Nevin Manimala

Complement Ther Clin Pract. 2021 Nov 11;46:101503. doi: 10.1016/j.ctcp.2021.101503. Online ahead of print.

ABSTRACT

BACKGROUND: Bloodletting therapy (BLT) is widely used to relieve acute gouty arthritis (AGA). However, limited evidence-based reports exist on the effectiveness and safety of BLT. This systematic review aims to evaluate the feasibility and safety of BLT in treating AGA.

METHODS: Seven databases were exhaustively screened from the date of establishment to July 31, 2020, irrespective of the publication source and language. The included articles were evaluated for bias risk by using the Cochrane risk of bias assessment tool. All statistical analyses were done with Review Manager 5.3.

RESULTS: Twelve studies involving 894 participants were included for the final analysis. Our meta-analysis revealed that BLT was highly effective in relieving pain (MD = -1.13, 95% CI [-1.60, -0.66], P < 0.00001), with marked alterations in the total effective (RR = 1.09, 95% [1.05, 1.14], P < 0.0001) and curative rates (RR = 1.37, 95%CI [1.17, 1.59], P < 0.0001). In addition, BLT could dramatically reduce serum C-reactive protein (CRP) level (MD = -3.64, 95%CI [-6.72, -0.55], P = 0.02). Both BLT and Western medicine (WM) produced comparable decreases in uric acid (MD = -18.72, 95%CI [-38.24, 0.81], P = 0.06) and erythrocyte sedimentation rate (ESR) levels (MD = -3.01, 95%CI [-6.89, 0.86], P = 0.13). Lastly, we demonstrated that BLT was safer than WM in treating AGA (RR = 0.36, 95%CI [0.13, 0.97], P = 0.04).

CONCLUSION: BLT is effective in alleviating pain and decreasing CRP level in AGA patients with a lower risk of evoking adverse reactions.

PMID:34814062 | DOI:10.1016/j.ctcp.2021.101503

Thromb Res. 2021 Nov 17;208:190-197. doi: 10.1016/j.thromres.2021.11.009. Online ahead of print.

ABSTRACT

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKIs) may increase the risk of thrombotic events of endocrine therapy (ET) in women with hormone-sensitive, HER2-negative advanced breast cancer (BC). Aim of our systematic review is the estimate of the risk of venous and arterial thromboembolism in women with advanced BC treated with CDKIs in phase III randomized controlled trials (RCTs).

METHODS: Studies were identified by electronic search of MEDLINE, EMBASE and CENTRAL database until October 2021. Risk of bias was assessed according to Cochrane criteria. Differences in thrombotic outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using both a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I² statistic.

RESULTS: We included 7 phase III RCTs (4415 patients) for a total of 15 papers (7 were the first published paper and 8 the follow-up papers). Reporting of thrombotic events was at high risk of bias. Women with advanced BC treated with CDKIs and ET had a two to threefold increased risk of venous thromboembolic event (VTE) compared to ET plus placebo arm [OR 2.90 (95% CI 1.32, 6.37; I² = 0%) in the main papers and OR 2.20 (95% CI 0.93, 5.20; I² = 49%) in the follow-up papers]. Women with advanced BC treated with CDKIs and ET had a non-significant mild increased risk of arterial thromboembolic event compared to ET plus placebo arm [OR 1.22 (95% CI 0.47, 3.18 I² = 0%)].

CONCLUSIONS: CDKIs in combination with endocrine therapy are associated with a two to threefold higher risk of VTE in comparison to endocrine therapy alone in women with advanced breast cancer, while the risk of arterial events is still to be defined.

PMID:34814055 | DOI:10.1016/j.thromres.2021.11.009

Clin Biomech (Bristol, Avon). 2021 Nov 5;91:105516. doi: 10.1016/j.clinbiomech.2021.105516. Online ahead of print.

ABSTRACT

BACKGROUND: Cement augmentation has been suggested to increase the stability of screw anchoring in osteoporotic humeral fractures. Initial results are promising but may be jeopardized by cement leakage into the joint and difficult implant removal. Absorbable cement might have advantages in this regard, but it is unclear if the primary stability of both techniques is equivalent to each other. Therefore, this study aimed to compare its primary stability with that of non-absorbable cement augmentation.

