Delirium caused by topical administration of cyclopentolate for cataract surgery in mild cognitive impairment due to Alzheimer's disease: A case report

Rationales:Cholinergic modification by anticholinergic medication can produce adverse effects in central nervous system (CNS) and cyclopentolate is an antimuscarinic agent widely used for ophthalmologic management. We demonstrate a rare case of hyperactive delirium caused by topical administration of cyclopentolate in a patient with amnestic mild cognitive impairment (MCI) due to Alzheimer''s disease (AD).Patient concerns:A 74-year-old man showed acute confusion after preparation for cataract operation in day surgery clinic. The patient became confused and agitated after instillation of topical cyclopentolate drop into the eye and the symptoms persisted over several hours.Diagnosis:Previously the patient had been diagnosed with amnestic MCI with the finding of bilateral medial temporal atrophy on brain magnetic resonance imaging. ¹⁸F-flutemetamol positron emission tomography scan demonstrated multifocal amyloid deposition in the brain.Interventions:The patient was closely observed with the supportive management.Outcomes:The patient began to recover 5 h after the onset of symptoms and the cognitive function was reverted to previous state within 24 h.Lessons:It is well known that several drugs with anticholinergic effects used in perioperative periods make the patients susceptible to delirium, but even the topical administration of cyclopentolate for cataract surgery also produce adverse CNS effects in a vulnerable patient who is diagnosed with MCI due to AD in this case.     

Longitudinal assessment of amyloid-beta deposition in initially amyloid-negative non-demented individuals with [11C]-PIB PET imaging

This study aimed to assess the longitudinal changes in amyloid beta (Aβ) deposition in cortical regions with [11C]-PIB PET in initially amyloid-negative non-demented subjects and evaluate whether amyloid-negative subjects convert to amyloid-positive.Sixteen cognitively normal (CN) and 7 mild cognitive impairment (MCI) subjects (aged 60–75 years), who were amyloid-negative at baseline, underwent 60-minute dynamic [11C]-PIB PET and cognitive assessment over 5.0 to 9.4 years of a long follow-up, and the apolipoprotein-E (APOE) genotype was assessed. Regions of interest were defined in the bilateral cortex on coregistered MRI. Quantitative analysis of [11C]-PIB was performed using the distribution value ratio (DVR). Longitudinal changes in global and regional PIB DVRs were evaluated in the same regions, and the annual rate of change in the PIB DVR was calculated.Seven (30.4%) of 23 initially amyloid-negative non-demented subjects converted to globally amyloid-positive (global PIB DVR ≥1.40) over a follow-up of 6.5 ± 1.4 years (converter). The global PIB DVR in converters increased from 1.22 ± 0.07 at baseline to 1.63 ± 0.15 (n = 7, P < .01) at last follow-up, and an annual increase of global PIB DVR was 0.057 ± 0.019/year (n = 7, P < .01). In contrast, the global PIB DVR in the remaining 16 subjects was 1.15 ± 0.07 at baseline and did not change over a follow-up period (stable). The APOE ε4 allele was present in 4 (57.1%) of the 7 converters, differing from 2 (12.5%) of 16 stable subjects (Fisher''s exact test, P < .05). Three amyloid-negative MCI subjects had an annual increase in global PIB DVR above 0.061/year and became positive at 2.8 ± 0.5 years of follow-up, which was faster than 5.0 ± 2.0 years in 4 CN subjects. The regional PIB DVR that increased early above the regional positivity threshold was most frequently found in the right lateral temporal cortex (71.4%), followed by the left frontal cortex (41.8%).Our results suggest that the initially amyloid-negative CN and MCI subjects, especially with APOE ε4, can become globally amyloid-positive over a longer time, based on early regional Aβ deposition in the lateral temporal cortex and/or frontal cortex.     

Predictive Accuracy of Amyloid Imaging for Progression From Mild Cognitive Impairment to Alzheimer Disease With Different Lengths of Follow-up: A Meta-analysis

