Nevin Manimala

Brain. 2022 Nov 29:awac439. doi: 10.1093/brain/awac439. Online ahead of print.

ABSTRACT

There is a lack of imaging markers revealing the functional characteristics of different brain regions in paediatric dystonia. In this observational study, we assessed the utility of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in understanding dystonia pathophysiology by revealing specific resting awake brain glucose metabolism patterns in different childhood dystonia subgroups. PET scans from 267 children with dystonia being evaluated for possible Deep Brain Stimulation (DBS) surgery between September 2007 and February 2018 at Evelina London Children’s Hospital (ELCH) United Kingdom were examined. Scans without gross anatomical abnormality (e.g. large cysts, significant ventriculomegaly; n = 240) were analysed with Statistical Parametric Mapping (SPM12). Glucose metabolism patterns were examined in the 144/240 (60%) cases with the ten commonest childhood-onset dystonias, focusing on nine anatomical regions. A group of thirty-nine adult controls was used for comparisons. The genetic dystonias were associated with the following genes: TOR1A, THAP1, SGCE, KMT2B, HPRT1 (Lesch Nyhan disease), PANK2 and GCDH (Glutaric Aciduria type 1). The acquired Cerebral Palsy (CP) cases were divided into those related to prematurity (CP-Preterm), neonatal jaundice/kernicterus (CP-Kernicterus) and hypoxic-ischaemic encephalopathy (CP-Term). Each dystonia subgroup had distinct patterns of altered FDG-PET uptake. Focal glucose hypometabolism of the pallidi, putamina, or both, was the commonest finding, except in PANK2, where basal ganglia metabolism appeared normal. HPRT1 uniquely showed glucose hypometabolism across all nine cerebral regions. Temporal lobe glucose hypometabolism was found in KMT2B, HPRT1 and CP-Kernicterus. Frontal lobe hypometabolism was found in SGCE, HPRT1, and PANK2. Thalamic and brainstem hypometabolism were seen only in HPRT1, CP-Preterm and CP-term dystonia cases. The combination of frontal and parietal lobe hypermetabolism was uniquely found in CP-term cases. PANK2 cases showed a distinct combination of parietal hypermetabolism with cerebellar hypometabolism but intact putaminal-pallidal glucose metabolism. HPRT1, PANK2, CP-kernicterus and CP-preterm cases had cerebellar and insula glucose hypometabolism as well as parietal glucose hypermetabolism. The study findings offer insights into the pathophysiology of dystonia and support the network theory for dystonia pathogenesis. “Signature” patterns for each dystonia subgroup could be a useful biomarker to guide differential diagnosis and inform personalised management strategies.

PMID:36445406 | DOI:10.1093/brain/awac439

Disabil Rehabil. 2022 Nov 29:1-4. doi: 10.1080/09638288.2022.2133174. Online ahead of print.

ABSTRACT

In the USA, low back pain related illness accounts for approximately 149 million workdays lost each year. Initial management of back pain typically involves allied healthcare professionals who implement various treatments, such as chiropractic manipulation, physiotherapy, and acupuncture which have varying outcomes and levels of supporting evidence. Another passive treatment for back pain is inversion table therapy (ITT). It is a form of spinal traction which is thought to have a role in relieving low back pain due to the gravity-facilitated traction of the spine which distracts the lumbar vertebrae. However, ITT is not without risk. According to the Food and Drug Administration (FDA) Medical Device Reporting Events Database, ITT has resulted in serious injuries including spinal cord injury, fractures, lacerations, and death. The FDA has regulated ITT for only manufacturers that indicated medical use; however, most manufacturers have not made such medical claims and were exempt from FDA regulation. This article discusses the risks of ITT, the current regulatory process for ITT, and the need for a better understanding of the role of ITT in the treatment of spinal pain while optimizing consumer safety.Implications for rehabilitationInversion table therapy (ITT) is a form of spinal traction which is thought to have a role in relieving low back pain due to the gravity-facilitated traction of the spine which distracts the lumbar vertebrae.According to the Food and Drug Administration (FDA) statistics, injuries due to non-powered traction from various medical devices have been rising since 2011.The FDA has regulated ITT for only manufacturers that indicated medical use; however, most manufacturers have not made such medical claims and were exempt from FDA regulation.This article discusses the risks of ITT, the current regulatory process for ITT, and the need for a better understanding of the role of ITT in the treatment of spinal pain while optimizing consumer safety.

PMID:36444821 | DOI:10.1080/09638288.2022.2133174

Epidemics. 2022 Nov 17;41:100654. doi: 10.1016/j.epidem.2022.100654. Online ahead of print.

