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1.
Qual Life Res ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724771

RESUMEN

PURPOSE: This study aimed to develop a Japanese value set for the EORTC QLU-C10D, a multi-attribute utility measure derived from the cancer-specific health-related quality-of-life (HRQL) questionnaire, the EORTC QLQ-C30. The QLU-C10D contains ten HRQL dimensions: physical, role, social and emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems. METHODS: Quota sampling of a Japanese online panel was used to achieve representativeness of the Japanese general population by sex and age (≥ 18 years). The valuation method was an online discrete choice experiment. Each participant considered 16 choice pairs, randomly assigned from 960 choice pairs. Each pair included two QLU-C10D health states and life expectancy. Data were analyzed using conditional logistic regression, parameterized to fit the quality-adjusted life-year framework. Preference weights were calculated as the ratio of each dimension-level coefficient to the coefficient for life expectancy. RESULTS: A total of 2809 eligible panel members consented, 2662/2809 (95%) completed at least one choice pair, and 2435/2662 (91%) completed all choice pairs. Within dimensions, preference weights were generally monotonic. Physical functioning, role functioning, and pain were associated with the largest utility weights. Intermediate utility weights were associated with social functioning and nausea; the remaining symptoms and emotional functioning were associated with smaller utility decrements. The value of the worst health state was - 0.221, lower than that seen in most other existing QLU-C10D country-specific value sets. CONCLUSIONS: The Japan-specific QLU-C10D value set is suitable for evaluating the cost and utility of oncology treatments for Japanese health technology assessment and decision-making.

2.
Environ Sci Technol ; 58(19): 8169-8181, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38690750

RESUMEN

Climate change-induced stressors are contributing to the emergence of infectious diseases, including those caused by marine bacterial pathogens such as Vibrio spp. These stressors alter Vibrio temporal and geographical distribution, resulting in increased spread, exposure, and infection rates, thus facilitating greater Vibrio-human interactions. Concurrently, wildfires are increasing in size, severity, frequency, and spread in the built environment due to climate change, resulting in the emission of contaminants of emerging concern. This study aimed to understand the potential effects of urban interface wildfire ashes on Vibrio vulnificus (V. vulnificus) growth and gene expression using transcriptomic approaches. V. vulnificus was exposed to structural and vegetation ashes and analyzed to identify differentially expressed genes using the HTSeq-DESeq2 strategy. Exposure to wildfire ash altered V. vulnificus growth and gene expression, depending on the trace metal composition of the ash. The high Fe content of the vegetation ash enhanced bacterial growth, while the high Cu, As, and Cr content of the structural ash suppressed growth. Additionally, the overall pattern of upregulated genes and pathways suggests increased virulence potential due to the selection of metal- and antibiotic-resistant strains. Therefore, mixed fire ashes transported and deposited into coastal zones may lead to the selection of environmental reservoirs of Vibrio strains with enhanced antibiotic resistance profiles, increasing public health risk.


Asunto(s)
Vibrio vulnificus , Vibrio vulnificus/genética , Incendios Forestales , Expresión Génica
3.
Proc Natl Acad Sci U S A ; 121(21): e2400426121, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38748579

RESUMEN

Encapsulins are protein nanocompartments that regulate cellular metabolism in several bacteria and archaea. Myxococcus xanthus encapsulins protect the bacterial cells against oxidative stress by sequestering cytosolic iron. These encapsulins are formed by the shell protein EncA and three cargo proteins: EncB, EncC, and EncD. EncB and EncC form rotationally symmetric decamers with ferroxidase centers (FOCs) that oxidize Fe+2 to Fe+3 for iron storage in mineral form. However, the structure and function of the third cargo protein, EncD, have yet to be determined. Here, we report the x-ray crystal structure of EncD in complex with flavin mononucleotide. EncD forms an α-helical hairpin arranged as an antiparallel dimer, but unlike other flavin-binding proteins, it has no ß-sheet, showing that EncD and its homologs represent a unique class of bacterial flavin-binding proteins. The cryo-EM structure of EncA-EncD encapsulins confirms that EncD binds to the interior of the EncA shell via its C-terminal targeting peptide. With only 100 amino acids, the EncD α-helical dimer forms the smallest flavin-binding domain observed to date. Unlike EncB and EncC, EncD lacks a FOC, and our biochemical results show that EncD instead is a NAD(P)H-dependent ferric reductase, indicating that the M. xanthus encapsulins act as an integrated system for iron homeostasis. Overall, this work contributes to our understanding of bacterial metabolism and could lead to the development of technologies for iron biomineralization and the production of iron-containing materials for the treatment of various diseases associated with oxidative stress.