In the past decade, amyloid deposition has been shown to begin many years before the clinical symptoms of dementia in mild cognitive impairment (MCI) due to Alzheimer disease (AD). Longitudinal studies with different follow-up durations have suggested that ¹¹C-Pittsburgh compound B positron emission tomography (¹¹C-PIB-PET) may play a role in stratifying patients with MCI into risk levels for developing AD. However, the predictive accuracy of amyloid imaging for the progression from MCI to AD with different follow-up durations has not yet been systematically evaluated. A formal systematic evaluation of the sensitivity, specificity, and other properties of ¹¹C-PIB-PET was performed.This study aimed to systematically review and meta-analyze published data on the diagnostic performance of ¹¹C-PIB-PET for predicting conversion to AD in patients with MCI and to determine whether long-term follow-up has a positive effect on predictive accuracy.Relevant studies were systematically identified through electronic searches, which were performed in MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (Ovid SP), and LILACS (Bireme). The methodological quality of each study was assessed by QUADAS-2. Sensitivities and specificities of ¹¹C-PIB-PET in individual studies were calculated, and the studies underwent meta-analysis with a random-effects model. A summary receiver-operating characteristic curve (SROC) was constructed with the Moses-Shapiro-Littenberg method. Pooled estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), diagnostic odds ratio (DOR), and the SROC curve of each subgroup were determined. Heterogeneity was tested, and potential sources for heterogeneity were explored by assessing whether certain covariates significantly influenced the relative DOR.Eleven eligible studies consisting of a total of 352 patients with MCI at baseline were included. Overall, the studies were of moderate-to-high methodological quality. The sensitivity and specificity of ¹¹C-PIB-PET for predicting conversion to AD ranged from 83.3% to 100% and 41.1% to 100%, respectively, with pooled estimates of 94.7% (95% confidence interval [CI]: 89.8%–97.7%) and 57.2% (95% CI: 50.1%–64.2%), respectively. Moderate heterogeneity was observed for specificity between the included studies (I² = 42.1%). The pooled estimates for the long-term follow-up subgroup were 95.5% sensitivity (95% CI: 84.5%–99.4%) and 72.4% specificity (95% CI: 59.1%–83.3.8%), whereas the pooled estimates for the short-term follow-up subgroup were 94.4% sensitivity (95% CI: 88.2%–97.9%) and 51.0% specificity (95% CI: 42.6%–59.5%). Homogeneity in each subgroup was significantly higher than that of the included studies, and most diagnostic indicators in the long-term follow-up subgroup were far superior to those in the short-term follow-up subgroup or the entire group.Not all of the methodological quality scores of studies included in this systematic review were high.Current evidence suggests that prolongation of the follow-up duration tended to yield greater accuracy of ¹¹C-PIB-PET for predicting the progression from MCI to AD. In particular, the specificity, which reflects the exploratory nature of the use of amyloid imaging to identify the process of MCI to AD, was improved with a longer follow-up period.     

Usefulness of 123I-BMIPP and 201TlCl nuclide scintigraphy in evaluation of myocarditis in patients with polymyositis or dermatomyositis

To investigate the usefulness of ¹²³I-BMIPP/²⁰¹TlCl scintigraphy for evaluating the presence of myocarditis in patients with polymyositis (PM) or dermatomyositis (DM).We performed a retrospective study of 26 patients diagnosed with new-onset active PM/DM who underwent ¹²³I-BMIPP/²⁰¹TlCl scintigraphy between 01 April 2010 and 20 March 2015. We determined the ¹²³I-BMIPP/²⁰¹TlCl ratio and grouped the patients according to presence or absence of a mismatch. We evaluated the relationship between mismatch and the laboratory and echocardiographic findings.Mismatch was found in 13 (50%) patients. There was no statistically significant difference in age, cardiac troponin T, myoglobin, myosin light chain, aldolase levels, E wave/A wave ratio, right ventricular systolic pressure between the mismatch and non-mismatch groups. Left ventricular end-diastolic and end-systolic dimensions were significantly greater in the mismatch group (45.0 vs 42.5 mm, P =  < .01 and 29.5 mm vs 25.0 mm, P < .01). Left ventricular ejection fraction was significantly lower in the mismatch group (63.5% vs 71.5%, P = .04). Significant inverse correlation (r = −0.44, P = .03) was observed between left ventricular ejection fraction and mismatch ratio.The use of ¹²³I-BMIPP/ ²⁰¹TlCl scintigraphy may be considered for evaluating myocarditis in patients with PM/DM.     