METHODS: Nineteen cadaveric humeri with two-part fracture models were treated with locking plate osteosynthesis and cement augmentation using either absorbable calcium phosphate cement (group 1) or polymethylmethacrylate (group 2). Fracture movement, stiffness, failure mode, and ultimate load under cyclic compressive loading were examined and compared between the groups.

FINDINGS: The absolute and relative stiffness values in group 1 were significantly smaller than those in group 2 after 50 cycles (group 1: 114 ± 38 N/mm and 94 ± 8% vs. group 2: 188 ± 71 N/mm and 106 ± 9%; p₅₀ = 0.022), 2000 cycles (group 1: 97 ± 34 N/mm and 81 ± 15% vs. group 2: 153 ± 47 N/mm and 88 ± 15%; p₂₀₀₀ = 0.028), and 5000 cycles (group 1: 98 ± 40 N/mm and 81 ± 22% vs. group 2: 158 ± 40 N/mm and 92 ± 16%; p₅₀₀₀ = 0.028). The failure load was not statistically significantly different between the groups.

INTERPRETATION: Although the PMAA group showed higher values for absolute and relative stiffness, no statistically significant difference was found in the primary stability between absorbable and non-absorbable cement augmentation supporting plate osteosynthesis in proximal humeral fractures. In view of the potential advantages of bio-absorbable cement during the healing process, its use should be considered for the augmentation and stabilization of osteoporotic fractures.

PMID:34814041 | DOI:10.1016/j.clinbiomech.2021.105516

Clin Neurophysiol. 2021 Nov 15;133:83-93. doi: 10.1016/j.clinph.2021.10.011. Online ahead of print.

ABSTRACT

OBJECTIVE: In epilepsy patients, Transcranial Magnetic Stimulation (TMS) may result in the induction and modulation of epileptiform discharges (EDs). We hereby investigate the modulatory effects of TMS on brain connectivity in Genetic Generalized Epilepsy (GGE) and explore their potential as a diagnostic biomarker in GGE.

METHODS: Patients with GGE (n=18) and healthy controls (n=11) were investigated with a paired-pulse TMS-EEG protocol. The brain network was studied at local and at global levels using Coherence as an EEG connectivity measure. Comparison of patients vs controls was performed in a time-resolved manner by analyzing comparatively pre- vs post-TMS brain networks.

RESULTS: There was statistically significant TMS-induced modulation of connectivity at specific frequency bands within groups and difference in TMS-induced modulation between the two groups. The most significant difference between patients and controls related to connectivity modulation in the γ band at 1-3 sec post-TMS (p=0.004).

CONCLUSIONS: TMS modulates the healthy and epileptic brain connectivity in different ways. Our results indicate that TMS-EEG connectivity analysis can be a basis for a diagnostic biomarker of GGE.

SIGNIFICANCE: The analysis identifies specific time periods and frequency bands of interest of TMS-induced connectivity modulation and elucidates the effect of TMS on the healthy and epileptic brain connectivity.

PMID:34814019 | DOI:10.1016/j.clinph.2021.10.011

J Stroke Cerebrovasc Dis. 2021 Nov 20;31(1):106212. doi: 10.1016/j.jstrokecerebrovasdis.2021.106212. Online ahead of print.

ABSTRACT

OBJECTIVES: Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r² > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.

MATERIALS AND METHODS: Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.

RESULTS: We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.

CONCLUSIONS: Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.

PMID:34814004 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106212

Behav Res Ther. 2021 Nov 17;148:103999. doi: 10.1016/j.brat.2021.103999. Online ahead of print.

ABSTRACT

OBJECTIVES: Social anxiety disorder (SAD) and alcohol use disorder (AUD) are highly comorbid and this comorbidity is associated with poorer clinical outcomes. Integrating exposure-based treatment for SAD into the context of typical AUD treatment programs should improve engagement and treatment outcomes for this population.

METHODS: After initial development of a fully integrated, intensive outpatient program (IOP) for individuals with comorbid SAD and AUD, patients with SAD and AUD were recruited from a community-based SUD specialty clinic (N = 56) and randomized to either (a) usual care (UC), consisting of the evidence-based Matrix Model of Addiction IOP; or (b) the Fully Integrated Treatment (FIT) for comorbid SAD and AUD IOP. Participants were assessed on indices of social anxiety and alcohol use.