Asunto(s)
Proteínas Bacterianas , FMN Reductasa , Myxococcus xanthus , Myxococcus xanthus/metabolismo , Myxococcus xanthus/enzimología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , FMN Reductasa/metabolismo , Cristalografía por Rayos X , Mononucleótido de Flavina/metabolismo , Hierro/metabolismo , Modelos Moleculares , Microscopía por Crioelectrón
4.
Temperature (Austin) ; 11(1): 4-26, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38567267

RESUMEN

The heat-related health burden is expected to persist and worsen in the coming years due to an aging global population and climate change. Defining the breadth and depth of our understanding of age-related changes in thermoregulation can identify underlying causes and strategies to protect vulnerable individuals from heat. We conducted the first systematic quantitative literature review to provide context to the historical experimental research of healthy older adults - compared to younger adults or unhealthy age matched cases - during exogenous heat strain, focusing on factors that influence thermoregulatory function (e.g. co-morbidities). We identified 4,455 articles, with 147 meeting eligibility criteria. Most studies were conducted in the US (39%), Canada (29%), or Japan (12%), with 71% of the 3,411 participants being male. About 71% of the studies compared younger and older adults, while 34% compared two groups of older adults with and without factors influencing thermoregulation. Key factors included age combined with another factor (23%), underlying biological mechanisms (18%), age independently (15%), influencing health conditions (15%), adaptation potential (12%), environmental conditions (9%), and therapeutic/pharmacological interventions (7%). Our results suggest that controlled experimental research should focus on the age-related changes in thermoregulation in the very old, females, those with overlooked chronic heat-sensitive health conditions (e.g. pulmonary, renal, mental disorders), the impact of multimorbidity, prolonged and cumulative effects of extreme heat, evidence-based policy of control measures (e.g. personal cooling strategies), pharmaceutical interactions, and interventions stimulating protective physiological adaptation. These controlled studies will inform the directions and use of limited resources in ecologically valid fieldwork studies.

5.
Exp Physiol ; 109(4): 549-561, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461483

RESUMEN

Changes in myonuclear architecture and positioning are associated with exercise adaptations and ageing. However, data on the positioning and number of myonuclei following exercise are inconsistent. Additionally, whether myonuclear domains (MNDs; i.e., the theoretical volume of cytoplasm within which a myonucleus is responsible for transcribing DNA) and myonuclear positioning are altered with age remains unclear. The aim of this investigation was to investigate relationships between age and activity status and myonuclear domains and positioning. Vastus lateralis muscle biopsies from younger endurance-trained (YT) and older endurance-trained (OT) individuals were compared with age-matched untrained counterparts (YU and OU; OU samples were acquired during surgical operation). Serial, optical z-slices were acquired throughout isolated muscle fibres and analysed to give three-dimensional coordinates for myonuclei and muscle fibre dimensions. The mean cross-sectional area (CSA) of muscle fibres from OU individuals was 33%-53% smaller compared with the other groups. The number of nuclei relative to fibre CSA was 90% greater in OU compared with YU muscle fibres. Additionally, scaling of MND volume with fibre size was altered in older untrained individuals. The myonuclear arrangement, in contrast, was similar across groups. Fibre CSA and most myonuclear parameters were significantly associated with age in untrained individuals, but not in trained individuals. These data indicate that regular endurance exercise throughout the lifespan might better preserve the size of muscle fibres in older age and maintain the relationship between fibre size and MND volumes. Inactivity, however, might result in reduced muscle fibre size and altered myonuclear parameters.