ABSTRACT

During the summers of 2020 and 2021, the number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Switzerland remained at relatively low levels, but grew steadily over time. It remains unclear to what extent epidemic growth during these periods was a result of the relaxation of local control measures or increased traveling and subsequent importation of cases. A better understanding of the role of cross-border-associated cases (imports) on the local epidemic dynamics will help to inform future surveillance strategies. We analyzed routine surveillance data of confirmed cases of SARS-CoV-2 in Switzerland from 1 June to 30 September 2020 and 2021. We used a stochastic branching process model that accounts for superspreading of SARS-CoV-2 to simulate epidemic trajectories in absence and in presence of imports during summer 2020 and 2021. The Swiss Federal Office of Public Health reported 22,919 and 145,840 confirmed cases of SARS-CoV-2 from 1 June to 30 September 2020 and 2021, respectively. Among cases with known place of exposure, 27% (3,276 of 12,088) and 25% (1,110 of 4,368) reported an exposure abroad in 2020 and 2021, respectively. Without considering the impact of imported cases, the steady growth of confirmed cases during summer periods would be consistent with a value of R_e that is significantly above the critical threshold of 1. In contrast, we estimated R_e at 0.84 (95% credible interval, CrI: 0.78-0.90) in 2020 and 0.82 (95% CrI: 0.74-0.90) in 2021 when imported cases were taken into account, indicating that the local R_e was below the critical threshold of 1 during summer. In Switzerland, cross-border-associated SARS-CoV-2 cases had a considerable impact on the local transmission dynamics and can explain the steady growth of the epidemic during the summers of 2020 and 2021.

PMID:36444785 | DOI:10.1016/j.epidem.2022.100654

Stat Med. 2022 Nov 29. doi: 10.1002/sim.9618. Online ahead of print.

ABSTRACT

Study of prognostic and predictive biomarkers plays an important role in the design and analysis of clinical trials. The Cox proportional hazards model is often used to study the biomarker main effect and the treatment-biomarker interaction effect for survival data. The estimated effects can be biased if the proportional hazards assumption is violated. The restricted mean survival time is becoming popular in clinical studies for having a clear intuitive interpretation. In this article, we first propose nonparametric methods to make statistical inference for the one-sample problem of the biomarker effect on the restricted mean survival time; we then extend the methods to the two-sample problem for studying the difference in the biomarker effects between treatment groups in clinical trials. For a given biomarker, the restricted mean survival time is estimated by kernel smoothing methods with the inverse probability of censoring weights. We prove the consistency for the estimates and develop simultaneous confidence bands for the biomarker effects on the restricted mean survival time. The simultaneous confidence bands are evaluated in extensive simulation studies and are found to have good finite sample performance. We then apply the proposed methods to a breast cancer study conducted by the Breast International Group (BIG) to illustrate how the Ki67 biomarker, a protein marker of cell proliferation, affects the survival time of patients, compared between the treatment groups.

PMID:36444774 | DOI:10.1002/sim.9618

Global Spine J. 2022 Nov 29:21925682221143991. doi: 10.1177/21925682221143991. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective.

OBJECTIVE: To compare the rate of positive pathology on thoracic MRI ordered by surgical spine specialists to those ordered by nonsurgical spine specialists.

METHODS: Outpatient thoracic MRIs from January-March 2019 were evaluated from a single academic health care system. Studies without a known ordering provider, imaging report, or patients with known presence of malignancy, multiple sclerosis, recent trauma, or surgery were excluded (n = 320). Imaging studies were categorized by type of provider placing the order (resident, attending, or advanced practice practitioner) and department. MRIs were deemed positive if they showed relevant pathology that correlated with indication for exam as determined by a radiologist. One-sided chi-squared analysis was performed to determine statistical significance.

RESULTS: Overall, our data demonstrated 17.2% of studies with positive pathology. Compared to nonspecialty clinicians, subspecialists showed 35/184 (19.0%) positivity rate versus the non-specialist with 20/136 (14.7%) positivity rate (P = .156). Posthoc analysis demonstrated that surgical specialists who order thoracic MRIs yield significantly higher positivity rates at 19/79 (24.0%) compared to nonsurgical specialists at 36/241 (14.9%) (P < .05). Overall, neurosurgery demonstrated the highest rate of positive thoracic MRIs at 14/40 (35.0%). Comparison between the rate of positivity between physicians and advanced practitioners was insignificant (P > .05).

CONCLUSIONS: Clinical diagnosis of symptomatic thoracic spine degenerative disease requires an expert physical exam combined with careful attention to radiology findings. Although the percent of relevant pathology on thoracic MRI is low, our data suggests evaluation by a surgical specialist should precede ordering a thoracic spine MRI.

PMID:36444762 | DOI:10.1177/21925682221143991

J Magn Reson Imaging. 2022 Nov 29. doi: 10.1002/jmri.28546. Online ahead of print.