RESULTS: By the 6-month follow-up, those in FIT showed superior improvement to UC on number of drinking days in the past 30 days and social anxiety severity at follow-up, but there were no differences between groups on quantity of alcohol consumed on drinking days. Alcohol-related problems improved in both groups, with no statistically significant differences. Within-group improvement was observed in FIT (but not in UC) on drinking to cope with social anxiety and avoidance of social situations without alcohol, but between-group effects were non-significant. In sum, the integrated treatment of SAD and AUD led to greater reductions in both the frequency of drinking and in social anxiety symptoms than usual care.

CONCLUSIONS: Targeting social anxiety in the context of AUD treatment is a promising approach to improving the treatment of this common comorbidity.

PMID:34813986 | DOI:10.1016/j.brat.2021.103999

Comput Methods Programs Biomed. 2021 Nov 12;213:106526. doi: 10.1016/j.cmpb.2021.106526. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Temporomandibular disorders (TMD) represent a group of diseases occurred in the temporomandibular joint (TMJ) and its surrounding tissues. In epidemiological studies, up to 75% of adults have shown at least one sign of temporomandibular disorders during their examinations. The incongruous biomechanical environment in the TMJ is the main pathogenic factor of TMD. This study attempts to determine the mechanical differences in different groups of TMD patients through biomechanics and to explain the mechanical pathogenesis of TMD according to various cases.

METHODS: Eleven control subjects and eleven TMD patients were selected and divided into three groups: the control group, bilateral TMD group, and unilateral TMD group. The contact stresses of the articular discs, condyles and temporal bones were analyzed using finite element method and statistical analysis of variance.

RESULTS: The results indicated that the contact stresses in the joints with TMD were significantly greater in the Bi-Group (Bilateral TMD patients) compared to the Control-Group. The TMD side always exhibited greater stresses in the Uni-Group [Unilateral TMD patients) under various conditions (clenching on the TMD side or asymptomatic side). The greatest stress of all the groups occurred at the contralateral side with TMD when clenching on the asymptomatic side.

CONCLUSIONS: Excessive protection would lead to greater stress on the affected side and increased TMD risk on the asymptomatic side. Clinically, the abnormal stress distributions of the disc represented poor buffering and articular clicking. The asymmetric distributions of the articular fossa manifested the deviation of mouth opening or inconsistent TMJ loading.

PMID:34813983 | DOI:10.1016/j.cmpb.2021.106526

Neuroimage. 2021 Nov 20:118729. doi: 10.1016/j.neuroimage.2021.118729. Online ahead of print.

ABSTRACT

The course of attention deficit hyperactivity disorder (ADHD) from adolescence into adulthood shows large variations between individuals; nonetheless determinants of interindividual differences in the course are not well understood. A frequent problem in ADHD, associated with worse outcomes, is emotion dysregulation. We investigated whether emotion dysregulation and integration of emotion-related functional brain networks affect interindividual differences in ADHD severity change. ADHD severity and resting state neuroimaging data were measured in ADHD and unaffected individuals at two points during adolescence and young adulthood. Bivariate latent change score models were applied to investigate whether emotion dysregulation and network integration affect ADHD severity changes. Emotion dysregulation was gauged from questionnaire subscales for conduct problems, emotional problems and emotional lability. Better emotion regulation was associated with a better course of ADHD (104 participants, 44 females, age range: 12-27). Using graph analysis, we determined network integration of emotion-related functional brain networks. Network integration was measured by nodal efficiency, i.e., the average inverse path distance from one node to all other nodes. A pattern of low nodal efficiency of cortical regions associated with emotion processing and high nodal efficiency in subcortical areas and cortical areas involved in implicit emotion regulation predicted a better ADHD course. Larger nodal efficiency of the right orbitofrontal cortex was related to a better course of ADHD (99 participants, 42 females, age range: 10-29). We demonstrated that neural and behavioral covariates associated with emotion regulation affect the course of ADHD severity throughout adolescence and early adulthood beyond baseline effects of ADHD severity.

