Decompressive craniectomy plus best medical treatment versus best medical treatment alone for spontaneous severe deep supratentorial intracerebral haemorrhage: a randomised controlled clinical trial.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Completion Pancreatectomy After Pancreatoduodenectomy: Who Needs It?

OBJECTIVE: The objective of this study was to identify the indications for and report the outcomes of completion pancreatectomy (CPLP) in the postoperative course after pancreatoduodenectomy (PD). BACKGROUND: CPLP may be considered or even inevitable for damage control after PD. METHODS: A prospectively maintained database of all patients undergoing PD between 2001 and 2019 was searched for patients who underwent CPLP in the postoperative course after PD. Baseline characteristics, perioperative details, and outcomes of CPLP patients were analyzed and specific indications for CPLP were identified. RESULTS: A total of 3953 consecutive patients underwent PD during the observation period. CPLP was performed in 120 patients (3%) after a median of 10 days following PD. The main indications for CPLP included postpancreatectomy acute necrotizing pancreatitis [n=47 (39%)] and postoperative pancreatic fistula complicated by hemorrhage [n=41 (34%)] or associated with uncontrollable leakage of the pancreatoenteric anastomosis [n=23 (19%)]. The overall 90-day mortality rate of all 3953 patients was 3.5% and 37% for patients undergoing CPLP. CONCLUSIONS: Our finding that only very few patients (3%) need CPLP suggests that conservative, interventional, and organ-preserving surgical measures are the mainstay of complication management after PD. Postpancreatectomy acute necrotizing pancreatitis, uncontrollable postoperative pancreatic fistula, and fistula-associated hemorrhage are highly dangerous and represent the main indications for CPLP after PD.

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND: There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS: Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS: In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS: Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies.

Long-term effect of everolimus in recurrent thymic neuroendocrine neoplasia.

PURPOSE: Neuroendocrine neoplasia (NEN) of the thymus is a very rare entity with a poor prognosis. None of the treatments was proofed by studies. Usually, therapy protocols for bronchopulmonary carcinoids are used. So far no data exist on the effect of mammalian target of rapamycin (mTOR) inhibitors. We describe our long-term experience with everolimus and give a thorough review of the therapeutic strategies used so far. PATIENTS AND METHODS: Four patients (mean age 46 years, range 37-55) with progressing thymic NEN (t-NEN) (two well-differentiated atypical carcinoids and two atypical carcinoids with large cell characteristics) were treated with everolimus 10 mg/day after the failure of at least one previous medical therapy. Everolimus was applied after a mean interval of 32.4 months (range 5-56) after the first diagnosis. The follow-up included clinical examination, imaging and chromogranin A testing in 3 or 6 monthly intervals. RESULTS: We observed stable disease for a mean of 20.8 months. Both patients with large cell characteristics t-NEN (Ki-67 of 20%) had rapid progress after 7 and 10 months and had more previous therapies (three and six) than the patients with well-differentiated t-NEN (Ki-67 5% and 10%, progress after 24 and 42 months, one and two previous therapies). No severe side effects occurred. In three of four patients, everolimus led to stable disease for the longest compared to the other nonsurgical therapies used. CONCLUSION: Comparing the sparse data available everolimus is a promising treatment for t-NEN at least in second-line therapy. A low Ki-67 index was associated with a better outcome.

How does occupational physical activity influence health? An umbrella review of 23 health outcomes across 158 observational studies.

OBJECTIVE: Physical activity (PA) has substantial benefits across a range of health outcomes. There is uncertainty about the PA-specific health effects, and in particular, the occupational domain. In this umbrella review, we synthesised available evidence on the associations between occupational PA (OPA) and health-related outcomes (including cancer, all-cause mortality and cardiovascular disease). This work informed the development of WHO's guidelines on PA and sedentary behaviour (2020). DESIGN: Umbrella review of systematic reviews. DATA SOURCE: We performed a literature search in PubMed, Web of Science, Embase, CINAHL and Sportdiscuss from database inception to 2 December 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included systematic reviews if they contained a quantitative assessment of OPA and its relationship with at least one health-related outcome. RESULTS: We summarised the evidence of 17 reviews covering 23 unique health-related outcomes. We graded most evidence as low or very low, or moderate quality. We found health benefits for those engaging in high versus low OPA for multiple cancer outcomes (including colon and prostate), ischaemic stroke, coronary heart disease and mental health (ie, mental well-being and life satisfaction). High OPA was associated with unfavourable health outcomes for all-cause mortality in men, mental ill health (ie, depression and anxiety), osteoarthritis, and sleep quality and duration. CONCLUSIONS: We found favourable associations for most health-related outcomes with high OPA levels, but we also found some evidence for unfavourable associations due to high OPA levels. At this point, there is a need for better quality evidence to provide a unequivocal statement on the health effects of OPA.