Asunto(s)
Envejecimiento , Fibras Musculares Esqueléticas , Humanos , Anciano , Fibras Musculares Esqueléticas/fisiología , Núcleo Celular , Músculo Cuádriceps , Terapia por Ejercicio , Músculo Esquelético
7.
Mem Cognit ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38353909

RESUMEN

In two experiments, we systematically investigated the reasons why people retained certain autobiographical events in their memory, as well as the properties of those events and their predicted memorability. The first experiment used three methods (word-cued, free-recalled, and "memorable, interesting, and/or important") to retrieve event memories, and examined memories from three different time-frames: very recent (within past 7 days), recent (past 2 weeks and 6 months), and older events (at least one year). In addition, data were also collected for an important transitional event recently experienced by all participants ("starting university"). The results revealed that people had access to three types of event memories: memories for life transitions, memories for older distinctive events, and memories for recent mundane events. Participants reported remembering events that were distinctive, first-time experiences, emotionally impactful, or simply because they were recent. They also predicted that older events would be more resistant to forgetting than very recent and recent events. The second experiment examined participants' memorable and forgettable events, and found that memorable events tended to be older, while forgettable events were more likely to be recent. These findings suggested that many retrievable memorable autobiographical memories were neither important nor transitional in nature. The studies contribute to our understanding of people's metamnemonic knowledge about their autobiographical memories.

8.
Cell Tissue Res ; 396(2): 177-195, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38366086

RESUMEN

Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer, the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.


Asunto(s)
Encéfalo , Cannabidiol , Ratas Sprague-Dawley , Animales , Cannabidiol/farmacología , Cannabidiol/sangre , Femenino , Encéfalo/metabolismo , Embarazo , Ratas , Feto/metabolismo , Placenta/metabolismo , Animales Recién Nacidos
9.
Pathophysiology ; 31(1): 89-99, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38390944

RESUMEN

Our purpose in this study was to identify the role played by oxidative stress in the changes to proteoglycans that occur under hyperglycemic conditions, using primary rat retinal microvascular endothelial cells (RRMEC) and cultured ophthalmic arteries. The cells and blood vessels obtained from rats were cultured in normal glucose (5.6 mM) and high glucose (25 mM) with or without N-acetylcysteine (NAC), an antioxidant. Intracellular oxidative stress was determined by measuring dihydroethidium (DHE) fluorescence and malondialdehyde (MDA)-modified protein levels. mRNA and protein levels were evaluated using quantitative real-time polymerase chain reaction and immunoblot, respectively. High glucose increased levels of glypican-1 mRNA and protein. The level of syndecan-1 mRNA also was increased, but its protein level was decreased, by high glucose. Evaluation of DHE and MDA showed that high glucose increased oxidative stress. These changes caused by high glucose were significantly reversed by NAC treatment. Matrix metalloproteinase-9 (MMP-9) levels, which increased under high glucose conditions, were suppressed by NAC treatment. Oxidative stress caused by hyperglycemia may be responsible for significant changes to the ocular endothelial glycocalyx.

11.
Memory ; 32(2): 283-291, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38300754

RESUMEN

The COVID-19 Pandemic is undoubtedly one of the most impactful and ubiquitous public events in recent history. In this study, we focused on how it affected the organisation of autobiographical memory by examining how often individuals referred to the COVID-19 Pandemic while estimating the date of their autobiographical memories. To that end, we collected word-cued memories from the recent past, event dating protocols, COVID-relatedness ratings, and the transitional impact scores from first-year undergraduates. We found that participants frequently recalled COVID-related memories, and often used the Pandemic as a temporal landmark for dating both COVID-related and unrelated memories. Importantly, reference to the Pandemic in dating estimates was as frequent as the references to other important life periods (high school, university). Despite affecting the lives of these individuals only moderately in psychological and material terms, these data indicate that the Pandemic has become a prominent landmark in autobiographical memory, shaping the way we remember and situate past experiences.


Asunto(s)
COVID-19 , Memoria Episódica , Humanos , Pandemias , Recuerdo Mental , Señales (Psicología)
13.
J Sci Med Sport ; 27(3): 172-178, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38218663

