Nevin Manimala

J Neurooncol. 2022 Jun 29. doi: 10.1007/s11060-022-04057-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Gliosarcomas are extremely rare malignant brain tumors, which can be classified as primary gliosarcoma (PGS) if the tumors arise de novo or secondary gliosarcoma (SGS) in patients who had previously been treated for glioblastoma. Given their rarity, it is unclear if PGS is clinically and genetically different from SGS. This meta-analysis aimed to investigate the clinicopathological features, prognostic survivals, and molecular profiles of these rare tumors.

METHODS: We searched PubMed and Web of Science for relevant studies. Odds ratio (OR), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model.

RESULTS: We included eight studies with 239 PGS and 79 SGS for meta-analyses. Compared to PGS, SGS occurred at a younger age and had lower rates of gross total resection and radiation therapy. Bevacizumab was more commonly administered in SGS. SGS patients had a significantly worse PFS (HR 0.60; 95% CI 0.40-0.89) and OS (HR 0.46; 95% CI 0.31-0.68) in comparison to PGS. The incidences of EGFR mutation, IDH mutation, and MGMT methylation were not statistically different between PGS and SGS.

CONCLUSION: Our results demonstrated that PGS and SGS had distinct clinicopathological profiles and prognoses but shared similar genetic profiles. This study facilitates our understanding of how these two malignant brain tumors behave clinically, but future studies will be required to elucidate the genetic pathways of PGS and SGS.

PMID:35768633 | DOI:10.1007/s11060-022-04057-w

Iran J Immunol. 2022 Jun;19(2):5. doi: 10.22034/iji.2022.91221.2065.

ABSTRACT

BACKGROUND: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases.

OBJECTIVES: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients’ characteristics.

METHODS: Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients’ demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients’ characteristics was statistically analyzed.

RESULTS: The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients’ characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity.

CONCLUSIONS: FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggested their association with the disease development and pathology.

PMID:35767890 | DOI:10.22034/iji.2022.91221.2065

Iran J Immunol. 2022 Jun;19(2):3. doi: 10.22034/iji.2022.90562.2014.

ABSTRACT

BACKGROUND: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however the mechanism is yet little understood.

OBJECTIVE: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms.

MATERIALS AND METHODS: Serum vitamin D, Interferon-γ (IFN-γ) and Interleukin (IL)-17 levels of the patients with UC were quantified using enzyme-linked immunosorbent assay (ELISA). Long non-coding RNAs (lncRNAs) levels were determined by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were collected from the healthy control subjects, stimulated with CD4+ T lymphocytes or helper T cells 17(Th17) differentiation conditions, and then exposed to calcitriol (vitamin D active form) or certain lentiviral treatment, followed by subsequent molecular level testing. For in vivo assay, mice were given 3% dextran sulfate sodium (DSS) to induce colitis.

RESULTS: Compared with the control group, vitamin D levels in the UCs were statistically lower, and there was a negative correlation between IL-17 and vitamin D in the UCs. The lncRNA OIP5-AS1 could decrease under calcitriol treatment in both CD4+ T cells and Th17 differentiation. The lncRNA OIP5-AS1 was a microRNA (miR)-26a-5p sponge and therefore modulated the Th17 cells and IL-6 expression. The lncRNA OIP5-AS1/miR-26a-5p/IL-6 axis mediated the regulation of calcitriol induced Th17 differentiation. Calcitriol had therapeutic effects on the UC mouse models by regulating the lncRNA OIP5-AS1 related pathway.

CONCLUSION: Vitamin D might have anti-inflammatory potential in the treatment of the UC.

PMID:35767888 | DOI:10.22034/iji.2022.90562.2014

Environ Sci Technol. 2022 Jun 29. doi: 10.1021/acs.est.2c00001. Online ahead of print.

