| 1. |
- Pocas, Juliana, et al.
(författare)
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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
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Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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| 2. |
- Kontakis, Michael G., et al.
(författare)
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Artificial disc replacement and adjacent-segment pathology : 10-year outcomes of a randomized trial
- 2022
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Ingår i: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 1547-5654 .- 1547-5646. ; 36:6, s. 945-953
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Artificial disc replacement (ADR) is designed to preserve motion and thus protect against adjacent-segment pathology (ASP) and act as an alternative treatment to fusion surgery. The question remains, how well do ADR devices perform after 10 years of follow-up compared with fusion surgery in terms of patient satisfaction, sustainability, and protection against ASP?METHODS: This was the 10-year follow-up study of 153 participants who underwent ADR or fusion surgery after anterior decompression due to cervical degenerative radiculopathy (ISRCTN registration no. 44347115). Scores on the Neck Disability Index (NDI), EQ-5D, and visual analog scale for neck and arm pain were obtained from the Swedish Spine Registry and analyzed using ANCOVA. Information about secondary surgical procedures was collected from medical records and presented as Kaplan-Meier curves. MRI and flexion-extension radiography were performed, and ASP was graded according to the Miyazaki classification system.RESULTS: Ten participants were lost to follow-up, which left 143 participants (80 underwent ADR and 65 underwent anterior cervical discectomy and fusion). There were no differences between groups in terms of patient-reported outcome measures (10-year difference in NDI scores 1.7 points, 95% CI -5.1 to 8.5, p = 0.61). Nineteen (24%) participants in the ADR group compared with 9 (14%) in the fusion group underwent secondary surgical procedures. The higher reoperation rate of the ADR group was mainly due to 11 female participants with device loosening. The rates of reoperation due to ASP were similar between groups, which was confirmed with MRI assessment of ASP that also showed no differences between the groups (p = 0.21).CONCLUSIONS: This was the first 10-year follow-up study to compare ADR with fusion surgery and to provide MRI information for the assessment of ASP. The authors found no benefit of ADR over fusion surgery after anterior decompression for cervical degenerative radiculopathy.
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| 3. |
- MacDowall, Anna, et al.
(författare)
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Artificial disc replacement versus fusion in patients with cervical degenerative disc disease and radiculopathy : a randomized controlled trial with 5-year outcomes
- 2019
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Ingår i: Journal of Neurosurgery. - 1547-5654 .- 1547-5646. ; 30:3, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThe method of artificial disc replacement (ADR) has been developed as an alternative treatment to fusion surgery after decompression for cervical degenerative disc disease (DDD) with radiculopathy. Preserving the motion of ADR devices aims to prevent immobilization side effects such as adjacent-segment pathology (ASP). However, long-term follow-up evaluations using MRI are needed to investigate if this intent is achieved.METHODSThe authors performed a randomized controlled trial with 153 patients (mean age 47 years) undergoing surgery for cervical radiculopathy. Eighty-three patients received an ADR and 70 patients underwent fusion surgery. Outcomes after 5 years were assessed using patient-reported outcome measures using the Neck Disability Index (NDI) score as the primary outcome; motion preservation and heterotopic ossification by radiography; ASP by MRI; and secondary surgical procedures.RESULTSScores on the NDI were approximately halved in both groups: the mean score after 5 years was 36 (95% confidence interval [CI] 31–41) in the ADR group and 32 (95% CI 27–38) in the fusion group (p = 0.48). There were no other significant differences between the groups in six other patient-related outcome measures. Fifty-four percent of the patients in the ADR group preserved motion at the operated cervical level and 25% of the ADRs were spontaneously fused. Seventeen ADR patients (21%) and 7 fusion patients (10%) underwent secondary surgery (p = 0.11), with 5 patients in each group due to clinical ASP.CONCLUSIONSIn patients with cervical DDD and radiculopathy decompression as well as ADR, surgery did not result in better clinical or radiological outcomes after 5 years compared with decompression and fusion surgery.
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| 4. |
- Marques, Catarina, 1969-, et al.
