Non-classical Groups Research Articles

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BackgroundPrimary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.MethodsThis prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.ResultsAt follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.ConclusionFor PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

CHARACTERIZING PUBLIC CLASSICAL SCHOOLS: PROMOTIONAL LANGUAGE IN MISSION AND VISION STATEMENTS

Little is known about primary and secondary public classical schooling in the United States despite a history of over 30 years and the increasing influence of classical organizations on individual states’ curriculum. The lack of information is ascribed to the lack of salient literature on the implementation of the classical approach in public school contexts. To begin to characterize classical public schooling, the researcher conducts a comparative content analysis of mission and vision statements from 47 classical and 50 non-classical public schools. Pointwise mutual information (PMI), an association metric, is used to meaningfully differentiate the promotional language employed by the classical and non-classical school groups to appeal to prospective families in a competitive public education market. Results indicate that classical public schools advertise curricular emphases on challenging academics and character formation, demonstrating an intriguing connection to the available literature on classical education despite the focus of that literature on private and religious contexts for learning.

Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes.

Clinical implications of unilateral primary aldosteronism (PA) histopathology remain to be determined in various ethnic populations. We examined the histopathology of unilateral PA using CYP11B2 immunostaining in relation to clinical phenotypes and postsurgical outcomes. Patients consecutively operated for unilateral PA from 2010 to 2020 at 3 tertiary hospitals in South Korea were retrospectively enrolled. Adrenals with solitary aldosterone-producing adenomas and/or dominant aldosterone-producing nodules were classified as the classical and the others as the nonclassical groups. The classical group was subdivided into mixed or solitary group according to whether other aldosterone-producing lesions coexist or not. Of the 240 cases, 124 were solitary, 86 mixed, and 30 nonclassical. Baseline serum potassium concentration was lower in the solitary group than the mixed or nonclassical group. Plasma aldosterone concentration after saline loading was the highest in the solitary group (median 31.65 ng/dL), followed by the mixed group (median 25.40 ng/dL), and the lowest in the nonclassical group (median 14.20 ng/dL). Solitary and mixed groups showed higher lateralization indices and lower contralateral indices than the nonclassical group. The contralateral index was lower in the solitary group than the mixed group. At 6 to 12 months after adrenalectomy, fewer antihypertensive medications were required for the solitary and mixed groups than the nonclassical group. The solitary group, followed by the mixed group, was associated with more severe hyperaldosteronism and more suppressed aldosterone production from the contralateral side than the nonclassical group. Histopathologic phenotypes were related to the clinical manifestations and may suggest postoperative prognosis.

Clinical outcomes of patients with advanced NSCLC with different EGFR exon 19 deletion subtypes treated with first-line tyrosine kinase inhibitors.

