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Peptide GAM immunoadsorption in anti-PLA2 R positive autoimmune membranous nephropathy. The PRISM trial

J Clin Apher. 2021 Nov 9. doi: 10.1002/jca.21949. Online ahead of print.

ABSTRACT

Membranous nephropathy associated with anti-PLA2 R autoantibody is a significant cause of nephrotic syndrome worldwide. Treatment remains empiric with a significant side-effect burden despite an increase in our understanding of the disease. We studied the effect of selectively removing this pathogenic autoantibody using immunoadsorption in adult patients with biopsy proven anti-PLA2 R membranous nephropathy. This was a multicenter, single-arm prospective clinical trial carried out in the United Kingdom. Twelve patients underwent five consecutive sessions of peptide GAM immunoadsorption with 12 months follow-up. Primary outcome was anti-PLA2 R titer at week 2. Secondary outcomes were safety and tolerability of therapy, antibody profile, and change in proteinuria, renal excretory function, serum albumin, total immunoglobulin, and quality of life at weeks 12, 24, and 52. Patients were also stratified by the presence or absence of the high-risk allele (heterozygous or homozygous for HLA-DQA1*05). Median pretreatment anti-PLA2 R was 702.50 U/mL, 1045.00 U/mL at week 2 (P-value .023) and 165.00 U/mL at week 52 (P-value .017). The treatment was well tolerated and safe. Two patients required rescue immunosuppression during the follow-up period. There was a significant improvement in serum albumin with a median at baseline of 20.50 g/L rising to 25.00 g/L at week 52 (P-value <.001). There was no statistical difference over the follow-up period in proteinuria or renal function. Patients in possession of a high-risk allele saw improvement in anti-PLA2 R titers, possibly representing a cohort more likely to benefit from immunoadsorption. Immunoadsorption therapy is a safe treatment and well-tolerated treatment in anti-PLA2 R positive autoimmune membranous nephropathy.

PMID:34753218 | DOI:10.1002/jca.21949

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Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) for the detection of bone, lung, and lymph node metastases in rhabdomyosarcoma

Cochrane Database Syst Rev. 2021 Nov 9;11:CD012325. doi: 10.1002/14651858.CD012325.pub2.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and can emerge throughout the whole body. For patients with newly diagnosed RMS, prognosis for survival depends on multiple factors such as histology, tumour site, and extent of the disease. Patients with metastatic disease at diagnosis have impaired prognosis compared to those with localised disease. Appropriate staging at diagnosis therefore plays an important role in choosing the right treatment regimen for an individual patient. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a functional molecular imaging technique that uses the increased glycolysis of cancer cells to visualise both structural information and metabolic activity. 18F-FDG-PET combined with computed tomography (CT) could help to accurately stage the extent of disease in patients with newly diagnosed RMS. In this review we aimed to evaluate whether 18F-FDG-PET could replace other imaging modalities for the staging of distant metastases in RMS.

OBJECTIVES: To determine the diagnostic accuracy of 18F-FDG-PET/CT imaging for the detection of bone, lung, and lymph node metastases in RMS patients at first diagnosis.

SEARCH METHODS: We searched MEDLINE in PubMed (from 1966 to 23 December 2020) and Embase in Ovid (from 1980 to 23 December 2020) for potentially relevant studies. We also checked the reference lists of relevant studies and review articles; scanned conference proceedings; and contacted the authors of included studies and other experts in the field of RMS for information about any ongoing or unpublished studies. We did not impose any language restrictions.

SELECTION CRITERIA: We included cross-sectional studies involving patients with newly diagnosed proven RMS, either prospective or retrospective, if they reported the diagnostic accuracy of 18F-FDG-PET/CT in diagnosing lymph node involvement or bone metastases or lung metastases or a combination of these metastases. We included studies that compared the results of the 18F-FDG-PET/CT imaging with those of histology or with evaluation by a multidisciplinary tumour board as reference standard.

DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and methodological quality assessement according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We analysed data for the three outcomes (nodal involvement and lung and bone metastases) separately. We used data from the 2 × 2 tables (consisting of true positives, false positives, true negatives, and false negatives) to calculate sensitivity and specificity in each study and corresponding 95% confidence intervals. We did not consider a formal meta-analysis to be relevant because of the small number of studies and substantial heterogeneity between studies.

