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Nevin Manimala Statistics

Atlas (C1) lateral mass screw placement using the intersection between lateral mass and inferomedial edge of the posterior arch: a cadaveric study

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

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Genetically predicted tobacco consumption and risk of intracranial aneurysm: a Mendelian randomization study

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

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Nevin Manimala Statistics

ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer

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

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Nevin Manimala Statistics

The prognostic impact of lead times in colorectal cancer patients undergoing cytoreductive surgery and HIPEC

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

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Imaging-based body fat depots and new-onset atrial fibrillation in general population: a prospective cohort study

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

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Oncological outcomes of anatomic versus non-anatomic resections for small hepatocellular carcinoma: systematic review and meta-analysis of propensity-score matched studies

World J Surg Oncol. 2022 Sep 19;20(1):299. doi: 10.1186/s12957-022-02770-4.

ABSTRACT

BACKGROUND: Primary liver cancer is the second-most commonly occurring cancer and has resulted in numerous deaths worldwide. Hepatic resection is of two main types, i.e., anatomic resection (AR) and non-anatomic resection (NAR). The oncological outcomes of hepatocellular carcinoma (HCC) patients after AR and NAR are still considered controversial. Therefore, we aimed to compare the impact of AR and NAR on the oncological outcomes of HCC patients with tumor diameters ≤ 5 cm using the propensity score matching method and research-based evidence.

METHOD: A systematic literature search was conducted. The main outcomes were disease-free survival (DFS), overall survival (OS), intrahepatic recurrence rate, and extrahepatic metastasis rate. Relative risk (RR) was calculated from forest plots and outcomes using random-effects model (REM).

RESULT: AR significantly improved DFS at 1, 3. and 5 years after surgery, compared to NAR (RR = 1.09, 95% CI = 1.04-1.15, P = 0.0003; RR = 1.16, 95% CI = 1.07-1.27, P = 0.0005; RR = 1.29, 95% CI = 1.07-1.55, P = 0.008). However, both of the difference in DFS at 7 years and OS at 1 and 3 years after AR versus that after NAR were not statistically significant. Nevertheless, the long-term OS associated with AR (5, 7, and 10 years) was superior to that associated with NAR (RR = 1.12, 95% CI = 1.03-1.21, P = 0.01; RR = 1.19, 95% CI = 1.04-1.36, P = 0.01; RR = 1.18, 95% CI = 1.05-1.34, P = 0.008). The difference in the intrahepatic recurrence rate after AR versus that after NAR was not statistically significant, but the extrahepatic metastasis rate after AR was significantly lower than that observed after NAR (RR = 0.61, 95% CI = 0.40-0.94, P = 0.03).

CONCLUSION: Therefore, AR should be the preferred surgical approach for HCC patients with tumor diameters ≤ 5 cm.

TRIAL REGISTRATION: PROSPERO registration number CRD42022330596.

PMID:36117165 | DOI:10.1186/s12957-022-02770-4

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Cavernous segment internal carotid artery stenosis specific to meningiomas compared to pituitary adenomas

J Neuroimaging. 2022 Sep 18. doi: 10.1111/jon.13051. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Pituitary macroadenomas and meningiomas are common neoplasms arising within the cavernous sinus. Imaging characteristics on MRI can often distinguish these tumors from one another; however, some cases may be more difficult to differentiate. This study compares patterns of cavernous segment internal carotid artery (CS-ICA) stenosis between the two tumor types to establish a novel radiographic method of differentiation.

METHODS: A retrospective analysis of patients with pathology-confirmed meningioma and pituitary adenomas at Tufts Medical Center was performed. The diameter of the CS-ICA at the narrowest point within the cavernous sinus was measured and compared to the ipsilateral petrous segment ICA and contralateral CS-ICA. The mean and range of percent stenosis and frequency of cases of CS-ICA stenosis >15% were determined. Statistical analysis to compare the groups was conducted using the Chi-squared test, Fisher’s exact test, and t-test.

RESULTS: There were a total of 78 out of 231 patients who were included in the study. The mean % ICA stenosis for all meningiomas was 9.3%, with increasing stenosis with increasing World Health Organization grade. Of all meningioma cases, 13 (33%) had greater than 15% ICA stenosis. Mean ICA stenosis for pituitary adenomas was -1.48%. There were no cases of pituitary adenomas causing ICA stenosis >15%.

CONCLUSIONS: Differentiating pituitary adenomas and intracavernous meningioma tumors can have important implications on surgical approach and outcome. Our study found that stenosis of the CS-ICA greater than 15% is highly specific to meningiomas and can serve as a radiologic sign to distinguish between these two tumors.

PMID:36117152 | DOI:10.1111/jon.13051

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Topical gabapentin 10% in the treatment of epidermolysis bullosa pruritus: A pilot, double-blind, split-site, randomized controlled trial

Dermatol Ther. 2022 Aug 11:e15767. doi: 10.1111/dth.15767. Online ahead of print.

