Category: Statistics

Eur J Surg Oncol. 2021 Aug 30:S0748-7983(21)00703-4. doi: 10.1016/j.ejso.2021.08.031. Online ahead of print.

ABSTRACT

INTRODUCTION: Minimally invasive techniques show improved short-term and comparable long-term outcomes compared to open techniques in the treatment of gastric cancer and improved survival has been seen with the implementation of multimodality treatment. Therefore, focus of research has shifted towards optimizing treatment regimens and improving quality of life.

MATERIALS AND METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients were randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG) after neoadjuvant chemotherapy. This study investigated patient reported outcome measures (PROMs) on health-related quality of life (HRQoL) following OTG or MITG, using the Euro-Qol-5D (EQ-5D) and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, modules C30 and STO22. Due to multiple testing a p-value < 0.001 was deemed statistically significant.

RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. A response compliance of 80% was achieved for all PROMs. The EQ5D overall health score one year after surgery was 85 (60-90) in the open group and 68 (50-83.8) in the minimally invasive group (P = 0.049). The median EORTC-QLQ-C30 overall health score one year postoperatively was 83,3 (66,7-83,3) in the open group and 58,3 (35,4-66,7) in the minimally invasive group (P = 0.002). This was not statistically significant.

CONCLUSION: No differences were observed between open total gastrectomy and minimally invasive total gastrectomy regarding HRQoL data, collected using the EQ-5D, EORTC QLQ-C30 and EORTC-QLQ-STO22 questionnaires.

PMID:34503850 | DOI:10.1016/j.ejso.2021.08.031

Z Orthop Unfall. 2021 Sep 9. doi: 10.1055/a-1527-7900. Online ahead of print.

ABSTRACT

OBJECTIVE: Degradative enzymes such as matrix metalloproteinase (MMP) and disintegrin metalloproteinase with platelet thrombin-sensitive protein-like motifs (ADAMTS) play a key role in the development of osteoarthritis (OA). We aimed to investigate the effects of OA subchondral osteoblasts on the expression of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 in chondrocytes and the regulation of mitogen-activated protein kinase (MAPK) signaling pathway.

METHODS: A rat knee OA model was constructed by cutting the anterior cruciate ligament of the knee joints, and normal rat articular cartilage chondrocytes (N-ACC), OA rat articular cartilage chondrocytes (O-ACC), normal subchondral bone osteoblasts (N-SBO), and OA subchondral bone osteoblasts (O-SBO) were isolated and extracted. The expressions of O-ACC and O-SBO COL1 and COL2 were detected respectively. Chondrocytes were identified by immunofluorescence of COL2 and toluidine blue staining, and osteoblasts were identified by COL1 immunofluorescence, alkaline phosphatase (ALP), and Alizarin Red staining. Gene expression of COL1, COL2, and aggrecan in normal chondrocytes and OA chondrocytes, and gene expression of osteoblast ALP and osteocalcin (OCN) were detected by RT-PCR to identify the two chondrocytes and the two osteoblast phenotypes. The constructing N-ACC group, O-ACC group, N-ACC + N-SBO group, N-ACC + O-SBO group, O-ACC + N-SBO group, O-ACC + O-SBO group, I + N-ACC + O-SBO group, and I + O-ACC + O-SBO group cell cultures, and the expression of ERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes in chondrocytes cultured for 0, 24, 48, and 72 h were detected by RT-PCR. The protein expressions of pERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 were detected by Western blot.

RESULTS: · The X-ray showed that the knee joint space of the affected limb became narrow.. · The results of RT-PCR of COL2 and aggrecan gene in OA and normal chondrocytes suggest that the relative expression of COL2 in OA articular chondrocytes (0.24 ± 0.07) is significantly lower than that in normal cartilage (0.61 ± 0.07) (p < 0.05). The relative expression of AGG (0.37 ± 0.16) in OA chondrocytes was significantly lower than that of normal chondrocytes AGG (1.30 ± 0.25) (p < 0.05). The expression of COL1 was very low, and was not statistically significant.. · The results of RT-PCR of the osteoblast ALP and OCN gene indicated that gene expression of ALP (12.30 ± 1.17) and OCN (20.47 ± 4.19)was upregulated when compared with the relative expression of ALP (4.66 ± 0.71) (p < 0.05) and OCN (12.17 ± 2.76) (p < 0.05) in normal osteoblasts, indicating that osteoblasts of OA have greater osteogenic potential than normal osteoblasts.. · The expressions of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes and proteins in OA chondrocytes or normal chondrocytes were basically unchanged when they were cocultured with normal osteoblasts. Indirect coculture of OA osteoblasts and chondrocytes could promote the expression of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes and proteins in chondrocytes. Overexpression of ADAMTS and MMP in coculture systems can be reversed by MAPK-ERK inhibitors..