MAIN RESULTS: Two studies met our inclusion criteria. The diagnostic accuracy of 18F-FDG-PET/CT was reported in both studies, which included a total of 36 participants. We considered both studies to be at high risk of bias for the domain reference standard. We considered one study to be at high risk of bias for the domain index test and flow and timing. Sensitivity and specificity of 18F-FDG-PET/CT for the detection of bone metastases was 100% in both studies (95% confidence interval (CI) for sensitivity was 29% to 100% in study one and 40% to 100% in study two; 95% CI for specificity was 83% to 100% in study one and 66% to 100% in study two). The reported sensitivity of 18F-FDG-PET/CT for the detection of lung metastases was not calculated since only two participants in study two showed lung metastases, of which one was detected by 18F-FDG-PET/CT. Reported specificity was 96% in study one (95% CI 78% to 100%) and 100% (95% CI 72% to 100%) in study two. The reported sensitivity for the detection of nodal involvement was 100% (95% CI 63% to 100% in study one and 40% to 100% in study two); the reported specificity was 100% (95% CI 78% to 100%) in study one and 89% (95% CI 52% to 100%) in study two.

AUTHORS’ CONCLUSIONS: The diagnostic accuracy of 18F-FDG-PET/CT for the detection of bone, lung, and lymph node metastases was reported in only two studies including a total of only 36 participants with newly diagnosed RMS. Because of the small number of studies (and participants), there is currently insufficient evidence to reliably determine the diagnostic accuracy of 18F-FDG-PET/CT in the detection of distant metastases. Larger series evaluating the diagnostic accuracy of 18F-FDG-PET/CT for the detection of metastases in patients with RMS are necessary.

PMID:34753195 | DOI:10.1002/14651858.CD012325.pub2

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Is Coronal Restoration a Predictor of Posttreatment Apical Periodontitis?

Eur J Dent. 2021 Nov 9. doi: 10.1055/s-0041-1735909. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the posttreatment apical periodontitis (AP) in endodontically treated teeth through a multivariate approach and to analyze the relative importance of quality and type of coronal restoration as predictors of periapical disease.

MATERIALS AND METHODS: The present study sample was drawn within 2-year period from the 1,072 consecutive patients older than 18 years, first time attending the Dental Clinic of the Clinical Hospital Center Rijeka, Croatia. A total of 1,350 endodontically treated teeth were included in the study. For each tooth, the periapical status, root filling quality, intracanal post, separated file presence, marginal bone loss, and quality and type of coronal restoration were recorded.

STATISTICAL ANALYSIS: Chi-square tests were used to analyze the variations in the periapical status, quality of root canal filling, and quality of coronal restoration in different tooth types. The effect of explanatory variables on periapical status was explored using univariate and multivariate logistic regression models. The outcome variable was set as the presence versus absence of AP in the tooth.

RESULTS: Multivariate logistic regression analysis revealed statistically significant associations and increased risk for AP presence in molars (odds ratio [OR] = 2.15; p < 0.001), teeth positioned in mandible (OR = 1.49; p = 0.007), teeth with short length of root filling (OR = 4.08; p < 0.001), overfilled teeth (OR = 2.99; p = 0.001), and teeth with inadequate density of root filling (OR = 4.14; p < 0.001). Considering variables related to coronal restoration, neither coronal restoration type nor quality was found to be predictive for posttreatment AP. Merely, the presence of intracanal post significantly increased the odds of AP presence (OR = 1.57; p = 0.009).

CONCLUSION: The results of the present study did not indicate that type or quality of coronal restoration may be predictors of posttreatment AP. Periapical disease was significantly associated with molars, mandibular teeth, substandard quality of root fillings, and intracanal post presence.

PMID:34753188 | DOI:10.1055/s-0041-1735909

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A Retrospective Study on the Etiological Factors of Orofacial Pain in a Malaysian Sample

Eur J Dent. 2021 Nov 9. doi: 10.1055/s-0041-1735443. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to examine the etiological factors of orofacial pain for patients attending dental clinic at Faculty of Dentistry, International Islamic University Malaysia (IIUM).

MATERIALS AND METHODS: This retrospective study examined the data of 248 patients who have attended dental clinic at Faculty of Dentistry IIUM and suffering from different types of orofacial pain. The data were collected from January 2010 to November 2018. The etiologies of pain were classified according to International Classification of Orofacial Pain, 1st edition (2020).

