Distribution Of Different Subtypes Research Articles

En Face Optical Coherence Tomography Illustrates the Trizonal Distribution of Drusen and Subretinal Drusenoid Deposits in the Macula

PurposeTo analyze the topographic distribution of macular drusen and subretinal drusenoid deposits (SDD) using single capture en face spectral domain optical coherence tomography (SD-OCT) imaging. DesignRetrospective case series. MethodsAnalysis of 33 eyes of 20 patients with evidence of SDD. Structural en face OCT images were reconstructed using a 40µ thick slab positioned from 48 to 88 µm above Bruch's membrane. The Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and a rod/cone density map were overlaid upon the en face OCT images and the distribution of different subtypes of SDD and macular drusen were assessed. ResultsA total of 31 eyes (94%) showed a trizonal distribution pattern of drusen and SDD. Whereas small to large drusen tended to aggregate in the central circle, dot SDD predominated in the inner ring and the inner portion of the outer ring of the ETDRS grid and ribbon SDD localized to the outer ring and outside the ETDRS grid. Of note, drusen colocalized to the region of greatest cone density, while ribbon SDD colocalized to the area of greatest rod density. The dot SDD mapped to the intermediate region with mixed rod and cone representation. ConclusionDot and ribbon subtypes of SDD and macular drusen show a characteristic trizonal distribution. The locations of these lesions co-localize according to the different densities of the cones and rods in the retina and may reflect varying pathophysiological activities of these photoreceptor subtypes.

Apical-basal distribution of different subtypes of spiral ganglion neurons in the cochlea and the changes during aging.

Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and whether the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2-5 months (young), 17-19 months (middle-age), and 28-32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype Ib SGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+ (subtype Ia), CB+ (subtype Ib), CR+CB+ (dual-labeled Ia/Ib), and CR-CB- (subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Ib and dual-labeled Ia/Ib SGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in Ic SGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of Ic SGNs, especially in the base. These findings corroborate the prior study based on RNAscope that SGN subtypes show differential vulnerability during aging. It suggests that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of Ic SGNs in the base may especially impact high-frequency hearing during ARHL.

Characterization of ginsenosides from Panax japonicus var. major (Zhu-Zi-Shen) based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry and desorption electrospray ionization-mass spectrometry imaging

BackgroundPanax japonicus var. major (PJM) belongs to the well-known ginseng species used in west China for hundreds of years, which has the effects of lung tonifying and yin nourishing, and exerts the analgesic, antitussive, and hemostatic activities. Compared with the other Panax species, the chemical composition and the spatial tissue distribution of the bioactive ginsenosides in PJM have seldom been investigated.MethodsUltra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) were integrated for the systematic characterization and spatial tissue distribution studies of ginsenosides in the rhizome of PJM. Considering the great difficulty in exposing the minor saponins, apart from the conventional Auto MS/MS (M1), two different precursor ions list-including data-dependent acquisition (PIL-DDA) approaches, involving the direct input of an in-house library containing 579 known ginsenosides (M2) and the inclusion of the target precursors screened from the MS1 data by mass defect filtering (M3), were developed. The in situ spatial distribution of various ginsenosides in PJM was profiled based on DESI-MSI with a mass range of m/z 100–1500 in the negative ion mode, with the imaging data processed by the High Definition Imaging (HDI) software.ResultsUnder the optimized condition, 272 ginsenosides were identified or tentatively characterized, and 138 thereof were possibly not ever reported from the Panax genus. They were composed by 75 oleanolic acid type, 22 protopanaxadiol type, 52 protopanaxatriol type, 16 octillol type, 19 malonylated, 35 C-17 side-chain varied, and 53 others. In addition, the DESI-MSI experiment unveiled the differentiated distribution of saponins, but the main location in the cork layer and phloem of the rhizome. The abundance of the oleanolic acid ginsenosides was high in the rhizome slice of PJM, which was consistent with the results obtained by UHPLC/QTOF-MS.ConclusionComprehensive characterization of the ginsenosides in the rhizome of PJM was achieved, with a large amount of unknown structures unveiled primarily. We, for the first time, reported the spatial tissue distribution of different subtypes of ginsenosides in the rhizome slice of PJM. These results can benefit the quality control and further development of PJM and the other ginseng species.

