The prevalence and predictors of discharge opioid overprescribing in opioid-naïve patients after breast, gynecologic, and head and neck cancer surgery: a prospective cohort study.

PURPOSE: The management of pain following cancer-related surgeries involves the use of opioid analgesics. Nevertheless, there is little evidence characterizing the utility and prescription patterns of opioids after these procedures. Our primary aim was to identify patients from three types of cancer surgery who were overprescribed with opioids. The secondary aim was to determine the potential predictors of overprescribing in the same period. METHODS: We conducted the study at a single cancer referral hospital. Opioid-naïve patients with breast, gynecologic, or head and neck cancer were studied. Patients were considered opioid-naïve if they had a history of opioid use ≤ 30 mg oral morphine equivalent daily dose for less than seven days in the preceding three months before surgery. We recruited eligible participants by convenience sampling on the wards until at least 102 patients were included in the final analysis. After discharge, we followed up on the participants on day 7 via telephone using a structured proforma including questions to identify the last date and amount of opioid dose taken. The equivalent days of opioid use were calculated by their 24-hr use before discharge and the number of doses prescribed for discharge. Our primary outcome was the prevalence of overprescribing in the three surgical specialties defined as the number of patients taking less than 50% of discharge opioids within the first seven days after discharge. We examined the predictors on incidents of overprescribing using multivariable Poisson regression as the secondary outcome. RESULTS: We recruited 119 patients, and 107 patients were included in the final analysis. There were 59/107 (55%) patients found to be overprescribed with opioids. At discharge, they exhibited lower mean numerical rating scale pain scores, lower mean pain severity scores, higher equivalent days of opioids prescribed, and not used opioids in the last 24 hr before discharge. The incidence of overprescribing was 2.4 times greater for patients prescribed with opioids without 24-hr opioid use (relative risk [RR], 2.38; 95% confidence interval [CI], 1.30 to 4.35; P = 0.005). Similarly, the incidence of overprescribing was 1.7 times greater for patients who had opioids 24 hr before discharge and were supplied with opioids for five equivalent days or more at the time of discharge (RR, 1.67; 95% CI, 1.09 to 2.56; P = 0.02). CONCLUSION: Our study shows that the majority of recruited patients undergoing breast, gynecologic, or head and neck cancer surgery were overprescribed opioids. Individualized assessments on patients' 24-hr opioid requirements before discharge and supplying for less than five days are important considerations to reduce overprescribing in opioid-naïve patients after cancer surgery.

