Proposal of three novel insect-associated Commensalibacter species: Commensalibacter melissae sp. nov., Commensalibacter communis sp. nov. and Commensalibacter papalotli sp. nov.

A recent modification of the Note to Rule 25a of the International Code for Nomenclature of Bacteria is used a posteriori by the List Editors of the International Journal of Systematic and Evolutionary Microbiology to justify the refusal to validate species protologues published in supplementary material prior to this formal decision. Authors are therefore forced to ask permission to reuse published data for the valid publication of such names. In the present letter we re-publish the species protologues of Commensalibacter melissae sp. nov., Commensalibacter communis sp. nov. and Commensalibacter papalotli sp. nov.

Eupransor demetentiae gen. nov., sp. nov., a novel fructophilic lactic acid bacterium from bumble bees.

Strain LMG 33000T was isolated from a Bombus lapidarius gut sample. It shared the highest percentage 16S rRNA sequence identity, average amino acid identity, and amino acid identity of conserved genes with Convivina intestini LMG 28291T (95.86 %, 69.9 and 76.2 %, respectively), and the highest percentage OrthoANIu value with Fructobacillus fructosus DSM 20349T (71.4 %). Phylogenomic analyses by means of 107 or 120 conserved genes consistently revealed Convivina as nearest neighbour genus. The draft genome of strain LMG 33000T was 1.44 Mbp in size and had a DNA G+C content of 46.1 mol%. Genomic and physiological analyses revealed that strain LMG 33000T was a typical obligately fructophilic lactic acid bacterium that lacked the adhE and aldh genes and that did not produce ethanol during glucose or fructose metabolism. In contrast, Convivina species have the adhE and aldh genes in their genomes and produced ethanol from glucose and fructose metabolism, which is typical for heterofermentative lactic acid bacteria. Moreover, strain LMG 33000T exhibited catalase activity, an unusual characteristic among lactic acid bacteria, that is not shared with Convivina species. Given its position in the phylogenomic trees, and the difference in genomic percentage G+C content and in physiological and metabolic characteristics between strain LMG 33000T and Convivina species, we considered it most appropriate to classify strain LMG 33000T into a novel genus and species within the Lactobacillaceae family for which we propose the name Eupransor demetentiae gen. nov., sp. nov., with LMG 33000T (=CECT 30958T) as the type strain.

Severe thrombocytopenia and microangiopathic hemolytic anemia in pregnancy: A guide for the consulting hematologist.

A hematologist receives a call from a maternal-fetal medicine (MFM) physician about a previously healthy patient who became ill at 25 weeks' gestation. Her mental status is deteriorating. There are signs of fetal distress. Platelet count and hemoglobin are falling. The MFM physician is considering the hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome. For the hematologist, everything seems unfamiliar. Our goal is to provide hematologists with the fundamental knowledge required for understanding and managing these patients who become suddenly and seriously ill during pregnancy and in whom thrombocytopenia and microangiopathic hemolytic anemia are part of their presentation.

The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia.

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.

Glanzmann thrombasthenia: genetic basis and clinical correlates.

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and ß3. These integrins are encoded by the ITGA2B and ITGB3 genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Refractory bleeding and platelet alloimmunization are common complications. In addition, pregnant patients pose unique management challenges. This review highlights clinical and molecular aspects in the approach to patients with GT, with particular emphasis on the significance of multidisciplinary care.

Are There Mandibular Morphological Differences in the Various Facial Asymmetry Etiologies? A Tomographic Three-Dimensional Reconstruction Study.