Breast Cancer Phenotypes in Africa: A Scoping Review and Meta-Analysis.

Africans have been associated with more aggressive forms of breast cancer (BC). However, there is a lack of data regarding the incidence and distribution of different subtypes on the basis of phenotypic classification. This scoping review and meta-analysis was undertaken to determine the distribution pattern of BC phenotypes (luminal, human epidermal growth factor receptor 2 [HER2]+, and triple-negative breast cancer [TNBC]) across the African region. Four online databases (PubMed, Scopus, ProQuest, and EBSCOhost) were accessed to identify studies published between 2000 and 2022 reporting the representation of receptor status (estrogen receptor, progesterone receptor, and HER2) in African patients with BC. Furthermore, the meta-analysis was carried out using a random-effects model and pooled using the inverse variance method and logit transformation. 95% CI and I2 statistics were calculated using the Clopper-Pearson method to estimate between-study heterogeneity. A total of 2,734 records were retrieved, of which 2,133 were retained for further screening. After the screening, 63 studies were finally selected for the scoping review and meta-analysis. The pooled frequency of luminal, HER2-positive (HER2+), and TNBC was estimated at 56.30%, 12.61%, and 28.10%, respectively. Northern Africa had the highest frequency of the luminal subtype, while West Africa showed higher frequencies of HER2+ and TNBC subtypes. The review also had a representation of only 24 countries in Africa. Our results highlight the disparity in the representation of molecular subtypes among the people in different regions of Africa. There is a need to incorporate routine molecular subtyping into the management of African patients with BC.

Distribution of non-Hodgkin lymphomas across US: Are Hispanics any different from non-Hispanics?

e18619 Background: Non-Hodgkin lymphoma (NHL) encompasses various subtypes that differ in incidence, etiology, clinical features, and survival. NHL subtypes can be divided into B-cell and T-cell lymphomas, when classifying them based on cell of origin. The distribution of NHL subtypes has been known to variate between geographic locations, and always results are reported without classifying them among ethnicities. Hispanics are by now, the largest ethnic minority in US, according to the latest 2020 US Census, and it is of utmost importance to understand variations related to ethnicity. This is to our knowledge, the largest retrospective study comparing NHL frequency of subtypes in Hispanics vs Non-Hispanics. Methods: Data were analyzed on NHL patients in the US and reported to the Surveillance, Epidemiology, and End Results (SEER) 18 database between 2000 and 2018. SEER 18 contains the most comprehensive population-based cancer information in the US, covering approximately 27% of the US population and up to 36% of HI alone. Racial groups analyzed included NH whites and HI whites. Results: There were 366516 patients diagnosed with NHL over the 8-year study period included in our study. Most of these patients belong to the B-cell NHL type, comprising 91% of the group. The distribution of the major subtypes of NHL is shown in the pie charts. We noted differences in the distribution of major NHL subtypes among NH and H. Among the B-Cell NHL subtypes, Hispanics had higher proportions of DLBCL (42% vs. 31%), FL (19% vs. 17%), and Burkitt lymphoma (4% vs. 2%) than NH. On the contrary, a significant difference was found, with a higher presence of CLL/SLL in NH, which was seen in 31% vs. 15% in H. Within the T-Cell NHL subtypes, compared with non-Hispanics, Hispanics had higher proportions of NK/T cell lymphoma (11% vs. 3%) and anaplastic large cell lymphoma (15 vs. 12%) but a lower proportion of mycosis (26% vs. 30) in NH and cutaneous T-cell lymphoma (9% vs. 13%). The rest of the subtypes showed to have similar proportion rates. Conclusions: In conclusion, our study shows evidence of a significant difference in subtype distribution between NH and H patients. The involvement of a complex process in developing NHL and the etiologic heterogeneity among subtypes has been previously described. These differences in subtype distribution across races may be due to geographic location, genetic variants, occupational exposures, infectious conditions, family history, and socioeconomic status. Analyzing and comparing multiple cancer subtypes can provide critical clues for future epidemiological investigations to improve care among our minorities. Due to the growing Hispanic population in the US, it is significantly vital to represent the differences in subtype presentation graphically.

Molecular epidemiology of Kaposi sarcoma virus in Spain.

