Tag: statistics

Cancer Immunol Immunother. 2024 Mar 2;73(4):70. doi: 10.1007/s00262-024-03643-3.

ABSTRACT

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed.

RESULTS: Prespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48-1.72) and 0.69 (0.39-1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs.

CONCLUSIONS: bTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME. Trial registration ClinicalTrials.gov identifier NCT02551159.

PMID:38430375 | DOI:10.1007/s00262-024-03643-3

Clin Oral Investig. 2024 Mar 2;28(3):187. doi: 10.1007/s00784-024-05574-w.

ABSTRACT

AIM: The present retrospective cohort study aimed to evaluate luxated permanent teeth for pulp prognosis and risk factors.

METHODOLOGY: Case records and radiographs of 224 patients, involving 427 luxated permanent teeth, referred for treatment at the Dental Trauma Center-School of Dentistry, Universidade Federal de Minas Gerais, (DTC-SD-UFMG) from 2014 to 2022, were assessed for pulp prognosis classified as vitality, necrosis and pulp canal obliteration (PCO). A competing risk survival analysis estimated the hazards of the three outcomes, and the effect of demographic, clinical and treatment variables was tested using a cause specific Cox regression model.

RESULTS: Pulp vitality was found in163 teeth (38.2%), pulp necrosis in 120 teeth (28.1%) and 55 teeth (12.9%) developed PCO. Pulp vitality decreased in the presence of concomitant crown fractures (HR 0.38 95% CI [0.2-0.8] p = 0.006). The risk of pulp necrosis (HR 0.62 95% CI [0.4-0.96] p = 0.03) was lower in cases with open apices but increased with concomitant crown fractures (HR 4.0 95% CI [2.6-6.1] p = 0.001) and intrusions (HR 2.3 95% CI [1.2-4.1] p = 0.007). Lateral or extrusive luxations (HR 3.0 95% CI [1.3-6.9] p = 0.001) and open apices (HR 2.4 95% CI [1.2-4.7] p = 0.01) showed higher rates of PCO.

CONCLUSION: Type of luxation, the diameter of the apical foramen, and the presence of concomitant crown fractures were main determinants of pulp prognosis after luxation injuries in permanent teeth.

CLINICAL RELEVANCE: Pulp prognosis after tooth luxation is dependent on the presence and direction of tooth displacement together with infection control.

CLINICAL TRIAL REGISTRATION: Not applicable.

PMID:38430349 | DOI:10.1007/s00784-024-05574-w

Biol Trace Elem Res. 2024 Mar 2. doi: 10.1007/s12011-024-04128-1. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the potential bioaccumulation of arsenic (As), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb) and mercury (Hg) in the haemolymph and corpus of Mytilus galloprovincialis and Tapes decussatus from Lake Faro. The lake is particularly prone to the accumulation of substances that are potentially toxic to aquatic organisms, due to the input of pollutants from urban and agricultural sources and the low rate of water exchange. The combination of saltwater from the Tyrrhenian Sea, the Strait of Messina and freshwater from hilly aquifers has created brackish conditions in the lake, resulting in an area of high commercial shellfish productivity. As, Cd, Cu, Pb and Zn were determined using a single quadrupole inductively coupled plasma mass spectrometer; Hg was determined using a direct mercury analyser (DMA-80). Physicochemical parameters of the water from Lake Faro were also performed. Statistical analysis was carried out using GraphPad Prism 9.0 (GraphPad Software, Inc., Boston, MA, USA) and Shapiro-Wilk normality was applied. Concentrations of Cd, Hg and Pb below the permitted MRLs in Mytilus galloprovincialis and Tapes decussatus used as ”biological indicators” show that Lake Faro is not at risk of contamination by these pollutants and, moreover, is free of health problems for the consumer based on regulatory limits.

PMID:38430347 | DOI:10.1007/s12011-024-04128-1

Curr Nutr Rep. 2024 Mar 2. doi: 10.1007/s13668-024-00522-2. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Acute Myeloid Leukaemia (AML) constitutes a mere 1% of global cancer cases. This scoping review aims to investigate the association between nutrition and the development of AML, providing a foundation for future research in this field.