e21034 Background: Epidermal growth factor receptor (EGFR) exon 19 deletion (Ex19del) in non-small cell lung cancer (NSCLC) consists of many subtypes, and their sensitivity to tyrosine kinase inhibitors (TKIs) has not been clearly defined. This study aimed to investigate the clinical outcomes of advanced NSCLC patients with different EGFR ex19del subtypes treated with different TKIs. Methods: We retrospectively analyzed stage IIIB-IV NSCLC patients with EGFR Ex19del and first-line TKIs therapy. E746_A750del was defined as classic group, and the others as non-classic group, which was further divided into subgroups according to deletion with or without insertion, starting codon or length of deletion. The primary endpoint was progression free survival (PFS). Results: There were 17 Ex19del subtypes identified in 101 patients. The frequency of E746_A750del was 64.4% (65/101), and the top three frequent non-classic subtypes were L747_T751del (6.9%, 7/101), L747_P753delinsS (5.9%, 6/101) and E746_S752delinsV (5.0%, 5/101). In all patients, the median PFS (mPFS) of first-line TKIs in classic and non-classic groups were 14.3 months (m) and 19.3 m ( p > 0.05). In non-classic group, the mPFS in deletion with insertion (delins) and without insertion subgroups were 25.3 m and 11.2 m; in deletion starting with E746 and with other codon subgroups were 29.7 m and 19.3 m; and in deletion length of 15 nucleotides (n) and of other length subgroups were 11.2 m and 25.3 m. The mPFS of these non-classic subgroups were not statistically different with that of classic group ( p > 0.05). In all patients, the mPFS of first-line therapy with the 1st, 2nd and 3rd generation TKIs were 17.4 m, 15.6 m and 20.5 m, respectively ( p＞0.05); in classic group, the mPFS were 14.3 m, 16.9 m and 20.5 m, respectively ( p＞0.05). However, in non-classic delins subgroup (29.7 m, 15.6 m and 11.9 m) and in deletion length of ≥18 n subgroup (25.3 m，12.3 m and 11.9 m), the 1st generation TKIs had an insignificantly longest mPFS ( p＞0.05). When resistant to 1st or 2nd generation TKIs, patients in classic group showed a trend of higher incidence of T790M mutation than non-classic group (72.0% vs 43.8%, p = 0.070). In multivariant analysis, pleural metastasis (PM) had interaction with Ex19del grouping, warranting stratification analysis. In patients without PM, the mPFS of first-line TKIs in classic group was significantly shorter than non-classic group (13.8 m and 29.7 m, p = 0.026). However, in patients with PM, the mPFS of classic group was numerically longer than non-classic group (16.9 m and 11.7 m, p > 0.05), with the shortest mPFS in non-classic without insertion subgroup, and in non-classic with 15 n deletion subgroup. Conclusions: In advanced NSCLC patients with EGFR Ex19del, the efficacy of first-line TKIs therapy was affected by the presence of pleural metastasis, Ex19del subtypes and different generation of TKIs.

The classification of kleinian groups of hausdorff dimension at most one

Abstract In this paper, we provide the complete classification of Kleinian group of Hausdorff dimensions less than 1. In particular, we prove that every convex cocompact Kleinian group of Hausdorff dimension < 1 is a classical Schottky group. This upper bound is sharp. The result implies that the converse of Burside’s conjecture [4] is true: all non-classical Schottky groups must have Hausdorff dimension $\ge1$. The upper bounds of Hausdorff dimensions of classical Schottky groups has long been established by Phillips–Sarnak [14] and Doyle [8]. The proof of the theorem relies on the result of Bowen [3] and Hou [10].

Imbalance of Circulating Monocyte Subsets in Subjects with Newly Emerged and Recurrent Hospital-Acquired Pneumonia.

Hospital-acquired pneumonia (HAP) is one of the most common diseases in the intensive care unit, where the development of disease is closely related with the host immune response. Monocytes play an important role in both innate and adaptive immune system. We aimed to investigate the changes of circulating monocyte subsets in subjects with HAP to explore its value in monitoring HAP. In total, 60 HAP patients and 18 healthy individuals were enrolled in this study. Human monocyte subsets are classified into 3 groups: nonclassical (NC), intermediate (ITM), and classical (CL). Also, programmed death ligand 1 (PD-L1) expression on circulating monocyte subsets was measured by flow cytometry. Data showed that the ratio of NC, ITM, and CL among monocytes was comparable between HAP patients and healthy controls (P > .05). There was a remarkable imbalance of NC and CL in newly emerged HAP compared to healthy controls (P < .05), subsequently reaching normalization in recurrent HAP (P > .05). Furthermore, although PD-L1 was seemly constitutively expressed by NC, ITM, and CL groups regardless of disease status, it was noted that PD-L1 was dominantly expressed in the CL group (P < .05). Given distinct PD-L1 expression, a shift of CL/NC in newly emerged HAP would constitute an inhibitory anti-pathogen immune response. Normalization of circulating monocyte subsets on recurrence of HAP might be the consequence of immune memory of bacterial infection.

Unusual Gram-negative bacteria cause more severe bacterial meningitis than the three classical agents in children.