Conversion of mild cognitive impairment to dementia in elderly subjects: a preliminary study in a memory and cognitive disorder unit

Prevalence and incidence of predementia syndromes vary as a result of different diagnostic criteria, as well as different sampling and assessment procedures. Mild cognitive impairment (MCI) is thought to be a prodromal phase of dementia and therefore highly predictive of subsequent conversion. The aim of our study was to investigate the risk of conversion to dementia for different MCI subtypes diagnosed according to standardized and recently revised criteria (amnestic; impairment of memory plus other cognitive domains; nonamnestic). Participants were recruited among the 2,866 patients referring to the Memory and Cognitive Disorders Unit of the Local Health Unit of Bologna, Maggiore Hospital, between October 2000 and February 2006. In this preliminary study we analyzed data from 52 elderly outpatients with a diagnosis of MCI and a mean follow-up of 1.21+/-0.61 years (range 0.23-3.10 years). Mean age was 72.8+/-6.6 years, males were 61.5%. Mean baseline mini mental state examination (MMSE) score was 27.1+/-1.5. There were 15 incident cases of dementia (28.8%), with Alzheimer's disease (AD) accounting for 53.3% of all cases, AD with cerebrovascular disease for 33.4% and fronto-temporal dementia for 13.3%. Overall rate of conversion was 23.8 per 100 person-years. During the same follow-up period, 53.8% of participants remained stable and 17.3% reverted to normal. Rates of conversion for the specific MCI subtypes were 38 per 100 person-years for amnestic MCI, 20 per 100 person- years for non-amnestic MCI, and 16 per 100 person-years for memory plus other cognitive domains MCI. With respect to non-converters, converters were generally older (76.1+/-4.2 vs. 71.5+/-7.0 years, p=0.021), had a lower MMSE score (26.4+/-1.66 vs. 27.4+/-1.4, p=0.035) and a higher prevalence of atrophy at neuroimaging (73.7% vs. 42.4%, p=0.047). Moreover, with respect to non-converters, converters tended to have higher serum high density lipoprotein (HDL) levels, and lower serum folate levels. No difference was observed for the other study variables, included MCI subtype. Our findings suggest that the current definitions for MCI subtypes, particularly those referring to individuals with multiple or non-amnestic cognitive impairment, include a substantial number of individuals who may not progress to dementia. The possible role of cortical atrophy and low folate in the conversion from MCI to dementia could have important implications, because both conditions are easily identifiable. Moreover, low folate status is potentially amenable to therapeutic options. Although discouraging with respect to the clinical usefulness of currently available MCI criteria, our results raise the possibility that defining a protocol of multiple clinical risk factors may be useful in identifying MCI individuals at increased risk of conversion.     

Predictive value of metabolic activity detected by pre-operative 18F FDG PET/CT in ampullary adenocarcinoma

In ampullary adenocarcinoma cases, the clinical effects of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) have not yet been well-studied, unlike other prognostic factors that have been reported till date. This study aimed to investigate the clinical impact of maximum standardized uptake value (SUVmax) in predicting the prognosis of ampullary adenocarcinoma.Thirty-eight patients who underwent pre-operative ¹⁸F-FDG PET/CT and curative-intent resection of ampullary adenocarcinoma at Pusan National University Hospital (Pusan, South Korea) between 2008 and 2017 were retrospectively analyzed in this study. We evaluated the clinicopathologic outcomes according to the SUVmax using univariate and multivariate Cox proportional hazard regression analyses and receiver operating characteristic analysis to arrive at a cutoff value.Lymph node metastasis was detected in 9 patients, and 15 patients experienced a recurrence during the follow-up period. Among 38 patients, 33 showed an increased FDG uptake by the main tumor. SUVmax of 4.55 was selected as a significant independent predictive factor for patient survival along with poor tumor differentiation and high neutrophil-to-lymphocyte ratio in multivariate analysis (P = .016, hazard ratio = 5.040). Patients with SUVmax under 4.55 exhibited significantly longer overall survival than the rest (<4.55 vs ≥4.55), and the 5-year overall survival was 82.8% versus 57.4% (P = .049).SUVmax of 4.55 on ¹⁸F-FDG PET/CT could be a predictive factor for tumor biology and long-term survival in patients with ampullary adenocarcinoma. Nevertheless, considering the cost aspect and its limited prognostic effect, this study seems to require more patient and multicenter studies.     

Conversion pattern and predictive factor of mild cognitive impairment in elderly Koreans

