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Functional outcome of surgical management of low mid-grade lumbar spondylolisthesis when considering the sagittal balance parameters preoperatively: a prospective study

Chin Neurosurg J. 2022 Nov 25;8(1):35. doi: 10.1186/s41016-022-00303-2.

ABSTRACT

BACKGROUND: Prospective study objectives. A sagittal balance is a good tool to improve the functional outcome of spine spondylolisthesis surgeries, primarily noted that it has a good impact in deformity surgery and then applied to every spine surgery and the aim of this study is to evaluate its functional outcome when considered in preoperative planning for non-dysplastic low- and mid-grade spondylolisthesis surgeries.

METHOD: Forty patients diagnosed as low- or mid-grade non-dysplastic spondylolisthesis had undergone surgery at Cairo University after failed medical treatment had been evaluated preoperatively by measuring the sagittal balance parameters which include SVA, spinopelvic angles, lumbar lordosis, pelvic tilt, sacral slope, and pelvic incidence and then measure it along a follow-up period of 1 year postoperatively started from February 2018 and correlate it with functional outcome using Oswestry score (ODI)and VAS. Correction of parameters has been estimated preoperatively by manual estimation and Surgimap application then applied during the operation.

RESULTS: All patients were treated by surgical treatment through posterior transpedicular screw fixation with conventional or reduction screws and fusion ± TLIF cages. The mean of lumbar lordosis and mean spinopelvic angles were increased in a statistically significant manner. Pelvis tilt was decreased in a statistically insignificant manner. The mean of pelvic incidence was not changed and statistically insignificant, and this is matching the fact that pelvic incidence is a constant parameter. The sacral slope was increased in a statistically insignificant manner. Final results showed that 37 had a statistically significant improvement in their ODI >20% at the last visit. Three patients had a poor clinical outcome with ODI scorFinal results showed that 37 had a statistically significant improvement in their ODI >20% at the last visit. Three patients had a poor clinical outcome with ODI score of >20% improvement, and we noticed that the level of pathology was at the level of L4L5, SVA was positive and worsen postoperatively, and also, it is accompanied by decreased lumbar lordosis. Change in ODI means statistically significant improvement when considering sagittal parameters preoperation and during operation.

CONCLUSION: Sagittal balance parameters should be considered in the surgical management of low-grade spondylolisthesis cases to improve their functional outcome.

PMID:36434653 | DOI:10.1186/s41016-022-00303-2

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Is there a role for lung surgery in initially unresectable non-small cell lung cancer after tyrosine kinase inhibitor treatment?

World J Surg Oncol. 2022 Nov 26;20(1):370. doi: 10.1186/s12957-022-02833-6.

ABSTRACT

BACKGROUND: The role of lung surgery in initially unresectable non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) treatment remains unclear. We aimed to assess the survival benefits of patients who underwent surgery for regressed or regrown tumors after receiving TKI treatment.

METHODS: The details of patients diagnosed with unresectable NSCLC treated with TKI followed by lung resection from 2010 to 2020 were retrieved from our database. The primary endpoint was 3-year overall survival (OS), whereas the secondary endpoints were a 2-year progression-free survival (PFS), feasibility, and the safety of pulmonary resection. The statistical tests used were Fisher’s exact test, Kruskal Wallis test, Kaplan-Meier method, Cox proportional hazards model, and Firth correction.

RESULTS: Nineteen out of thirty-two patients were selected for the study. The patients underwent lung surgery after confirmed tumor regression (17 [89.5%]) and regrowth (two [10.5%]). All surgeries were performed via video-assisted thoracoscopic surgery: 14 (73.7%) lobectomies and five (26.3%) sublobar resections after a median duration of 5 months of TKI. Two (10.5%) postoperative complications and no 30-day postoperative mortality were observed. The median postoperative follow-up was 22 months. The 2-year PFS and 3-year OS rates were 43.9% and 61.5%, respectively. Patients who underwent surgery for regressed disease showed a significantly better OS than for regrowth disease (HR=0.086, 95% CI 0.008-0.957, p=0.046). TKI-adjuvant demonstrated a better PFS than non-TKI adjuvant (HR=0.146, 95% CI 0.027-0.782, p=0.025).

CONCLUSION: Lung surgery after TKI treatment is feasible and safe and prolongs survival via local control and directed consequential therapy. Lung surgery should be adopted in multimodality therapy for initially unresectable NSCLC.

PMID:36434641 | DOI:10.1186/s12957-022-02833-6

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Hyperbaric Oxygen Therapy for Veterans With Treatment-resistant PTSD: A Longitudinal Follow-up Study

Mil Med. 2022 Nov 26:usac360. doi: 10.1093/milmed/usac360. Online ahead of print.