Autotransplantation of parathyroid grafts into the tibialis anterior muscle after parathyroidectomy: a novel autotransplantation site.

BACKGROUND: Surgical management of renal secondary hyperparathyroidism (sHPT) is varying. Total parathyroidectomy with heterotopic autotransplantation (TPTX + AT) is one of the standard surgical procedures in sHPT, but there is no consensus about the optimal site for graft insertion. At the surgical department of the University Hospital of Heidelberg we prefer the autotransplantation into the tibialis anterior muscle. The aim of this study was to assess the long-term function of the auto-transplanted parathyroid tissue in this type of surgical procedure. METHODS: The function of the autograft of 42 patients was assessed 8.2 ± 2.5 years after surgery, using a modified Casanova-test of the leg bearing the parathyroid tissue. Ischemic blockage was induced by tourniquet and the levels of parathyroid hormone (PTH) were assessed during the test. RESULTS: At the point of assessment, the ischemic blockage led to a significant reduction in the concentration of PTH (≥50% of the baseline value) in 19 patients (45%) indicating well-functioning autografts. In 11 patients (26%), ischemic blockage did not cause any change in the concentration of PTH (≤20% of the baseline value), indicating functioning residual parathyroid tissue from another site. The source of PTH production was classified as unidentifiable in five patients (12%). Two patients had developed graft-dependent recurrent HPT (5%) without therapeutic consequences and three patients suffered from persistent symptomatic hypoparathyroidism (7%). CONCLUSIONS: These results indicate that TPTX + AT into the tibialis anterior muscle is a successful surgical treatment for renal HPT and that the modified Casanova-test is a suitable diagnostic tool for autografts function.

Immunohistochemical FAP Expression Reflects 68Ga-FAPI PET Imaging Properties of Low- and High-Grade Intraductal Papillary Mucinous Neoplasms and Pancreatic Ductal Adenocarcinoma.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are grossly visible (typically > 5 mm) intraductal epithelial neoplasms of mucin-producing cells, arising in the main pancreatic duct or its branches. According to the current 2-tiered grading scheme, these lesions are categorized as having either low-grade (LG) dysplasia, which has a benign prognosis, or high-grade (HG) dysplasia, which formally represents a carcinoma in situ and thus can transform to pancreatic ductal adenocarcinoma (PDAC). Because both entities require different treatments according to their risk of becoming malignant, a precise pretherapeutic diagnostic differentiation is inevitable for adequate patient management. Recently, our group has demonstrated that 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT shows great potential for the differentiation of LG IPMNs, HG IPMNs, and PDAC according to marked differences in signal intensity and tracer dynamics. The purpose of this study was to biologically validate FAP as a target for PET imaging by analyzing immunohistochemical FAP expression in LG IPMNs, HG IPMNs, and PDAC and comparing with SUV and time to peak (TTP) measured in our prior study. Methods: To evaluate the correlation of the expression level of FAP and α-smooth muscle actin (αSMA) in neoplasm-associated stroma depending on the degree of dysplasia in IPMNs, 98 patients with a diagnosis of LG IPMN, HG IPMN, PDAC with associated HG IPMN, or PDAC who underwent pancreatic surgery at the University Hospital Heidelberg between 2017 and 2023 were identified using the database of the Institute of Pathology, University Hospital Heidelberg. In a reevaluation of hematoxylin- and eosin-stained tissue sections of formalin-fixed and paraffin-embedded resection material from the archive, which was originally generated for histopathologic routine diagnostics, a regrading of IPMNs was performed by a pathologist according to the current 2-tiered grading scheme, consequently eliminating the former diagnosis of "IPMN with intermediate-grade dysplasia." For each case, semithin tissue sections of 3 paraffin blocks containing neoplasm were immunohistologically stained with antibodies directed against FAP and αSMA. In a masked approach, a semiquantitative analysis of the immunohistochemically stained slides was finally performed by a pathologist by adapting the immunoreactive score (IRS) and human epidermal growth factor receptor 2 (Her2)/neu score to determine the intensity and percentage of FAP- and αSMA-positive cells. Afterward, the IRS of 14 patients who underwent 68Ga-FAPI-74 PET/CT in our previous study was compared with their SUVmax, SUVmean, and TTP for result validation. Results: From 98 patients, 294 specimens (3 replicates per patient) were immunohistochemically stained for FAP and αSMA. Twenty-three patients had LG IPMNs, 11 had HG IPMNs, 10 had HG IPMNs plus PDAC, and 54 had PDAC. The tumor stroma was in all cases variably positive for FAP. The staining intensity, percentage of FAP-positive stroma, IRS, and Her2/neu score increased with higher malignancy. αSMA expression could be shown in normal pancreatic stroma as well as within peri- and intraneoplastic desmoplastic reaction. No homogeneous increase in intensity, percentage, IRS, and Her2/neu score with higher malignancy was observed for αSMA. The comparison of the mean IRS of FAP with the mean SUVmax, SUVmean, and TTP of 68Ga-GAPI-74 PET/CT showed a matching value increasing with higher malignancy in 68Ga-FAPI-74 PET imaging and immunohistochemical FAP expression. Conclusion: The immunohistochemical staining of IPMNs and PDAC validates FAP as a biology-based stromal target for in vivo imaging. Increasing expression of FAP in lesions with a higher degree of malignancy matches the expectation of a stronger FAP expression in PDAC and HG IPMNs than in LG IPMNs and corroborates our previous findings of higher SUVs and a longer TTP in PDAC and HG IPMNs than in LG IPMNs.