ObjectiveWe aimed to understand conversion characteristics of mild cognitive impairment (MCI) in elderly Koreans.MethodsWe analyzed clinical data of 760 individuals who participated in a two-year follow-up study. Neuropsychological assessments and clinical examination were conducted in the follow-ups. Logistic regression model was used to estimate predictive risk factors of MCI conversion.ResultThe participants at baseline (n = 760) represented 462 cognitively normal individuals (60.8%), 286 individuals with MCI (37.6%), and 12 individuals with dementia (1.6%). Among the cognitively normal individuals (n = 462), 108 (23.4%) progressed to MCI during the two-year follow-up period, including 92 with amnestic mild cognitive impairment (aMCI; 19.9%) and 16 with non-amnestic mild cognitive impairment (non-aMCI; 3.5%). Interestingly, 3.7% of participants with aMCI converted to non-aMCI, while 45.5% of participants with non-aMCI converted to aMCI. Moreover, a higher proportion of non-aMCI (27.3%) reverted to a cognitively normal state, compared to aMCI participants (18.6%), indicating that non-amnestic cognitive impairment is more unstable than amnestic cognitive impairment, and probably converges toward aMCI. Additionally, we found that weight loss was associated with incident MCI and future MCI. Weight loss was negatively correlated with Clinical Dementia Rating (p = 0.005), and significantly associated with a higher risk of MCI conversion from a cognitively normal state (OR = 1.10, 95% CI: 1.00–1.21, p = 0.042).ConclusionThis study supports that non-amnestic MCI is prone to converge toward amnestic MCI, and the elderly people with weight loss are at risk for developing cognitive decline.     

Incidence and computed tomography findings of lenvatinib-induced pancreatobiliary inflammation: A single-center,retrospective study

In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ± standard deviation, 69.8 ± 9.4 years, range: 39–84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016–September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.     

Efficacy of 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane positron emission tomography combined with 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of early Parkinson disease: A protocol for systematic review and meta analysis

Background:Parkinson''s disease (PD) has a high incidence in the elderly, and the late stage seriously affects the daily life of the patients. Most of the initial symptoms of PD are not obvious or atypical, which brings difficulties to the early diagnosis. Replacement therapy and neuroprotection after early diagnosis can significantly improve the prognosis and quality of life of patients. More and more evidence shows that ¹¹C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane positron emission tomography ( ¹¹C-CFT PET) combined with ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) can effectively improve the accuracy of early diagnosis. However, there is no consistent conclusion at present. The purpose of this study is to evaluate the efficacy of ¹¹C-CFT PET combined with ¹⁸F-FDG PET in the diagnosis of early PD.Methods:We will search 7 electronic databases (PubMed, EMBASE, Web of Science, Cochrane library, PsycINFO, AMED, Scopus), ongoing trials and grey literature to collect related randomized controlled trials and will use Review Manager Software 5.2 and STATA Software 16.0 for analysis and synthesis.Results:We will integrate the existing randomized controlled trials to evaluate the value of ¹¹C-CFT PET combined with ¹⁸F-FDG PET in the diagnosis of early PD.Conclusion:Our study may prove that ¹¹C-CFT PET combined with ¹⁸F-FDG PET can effectively diagnose early PD.Registration number:International Prospective Register of Systematic Reviews (PROSPERO): CRD42020203442.     

Outcome of Hepatitis E Virus Infection in Patients With Inflammatory Arthritides Treated With Immunosuppressants: A French Retrospective Multicenter Study

The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs.All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire.From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2–20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3–55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed.Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure.Hepatitis E virus (HEV) infection is ubiquitous and is due to a small nonenveloped virus with a positive-sense, single-stranded RNA genome. The virus was discovered in the 1980s. Four major genotypes representing a single serotype have been recognized: HEV1 and HEV2 are restricted to humans and transmitted via contaminated water in developing countries; HEV3 and HEV4 infect humans, pigs, and other mammalian species and are responsible for sporadic cases of autochthonous HEV infection in Western countries. In this setting, HEV infection causes acute disease, mainly in middle-aged and older men. Such an infection might be mistaken for drug-induced liver injury.¹ Acute HEV infection might range in severity from subclinical to fulminant, in particular in the risk group of pregnant women, whose death rate in the course of HEV infection could approach 15% to 20%.^2,3 However, in the rest of the population and in immunosuppressed patients,⁴ acute HEV infection is usually asymptomatic. Thus, in a French study of kidney transplant recipients, acute HEV infection was asymptomatic in 14 of 16 patients (87.5%).⁵ Some extrahepatic manifestations of HEV infection were reported. Kamar et al⁶ reported neurologic disorders among 126 patients with HEV infection: inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Hematological disorders, notably acute immune thrombocytopenia,⁷ were also reported.Recent efforts to develop and standardize the HEV serology led to data showing increasingly recognized cases of HEV infection. HEV infection might correspond to about 10% of cases of non-A–D acute viral hepatitis in Western countries among nontravelers.⁸Another feature of HEV is its ability to cause chronic infection, defined as a persistent infection lasting >6 months, usually in severely immunocompromised patients.⁹ In 3 well-known circumstances of immunodeficiency—AIDS, kidney or liver transplantation, and haematological malignancies—HEV infection can develop into chronic infection.^10,11 In liver transplant recipients,¹² chronic infection with HEV can result in HEV-related cirrhosis.¹³ However, little is known about the incidence and severity of acute and chronic HEV infection in patients with inflammatory rheumatic diseases. We therefore addressed this issue of HEV infection in patients receiving treatment for inflammatory arthritides.     

