Nevin Manimala

Cancer Biomark. 2022 Sep 9. doi: 10.3233/CBM-210539. Online ahead of print.

ABSTRACT

BACKGROUND: CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer.

OBJECTIVES: To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics.

METHODS: One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020.

RESULTS: There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, Cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012).

CONCLUSIONS: Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.

PMID:36120770 | DOI:10.3233/CBM-210539

J Back Musculoskelet Rehabil. 2022 Sep 9. doi: 10.3233/BMR-220067. Online ahead of print.

ABSTRACT

BACKGROUND: Determining the association between radiographic spinal instability assessment and lower back lumbar diseases with lower limb symptoms can contribute to evidence-based assessment and treatment in clinical practice and rehabilitation. Therefore, radiological evidence of lumbar spine instability assessment, such as sagittal translation (ST) and segmental angulation (SA), is clinically important.

OBJECTIVE: To identify factors associated with the assessment of spinal instability in discogenic low back pain and lumbar disc herniation with leg pain using ST and SA.

METHODS: We examined 116 patients with discogenic low back pain and 112 with lumbar disc herniation with leg pain at our clinic from August 2016 to May 2021. Data on age, gender, sports activities, and occupation were collected from medical records. Additionally, ST and SA of L4 and L5 during maximum trunk flexion and extension were measured using radiography. Simple and multiple logistic regression analyses were used for statistical analysis.

RESULTS: Simple logistic regression analysis showed that ST and SA (odds ratio [OR]: 1.11; 95% confidence interval [CI]: 1.03-1.19) were associated with lumbar disc herniation. Multiple logistic regression analysis showed that only ST was associated with lumbar disc herniation (OR: 2.29; 95% CI: 1.78-3.00).

CONCLUSION: Multiple logistic regression analysis showed that ST was associated with lumbar disc herniation with leg pain and had a stronger association than SA.

PMID:36120768 | DOI:10.3233/BMR-220067

J Back Musculoskelet Rehabil. 2022 Sep 9. doi: 10.3233/BMR-220061. Online ahead of print.

ABSTRACT

BACKGROUND: Lateral elbow tendinopathy (LET) is one of the most common lesions of the upper extremity. The level of evidence from studies on LET treatment protocols is insufficient.

OBJECTIVE: The aim of this study was to compare the acute effects of mobilization with movement (MWM) and muscle energy technique (MET) on pain, grip strength, and functionality in patients diagnosed with LET.

METHODS: Forty-five patients with LET aged 30-55 years were enrolled in this study. Patients were divided into three groups: MWM, MET, and control group. The control group received a 4-week home exercise program. In addition to the home exercise program in the MWM group, 12 sessions of MWM and 12 sessions of MET were performed in the MET group. Participants’ pain, grip strength, and functionality were assessed before and after the study.

RESULTS: After the treatment period, greater improvement in pain, grip strength, finger strength, and functionality were observed in the MWM and MET groups than in the control group (p< 0.05), but no statistically significant difference was found between the MWM and MET groups (p> 0.05).

CONCLUSIONS: This study shows that MWM and MET, used in addition to home exercises, can be used to relieve pain and increase grip strength, finger strength, and functionality.

PMID:36120766 | DOI:10.3233/BMR-220061

J Am Geriatr Soc. 2022 Sep 18. doi: 10.1111/jgs.18030. Online ahead of print.

ABSTRACT

BACKGROUND: Opioids are frequently prescribed to alleviate pain in older adults, yet the relationships between prescription opioids and long-term cognitive function are unclear.

METHODS: In this analysis of the Mayo Clinic Study of Aging, a longitudinal population-based cohort study of older adults with formal neuropsychological testing and cognitive evaluations performed every 15 months, the associations between prescription opioids, global and domain-specific cognitive function, and mild cognitive impairment were evaluated through time-dependent linear mixed effects and Cox proportional hazards models.