(författare)
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Accuracy and Reliability of X-ray Measurements in the Cervical Spine
- 2020
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Ingår i: Asian Spine Journal. - : KOREAN SOC SPINE SURGERY. - 1976-1902 .- 1976-7846. ; 14:2, s. 169-176
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Tidskriftsartikel (refereegranskat)abstract
- Study Design: This study is a post hoc analysis of a multicenter prospective randomized controlled trial which compared artificial disc replacement and anterior cervical discectomy and fusion. Purpose: Useful radiographic parameters for assessing cervical alignment include the Cobb angles, T1 slope (TS), occipitocervical inclination (OCI). K-line tilt (KLT), and cervical sagittal vertical axis (cSVA). This study aimed to determine measurement accuracy and reliability for these parameters. Overview of Literature: Various authors have assessed repeatability by comparing different methods of measurement, but knowledge of measurement error and minimal detectable change is scarce. Methods: We evaluated 75B lateral cervical radiographs. One medical student and one spine surgeon (i.e., measured x2 within 4 weeks) independently measured the parameters obtaining 5,850 values. Standard error of measurement (SEm) and minimum detectable change (MDC) were calculated for each parameter. The accuracy and reliability of the Cobb angle measurements were calculated for the different types of angles: cervical lordosis, prosthesis angle, segmental angle with two hone surfaces (SABB), and segmental angle with one bone and one metal surface. Reliability was determined with intraclass correlation coefficient (ICC). Results: SEm was 1.8 degrees and MDC was 5.0 degrees for the Cobb angle, with an intraobserver/interobserver ICC of 0.958/0.8B6. All the different subtypes of Cobb angles had an ICC higher than 0.950, except SABB (intraobserver/interobserver ICC of 0.922/0.716). The most accurate and reliable measurement was for KLT. Conclusions: This study provides normative data on SEm and MDC for Cobb angles, T1S, KLT, OCI, and cSVA in cervicalcervicai lateral radiographs. Reliability was excellent for all parameters except SABB (e.g., good).
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| 5. |
- Marques, Catarina, 1969-
(författare)
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Studies on Cervical Artificial Disc Replacement
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Artificial disc replacement (ADR) was developed as an alternative to anterior fusion after decompression for cervical degenerative radiculopathy. By preserving motion, it was expected to prevent acceleration of adjacent segment pathology (ASP) associated with fusion, and lead to better clinical outcomes. The aims of this thesis were to evaluate whether ADR surgery leads to better outcomes than fusion surgery, to investigate if it prevents the acceleration of ASP, and to analyze its potential complications. In a multicenter randomized controlled trial (RCT) 153 patients were randomized to ADR (DiscoverTM implant) or fusion surgery (autograft, plate and screws). The outcomes at 5 and 10 years postoperatively were analyzed with Neck Disability Index (NDI) as primary measure. Heterotopic ossification (HO), ASP, and secondary surgery where analyzed. The measurements of radiographic parameters used in the assessment of cervical alignment where validated.To further analyze secondary surgery after ADR, a descriptive register cohort study was done with 42 patients whose data were retrieved from Swespine and completed with medical charts, images, and a telephone interview. There was no difference in NDI scores between groups in the RCT, 5 or 10 years postoperatively. Radiological and clinically significant ASP were similar in both groups. There was more secondary surgery in the ADR group compared with the fusion group, mainly due to device loosening in women. Severe HO was seen in 71% of the ADR implants 5 years postoperatively, and 27% were fused, male sex being a clear risk factor.Normative data for measurement error were provided on the cervical alignment measurements, and the most reliable were the K-line tilt and the cervical sagittal vertical axis (cSVA). In the 42 patients in the register cohort study the most common diagnosis leading to reoperation was loosening of the ADR implant and/or ASP, predominantly treated with fusion surgery. Reoperation resulted in good outcomes in the vast majority of patients. At the long-term, there is no clinical benefit of ADR over fusion surgery after decompression for cervical degenerative radiculopathy. ADR, compared with fusion surgery, does not prevent acceleration of ASP, and results in more reoperations. Revision surgery for failed cervical ADRs is effective and justified.
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| 6. |
- Marques, Catarina, 1969-, et al.