ABSTRACT

Pruritus is a symptom that adversely affects the quality of life of patients with epidermolysis bullosa (EB). Although studies indicate the positive effect of gabapentin on some types of pruritus, its effect on pruritus due to EB remains unexplored. Hence, this study investigated the efficacy of topical gabapentin in treating EB pruritus. We piloted a 6-week, double-blind, split-site, randomized controlled trial on 14 patients with EB pruritus. In each patient, one pruritic lesion received topical gabapentin and the other a placebo. The items of the Leuven Itch Scale were evaluated before and after therapy; the lesions were photographed, and their appearance (i.e., erythema and excoriation severity, pruritic geometric area) was objectively assessed. Statistical analyses were made using SPSS v. 25. Quantitative data were reported as median (interquartile range) or mean ± standard deviation as appropriate. The median age of the 14 patients was 18 years (12-37), and the majority (64.3%) were male. A significant improvement was seen in the geometric area of the pruritic lesion in the intervention group (p = 0.005) but not in the control group (p = 0.054). Erythema severity, excoriation intensity, pruritus frequency and duration, and symptom-related distress significantly improved in both groups (p < 0.05 in all cases), but topical gabapentin failed to offer any statistical superiority relative to the placebo in the between-group analysis (p > 0.05). This study showed no significant difference between topical gabapentin and placebo in erythema severity, excoriation intensity, pruritus frequency and duration, and symptom-related distress among EB patients. However, the lesion area decreased only in the gabapentin group.

PMID:36117146 | DOI:10.1111/dth.15767

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Robust analysis of cancer heterogeneity for high-dimensional data

Stat Med. 2022 Sep 18. doi: 10.1002/sim.9578. Online ahead of print.

ABSTRACT

Cancer heterogeneity plays an important role in the understanding of tumor etiology, progression, and response to treatment. To accommodate heterogeneity, cancer subgroup analysis has been extensively conducted. However, most of the existing studies share the limitation that they cannot accommodate heavy-tailed or contaminated outcomes and also high dimensional covariates, both of which are not uncommon in biomedical research. In this study, we propose a robust subgroup identification approach based on M-estimators together with concave and pairwise fusion penalties, which advances from existing studies by effectively accommodating high-dimensional data containing some outliers. The penalties are applied on both latent heterogeneity factors and covariates, where the estimation is expected to achieve subgroup identification and variable selection simultaneously, with the number of subgroups being apriori unknown. We innovatively develop an algorithm based on parallel computing strategy, with a significant advantage of capable of processing large-scale data. The convergence property of the proposed algorithm, oracle property of the penalized M-estimators, and selection consistency of the proposed BIC criterion are carefully established. Simulation and analysis of TCGA breast cancer data demonstrate that the proposed approach is promising to efficiently identify underlying subgroups in high-dimensional data.

PMID:36117143 | DOI:10.1002/sim.9578

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Thoracodorsal artery perforator flap, muscle-sparing latissimus dorsi, and descending branch latissimus dorsi: A multicenter retrospective study on early complications and meta-analysis of the literature

J Plast Reconstr Aesthet Surg. 2022 Jun 29:S1748-6815(22)00407-7. doi: 10.1016/j.bjps.2022.06.083. Online ahead of print.

ABSTRACT

The thoracodorsal (TD) vessels represent a complex vascular system that offers a variety of pedicled and free flaps. Variations of the classical latissimus dorsi (LD) flap have been developed to overcome its major drawbacks. The thoracodorsal artery perforator (TDAP) flap described by Angrigiani represents one of these options. Other techniques have been defined as “muscle-sparing” latissimus dorsi (MSLD) due to the preservation of the LD muscle and the TD nerve, in whole or in part. Nevertheless, the term “muscle sparing” has also been applied to the descending branch LD (DB-LD) flap which requires the denervation of the LD muscle. According to our knowledge, there are no articles in the literature reviewing and comparing the reconstructive options based on the TD vessels. We performed a systematic search in PubMed, Web of Science, and Cochrane databases to perform a literature review and meta-analysis about the reconstructive options based on the TD vessels. The primary outcome of interest was the percentage of flaps developing a specific early complication, i.e., hematoma of the donor site, seroma of the donor site, partial flap loss, total flap loss, wound dehiscence, and wound infection. Moreover, we analyzed the outcomes and complications of our cases, comparing the MSLD flaps, the DB-LD flaps, and the TDAP flaps. According to both our casuistry and the literature, the three techniques can be considered safe in terms of early donor site complications. According to the literature, MSLD has been shown to develop partial flap necrosis more frequently than the TDAP flap.

PMID:36117135 | DOI:10.1016/j.bjps.2022.06.083