RESULTS: Four thousand two hundred eighteen participants (51% male) were included with enrollment between 11/1/2004 and 4/1/2019 and median age of 76 (interquartile range 72, 82) years. Two thousand nine hundred seventy-seven subjects (71%) received at least 1 opioid prescription during a median follow-up of 7.5 (5.0, 10.7) years. Overall, there was an estimated 0.096 reduction in the global cognitive Z-score per year, including decreases of 0.050 in memory, 0.080 in language, 0.044 in visual-spatial cognition, and 0.112 in attention. In multivariable analyses, each receipt of an opioid prescription resulted in an additional -0.007 (95% CI -0.009, -0.005) change in global cognitive Z-score (p < 0.001), with significant effects seen in the domains of memory (-0.005, 95% CI -0.007, -0.003; p < 0.001), language (-0.002, 95% CI -0.003, 0.000; p = 0.024) and attention (-0.004, 95% CI -0.006, -0.002; p < 0.001) but not visual-spatial function (0.000, 95% CI -0.001, 0.001; p = 0.897). Opioid prescriptions were associated with incident mild cognitive impairment (MCI) in adjusted analysis (hazard ratio 1.21, 95% CI 1.04, 1.42; p = 0.014).

CONCLUSION: Prescription opioids are associated with small but statistically significant declines in long-term cognitive function in older adults, which may represent effects of opioids or other related factors.

PMID:36117241 | DOI:10.1111/jgs.18030

Stat Med. 2022 Sep 18. doi: 10.1002/sim.9580. Online ahead of print.

ABSTRACT

The primary analysis in two-arm clinical trials usually involves inference on a scalar treatment effect parameter; for example, depending on the outcome, the difference of treatment-specific means, risk difference, risk ratio, or odds ratio. Most clinical trials are monitored for the possibility of early stopping. Because ordinarily the outcome on any given subject can be ascertained only after some time lag, at the time of an interim analysis, among the subjects already enrolled, the outcome is known for only a subset and is effectively censored for those who have not been enrolled sufficiently long for it to be observed. Typically, the interim analysis is based only on the data from subjects for whom the outcome has been ascertained. A goal of an interim analysis is to stop the trial as soon as the evidence is strong enough to do so, suggesting that the analysis ideally should make the most efficient use of all available data, thus including information on censoring as well as other baseline and time-dependent covariates in a principled way. A general group sequential framework is proposed for clinical trials with a time-lagged outcome. Treatment effect estimators that take account of censoring and incorporate covariate information at an interim analysis are derived using semiparametric theory and are demonstrated to lead to stronger evidence for early stopping than standard approaches. The associated test statistics are shown to have the independent increments structure, so that standard software can be used to obtain stopping boundaries.

PMID:36117235 | DOI:10.1002/sim.9580

Eur Spine J. 2022 Sep 19. doi: 10.1007/s00586-022-07385-7. Online ahead of print.

ABSTRACT

PURPOSE: To compare the Atlas (C1) lateral mass screw placement between screw trajectories of 0° and 15° medial angulation while using the intersection between lateral mass and inferomedial edge of the posterior arch.

METHODS: Forty-eight Atlas lateral masses were prepared and divided into 2 groups: Group 1; screws inserted at 3 mm lateral to the reference point with screw trajectory of 0° angulation(N = 24) and Group 2; those inserted with screw trajectory of 15° medial angulation(N = 24). We evaluated the atlas anatomy, screw purchase and the presence of any breaches using CT scan.

