Category: Statistics

BMC Cancer. 2022 Aug 3;22(1):844. doi: 10.1186/s12885-022-09910-9.

ABSTRACT

Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate different aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess GBM invasiveness based on detecting tumor-specific anti-luciferase staining in brain slices, we found that U251-RedFLuc cells are more invasive than U87-luc2 cells. Lastly, we determined expression levels of ABC transporters in both models. Our findings indicate that U87-luc2 and U251-RedFLuc GBM models recapitulate different aspects of GBM heterogeneity that need to be considered in preclinical research.

PMID:35922758 | DOI:10.1186/s12885-022-09910-9

J Speech Lang Hear Res. 2022 Aug 3:1-14. doi: 10.1044/2022_JSLHR-22-00151. Online ahead of print.

ABSTRACT

PURPOSE: Although fatigue is recognized as clinically relevant to swallowing performance, its prevalence and significance in dysphagic and nondysphagic adults have not been sufficiently examined. In this study, an online survey was used to examine swallowing- and eating-related fatigue (SERF) symptoms, the relationship between perceived SERF and other dysphagia-related health outcomes, and whether perceived SERF predicts risk for dysphagia or malnutrition.

METHOD: An online survey of older adults (aged 60 years or older) was conducted. A novel 12-item scale was developed to capture perceived SERF. Previously validated scales were used to measure dysphagia risk, sarcopenia, general fatigue, malnutrition risk, and quality of life. Logistic regression was used to examine whether SERF predicted risk for dysphagia and/or malnutrition.

RESULTS: Complete responses were collected from 417 community-dwelling adults (M _age = 70.6 years, SD = 4.9; 263 women); 75% (n = 312) reported at least some degree of SERF. SERF was significantly correlated with dysphagia risk, sarcopenia, general fatigue, malnutrition risk, and quality of life. SERF was a significant predictor of dysphagia risk while controlling for age, gender, and other health outcomes (odds ratio [OR] = 1.2, 95% confidence interval [CI; 1.16, 1.27], p < .001). For every unit increase in SERF score, the odds of being at risk for dysphagia were associated with an increase of 22%. Significant predictors for malnutrition risk included SERF (OR = 0.94, 95% CI [0.91, 0.98]), general fatigue (OR = 0.95, 95% CI [0.92, 0.99]), and quality of life (OR = 1.04, 95% CI [1.0, 1.1]).

CONCLUSIONS: Fatigue during swallowing and mealtimes is experienced by community-dwelling older adults and predicted dysphagia risk and malnutrition risk. Further research is needed to refine and validate a patient-reported outcome measure for SERF and examine the effects of fatigue on swallowing function and physiology under imaging.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20405835.

PMID:35921661 | DOI:10.1044/2022_JSLHR-22-00151

J Speech Lang Hear Res. 2022 Aug 3:1-14. doi: 10.1044/2022_JSLHR-21-00619. Online ahead of print.

ABSTRACT

PURPOSE: Amyotrophic lateral sclerosis (ALS) impacts bulbar and respiratory musculature, which may contribute to impaired swallow function (dysphagia) and respiratory-swallow coordination. The purpose of this pilot study was to examine if respiratory-swallow coordination in individuals with ALS was perturbed compared to healthy controls. We further explored relationships between measures of respiratory function and self-reported swallowing outcomes on respiratory-swallow coordination.

METHOD: We employed a cross-sectional design with eight participants with ALS and eight age- and sex-matched healthy participants. Respiratory inductance plethysmography and a nasal cannula were used to capture respiratory-swallow phase patterns during a standardized clinical swallow examination. The advantageous respiratory-swallow phase pattern was defined if exhalation surrounded the swallow (E-E). Spirometry was used to capture indices of respiratory function (forced vital capacity % predicted, peak cough flow [PCF]). Validated questionnaires were used to collect information regarding ALS-related bulbar functional status and swallowing-related concerns.

RESULTS: Compared to the matched healthy cohort, individuals with ALS demonstrated higher rates of non-E-E respiratory-swallow phase patterning and worse bulbar/swallow dysfunction. Group (ALS), swallow tasks, and PCF were significantly associated with respiratory-swallow phase pattern.