ABSTRACT

INTRODUCTION: PTSD is common among veteran combatants. PTSD is characterized by brain changes, for which available treatments have shown limited effect. In a short-term study, we showed that hyperbaric oxygen therapy (HBOT) induced neuroplasticity and improved clinical symptoms of veterans with treatment-resistant PTSD. Here, we evaluated the long-term clinical symptoms of the participants of that study.

MATERIALS AND METHODS: Veterans from our short-term study were recruited 1 or more years after completing HBOT. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and self-reported questionnaires were administered at a single site visit. Changes in clinical scores between long-term, short-term, and pretreatment evaluations were analyzed.

RESULTS: Of the 28 participants who received HBOT during or following the short-term study, 22 agreed to participate in the current study. At a mean of 704 ± 230 days after completing the HBOT course, the mean CAPS-5 score (26.6 ± 14.4) was significantly better (lower) than at the pre-HBOT evaluation (47.5 ± 13.1, P < .001) and not statistically different from the short-term evaluation (28.6 ± 16.7, P = .745). However, for the CAPS-5 subcategory D (cognition and mood symptoms), the mean score was significantly better (lower) at long-term than at short-term evaluation (7.6 ± 5.1 vs. 10.0 ± 6.0, P < .001). At the long-term compared to the pretreatment evaluation, higher proportions of the participants were living with life partners (10 (46%) vs. 17 (77%), P = .011) and were working (9 (41%) vs. 16 (73%), P = .033). Decreases were observed between pretreatment and the long-term follow-up, in the number of benzodiazepine users (from 10 (46%) to 4 (18%), P = .07) and in the median (range) cannabis daily dose (from 40.0 g (0-50) to 22.5 g (0-30), P = .046).

CONCLUSIONS: The beneficial clinical effects of HBOT are persistent and were not attenuated at long-term follow-up of about 2 years after completion of HBOT. Additional long-term effects of the treatment were observed in social function and in decreased medication use.

PMID:36433746 | DOI:10.1093/milmed/usac360

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Toxicity determination, pollution source delineation, and microbial diversity evaluation of PAHs-contaminated sediments for an urban river

Water Environ Res. 2022 Nov 7;94(11):e10810. doi: 10.1002/wer.10810. Online ahead of print.

ABSTRACT

The Feng-Sang River is a metropolitan river in Kaohsiung City, Taiwan. In this study, Feng-Sang River sediments were analyzed to investigate the distributions and sources of polycyclic aromatic hydrocarbons (PAHs). The Sediment Quality Guidelines (SQGs), potentially carcinogenic PAHs (TEQcarc ), and toxic equivalence quotient (TEQ) were applied to evaluate influences of PAHs on ecosystems and microbial diversities. Results indicate that PAHs concentrations varied between seasons and locations. The concentrations of ∑16 PAHs ranged from 73.6 to 603.8 ng/kg in dry seasons and from 2.3 to 199.3 ng/kg in wet seasons. This could be because of the flushing effect during wet seasons, which caused the movement and dilution of the PAH-contaminated sediments. Diagnostic ratio analysis infers that high PAHs levels were generated by combustion processes and vehicle traffic, and results from multivariate descriptive statistical analysis also demonstrate that the vehicular traffic pollution could be the major emission source of PAHs contamination. Comparisons of PAHs with SQGs indicate that PAHs concentrations in sediment were below the effects range low (ERL) values, and thus, the immediate threat to organisms might not be significant. The diagnostic ratio analyses are effective methods for PAH source appointment. The metagenomic assay results imply that sediments contained essential microbial species with eminent diversity. The detected PAH-degrading bacteria (Desulfatiglans, Dechloromonas, Sphingomonas, Methylobacterium, Rhodobacter, Clostridium, and Exiguobacterium) played a key role in PAHs biotransformation, and Dechloromonas and Rhodobacter had a higher relative abundance. Results of microbial diversity analyses indicate that the contaminated environment induced the changes of governing microbial groups in sediments. PRACTITIONER POINTS: Diagnostic ratio analyses are effective methods for PAHs source appointment. Microbial composition in sediments are highly affected by anthropogenic pollution. Combustion and vehicle traffic contribute to urban river sediments pollution by PAHs. Dechloromonas and Rhodobacter are dominant PAHs-degrading bacteria in sediments.

PMID:36433735 | DOI:10.1002/wer.10810

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Effects of Different Exercises on Respiratory Parameters: A Randomized Controlled Trial

Clin Physiol Funct Imaging. 2022 Nov 26. doi: 10.1111/cpf.12804. Online ahead of print.