AimTo compare the characteristics, mortality and sequelae at hospital discharge of childhood bacterial meningitis (BM) caused by the three “classical” agents Neisseria meningitidis, Haemophilus influenzae or Streptococcus pneumoniae versus BM due to other aetiology in Finland, Latin America and Angola.MethodsThis observational study is a secondary analysis of data from five prospective treatment trials on non‐neonatal BM in Finland, Latin America and Angola in 1984–2017.ResultsOf the 1568 cases, 1459 (93%) were caused by the classics, 80 (5%) by other Gram‐negative and 29 (2%) by other Gram‐positive bacteria. Nonclassical Gram‐negative disease was encountered especially in Angola (p < 0.0001). Overall, children in the nonclassical group presented later for treatment and were more often underweight and anaemic (p < 0.001). In multivariate analysis, even if the area was strongest predictor of poor outcome, nonclassical Gram‐negative BM increased the odds for death twofold and the odds for death or severe sequelae 2.5‐fold.ConclusionBM of a nonclassical aetiology is a particularly severe disease affecting especially Angolan children poorly armoured to fight infections. Since vaccinations are diminishing the role of classical agents, that of nonclassical agents is growing.

Should we change our carotid stenting technique? Does balloon postdilatation increase periprocedural cranial embolism? A diffusion-weighted magnetic resonance imaging study.

IntroductionSilent cranial embolism has been demonstrated to cause dementia, cognitive decline and even ischemic stroke.AimTo compare the periprocedural asymptomatic cranial embolism rates of classical carotid artery stenting (CAS) and non-classical CAS methods using cranial diffusion-weighted magnetic resonance imaging (DW-MRI).Material and methods367 clinically uncomplicated patients who underwent CAS at our center between December 2010 and June 2020 (mean age: 69.3 ±11.9) were analyzed retrospectively. The patients were divided into 2 groups, classical CAS (130 patients) and non-classical CAS (237 patients). Classical CAS patients were defined as those who received a stent after suboptimal balloon dilatation (with a 3.0–4.0 mm balloon at 8–10 atmosphere (atm)) and underwent balloon postdilatation after stent deployment (with a 5.0–5.5 mm balloon at 8–10 atm). Non-classical CAS patients were defined as those in whom a stent was deployed after optimal balloon dilatation (with a 4.0–5.0 mm balloon at 10–14 atm) and did not undergo balloon postdilatation.ResultsPeriprocedural asymptomatic ipsilateral microembolism on cranial DW-MRI was detected in 25 (10.5%) patients in the non-classical CAS group and 24 (18.5%) in the classical CAS group. This difference between the two groups was found to be statistically significant (p = 0.033).ConclusionsThe rate of ipsilateral asymptomatic cranial embolism detected on cranial DW-MRI was lower in the CAS procedures in which optimal predilatation was performed but postdilatation after stent deployment was not performed compared to the CAS procedures in which suboptimal predilatation and postdilatation after stent deployment were performed.

Single-Center Prospective Cohort Study on the Histopathology, Genotype, and Postsurgical Outcomes of Patients With Primary Aldosteronism.

[Figure: see text].

Clinical characteristics of "classical" and "non-classical" paraneoplastic neurological syndrome

Objective: To explore the clinical features of classical and non-classical paraneoplastic neurological syndrome (PNS). Methods: From 2015 to 2020, 48 cases of definite PNS admitted to the First Affiliated Hospital of University of Science and Technology of China were retrospectively collected, and classification, clinical characteristics, onconeural antibodies and primary tumors were analyzed. The included cases were divided into classical and non-classical groups according to Graus criteria, and the differences of clinical characteristics, onconeural antibodies, combined tumors, time of diagnosis and mortality were compared between the two groups. Results: Among the 48 confirmed patients, 21 (43.8%) were positive for well-characterized onconeural antibodies. There were 28 cases (58.3%) and 20 cases (41.7%) in classic and non-classical PNS groups, respectively. No significant differences of age, sex, clinical involvement site, characteristic positive antibody type, tumor diagnosis rate and follow-up mortality were found between the two groups (all P>0.05). The time of diagnosis in the non-classical PNS group was 3.0 (2.0, 6.5) months, which was significantly longer than that in the classical PNS group 1.0(0.6, 3.0) months (P<0.05). Meanwhile, the combination rate of non-characteristic antibodies in the classical PNS group (10 cases, 35.7%) was significantly higher than that in the non-classical PNS group (1 case, 5.0%) (P=0.016). During the follow-up, 39 patients (81.3%) with tumor were confirmed, and 29 patients (60.4%) were diagnosed with PNS before the tumor was found. Conclusions: The"non-classical"PNSs are common in clinical settings. Diagnosis may be delayed due to the nonclassical symptoms of the patients. When patients have clinical symptoms related to PNS, onconeural antibodies should be detected and the relevant tumors should also be screened. Patients have positive antibodies but with no tumors should be closely followed up for more than 5 years.