ABSTRACT

Unconventional oil and gas development (UOGD) sometimes impacts water resources, including incidents of methane (CH₄) migration from compromised wells and spills that degrade water with salts, organics, and metals. We hypothesized that contamination may be more common where UOGD overlaps with legacy coal, oil, and gas extraction. We tested this hypothesis on ∼7000 groundwater analyses from the largest U.S. shale gas play (Marcellus), using data mining techniques to explore UOGD contamination frequency. Corroborating the hypothesis, we discovered small, statistically significant regional correlations between groundwater chloride concentrations ([Cl]) and UOGD proximity and density where legacy extraction was extremely dense (southwestern Pennsylvania (SWPA)) but no such correlations where it was minimal (northeastern Pennsylvania). On the other hand, legacy extraction of shallow gas in SWPA may have lessened today’s gas leakage, as no regional correlation was detected for [CH₄] in SWPA. We identify hotspots where [Cl] and [CH₄] increase by 3.6 and 3.0 mg/L, respectively, per UOG well drilled in SWPA. If the [Cl] correlations document contamination via brines leaked from wellbores, impoundments, or spills, we calculate that thallium concentrations could exceed EPA limits in the most densely developed hotspots, thus posing a potential human health risk.

PMID:35767873 | DOI:10.1021/acs.est.2c00001

J Gerontol B Psychol Sci Soc Sci. 2022 Jun 29:gbac087. doi: 10.1093/geronb/gbac087. Online ahead of print.

ABSTRACT

OBJECTIVES: There is evidence that loneliness is detrimental to the subjective well-being of older adults. However, little is known on this topic for the cohort of those in advanced age (80 years or over) which today is the fastest growing age group in the New Zealand population. We examined the relationships between loneliness and selected subjective well-being outcomes over five years.

METHODS: We used a regional, bicultural sample of those in advanced age from 2010 to 2015 (LiLACS NZ). The first wave enrolled 937 people (92% of whom were living in the community): 421 Māori (Indigenous New Zealanders aged 80-90 years) and 516 non-Māori aged 85 years. We applied standard regression techniques to baseline data and mixed effects models to longitudinal data, while adjusting for socio-demographic factors.

RESULTS: For both Māori and non-Māori, strong negative associations between loneliness and subjective well-being were found at baseline. In longitudinal analyses, we found that loneliness was negatively associated with life satisfaction as well as with mental health-related quality of life.

DISCUSSION: Our findings of adverse impacts on subjective well-being corroborate other evidence, highlighting loneliness as a prime candidate for intervention – appropriate to cultural context – to improve well-being for adults in advanced age.

PMID:35767846 | DOI:10.1093/geronb/gbac087

Clin Orthop Relat Res. 2022 Jun 21. doi: 10.1097/CORR.0000000000002282. Online ahead of print.

ABSTRACT

BACKGROUND: Large national databases have become a common source of information on patterns of cancer care in the United States, particularly for low-incidence diseases such as sarcoma. Although aggregating information from many hospitals can achieve statistical power, this may come at a cost when complex variables must be abstracted from the medical record. There is a current lack of understanding of the frequency of use of the Surveillance, Epidemiology, and End Results (SEER) database and the National Cancer Database (NCDB) over the last two decades in musculoskeletal sarcoma research and whether their use tends to produce papers with conflicting findings.

QUESTIONS/PURPOSES: (1) Is the number of published studies using the SEER and NCDB databases in musculoskeletal sarcoma research increasing over time? (2) What are the author, journal, and content characteristics of these studies? (3) Do studies using the SEER and the NCDB databases for similar diagnoses and study questions report concordant or discordant key findings? (4) Are the administrative data reported by our institution to the SEER and the NCDB databases concordant with the data in our longitudinally maintained, physician-run orthopaedic oncology dataset?

METHODS: To answer our first three questions, PubMed was searched from 2001 through 2020 for all studies using the SEER or the NCDB databases to evaluate sarcoma. Studies were excluded from the review if they did not use these databases or studied anatomic locations other than the extremities, nonretroperitoneal pelvis, trunk, chest wall, or spine. To answer our first question, the number of SEER and NCDB studies were counted by year. The publication rate over the 20-year span was assessed with simple linear regression modeling. The difference in the mean number of studies between 5-year intervals (2001-2005, 2006-2010, 2011-2015, 2016-2020) was also assessed with Student t-tests. To answer our second question, we recorded and summarized descriptive data regarding author, journal, and content for these studies. To answer our third question, we grouped all studies by diagnosis, and then identified studies that shared the same diagnosis and a similar major study question with at least one other study. We then categorized study questions (and their associated studies) as having concordant findings, discordant findings, or mixed findings. Proportions of studies with concordant, discordant, or mixed findings were compared. To answer our fourth question, a coding audit was performed assessing the concordance of nationally reported administrative data from our institution with data from our longitudinally maintained, physician-run orthopaedic oncology dataset in a series of patients during the past 3 years. Our orthopaedic oncology dataset is maintained on a weekly basis by the senior author who manually records data directly from the medical record and sarcoma tumor board consensus notes; this dataset served as the gold standard for data comparison. We compared date of birth, surgery date, margin status, tumor size, clinical stage, and adjuvant treatment.