ABSTRACT

BACKGROUND: Reactive stroma is recognized as one of the independent prognostic factors in prostate cancer (PCa). Intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) may be useful for assessing the reactive stromal grade (RSG).

PURPOSE: To investigate whether IVIM and DKI models can evaluate RSG in PCa patients.

STUDY TYPE: Retrospective.

SUBJECTS: A total of 56 PCa patients aged 73 years on average confirmed by MRI and transrectal ultrasound (MRI/TRUS) fusion biopsy divided into two subgroups (18 high RSG and 38 low RSG).

FIELD STRENGTH/SEQUENCE: A 3 T/T₁ WI-fs, T₁ WI, T₂ WI-fs, T₂ WI, DWI, IVIM, and DKI.

ASSESSMENT: Apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK) were obtained. Patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups on hematoxylin and eosin (H&E) stained sections.

STATISTICAL TESTS: Spearman correlation and independent sample t-test or Wilcoxon’s rank sum test was used to investigate the relationship between each imaging parameter and RSG. The combined parameters were calculated using a binary logistic regression model. Receiver operating characteristic (ROC) analysis was used to explore the value of individual and combined parameters to differentiate between high and low RSG group. Area under the ROC curves (AUC) > 0.7 were used as reference standards.

RESULTS: ADC, D, f, and MD values showed positive correlation with RSG (r = 0.489, 0.619, 0.318, and 0.544, respectively); MK showed negative correlation with RSG (r = -0.444). ADC, D, f, and MD values were significantly lower in the low RSG group than in the high RSG group. The combined model showed the best diagnostic ability to differentiate low and high RSG groups (AUC = 0.887).

DATA CONCLUSION: Parameters of IVIM and DKI may be promising methods for assessment of RSG in PCa patients.

EVIDENCE LEVEL: 3.

TECHNICAL EFFICACY: Stage 3.

PMID:36444747 | DOI:10.1002/jmri.28546

Clin Oral Implants Res. 2022 Nov 29. doi: 10.1111/clr.14022. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the fracture strength and potential phase transformation of an injection-molded two-piece zirconia implant restored with a zirconia abutment after loading and/or aging.

METHODS: Thirty-two two-piece zirconia implants (4.0 mm diameter) restored with zirconia abutments were embedded according to ISO 14801 and divided into four groups (n=8/group): Three groups were either exclusively hydrothermally treated (group HT; 85°C), dynamically loaded (group DL; 10⁷ cycles; 98 N) or subjected to both treatments simultaneously (group DL/HT). One group remained untreated (group 0). A sample from each group was cross-sectioned and examined by scanning electron microscopy for possible crystal phase transformation. The remaining samples were then loaded to fracture in a static loading test. A one-way ANOVA was used for statistical analyses.

RESULTS: During dynamic loading, three implants of group DL and six implants of group DL/HT fractured at a load of 98 N. The fracture strength of group DL/HT (108±141 Ncm) was significantly reduced compared to the other groups (group 0: 342±36 Ncm; HT: 363±49 Ncm; DL: 264±198 Ncm) (p<0.05). Fractures from group 0 and HT occurred at both implant and abutment level, whereas implants from group DL and DL/HT fractured only at implant level. A shallow monoclinic transformation zone of approximately 2 μm was observed following hydrothermal treatment.

CONCLUSIONS: Within the limitations of this study, it can be concluded that dynamic loading and the combination of loading and aging reduced the fracture strength of the implant abutment combination. Hydrothermal treatment caused a shallow transformation zone which had no influence on the fracture strength.

PMID:36444693 | DOI:10.1111/clr.14022

Immun Inflamm Dis. 2022 Dec;10(12):e747. doi: 10.1002/iid3.747.

ABSTRACT

BACKGROUND: There have been many reports on biomarkers for predicting the severity of acute pancreatitis (AP), but few studies on biomarkers for predicting complications; some simple and inexpensive indicators, in particular, are worth exploring.

METHODS: We retrospectively collected clinical data of 809 AP patients, including medical history and results of routine blood tests, and grouped them according to the occurrence of complications. Differences in clinical characteristics between groups with and without complications were compared using t-test or χ² test. Receiver operating curve (ROC) and area under the curve were calculated to evaluate the ability of predicting the occurrence of complications for the routine blood parameters with statistical differences. Then, through univariate and multivariate analyses, independent risk factors closely associated with complications were identified. Finally, we built a three-parameter prediction system and evaluated its ability to predict AP complications.