Since human herpesvirus 8 (HHV-8) infection may be underestimated and HHV-8 subtype circulation in Spain remains unknown, a molecular epidemiologic study is highly desirable. This study aimed to analyse HHV-8 subtype diversity and their distribution in Spain. The study included 142 HHV-8 infected patients. A nested PCR was developed in order to permit Sanger sequencing of HHV-8 K1 ORF directly from clinical samples received at the CNM from 2013 to 2021. Phylogenetic characterization was performed. Genotypes A and C comprised 55.6% and 42.3% of strains. Regarding subtypes, 25.4% of strains were C3, 19.7% were A3, 14.1% were A5, and C2, A1, A4, C1, A2, C7 were 11.3%, 11.3%, 8.5%, 4.2%, 2.1% and 1.4%, respectively. Subtype E1, E2 and B1 were found in only one patient each (0.7%). The Madrid region accounted for 52.1% of patients and showed a significantly different subtype distribution compared to the others (P = 0.018). Subtypes B1, E1, and E2 were observed to appear sporadically, although overall genotypes A and subtype C3 remained the most frequent and unwavering. Subtype A3 presented the highest diversity as displayed by the highest number of clusters in phylogenetic analysis. Non-significant differences in viral loads between genotypes were found, but significantly higher viral loads in subtype C2 compared to subtype C3 was found, while no significant subtype differences were observed between subtypes within genotype A. Infections with HHV-8 were detected in 94 (66.2%) patients without KS and compared to patients with KS non-significant differences in subtype distribution were found. Subtype prevalence and regional distribution followed a similar pattern compared to other western European countries. Our study is the first to report HHV-8 subtypes E1 and E2 circulating in Europe that might be reflective of migration of population from Caribbean countries. Our study suggests that infection by HHV-8 is underestimated, and wider screening should be recommended for risk groups.

Characterizing molecular subtypes of high-risk non-muscle-invasive bladder cancer in African American patients.

We sought to determine whether differences in subtype distribution and differentially expressed genes exist between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC). We performed a retrospective cohort study including 26 patients (14 AAs and 12 EAs) from the University of Texas Medical Branch and the Durham Veterans Affair Health Care System from 2010 to 2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions were performed using the UROMOL classification system. UROMOL racial subtype distributions were similar with class 2a being most common with 10 genes commonly upregulated in AAs compared to EAs including EFEMP1, S100A16, and MCL1 which are associated with progression to muscle-invasive bladder cancer, mitomycin C resistance, and bacillus Calmette-Guérin durability, respectively. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which 5 distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction abilities. We mapped the expression of the 10 genes commonly upregulated by race as a function of the 5 malignant subtypes. This showed borderline (P = 0.056) difference among the subtypes suggesting AAs and EAs may be expected to have different therapeutic responses to treatments for bladder cancer. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3/CDH12 bladder tumor cell population. While premature, gene expression differed between AAs and EAs, supporting potential race-based etiologies for muscle-invasion, response to treatments, and transcriptome pathway regulations.

PTPN11 Gene Mutations and Its Association with the Risk of Congenital Heart Disease.

Congenital heart disease (CHD) is the most common congenital birth defect, with a prevalence of 8.98‰ of all live births in China. PTPN11 has been known to be closely involved in heart developments. In this research, we carried out whole-exome sequencing in nine CHD families and identified eight rare deleterious missense variants of PTPN11 gene in nine probands by stringently filtering criteria. Sanger sequencing of these probands and their unaffected familiar members revealed that six damaging variants were de novo in seven CHD families. Then, targeted sequencing was used to assess the PTPN11 exon variants in 672 sporadic CHD cases and 399 unrelated controls and identified 7 deleterious missense variants in 8 patients. Fisher's exact test reveals a significant association of PTPN11 variations with CHD (P = 0.0289). We observed the distribution of different subtypes in CHD patients with PTPN11 variants and found atrial septal defect (ASD) is a prominent phenotype (58.8%, 10/17). In vitro functional assays revealed that the predicted PTPN11 variants disturb RAS-mitogen-activated protein kinase signaling activity by influencing the phosphorylation level of pathway proteins and increasing the proliferation and migration abilities of cardiomyocytes to different extents. Our findings demonstrated that PTPN11 variants were associated with increased risk of CHD development and may be served as an important susceptible genetic event for CHD, especially the ASD subphenotype.