RéSUMé: OBJECTIF: La prise en charge de la douleur à la suite d'interventions chirurgicales liées au cancer passe par l'utilisation d'analgésiques opioïdes. Néanmoins, il existe peu de données probantes caractérisant l'utilité et les habitudes de prescription des opioïdes après ces interventions. Notre objectif principal était d'identifier les patient·es de trois types de chirurgie du cancer auxquel·les des opioïdes avaient été surprescrits. L'objectif secondaire était de déterminer les prédicteurs potentiels de surprescription au cours de la même période. MéTHODE: Nous avons mené cette étude dans un seul hôpital de référence pour le cancer. La patientèle naïve aux opioïdes atteinte de cancer du sein, gynécologique ou de la tête et du cou a été étudiée. Les patient·es étaient considéré·es comme naïfs ou naïves aux opioïdes si leurs antécédents d'utilisation d'opioïdes étaient inférieurs ou égaux à une dose quotidienne équivalente à 30 mg de morphine orale pendant moins de sept jours au cours des trois mois précédant la chirurgie. Nous avons recruté les participant·es éligibles par échantillonnage de commodité dans les services jusqu'à ce qu'au moins 102 personnes soient incluses dans l'analyse finale. Après le congé, nous avons fait un suivi téléphonique auprès des participant·es le 7e jour à l'aide d'un formulaire structuré comprenant des questions visant à identifier la dernière date et la dose d'opioïdes prise. Les jours équivalents de consommation d'opioïdes ont été calculés en fonction de leur utilisation dans les 24 heures précédant le congé et du nombre de doses prescrites pour le congé. Notre critère d'évaluation principal était la prévalence de la surprescription dans les trois spécialités chirurgicales, définie comme le nombre de patient·es prenant moins de 50 % des opioïdes reçus au congé dans les sept premiers jours suivant le congé. Nous avons examiné les prédicteurs d'incidents de surprescription en utilisant la régression de Poisson multivariée comme critère d'évaluation secondaire. RéSULTATS: Nous avons recruté 119 patient·es, et 107 patient·es ont été inclus·es dans l'analyse finale. Une surprescription d'opioïdes a été observée pour 59 patient·es sur 107 (55 %). À leur congé, ces personnes présentaient des scores de douleur moyens plus faibles sur l'échelle d'évaluation numérique, des scores moyens de gravité de la douleur plus faibles, des jours équivalents d'opioïdes prescrits plus élevés et n'avaient pas utilisé d'opioïdes dans les 24 heures précédant le congé. L'incidence de surprescription était 2,4 fois plus élevée chez les patient·es à qui l'on avait prescrit des opioïdes sans utilisation d'opioïdes dans les 24 heures (risque relatif [RR], 2,38; intervalle de confiance [IC] à 95 %, 1,30 à 4,35; P = 0,005). De même, l'incidence de surprescription était 1,7 fois plus élevée chez les patient·es qui avaient reçu des opioïdes 24 heures avant le congé et qui avaient reçu des opioïdes pendant cinq jours équivalents ou plus au moment du congé (RR, 1,67; IC 95 %, 1,09 à 2,56; P = 0,02). CONCLUSION: Notre étude montre qu'il y a eu surprescription d'opioïdes pour la majorité des patient·es recruté·es bénéficiant d'une chirurgie de cancer du sein, gynécologique ou de la tête et du cou. Des évaluations individualisées des besoins en opioïdes des patient·es dans les 24 heures avant leur congé et une administration pendant moins de cinq jours sont des considérations importantes pour réduire la surprescription chez les personnes naïves aux opioïdes après une chirurgie oncologique.

TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present.

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.

PD-L1 Expression in Ampullary Adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma is a rare neoplasm often treated by the complex Whipple's procedure. Several histological factors predict poor prognosis including pancreatobiliary morphology, presence of lymphovascular, perineural invasion and local or distant metastasis. Systemic therapy with gemcitabine, 5-fluorouracil regimens are given with variable benefits. Immunotherapy checkpoint inhibitors have shown beneficial anti-tumor effects in several carcinomas, the most remarkable being in non-small cell lung cancer. Administration of these novel drugs is based on immunohistochemical expression (which may or may not be indicative of response to therapy) along with meticulous decision making by the multidisciplinary team. Immunohistochemistry (IHC) is an effective means of immune marker demonstration and has been used in various tumor types for predictive and prognostic purposes. METHODS: PD-L1 IHC (clone E1L3N) was applied in 101 cases of ampullary adenocarcinoma. Tumor infiltrating lymphocytes were also evaluated. The immunoreactivity was assessed and categorized into following staining thresholds: <1%, <5%, <10% and ≥10% for tumor cells (membranous and/or cytoplasmic staining pattern), and 5% and 10% cut-offs for immune cells. RESULTS: We found that at a 10% cut-off, 73.3% (74/101) patients were men (P = .006) older than 50 years of age (P < .001) presenting with a tumor measuring <3 cm (P = .001). It was significantly associated with intestinal differentiation (P = .004) and grade 1 tumors (P = .001). Twelve patients presented with recurrence as well (P = .03). CONCLUSION: In the context of ampullary adenocarcinoma, this study highlights the positivity observed with the PD-L1 IHC clone E1L3N at different thresholds, with the particularly stronger associations being evident at a 10% cut-off.