RESULTS: The number of musculoskeletal sarcoma studies using the SEER and the NCDB databases has steadily increased over time in a linear regression model (β = 2.51; p < 0.001). The mean number of studies per year more than tripled during 2016-2020 compared with 2011-2015 (39 versus 13 studies; mean difference 26 ± 11; p = 0.03). Of the 299 studies in total, 56% (168 of 299) have been published since 2018. Nineteen institutions published more than five studies, and the most studies from one institution was 13. Orthopaedic surgeons authored 35% (104 of 299) of studies, and medical oncology journals published 44% (130 of 299). Of the 94 studies (31% of total [94 of 299]) that shared a major study question with at least one other study, 35% (33 of 94) reported discordant key findings, 29% (27 of 94) reported mixed key findings, and 44% (41 of 94) reported concordant key findings. Both concordant and discordant groups included papers on prognostic factors, demographic factors, and treatment strategies. When we compared nationally reported administrative data from our institution with our orthopaedic oncology dataset, we found clinically important discrepancies in adjuvant treatment (19% [15 of 77]), tumor size (21% [16 of 77]), surgery date (23% [18 of 77]), surgical margins (38% [29 of 77]), and clinical stage (77% [59 of 77]).

CONCLUSION: Appropriate use of databases in musculoskeletal cancer research is essential to promote clear interpretation of findings, as almost two-thirds of studies we evaluated that asked similar study questions produced discordant or mixed key findings. Readers should be mindful of the differences in what each database seeks to convey because asking the same questions of different databases may result in different answers depending on what information each database captures. Likewise, differences in how studies determine which patients to include or exclude, how they handle missing data, and what they choose to emphasize may result in different messages getting drawn from large-database studies. Still, given the rarity and heterogeneity of sarcomas, these databases remain particularly useful in musculoskeletal cancer research for nationwide incidence estimations, risk factor/prognostic factor assessment, patient demographic and hospital-level variable assessment, patterns of care over time, and hypothesis generation for future prospective studies.

LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID:35767810 | DOI:10.1097/CORR.0000000000002282

Clin Orthop Relat Res. 2022 Jun 20. doi: 10.1097/CORR.0000000000002276. Online ahead of print.

ABSTRACT

BACKGROUND: Aseptic revision THA and TKA are associated with an increased risk of adverse outcomes compared with primary THA and TKA. Understanding the risk profiles for patients undergoing aseptic revision THA or TKA may provide an opportunity to decrease the risk of postsurgical complications. There are risk stratification tools for postoperative complications after aseptic revision TKA or THA; however, current tools only include nonmodifiable risk factors, such as medical comorbidities, and do not include modifiable risk factors.

QUESTIONS/PURPOSES: (1) Can machine learning predict 30-day mortality and complications for patients undergoing aseptic revision THA or TKA using a cohort from the American College of Surgeons National Surgical Quality Improvement Program database? (2) Which patient variables are the most relevant in predicting complications?