Is There Any Evidence of Monocytes Involvement in Alzheimer's Disease? A Pilot Study on Human Postmortem Brain.

Background:The role of neuroinflammation has become more evident in the pathogenesis of neurodegenerative diseases. Increased expression of microglial markers is widely reported in Alzheimer’s disease (AD), but much less is known about the role of monocytes in AD pathogenesis. In AD animal models, bone marrow-derived monocytes appear to infiltrate the parenchyma and contribute to the phagocytosis of amyloid-β depositions, but this infiltration has not been established in systematic studies of the human brain postmortem.Objective:In addition to assessing the distribution of different subtypes of microglia by immunostaining for CD68, HLA-DR, CD163, and CD206, we focused on the involvement of C-chemokine receptor type2 (CCR2) positive monocytes during the AD course.Methods:We used formalin-fixed and paraffin-embedded tissue from four vulnerable brain regions (hippocampus, occipital lobe, brainstem, and cerebellum) from neuropathologically characterized AD cases at different Braak stages and age-matched controls.Results:Only singular migrated CCR2-positive cells were found in all brain regions and stages. The brainstem showed the highest number of positive cells overall, followed by the hippocampus. This mechanism of recruitment seems to work less efficiently in the human brain at an advanced age, and the ingress of monocytes obviously takes place in much reduced numbers or not at all.Conclusion:In contrast to studies on animal models, we observed only a quite low level of myeloid monocytes associated with AD pathology. Furthermore, we provide evidence associating early microglial reactions carried out in particular by pro-inflammatory cells with early effects on tangle- and plaque-positive vulnerable brain regions.

Magnetic Resonance Imaging (MRI) Differential Diagnosis of Meningiomas Using ANOVA.

This work explored the diagnostic value of different subtypes of meningiomas under T2WI low signal based on analysis of variance (ANOVA), and the expression differences of Ki67, VEGF, and P73 in different subtypes were analyzed. 67 patients with meningioma confirmed surgically and pathologically in hospital were selected as the research subjects, whose pathological classification occurs with obvious low signal on T2WI. First, the age distribution of the subjects and the distribution of different subtypes were counted. Then, ANOVA was adopted to analyze the MRI imaging signs of patients with different subtypes of meningioma. Finally, the differences of Ki67, VEGF, and P73 proteins and mRNA expression levels in different subtypes were detected via immunohistochemical assay and qPCR. The results showed that the proportion of patients with transitional meningioma was the most, which was 43.28%, while the proportion of patients with meningeal melanoma was the least, which was 7.46%. In patients with transitional meningioma, the MRI images showed mixed signals in different layers. Fibrous MRI images showed hyalinosis and calcification of collagen fibers in the tumor, with low T2WI signal. Sand-shape MRI images showed double low signals. MRI images of meningeal melanoma showed high signal on T1-weighted Imaging (T1WI) and low signal on T2WI. The protein expression and mRNA levels of Ki67 and P73 in transitional meningioma were evidently higher in contrast to those in fibrous meningioma (P < 0.05). The expression level of VEGF protein and mRNA in meningeal melanoma were notably higher in contrast to those in fibro meningioma (P < 0.05). It was revealed that the MRI images of the four subtypes of meningiomas under ANOVA-based T2WI low signal were quite different, and the expressions of Ki67, P73, and VEGF in different subtypes had significant differences. This work provided a reference basis for the preoperative diagnosis, treatment, and prognosis of meningiomas.