Non-Small Cell Lung Cancer: Targetable Variants in Concurrent Tissue and Liquid Biopsy Testing in a North Indian Cohort.

OBJECTIVES: Testing for EGFR, ALK, ROS1 and MET alterations in paired tissue and plasma samples of treatment-naïve patients of NSCLC and correlating their status with overall survival. MATERIALS AND METHODS: One hundred treatment-naïve patients were recruited after obtaining informed consent. Ten ml of blood was collected within a period of two weeks from histological diagnosis, prior to the start of any treatment. DNA & RNA extraction was done from formalin-fixed paraffin embedded (FFPE) tissue and total cell-free nucleic acid extraction was done from plasma samples. EGFR mutation, ALK, ROS1 and MET rearrangements were tested by ARMS (Amplification Refractory Mutation System) PCR. All statistical analyses were conducted in R version 4.1.1. RESULTS: A total of 61 cases showed molecular alterations in tissue samples which included EGFR mutations (47), ALK rearrangements (12), ROS1 fusion (2). MET alteration was not detected. Forty-three cases showed EGFR mutations in plasma, 26 of which were concurrently positive in tissue. Concordance observed was 62%. ALK-EML4 rearrangement, ROS1 fusion and MET were not detected in plasma samples. Sensitivity and specificity for detection of EGFR mutation in plasma were 55.3% and 67.9% respectively. Univariate Cox regression analysis showed a positive association between EGFR mutation in tissue and overall survival (HR = 0.4; 95% CI: 0.2-0.7; p = 0.003) and improved overall survival in those who received targeted therapy (HR = 0.29; 95% CI: 0.1-0.8; p = 0.02). CONCLUSION: Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.

From the archives of MD Anderson Cancer Center: Sporadic Burkitt lymphoma with a complex karyotype and SOX11 expression.

Burkitt lymphoma (BL) is a mature B-cell neoplasm arising from germinal center B-cells. There are three epidemiological variants of which the sporadic variant is most prevalent in developed countries representing 1-2 % of all lymphomas in adults. Patients usually present with bulky abdominal masses and ~ 30 % have bone marrow involvement. BL is characterized by a germinal center B-cell immunophenotype and usually has a simple karyotype. Here we report an unusual case of sporadic BL in a 44-year-old man and we use this case to review sporadic BL in adults. The patient presented with a cecal mass and bone marrow involvement. Biopsy of the cecal mass and bone marrow evaluation showed infiltration by intermediate-size lymphoma cells positive for monotypic kappa, CD10, CD19, CD20, CD22, CD38 bright, CD43, CD45, Bcl6 and ROR1, and negative for CD11c, CD23, CD30, CD44, CD200 and Bcl2. As expected, the lymphoma cells were strongly positive for MYC and Ki-67 showed a proliferation rate of nearly 100 %, but the cells were also positive for SOX11 and cytoplasmic LEF1. Conventional chromosomal analysis revealed t(8;14) as part of a complex karyotype. Based on our literature review, and is shown in this case, sporadic BL in adults shows some differences with the classic description of BL in children. We also discuss the differential diagnosis of BL.

A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

Utility of morphologic assessment of bone marrow biopsy in diagnosis of lysosomal storage disorders.