METHODS: This was a temporally validated, retrospective study analyzing the 2014 to 2019 National Surgical Quality Improvement Program database, as this database captures a large cohort of aseptic revision THA and TKA patients across a broad range of clinical settings and includes preoperative laboratory values. The training data set was 2014 to 2018, and 2019 was the validation data set. Given that predictive models learn expected prevalence of outcomes, this split allows assessment of model performance in contemporary patients. Between 2014 and 2019, a total of 24,682 patients underwent aseptic revision TKA and 17,871 patients underwent aseptic revision THA. Of those, patients with CPT codes corresponding to aseptic revision TKA or THA were considered as potentially eligible. Based on excluding procedures involving unclean wounds, 78% (19,345 of 24,682) of aseptic revision TKA procedures and 82% (14,711 of 17,871) of aseptic revision THA procedures were eligible. Ten percent of patients in each of the training and validation cohorts had missing predictor variables. Most of these missing data were preoperative sodium or hematocrit (8% in both the training and validation cohorts). No patients had missing outcome data. No patients were excluded due to missing data. The mean patient was age 66 ± 12 years, the mean BMI was 32 ± 7 kg/m2, and the mean American Society of Anesthesiologists (ASA) Physical Score was 3 (56%). XGBoost was then used to create a scoring tool for 30-day adverse outcomes. XGBoost was chosen because it can handle missing data, it is nonlinear, it can assess nuanced relationships between variables, it incorporates techniques to reduce model complexity, and it has a demonstrated record of producing highly accurate machine-learning models. Performance metrics included discrimination and calibration. Discrimination was assessed by c-statistics, which describe the area under the receiver operating characteristic curve. This quantifies how well a predictive model discriminates between patients who have the outcome of interest versus those who do not. Relevant ranges for c-statistics include good (0.70 to 0.79), excellent (0.80 to 0.89), and outstanding (> 0.90). We estimated 95% confidence intervals (CIs) for c-statistics by 500-sample bootstrapping. Calibration curves quantify reliability of model predictions. Reliable models produce prediction probabilities for outcomes that are similar to observed probabilities of those outcomes, so a well-calibrated model should demonstrate a calibration curve that does not deviate substantially from a line of slope 1 and intercept 0. Calibration curves were generated on the 2019 validation data. Shapley Additive Explanations (SHAP) visualizations were used to investigate feature importance to gain insight into how models made predictions. The models were built into an online calculator for ongoing testing and validation. The risk calculator, which is freely available (http://nb-group.org/rev2/), allows a user to input patient data to calculate postoperative risk of 30-day mortality, cardiac, and respiratory complications after aseptic revision TKA or THA. A post hoc analysis was performed to assess whether using data from 2020 would improve calibration on 2019 data.

RESULTS: The model accurately predicted mortality, cardiac complications, and respiratory complications after aseptic revision THA or TKA, with c-statistics of 0.88 (95% CI 0.83 to 0.93), 0.80 (95% CI 0.75 to 0.84), and 0.78 (95% CI 0.74 to 0.82), respectively, on internal validation and 0.87 (95% CI 0.77 to 0.96), 0.70 (95% CI 0.61 to 0.78), and 0.82 (95% CI 0.75 to 0.88), respectively, on temporal validation. Calibration curves demonstrated slight over-confidence in predictions (most predicted probabilities were higher than observed probabilities). Post hoc analysis of 2020 data did not yield improved calibration on the 2019 validation set. Important risk factors for all models included increased age and higher ASA, BMI, hematocrit level, and sodium level. Hematocrit and ASA were in the top three most important features for all models. The factor with the strongest association for mortality and cardiac complication models was age, and for the respiratory model, chronic obstructive pulmonary disease. Risk related to sodium followed a U-shaped curve. Preoperative hyponatremia and hypernatremia predicted an increased risk of mortality and respiratory complications, with a nadir of 138 mmol/L; hyponatremia was more strongly associated with mortality than hypernatremia. A hematocrit level less than 36% predicted an increased risk of all three adverse outcomes. A BMI less than 24 kg/m2-and especially less than 20 kg/m2-predicted an increased risk of all three adverse outcomes, with little to no effect for higher BMI.

CONCLUSION: This temporally validated model predicted 30-day mortality, cardiac complications, and respiratory complications after aseptic revision THA or TKA with c-statistics ranging from 0.78 to 0.88. This freely available risk calculator can be used preoperatively by surgeons to educate patients on their individual postoperative risk of these specific adverse outcomes. Unanswered questions that remain include whether altering the studied preoperative patient variables, such as sodium or hematocrit, would affect postoperative risk of adverse outcomes; however, a prospective cohort study is needed to answer this question.

LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID:35767804 | DOI:10.1097/CORR.0000000000002276

J Clin Oncol. 2022 Jun 29:JCO2101811. doi: 10.1200/JCO.21.01811. Online ahead of print.