Abstract PS18-11: Molecular characterization of advanced breast cancer according to site of metastasis

Abstract Background: There is an increasing need in the clinic to biopsy metastatic disease in patients with advanced breast cancer (ABC). However, the microenvironment and tumor cell biology of breast cancer metastasis is largely unknown. Here, we report a molecular characterization of ABC according to the site of metastasis. Methods: RNA from 184 FFPE metastatic samples were evaluated using the nCounter BC 360 Panel, which includes the expression of 689 BC-related genes and 82 immune-related genes. PAM50 subtypes (Basal-like, HER2-enriched [HER2-E], Luminal A, Luminal B and Normal-like) were also determined. HER2 protein expression was assessed by immunohistochemistry (IHC) in 115 tumor samples, and HER2-low tumors (i.e. 1+ or 2+ and ISH-negative) were identified. Descriptive statistics, significance analysis of microarrays (using False Discovery Rate [FDR]) and logistic regressions were used to identify organ-specific gene expression profiles. Finally, we derived an organ-specific predictor of 209-genes from our cohort, and applied it to the RNAseq-based TCGA PanCancer dataset, which includes 174 glioblastomas multiforme, 424 liver hepatocellular carcinomas and 576 lung adenocarcinomas, among other cancer-types. Results: A single metastatic tumor sample from 184 individual patients with ABC was obtained from bone (18%), liver (17%), skin (15%), brain (12%), breast (13%), lymph nodes (9%), lung (7%), pleura (5%), ovary (2%), muscle (1%) and peritoneum (1%). All PAM50 subtypes were identified across the main organ sites; however, significant differences in subtype distribution were observed (p&amp;lt;0.001). Basal-like subtype was more prevalent in brain, lung and skin metastasis (FDR=0.3%). Unsupervised analysis and principal component analysis revealed brain and liver metastasis as the most distinct. Supervised analysis identified organ-specific genes independently of PAM50 subtype, i.e.: bone-specific genes (WIF1, IBSP, MMP9 and ITGB3); brain-specific genes (CRYAB, SOX10, FGF1 and CHI3L1); liver-specific genes (ALDH1A1, CYP4F3, PCK1, and SFRP2); lung-specific genes (CAV1, WNT5A, PTGS2 and IL6); skin-specific genes (KRT14, KRT5, S100A7 and SERPINB5). Among the organ-specific gene list, 15 (30%) of the 50 PAM50 genes were identified, including up-regulation of FGFR4 in liver, ESR1 in bone, ERBB2 in lung and KRT5 and KRT14 in skin. Regarding ERBB2, a high correlation between ERBB2 mRNA and HER2 IHC expression (0, 1+, 2+ and 3+) was observed (p&amp;lt;0.001). Interestingly, HER2-low disease was identified across all PAM50 subtypes and organ sites, including bone metastasis. Regarding immune-genes, all were found differentially expressed across the main organ sites (FDR&amp;lt;5%) with lung metastasis showing the highest expression (i.e. PDCD1, CD8A, GMZA, IL1B) and liver and brain metastasis the lowest. Finally, the 209-gene organ-specific predictor in PanCancer TCGA identified 96% of glioblastomas multiforme as brain, 98.6% of liver hepatocellular carcinomas as liver and 57.1% of lung adenocarcinoma as lung. Conclusions: The main sites of metastasis in ABC have unique biological features independently of tumor molecular subtype. Our results suggest that treatment strategies based on the site(s) of metastasis should be explored. Citation Format: Fara Brasó-Maristany, Laia Paré, Núria Chic, Olga Martínez-Sáez, Tomás Pascual, Meritxell Mallafré, Blanca González-Farré, Esther Sanfeliu, Débora Martínez, Patricia Galván, Belinda Salinas, Barbara Adamo, Reinaldo Moreno, Maria Vidal, Montserrat Muñoz, Aleix Prat. Molecular characterization of advanced breast cancer according to site of metastasis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-11.

Comparative genomics revealed adaptive admixture in Cryptosporidium hominis in Africa.

Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 (gp60) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C. hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide diversity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses; (2) local anthroponotic transmission underpins the spread of this pathogen in Africa; (3) hybridization occurs between distinct geographical lineages; and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host–parasite coevolution.