A sufficiently complicated noded Schottky group of rank three

In 1974, Marden proved the existence of non-classical Schottky groups by a theoretical and non-constructive argument. Explicit examples are only known in rank two; the first one by Yamamoto in 1991 and later by Williams in 2009. In 2006, Maskit and the author provided a theoretical method to construct non-classical Schottky groups in any rank. The method assumes the knowledge of certain algebraic limits of Schottky groups, called sufficiently complicated noded Schottky groups. The aim of this paper is to provide explicitly a sufficiently complicated noded Schottky group of rank three and explain how to use it to construct explicit non-classical Schottky groups.

On the minimal dimension of a finite simple group

Let G be a finite group and let M be a set of maximal subgroups of G. We say that M is irredundant if the intersection of the subgroups in M is not equal to the intersection of any proper subset. The minimal dimension of G, denoted Mindim(G), is the minimal size of a maximal irredundant set of maximal subgroups of G. This invariant was recently introduced by Garonzi and Lucchini and they computed the minimal dimension of the alternating groups. In this paper, we prove that Mindim(G)⩽3 for all finite simple groups, which is best possible, and we compute the exact value for all non-classical simple groups. We also introduce and study two closely related invariants denoted by α(G) and β(G). Here α(G) (respectively β(G)) is the minimal size of a set of maximal subgroups (respectively, conjugate maximal subgroups) of G whose intersection coincides with the Frattini subgroup of G. Evidently, Mindim(G)⩽α(G)⩽β(G). For a simple group G we show that β(G)⩽4 and β(G)−α(G)⩽1, and both upper bounds are best possible.

Effect of a Gluten-free Diet on Quality of Life in Patients With Nonclassical Versus Classical Presentations of Celiac Disease.

Celiac disease (CD) often presents with symptoms of diarrhea and malabsorption, termed classical CD. However, it can also present as nonclassical CD, which is commonly associated with nongastrointestinal symptoms. Studies suggest that nonclassical CD tends to have less severe symptoms than classical CD, which may affect both adherence to a gluten-free diet (GFD) and psychological stress. Therefore, we compared adherence to a GFD and psychological measures, including quality of life (QOL) and somatization, between patients with nonclassical and classical presentations of CD. Patients at a tertiary care center with biopsy-proven CD, who completed a Talley Bowel Disease Questionnaire and the Short Form-36 at diagnosis and who had been on a GFD for at least 1 year, were included in this study. Patients were further surveyed to assess gastrointestinal symptoms, QOL, Somatization Symptom Checklist (SSC), and adherence to a GFD. Results were compared between patients with classical versus nonclassical CD presentation. Among 122 patients included in this study, 62 had classical CD and 60 had nonclassical CD. At diagnosis, health-related QOL was lower in the classical CD group than in the nonclassical CD group. After following a GFD, both groups had improved QOL after following a GFD, and body mass index significantly increased in both groups. Most subscales of QOL, SSC scores, and adherence to the GFD were similar between the groups, except the Short Form-36 Mental Component summary scores that were still lower in the classical CD (48.4 vs. 52.6 nonclassical CD group; P=0.03). Despite QOL at diagnosis being higher in those with nonclassical CD versus lower in those with classical CD, both groups had improved QOL and achieved a similar QOL after following a GFD.

Why do we need to investigate non-classical musicians to reduce the burden of musicians' musculoskeletal symptoms?

Musculoskeletal symptoms (MSSs) are common among professional musicians; however, most of the research has focused on orchestral/classical musicians. In some countries orchestral and classical musicians are in the minority; hence targeting research towards these specific sub-groups of musicians is unlikely to address the overall burden of musicians’ MSSs, unless the research is generalizable to other types of musicians. This multidisciplinary narrative review seeks to answer the question: “why do we need to examine the MSSs of non-classical groups of performing musicians in order to reduce the burden of musicians’ MSSs?”. There are differences in the education, posture, tasks (e.g. military training for military band musicians, dancing for those in musical theatre), venues and management of MSSs for different types of musicians. Future research should compare classical and non-classical musicians in order to determine which specific sub-groups (e.g. military band musicians) have the greatest MSS burden, such that further research into the risk factors of and interventions for MSSs can be targeted towards the sub-groups of musicians with the greatest MSS burden. In doing so, we maximise the likelihood of being able to introduce interventions, policies and practice that reduce the burden of musicians’ MSSs.

