bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Prick Test Versus Phadiatop as a Tool for Diagnosis of Allergic Rhinitis in Children
Authors: Traiyan Sasiwimon , Manuyakorn Wiparat , Kanchongkittiphon Watcharoot , Sasisakulporn Cherapat , Jotikasthira Wanlapa , Kiewngam Potjanee , Kamchaisatian Wasu , Benjaponpitak Suwat
Published: June 2020

Background

Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization.

Objective

To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard.

Methods

Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens.

Results

One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p < 0.001. Using NPT as a comparative standard for diagnosis for AR, SPT showed a sensitivity of 89.6% and specificity of 88.3% and Phadiatop provided the sensitivity of 88.6% and specificity of 95.3%.

Conclusions

SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.
Does practising hypnosis-derived communication techniques by oncology nurses translate into reduced pain and distress in their patients? An exploratory study
Authors: Ogez David , Aramideh Jennifer , Mizrahi Terry , Charest Marie-Claude , Plante Caroline , Duval Michel , Sultan Serge
Published: June 2020

Objectives:

To explore the effects of a hypnotic communication (HC) training for paediatric nurses in decreasing patients’ pain and distress during venipunctures.

Methods:

A 4-day theoretical and practical HC training was offered to five paediatric oncology nurses. The effects of HC were tested with 22 young cancer patients (13 girls, 9 boys, 10 ± 4 years) over four time points, with 88 encounters being video-recorded and coded in stable professional-patient dyads. Patients’ pain and distress were rated by patients and parents with visual analogue scales and coded from recordings using the Faces, Legs, Activity, Cry and Consolability (FLACC) scale.

Results:

We observed a significant decrease in pre-post distress reported by parents ( d = 0.45, p = 0.046). Two out of five nurses with higher skills acquisition had larger reduction in patients’ self-reported pain ( d = 1.03, p = 0.028), parents perceived pain ( d = 1.09, p = 0.042), distress ( d = 1.05, p = 0.043) as well as observed pain ( d = 1.22, p = 0.025). Favourable results on pain and distress did not maintain at follow-up.

Conclusion and clinical implications:

Training nurses in HC may translate into improved pain and distress in patients, both self-rated and observed provided that skills are used in practice. HC training is a promising non-pharmacological intervention to address pain in paediatrics.
Psycho-sensory relationships in chronic pain
Authors: Harvie Daniel S , Vasco Daniela , Sterling Michele , Low-Choy Samantha , Niederstrasser Nils G
Published: June 2020

Background:

Psychological variables contribute to pain- and injury-related outcomes. We examined the hypothesis that anatomical spread and intensity of persistent pain relate to anxiety-related variables: generalised anxiety, fear of pain and pain catastrophising.

Methods:

An online survey was used to gather data from 413 women with persistent pain (low back pain, n = 139; fibromyalgia syndrome, n = 95; neck pain, n = 55; whiplash, n = 41; rheumatoid arthritis, n = 37; migraine, n = 46). The spread and intensity of pain were assessed using the McGill pain chart and a Numerical Rating Scale. A Bayesian Structural Equation Model assessed if the intensity and spread of pain increased with anxiety-related variables. Men were also surveyed (n = 80), but the sample size was only sufficient for analysing if their data were consistent with the model for women.

Results:

Across subgroups of women, one standard deviation increase in catastrophising, generalised anxiety and fear corresponded to 27%, 7% and −1% additional pain areas and a 1.1, 0 and –0.1 change in pain intensity (on 0–10 scale), respectively. Overall, our clinical significance criterion – a 30% shift in pain variable in relation to one standard deviation increase in psychological variable – was not met. However, in subgroups it was met for pain spread (low back pain, neck pain and migraine) and pain intensity (migraine and neck pain) in relation to pain catastrophising. The model generally had low goodness-of-fit to men.

Conclusion:

These data support a meaningful relationship between some anxiety-related variables and pain in women for some conditions. Since the model did not consistently fit the men, we may conclude that the relationships are moderated by sex. Clinician attention to psychological variables as potential contributing factors can be justified; however, research is needed to understand the relationship and whether psychological treatment can reduce pain.
Applying Qualitative Methods to Investigate Social Actions for Justice Using Social Media: Illustrations From Facebook
Authors: Orth Zaida , Andipatin Michelle , Mukumbang Ferdinand C , van Wyk Brian
Published: June 2020

Social media is becoming a valuable resource for hosting activism as illustrated in the rise of the hashtag movements, such as #MeToo and #Endrapeculture, used to speak out against rape culture. In this article, we discuss the use of social media as the source and object of research, using the case of the 2016 South African #nakedprotest. We used naturalistic observation on Facebook comment threads and followed these up with online Facebook focus groups. Qualitative content analysis and thematic decomposition analysis were used, respectively, to explore online discourses of rape culture. We found that the use of social media as a medium for data collection is valuable for exploring trending social issues such as the rape culture #nakedprotest. We uncovered that social media offers researchers the opportunity to collect, analyze, and triangulate rich qualitative data for the exploration of social phenomena. This study illustrates the usefulness of social media as a pedagogical instrument.
Primary Care Physicians’ Knowledge, Perceptions, and Comfort Level in Managing Patients Fasting in Ramadan
Authors: Hamodat Hayam , Syed Saif , Ali Malik , Sardiwalla Yaeesh , Imran Fatima , Jarrar Ameer , Rafiq Farina , Zimmo Khader , Eissa Mohamed , Haroon Babar
Published: June 2020