PURPOSE: Facial asymmetries (FAs) have been classified according to the mandibular morphological differences to obtain better diagnostic and treatment decisions. The purpose of the present study was to establish diagnostic differentiation among FAs using computed tomography (CT) and 3-dimensional (3D) reconstruction. MATERIALS AND METHODS: We performed a cross-sectional study of patients with a diagnosis of FA, who had been evaluated by CT and 3D reconstruction in the same clinical center from 2015 to 2018. The following mandibular anatomic characteristics were compared between the 2 sides (deviated side vs contralateral side) and type of FA: condylar length, mandibular ramus length and width, mandibular body length, and symphysis deviation. RESULTS: The 53 patients included 23 men and 30 women (age range, 16 to 25 years). Six categories of FA were identified: hemimandibular elongation (n = 25), hemimandibular hyperplasia (n = 2), hybrid hyperplasia (n = 3), asymmetric mandibular prognathism (n = 14), asymmetry of the glenoid fossa (n = 2), and functional laterognathism (n = 7). The condylar length and mandibular ramus width were greater in the displaced side than in the contralateral side, with differences of -2.0 ± 2.8 mm (P < .001) and -0.5 ± 1.7 mm (P = .009), respectively. The mandibular body length was greater on the contralateral side (mean difference, 2.1 ± 3.5 mm; P < .001). The symphysis deviation was 5.0 ± 3.4 mm, and those with a hybrid form presented with a greater deviation, with values greater than 10 mm, followed by those with hemimandibular elongation. CONCLUSIONS: The evaluation of the CT images and 3D reconstructions in patients with FA provided detailed information of the mandibular structure that is useful to compare the differences between sides and to classify the entities associated with FA.

Factor IX Gene (F9) Genotyping Trends and Spectrum of Mutations Identified: A Reference Laboratory Experience.

In hemophilia B (HB), factor IX gene (F9) genotyping is used for molecular confirmation of affected individuals, for carrier testing, to facilitate the identification of those at risk for anaphylaxis/inhibitors (associated with large deletions), and to assist in assigning disease severity. Owing to test costs, optimal test utilization involves pre/post-test counseling and appropriate patient and test selection (e.g., mutation screening [F9MS] vs. known mutation [F9KM] testing). This article aims to review the trends and outcomes of F9-genotyping orders and describe the spectrum of variants identified in a sample of individuals in our reference laboratory. We performed a retrospective review of consecutive orders submitted to the Special Coagulation DNA Diagnostic Laboratory, Mayo Clinic, between 2012 and 2015. A total of 133 orders (38%) were identified for men: 118 (88%) were F9MS and 15 (12%) were F9KM. Thirteen orders (10%) were cancelled. A total of 209 orders were identified for women: 178 (85%) were F9MS and 31 (15%) were F9KM. Thirty-seven orders (18%) were cancelled and 30% of the tests performed yielded negative results. A total of 164 samples (47%) were received without clinical information. Seventeen previously unreported variants were identified. F9 genotyping provides useful information for HB management; however, 18% of our orders were cancelled and almost half were received without relevant clinical information, thus reaffirming the need for ongoing scrutiny of submitted orders. Optimal patient and test selection is important as is the accurate interpretation of variants identified. Most of the pathogenic variants identified were point mutations, with very few large deletions, consistent with the literature.

Hermansky-Pudlak syndrome subtype 5 (HPS-5) novel mutation in a 65 year-old with oculocutaneous hypopigmentation and mild bleeding diathesis: The importance of recognizing a subtle phenotype.

Hermansky-Pudlak syndrome (HPS) - characterized by the distinct clinical phenotypes of both oculocutaneous albinism and mild bleeding diathesis-is caused by mutations in genes that have crucial roles in the assembly of cellular organelles (skin melanosomes, platelet delta [dense] granules, lung lamellar bodies, and cytotoxic T-cell lymphocyte granules). Immunodeficiency, pulmonary fibrosis and granulomatous colitis are associated with some, but not all subtypes of HPS, with varying degrees of clinical severity. We describe a patient diagnosed with platelet dense granule storage pool deficiency (DG-SPD) at age 38 years after he presented with spontaneous intracranial hemorrhage. His mild oculocutaneous hypopigmentation was subtle. In the following 27 years, he did not develop severe bleeding nor pulmonary or gastrointestinal complications. A novel homozygous c.1960A>T; p.Lys654* mutation in the HPS-5 protein gene (HPS5) was identified through next generation sequencing, (NGS) which is consistent with the patient's clinical and laboratory phenotypes. This case underscores the importance of recognizing the mild clinical phenotype of HPS-5 and utilization of both laboratory and molecular testing for diagnosis, prognostication, and surveillance for end organ damage in patients affected with HPS.

A proof-of-concept trial of protein kinase C iota inhibition with auranofin for the paclitaxel-induced acute pain syndrome.