CONCLUSIONS: These preliminary findings support altered respiratory-swallow phase patterning in ALS. Future work should employ an instrumental assessment to quantify swallowing physiology and elucidate the relationship between perturbed respiratory-swallow coordination and swallowing function.

PMID:35921660 | DOI:10.1044/2022_JSLHR-21-00619

Plast Reconstr Surg. 2022 Jul 29. doi: 10.1097/PRS.0000000000009573. Online ahead of print.

ABSTRACT

BACKGROUND: To compare the clinical effects of long-pulse-width 1064nm Nd:YAG laser assisted ear correction model and simple ear correction model in the treatment of congenital auricular deformities in over-aged ears.

METHODS: 129 children (179 ears) with congenital auricular deformities aged more than 2 months were included in the study. Among them, 84 cases (observation group, 119 ears) were treated with the ear correction model after long-pulse-width 1064nm Nd:YAG laser irradiation, while 45 cases (60 ears) were treated with the ear correction model only. The affected ears of the two groups were measured, the correction time was calculated, and the family members of the patients filled in the satisfaction questionnaire before and after the treatment.

RESULTS: The level of satisfaction of the two groups after the treatment improved. The level of satisfaction of the observation group was higher than that of the control group. The days of correction in the observation group was less than that in the control group (P＜0.05). The measurements of the affected ears in the two groups were significantly different after treatment. The difference after treatment of each measurement in the observation group was higher than that in the control group. The therapeutic effect of the observation group was significantly better than that of the control group, and the differences were statistically significant.

CONCLUSION: Long-pulse-width 1064nm Nd:YAG laser combined with the ear correction model can effectively improve the success rate of correction of congenital auricular deformities in over-aged ears.

PMID:35921652 | DOI:10.1097/PRS.0000000000009573

Pediatrics. 2022 Jul 1;150(1):e2022057991. doi: 10.1542/peds.2022-057991.

ABSTRACT

Every year in the United States, approximately 3500 infants die of sleep-related infant deaths, including sudden infant death syndrome (SIDS) (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10] R95), ill-defined deaths (ICD-10 R99), and accidental suffocation and strangulation in bed (ICD-10 W75). After a substantial decline in sleep-related deaths in the 1990s, the overall death rate attributable to sleep-related infant deaths have remained stagnant since 2000, and disparities persist. The triple risk model proposes that SIDS occurs when an infant with intrinsic vulnerability (often manifested by impaired arousal, cardiorespiratory, and/or autonomic responses) undergoes an exogenous trigger event (eg, exposure to an unsafe sleeping environment) during a critical developmental period. The American Academy of Pediatrics recommends a safe sleep environment to reduce the risk of all sleep-related deaths. This includes supine positioning; use of a firm, noninclined sleep surface; room sharing without bed sharing; and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include human milk feeding; avoidance of exposure to nicotine, alcohol, marijuana, opioids, and illicit drugs; routine immunization; and use of a pacifier. New recommendations are presented regarding noninclined sleep surfaces, short-term emergency sleep locations, use of cardboard boxes as a sleep location, bed sharing, substance use, home cardiorespiratory monitors, and tummy time. In addition, additional information to assist parents, physicians, and nonphysician clinicians in assessing the risk of specific bed-sharing situations is included. The recommendations and strength of evidence for each recommendation are published in the accompanying policy statement, which is included in this issue.

PMID:35921639 | DOI:10.1542/peds.2022-057991

Sports Med Arthrosc Rev. 2022 Sep 1;30(3):162-165. doi: 10.1097/JSA.0000000000000350. Epub 2022 Aug 3.