Introduction: Lysosomal storage disorders (LSDs) are rare disorders and pose a diagnostic challenge for clinicians owing to their generalized symptomatology. In this study, we aim to classify LSDs into two broad categories, namely, Gaucher disease (GD) and Niemann-Pick/Niemann-Pick-like diseases (NP/NP-like diseases) based on the morphology of the storage cells in the bone marrow (BM) aspiration smears and trephine biopsy sections. Materials and Method: This retrospective study includes 32 BM specimens morphologically diagnosed as LSDs at our institute, in the last 10 years. Subsequently, they were subclassified into GD and NP/NP-like diseases. Further, we have compared and analyzed the clinical, hematological, and biochemical parameters for the two groups of LSDs. Results: Based on BM morphology, 59.4% (n = 19) cases were diagnosed as NP/NP-like diseases and 40.6% (n = 13) cases as GD. Abdominal distension and failure to thrive were the most common clinical manifestations in both groups of LSDs. Anemia and thrombocytopenia were frequently seen in either of the LSDs. On the assessment of metabolic profile, elevated total/direct bilirubin and liver enzymes were more commonly seen in NP/NP-like diseases when compared with GD. Conclusion: We have classified LSDs into GD and NP/NP-like diseases based on the morphology of the storage cells in the BM specimen. The hallmark findings on BM biopsy annexed with the comparative features of the two proposed categories can aid the clinician in clinching the diagnosis. Formulation of such a methodology will prove instrumental for patient care in an underresourced setting.

Frequency Of CD34 Expression In Acute Lymphoblastic Leukaemia And Its Correlation With Clinicopathological Characteristics: A Single Centre Experience From Pakistan.

Background: This study was carried out to determine the frequency of CD34 positivity in acute lymphoblastic leukaemia (B-ALL) in our population and to report its association with the clinicopathological profile at the time of diagnosis. Methods: The cross-sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from March 2020 till December 2020.Newly diagnosed patients were selected, from both genders and all age groups. Relevant history and findings of physical examination were recorded. Immunohistochemistry was done on trephine biopsy and molecular studies were carried on bone marrow aspirates or peripheral blood samples. Results: Out of 105 patients enrolled, 67 (63.8%) were males, with a male to female ratio (M: F) 1.8:1. Of the total patients, 62 (59.04%) were above 15 years of age. CD34 was expressed in 73 (69.5%) cases. Lymphadenopathy, splenomegaly, and hepatomegaly were separately noted in context to CD 34 expression in 22 (66.6%), 24 (64.8%), and 14 (58.3%) patients, respectively. CNS disease was seen in a total of 3(2.75%) subjects, in which 2 (66.6%) of the patients had CD34 expression. Total 81 patients in our study fall into the high-risk group out of which CD 34 expression was seen in 58(71.6%) subjects. Cytogenetic analysis, BCR-ABL p190, and MLL gene rearrangement were investigated in all participants. Cytogenetic analysis revealed an abnormality in 20 (19%) cases out of which 13 (17.8%) cases were from CD34 positive group. Conclusion: Our study reported CD34 expression in more than two-thirds of cases. High-risk disease was significantly associated with CD34 expression.

Pregnancy Outcomes With COVID-19 Lessons Learned From the Pandemic.

Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes Coronavirus disease has caused one of the most damaging pandemics in the recorded human history. Objective To assess pregnancy outcomes with COVID-19 lessons learned from the pandemic. Study design This retrospective observational study was conducted at Teerthanker Mahaveer Medical College and Research Centre, Moradabad, a level 3 COVID hospital in Northern India, with a patient pool of all the antenatal females diagnosed COVID 19 positive via a positive quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) test of maternal pharyngeal and nasal swab samples in the given time period of three months and ten days, i.e., May 25, 2020 to September 3, 2020. In conjunction with maternal outcomes, neonatal outcomes including evidence of perinatal transmission of SARS-CoV-2 was assessed by testing neonatal pharyngeal swab samples. Results Out of 100 COVID-19 positive patients, the average age of women was 26.2 years, 73 women (73%) were asymptomatic, and 50 patients (50%) women had associated co-morbidities such as anaemia in 38 (38%) women, gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) in four patients (4%) each, respectively. No case of spontaneous abortion in early gestation was reported. Out of 100 patients, 32 (32%) patients delivered during their stay, out of which 17 women (53.1%) delivered via cesarean section which was performed mainly due to obstetric indications. One maternal death was reported due to antepartum eclampsia which was unrelated to COVID-19 complications. Five neonates were born prematurely, out of which three were delivered followed by spontaneous premature preterm rupture of membranes (PPROM). The Appearance Pulse Grimace Activity Respiration (APGAR) score was recorded to be ≥9 at the five minutes mark in 28 out of 30 live babies (93.3%) and the birth weight of the babies ranged from 1.8 to 3.5 kg) with an average birth weight of 2.71 kg. Two neonatal deaths were reported due to respiratory distress. There were two documented intrauterine demise (IUD) cases both due to PIH. Furthermore, all 30 live neonates tested for SARS CoV-2 had negative results. Conclusion The spectrum of Coronavirus infection leans more towards asymptomatic and mild symptomatic clinical presentation. Favourably, the likelihood of spontaneous preterm birth was not escalated in our current study and remained low. The rate of intrauterine fetal demise and neonatal death were less. As none of the neonates tested positive for COVID-19, there is no corroborative proof of vertical perinatal transmission.