Biomarkers involved in evaluation of platelets function in South-Eastern Romanian patients with hematological malignancies subtypes

At present, various researches presented how subtypes of hematological malignancies are related to stages of the immune response, because the activated immune system represents a promising form in cancer treatment. This study explores the relationship between the adaptive immune system (T cells), and the coagulation system (platelets, platelet membrane glycoproteins, platelets derivate microparticles) which seems to play an important role in host immune defense of patients with acute myeloblastic leukemia (AML) or B cell lymphoma (BCL), 2 of the most common hematological malignancies subtypes.Blood samples (n = 114) obtained from patients with AML or BCL were analyzed for platelet membrane glycoproteins (CD42b, CD61), glycoprotein found on the surface of the T helper cells (CD4⁺), protein complex-specific antigen for T cells (CD3⁺), platelet-derived microparticles (CD61 PMP) biomarkers by flow cytometry, and hematological parameters were quantified by usual methods.In patients with AML, the means of the percentage of the expressions of the molecules on platelet surfaces (CD61 and CD42b, P < .01; paired T test) were lower as compared to both control subgroups. The expression of cytoplasmic granules content (CD61 PMP) had a significantly higher value in patients with AML reported to controlling subgroups (P < .01; paired T test), which is suggesting an intravascular activation of platelets.The platelet activation status was presented in patients with low stage BCL because CD61 and CD42b expressions were significantly higher than control subgroups, but the expression of CD 61 PMP had a significantly decreased value reported to control subgroups (all P < .01; paired T test). T helper/inducer lineage CD4⁺ and T lymphoid lineage CD3⁺ expressions presented significant differences between patients with AML or low stage BCL reported to control subgroups (all P < .01; paired T test).Platelet–lymphocyte interactions are involved in malignant disorders, and CD61, CD42b present on platelet membranes, as functionally active surface receptors mediate the adhesion of active platelets to lymphocytes, endothelial cells, and cancer cells.     

A pilot study on EORTC or PERCIST for the prediction of progression-free survival with nivolumab therapy in advanced or metastatic gastric cancers: A STROBE-compliant article

Recent breakthrough results from immune checkpoint inhibitors (ICIs) have paved the way to a new era of cancer immunotherapy, and have thus led to a paradigm shift of cancer treatment. In particular, inhibition of the antiprogrammed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with ICI, including nivolumab and pembrolizumab, has been emerging as a novel treatment strategy for advanced gastric cancers. An accurate noninvasive assessment of the response to ICI is important for the management of patients with advanced or metastatic gastric cancer.To examine whether the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumors (PERCIST) are valuable for predicting progression-free survival (PFS) in patients with advanced or metastatic gastric cancers treated with nivolumab.Six patients with advanced or metastatic gastric cancers who underwent ¹⁸F-FDG-PET/computed tomography (CT) scans before, and from 2 to 6 months after initiation of nivolumab therapy between September 2017 and August 2019, were evaluated retrospectively. The correlation between tumor progression and EORTC or PERCIST was assessed with the Fisher''s exact test. The PFS was assessed with the Kaplan–Meier method.Two patients were alive without progression, and the remaining 4 patients exhibited tumor progression. Two patients without progression were classified as partial metabolic response (PMR) patients based on EORTC or PERCIST, while the other 4 patients with progression were classified as progressive metabolic disease (PMD) patients based on EORTC (P = .067), or stable metabolic disease (SMD) patients, or PMD patients based on PERCIST (P = .067).The mean and median PFS of all patients was 12.7 months (95% confidence interval [CI], 4.9–20.4 months) and 5 months (95%CI, 4.0–11.0 months). Two EORTC or PERCIST PMR patients showed significantly longer median PFS compared with 4 non-PMR patients (not reached vs 4.0 months, P = .044). Three PERCIST PMR or SMD patients also showed significantly longer median PFS compared with 3 PMD patients (not reached vs 4.0 months, P = .022). These results suggest that EORTC or PERCIST has the potential to predict PFS of patients with advanced or metastatic gastric cancers treated by nivolumab and further studies are needed to determine its value in larger study populations.     