Clinicopathological spectrum and treatment outcome of idiopathic steroid-resistant nephrotic syndrome in children at a tertiary care center

BackgroundIdiopathic steroid-resistant nephrotic syndrome (iSRNS) is a common problem in pediatric nephrology. About 10%–20% of children with nephrotic syndrome have iSRNS and almost 50 percent progress to end-stage renal disease. Very few studies have tried to study the histopathological spectrum, correlate clinical features, renal biopsy patterns and treatment outcome in children presenting with iSRNS in India. In this study, we compared the histopathologic distribution of different subtypes of glomerular morphologic patterns in iSRNS and the clinical and biochemical parameters at the time of diagnosis and outcome of patients after immunosuppressive therapy. MethodsIt is a retrospective cross-sectional study involving review of records of all children with iSRNS presenting to our pediatric nephrology OPD who underwent renal needle biopsy and followed-up for a period of atleast six months post biopsy. Histopathological subtypes were correlated with clinical features (viz. age of onset, gender, oliguria, microscopic hematuria, hypertension, serum creatinine at presentation, serum total protein, serum albumin, 24 h urine protein, persistent proteinuria after 12 weeks of calcineurin inhibitor therapy, and progress to end stage renal disease (ERSD), if any, outcome. ResultIt was found that minimal change disease (MCD) was overall the most common cause of iSRNS. These patients have a significantly greater incidence of remission with immunosuppression as compared with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy subgroup. ConclusionKidney biopsy is of prognostic value in children with iSRNS. The prognosis of children with SRNS owing to MCD is much better than with other nephropathy.

Differences in clinicopathologic features and subtype distribution of invasive breast cancer between elderly and non-elderly women.

This study aimed to investigate the clinicopathologic features and subtype distribution of invasive breast cancer in elderly women (≥70 years of age). This retrospective study of 1,130 women compared the clinicopathologic characteristics and subtype distribution of invasive breast cancer in elderly (≥70 years) versus non-elderly (<70 years) women. Tumors were classified into five distinct subtypes based on the immunohistochemistry status of estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2). The two patient groups did not differ significantly regarding ER and HER2 status. Breast cancers in elderly women were more likely to have negative PR status (40.4% vs. 32.6%, P=0.033) and low Ki67 expression (62.0% vs. 54.4%, P=0.047) than those in non-elderly women. Elderly women were less likely to undergo axillary lymph node dissection and axillary surgery (P<0.001). Consequently, unknown node status was more common in elderly women than non-elderly women (11.1% vs. 1.4%, respectively, P<0.001), while node involvement was less common in elderly women than non-elderly women (26.9% vs. 37.7%, respectively, P<0.001). There was no significant difference in the distribution of subtypes between the two groups. Breast cancers in elderly women were less frequently node positive and more frequently PR negative and with low Ki67 expression than those in non-elderly women. Moreover, there was no difference in subtype distribution between the two age groups.

Effects of Alemtuzumab on (Auto)antigen-Specific Immune Responses.

Alemtuzumab (anti-CD52 mAb) leads to a long-lasting disease activity suppression in patients with relapsing forms of multiple sclerosis (MS). In this study, we examined the change of the immune cell repertoire and the cellular reactivity after treatment with alemtuzumab. We analyzed the number of IFN-γ–secreting cells in presence of several peptides which had been eluted from the central nervous system (CNS) of MS patients and are possible targets of autoreactive T cells in MS. The patients showed a stabilized disease activity measured in clinical parameters and lesion formation after the treatment. We detected a reduction of the number of IFN-γ–secreting cells in the presence of every tested self-antigen. The number of IFN-γ–secreting cells was also reduced in the presence of non-self-antigens. We also found a clear change in the immune cell repertoire. After an almost complete depletion of all lymphocytes, the cell specificities showed different reconstitution patterns, resulting in different cell fractions. The percentage of CD4+ T cells was clearly reduced after therapy, whereas the fractions of B and NK cells were elevated. When we evaluated the number of IFN-γ–secreting cells in relation to the number of present CD4+ T cells, we still found a significant reduction. We conclude that the reduction of IFN-γ–secreting cells by alemtuzumab is not only due to a reduction of the CD4+ T cell fraction within the peripheral blood mononuclear cell (PBMC) compartment but might also be caused by functional changes or a shift in the distribution of different subtypes in the CD4+ T cell pool.