Large Single Crystals of Two-Dimensional π-Conjugated Metal-Organic Frameworks via Biphasic Solution-Solid Growth.

Two-dimensional (2D) π-conjugated metal-organic frameworks (πMOFs) are a new class of designer electronic materials that are porous and tunable through the constituent organic molecules and choice of metal ions. Unlike typical MOFs, 2D πMOFs exhibit high conductivity mediated by delocalized π-electrons and have promising applications in a range of electrical devices as well as exotic physical properties. Here, we develop a growth method that generates single-crystal plates with lateral dimensions exceeding 10 µm, orders of magnitude bigger than previous methods. Synthesis of large single crystals eliminates a significant impediment to the fundamental characterization of the materials, allowing determination of the intrinsic conductivity and mobility along the 2D plane of πMOFs. A representative 2D πMOF, Ni-CAT-1, exhibits a conductivity of up to 2 S/cm, and Hall measurement reveals the origin of the high conductivity. Characterization of crystalline 2D πMOFs creates the foundation for developing electronic applications of this promising and highly diverse class of materials.

A cross-sectional study of hard ticks (acari: ixodidae) on horse farms to assess the risk factors associated with tick-borne diseases.

Zoonotic diseases are significant public health issues. There is an urgent need to focus our efforts on the development of strategies that prevent and control potential arthropod vector-borne pathogens. Hard ticks transmit a variety of viral, bacterial and protozoan pathogens to their vertebrate hosts. This is becoming of more concern, as anthropogenic alterations of the environment may unleash the spread of tick-borne diseases throughout the world. Developing countries that are highly dependent on the livestock economy are a hot spot for tick-borne infectious diseases. In this work, through a cross-sectional approach that included a bibliographic survey, field collection and epidemiological questionnaire, we identified five tick species that were found to parasitize equines and transmit tick-borne pathogens. Our data revealed a gap in fundamental knowledge of ticks and tick-borne infectious diseases among equine breeders and owners. This article highlights the relevant risk factors that were found and the urgent actions that are needed to prevent the wide spread of hard ticks and their associated zoonotic diseases.

IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero-positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero-positive individuals improved pre-existing gB-specific IgA and IgG levels and induced de novo gB-specific IgA and IgG responses in sero-negative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination, but de novo AD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breastmilk samples. All antibodies binding AD-2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region-matched AD-2-specific recombinant IgG and IgA bound both to gB and to AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk, which may function to protect neonates from HCMV.