RESULTS: The radiographic parameters for Groups 1 and 2 were found statistically different (p-value < 0.05): bilateral intraosseous screw lengths (17.92 ± 1.47 mm. vs. 20.71 ± 2.4 mm.), bilateral screw length (29.92 ± 1.72 mm. vs. 33.13 ± 1.78 mm.), left screw medial angulation (x°) (0.67° ± 0.78° vs.14.17° ± 3.51°), right screw medial angulation (y°) (0.83° ± 1.03° vs.14.25° ± 2.53°) and bilateral screw medial angulation (0.75° ± 0.9° vs. 14.21° ± 2.99°). Twenty-two screws (91.67%) using the 0° medial angulation and nineteen screws (79.17%) using the 15° medial angulation had no cortical violations (Grade 0). However, two screws (8.33%) with 0° medial angulation and five screws (20.83%) with 15° medial angulation had breach less than 2 mm (Grade 1). There were no screws with breach between 2 and 4 mm (Grade 2) or greater than 4 mm. (Grade 3).

CONCLUSION: A starting point of 3-mm lateral to the intersection between lateral mass and inferomedial edge of the Atlas posterior arch can be safely and effectively used to insert C1 lateral mass using both 0° and 15° medial angulation.

PMID:36117232 | DOI:10.1007/s00586-022-07385-7

Environ Sci Pollut Res Int. 2022 Sep 19. doi: 10.1007/s11356-022-23074-w. Online ahead of print.

ABSTRACT

Several observational studies have suggested that tobacco consumption is a risk factor for intracranial aneurysms (IAs). We here genetically predict the causal association between specific smoking features and biomarkers for smokers and IA risk. The Mendelian randomization (MR) analysis considered summary statistics from the largest current genome-wide association studies of smoking and IA. The inverse-variance weighted (IVW) method, weighted median method, MR-RAPS, and multiple variants Mendelian randomization (MVMR) were performed to estimate the effect of different smoking features and drinking in IA. We observed significant causal effects of smoking on the risk of both aneurysmal subarachnoid hemorrhage (aSAH) and unruptured IA (uIA). The ORs of IAs based on the IVW method were 1.890 (95% CI 1.486-2.405) of ever smoking regularly. MVMR analysis afforded odds ratios of 1.685 (95% CI 1.136-2.501). In the further subgroup analysis, a similar causal relationship was observed in aSAH. Moreover, our analyses suggested that higher blood cotinine level and cadmium increases aSAH risk, and ORs were 1.235 (95%CI 1.009-1.186) and 1.235 (95%CI 1.046-1.458), respectively. Our study suggests that ever smoking regularly is associated with the IA risk, which includes both uIA and aSAH. Besides, higher blood cadmium and cotinine level may increases IA and aSAH risk. Thus, tobacco control should be promoted as primordial prevention for IAs, and screening for patients with a smoking history is emphasized.

PMID:36117221 | DOI:10.1007/s11356-022-23074-w

Nat Commun. 2022 Sep 19;13(1):5478. doi: 10.1038/s41467-022-33172-5.

ABSTRACT

Most colorectal (CRC) tumors are dependent on EGFR/KRAS/BRAF/MAPK signaling activation. ARID1A is an epigenetic regulator mutated in approximately 5% of non-hypermutated CRC tumors. Here we show that anti-EGFR but not anti-VEGF treatment enriches for emerging ARID1A mutations in CRC patients. In addition, we find that patients with ARID1A mutations, at baseline, are associated with worse outcome when treated with cetuximab- but not bevacizumab-containing therapies; thus, this suggests that ARID1A mutations may provide both an acquired and intrinsic mechanism of resistance to anti-EGFR therapies. We find that, ARID1A and EGFR-pathway genetic alterations are mutually exclusive across lung and colorectal cancers, further supporting a functional connection between these pathways. Our results not only suggest that ARID1A could be potentially used as a predictive biomarker for cetuximab treatment decisions but also provide a rationale for exploring therapeutic MAPK inhibition in an unexpected but genetically defined segment of CRC patients.

PMID:36117191 | DOI:10.1038/s41467-022-33172-5

World J Surg Oncol. 2022 Sep 19;20(1):300. doi: 10.1186/s12957-022-02765-1.