ABSTRACT

Interest in use of perinatal allogenic tissues including clinical-grade minimally manipulated umbilical cord tissue-derived allograft formulations to treat knee osteoarthritis (OA) patients is increasing. Limited studies have characterized these formulations and evaluated their safety and efficacy in knee OA patients. We developed such formulation and reported the presence of growth factors, cytokines, hyaluronic acid, and exosomes. We reported that its administration is safe, and resulted in 50% pain reduction and improvement in knee injury and osteoarthritis outcome score (over 10%) and 36-item short form survey (25%). Another study reported no adverse events post injection of similar formulation and statistically significant (P<0.001) improvement in visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index scores and reduction in medication usage in patients (77.8%). We also summarized the clinical trials registered on ClinicalTrials.gov utilizing umbilical cord tissue for knee OA treatment. In conclusion, available studies are preliminary but pave the way to higher level appropriately powered investigations, and these formulations should be considered as nonoperative alternative to manage knee OA.

PMID:35921598 | DOI:10.1097/JSA.0000000000000350

J Infect Dis. 2022 Aug 3:jiac318. doi: 10.1093/infdis/jiac318. Online ahead of print.

ABSTRACT

To inform public health policy, it is critical to monitor COVID-19 vaccine effectiveness (VE), including against acquiring infection. We estimated VE using self-reported vaccination in a retrospective cohort of repeat blood donors who donated during the first half of 2021, demonstrating a viable approach for monitoring of VE via serological surveillance. Using Poisson regression, we estimated an overall VE of 88.8% (95% CI: 86.2-91.1), adjusted for demographic covariates and variable baseline risk. Time since first reporting vaccination, age, race-ethnicity, region, and calendar time were statistically significant predictors of incident infection.

PMID:35921537 | DOI:10.1093/infdis/jiac318

Gut Microbes. 2022 Jan-Dec;14(1):2106103. doi: 10.1080/19490976.2022.2106103.

ABSTRACT

How the gut microbiota is organized across space is postulated to influence microbial succession and its mutualistic relationships with the host. The lack of dynamic or perturbed abundance data poses considerable challenges for characterizing the spatial pattern of microbial interactions. We integrate allometric scaling theory, evolutionary game theory, and prey-predator theory into a unified framework under which quasi-dynamic microbial networks can be inferred from static abundance data. We illustrate that such networks can capture the full properties of microbial interactions, including causality, the sign of the causality, strength, and feedback loop, and are dynamically adaptive along spatial gradients, and context-specific, characterizing variability between individuals and within the same individual across time and space. We design and conduct a gut microbiota study to validate the model, characterizing key spatial determinants of the microbial differences between ulcerative colitis and healthy controls. Our model provides a sophisticated means of unraveling a complete atlas of how microbial interactions vary across space and quantifying causal relationships between such spatial variability and change in health state.

PMID:35921525 | DOI:10.1080/19490976.2022.2106103

Hepatology. 2022 Aug 3. doi: 10.1002/hep.32704. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in cirrhotic patients with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (≥70 years) is debated and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults.

APPROACH & RESULTS: We prospectively enrolled 411 consecutive patients observed at 4 referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76 respectively. A cause-specific Cox competing risks model was used to predict liver-related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver-related death by multivariable analysis.

CONCLUSIONS: After TIPS implantation, mortality is increased by ageing, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.

PMID:35921493 | DOI:10.1002/hep.32704

Sci Transl Med. 2022 Aug 3;14(656):eabn7571. doi: 10.1126/scitranslmed.abn7571. Epub 2022 Aug 3.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, and archival patient samples exhibited large populations in vivo of hybrid E/M cells that lead invasion ex vivo while expressing both epithelial and mesenchymal characteristics. The mesenchymal marker vimentin promoted invasion and repressed metastatic outgrowth. We next tested the requirement for five EMT transcription factors and observed distinct patterns of utilization during invasion and colony formation. These differences suggested a sequential activation of multiple EMT molecular programs during the metastatic cascade. Consistent with this model, our longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns. We observed cancer cells progressing from epithelial to hybrid E/M and strongly mesenchymal patterns during invasion and from epithelial to a hybrid E/M pattern during colony formation. We next investigated the relative epithelial versus mesenchymal state of cancer cells in both GEMM and patient metastases. In both contexts, we observed heterogeneity between and within metastases in the same individual. We observed a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases, suggesting that there are multiple successful molecular strategies for distant organ colonization. Together, our results demonstrate an important and complex role for EMT programs during TNBC metastasis.

PMID:35921474 | DOI:10.1126/scitranslmed.abn7571