ABSTRACT

This study was designed to compare the effects of core stabilisation and auxiliary respiratory muscle strengthening exercises on oxygen consumption and respiratory parameters. A total of 51 participants were divided into 3 groups with block randomization method according to age and gender: Core Stabilisation (CS) Group (n = 17), Auxiliary Respiratory Muscles Exercise (ARM) Group (n = 17) and Control (C) Group (n = 17). VO2 max, first second of forced expiration (FEV1)/Forced vital capacity (FVC), and maximal voluntary ventilation (MVV) values were evaluated before and after the study. CS and ARM strengthening exercises were applied 3 days a week for 6 weeks. The increase in the FEV1/VC values was higher in the CS and ARM groups than in the C group (p<0.05), whereas no statistically significant difference was observed between the ARM and CS groups (p<0.05). There was no statistically significant difference between the groups in terms of VO2 max values before and after the study (p>0.05). The increase in the MVV values was higher in the CS and ARM groups than in the C group (p<0.05), whereas no statistically significant difference was observed between the ARM and CS groups (p>0.05). CS and ARM exercises had positive effects on FEV1/FVC and MVV. This article is protected by copyright. All rights reserved.

PMID:36433716 | DOI:10.1111/cpf.12804

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Evaluation of the United States definitions for COVID-19 community risk levels

Clin Infect Dis. 2022 Nov 26:ciac922. doi: 10.1093/cid/ciac922. Online ahead of print.

ABSTRACT

The United States CDC defines a county metric of COVID-19 Community Levels to inform public health measures. We find that the COVID-19 Community Levels vary frequently over time, which may not be optimal for decision making. Alternative metric formulations that do not compromise predictive ability are shown to reduce variability.

PMID:36433715 | DOI:10.1093/cid/ciac922

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Model-Free and Model-based Parameters Derived From CAIPIRINHA-Dixon-TWIST-VIBE DCE-MRI: Associations With Prognostic Factors and Molecular Subtypes of Invasive Ductal Breast Cancer

J Magn Reson Imaging. 2022 Nov 26. doi: 10.1002/jmri.28533. Online ahead of print.

ABSTRACT

BACKGROUND: CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) dynamic contrast-enhanced MRI (DCE-MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model-free and model-based parameters has not been investigated.

PURPOSE: To compare model-free and model-based parameters of CDTV DCE-MRI with both clinicopathologic factors and molecular subtypes of IDC.

STUDY TYPE: Prospective.

POPULATION: A total of 152 patients (mean age, 52 years) with IDC including 42 luminal A, 64 luminal B, 22 human epidermal growth factor receptor-2 (HER2) positive, and 24 triple-negative subtypes.

FIELD STRENGTH/SEQUENCE: A 3 T; turbo-FLASH, Dixon VIBE, and CDTV.

ASSESSMENT: Model-free parameters (initial enhancement rate [IER] and maximum slope [MS]) were estimated from the time-intensity curve. The mean, minimum, maximum, and range between the minimum and maximum values of inline model-based parameters (Ktrans , kep , and ve ) were measured to assess intratumoral heterogeneity of IDC lesions.

STATISTICAL TESTS: Student’s t tests, Mann-Whitney U tests, Kruskal-Wallis tests, post hoc Steel-Dwass tests, and receiver operating characteristic (ROC) curves. P < 0.05 was considered significant.

RESULTS: No significant differences in IER and MS values were seen among the clinicopathologic factors and molecular subtypes (Bonferroni-corrected P = 0.011-0.862, P = 0.145-0.601, respectively). The minimum kep values in HER2-positive IDC were significantly lower than those in HER2-negative IDC. The mean and range kep values were independent predictors for distinguishing the high (grade 3) and low (grade 1 or 2) nuclear grade groups according to multivariable analyses. The post hoc test showed that the kep minimum and kep range values were significantly different between luminal A and HER2-positive tumor subtypes, yielding an area-under-the-curve of 0.820.

DATA CONCLUSION: Compared with the model-free parameters, inline kep related model-based parameters on CDTV DCE-MRI can be applied as a feasible tool to differentiate luminal A from HER2-positive breast cancers.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

PMID:36433714 | DOI:10.1002/jmri.28533

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Basal cell carcinoma: epidemiological impact of clinical versus histopathological diagnosis

J Eur Acad Dermatol Venereol. 2022 Nov 25. doi: 10.1111/jdv.18774. Online ahead of print.