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment.

The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an “interface” between the embryo/fetus and the maternal immune system. Trophoblasts do not express the “original” HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.

All finitely generated Kleinian groups of small Hausdorff dimension are classical Schottky groups

This is the second part of the works on Hausdorff dimensions of Schottky groups. It has been conjectured that the Hausdorff dimensions of nonclassical Schottky groups are strictly bounded from below. In this second part of our works we provide a resolution of this conjecture, we prove that there exists a universal positive number $\lambda>0$, such that any finitely-generated non-elementary Kleinian groups with limit set of Hausdorff dimension $<\lambda$ are classical Schottky groups. We will generalize our previous technologies given in \cite{HS} to prove our general result. Our result can be consider as a converse to \cite{Doyle}.

Abstract P3-10-12: ERBB2 copy number analysis of invasive breast carcinoma using digital droplet PCR and targeted next-generation sequencing: A focus on 'non-classical' HER2 FISH groups using the 2018 ASCO/CAP HER2 testing guideline

Abstract Background: Non-classical HER2 FISH results were recently reclassified in the 2018 HER2 guidelines update, and concurrent IHC testing was recommended as part of additional workup to determine the final HER2 status in these groups. In this study, we explored the genomic landscape of HER2 FISH groups using digital droplet PCR (ddPCR) and targeted next-generation sequencing (NGS) on invasive breast carcinomas. Methods: Fifty-one clinical samples with HER2 FISH and IHC results were included in our analysis and classified into FISH groups based on the updated 2018 ASCO/CAP HER2 testing guideline: (i) Group 1A with ratio ≥2 and signals/cell ≥6, (ii) Group 1B with ratio ≥2 and signals/cell ≥4 and &amp;lt;6, (iii) Group 2 with ratio ≥2 and signals/cell &amp;lt;4, (iv) Group 3 with ratio &amp;lt;2 and signals/cell ≥6, (v) Group 4 with ratio &amp;lt;2 and signals/cell ≥4 and &amp;lt;6, and (vi) Group 5 with ratio &amp;lt;2 and signals/cell &amp;lt;4. Formalin-fixed paraffin-embedded samples were analyzed using two ddPCR assays each targeting an exon in the ERBB2 tyrosine kinase domain (exon 19 and 21, respectively) and a 130-gene NGS-based assay. For ddPCR, ERBB2 amplification status was determined from ddPCR ratios by using a recently published algorithm (Otsuji et al. 2017). For targeted NGS, ERBB2 amplification was called when copy number gains were detected in the majority of exons in ERBB2 (&amp;gt;50% of exons). Results: Mean ddPCR ratios varied amongst the different FISH groups (P &amp;lt; 0.0001). As expected, patients with Group 1A had the highest mean ddPCR ratios compared to those with other FISH findings (P &amp;lt; 0.0001). Furthermore, there was a correlation between ERBB2 ddPCR ratios and HER2 FISH ratios (ρe19 = 0.4435, P = 0.001 and ρe21 = 0.4644, P = 0.0006). Using ddPCR, ERBB2 amplifications were detected in all classically amplified Group 1A cases (5/5) and in none of the classically non-amplified Group 5 cases (0/12). Interestingly, ddPCR assays called ERBB2 amplification in four cases with non-classical results: one in Group 2 (1/6), two in Group 3 (2/6), and one in Group 4 (1/17), including two cases in Groups 3 and 4 which also showed concomitant HER2 overexpression by IHC (3+). Similarly, targeted NGS revealed ERBB2 amplification in all Group 1A cases (5/5) and in none of the Group 5 cases (0/12). Furthermore, NGS detected amplification in three non-classical cases: one in Group 1B (1/5), one in Group 3 (1/6), and one in Group 4 (1/17), including one case in Group 1B which was not called amplified by ddPCR. Notably, the three cases with amplification by NGS were the only three cases in the non-classical groups with HER2 overexpression by IHC. Overall, there was a strong concordance between ERBB2 amplification status by ddPCR/NGS and HER2 overexpression by IHC (κe19 = 0.79, κe21 = 0.92, κNGS = 1.0). Conclusion: ERBB2 amplification using ddPCR and NGS is correlated with HER2 overexpression in both classical and non-classical FISH groups, thus providing genomic evidence to support the recent recommendation for concurrent IHC testing in cases with unusual FISH results. Our findings also highlight a potential role of ddPCR and targeted NGS in the workup of challenging HER2 cases. Citation Format: Yang S-R, Bouhlal Y, De La Vega FM, Ballard M, West RB, Sibley RK, Kuo CJ, Vilborg A, Allison KH. ERBB2 copy number analysis of invasive breast carcinoma using digital droplet PCR and targeted next-generation sequencing: A focus on 'non-classical' HER2 FISH groups using the 2018 ASCO/CAP HER2 testing guideline [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-12.