Background: Once a year, Muslims fast from dawn to sunset during the month of Ramadan. While fasting has many positive health implications, it may pose risks to individuals with underlying health issues. Despite the exemption from fasting for those who are ill, many Muslims with chronic conditions choose to fast. It is unclear how many Muslim patients receive counseling on fasting. As such, the purpose of this pilot project was to assess the knowledge, perception, and comfort level of primary care physicians (PCPs) at Dalhousie University’s Department of Family Medicine in managing patients choosing to fast during Ramadan. Methods: A 16-item anonymous, self-administered, structured online survey was distributed to PCPs with an academic affiliation with the Department of Family Medicine at Dalhousie University. Participants rated their level of comfort, objective knowledge, and perceptions of managing patients fasting in Ramadan. Results: Many PCPs perceived the importance of understanding Ramadan fasting and its relevance to their patients’ health, however, they did not have adequate knowledge about the matter. The majority of PCPs felt they received inadequate training in this area and did not feel comfortable counseling and managing the health of these patients. Conclusions: The findings of this study have outlined a knowledge gap that exists within our PCP community and will help inform and prioritize educational needs and direct efforts to ensure safe patient management during Ramadan.
Diagnosis of Skin Lesions Using Photographs Taken With a Mobile Phone: An Online Survey of Primary Care Physicians
Authors: Marin-Gomez Francesc X. , Vidal-Alaball Josep , Poch Pere Roura , Sariola Carles Janes , Ferrer Rosa Taberner , Peña Jacobo Mendioroz
Published: June 2020

Skin conditions are one of the most frequent reasons for visiting a primary health care facility, making it of vital importance that general practitioners (GPs) have the right knowledge and tools to diagnose the most frequent dermatological conditions. Methods: This study evaluates the accuracy of dermatological diagnoses made by 120 GPs based on photographs taken with a smartphone by an anonymous online cross-sectional survey. Results: The study was carried out between August and October 2018. The results show that the majority of the participants are in favor of using mobile phones to communicate with other professionals and use them to consult medical images. The majority (69%) took dermatological photographs and the preferred device was a smartphone (70%). From 22 different images evaluated, in 69% of responses, participants expressed a high degree of confidence in their ability to diagnose the lesion shown and in 72% of the cases, the diagnosis chosen was correct. Conclusions: The study confirms that the use of smartphone to send medical images is growing rapidly and its potential for taking medical images is an opportunity to help primary care teams deal with dermatological problems. The results suggest that GPs need further training in interpreting dermatological images, to increase their diagnostic confidence and to avoid the need for referrals to face-to-face visits.
Expression of Key Androgen-Activating Enzymes in Ovarian Steroid Cell Tumor, Not Otherwise Specified
Authors: Valenzuela Scheker Evana , Kathuria Amita , Esnakula Ashwini , Sasano Hironobu , Yamazaki Yuto , Tevosian Sergei , Auchus Richard J. , Ghayee Hans K. , Dhir Gauri
Published: June 2020

To characterize the expression of steroidogenic enzymes implicated in the development of ovarian steroid cell tumors, not otherwise specified (SCT-NOS). We present 4 ovarian SCT-NOS evaluated by immunohistochemical staining of steroidogenic enzymes as an approach to define this entity pathologically. All 4 ovarian SCT-NOS showed increased expression for cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase (CYP17A1), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), aldo-ketoreductase type 1 C3 (AKR1C3), 3β-hydroxysteroid dehydrogenase 2 (HSD3B2), 5α-reductase type 2 (SRD5A2), steroid sulfatase (SULT2A1), estrogen sulfotransferase (EST), and aromatase (CYP19A1). Expression was negative for 21-hydroxylase (CYP21A2) and 17β-hydroxysteroid dehydrogenase 2 (HSD17B2). 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) and 5α-reductase type 1 (SRD5A1) showed variable expression. Our analysis reveals a novel finding of increased expression of AKR1C3, HSD17B1, SRD5A2, SULT2A1, and EST in ovarian SCT-NOS, which is clinically associated with androgen excess and virilization. Further studies are needed to validate these enzymes as new markers in the evaluation of hyperandrogenic ovarian conditions.
The Subhedar’s Son: A Narrative of Brahmin-Christian Conversion from Nineteenth-Century Maharashtra, edited by Deepra Dandekar
Authors: Frykenberg Robert Eric
Published: June 2020

This son of a former local ruler, from the elite Brahman community that had presided over the fortunes of the Maratha Empire before its defeat by the British Raj, became a Christian convert and then served as a pastor of local churches in Western India for nearly forty years. His autobiography was later turned into a prize-winning novel. This rare pioneering vernacular account, reflecting the highly complex, multilayered cultural legacy of an emerging hybrid Christianity, represented a new genre of nativist devotion and piety. Subjected to a carefully contextualized and critical scholarship, we now have this work in English.
Development of vaccines against the sexually transmitted infections gonorrhoea, syphilis, Chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus
Authors: McIntosh Edwin David G.
Published: June 2020

The success in preventing hepatitis B virus and human papillomavirus infections by means of vaccination paves the way for the development of other vaccines to prevent sexually transmitted infections (STIs) such as gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus. The current status of vaccine development for these infections will be explored in this review.