18F-FDG PET/CT imaging in the diagnosis of drug-induced lung disease and pulmonary infection in lymphoma

Objective:Lymphoma is a hematological disease with high prevalence. Multi-cycle chemotherapy (CHT) or local radiotherapy is applied usually; however, adverse events have been reported, such as drug-induced lung disease (DILD). Positron emission tomography/computed tomography (PET/CT) is often used to evaluate the lesion, treatment effect, and prognosis of lymphoma. We investigated DILD and pulmonary infection (PI) after multi-cycle CHT in lymphoma patients, to identify DILD and PI, provide guidance for later treatment for them.Methods:In all, 677 patients diagnosed with lymphoma and who underwent CHT were included. These patients underwent ¹⁸fluorodeoxyglucose (¹⁸F-FDG) PET/CT before and after CHT at Shandong Cancer Hospital (affiliated with Shandong University) between April 2015 and November 2019. Fifty patients developed DILD, 41 patients had lung infections; lesion characteristics were analyzed based on clinical characteristics, laboratory examinations, and PET/CT imaging.Results:Among the 677 lymphoma patients, there were 50 cases of DILD, with an incidence rate of 7.4%. PET/CT showed an elevated ¹⁸fluorodeoxyglucose uptake lung background, septal thickening and reticulation, multiple ground glass-like shadows, and grid-shaped blur shadows, which were more common in the lung periphery and under the pleura. The maximum standardized uptake value in the lung was 2.45 ± 0.52. Pulmonary infections occurred in 41 patients, and the maximum standardized uptake value was 4.05 ± 1.42. Age, sex, CHT cycle, Ann-Arbor stage, and lymphocyte levels were not significantly different between DILD and PI patients. Leukocyte and neutrophils showed significant differences; the PI patients had increased laboratory indexes of leukocyte and neutrophils. The mean number of CHT cycles was 4 cycles for DILD and PI.Conclusions:PET/CT imaging has high sensitivity and detection rates for primary and metastatic lymphoma lesions. DILD mostly occurs in the middle and late stages of CHT. Laboratory tests and PET/CT can evaluate the lesions and treatment effects, and provide guidance for subsequent treatment plans for patients.     

Prognostic value of metabolic parameters measured by pretreatment dual-time-point 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with intrahepatic or perihilar cholangiocarcinoma: A STROBE study

The purpose of this study was to determine the glucose metabolism at delay phase measured by pretreatment dual-time-point ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/ computed tomography (CT) provides prognostic information independent of well-known prognostic factors in patients with intrahepatic or perihilar cholangiocarcinoma (ICC or PCC).From July 2012 to December 2017, 55 patients (men 27, women 28, mean age 68 ± 11 years) with pathologically proven ICC or PCC were enrolled in this retrospective study. The dual-time-point ¹⁸F-FDG PET/CT as part of a staging workup was performed in all patients. The patient''s data includes age, sex, serum CA19-9, presence of LN or distant metastasis, early SUVmax (early maximum standardized uptake value [eSUV]), delay SUVmax (delay maximum standardized uptake value [dSUV]), retention index of SUVmax (percent change of maximum standardized uptake values [ΔSUV]), neutrophil to lymphocyte ratio (NLR) and histopathology including pCEA, p53, Ki-67 index. The analysis of the relationship between metabolic parameters and survival was done using the Kaplan–Meier curve and Cox proportional hazards regression model.Median survival for all patients was 357 days. Median early and delay SUVmax was 5.2 (range: 2.0–21.4) and 6.5 (range 2.7–24.5), respectively. The overall survival was found to be significantly related to eSUV, dSUV, ΔSUV, age, serum CA19-9 and NLR in univariate analysis. In multivariate analysis, dSUV (P = .014, 95%CI; 1.30–10.7, HR 3.74) and ΔSUVmax (P = .037, 95%CI; 1.05–6.12, HR 2.5) were independent factors of overall survival. Kaplan–Meier curve analysis clearly showed the significant difference of overall survival between 2 groups (high eSUV, low eSUV + high ΔSUV vs low eSUV and ΔSUV, P < .001) among the comparisons of the SUV parameters on FDG PET. In the receiver operating characteristic analysis using combinations of the SUV parameters, the 2 groups [eSUV + ΔSUV (P = .0001, area under the curve [AUC] 0.68) and dSUV + ΔSUV (P = .0002, AUC 0.71)] showed significantly larger AUC than the other groups applying eSUV or dSUV alone (AUC 0.61 and AUC 0.68).dSUV and ΔSUV on pretreatment dual-time-point ¹⁸F-FDG PET/CT can be useful parameters in the prediction of survival in patients with ICC or PCC.     