(författare)
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The fate of failed cervical arthroplasties: outcome of revision surgery
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To analyze the diagnoses leading to secondary surgery, the surgical methods used in reoperations, and the final clinical outcomes, in patients reoperated after a primary reconstruction with a cervical artificial disc replacement (ADR). Methods: Descriptive cohort study of 42 ADR patients who underwent secondary surgery at the index or adjacent level. Data collected from the National Swedish Register for Spine Surgery 2006 through 2018, completed with information from patients’ charts, images, and a telephone interview with the patients. Analysis of time to reoperation, diagnosis leading to reoperation, surgical method, and outcome at 2 years, measured as change in neck pain, arm pain and function, as well as overall patient satisfaction. Results: The most common diagnosis leading to reoperation was loosening (n=16), clinical adjacent segment pathology (ASP) (n=8), or a combination thereof (n=6). Thirty-four of the surgeries were performed at the index level. Mean time to reoperation was 44 months.Reoperation consisted of extraction of the ADR and fusion surgery in 32 cases. Function improved after the reoperation in 32 patients. Twenty-four of 30 patients who had neck pain, and 28 of 32 who had arm pain improved after the reoperation. No patients reported post-operative aggravation of symptoms.Conclusion: Failure of ADR is mainly due to loosening of the implant and/or ASP, and is predominantly treated with fusion surgery. Reoperation results in good outcomes (complete or nearly complete recovery) in the vast majority of patients. We conclude that revision surgery for failed cervical arthroplasty is effective and justified.
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| 7. |
- Marques, Catarina, 1969-, et al.
(författare)
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Unintended fusion in cervical artificial disk replacement : a prospective study on heterotopic ossification, progression, and clinical outcome, with 5-year follow-up
- 2021
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Ingår i: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 30:6, s. 1662-1669
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Heterotopic ossification (HO) may cause unintended fusion in artificial disk replacement (ADR), failing to preserve motion. The reported incidence of HO varies hugely. This study aimed to determine prevalence of HO, progression, predisposing factors to occurrence and to progression, and potential effect on clinical outcomes. Methods Eighty-three patients treated with ADRs for cervical radiculopathy at one or two segments were extracted from a previously published RCT. Of the 83 patients, 59 had remaining ADR (79 implants) and sufficiently high-quality X-rays at 5 years of follow-up to allow analysis. HO was graded on plain films according to Mehren/Suchomel. Prevalence, progression, predisposing factors and effect on clinical outcome (Neck Disability Index-NDI) were analyzed. Results At 2 years, HO was seen in 46/55 ADR implants (84%), severe enough to affect mobility in 27/55 (49%). At 5 years, HO was seen in 92% of 79 implants, severe in 71%. Male sex was a predisposing factor to HO. No predisposing factors to progression were identified. NDI was not affected by the severity of HO. Conclusion Almost all ADR implants in our study have HO at 5 years of follow-up. Male sex is a risk factor. Severe HO did not affect clinical outcome.
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| 8. |
- Marques Ramos, Pedro, et al.
(författare)
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Next-generation sequencing of baseline genetic mutations and outcomes of eltrombopag and azacitidine therapy in patients with myelodysplastic syndromes and thrombocytopenia : Data from the SUPPORT clinical trial
- 2023
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Ingår i: eJHaem. - : John Wiley & Sons. - 2688-6146. ; 4:3, s. 876-881
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Tidskriftsartikel (refereegranskat)abstract
- Eltrombopag has been previously shown to be effective in reversing azacitidine-mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate- to high-risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort were associated with treatment outcomes. Based on the available data, we observed no imbalance in the mutational profiles between treatment arms or a clear association between identified somatic mutations and clinical outcomes.
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| 9. |
- Vigliar, Elena, et al.
(författare)
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COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study
- 2022
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Ingår i: Cancer Cytopathology. - : WILEY. - 1934-662X .- 1934-6638. ; 130:5, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Background In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
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| 10. |
- Vigliar, Elena, et al.
(författare)
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Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries
- 2020
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Ingår i: Cancer Cytopathology. - : WILEY. - 1934-662X .- 1934-6638. ; 128:12, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- Background To the authors knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. Methods Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. Results Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). Conclusions The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
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