Optimal quantum-enhanced interferometry using a laser power source.

We consider an interferometer powered by laser light (a coherent state) into one input port and ask the following question: what is the best state to inject into the second input port, given a constraint on the mean number of photons this state can carry, in order to optimize the interferometer's phase sensitivity? This question is the practical question for high-sensitivity interferometry. We answer the question by considering the quantum Cramér-Rao bound for such a setup. The answer is squeezed vacuum.

Targeted therapy with vemurafenib in BRAF(V600E)-mutated anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies, representing less than 5% of all thyroid carcinomas. Τhe median survival is limited to months due to the resistance of ATC to surgery, radioiodine therapy, radiotherapy and chemotherapy. This review will cover novel agents involving several cellular signaling pathways including the BRAF pathway. The BRAF inhibitor vemurafenib improves survival among patients with metastatic melanoma, hairy-cell leukemia and intracranial neoplasms with BRAF gene mutations. The frequency of a BRAF (V600E) mutation in ATC is about 25%. CASE PRESENTATION: We report the first case of a marked partial response to adjuvant first line monotherapy with vemurafenib in BRAF V600E-mutated ATC. The 78-year-old man showed a sustained response for 7 months, thereafter scans revealed progressive disease and the patient died 10 months after first diagnosis. This case report is accompanied by a comprehensive review of current strategies and tools for ATC treatment. CONCLUSIONS: This case and the review of current data confirm the benefit of BRAF inhibition in BRAF-mutated ATC, limited by acquired resistance to targeted therapy.

Comparison of clinicopathological features and survival analysis between esophageal neuroendocrine carcinoma and esophageal squamous cell carcinoma based on the SEER database, alongside nomogram analysis for esophageal neuroendocrine carcinoma.

Background: Esophageal neuroendocrine carcinoma (ENEC) is a rare subtype of esophageal cancer (EC). It presents distinctive clinical and pathological features in comparison to esophageal squamous cell carcinoma (ESCC). To better elucidate the disparities between the two and establish a prognostic prediction model for ENEC, we conducted this study. Methods: Data of ENEC and ESCC patients (1975 to 2016) were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Patients with a confirmed pathological diagnosis of ENEC and ESCC were enrolled in the study. The Chi-square test was employed to compare categorical variables, and the median survival time was analyzed using the Kaplan-Meier curve. Training and validation groups were randomly assigned at a ratio of 7:3. Factors with a significance level of <0.05 in the multifactor regression model as well as age were integrated into the nomogram model. Concordance index (C-index), calibration curves, and decision curve analyses (DCA) were generated for model validation. Results: This study encompassed a total of 737 ENEC patients and 29,420 ESCC. Compared to ESCC, ENEC patients had higher probability of liver metastasis (13.8% vs. 1.9%, P<0.001), poor differentiation (68.0% vs. 37.1%, P<0.001), and late SEER stage (52.8% vs. 26.9%, P<0.001). Patients who received either surgery, radiotherapy (RT), or chemotherapy had a significantly longer disease-specific survival (DSS) and overall survival (OS) (all P<0.001). After propensity score matching (PSM), ENEC patients were associated with shorter DSS (7.0 months vs. not reached, P<0.0001) and OS (7.0 vs. 12.0 months, P<0.0001) compared to ESCC. Race, SEER stage, surgery, RT, and chemotherapy were identified as predictors of DSS and were incorporated into the nomogram model together with age. The validation of the model using C-index (0.751 and 0.706, respectively) and calibration curves reflected the better discrimination power of the model. In addition, DCA supported the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on the nomogram also verified the reliability of the model. Conclusions: ENEC and ESCC exhibit distinct clinicopathological features. Patients with ENEC experience significantly poorer survival outcomes compared to those with ESCC. Surgical intervention, radiation therapy, and chemotherapy significantly improve OS and DSS for ENEC patients. The nomogram prediction model, constructed based on age, race, stage, and treatment regimen, demonstrates accurate and effective predictive capabilities for prognostic factors in ENEC patients.

