Nat Commun. 2022 Oct 26;13(1):6380. doi: 10.1038/s41467-022-34002-4.
NO ABSTRACT
PMID:36289216 | DOI:10.1038/s41467-022-34002-4
Category: Nevin Manimala
Nat Commun. 2022 Oct 26;13(1):6360. doi: 10.1038/s41467-022-33870-0.
ABSTRACT
Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies. We use primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number is associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC is statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway is independently observed in squamous lung cancer and triple negative breast cancer. In this work, we show that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.
PMID:36289203 | DOI:10.1038/s41467-022-33870-0
Blood Res. 2022 Oct 27. doi: 10.5045/br.2022.2022097. Online ahead of print.
ABSTRACT
BACKGROUND: The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation involves adding a methyl group to the carbon 5 position of cytosine. Besides comparing SOCS-1 gene methylation status between patients with multiple myeloma (MM) and healthy controls, this study also aimed to demonstrate the effect of SOCS-1 gene distribution and the effect of methylation of SOCS-1 on progression-free survival (PFS) and overall survival (OS).
MATERIALS AND METHODS: This study included 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals. The distribution of the SOCS-1 genotypes was statistically compared between MM patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined.
RESULTS: The CA/CA genotype of SOCS-1 was significantly higher in healthy controls (P=0.001), while the Del/Del genotype was significantly higher in patients with MM (P=0.034). The percent methylated reference (PMR) value of the SOCS-1 gene was significantly higher in the healthy controls (median, 43.48; range, 2.76-247.75; P=0.001). Patients with a PMR value of ≥43.48 were 3.125 times more likely to develop progression than those with a PMR value of <43.48.
CONCLUSION: The effects of SOCS-1 polymorphisms on the pathogenesis of MM and SOCS-1 methylation will further shed light on the pathophysiology of MM.
PMID:36289192 | DOI:10.5045/br.2022.2022097
Ther Innov Regul Sci. 2022 Oct 26. doi: 10.1007/s43441-022-00471-4. Online ahead of print.
ABSTRACT
The two trials paradigm plays a prominent role in drug development and has been widely and controversially discussed. Its purpose is to ensure replicability or substantiation of study results. This note investigates a simple generalization of the paradigm to more than two trials that preserves the project wise type-I error rate and power.
PMID:36289189 | DOI:10.1007/s43441-022-00471-4
Can J Anaesth. 2022 Oct 26. doi: 10.1007/s12630-022-02344-8. Online ahead of print.
ABSTRACT
PURPOSE: Awake tracheal intubation (ATI) is recommended in airway management guidelines when significant difficulty is predicted with airway management. Use of the technique may be declining, which may have implications for patient safety or for skills acquisition and maintenance. This historical cohort database study sought to determine if the use of ATI was decreasing in our adult tertiary care center.
METHODS: With institutional research ethics board approval, we queried our anesthesia information management system for cases with ATI descriptors for each year from 2014 to 2020. Records of the retrieved cases were independently reviewed by all three authors to verify they met inclusion criteria for the ATI cohort prior to analysis for the primary outcome. Secondary outcome measures included airway device and route used for ATI, first attempt and ultimate success rates, and reported adverse issues recorded in cases of failed ATI or those requiring more than one attempt.
RESULTS: A total of 692 cases of ATI were identified between 2014 and 2020. There was a statistically significant decrease in yearly ATIs over the seven-year study period (Chi square goodness of fit, P < 0.001), with ATI use decreasing by about 50%. First attempt success was significantly greater with use of flexible bronchoscopy vs video laryngoscopy to facilitate ATI (84% vs 60%; P < 0.001), while there was no difference in first attempt success with the oral vs nasal route (82% vs 82%; P = 1.0).
CONCLUSION: In this single-center historical cohort study, the use of ATI decreased significantly from 2014 to 2020. Whether this decrease will result in morbidity or mortality related to airway management is currently unclear. Regardless, it has implications for training opportunities and maintenance of competence in performing the procedure.
PMID:36289151 | DOI:10.1007/s12630-022-02344-8
Clin Exp Med. 2022 Oct 27. doi: 10.1007/s10238-022-00919-9. Online ahead of print.
