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Nevin Manimala Statistics

Analysis of disease progression rate and related factors in amyotrophic lateral sclerosis patients at initial visit

Zhonghua Yi Xue Za Zhi. 2022 Jan 18;102(3):222-227. doi: 10.3760/cma.j.cn112137-20210728-01681.

ABSTRACT

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.

PMID:35042292 | DOI:10.3760/cma.j.cn112137-20210728-01681

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Nevin Manimala Statistics

Impact of Gleason pattern 5 on prognosis for newly diagnosed metastatic hormone-sensitive prostate cancer with Gleason score ≥8

Int J Urol. 2022 Jan 18. doi: 10.1111/iju.14781. Online ahead of print.

ABSTRACT

OBJECTIVE: We evaluated the impact of Gleason pattern 5 presence on prognosis among de novo metastatic hormone-sensitive prostate cancer patients with a Gleason score ≥8.

METHODS: The data of 559 patients diagnosed as metastatic hormone-sensitive prostate cancer with a Gleason score ≥8, who were initially treated with androgen deprivation therapy from 2008 to 2016, were retrospectively collected. Patients were divided into two groups as high and low volume based on the CHAARTED trial criteria.

RESULTS: The median overall survival of the 559 metastatic hormone-sensitive prostate cancer patients with Gleason score ≥8 was 70 months, with a median follow-up period of 36 months. Gleason pattern 5 was confirmed in 341 patients (61.0%), in which primary Gleason pattern 5 was confirmed in 164 patients (29.3%). The number of patients with high metastatic volume group was 363 (64.9%). In total and high metastatic volume groups, hemoglobin and lactate dehydrogenase were significant factors for predicting overall survival, but both Gleason pattern 5 and primary Gleason pattern 5 did not show a statistically significant difference. In the low-volume metastatic group, the median overall survival in patients with or without primary Gleason pattern 5 was 40 and 78 months, respectively. In multivariate analysis, only primary Gleason pattern 5 was an independent predictive factor for overall survival in the low-volume metastatic group (hazard ratio 2.76, 95% confidence interval 1.88-8.67; P = 0.0026).

CONCLUSION: The presence of Gleason pattern 5 was not associated with overall survival in metastatic hormone-sensitive prostate cancer with a Gleason score ≥8. In low-metastatic volume metastatic hormone-sensitive prostate cancer, primary Gleason pattern 5 was a poor prognostic factor, which might show a separate treatment option for this group.

PMID:35042278 | DOI:10.1111/iju.14781

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Nevin Manimala Statistics

Radiation Effects on Late-life Neurocognitive Function in Childhood Atomic Bomb Survivors: A Radiation Effects Research Foundation Adult Health Study

Radiat Res. 2022 Jan 18. doi: 10.1667/RADE-21-00122.1. Online ahead of print.

ABSTRACT

High-dose radiation in childhood such as is used in radiation therapy causes cognitive decline, but there is insufficient research on the cognitive effects of low- to medium-dose radiation. We aimed to reveal the association between atomic bomb radiation exposure in childhood and late-life neurocognitive function. In 2011 and 2013, we mailed the Neurocognitive Questionnaire (NCQ) to subjects who were 12 years old or younger at the time of the atomic bombing. We converted the four NCQ subscales (metacognition, emotional regulation, motivation/organization, and processing speed) to T scores and defined the highest 10% of the controls (exposure dose < 5 mGy) as impaired. We used a generalized linear mixed model to evaluate the effect of radiation exposure on T scores and percentage impaired. We enrolled 859 participants. At the time of the bombing, the mean (SD) age was 6.7 (3.8) years for the control (N = 390) and 6.1 (3.8) years for the exposed (N = 469). At the time of replying to the questionnaire, the mean age of all the participants was 73.7 (3.8) years of age. After adjusting for cofactors, older age was related to the decline of all neurocognitive subscales. Sex and education level had relevance to some of the subscales. For neurocognitive function, exposure dose was not related except to percentage impaired, motivation/organization. Late-life neurocognitive function in atomic bomb survivors exposed as children was associated with age, but not clearly with radiation dose. More studies are needed to evaluate the effect of low-dose radiation during childhood on long-term neurocognitive function.