PURPOSE: Paclitaxel causes the paclitaxel-induced acute pain (PIAP) syndrome. Based on preclinical data, we hypothesized that the protein kinase C (PKC) iota inhibitor, auranofin (a gold salt used for other pain conditions), palliates this pain. METHODS: In a randomized, double-blinded manner, patients who had suffered this syndrome were assigned a one-time dose of auranofin 6 mg orally on day #2 of the chemotherapy cycle (post-paclitaxel) versus placebo. Patients completed the Brief Pain Inventory and a pain diary on days 2 through 8 and at the end of the cycle. The primary endpoint was pain scores, as calculated by area under the curve, in response to "Please rate your pain by circling the one number that best describes your pain at its worse in the last 24 hours." RESULTS: Thirty patients were enrolled. For the primary endpoint, mean area under the curve of 55 units (standard deviation 19) and 61 units (standard deviation 22) were observed in auranofin-treated and placebo-exposed patients, respectively (p = 0.44). On day 8 and at the end of the cycle, pain scores in auranofin-treated patients were more favorable, although differences were not statistically significant. CONCLUSIONS: In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.

Capturing and Incorporating Patient-Reported Outcomes into Clinical Trials: Practical Considerations for Clinicians.

Patient centeredness as the focus of healthcare delivery requires the incorporation of patient-reported outcomes into clinical trials. Clearly defining measurable outcomes as well as selecting the most appropriate validated collection tool to use is imperative for success. Creating and validating one's own instrument is also possible, albeit more cumbersome. Meticulous data collection to avoid missing data is key, as is limiting the number of data collection points to prevent survey fatigue and using electronic systems to facilitate data gathering and analysis. Working in a multidisciplinary team that includes statisticians with expertise in patient reported outcomes is essential to navigate the complexities of statistical analysis of these variables. Use of available and emerging technologies for data collection and analysis as well as data sharing will greatly facilitate the process of incorporating patient-reported outcomes into trials and routine clinical practice.

Clinical and laboratory characteristics in congenital ANKRD26 mutation-associated thrombocytopenia: A detailed phenotypic study of a family.

The clinical and laboratory characteristics of patients with non-syndromic, autosomal dominant thrombocytopenia secondary to germ line ANKRD26 mutations appear to be heterogeneous. Except for a targeted molecular genotyping approach, there is no distinct clinical or laboratory phenotype that has been specifically associated with this particular gene mutation. Such heterogeneity could be due to variations in mutation and genetic background in different families. To understand the phenotypic heterogeneity, we thoroughly studied one affected family using the International Society for Thrombosis and Haemostasis bleeding assessment tool and both clinically validated standard and esoteric platelet testing (electron microscopy (EM) and flow cytometry). We found that decreased platelet aggregation with arachidonic acid and epinephrine agonists was common in affected family members. EM studies demonstrated persistent borderline low mean dense granules per platelet, decreased alpha granules and an increased canalicular network pattern in all affected members. Since these characteristics are subtle or non-pathognomonic, molecular testing for ANKRD26 mutation remains the most reliable test to render a diagnosis and should be considered when evaluating a patient or family with congenital thrombocytopenia, particularly if there is a history of myeloid neoplasms.

A comparative genomic analysis of Fructobacillus evanidus sp. nov. from bumble bees.

The increase in studies on bee microbiomes is prompted by concerns over global pollinator declines. Bumble bees host core and non-core microbiota which may contribute to increased lifetime fitness. The presence of Fructobacillus in the gut microbiomes of bumble bee workers, or the replacement of core symbionts with Fructobacillus bacteria, has been considered a marker of dysbiosis. A phylogenomic analysis and functional genomic characterization of the genomes of 21 Fructobacillus isolates from bumble bees demonstrated that they represented four species, i.e. Fructobacillus cardui, Fructobacillus fructosus, Fructobacillus tropaeoli, and the novel species Fructobacillus evanidus sp. nov. Our results confirmed and substantiated the presence of two phylogenetically and functionally distinct Fructobacillus species clades that differ in genome size, percentage G + C content, the number of coding DNA sequences and metabolic characteristics. Clade 1 and clade 2 species differed in amino acid and, to a lesser extent, in carbohydrate metabolism, with F. evanidus and F. tropaeoli genomes featuring a higher number of complete metabolic pathways. While Fructobacillus genomes encoded genes that allow adhesion, biofilm formation, antibacterial activity and detoxification, other bacteria isolated from the bumble bee gut appeared better equipped to co-exist with the bumble bee host. The isolation and identification of multiple Fructobacillus species from several bumble bee gut samples in the present study also argued against a specific partnership between Fructobacillus species and their bumble bee hosts.