ABSTRACT
The vitamin D receptor (VDR) is a nuclear transcription factor that acts as the main transducer in response to vitamin D (VD), regulating about 3% of the gene expression in the human genome. This study investigated the expression of VDR in the liver of patients with chronic hepatitis B virus (HBV) infection and determined its correlation with liver inflammation and fibrosis. We evaluated the effects of HBV infection on the expression of VDR in vivo and in vitro and further investigate the potential mechanism. Subsequently, the associations between hepatic VDR expression with liver inflammation and fibrosis were statistically analyzed. Results showed that hepatic VDR expression was significantly decreased in patients with chronic HBV infection as compared to healthy individuals. Similarly, in vitro experiments further confirmed that HBV infection could inhibit the expression of VDR in hepatocytes. Mechanistically, HBV was able to directly induce the expression of miR-125a which inhibited the mRNA and protein levels of VDR. Statistical analysis showed that hepatic VDR expression was significantly negatively correlated with liver inflammation and fibrosis in patients. We conclude that inhibition of hepatic vitamin D receptor expression by HBV/miR-125a is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection.
PMID:36289101 | DOI:10.1007/s10238-022-00919-9
Surg Endosc. 2022 Oct 26. doi: 10.1007/s00464-022-09712-x. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: Surgical cholecystectomy is the gold standard strategy for the management of acute cholecystitis (AC). However, some patients are considered unfit for surgery due to certain comorbid conditions. As such, we aimed to compare less invasive treatment strategies such as endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) and percutaneous gallbladder drainage (PT-GBD) for the management of patients with AC who are suboptimal candidates for surgical cholecystectomy.
METHODS: A comprehensive search of multiple electronic databases was performed to identify all the studies comparing EUS-GBD versus PT-GBD for patients with AC who were unfit for surgery. A subgroup analysis was also performed for comparison of the group undergoing drainage via cautery-enhanced lumen-apposing metal stents (LAMS) versus PT-GBD. The outcomes included technical and clinical success, adverse events (AEs), recurrent cholecystitis, reintervention, and hospital readmission.
RESULTS: Eleven studies including 1155 patients were included in the statistical analysis. There was no difference between PT-GBD and EUS-GBD in all the evaluated outcomes. On the subgroup analysis, the endoscopic approach with cautery-enhanced LAMS was associated with lower rates of adverse events (RD = – 0.33 (95% CI – 0.52 to – 0.14; p = 0.0006), recurrent cholecystitis (- 0.05 RD (95% CI – 0.09 to – 0.02; p = 0.02), and hospital readmission (- 0.36 RD (95% CI-0.70 to – 0.03; p = 0.03) when compared to PT-GBD. All other outcomes were similar in the subgroup analyses.
CONCLUSIONS: EUS-GBD using cautery-enhanced LAMS is superior to PT-GBD in terms of safety profile, recurrent cholecystitis, and hospital readmission rates in the management of patients with acute cholecystitis who are suboptimal candidates for cholecystectomy. However, when cautery-enhanced LAMS are not used, the outcomes of EUS-GBD and PT-GBD are similar. Thus, EUS-GBD with cautery-enhanced LAMS should be considered the preferable approach for gallbladder drainage for this challenging population.
PMID:36289089 | DOI:10.1007/s00464-022-09712-x
Environ Manage. 2022 Oct 26. doi: 10.1007/s00267-022-01731-7. Online ahead of print.
ABSTRACT
Chromium (Cr) is a potentially toxic metal occurring in the soil as a result of natural and anthropogenic activities and is mainly found in Cr3+ and Cr6+. The hexavalent chromium has toxic effects on plants, animals, humans and microorganisms depending on exposure level, duration and doses. Biochar is a stable carbon-based material that has been widely documented to immobilize metals in contaminated soils and for soil remediation effectively. The present 90 days incubation study was conducted to investigate the potential use of rice stubble and sawdust-derived modified biochars on Cr6+ remediation and their effects on nutrient availability. Among the treatments, modified rice stubble biochar (RSB-M) contained the highest surface area, pore volume and CEC. The unmodified and modified biochars significantly increased soil pH, EC, CEC, and N, K availability ((p < 0.001)). Statistical analysis showed that modified rice stubble (RSB-M) and sawdust biochars (SDB-M) significantly reduced the Cr6+ with incubation days compared to unmodified biochars, possibly due to the greater porous structure and various functional groups. The submerged incubation condition also greatly impacted Cr6+ reduction since a gradual decrease (up to ~70 mg kg-1 of Cr6+) was observed in control treatments. Therefore, applying modified biochars is imperative to alleviate Cr6+ polluted soils and improve soil fertility.