Diversity and Distribution of Escherichia coli in Three Species of Free-Ranging Australian Pinniped Pups

Anthropogenic activities and pollution are impacting marine environments globally. This has resulted in increasing numbers of human-associated phylotypes of Escherichia coli, an indicator of faecal contamination, being found in both aquatic environments and upper trophic marine mammals that are considered sentinels for marine health. The objective of this study was to determine the presence and diversity of E. coli in pups of three species of free-ranging pinnipeds in Australia. Faecal samples (n = 964) were collected between 2016 and 2019 from Australian sea lion (Neophoca cinerea), Australian fur seal (Arctocephalus pusillus doriferus) and long-nosed fur seal (Arctocephalus forsteri) pups from eight breeding colonies extending along the Southern Australian coast. E. coli were isolated from 842 (87.3%) samples and molecular screening was applied to assign isolates to E. coli phylotypes and sub-types. The human associated E. coli phylotype B2 was the most frequently isolated in all species at seven of the eight colonies, with 73.7% of all E. coli isolates belonging to this phylotype. Phylotype distribution did not differ significantly within or across species, breeding colonies or breeding seasons. Further analysis of B2 isolates into sub-types showed a significant difference in sub-type distribution across breeding seasons at two colonies (Seal Rocks and Cape Gantheaume). The predominance of the B2 phylotype could indicate that all colonies are exposed to similar levels of anthropogenic pollution. This widespread occurrence of the human-associated E. coli phylotypes highlights the imperative for ongoing monitoring and surveillance of microbes in both the marine environment and sentinel species.

ABCL-119: Epidemiology and Subtype Distribution of Non-Hodgkin Lymphoma Neoplasms from Two Institutions in Lebanon Between 1984 and 2019

Context: Patients diagnosed with Non-Hodgkin Lymphoma (NHL) have been the subject of many epidemiologic studies done at the time that aimed to explain the distribution of different subtypes among different countries. Because there is unpublished data and only a small percentage of all newly Lebanese cancer cases are diagnosed in tertiary hospitals, there is constant need of studies to supplement the literature. Objective: To establish a descriptive status of NHL histological subtypes distribution in Lebanon, thus identifying the most common types, knowing that the literature is poor regarding the distribution of lymphoid malignancies, particularly NHLs in Lebanon. Design: Multicenter retrospective cohort data analysis. Setting: Two Lebanese medical centers. Patients or other participants: Patients aged above 18 years, diagnosed with NHL between January 1984 and March 2019 inclusive, were included in the study. Interventions: 699 medical files were extracted from the hospital archives and reviewed. The baseline characteristics of the patients and the disease at presentation were collected. Histological classification was based on the Working Formulation (WF) and the World Health Organization (WHO) classification systems for patients diagnosed before and after 2001, respectively, whereas staging was based on the Ann Arbor system. Disease status and response to chemotherapy regimens were monitored with imaging studies. Results: The mean age at diagnosis was 53.52 ± 17.46 years in the studied population, with 380 (54.4%) males and 319 (45.6%) females. The mean age for males was 53.56 ± 17.95 years, and for female 53.48 ± 16.87 years (p=0.954). B-cell lymphoma (BCL) accounted for 86.3% while T-cell neoplasms accounted for 13.7%. The most common subtype was diffuse large B-cell lymphoma (54%) followed by follicular lymphoma (17.2%). Mantle cell lymphoma represents 3% of all BCL and small lymphocytic lymphoma comprised less than 2%. MALT and Burkitt lymphomas represented 3% and 1.7%, respectively. 36.5% of the patients had extranodal disease at diagnosis. High-grade tumor represented 80.1% with 33.1% stage IV disease. Conclusions: These observations indicate that the epidemiological patterns of NHLs in Lebanon were slightly comparable to Western countries. Aggressive lymphomas account for the majority of NHLs in Lebanon.

Immunohistochemical profile and distribution of Non-Hodgkin and Hodgkin lymphoma - An experience in a medical college hospital in Tamil Nadu