RESUMEN

OBJECTIVES: This study investigated relationships between isometric trunk and hip extensor strength, lumbar muscle morphology, and the risk of hamstring and knee ligament injuries in Australian Football League and National Rugby League players. DESIGN: Prospective cohort study. METHODS: Trunk and hip extensor strength, multifidus and quadratus lumborum cross-sectional area were measured during the 2020 pre-season. Logistic regressions and decision trees were employed to explore associations between maximum strength, strength endurance, multifidus and quadratus lumborum cross-sectional area, age, previous injuries, and hamstring and knee ligament injury risk. RESULTS: Greater strength endurance [odds ratio = 0.42 (0.23-0.74), p = 0.004] and maximum strength [odds ratio = 0.55 (0.31-0.94), p = 0.039] reduced hamstring injury risk. Increased risk of knee ligament injuries was associated with larger multifidus [odds ratio = 1.66 (1.14-2.45), p = 0.008] and higher multifidus to quadratus lumborum ratio (odds ratio = 1.57 (1.13-2.23), p = 0.008]. Decision tree models indicated that low strength endurance (< 99 Nm) characterised hamstring strains, while high (≥ 1.33) multifidus to quadratus lumborum ratio mitigated risk. Knee ligament injuries were associated with larger (≥ 8.49 cm2) multifidus, greater (≥ 1.25) multifidus to quadratus lumborum ratio, and lower maximum strength (< 9.24 N/kg). CONCLUSIONS: Players with lower trunk and hip extensor maximum strength and strength endurance had increased risk of hamstring injuries, while knee ligament injury risk was elevated with larger multifidus cross-sectional area, higher multifidus to quadratus lumborum ratio, and lower maximum trunk and hip extensor strength.


Asunto(s)
Traumatismos en Atletas , Músculos Isquiosurales , Traumatismos de la Rodilla , Traumatismos de la Pierna , Humanos , Australia , Estudios Prospectivos , Rugby , Traumatismos en Atletas/epidemiología , Fuerza Muscular , Músculos Paraespinales/fisiología
14.
Sci Total Environ ; 917: 170345, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38272099

RESUMEN

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the use of wastewater-based surveillance (WBS) has increased dramatically along with associated infrastructure globally. However, due to the global nature of its application, and various workflow adaptations (e.g., sample collection, water concentration, RNA extraction kits), numerous methods for back-calculation of gene copies per volume (gc/L) of sewage have also emerged. Many studies have considered the comparability of processing methods (e.g., water concentration, RNA extraction); however, for equations used to calculate gene copies in a wastewater sample and subsequent influences on monitoring viral trends in a community and its association with epidemiological data, less is known. Due to limited information on how many formulas exist for the calculation of SARS-CoV-2 gene copies in wastewater, we initially attempted to quantify how many equations existed in the referred literature. We identified 23 unique equations, which were subsequently applied to an existing wastewater dataset. We observed a range of gene copies based on use of different equations, along with variability of AUC curve values, and results from correlation and regression analyses. Though a number of individual laboratories appear to have independently converged on a similar formula for back-calculation of viral load in wastewater, and share similar relationships with epidemiological data, differential influences of various equations were observed for variation in PCR volumes, RNA extraction volumes, or PCR assay parameters. Such observations highlight challenges when performing comparisons among WBS studies when numerous methodologies and back-calculation methods exist. To facilitate reproducibility among studies, the different gc/L equations were packaged as an R Shiny app, which provides end users the ability to investigate variability within their datasets and support comparisons among studies.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , Reproducibilidad de los Resultados , SARS-CoV-2/genética , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas Residuales , Agua , ARN
15.
Pharmacoecon Open ; 8(1): 49-63, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38060096

RESUMEN

OBJECTIVES: To develop a value set reflecting the United States (US) general population's preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. METHODS: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. RESULTS: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state's value was -0.33. CONCLUSIONS: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments.

17.
Exp Physiol ; 109(3): 427-444, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38059686

RESUMEN

Solute carriers (SLCs) regulate transfer of a wide range of molecules across cell membranes using facilitative or secondary active transport. In pregnancy, these transporters, expressed at the placental barrier, are important for delivery of nutrients to the fetus, whilst also limiting entry of potentially harmful substances, such as drugs. In the present study, RNA-sequencing analysis was used to investigate expression of SLCs in the fetal (embryonic day 19) rat brain, choroid plexus and placenta in untreated control animals and following maternal paracetamol treatment. In the treated group, paracetamol (15 mg/kg) was administered to dams twice daily for 5 days (from embryonic day 15 to 19). In untreated animals, overall expression of SLCs was highest in the placenta. In the paracetamol treatment group, expression of several SLCs was significantly different compared with control animals, with ion, amino acid, neurotransmitter and sugar transporters most affected. The number of SLC transcripts that changed significantly following treatment was the highest in the choroid plexus and lowest in the brain. All SLC transcripts that changed in the placenta following paracetamol treatment were downregulated. These results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development, resulting in major consequences for the neonate and extending into childhood.