Novel Genetic Variations in Acute Myeloid Leukemia in Pakistani Population.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal expansion of blast cells that exhibit great genetic heterogeneity. In this study, we describe the mutational landscape and its clinico-pathological significance in 26 myeloid neoplasm patients from a South Asian population (Pakistan) by using ultra-deep targeted next-generation DNA sequencing of 54 genes (∼5000×) and its subsequent bioinformatics analysis. The data analysis indicated novel non-silent somatic mutational events previously not reported in AML, including nine non-synonymous and one stop-gain mutations. Notably, two recurrent somatic non-synonymous mutations, i.e., STAG2 (causing p.L526F) and BCORL1 (p.A400V), were observed in three unrelated cases each. The BCOR was found to have three independent non-synonymous somatic mutations in three cases. Further, the SRSF2 with a protein truncating somatic mutation (p.Q88X) was observed for the first time in AML in this study. The prioritization of germline mutations with ClinVar, SIFT, Polyphen2, and Combined Annotation Dependent Depletion (CADD) highlighted 18 predicted deleterious/pathogenic mutations, including two recurrent deleterious mutations, i.e., a novel heterozygous non-synonymous SNV in GATA2 (p.T358P) and a frameshift insertion in NPM1 (p.L258fs), found in two unrelated cases each. The WT1 was observed with three independent potential detrimental germline mutations in three different cases. Collectively, non-silent somatic and/or germline mutations were observed in 23 (88.46%) of the cases (0.92 mutation per case). Furthermore, the pharmGKB database exploration showed a missense SNV rs1042522 in TP53, exhibiting decreased response to anti-cancer drugs, in 19 (73%) of the cases. This genomic profiling of AML provides deep insight into the disease pathophysiology. Identification of pharmacogenomics markers will help to adopt personalized approach for the management of AML patients in Pakistan.

Peripheral Blood Stem Cell Harvest HPC Count Is an Effective Surrogate Marker for CD34+ Cell Count in Allogeneic Stem Cell Transplant Setting.

OBJECTIVE: We assessed the predictive potential of XN-HPC for CD34+ cell count as obtained through Sysmex automated hematology analyzers (XN-1000). METHODS: This study was conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation in 84 donors between December 2012 and December 2017 in the first phase and later validated in 112 donors between December 2017 and December 2018. Sysmex XN-1000 and BD FACS Calibur estimated XN-HPC and CD34+ cells of peripheral blood apheresis product, respectively. Spearman's correlation was assessed between XN-HPC and CD34+ cell count followed by receiver operating characteristic curve calculation to determine the XN-HPC cutoff for a CD34+ count of ≥2 million cells/kg of recipient's body weight RESULTS: There is a moderately positive correlation (P value = .003) between XN-HPC and CD34+ count. Receiver operating characteristic curve analyses demonstrated that a cutoff value for XN-HPC of ≥1·845×106cells/kg of recipient's body weight has a specificity and sensitivity of 100% and 78·2%, respectively, for predicting the CD34+ count of ≥2 million cells/kg of recipient's body weight. This cutoff value of XN-HPC was prospectively validated in 112 donors. The positive predictive value was found to be 100%, while negative predictive value was 17%. CONCLUSION: XN-HPC has a highly promising potential to serve as a cost-effective and time-saving surrogate for CD34+ cell count.

Magnetic Domain Wall Based Synaptic and Activation Function Generator for Neuromorphic Accelerators.

Magnetic domain walls are information tokens in both logic and memory devices and hold particular interest in applications such as neuromorphic accelerators that combine logic in memory. Here, we show that devices based on the electrical manipulation of magnetic domain walls are capable of implementing linear, as well as programmable nonlinear, functions. Unlike other approaches, domain-wall-based devices are ideal for application to both synaptic weight generators and thresholding in deep neural networks. Prototype micrometer-size devices operate with 8 ns current pulses and the energy consumption required for weight modulation is ≤16 pJ. Both speed and energy consumption compare favorably to other synaptic nonvolatile devices, with the expected energy dissipation for scaled 20 nm devices close to that of biological neurons.

Mutual control of coherent spin waves and magnetic domain walls in a magnonic device.

The successful implementation of spin-wave devices requires efficient modulation of spin-wave propagation. Using cobalt/nickel multilayer films, we experimentally demonstrate that nanometer-wide magnetic domain walls can be applied to manipulate the phase and magnitude of coherent spin waves in a nonvolatile manner. We further show that a spin wave can, in turn, be used to change the position of magnetic domain walls by means of the spin-transfer torque effect generated from magnon spin current. This mutual interaction between spin waves and magnetic domain walls opens up the possibility of realizing all-magnon spintronic devices, in which one spin-wave signal can be used to control others by reconfiguring magnetic domain structures.

