULTS: Antibiotic resistance was 13.6% for nitrofurantoin, 11.9% for cefazolin, 12.8% for ciprofloxacin, and 17.1% for trimethoprim-sulfamethoxazole. In multivariable analysis, significant independent associations with an increased likelihood of resistance to nitrofurantoin were observed for less urine blood (OR [per 1 category increase of score] 0.81; P = 0.02); greater mucous (OR [per 1 category increase of score] 1.22; P = 0.02); less specific gravity urine (OR [per 1 category increase] 0.87; P = 0.04), and presence of any history of kidney stones (OR 3.24; P = 0.01). There were no significant predictors for cefazolin resistance (all P ≥0.06); age was the only significant predictor of ciprofloxacin resistance (OR per 10 year increase] 1.10, P = 0.05), and lower specific gravity urine was significantly associated with an increased risk of resistance to trimethoprim- sulfamethoxazole (OR [per 1 category increase] 0.88, P = 0.04). CONCLUSION: Women with any history of kidney stones may have bacteriuria resistant to nitrofurantoin, suggesting that providers might consider alternative antibiotic therapies in this scenario.
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Cálculos Renales , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cefazolina , Ciprofloxacina , Farmacorresistencia Microbiana , Femenino , Humanos , Cálculos Renales/tratamiento farmacológico , Nitrofurantoína/farmacología , Nitrofurantoína/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/farmacología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Urinálisis , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
PURPOSE: Prior studies on compressive optic neuropathy (CON) have come from large tertiary centers, which may contain referral bias toward more severe or atypical disease. To our knowledge, there are no studies to determine the population-based etiologies and clinical outcomes of compressive optic neuropathy (CON). This study aims to bridge that gap using the Rochester Epidemiology Project database. DESIGN: Retrospective, population-based cohort. METHODS: Medical records of all residents living in Olmsted County, Minnesota, from January 1, 2000, through December 31, 2018, were screened for CON. Demographic and clinical information were collected before and after treatment. RESULTS: Twenty-three patients had a confirmed diagnosis of CON during our study period, which provided an overall incidence of 1.14 per 100 000 per year. Average age at onset of CON was 51 years (SD 24), and 39% were male. The most common etiologies were pituitary adenoma and meningioma. There was significant improvement in visual fields (P < .003) but not in visual acuity (P = .08) after patients underwent treatment for CON. There was also a significant relationship between the time until treatment and the degree of visual field improvement at follow-up (Pearson correlation rho = -0.58, P < .047). CONCLUSION: To our knowledge, this study provides the first population-based incidence of CON. The finding that earlier treatment leads to better visual outcomes stresses the importance of having CON on the differential diagnosis of patients with optic neuropathy.