RECENT FINDINGS: A systematic search was conducted across PubMed, EBSCO, Taylor and Francis, Science Direct and Cochrane Library using specific keywords. Inclusion criteria comprised observational studies and clinical trials examining the association between nutrition and the development of AML. Articles selected for analysis were restricted to those published in English between 1990-2023, and available as full text articles. Among the twenty-five articles that were screened, only six met the criteria for data extraction. Four studies did not reveal statistically significant correlations between nutrition and the development of AML, while two studies provided evidence for significant associations. The findings indicated increased AML risk associated with (a) heightened caloric intake, consumption of white potatoes, and red meat (pork and beef) and (b) diminished consumption of vegetables, seafood, nuts, and seeds. The scarcity of comprehensive studies exploring the connection between nutrition and AML, highlights the urgent need for additional research, encompassing pre-clinical studies. This imperative is critical for enhancing our understanding of the molecular mechanisms that underlie the connection between diet and the aetiology of AML. Such knowledge is paramount in advancing effective strategies for both prevention and management of this significant disease.

PMID:38430336 | DOI:10.1007/s13668-024-00522-2

Clin Oral Investig. 2024 Mar 2;28(3):190. doi: 10.1007/s00784-023-05446-9.

ABSTRACT

OBJECTIVES: An adjunct in non-surgical periodontal therapy might be sodium hypochlorite (NaOCl)-based agents. The purpose of the present in vitro study was to get deeper knowledge on the influence of different parameters as time after mixing, pH, and chemical composition of an amino acid 0.475% NaOCl (AA-NaOCl) gel consisting of two components on its anti-biofilm activity.

MATERIALS AND METHODS: Six-species biofilms were cultured for 5 days, before AA-NaOCl gel was applied. In the different series, the influence of the time after mixing of the two components before application, of the concentration of NaOCl in the gel mixture, of the pH of the gel mixture, and of an exchange of the amino acid component by hyaluronic acid (HA), was analyzed.

RESULTS: Mixing time point experiments showed that the AA-NaOCl gel is capable of statistically significantly reducing colony-forming unit (cfu) counts up to 30 min after mixing, but only up to 20 min after mixing the reduction was more than 2 log10 cfu. The pH experiments indicate that a reduced pH results in a reduced activity of the NaOCl formulation. NaOCl concentrations in the formulation in the range from 0.475 to 0.2% provide adequate activity on biofilms. A HA/NaOCl gel was equally active against the biofilm as the AA-NaOCl gel.

CONCLUSION: Mixing of the components should be made in a timeframe of 20 min before applications. An optimization of the composition of the NaOCl formulation might be possible and should be a topic in further in vitro studies.

CLINICAL RELEVANCE: The AA-NaOCl gel formulation can be mixed up to 20 min before application. Further, the study indicates that the composition of the NaOCl gel formulation can be optimized.

PMID:38430333 | DOI:10.1007/s00784-023-05446-9

Int J Clin Oncol. 2024 Mar 2. doi: 10.1007/s10147-024-02475-6. Online ahead of print.

ABSTRACT

BACKGROUND: The D-dimer test is a simple test frequently used in routine clinical screening for venous thromboembolism (VTE). The Cancer-VTE Registry was a large-scale, multicenter, prospective, observational study in Japanese patients with cancer. This study aimed to clarify the relationship between D-dimer level at cancer diagnosis (baseline) and the incidence of events during cancer treatment (1-year follow-up period).

METHODS: This was a post hoc sub-analysis of patients from the Cancer-VTE Registry whose D-dimer levels were measured at baseline. The incidence of events during the 1-year follow-up period was evaluated stratified by baseline D-dimer level. Adjusted hazard ratios for D-dimer level and events during the follow-up period were evaluated.

RESULTS: Among the total enrolled patients, baseline D-dimer level was measured in 9020 patients. The mean ± standard deviation baseline D-dimer level was 1.57 ± 3.94 µg/mL. During the follow-up period, the incidence of VTE, cerebral infarction/transient ischemic attack (TIA)/systemic embolic events (SEE), bleeding, and all-cause death increased with increasing baseline D-dimer level. The incidence of all-cause death increased with increasing D-dimer level regardless of cancer stage. The adjusted hazard ratio of all-cause death was 1.03 (95% confidence interval: 1.02-1.03) per 1.0-µg/mL increase in baseline D-dimer level.

CONCLUSIONS: Increases in D-dimer levels were associated with a higher risk of thrombotic events, such as VTE and cerebral infarction/TIA/SEE, during cancer treatment. Furthermore, higher D-dimer levels at cancer diagnosis were associated with a higher mortality rate, regardless of cancer stage.

PMID:38430303 | DOI:10.1007/s10147-024-02475-6

Gastric Cancer. 2024 Mar 2. doi: 10.1007/s10120-024-01487-5. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma.

METHODS: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality.

RESULTS: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1.

CONCLUSIONS: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

PMID:38430275 | DOI:10.1007/s10120-024-01487-5

J Neurosurg Pediatr. 2024 Mar 1:1-6. doi: 10.3171/2023.11.PEDS23278. Online ahead of print.