STATISTICAL ANALYSIS: The association of age and gender with orofacial pain was evaluated by using the Chi-square test, and the significance level was set to 0.05.

RESULTS: Collected data showed that orofacial pain has different etiologies among the patients attending the dental clinic at Faculty of Dentistry IIUM. Moreover, a statistically significant relation was observed between orofacial pain toward gender and different age group.

CONCLUSION: The findings proposed that the orofacial pain has a variety of etiological factors with the highest percentage of orofacial pain attributed to disorders of dentoalveolar and anatomically related structures among patients attending dental clinic at Faculty of Dentistry IIUM.

PMID:34753187 | DOI:10.1055/s-0041-1735443

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Pigmented Oral Lesions: A Multicenter Study

Eur J Dent. 2021 Nov 9. doi: 10.1055/s-0041-1735790. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to determine the prevalence and clinical features of pigmented oral lesions from Thailand.

MATERIALS AND METHODS: Biopsy records of the Department of Oral Pathology, Chulalongkorn University, Department of Oral Diagnosis, KhonKaen University, Department of Oral Biology and Oral Diagnostic Sciences, Chiangmai University, Department of Stomatology, Prince of Songkla University, and Rangsit University were reviewed for oral pigmented lesions diagnosed during 1999 to 2019. Demographic data were culled from the biopsy records. Ages of the patients were subdivided into 10-year intervals. Locations of the lesions were classified as gingiva, labial/buccal mucosa, palate, floor of the mouth, tongue, as well as the combination of sites. Data were analyzed by descriptive statistics using SPSS version 20.0.

RESULTS: Of the 47,175 accessioned cases, 241 cases (0.51%) were diagnosed in the category of pigmented oral lesions. The age of the patients ranged from 1 month to 88 years with the mean ± standard deviation = 38.74 ± 20.96 years. Regarding gender, 172 patients (71.37%) with pigmented lesions were females, while 69 patients (28.63%) were males. The female-to-male ratio was 2.49:1. The majority of the pigmented lesions were encountered at the gingiva (29.88%) followed by labial/buccal mucosa (26.97%), palate (14.94%), lip (10.79%), alveolar mucosa (9.54%), and others (7.88%), respectively. The three most common pigmented oral lesions in the present study were nevus (39.83%), followed by melanotic macule (28.63%) and amalgam tattoo (17.43%), respectively.

CONCLUSIONS: The most common pigmented oral lesion in the present study is nevus. Demographic data of the patients in the present study are in accordance with previous studies with minor differences. Even though pigmented lesions of the oral cavity constitute a small portion of the oral pathology biopsies, accurate diagnosis is important since there is an overlap in clinical appearance of benign pigmented lesions and melanoma.

PMID:34753186 | DOI:10.1055/s-0041-1735790

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Using negative control outcomes and difference-in-differences to estimate treatment effects in an entirely treated cohort: the effect of ivacaftor in cystic fibrosis

Am J Epidemiol. 2021 Nov 9:kwab263. doi: 10.1093/aje/kwab263. Online ahead of print.

ABSTRACT

When an entire cohort of patients receives a treatment it is difficult to estimate the treatment effect in the treated because there are no directly comparable untreated patients. Attempts can be made to find a suitable control group, (e.g. historical controls), but underlying differences between the treated and untreated can result in bias. We show how negative control outcomes (NCO) combined with difference-in-differences analysis can be used to assess bias in treatment effect estimates and obtain unbiased estimates under certain assumptions. Causal diagrams and potential outcomes are used to explain the methods and assumptions. We apply the methods to UK Cystic Fibrosis (CF) Registry data to investigate the effect of ivacaftor, introduced in 2012 for a subset of the CF population with a particular genotype, on lung function and days receiving intravenous antibiotics (IV days). We consider two NCOs: outcomes measured in the pre-ivacaftor period and outcomes in individuals ineligible for ivacaftor due to their genotype. Ivacaftor was found to improve lung function in year one (~6.5 increase in FEV1%), was associated with reduced lung function decline (~0.5 decrease in annual FEV1% decline, though confidence intervals include 0), and reduced the rate of IV days (~60% over 3 years).