CONCLUSIONS: · OA subchondral bone osteoblasts can promote the overexpression of ADAMTS and MMPs in chondrocytes.. · The ERK signaling pathway may be involved in the regulation of the effect of subchondral bone osteoblasts on chondrocytes..

PMID:34500490 | DOI:10.1055/a-1527-7900

Epilepsy Behav. 2021 Sep 6;123:108280. doi: 10.1016/j.yebeh.2021.108280. Online ahead of print.

ABSTRACT

BACKGROUND: Knowledge and attitude of doctors toward epilepsy surgery are essential for management and timely referral of people with Drug refractory epilepsy (DRE). This study aimed at analyzing knowledge, attitude, and barriers for epilepsy surgery among medical residents.

METHODS: A survey consisting of 16 statements in a Likert-like scale and one open-ended question was conducted among residents joining different postgraduate courses after MBBS (GR) and super-specialty courses after MD (PG) within 2 months of joining the institute. PGs with a postgraduate degree in internal medicine, pediatrics, or psychiatry were included. Demographic data were analyzed using descriptive statistics. Difference in response to the survey statements was analyzed using independent t test.

RESULTS: 115 participated in the survey of which 97 were GRs. Participants belonged to 22 different states and 3 were foreign nationals. 45% of participants did not know the definition of DRE. There was a difference of opinion among GRs and PGs regarding surgery as a treatment option for epilepsy and feasibility of epilepsy surgery in children (p < .05). PGs were more confident in treating PWE and preferred to refer people with DRE to a higher center early (p < .05). Lack of knowledge was the commonest barrier for epilepsy surgery.

CONCLUSION: A substantial number of participants lacked the basic knowledge of DRE and epilepsy surgery. Lack of knowledge was perceived to be the commonest barrier for epilepsy surgery. Dissemination of basic knowledge and development of protocols for identification and referral of people with DRE are the need of the hour.

PMID:34500435 | DOI:10.1016/j.yebeh.2021.108280

Blood Adv. 2021 Sep 9:bloodadvances.2021004932. doi: 10.1182/bloodadvances.2021004932. Online ahead of print.

ABSTRACT

Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years old. Treatment outcomes were compared with those of 1,792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% versus 29%, respectively; P<0.001), with a much higher proportion of patients receiving allo-HCT (80% versus 34%, respectively; P<0.001) and a shorter interval from diagnosis to allo-HCT (median, 128 versus 170 days, respectively; P<0.001). Among the 90 patients who received allo-HCT (cord blood, n=30; HLA-haploidentical related donors, n=20; other related donors, n=14; other unrelated donors, n=26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered with the UMIN Clinical Trials Registry (UMIN 000017672).

PMID:34500464 | DOI:10.1182/bloodadvances.2021004932

Knee. 2021 Sep 6;32:173-182. doi: 10.1016/j.knee.2021.08.008. Online ahead of print.

ABSTRACT

PURPOSE: Osteoarthritis (OA) is a debilitating joint disease characterized by progressive loss of articular cartilage. Intra-articular injections are a mainstay of nonoperative treatment, however, there is controversy as to the optimal injectable for these patients. The purpose of the current study is to perform a network meta-analysis of the randomized control trials in the literature to ascertain whether there is a superior injectable nonoperative treatment for knee OA.

METHODS: The literature search was conducted based on the PRISMA guidelines. Randomized control trials (RCTs) evaluating intra-articular injectables in osteoarthritic knees were included. Data was extracted and Visual Analogue Scale (VAS) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, where available were analyzed at 1, 3, 6 and 12 months. Clinical outcomes were compared using a frequentist approach to network meta-analysis, with statistical analysis performed using R. The treatment options were ranked using the P-Score.