What are the predictors for recurrence of Crohn's disease after surgery?

Surgical resection is an unavoidable part of the current treatment options for Crohn''s disease (CD), and more than half of patients develop recurrence. The aim of this study was to investigate the predictors for recurrence in the long-term follow-up of CD patients after surgery.Medical records of consecutive CD patients who were operated on between January 2003 and January 2015 were retrospectively analyzed. Data including demographic and clinical characteristics of the patients were recorded. Recurrence was evaluated based on the Crohn''s Disease Activity Index or endoscopic findings.The majority of 112 patients were males (n = 64, 57.1%), and 61 (54.4%) of them were active smokers. The median follow-up was 113 (range: 61–197) months. Disease recurrence occurred in 16 (14.3%) patients at a median of 13.5 months. The endoscopic recurrence rate was 8% (n = 9) at 1 year, 12.5% (n = 14) at 5 years, and 13.4% (n = 15) at 10 years. One (0.9%) patient underwent colonoscopic balloon dilatation at 1 year, and 7 (6.3%) patients needed re-resection at a median of 36 months. The age of the patient at the time of diagnosis (P = .033), penetrating disease behavior (P = .011), intra-abdominal abscess (P = 0.040) and, concomitant fistula and intra-abdominal abscess (P = .017) were associated with disease recurrence.Our study results suggest that the patients’ age at the time of diagnosis, penetrating disease, intra-abdominal abscess, and concomitant fistula and abscess are the risk factors for CD recurrence after surgery.     

Functional assessment of coronary artery stenosis by Doppler derived absolute and relative coronary blood flow velocity reserve in comparison with 99mTc MIBI SPECT

OBJECTIVE—To determine the relation between the relative and absolute coronary blood flow velocity reserve (CFVR) compared with the results of ^99mTc MIBI single photon emission computed tomography (SPECT).
METHODS—In 37 patients with one vessel disease, ^99mTc MIBI SPECT was performed before angioplasty, two to three weeks after angioplasty, and at six months' follow up. CFVR was measured distal to the stenosis (dCFVR) as well as in a reference coronary artery before angioplasty, immediately after angioplasty, and at late follow up. Relative CFVR (rCFVR) was calculated as the ratio between dCFVR and CFVR measured in the reference coronary artery. The optimal thresholds for reversible perfusion defects were calculated using receiver operating characteristic curves.
RESULTS—The agreement for the full range of coronary artery stenosis (n = 107, mean (SD) diameter stenosis 48 (28)%, range 0-98%) between dCFVR (cut off value 1.9) and rCFVR (cut off value 0.65) with ^99mTc MIBI SPECT was 81% and 85%, respectively. In intermediate lesions (n = 49, diameter stenosis range 30-75%) the agreement between dCFVR (cut off value 2.0) and ^99mTc MIBI SPECT was 72%, which increased to 78% using the rCFVR (cut off value 0.65).There was a strong linear relation between dCFVR and rCFVR (r = 0.93, p < 0.0001).
CONCLUSIONS—A best cut off value for dCFVR of 1.9 corresponds with a best cut off value of 0.65 for rCFVR, within the full range of coronary narrowings. Intracoronary blood flow velocity analysis could obviate the need for additional myocardial perfusion scintigraphy in the majority of patients.


Keywords: intracoronary Doppler; relative coronary blood flow velocity reserve; ^99mTc MIBI single photon emission computed tomography     

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 ¹¹C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) ¹¹C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on ¹¹C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 ¹¹C-choline-PET/CT scans, respectively. In 27 cases (48.2%), ¹¹C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ± 3.21, 5.95 ± 3.96, 6.73 ± 5.04, and 7.91 ± 3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.     