ABSTRACT

BACKGROUND: National lead time goals have been implemented across Sweden to standardize and improve cancer patient care. However, the prognostic impact of lead times has not yet been studied in patients with colorectal cancer and peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).

AIM: To study the correlation between lead times and overall survival and operability.

METHODS: One hundred forty-eight patients with peritoneal metastases originating from colorectal cancer and scheduled for CRS + HIPEC from June 2012 to December 2019 were identified using a HIPEC register at Uppsala University Hospital. Data were collected from medical records concerning operability, overall survival, recurrence and time from diagnosis, and decision to operate to the date of surgery. Patients who had neoadjuvant therapy or no malignant cells in the resected specimens were excluded. Statistical calculations were made with the chi-squared test, Cox regression analysis, and log-rank test.

RESULTS: The median age was 66 years (27-82). Ninety-five were women and 53 were men. One hundred six underwent CRS + HIPEC, 13 CRS only, and 29 were inoperable (open-close). No difference in overall survival was seen when comparing patients with lead times ≤ 34 days and ≥ 35 days from the decision to operate at the multidisciplinary conference to the surgery but there was a higher frequency of open-close (p = 0.023) in the group with longer lead time. Factors that impacted overall survival were open-close (p < 0.001), liver metastases (p = 0.003), and peritoneal cancer index score ≥ 20 (p < 0.001).

CONCLUSION: A long lead time from multidisciplinary conference to surgery has no direct impact on overall survival but can result in more cases of inoperability. In a larger cohort, this might translate into decreased survival, and efforts should therefore be made to complete preoperative work up as soon as possible and reduce overall time span. Important factors for survival are related to patient selection and extent of disease.

PMID:36117176 | DOI:10.1186/s12957-022-02765-1

BMC Med. 2022 Sep 19;20(1):317. doi: 10.1186/s12916-022-02505-y.

ABSTRACT

BACKGROUND: Obesity is a well-established risk factor for atrial fibrillation (AF). Whether body fat depots differentially associate with AF development remains unknown.

METHODS: In the prospective population-based Rotterdam Study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and liver and epicardial fat using computed tomography (CT). A body composition score was constructed by adding tertile scores of each fat depot. Principal component analysis was conducted to identify potential body fat distribution patterns. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (HR; 95% CI) per 1-standard deviation increase in corresponding fat depots to enable comparisons.

RESULTS: Over a median follow-up of 9.6 and 8.6 years, 395 (11.4%) and 172 (8.0%) AF cases were ascertained in the DXA and the CT analyses, respectively. After adjustments for cardiovascular risk factors, absolute fat mass (HR; 95% CI 1.33; 1.05-1.68), gynoid fat mass (HR; 95% CI 1.36; 1.12-1.65), epicardial fat mass (HR; 95% CI 1.27; 1.09-1.48), and android-to-gynoid fat ratio (HR; 95% CI 0.81; 0.70-0.94) were independently associated with new-onset AF. After further adjustment for lean mass, associations between fat mass (HR; 95% CI 1.17; 1.04-1.32), gynoid fat mass (HR; 95% CI 1.21; 1.08-1.37), and android-to-gynoid fat ratio (HR; 95% CI 0.84; 0.72-0.97) remained statistically significant. Larger body fat score was associated with a higher AF risk (HR; 95% CI 1.10; 1.02-1.20). Borderline significant association was found between a subcutaneous fat predominant pattern with AF onset (HR; 95% CI 1.21; 0.98-1.49).

CONCLUSIONS: Various body fat depots were associated with new-onset AF. Total fat mass and gynoid fat mass were independently associated with AF after adjustment for body size. The inverse association between android-to-gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and AF was observed. Our results underscore the predominant role of subcutaneous fat on AF development among a middle-aged and elderly population. Associations betw2een body fat depots, fat distribution and new-onset atrial fibrillation.

ABBREVIATIONS: AF, atrial fibrillation.

PMID:36117169 | DOI:10.1186/s12916-022-02505-y