ABSTRACT

BACKGROUND: Low-risk basal cell carcinomas (BCCs) are to an increasing extent diagnosed by dermatologists through dermoscopic examination only and treated with non-surgical methods. Reports on increasing incidence as well as trends regarding subtypes, anatomical sites and differences related to gender are based solely on histopathologically verified tumours. How unreported clinically diagnosed BCCs affect the epidemiological data has not been sufficiently investigated.

OBJECTIVES: To analyze tumour and patient characteristics of clinically diagnosed versus histopathologically confirmed primary BCCs and to make a gross estimate on how unreported BCCs could influence the total number of new cases.

METHODS: We retrospectively reviewed all primary BCCs diagnosed in 2016 at the Department of Dermatology, Sahlgrenska University Hospital in Gothenburg, Sweden. We also reviewed all histopathologically verified primary BCCs at the two largest pathology laboratories in Western Sweden during the same year to estimate the proportion of BCCs diagnosed by dermatologists.

RESULTS: In total, 2,365 primary BCCs were diagnosed at our center. More than half of these tumours were clinically diagnosed (55.8%). Superficial subtype (41.7%), location on the trunk (46.3%) and destructive treatment methods (60.0%) were most common. Reports from the two pathology laboratories showed that histopathologically verified BCCs (n=5,837) were more commonly of the infiltrative or nodular subtype and located in the head and neck area. Dermatologists managed 56.0% of them.

CONCLUSIONS: This study indicates that a substantial number of BCCs are not visualized in the official statistics which are solely based on reports from pathology laboratories. When taking clinically diagnosed tumours into account, truncal location and superficial subtype are more common than previously believed. Further, based on regional calculations, the real burden of BCC in Sweden might be up to 70% higher than what is reported in official statistics.

PMID:36433707 | DOI:10.1111/jdv.18774

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Evaluation of geranylgeranyl diphosphate synthase inhibition as a novel strategy for the treatment of osteosarcoma and Ewing sarcoma

Drug Dev Res. 2022 Nov 25. doi: 10.1002/ddr.22012. Online ahead of print.

ABSTRACT

Rab GTPases are critical regulators of protein trafficking in the cell. To ensure proper cellular localization and function, Rab proteins must undergo a posttranslational modification, termed geranylgeranylation. In the isoprenoid biosynthesis pathway, the enzyme geranylgeranyl diphosphate synthase (GGDPS) generates the 20-carbon isoprenoid donor (geranylgeranyl pyrophosphate [GGPP]), which is utilized in the prenylation of Rab proteins. We have pursued the development of GGDPS inhibitors (GGSI) as a novel means to target Rab activity in cancer cells. Osteosarcoma (OS) and Ewing sarcoma (ES) are aggressive childhood bone cancers with stagnant survival statistics and limited treatment options. Here we show that GGSI treatment induces markers of the unfolded protein response (UPR) and triggers apoptotic cell death in a variety of OS and ES cell lines. Confirmation that these effects were secondary to cellular depletion of GGPP and disruption of Rab geranylgeranylation was confirmed via experiments using exogenous GGPP or specific geranylgeranyl transferase inhibitors. Furthermore, GGSI treatment disrupts cellular migration and invasion in vitro. Metabolomic profiles of OS and ES cell lines identify distinct changes in purine metabolism in GGSI-treated cells. Lastly, we demonstrate that GGSI treatment slows tumor growth in a mouse model of ES. Collectively, these studies support further development of GGSIs as a novel treatment for OS and ES.

PMID:36433690 | DOI:10.1002/ddr.22012

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Real world outcomes using PD-1 antibodies and BRAF+MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

J Eur Acad Dermatol Venereol. 2022 Nov 25. doi: 10.1111/jdv.18779. Online ahead of print.

ABSTRACT

BACKGROUND: PD-1 antibodies and BRAF+MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland.

METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib+trametinib (D+T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence.

RESULTS: 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analyzed. The vast majority received anti PD-1 therapies (n=1003). 12-month RFS for anti PD-1 and BRAF+MEK inhibitor treated patients were 78.1% and 86.5% respectively (hazard ratio [HR] 1.998 [95%CI 1.335-2.991]; p=0.001). There was no statistically significant difference in overall survival in anti PD-1 (95.8%) and BRAF+MEK inhibitor (96.9%) treated patients (p>0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95%CI 0.443-0.754], p=0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p>0.05). In both, anti PD-1 and BRAF+MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection versus sentinel lymph node biopsy only (p>0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC=0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials.

CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that total lymph node dissection does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

PMID:36433688 | DOI:10.1111/jdv.18779