Epidemiology and clinical outcomes of invasive mould infections in Indian intensive care units (FISF study)

Background and aimDue to limited data on invasive mould infections (IMIs) in the intensive care units (ICUs) of developing countries, we ascertain epidemiology and management of IMIs at 11 ICUs across India. MethodsConsecutive patients with proven or probable/putative IMIs were enrolled during the study period. Subjects were categorized into classical (neutropenia, malignancy, transplant recipients on immunosuppression) and non-classical (chronic obstructive pulmonary disease, diabetes, liver disease and glucocorticoids) risk groups. We analyzed the demographic, laboratory variables and outcomes of these patients. Results398 patients with IMIs (96 proven, 302 probable) were identified, amounting to a prevalence of 9.5 cases/1000 ICU admissions. The mean ± SD age of the participants was 45.6 ± 21.9 years. The mean ± SD APACHE II score was 14.3 ± 11.4. The IMIs were diagnosed at a median of 4 days after ICU admission. There were 145 and 253 subjects with classical and non-classical risk groups, respectively. Although Aspergillus spp. were the commonest (82.1%) isolates, Mucorales were detected in 14.4% subjects. A high APACHE II score and IMI due to mucormycosis were significant predictors of mortality. ConclusionsThe study highlights the distinct epidemiology of IMIs in India ICUs with high burden, new susceptible patient groups and considerable number of non-Aspergillus mould infections. [clinicaltrials.gov: NCT02683642].

Transcriptome and excretory-secretory proteome of infective-stage larvae of the nematode Gnathostoma spinigerum reveal potential immunodiagnostic targets for development.

Background: Gnathostoma spinigerum is a harmful parasitic nematode that causes severe morbidity and mortality in humans and animals. Effective drugs and vaccines and reliable diagnostic methods are needed to prevent and control the associated diseases; however, the lack of genome, transcriptome, and proteome databases remains a major limitation. In this study, transcriptomic and secretomic analyses of advanced third-stage larvae of G. spinigerum (aL3Gs) were performed using next-generation sequencing, bioinformatics, and proteomics. Results: An analysis that incorporated transcriptome and bioinformatics data to predict excretory–secretory proteins (ESPs) classified 171 and 292 proteins into classical and non-classical secretory groups, respectively. Proteins with proteolytic (metalloprotease), cell signaling regulatory (i.e., kinases and phosphatase), and metabolic regulatory function (i.e., glucose and lipid metabolism) were significantly upregulated in the transcriptome and secretome. A two-dimensional (2D) immunomic analysis of aL3Gs-ESPs with G. spinigerum-infected human sera and related helminthiases suggested that the serine protease inhibitor (serpin) was a promising antigenic target for the further development of gnathostomiasis immunodiagnostic methods. Conclusions: The transcriptome and excretory–secretory proteome of aL3Gs can facilitate an understanding of the basic molecular biology of the parasite and identifying multiple associated factors, possibly promoting the discovery of novel drugs and vaccines. The 2D-immunomic analysis identified serpin, a protein secreted from aL3Gs, as an interesting candidate for immunodiagnosis that warrants immediate evaluation and validation.