PMID:35042238 | DOI:10.1667/RADE-21-00122.1

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Nevin Manimala Statistics

Risk Factors for High Blood Product Use in Patients with Stanford Type A Dissection

Thorac Cardiovasc Surg. 2022 Jan 18. doi: 10.1055/s-0041-1741004. Online ahead of print.

ABSTRACT

BACKGROUND: Intraoperative and postoperative bleeding associated with allogeneic blood transfusion and reoperation is still a common and feared complication in patients undergoing surgery due to acute Type A Aortic Dissection (aTAAD). The aim of our study was to identify risk factors for higher transfusion rates.

METHODS: In this retrospective single center study we evaluated pre -, intra-, and postoperative data of 121 patients with aTAAD. Depending on the median of received packed red blood cells (PRBCs), patients were divided into Group A (<8 PRBC, n = 53) and Group B (≥8 PRBC n = 68). Statistical analyses (descriptive statistics, univariable and multivariable logistic regression) were performed using SPSS software 25.0. Statistical significance was assumed at p-value <0.05.

RESULTS: A total of 120 patients received a blood product during their perioperative course. Among others we identified age, hemorrhagic pericardial effusion, and dual antiplatelet therapy as preoperative risk factors, low rectal temperature as intraoperative risk factor and low body temperature, positive fluid balance, high lactate level and beginning development of acute renal failure as postoperative risk factors.

CONCLUSION: Our study identifies several factors which predict a higher likelihood of bleeding and consecutive blood transfusion. Knowledge of these factors could influence the therapy to reduce transfusion requirements and lead to a targeted and more efficient use of coagulation products.

PMID:35042245 | DOI:10.1055/s-0041-1741004

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Neurofilament light chain serum levels correlate with the severity of neurotoxicity after CAR T cell treatment

Blood Adv. 2022 Jan 18:bloodadvances.2021006144. doi: 10.1182/bloodadvances.2021006144. Online ahead of print.

ABSTRACT

Antitumor therapy with CD19-targeted chimeric antigen-receptor-modified T (CAR T) cells is highly efficient. However, treatment is often complicated by a unique profile of unpredictable neurotoxic side effects of varying degrees known as immune effector cell-associated neurotoxicity syndrome (ICANS). Here, in 96 patients receiving CAR T-cells for refractory B-cell malignancies at two major CAR T-cell centers, we examined whether serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, correlate with the severity of ICANS. Serum NfL levels were measured before and after infusion of CAR T cells using a single-molecule enzyme-linked immunosorbent assay and correlated with the severity of ICANS. Elevated NfL serum levels prior to treatment were associated with more severe ICANS, in both unadjusted and adjusted analyses (p<0.01). Multivariate statistical models revealed a significant increase in NfL levels after CAR T-cell infusion (p<0.05), which correlated with the severity of ICANS (p<0.001). Pre-existing neuroaxonal injury, characterized by higher NfL levels before CAR T-cell treatment, correlated with the severity of subsequent ICANS. Thus, serum NfL level might serve as a predictive biomarker for assessing the severity of ICANS and for improving patient monitoring following CAR T-cell transfusion. However, these preliminary results should be validated in a larger prospective cohort of patients.

PMID:35042236 | DOI:10.1182/bloodadvances.2021006144

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Nevin Manimala Statistics

Comparison of 5 Normalization Methods for Knee Joint Moments in the Single-Leg Squat

J Appl Biomech. 2022 Jan 17:1-10. doi: 10.1123/jab.2021-0143. Online ahead of print.