PMID:36289071 | DOI:10.1007/s00267-022-01731-7
Pain Physician. 2022 Oct;25(7):E1121-E1128.
ABSTRACT
BACKGROUND: Pulsed radiofrequency (PRF) is a percutaneous, micro-invasive, and micro-destructive neuromodulation technology. It has been reported to be useful in the treatment of supraorbital neuralgia (SN). However, the long-term effectiveness and safety of this technique in SN has not been reported yet.
OBJECTIVES: To investigate the outcomes of PRF on supraorbital neuralgia (SN) in multi-centers and a long-term perspective.
STUDY DESIGN: Retrospective case series.
METHODS: Patients who underwent PRF for SN at 4 hospitals in Beijing between Jan 2007 and Jan 2021 were identified and reviewed for inclusion. Their demographic data and baseline conditions were statistically described, and their conditions of pain control were analyzed using Kaplan-Meier survival analyses. A survival curve was plotted, the cumulative proportion of pain-free at specific time points was determined, and the median pain-free time was estimated. Complications related to PRF treatment were summarized. The risk factors for initial pain control and pain-free survival were analyzed using logistic regression and Cox regression.
RESULTS: A total of 116 patients were included; 91 (78.4%) patients got initial pain control with just one attempt of PRF. The maximum length of follow-up was 127 months, with a median of 18 months. During follow-up, 29 (31.9%) patients suffered from pain recurrence, and 11 (12.1%) were lost. The cumulative pain-free survival at 6 months, 1 year, 2 years, 3 years, 5 years, 8 years, and 10 years were estimated as 70%, 64%, 59%, 55%, 44%, 37%, and 37%, respectively. The median pain-free time was 52 months. No severe complications were observed or reported. Duration of disease could significantly influence initial pain control, while no risk factors for pain-free survival were recognized.
LIMITATIONS: A retrospective study setting without a control group.
CONCLUSION: The performance of PRF for the treatment of SN was confirmed to be favorable in a multicentric, relatively large scale, and long-term perspective.
PMID:36288599
Pain Physician. 2022 Oct;25(7):E1087-E1094.
ABSTRACT
BACKGROUND: Percutaneous cervical nucleoplasty (PCN) is a minimally invasive technique used for the treatment of cervical disc herniation. However, if the lesion is located at the neural foramen, complete access and effective neural decompression are often challenging because of the special anatomical condition of the uncovertebral joint, osteophyte, and facet joint of the cervical foraminal space.
OBJECTIVES: To investigate the effect of PCN on radiculopathy caused by foraminal cervical disc herniation (FCDH).
STUDY DESIGN: Retrospective case series.
SETTING: Single-center tertiary hospital.
METHODS: This study included 44 patients with radiculopathy caused by FCDH who were treated with PCN. Visual analog scale (VAS) scores, preoperative, 1 week, and 3 months postoperatively, and at the last follow-up, as well as the Macnab criteria, were used to evaluate clinical outcomes. A paired t-test was used to compare the preoperative and follow-up VAS scores. The percentage of patients with VAS scores <= 3 at each follow-up time point was also investigated. Statistical significance was set at P < 0.05.
RESULTS: Twenty-seven men (62.4%) and 17 women (38.6%) were enrolled in this study. The mean age was 54.5 years (range 31-81). The average follow-up period after the operation was 15.4 months (range 3.7-30.8). The mean preoperative VAS was 7.50 ± 1.21. The VAS scores at 1 week, 3 months, and the last follow-up were 4.36 ± 2.46, 3.20 ± 2.58, and 2.91 ± 2.74, respectively, showing a significant improvement in pain compared to before the operation (P < 0.001 for all). The number of patients (percentage) with a VAS score of <= 3 was 20 (45.5%), 28 (63.6%), and 31 (70.5%) of 44 patients at 1 week, 3 months, and the last follow-up, respectively. The number of patients (percentage) with excellent, good, fair, or poor satisfaction according to the Macnab criteria was 17 (38.6%), 9 (20.5%), 8 (18.2%), and 10 (22.7%) of 44, respectively. No patients experienced postoperative complications.
LIMITATIONS: This study was retrospective and included a small number of patients from a single center.
CONCLUSIONS: Although PCN for radiculopathy caused by FCDH is thought to have limitations because of the surrounding bony structure, the clinical outcome seemed favorable. If PCN is not contraindicated, it may be a viable treatment option for CR due to FCDH.
PMID:36288595