Asunto(s)
Acetaminofén , Placenta , Humanos , Embarazo , Femenino , Animales , Ratas , Niño , Acetaminofén/farmacología , Plexo Coroideo , Feto , Encéfalo
18.
Int J Pediatr Otorhinolaryngol ; 176: 111799, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38081110

RESUMEN

OBJECTIVE: Postviral olfactory dysfunction (OD) including corona 2019 viral disease (COVID-19) OD occurs in both adults and children. Despite limited reports of efficacy in treating adult postviral including COVID-19 OD with olfactory training (OT), its effects on children in general, and post-COVID-19 in specific, is unknown. The study aimed at evaluating the effects of OT in a COVID-19 OD pediatric cohort. METHODS: A single-arm prospective study of pediatric COVID-19 OD subjects confirmed by the University of Pennsylvania Smell Identification Test (UPSIT), was conducted. All subjects underwent OT by sniffing 4 odorants (lavender, orange, peppermint, and eucalyptus) for 1 min twice a day for 3 months. Subjects underwent an odorant identification test (OIT) of the 4 odorants each visit. A repeat UPSIT was administered at the 4th visit. RESULTS: The study enrolled a total of 37 subjects [11 males/26 females with mean age/standard deviation (std) of 15.6(2.1) years]. The time interval between COVID-19 and entry was 5.3(2.4) months. The mean pre/post study UPSIT score improvement was 2.3(4.7), p = .09. OIT scores between entry and 3 subsequent visits showed a mean improvement of 1.8(1.5), 1.8(1.9) and 2.3(1.9) odorants, respectively, with P < .001 for all 3 comparisons. CONCLUSIONS: OT subjects were predominantly female teens with substantial OD lasting greater than 5 months. OT did not affect OD as measured by UPSIT but OIT scores improved during OT. We postulate that OT likely has a role in pediatric post-COVID OD recovery, but UPSIT likely is too rigid to detect disparate odorant improvement.


Asunto(s)
COVID-19 , Trastornos del Olfato , Adulto , Masculino , Adolescente , Humanos , Femenino , Niño , Olfato , Estudios Prospectivos , Entrenamiento Olfativo , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/etiología , Trastornos del Olfato/terapia , Odorantes
19.
Eur Urol ; 85(1): 35-46, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37778954

RESUMEN

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Humanos , Masculino , Biopsia/métodos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia
20.
Otolaryngol Head Neck Surg ; 170(1): 277-283, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37668178

RESUMEN

OBJECTIVE: To analyze the growth trajectory of children with obesity before and after adenotonsillectomy (T&A). We hypothesize that T&A will not affect the growth trajectory but children in a multidisciplinary weight management program (MWMP) will have a healthier growth trajectory. STUDY DESIGN: Retrospective review. SETTING: Tertiary Children's Hospital. METHODS: Body mass index (BMI) trajectories of nonsyndromic children with obesity and obstructive sleep apnea (OSA) who underwent T&A were analyzed. A linear mixed effects model was fit to the BMI expressed as a percentage of the 95th percentile (%BMIp95 ) data. Covariates included demographic variables, pre- and postoperative participation in an MWMP, baseline obesity class, and time. We explored clinically meaningful interactions. BMI slope estimates before and after surgery were calculated and compared for baseline obesity classification and postoperative MWMP visits. RESULTS: A total of 177 patients, 58% male with a mean age of 9.7 years at the time of surgery, were studied. Higher baseline obesity class (II and III), time, the interaction between obesity class III and elapsed time relative to surgical date, and the interaction between obesity class III and the postsurgical period were all significantly associated with the outcome of %BMIp95 (P < .05). There was a significantly higher %BMIp95 trajectory following surgery in patients with baseline obesity class III who did not have any postoperative MWMP visits (P < .001). Preoperative obesity visits, however, were not significantly associated with postoperative growth. CONCLUSION: The association between T&A and weight trajectory depends upon obesity class and participation in a MWMP. Coordinated care of children with obesity between otolaryngologists and an MWMP may improve OSA and obesity outcomes. LEVEL OF EVIDENCE: The level of evidence: 3.


Asunto(s)
Apnea Obstructiva del Sueño , Tonsilectomía , Niño , Humanos , Masculino , Femenino , Polisomnografía , Adenoidectomía , Obesidad/complicaciones , Estudios Retrospectivos
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