ABSTRACT

Ratio scaling is the most common magnitude normalization approach for net joint moment (NJM) data. Generally, researchers compute a ratio between NJM and (some combination of) physical body characteristics (eg, mass, height, limb length, etc). However, 3 assumptions must be verified when normalizing NJM data this way. First, the regression line between NJM and the characteristic(s) used passes through the origin. Second, normalizing NJM eliminates its correlation with the characteristic(s). Third, the statistical interpretations following normalization are consistent with adjusted linear models. The study purpose was to assess these assumptions using data collected from 16 males and 16 females who performed a single-leg squat. Standard inverse dynamics analyses were conducted, and ratios were computed between the mediolateral and anteroposterior components of the knee NJM and participant mass, height, leg length, mass × height, and mass × leg length. Normalizing NJM-mediolateral by mass × height and mass × leg length satisfied all 3 assumptions. Normalizing NJM-anteroposterior by height and leg length satisfied all 3 assumptions. Therefore, if normalization of the knee NJM is deemed necessary to address a given research question, it can neither be assumed that using (any combination of) participant mass, height, or leg length as the denominator is appropriate nor consistent across joint axes.

PMID:35042188 | DOI:10.1123/jab.2021-0143

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Nevin Manimala Statistics

Tracking the stochastic growth of bacterial populations in microfluidic droplets

Phys Biol. 2022 Jan 18. doi: 10.1088/1478-3975/ac4c9b. Online ahead of print.

ABSTRACT

Bacterial growth in microfluidic droplets is relevant in biotechnology, in microbial ecology, and in understanding stochastic population dynamics in small populations. However, it has proved challenging to automate measurement of absolute bacterial numbers within droplets, forcing the use of proxy measures for population size. Here we present a microfluidic device and imaging protocol that allows high-resolution imaging of thousands of droplets, such that individual bacteria stay in the focal plane and can be counted automatically. Using this approach, we track the stochastic growth of hundreds of replicate Escherichia coli populations within droplets. {We find that, for early times, the statistics of the growth trajectories obey the predictions of the Bellman-Harris model, in which there is no inheritance of division time. Our approach should allow further testing of models for stochastic growth dynamics, as well as contributing to broader applications of droplet-based bacterial culture.

PMID:35042205 | DOI:10.1088/1478-3975/ac4c9b

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Plasma and amniotic fluid concentrations of nitric oxide: Effects on uterine artery and placental vasculature in women who underwent voluntary pregnancy termination and in women with missed and threatened abortion. A pilot study

Eur J Obstet Gynecol Reprod Biol. 2022 Jan 6;270:105-110. doi: 10.1016/j.ejogrb.2022.01.001. Online ahead of print.

ABSTRACT

OBJECTIVES: First trimester miscarriage is a multifactorial event. Various angiogenic factors have been proposed as possible early markers of non-viable pregnancies. The aim of the present study was to evaluate the systemic nitric oxide (NO) production in healthy early pregnancy and its possible role in first trimester miscarriage.

STUDY DESIGN: We prospectively enrolled women referred to our Unit for elective termination of pregnancy, threatened abortion or missed abortion. Blood samples were taken for testing circulating NO plasma levels. Subsequently, all patients underwent 2-D ultrasonographic analysis and Color Doppler imaging to assess the pulsatility index of the uterine arteries. 3-D ultrasonographic and power Doppler analysis allowed a volumetric and vascular reconstruction of the placenta. During dilatation and vacuum aspiration, amniotic fluid was collected.

RESULTS: Seventy-two patients were enrolled: 25 with elective termination of pregnancy (Group I); 17 with threatened abortion (Group II); 30 with missed abortion (Group III). Group II showed greater placental volume and lower uterine arteries PI than others. The plasma NO concentration resulted statistically higher in women with threatened abortion, while amniotic fluid NO concentration were higher in the viable pregnancies (Group I) than in the aborted fetuses (Group III). Plasma NO was inversely correlated with both mean arterial pressure and uterine artery PI and was positively correlated with amniotic fluid NO and CRL; amniotic fluid NO was positively correlated with placental Vascularization Index and Vascularization-Flow Index.

CONCLUSION: Amniotic NO concentration was higher in viable pregnancies and positively related to Doppler 3D indices of vascularization and blood flow within the placenta. Further studies are needed to elucidate its role in first trimester miscarriage.

PMID:35042176 | DOI:10.1016/j.ejogrb.2022.01.001

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Nevin Manimala Statistics

Effects of 7 Consecutive Systematic Applications of Cryotherapy With Compression

J Sport Rehabil. 2022 Jan 18:1-6. doi: 10.1123/jsr.2021-0208. Online ahead of print.