RESULTS: Compared with the group without complications, the patients in the complication group had higher white blood cells, neutrophils, C-reactive protein, and erythrocyte sedimentation rate (ESR), and lower red blood cells and hemoglobin (Hb) (all p < .05), and most of them had severe pancreatitis. In addition, pseudocysts were more common in patients with alcoholic etiology, recurrence, low BMI, and high platelet (PLT) and plateletocrit. Acute respiratory failure was more common in patients with first onset and high mean PLT volume (MPV). Sepsis was more common in patients with lipogenic etiology, high MPV, and low lymphocytes. Infectious pancreatic necrosis was more common in patients with alcoholic etiology. Acute renal failure was more common in patients with monocytes and high MPV and low PLT. Multivariate analysis showed that PLT and ESR were risk factors for pseudocyst development. The ROC showed that the combination of Hb, PLT and ESR had a significantly higher predictive ability for pseudocyst than the single parameter.

CONCLUSION: Routine blood parameters can be used to predict the complications of AP. A predictive model combining ESR, PLT, and Hb may be an effective tool for identifying pseudocysts in AP patients.

PMID:36444624 | DOI:10.1002/iid3.747

Immun Inflamm Dis. 2022 Dec;10(12):e737. doi: 10.1002/iid3.737.

ABSTRACT

INTRODUCTION: It is important to control both inflammation and immunosuppression after severe insults, such as sepsis, trauma, and surgery. Endotoxin tolerance is one of the immunosuppressive conditions and it has been known that endotoxin tolerance relates to poorer clinical outcomes in patients with severe insults. This study investigated whether whey protein hydrolysate (WPH) mitigates inflammation and endotoxin tolerance in THP-1 human monocytic leukemia cells.

METHODS: Endotoxin tolerance can be experimentally reproduced by two consecutive stimulations with lipopolysaccharide (LPS). THP-1 cells were incubated with LPS and WPH (first stimulation). After collecting the culture supernatant to evaluate the effect on inflammation, the cells were washed and restimulated by 100 ng/ml LPS (second stimulation). The culture supernatant was again collected to evaluate the effect on endotoxin tolerance. Concentrations of LPS and WPH in the first stimulation were adjusted to evaluate their dose dependency. Cytokine levels in the supernatant were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed using the student’s t-test or Dunnett’s test.

RESULTS: Five mg/ml WPH significantly decreased interleukin (IL)-6 (p = .006) and IL-10 (p < .001) levels after the first LPS stimulation (1000 ng/ml). WPH significantly increased tumor necrosis factor-alpha (p < .001) and IL-10 (p = .014) levels after the second LPS stimulation. The suppressive effect of WPH on inflammation and endotoxin tolerance was dependent on the concentrations of LPS and WPH. The effective dose of WPH for endotoxin tolerance was lower than its effective dose for inflammation.

CONCLUSION: WPH mitigated both inflammation and endotoxin tolerance. Therefore, WPH might be a candidate for valuable food ingredients to control both inflammation and immunosuppression after severe insults.

PMID:36444621 | DOI:10.1002/iid3.737

Asian Pac J Cancer Prev. 2022 Nov 1;23(11):3947-3952. doi: 10.31557/APJCP.2022.23.11.3947.

ABSTRACT

BACKGROUND AND OBJECTIVE: High LIMCH1 expression in lung and renal cancer is determined as a favorable prognostic factor. However, prognostic value of LIMCH1 expression in breast cancer has not been studied yet. Therefore, this study was performed to determine the prognostic value of LIMCH1 expression in breast cancer patients.

METHODS: This retrospective study included 89 patients with invasive breast carcinoma of no special type. These patients referred to Cancer Research Institute of Tomsk National Research Medical Center from 2007 to 2018. LIMCH1 protein expression in tumor cells was detected by immunohistochemical analysis in this study. Statistical analysis was done to investigate the possible relationship between LIMCH1 protein expression and clinicopathological parameters, risk of metastasis, distant metastasis free survival, and overall survival.

RESULTS: IHC analysis of breast cancer tissue samples revealed that LIMHC1 protein expression was found in 29.2% (26/89) of the cases. Lymph node and distant metastases were more frequent in patients with LIMCH1 protein expression. LIMCH1 protein expression increased the risk of distant metastasis based on our findings. LIMCH1 protein affected metastatic-free survival regardless of the T, as well as other clinical and pathological parameters (p=0.0146, HR=3.2058 (1.26; 8.17)). Moreover, LIMCH1 protein expression was associated with worse overall survival (p=0.0071, HR=2.73 (1.28; 5.85)) in our breast cancer patients.

CONCLUSION: LIMCH1 protein expression was associate with metastases development, providing prognostic stratification. In breast cancer, LIMCH1 protein expression was found as an unfavorable prognostic factor of distant metastasis-free survival based on our findings.

PMID:36444609 | DOI:10.31557/APJCP.2022.23.11.3947