AbstractContext: The subtype distribution of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) shows distinct pattern across geographic regions. This study analyzes the subtype distribution of lymphomas based on the WHO 2017 Classification using immunohistochemistry (IHC) and also investigates the IHC profile of various lymphomas. Subjects and Methods: Fifty consecutive cases of lymphoma diagnosed in the department of pathology in a medical college hospital were included in the study. The cases were subcategorized using panels of IHC based on the light microscopic findings. Results: The ratio of NHL to HL was 4.5:1. B-NHL formed 78.5% (n = 32), while T-cell NHL formed 21.5% (n = 9). Among the B-NHL cases, small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) (34.4%) was the most common, followed by diffuse large B-cell lymphoma, NOS (DLBCL NOS) (31.2%), follicular lymphoma (FL) (25%), and then by Burkitt's lymphoma (BL) constituting 9.4%. Peripheral T-cell lymphoma, NOS (PTCL NOS) (14.1%) (n = 6) was the most common T-cell NHL, followed by angioimmunoblastic T-cell lymphoma (4.8%), and then by lymphoblastic lymphoma (T-LL) (2.4%). Among Hodgkin lymphomas, mixed cellularity (MC) accounted for 55.6% (n = 5), lymphocyte depleted type (LD) being 22.2%, while nodular lymphocyte predominant and lymphocyte rich type each constituted 11.1%. Conclusion: SLL/CLL was the most common lymphoma reported in the study followed by DLBCL which is different from the other Indian studies where DLBCL was most common. CD5 expression was noted in 21% of FLs. PTCL-NOS constituted the most common T-cell lymphoma and MC, the most frequent subtype of classical HL. Further replication studies including larger sample size will be needed to understand the difference in subtype distribution in our population.

Epidemiology of HTLV-1 Infection and ATL in Japan: An Update.

Adult T-cell leukemia-lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection that often occurs in HTLV-1-endemic areas, such as Japan, the Caribbean islands, Central and South America, Intertropical Africa, and the Middle East. In Japan, the nationwide estimation of the number of HTLV-1 carriers was at least 1.08 million in 2006–2007. Furthermore, in 2016, the nationwide annual incidence of newly infected with HTLV-1 was first estimated to be 3.8 per 100,000 person-years based on the age-specific seroconversion rates of blood donors in almost all areas of Japan. The incidence rate was three times higher in women than in men, and it was estimated that at least 4,000 new HTLV-1 infections occur yearly among adolescents and adults in Japan. As well known that HTLV-1 infection alone is not a sufficient condition for ATL to develop. To date, a variety of molecular abnormalities and host susceptibilities have been reported as candidate progression factors for the development of ATL in HTLV-1-carriers. In particular, quite recently in Japan, a variety of immunosuppressive conditions have been recognized as the most important host susceptibilities associated with the development of ATL from HTLV-1-carrier status. Furthermore, in 2013–2016 in Japan, a new nationwide epidemiological study of ATL was conducted targeting patients newly diagnosed with ATL in 2010–2011, from which the most current knowledge about the epidemiological characteristics of Japanese patients with ATL was updated as follows: (1) continuing regional unevenness of the distribution of people with HTLV-1, (2) further aging, with the mean age at diagnosis being 67.5 years, (3) declining M/F ratio, (4) increase of the lymphoma subtype, (5) sex differences in subtype distribution, (6) age differences in subtype distribution, and (7) comorbidity condition. In particular, 32.2% of ATL patients had comorbid malignancies other than ATL. However, the number of deaths due to ATL in Japan has been relatively stable, at around 1,000 patients annually, without significant decline from 1999 to 2017. Because the current epidemiological evidence about HTLV-1 and ATL is insufficient, further epidemiological studies are required.

The role of disease duration and severity on novel clinical subtypes of Parkinson disease

IntroductionOne of the latest subtyping systems of Parkinson disease (PD) identifies motor severity, cognitive dysfunction, dysautonomia, and rapid eye movement behavior disorder as key features for phenotyping patients into three different subtypes (i.e., mild motor-predominant, diffuse-malignant and intermediate). Since PD subtypes are clinically most relevant if they are mutually exclusive and consistent over-time, we explored the impact of disease stage and duration on these novel subtypes. MethodsOne-hundred-twenty-two consecutive patients, with a disease duration ranging from 0 to 20 years, were allocated as suggested into these three subtypes. The relationship between either disease duration or stage, as measured by the Hoehn and Yahr staging, and subtype allocation was explored. ResultsSignificant differences in subtype distribution were observed across patients stratified according to either disease duration or staging, with the diffuse-malignant subtypes increasing in prevalence as the disease advanced. Both disease duration and staging were independent predictors of subtype allocation. ConclusionsThese novel PD subtypes are significantly influenced by disease duration and staging, which might suggest that they do not represent mutually exclusive disease pathways. This should be taken into account when attempting correlations with putative biomarkers of disease progression.