ABSTRACT

CONTEXT: Postsurgical and acute orthopedic patients are frequently treated with consecutive systematic cryotherapy despite the void of data to support treatment safety or effectiveness. The purpose of this study was to examine the occurrence of frostbite and measure skin temperatures during the systematic application of 2 cryocompression protocols.

DESIGN: A repeated-measures design guided this study.

METHODS: Nine healthy, college-aged participants (4 men and 5 women; age = 20.7 [1.2] y; height = 174 [11.01] cm; mass = 74 [14] kg) received both cryocompression protocols separated by ≥ 1 week. The static cryocompression protocol consisted of seven 40-minute “on” cycles of cryotherapy (4.4°C) with 45 mm Hg of compression, each followed by a 30-minute “off” cycle (no cryotherapy, compression set at 5 mm Hg). The intermittent cryocompression protocol consisted of seven 40-minute “on” cycles of cryotherapy (4.4°C) with compression alternating between 5 and 45 mm Hg, each followed by a 30-minute “off” cycle (no cryotherapy, compression set at 5 mmHg). At the end of each “on” and “off” cycle, we used a checklist to assess for frostbite, a PT-6 thermocouple to measure skin temperature (in degrees Celsius), and a 10-cm Likert scale to assess comfort.

RESULTS: None of the participants experienced any signs or symptoms of frostbite. There were no differences in skin temperature between the compression conditions over time (F14,112 = 1.43; P = .149) nor were there any differences between the 2 compression conditions (F1,8 = 3.75; P = .087; 1-β = 0.40). The skin temperatures were statistically different over the course of all 7 “on” and “off” cycles (F14,112 = 95.12; P < .001). There was no difference between the skin temperatures produced at the end of each “on” cycle.

CONCLUSIONS: The application of 7 consecutive cryotherapy treatments with compression did not result in any signs or symptoms of frostbite and produced similar skin temperatures with each “on” cycle.

PMID:35042184 | DOI:10.1123/jsr.2021-0208

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Nevin Manimala Statistics

Fluoxetine ameliorates Alzheimer’s disease progression and prevents the exacerbation of cardiovascular dysfunction of socially isolated depressed rats through activation of Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathway

Int Immunopharmacol. 2022 Jan 15;104:108488. doi: 10.1016/j.intimp.2021.108488. Online ahead of print.

ABSTRACT

Depression is a risk factor for Alzheimer’s (AD) and cardiovascular diseases (CVD). Therefore, depression treatment restricts its deteriorating effects on mood, memory and CV system. Fluoxetine is the most widely used antidepressant drug, it has neuroprotective effect through its antioxidant/anti-inflammatory properties. The current study investigated for the first-time the cross link between depression, AD and CVD besides, role of fluoxetine in mitigating such disorders. Depression was induced in rats by social isolation (SI) for 12 weeks, AlCL3 (70 mg/kg/day, i.p.) was used to induce AD which was administered either in SI or normal control (NC) grouped rats starting at 8th week till the end of the experiment, fluoxetine (10 mg/kg/day, p.o) treatment also was started at 8th week. SI and AD showed a statistically significant deteriorated effect on behavioral, neurochemical and histopathological analysis which was exaggerated when two disorder combined than each alone. Fluoxetine treatment showed protective effect against SI, AD and prevents exacerbation of CVD. Fluoxetine improved animals’ behavior, increased brain monoamines, BDNF besides increased antioxidant defense mechanism of SOD, TAC contents and increased protein expression of Nrf2/HO-1 with significant decrease of AChE activity, β-amyloid, Tau protein, MDA, TNF-α, IL1β contents as well as decreased protein expression of NF-kB, TLR4, NLRP3 and caspase1. It also showed cardioprotective effects as it improved lipid profile with pronounced decrease of cardiac enzymes of CK-MB, troponin and MEF2. In conclusion, fluoxetine represents as a promising drug against central and peripheral disorders through its anti-inflammatory/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.

PMID:35042170 | DOI:10.1016/j.intimp.2021.108488