PMID:34813971 | DOI:10.1016/j.neuroimage.2021.118729

J Stomatol Oral Maxillofac Surg. 2021 Nov 20:S2468-7855(21)00263-9. doi: 10.1016/j.jormas.2021.11.004. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate, by means of cone beam computed tomography (CBCT), the volume change of maxillary sinuses in patients that underwent orthodontic maxillary posterior en masse intrusion anchored with miniplates.

MATERIALS AND METHODS: The sample consisted of pretreatment (T1) and posttreatment (T2) CBCT scans obtained from 14 patients (4 male and 10 female), with a mean age of 32.4 years, that underwent orthodontic maxillary posterior en masse intrusion anchored with miniplates in the zygomatic crest. The mean treatment duration was 20 months and the mean intrusion movement was 2.4 mm. Maxillary sinus volume was measured by means of the software ITK SNAP (version 3.8.0) in T1 and T2 CBCT scans. The changes in sinuses volume were calculated by T1-T2 values. Data were analyzed statistically with Wilcoxon test at 5% of level of significance and the method error was analyzed with Wilcoxon test, intraclass correlation and Dahlberg’s formula.

RESULTS: The mean difference (T1-T2) was -242.85 mm³ (p = 0.396) for the right sinus and -32.5 mm³ (p = 0.875) for the left sinus. A slight increase in the volume of the sinuses was shown although these results were not statistically significant.

CONCLUSION: The orthodontic maxillary posterior en masse intrusion anchored with miniplates did not influence significantly the maxillary sinus volume.

PMID:34813966 | DOI:10.1016/j.jormas.2021.11.004

Spine J. 2021 Nov 20:S1529-9430(21)01028-7. doi: 10.1016/j.spinee.2021.11.007. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Prolonged bedrest induces accumulation of intramuscular lipid concentration (ILC) in the lumbar musculature; however, spatial distribution of ILC has not been determined. Artificial gravity (AG) mitigates some adaptations induced by 60-day bedrest by creating a head-to-feet force while participants are in a supine position.

PURPOSE: To quantify the spatial distribution of accumulation of ILC in the lumbar musculature after 60-day bedrest, and whether this can be mitigated by AG exposure.

STUDY DESIGN: Prospective longitudinal study.

PATIENT SAMPLE: Twenty-four healthy individuals (8 females) participated in the study: Eight received 30 min continuous AG (cAG); Eight received 6 × 5min AG (iAG), interspersed with rests; Eight were not exposed to AG (CRTL).

OUTCOME MEASURES: From 3T magnetic resonance imaging (MRI), axial images were selected to assess lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 intervertebral disc levels. Chemical shift-based 2-echo lipid/water Dixon sequence was used to measure tissue composition. Each lumbar muscle was segmented into four equal quartiles (from medial to lateral).

METHODS: Participants arrived at the facility for the baseline data collection before undergoing a 60-day strict 6° head-down tilt (HDT) bedrest period. MRI of the lumbopelvic region was conducted at baseline and Day-59 of bedrest. Participants performed all activities, including hygiene, in 6° HDT and were discouraged from moving excessively or unnecessarily.

RESULTS: At the L4/L5 and L5/S1 intervertebral disc levels, 60-day bedrest induced a greater increase in ILC in medial and lateral regions (∼+4%) of the LM than central regions (∼+2%; P<0.05). A smaller increase in ILC was induced in the lateral region of LES (∼+1%) at L1/L2 and L2/L3 than at the centro-medial region (∼+2%; P<0.05). There was no difference between CRTL and intervention groups.

CONCLUSIONS: Inhomogeneous spatial distribution of accumulation of ILC was found in the lumbar musculature after 60-day bedrest. These findings might reflect pathophysiological mechanisms related to muscle disuse and contribute to localized lumbar spine dysfunction. Altered spatial distribution of ILC may impair lumbar spine function after prolonged body unloading, which could increase injury risk to vulnerable soft tissues, such as the lumbar intervertebral discs. These novel results may represent a new biomarker of lumbar deconditioning for astronauts, bedridden, sedentary individuals, or those with chronic back pain. Changes are potentially modifiable but not by the AG protocols tested here.

PMID:34813960 | DOI:10.1016/j.spinee.2021.11.007