Static and Dynamic 68Ga-FAPI PET/CT for the Detection of Malignant Transformation of Intraductal Papillary Mucinous Neoplasia of the Pancreas.

Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, nonoperative differentiation by ultrasound, CT, MRI, and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory. Here, we assessed the clinical feasibility of additional assessment of malignancy by PET using 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI PET) in 25 patients with MRI- or CT-proven cystic pancreatic lesions. Methods: Twenty-five patients with cystic pancreatic lesions who were followed up in the European Pancreas Center of Heidelberg University hospital and who were led to surgical resection or fine-needle aspiration due to suspicious clinical, laboratory chemistry, or radiologic findings were examined by static (all patients) and dynamic (20 patients) 68Ga-FAPI PET. Cystic pancreatic lesions were delineated and SUVmax and SUVmean were determined. Time-activity curves and dynamic parameters (time to peak, K 1, k 2, K3, k 4) were extracted from dynamic PET data. Receiver-operating curves of static and dynamic PET parameters were calculated. Results: Eleven of the patients had menacing IPMN (high-grade IPMN with [6 cases] or without [5 cases] progression into PDAC) and 11 low-grade IPMN; 3 patients had other benign entities. Menacing IMPN showed significantly elevated 68Ga-FAPI uptake compared with low-grade IPMN and other benign cystic lesions. In dynamic imaging, menacing IPMN showed increasing time-activity curves followed by slow decrease afterward; time-activity curves of low-grade IPMN showed an immediate peak followed by rapid decrease for about 10 min and slower decrease for the rest of the time. Receiver-operating curves showed high sensitivity and specificity (area under the curve greater than 80%) of static and dynamic PET parameters for the differentiation of IPMN subtypes. Conclusion: 68Ga-FAPI PET is a helpful new tool for the differentiation of menacing and low-grade IPMN and shows the potential to avoid unnecessary surgery for nonmalignant pancreatic IPMN.

Middle Segment-Preserving Pancreatectomy to Avoid Pancreatic Insufficiency: Individual Patient Data Analysis of All Published Cases from 2003-2021.

Middle segment-preserving pancreatectomy (MPP) can treat multilocular diseases in the pancreatic head and tail while avoiding impairments caused by total pancreatectomy (TP). We conducted a systematic literature review of MPP cases and collected individual patient data (IPD). MPP patients (N = 29) were analyzed and compared to a group of TP patients (N = 14) in terms of clinical baseline characteristics, intraoperative course, and postoperative outcomes. We also conducted a limited survival analysis following MPP. Pancreatic functionality was better preserved following MPP than TP, as new-onset diabetes and exocrine insufficiency each occurred in 29% of MPP patients compared to near-ubiquitous prevalence among TP patients. Nevertheless, POPF Grade B occurred in 54% of MPP patients, a complication avoidable with TP. Longer pancreatic remnants were a prognostic indicator for shorter and less eventful hospital stays with fewer complications, whereas complications of endocrine functionality were associated with older patients. Long-term survival prospects after MPP appeared strong (median up to 110 months), but survival was lower in cases with recurring malignancies and metastases (median < 40 months). This study demonstrates MPP is a feasible treatment alternative to TP for selected cases because it can avoid pancreoprivic impairments, but at the risk of perioperative morbidity.

Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas.

Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses.

Association of Intravenous Thrombolysis with Delayed Reperfusion After Incomplete Mechanical Thrombectomy.

PURPOSE: Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT. METHODS: Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed. RESULTS: In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively). CONCLUSION: A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required.

Impact of 68Ga-FAPI PET/CT Imaging on the Therapeutic Management of Primary and Recurrent Pancreatic Ductal Adenocarcinomas.