ABSTRACT

OBJECTIVE: Among patients with a history of prior lipomyelomeningocele repair, an association between increased lumbosacral angle (LSA) and cord retethering has been described. The authors sought to build a predictive algorithm to determine which complex tethered cord patients will develop the symptoms of spinal cord retethering after initial surgical repair with a focus on spinopelvic parameters.

METHODS: An electronic medical record database was reviewed to identify patients with complex tethered cord (e.g., lipomyelomeningocele, lipomyeloschisis, myelocystocele) who underwent detethering before 12 months of age between January 1, 2008, and June 30, 2022. Descriptive statistics were used to characterize the patient population. The Caret package in R was used to develop a machine learning model that predicted symptom development by using spinopelvic parameters.

RESULTS: A total of 72 patients were identified (28/72 [38.9%] were male). The most commonly observed dysraphism was lipomyelomeningocele (41/72 [56.9%]). The mean ± SD age at index MRI was 2.1 ± 2.2 months, at which time 87.5% of patients (63/72) were asymptomatic. The mean ± SD lumbar lordosis at the time of index MRI was 23.8° ± 11.1°, LSA was 36.5° ± 12.3°, sacral inclination was 30.4° ± 11.3°, and sacral slope was 23.0° ± 10.5°. Overall, 39.6% (25/63) of previously asymptomatic patients developed new symptoms during the mean ± SD follow-up period of 44.9 ± 47.2 months. In the recursive partitioning model, patients whose LSA increased at a rate ≥ 5.84°/year remained asymptomatic, whereas those with slower rates of LSA change experienced neurological decline (sensitivity 77.5%, specificity 84.9%, positive predictive value 88.9%, and negative predictive value 70.9%).

CONCLUSIONS: This is the first study to build a machine learning algorithm to predict symptom development of spinal cord retethering after initial surgical repair. The authors found that, after initial surgery, patients who demonstrate a slower rate of LSA change per year may be at risk of developing neurological symptoms.

PMID:38428005 | DOI:10.3171/2023.11.PEDS23278

J Neurosurg Spine. 2024 Mar 1:1-11. doi: 10.3171/2023.12.SPINE23824. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the efffectiveness of a titanium vertebral augmentation device (SpineJack system) in terms of back pain, radiological outcomes, and economic burden compared with nonsurgical management (NSM) (bracing) for the treatment of vertebral compression fractures. Complications were also evaluated for both treatment methods.

METHODS: A prospective multicenter randomized study was performed at 9 French sites. Patients (n = 100) with acute traumatic Magerl type A1 and A3.1 vertebral fractures were enrolled and randomized to treatment with the SpineJack system or NSM consisting of bracing and administration of pain medication. Participants were monitored at admission, during the procedure, and at 1, 12, and 24 months after treatment initiation. Primary outcomes included visual analog scale back pain score, and secondary outcomes included disability (Oswestry Disability Index [ODI] score), health-related quality of life (EQ-5D score), radiological measures (vertebral kyphosis angle [VKA] and regional traumatic angulation [RTA]), and economic outcomes (costs, procedures, hours of help, and time to return to work).

RESULTS: Ninety-five patients were included in the analysis, with 48 in the SpineJack group and 47 in the NSM group. Back pain improved significantly for all participants with no significant differences between groups. ODI and EQ-5D scores improved significantly between baseline and follow-up (1, 12, and 24 months) for all participants, with the SpineJack group showing a larger improvement than the NSM group between baseline and 1 month. VKA was significantly lower (p < 0.001) (i.e., better) in the SpineJack group than in the NSM group at 1, 12, and 24 months of follow-up. There was no significant change over time in RTA for the SpineJack group, but the NSM group showed a significant worsening in RTA over time. SpineJack treatment was associated with higher costs than NSM but involved a shorter hospital stay, fewer medical visits, and fewer hours of nursing care. Time to return to work was significantly shorter for the SpineJack group than for the NSM group. There were no significant differences in complications between the two treatments.

CONCLUSIONS: Overall, there was no statistical difference in the primary outcomes between the SpineJack treatment group and the NSM group. In terms of secondary outcomes, SpineJack treatment was associated with better radiological outcomes, shorter hospital stays, faster return to work, and fewer hours of nursing care.

PMID:38427996 | DOI:10.3171/2023.12.SPINE23824

J Neurosurg. 2024 Mar 1:1-8. doi: 10.3171/2023.12.JNS231451. Online ahead of print.

ABSTRACT

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding.

METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites.

RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts.

CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

PMID:38427994 | DOI:10.3171/2023.12.JNS231451