PMID:34753177 | DOI:10.1093/aje/kwab263

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Effectiveness of Vapocoolant Spray on Venipuncture Pain in Young Male Donors: A Randomized Controlled Trial

J Infus Nurs. 2021 Nov-Dec 01;44(6):339-345. doi: 10.1097/NAN.0000000000000443.

ABSTRACT

The aim of this single-blinded, randomized controlled study was to determine the effectiveness of vapocoolant spray in reducing pain related to venipuncture in young, healthy male blood donors. The participants were separated into 2 groups by randomization. The donors in the control group (n = 44) were not given any intervention during the blood collection process. Vapocoolant spray was applied to the donors in the vapocoolant spray group (n = 44). The pain score was 1.90 ± 1.47 for the vapocoolant spray group and 3.23 ± 2.21 for the control group, and the difference between the groups was found to be statistically significant (P = .02). The study result showed that the use of vapocoolant spray for pain management is an effective method of reducing pain related to venipuncture during the process of blood donation in young male donors.

PMID:34753153 | DOI:10.1097/NAN.0000000000000443

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Micro-Embolic Signals and Dissection: Association or Causation for Stroke? A Systematic Review and Meta-Analysis

Cerebrovasc Dis. 2021 Nov 9:1-8. doi: 10.1159/000519553. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Although the mechanism of stroke in cervical artery dissection (CAD) has been hypothesized to be embolization rather than hemodynamic compromise, there are a limited number of studies supporting this hypothesis. Detection of micro-embolic signals (MESs) using transcranial Doppler (TCD) helps in understanding the mechanism in these patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke outcomes in patients with acute stroke/TIA secondary to dissection.

METHODS: A comprehensive literature search was conducted for studies before January 26, 2021, in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies were identified that used TCD to detect MES in stroke/TIA patients secondary to CAD. Pooled prevalence was calculated. Entire statistical analysis was conducted in R version 3.6.2.

RESULTS: Eleven studies involving 112 patients (50 MES+, 62 MES-) were included in our meta-analysis. The pooled prevalence of MES among acute stroke/TIA patients secondary to dissection was 46.0% (95% CI 26.0-67.0%). The presence of MES was associated with an increased risk of early ischemic recurrence in patients with CAD. We could not estimate the functional outcome and mortality associated with the presence of MES due to the scarcity of data.

CONCLUSIONS: Our meta-analysis showed 46% prevalence of MES in the studies which looked at acute stroke/TIA secondary to CAD using TCD. This finding supports the assumption that embolism may be a major cause of stroke in patients with dissection although this could be determined only in a small population.

PMID:34753137 | DOI:10.1159/000519553

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Associations between Intra-Pancreatic Fat Deposition, Pancreas Size, and Pancreatic Enzymes in Health and after an Attack of Acute Pancreatitis

Obes Facts. 2021 Nov 9:1-13. doi: 10.1159/000519621. Online ahead of print.

ABSTRACT

INTRODUCTION: Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes.

METHODS: This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders.

RESULTS: A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (β = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (β = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (β = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (β = -10.533, p = 0.024 in the most adjusted model).

CONCLUSION: Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.

PMID:34753126 | DOI:10.1159/000519621

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Differentiation between normal and tumor mammary glands with depth-resolved attenuation coefficient from optical coherence tomography

Biomed Phys Eng Express. 2021 Nov 9. doi: 10.1088/2057-1976/ac37ca. Online ahead of print.

ABSTRACT

Optical coherence tomography (OCT) is a well-established imaging technology for high-resolution, cross-sectional imaging of biological tissues. Imaging processing and light attenuation coefficient estimation allows to further improve the OCT diagnostic capability. In this paper we use a commercial OCT system, Telesto II-1325LR from Thorlabs, and demonstrate its ability to differentiate normal and tumor mammary mouse glands with the OCT attenuation coefficient. Using several OCT images of normal and tumor mammary mouse glands (n=26), a statistical analysis was performed. The attenuation coefficient was calculated in depth, considering a slope of 0.5 mm. The normal glands present a median attenuation coefficient of 0.403 mm-1, comparatively to 0.561 mm-1obtained for tumor mammary glands. This translates in an attenuation coefficient approximately 39 % higher for tumor mammary glands when compared to normal mammary glands. The OCT attenuation coefficient estimation eliminates the subjective analysis provided by direct visualization of the OCT images.

PMID:34753120 | DOI:10.1088/2057-1976/ac37ca