ABSTRACT

A statistical test for the presence of treatment effects on survival will be based on a null hypothesis (absence of effects) and an alternative (presence of effects). The null is very simply expressed. The most common alternative, also simply expressed, is that of proportional hazards. For this situation, not only do we have a very powerful test in the log-rank test but also the outcome is readily interpreted. However, many modern treatments fall outside this relatively straightforward paradigm and, as such, have attracted attention from statisticians eager to do their best to avoid losing power as well as to maintain interpretability when the alternative hypothesis is less simple. Examples include trials where the treatment effect decays with time, immunotherapy trials where treatment effects may be slow to manifest themselves as well as the so-called crossing hazards problem. We review some of the solutions that have been proposed to deal with these issues. We pay particular attention to the integrated log-rank test and how it can be combined with the log-rank test itself to obtain powerful tests for these more complex situations.

PMID:35767775 | DOI:10.1200/JCO.21.01811

Ann Agric Environ Med. 2022 Jun 24;29(2):316-320. doi: 10.26444/aaem/150522. Epub 2022 Jun 9.

ABSTRACT

INTRODUCTION: Between 2015-2020, the concentrations and diversity of filamentous fungi as well as the levels of mycotoxins in 4 classes of vegetables and fruits were studied in samples from farms located in eastern Poland. The short communication summarizes the results with the use of statistical analysis and indicates the potential health hazards associated with the consumption of the produce contaminated with fungi and/or mycotoxins. The concentrations of filamentous fungi in all examined samples were moderate (2.813 – 4.146 log₁₀ CFU g ^-1). The highest values were noted in root vegetables, whereas the lowest values in fruit vegetables. The mycobiota revealed a marked biodiversity (67 species and 33 genera). Penicillium and Fusarium prevailed in the mycobiota of root vegetables, whereas Cladosporium and Alternaria in the remaining classes. Most of identified species (88.1%) were described as potentially pathogenic. The importance of mycotoxins as a potential health risk factor for vegetable consumers, was confirmed by the detection of a high prevalence (>55%) of total aflatoxin (AFT). The level of AFT in berry fruits was significantly higher than in other classes. The high prevalence (58.5%) of deoxynivalenol was noted in raspberries.

CONCLUSIONS: Filamentous fungi present in the examined vegetables and fruits may pose a potential health risk for consumers due to a high prevalence of potentially pathogenic species, mostly those producing mycotoxins.

PMID:35767771 | DOI:10.26444/aaem/150522

J Dual Diagn. 2022 Jun 29:1-9. doi: 10.1080/15504263.2022.2090650. Online ahead of print.

ABSTRACT

Objective: It is well-established that Bipolar Disorder (BD) has comorbidity with Alcohol Use Disorder (AUD) and could present the same symptoms of an underlying diagnosis of BD, therefore delaying the proper relevant treatment. Recent studies show the occurrence of alterations in the circulating levels of inflammatory mediators in patients dealing with AUD as well as those with BD. The objective of this study is to get an assessment of whether patients with AUD and BD comorbidity [BD(+)] would present different ratios of the Complete Blood Count (CBC) in comparison with patients with AUD but without a BD comorbidity [BD(-)]. Methods: This is a retrospective study, conducted through a selection of patients files who were admitted to the psychiatric department at Hôtel-Dieu de France University Hospital in Beirut, Lebanon, between January of the year 2016 and May of the year 2021. Overall, 83 files of patients dealing with AUD were included in this study. Results: Patients with BD(+) showed a higher Eosinophils to Lymphocytes Ratio (ELR) in comparison to those with BD(-). The Receiver Operation Characteristic (ROC) analysis had an area under the curve at 0.719 with a p = .001. The cutoff value of ELR that best differentiates BD(-) from BD(+) was 0.087 (Sensitivity = 81.3%; Specificity = 63.6%). The logistic regression analysis showed that an ELR superior to 0.087 presented a statistically significant difference, exposing patients belonging to the BD(+) group (OR = 11.66; p < .001). Conclusions: Our data suggest that ELR may be a valuable, reproducible, easily accessible, and cost-effective inflammatory marker, pointing at the presence of a BD comorbidity with AUD.

PMID:35767724 | DOI:10.1080/15504263.2022.2090650