An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a ...long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.
Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular ...thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 95% CI, 1.3-2.7
=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%,
=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.
We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel ...occlusion ischemic stroke.
Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2.
Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI (
<0.001) and collateral status (
<0.001) were among independent predictors of final infarct volumes. However, mTICI (
<0.001), but not collateral status (
=0.058), predicted favorable outcome at discharge.
In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.
Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative ...cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001–2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.
Interferons and osteosarcoma Strander, Hans
Cytokine & growth factor reviews,
10/2007, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Abstract In 1970, we initiated studies at the Karolinska hospital to find out whether biologically meaningful doses of interferon (IFN) alpha preparations could be administered systemically to ...patients with viral and tumour diseases without causing unacceptable side effects. Antiviral and antitumour efficiency was demonstrated. Only a limited number of patients were injected due to shortage of high dose IFN preparations. Osteosarcoma patients participated in these early attempts. Due to clinical observations on one patient and due to lack of meaningful systemic standard treatment for osteosarcoma at the time, we decided to continue to give adjuvant IFN treatment to a consecutive series of osteosarcoma patients attending our hospital .We were encouraged by the preliminary follow up results of the series and continued to use this therapeutic principle up to 1990. The clinical results achieved are briefly summarized in this mini-review as are the results obtained in simultaneously ongoing model experiments in vitro and in vivo. A randomized large scale ongoing trial, involving the use of adjuvant IFN treatment of osteosarcoma patients, has been initiated by the European and American osteosarcoma study group 35 years after the first osteosarcoma patient received IFN. The trial is briefly outlined in this article.
Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we ...evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression. Results- Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth ( P=0.036) and final infarct volume ( P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0-2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome ( P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04-1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07-1.38; P=0.003). The association between aMAP and outcome was also significant at discharge ( P=0.002) and 90 days ( P=0.001). Conclusions- Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.
This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or ...equal to grade 2 severity (CIN2+).
VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation.
495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live- and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors.
Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available.
Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014). The trial was retrospectively registered in the Clinical Trails Registry of India CTRI/2018/03/012470 .
Background and Purpose- Optimal blood pressure (BP) management during the early stages of aneurysmal subarachnoid hemorrhage remains uncertain. Observational studies have found worse outcomes in ...patients with increased hemodynamic variability, suggesting BP optimization as a potential neuroprotective strategy. In this study, we calculated personalized BP targets at which cerebral autoregulation was best preserved. We analyzed how deviation from these limits correlates with functional outcome. Methods- We prospectively enrolled 31 patients with aneurysmal subarachnoid hemorrhage. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation-a surrogate for cerebral blood flow-as well as intracranial pressure (ICP) in response to changes in mean arterial pressure using time-correlation analysis. The resulting autoregulatory indices were used to identify the upper and lower limit of autoregulation. Percent time that mean arterial pressure exceeded limits of autoregulation was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using ordinal multivariate logistic regression. Results- Personalized limits of autoregulation were computed in all patients (age 57.5±13.4, 23F, mean World Federation of Neurological Surgeons 2±1, monitoring time 67.8±50.8 hours). Optimal BP and limits of autoregulation were calculated on average for 89.5±6.7% of the total monitoring period. ICP- and NIRS-derived optimal pressures strongly correlated with one another (
<0.0001). Percent time that mean arterial pressure deviated from limits of autoregulation significantly associated with worse functional outcome at discharge (NIRS,
=0.001; ICP,
=0.004) and 90 days (NIRS,
=0.002; ICP,
=0.003), adjusting separately for age, World Federation of Neurological Surgeons, vasospasm, and delayed cerebral ischemia. Conclusions- Both invasive (ICP) and noninvasive (NIRS) determination of personalized BP targets after aneurysmal subarachnoid hemorrhage is feasible, and these 2 approaches revealed significant collinearity. Furthermore, exceeding individualized limits of autoregulation was associated with poor functional outcomes.
A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the ...scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for soft tissue sarcomas (STS) is based on data from five randomized trials. Moreover, data from 6 prospective studies, 25 retrospective studies and 3 other articles were used. In total, 39 scientific articles are included, involving 4 579 patients. The results were compared with those of a similar overview from 1996 which included 3 344 patients. The conclusions reached can be summarized as follows: The well-established prognostic factors for tumour-related death from STS--histological grade, tumour size and age--are well documented. The importance of superficial versus deep site as well as the anatomic site is also reaffirmed to some extent. There is strong evidence that adjuvant radiotherapy improves the local control rate in combination with conservative surgery in the treatment of STS of extremities and trunk in patients with negative, marginal or minimal microscopic positive surgical margins. A local control rate of 90% has been achieved. Improvement is obtained with radiotherapy added in the case of intralesional surgery, but the local control rate is somewhat lower. More studies are needed on this issue. For STS in other anatomic sites, retroperitoneum, head and neck, breast and uterus, there is only weak indication of a benefit for the local control rate, with the use of adjuvant radiotherapy. There is still insufficient data to establish that preoperative radiotherapy is favourable compared to postoperative radiotherapy for local control in patients presenting primarily with large tumours. One small study has shown a possible survival benefit for preoperative radiotherapy. There is fairly good evidence to suggest that the preoperative setting results in more wound complications. There is no randomized study comparing external beam radiotherapy and brachytherapy. The data suggest that external beam radiotherapy and low dose rate brachytherapy result in comparable local control for high-grade tumours. Some patients with low-grade soft tissue sarcomas benefit from external beam radiotherapy in terms of local control. Brachytherapy with low dose rate for low-grade tumours seems to be of no benefit, but data are sparse. The available data are inconclusive concerning the effect of intraoperative high dose rate radiotherapy for retroperitoneal STS. Further studies are needed. Neutron radiotherapy might be beneficial for patients with low- and intermediate-grade tumours considered inoperable and for those operated with intralesional margins. More severe side effects for neutrons have been registered. In two small studies investigating hyperfractionation schedules there was no indication of improvements compared to daily fractions of 2 Gy. Further studies should be encouraged. One small study using preoperative limb perfusion with TNFα melphalan and ±interferon γ combined with postoperative radiotherapy in the case of marginal or positive surgical margin has shown excellent local control without enhanced morbidity.
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