Evaluating the clinical validity of genes related to hemostasis and thrombosis using the Clinical Genome Resource gene curation framework.

BACKGROUND: Inherited bleeding, thrombotic, and platelet disorders (BTPDs) are a heterogeneous set of diseases, many of which are very rare globally. Over the past 5 decades, the genetic basis of some of these disorders has been identified, and recently, high-throughput sequencing has become the primary means of identifying disease-causing genetic variants. OBJECTIVES: Knowledge of the clinical validity of a gene-disease relationship is essential to provide an accurate diagnosis based on results of diagnostic gene panel tests and inform the construction of such panels. The Scientific and Standardization Committee for Genetics in Thrombosis and Hemostasis undertook a curation process for selecting 96 TIER1 genes for BTPDs. The purpose of the process was to evaluate the evidence supporting each gene-disease relationship and provide an expert-reviewed classification for the clinical validity of genes associated with BTPDs. METHODS: The Clinical Genome Resource (ClinGen) Hemostasis/Thrombosis Gene Curation Expert Panel assessed the strength of evidence for TIER1 genes using the semiquantitative ClinGen gene-disease clinical validity framework. ClinGen Lumping and Splitting guidelines were used to determine the appropriate disease entity or entities for each gene, and 101 gene-disease relationships were identified for curation. RESULTS: The final outcome included 68 Definitive (67%), 26 Moderate (26%), and 7 Limited (7%) classifications. The summary of each curation is available on the ClinGen website. CONCLUSION: Expert-reviewed assignment of gene-disease relationships by the ClinGen Hemostasis/Thrombosis Gene Curation Expert Panel facilitates accurate molecular diagnoses of BTPDs by clinicians and diagnostic laboratories. These curation efforts can allow genetic testing to focus on genes with a validated role in disease.

Labor and delivery: DIC, HELLP, preeclampsia.

Hematologists are often needed to assist with the management of microangiopathic emergencies in pregnancy. A firm understanding of the diagnosis and management of preeclampsia with severe features, hemolysis elevated liver enzyme and low platelet syndrome, and disseminated intravascular coagulation, which are the most common causes of microangiopathic emergencies, is critical. However, being able to consider when other microangiopathic emergencies (acute fatty liver of pregnancy, congenital and acquired thrombotic thrombocytopenic purpura, complement mediated microangiopathy, antiphospholipid syndrome) should be considered is imperative. The hematologist and obstetric team should work together to optimize the care of common as well as rare hematologic emergencies.

More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant.

Key Clinical Message: In the evaluation of patients with longstanding mild thrombocytopenia, emphasis on family history, genetic testing, and collaborative clinical and laboratory-based family studies can ensure proper diagnosis and monitoring for malignancies. Abstract: We report the diagnostic approach to mild and non-specific thrombocytopenia with unclear genetic findings in two sisters. Genetic sequencing revealed a rare variant in ETS Variant Transcription Factor 6, which is associated with inherited thrombocytopenia with predisposition to hematologic malignancy. Familial studies provided sufficient evidence for a likely pathogenic classification.

Peripartum management of deep venous thrombosis in the context of antithrombin deficiency and May-Thurner syndrome.

Literature regarding the management of thrombus refractory to first-line treatment in the setting of pregnancy is limited, and management is made even more complicated in the context of thrombophilia. This case reviews the management of a patient with antithrombin deficiency who developed a massive thrombus during pregnancy, which was complicated by May-Thurner syndrome, lack of improvement with heparin, and preterm labor. The patient received multidisciplinary care throughout the pregnancy. At 35 weeks, anticoagulation was paused as she underwent induction of labor and delivery followed by postpartum placement of inferior vena cava filter and restarting heparin. Successful management of our pregnant patient with thrombus refractory to heparin hinged on individualized treatment for medical optimization with anticoagulation and antithrombin concentrate prior to labor followed by immediate postpartum placement of inferior vena cava filter.