Pancreatic ductal carcinoma (PDAC) is a highly lethal cancer, and early detection and accurate staging are critical to prolonging survival. PDAC typically has a prominent stroma including cancer-associated fibroblasts that express fibroblast activation protein (FAP). FAP is a new target molecule for PET imaging of various tumors. In this retrospective study, we describe the clinical impact of PET/CT imaging using 68Ga-labeled FAP-inhibitors (68Ga-FAPI PET/CT) in 19 patients with PDAC (7 primary, 12 progressive/recurrent). Methods: All patients underwent contrast-enhanced CT (ceCT) for TNM staging before 68Ga-FAPI PET/CT imaging. PET scans were acquired 60 min after administration of 150-250 MBq of 68Ga-labeled FAP-specific tracers. To characterize 68Ga-FAPI uptake over time, additional scans after 10 or 180 min were acquired in 6 patients. SUVmax and SUVmean values of PDAC manifestations and healthy organs were analyzed. The tumor burden according to 68Ga-FAPI PET/CT was compared with TNM staging based on ceCT and changes in oncologic management were recorded. Results: Compared with ceCT, 68Ga-FAPI PET/CT results led to changes in TNM staging in 10 of 19 patients. Eight of 12 patients with recurrent/progressive disease were upstaged, 1 was downstaged, and 3 had no change. In newly diagnosed PDAC, 1 of 7 patients was upstaged, and the staging of 6 patients did not change. Changes in oncologic management occurred in 7 patients. Markedly elevated uptake of 68Ga-FAPI in PDAC manifestations after 1 h was seen in most cases. Differentiation from pancreatitis based on static imaging 1 h after injection was challenging. With respect to imaging after multiple time points, PDAC and pancreatitis showed a trend for differential uptake kinetics. Conclusion:68Ga-FAPI PET/CT led to restaging in half of the patients with PDAC and most patients with recurrent disease compared with standard of care imaging. The clinical value of 68Ga-FAPI PET/CT should be further investigated.

Quantum discord and the geometry of Bell-diagonal states.

The set of Bell-diagonal states for two qubits can be depicted as a tetrahedron in three dimensions. We consider the level surfaces of entanglement and quantum discord for Bell-diagonal states. This provides a complete picture of the structure of entanglement and discord for this simple case and, in particular, of their nonanalytic behavior under decoherence. The pictorial approach also indicates how to show that discord is neither convex nor concave.

The Brønsted acid catalyzed, enantioselective vinylogous Mannich reaction.

The first catalytic, enantioselective vinylogous Mannich reaction of acyclic silyl dienolates is reported. A second-generation 2,2'-dihydroxy-1,1'-binaphthyl (BINOL)-based phosphoric acid has been developed and further optimized as an enantioselective organocatalyst. Upon protonation of the imines, chiral contact ion pairs are generated in situ and attacked highly diastereoselectively by the nucleophile. gamma-Substituted silyl dienolates that lead to more highly substituted Mannich products with a second stereogenic center in good diastereoselectivity have been employed in these reactions. The reaction path has been elucidated with NMR spectroscopy and mass spectrometry, which suggest that the protic reaction medium found to be optimal in these reactions serves to trap the cationic silicon species as silanol. A crystal structure of a phosphoric acid bound imine was obtained that provides insight into the binding mode and a rationale for the stereochemical course of the reaction.

Infarct in new territory after endovascular stroke treatment: A diffusion-weighted imaging study.

Data on infarcts in new territory (INT) in patients undergoing endovascular stroke treatment for acute large-vessel occlusions are sparse. Aim of this study was to assess the prevalence, risk factors, and clinical relevance of INT. For this purpose, all patients in a single-center prospective registry who underwent endovascular stroke treatment and received pre- and post-interventional diffusion-weighted imaging were included (N = 259). Using an established scoring system, INT were classified according to size (I-III, ≤2 mm, >2 mm ≤20 mm, >20 mm) and likelihood of being related to the intervention (A, high likelihood; B, low likelihood). Additionally, a new type of infarct, that occurred in a territory distal to the occlusion, but was initially not hypoperfused, was defined as an infarct in initially not hypoperfused territory (IINHT). A total of 180 INT and 38 IINHT were observed in 32.8% (N = 85/259) of patients. In most patients, INT were angiographically occult (90.2%), and 13 patients had INT/IINHT larger than 2 cm (type III). Absence of protection during stent-retrieval and a cardio-embolic stroke origin were associated with higher incidence of INT/IINHT, whereas pretreatment with IV tPA showed no association, even when different bolus timing was considered. INT/IINHT were associated with lower rates of functional independence with increasing size type after adjusting for confounders (adjusted Odds Ratio per size group increase 0.63, 95% confidence interval 0.46-0.86). In conclusion, INT and IINHT are not rare, are associated with poor outcome with increasing size, and they may serve as a surrogate endpoint for safety evaluation of new devices and endovascular techniques. Further research on associated factors is warranted.

68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer.

The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods:68Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUVmax and SUVmean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUVmax (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax < 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate (SUV 6-12). SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUVmax < 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6-fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.