Regional distribution of 2-deoxy-2[18F]-fluoro-D-glucose for metabolic imaging using positron emission tomography

Radiopharmaceutical availability is one of the reasons dissemination and growth of clinical PET imaging remains problematic. A regional cyclotron-radiopharmacy facility for the production of the positron emitting radionuclide 2-deoxy-2[¹⁸F]-fluoro-D-glucose (FDG), has been operational for over 2 years and supplies this radiopharmaceutical to five camera facilities, four distant and one on-site. The RDS 11 MeV cyclotron is capable of dual bombardment of targets yielding 60 GBq (1600 mCi) of F-18 in a 90 minute period. F-18 labelled FDG is produced by an automated synthesis module yielding 22.2 GBq (600 mCi) FDG. The PET radiopharmacy is required to perform extensive quality assurance activities including a number of tests to insure final product and safety. [¹⁸F]FDG is shipped in unit dose vials, 6 ml, two per shielded container, meeting Department of Transportation (DOT) specifications (43 × 43 cm cubes, styrofoam packing, 22 lb. lead shield). This adheres to regulations requiring no more than 200 millirem per hour (mR/Hr) exposure at the container surface, and 10 mR/hr at a distance of 1 meter. Total transport time, utilizing private air and ground couriers, to distant facilities is approximately 100–120 minutes. Based on patient scheduling and protocol used, allowing 45–60 minutes between dose administrations, and availability of 22.2 GBq (600 mCi), 20–22 unit doses can be supplied, divided and shipped in a number of ways. The regional-commercial distribution of PET radiopharmaceuticals, specifically [¹⁸F]FDG, is feasible. This provides availability of metabolic imaging at sites distant to radiopharmaceutical production.     

Diagnostic value and potential clinical significance of duodenal lipoma based on computed tomography imaging data

Background:To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings.Methods:Clinicopathological and CT data from 57 patients, who were diagnosed with duodenal lipoma at the first affiliated Hospital of Zhengzhou University (Zhengzhou, China) between June 2014 and March 2019, were retrospectively reviewed. Data collected included location and size of the tumor, morphological manifestations (shape, density, boundary), concomitant diseases, pathology and gastroscopy results, and follow-up. Follow-up was performed via telephone, and surgical patients were followed-up for recurrence, metastasis and tumor size, and morphological changes. The follow-up period was up to January 2019.Results:Of the 57 patients with duodenal lipoma, contrast-enhanced scanning was performed in 7 cases. The tumor was located in the descending duodenum in 33 cases, the ascending in 4 cases, the horizontal in 16 cases, and the bulb in 4 cases. Mean tumor size was 13.0 ± 5.8 mm. CT morphological features of the tumor were as follows: tumor shape, round, quasi-round, or oval (n = 42); long strip (n = 3); nodular (n = 2); triangular (n = 1); and irregular lobulated (n = 9). Among the 57 patients, tumor density was homogeneous in 52 cases, inhomogeneous in 4 cases, and nodular with calcification in 1 case. The tumor boundary was classified as clear and with no capsule. Diseases concomitant with the tumor were as follows: gastritis (n = 23), gastric adenocarcinoma (n = 1), and gastric lymphoma (n = 1). Esophageal disease was found in 16 cases, including reflux esophagitis (n = 12) and esophageal cancer (n = 4). There were 13 cases of gallbladder and biliary disease, including cholecystolithiasis and cholecystitis (n = 9), common bile duct disease (n = 2), colorectal cancer (n = 4), lung cancer (n = 2), duodenal carcinoma with obstruction (n = 1), and ureteral space narrowing (n = 1).Conclusion:CT was an effective, non-invasive method for diagnosis of duodenal lipoma. CT imaging could clearly discern location, size, shape, and nature of duodenal lipomas. Duodenal lipoma can be associated with digestive tract inflammatory diseases and tumors in different locations, and its diagnosis is potentially valuable for their prevention and treatment.     

Efficacy of Oral Etoposide in Pretreated Metastatic Breast Cancer: A Multicenter Phase 2 Study

No standard chemotherapy has been defined for metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes. A multicenter phase 2 study was conducted to evaluate the safety and efficacy of oral etoposide in patients with MBC.Eligible patients were treated with repeated cycles of oral etoposide (60 mg/m²/d on days 1–10, followed by 11 days of rest). The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate, clinical benefit rate (CBR), and toxicity profiles.Seventy-five women with MBC were enrolled at 10 centers in China. Seven (9.3%) patients achieved partial response (PR) and 29 (38.7%) had stable disease (SD). Nine patients (12%) had SD for >24 weeks and the CBR was 21.3% (16/75). The median PFS was 4.5 (range, 1.3–7.7) months. Of the 38 patients who received ≥3 regimens prior to this study, 2 (5.3%) had PR and 3 (7.9%) had SD for >24 weeks, with a CBR of 13.2%. The reported grade 3/4 adverse events included leukopenia (13.3%, n = 10), neutropenia (17.9%, n = 14), anemia (2.7%, n = 2), vomiting (2.6%, n = 2), and alopecia (1.3%, n = 1).Oral etoposide was effective and well tolerated in Chinese women with pretreated MBC.