A Cancer Patient Journey: Complete Review During Acute Treatment Phase.

Purpose: Cancer is a chronic illness with acute episodes lasting for years. Most cancer patients have coexisting comorbidities, which affect cancer treatment outcomes and make a shared care model for chronic diseases essential. There is a considerable gap between the achievable and delivered quality of care for cancer patients. Methods: We used a case study approach to examine the complexity of cancer management, from the perspective of one person's case as interpreted by the care team. It allowed the complexity of cancer management to retain its holistic and meaningful characteristics. We interviewed the patient, caregiver, primary care physician (PCP), and oncologist. Interviews were audio recorded and analyzed with ATLASti, qualitative statistical software. Participants also completed a basic demographic survey. Common themes were identified, analyzed, and discussed. Results: Main themes were lack of longitudinal relationship with PCP, communication barriers, and ambiguous health care provider roles. Communication barriers can be associated with the other two main themes. Conclusion: Our results showed that shared care for cancer management is lacking during the acute cancer treatment phase. Communication barriers between the PCP and oncologist along with lack of continuity of care and unclear role of the PCP are major contributors for fragmented cancer care in U.S. health care system.

A Novel Nonsense Mutation in FERMT3 Causes LAD-III in a Pakistani Family.

Leukocyte adhesion deficiency-III (LAD3) is an extremely rare primary immunodeficiency disorder, transmitted with autosomal-recessive inheritance. It is caused by genetic alteration in the FERMT3 gene, which leads to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of integrin activation. LAD3 has features like bleeding syndrome of Glanzmann-type and leukocyte adhesion deficiency. FERMT3 mutation(s) have not been well characterized in Pakistani patients with LAD3. In this study, an infant and his family of Pakistani origin, presenting with clinical features of LAD, were investigated to determine the underlying genetic defect. Targeted next generation sequencing (TGS) and Sanger sequencing were performed to identify and confirm the causative mutations, respectively, and their segregation within the family. A novel, homozygous FERMT3 nonsense mutation (c.286C > T, p.Q96∗) was found in the proband, and its co-segregation with LAD3 phenotype within the family was consistent with an autosomal recessive inheritance. Both parents were carriers of the same mutation. This family was offered prenatal diagnosis during first trimester of the subsequent pregnancy; the fetus carried the variant. In conclusion, our study is the first report to identify the novel homozygous variant c.286C > T, p.Q96∗in the FERMT3 gene, which might be the causative mutation for LAD3 patients of Pakistani origin.

Laboratory diagnosis for thalassemia intermedia: Are we there yet?

BACKGROUND: Differentiation between thalassemia major and thalassemia intermedia at presentation is not uniformly characterized, for which an absolute criteria needs to be developed. This study investigated the primary and secondary genetic modifiers to develop a laboratory finding by forming different genetic mutational combinations seen among thalassemia intermedia patients and comparing them with thalassemia major. METHODS: This cross-sectional study analyzed 315 thalassemia intermedia patients. One hundred and five thalassemia major patients were recruited on the basis of documented evidence of diagnosis and were receiving blood transfusion therapy regularly. Various mutational combinations were identified, and comparison was performed between thalassemia intermedia and major using statistical software STATA 11.1. RESULTS: The mean age of the total population was 5.9 ± 5.32 years of which 165 (52%) were males. Of the two groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9 were more prevalent among the thalassemia intermedia cohort. When comparison was performed between the thalassemia intermedia and thalassemia major patients, it showed significant results for the presence of Xmn-1 polymorphism. CONCLUSION: The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd 30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either with or without Xmn-1 prove to be strong indicators towards diagnosis of thalassemia intermedia.