RESULTS: Seventy-nine RCTs with 8761 patients were included in this review. Intra-articular injectables evaluated included autologous conditioned serum (ACS), bone marrow aspirate concentrate (BMAC), botulinum toxin, corticosteroids (CS), hyaluronic acid (HA), mesenchymal stem cells (MSC), ozone, saline placebo, platelet-rich plasma (PRP), plasma rich in growth factor (PRGF), and stromal vascular fraction (SVF). At 4-6 weeks and 3 months of follow-up, the treatment with the highest P-Score for WOMAC score was high molecular weight (HMW) HA + CS [P-Score = 0.9500 and 8503, respectively]. At 6-months follow-up, the treatment with the highest P-Score for WOMAC score was PRP [P-Score = 0.7676]. At all post-injection time points, the treatment with the highest P-Score for VAS score [P-Score Range = 0.8631-9927] and Womac score at 12 Months [P-Score = 0.9044] was SVF.

CONCLUSIONS: The current evidence shows that SVF injections result in the greatest improvement in pain and functional outcomes in patients with knee OA at up to 1 year of follow-up.

PMID:34500430 | DOI:10.1016/j.knee.2021.08.008

Knee. 2021 Sep 6;32:183-191. doi: 10.1016/j.knee.2021.08.016. Online ahead of print.

ABSTRACT

BACKGROUND: Prosthetic joint infection (PJI) causes significant morbidity and mortality following knee replacement surgery. Identifying causative organisms and antibiotic sensitivities is critical in increasing the chance of infection eradication. This study investigated whether biopsy alone was superior to aspiration alone for serological diagnosis in PJI following knee replacement. Secondly, we investigated whether biopsy identifies the same or new/different microbiological flora as aspiration.

METHODS: Since December 2014, the Exeter Knee Reconstruction Unit (EKRU) has prospectively collated data regarding all PJIs referred from our local/regional network which have been reviewed via our Multi-Disciplinary Team (MDT). We identified and included consecutive patients from this MDT from Dec.2014-Mar.2020 and analysed their electronic records. Statistical analysis was performed using Stata.

RESULTS: 65/100 patients studied had both pre-operative aspiration and biopsy. 31/65 (48%) had positive aspiration and biopsies. No aspirate samples were positive with corresponding biopsies negative. In 19/65 (29%) of infection positive patients, biopsy identified new (7) or additional (12) organisms not identified by aspiration. Aspiration had a sensitivity of 70%, specificity of 88%, positive predictive value of 90.3% and negative predictive value of 64.7%. Biopsy had a sensitivity of 97.5%, specificity of 88%, positive predictive value of 92.9% and negative predictive value of 95.7%.

CONCLUSION: In 29% of confirmed PJI cases, arthroscopic biopsy identified either additional organisms in a polymicrobial PJI when compared to aspiration, or new positive results when aspiration alone was negative. This study demonstrates the benefits of arthroscopic biopsy for serological diagnosis in cases of knee PJI and aids treatment planning.

PMID:34500431 | DOI:10.1016/j.knee.2021.08.016

Environ Int. 2021 Sep 6;157:106853. doi: 10.1016/j.envint.2021.106853. Online ahead of print.

ABSTRACT

Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.

PMID:34500361 | DOI:10.1016/j.envint.2021.106853

Environ Pollut. 2021 Sep 5;290:118122. doi: 10.1016/j.envpol.2021.118122. Online ahead of print.

ABSTRACT

Children in urban environments are exposed to potential harmful elements (PHEs) through variable exposure media. Playing activities in outdoor playgrounds have been considered of high concern due to children’s exposure to sand-bound PHEs through unintentional or intentional sand ingestion. Furthermore, the affinity of magnetic particles with dust-bound PHEs in playgrounds has been reported. In this study, playground sands (PG sands) from public playgrounds in the city of Thessaloniki, N. Greece were sampled and the levels, the contamination degree, oral bioaccessibility and exposure assessment of PHEs were evaluated. In addition, low-cost and fast magnetic measurements (i.e. mass specific magnetic susceptibility, χ_lf) were explored as potential pollution and health risk proxies. Mineralogically, siliceous PG sands dominated, while morphologically angular magnetic particles and Fe-rich “spherules” of anthropogenic origin were revealed and verified by enhanced χ_lf values. The average total elemental contents exhibited a descending order of Mn > Ba > Cr > Zn > Ni > Pb > Cu > Co > As > Sn > Bi > Cd, however only Cd, Bi, Pb, Cr, As and Zn were presented anthropogenically enhanced. Notable increase on PHEs levels and finer sand fractions were observed with continuous sand use. Anthropogenically derived elements (i.e. Cd and Pb with high I_geo values) exhibited higher bioaccessible fractions in PG sands and considered easily soluble in gastric fluids through ingestion. However, increased risks were found for specific PHEs (especially Pb) only in a worst case exposure scenario of an intentional sand ingestion (pica disorder). Statistical analysis results revealed a linkage of anthropogenic components with sand-bound magnetic particles. Moreover, the recorded high affinity of Pb contents (in an enhanced magnetized sub-set of PG sands) and bioaccessible Cd fractions with χ_lf provide a preliminary indication on the successful applicability of low-cost and fast magnetic measurements in high impacted playground environments.

PMID:34500396 | DOI:10.1016/j.envpol.2021.118122

Clin Neurol Neurosurg. 2021 Aug 28;209:106918. doi: 10.1016/j.clineuro.2021.106918. Online ahead of print.

ABSTRACT

OBJECTIVES: Vagus nerve stimulation (VNS) has been widely used as an effective treatment for patients with drug-resistant epilepsy (DRE). However, little is known about grey matter (GM) and white matter (WM) microstructure changes caused by VNS. This study aimed to detect consistent GM and WM alterations in epilepsy patients with vagus nerve stimulators.

METHODS: The diffusion tensor imaging data was acquired from 15 patients who underwent VNS implantation. The voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to detect group differences in GM and WM microstructure and explore their correlation with postoperative seizure reduction.

RESULTS: After 3 months of stimulation, GM density reduced in right cerebellum, left superior temporal gyrus, right inferior temporal gyrus and left thalamus, and increased in left cerebellum, left inferior parietal lobule, left middle occipital gyrus and left gyrus rectus. No significant volume changes had been found in 14 subcortical nuclei. The fractional anisotropy (FA) values reduced in left superior longitudinal fasciculus and left corticospinal tract, and increased in bilateral cingulum and body of corpus callosum. The mean diffusivity (MD) values reduced in right retrolenticular part of internal capsule, right posterior corona radiata and right superior longitudinal fasciculus. The seizure reduction had positive correlation trends with the volume reduction in left nucleus accumbens and right amygdala, and MD reduction in right medial lemniscus and right posterior corona radiata.

CONCLUSIONS: The results showed that VNS could cause changes of GM density, WM FA and MD values in epilepsy patients. The volume and MD reduction in some subcortical structures might participate in the seizure frequency reduction of VNS.

PMID:34500340 | DOI:10.1016/j.clineuro.2021.106918

J Psychiatr Res. 2021 Sep 3;143:163-175. doi: 10.1016/j.jpsychires.2021.09.001. Online ahead of print.

ABSTRACT

Through imaging studies, a significant increase in cerebral activity has been detected in fronto-temporal areas in patients experiencing auditory verbal hallucinations. Therefore, non-invasive neuromodulation, in particular transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), has been considered as a therapeutic intervention for medication-resistant auditory verbal hallucinations in schizophrenia. We aimed to synthesize results from randomized trials on either rTMS or tDCS versus placebo in patients with schizophrenia by including five recently published trials in the field. A systematic review and meta-analysis of relevant literature was conducted. Studies were included on the basis of pre-defined selection criteria. The quality of the studies was assessed by the Cochrane Risk of Bias Tool for Randomized Controlled Trials. RevMan 5.3 was used to conduct the statistical analysis. Including 465 and 960 patients, respectively, 12 tDCS and 27 rTMS studies were included. Regarding treatment of medication refractory auditory verbal hallucinations, no significant effect of tDCS (-0.23 [-0.49, 0.02], p = 0.08) or rTMS (-0.19 [-0.50, 0,11], p = 0.21) was found compared to sham in this meta-analysis. The current study found that it cannot be concluded that rTMS and tDCS are efficacious in treating medication-resistant auditory verbal hallucinations. Larger randomized controlled tDCS trials of a higher quality should be conducted in the future to establish substantial evidence of tDCS. The interventions appear safe and may have beneficial effects on other outcomes.

PMID:34500345 | DOI:10.1016/j.jpsychires.2021.09.001