The general principles for success include the need for prevention of latency, persistence and repeat infections. A reduction in transmission of STIs would reduce the global burden of disease. Therapeutic activity of vaccines against STIs would be advantageous over preventative activity alone, and prevention of congenital and neonatal infections would be an added benefit. There would be an added value in the prevention of long-term consequences of STIs. It may be possible to re-purpose ‘old’ vaccines for new indications. One of the major challenges is the determination of the target populations for STI vaccination.
Victimology of Sexual Harassment on Public Transportation: Evidence from India
Authors: Valan Michael L.
Published: June 2020

It is evident from the daily lives of cross sections of the urban society that most working women choose to opt for public transportation. Regrettably, during the course of their commute, they are susceptible to verbal, physical, psychological and financial harassment at the hands of their fellow travellers and bus operators. Underreporting ensures that cases of this kind do not surface in mainstream media. In the recent past, to the best of the knowledge of the researcher, very few studies have been conducted around the world on this subject in general, and in India in particular. Hence, the present research assumes significance. In this connection, an attempt has been made to measure the prevalence and nature of harassment suffered by women using public transportation in Chennai city in victimological perspective. A convenience sample of 530 women riding public transportation was identified and data was collected from them using a self-reported questionnaire. The findings revealed that around 35 per cent of all young women have been harassed in one of the forms mentioned above in the last six months. Further results and implications are discussed in the article.
Online visual monitoring and ultrasonic feedback detection in the ultrasonic precision bonding of polymers
Authors: Sun Yibo , Feng Yuqi , Hu Pengfei , Zhao Xing , Yang Xinhua , Wu Guoxiong
Published: June 2020

Ultrasonic bonding is a convenient bonding technology, which features sufficient cleanliness, high efficiency, no need for additional bonding aids, and other outstanding advantages. In recent years, it has been introduced into the field of the micro–nano assembly of polymer micro–nano devices, but it is still difficult for current ultrasonic bonding technology to meet the accuracy requirements of the micro–nano assembly. To improve the control accuracy of the hot-melt interface in the process of ultrasonic bonding, an online hot-melt interface monitoring method and an online ultrasonic transmission efficiency detection method are proposed in this article. With these detection methods, the real-time monitoring of the hot-melt interface can be realized on the basis of machine vision, while high-frequency dynamic force sensors can be used to detect the ultrasonic vibration transmitted from the ultrasonic horn to the anvil. Based on these methods, a functional anvil based on visual monitoring and ultrasonic detection is developed, the finite element method has been used to analyze the transmission characteristics of ultrasonic vibration, and experiments are carried out regarding online detection in the process of ultrasonic bonding. The results show that this system can realize the online detection of the hot-melt interface and ultrasonic transmission information, providing a new control method for ultrasonic bonding technology.
Prenatal Diagnosis of Placental Invasion: A Systematic Review and Meta-analysis on Accuracy of Ultrasonography and MRI in Diagnosis of Placental Invasion
Authors: Dahmarde Hamid , Parooie Fateme , Salarzaei Morteza
Published: June 2020

Objective:

The aim of this systematic review and meta-analysis was to evaluate and compare the diagnostic accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in the diagnosis of placental invasion.

Method:

Two independent scientists carried out a series of searches to obtain relevant research, released from January 1, 2009, to December 31, 2018. National databases (Magiran and SID), KoreaMed, and LILACS were reviewed for literature, released in other languages. A series of MeSH keywords was employed as part of the searching strategy (e.g., pregnancy, pregnant, placental invasion, accreta). A forest plot was built with Meta-DiSc, version 1.4.

Results:

For placental invasion, the sensitivity and specificity of MRI were 89% (95% confidence interval [CI], 83%–93% with a 95% confidence interval) and 97% (95% CI, 93%–99%), respectively. The sensitivity and specificity of US were 73% (95% CI, 66%–79%) and 89% (95% CI, 84%–93%), respectively. In the detection of placenta accreta solely (as the first grade of placental invasion), the sensitivity and specificity of MRI were 89.3% (95% CI, 86%–92%) and 84% (95% CI, 77%–89.6%). The sensitivity and specificity of US detection were 95.4% (95% CI, 93.8%–96.6%) and 87.3% (95% CI, 81.4%–91.9%), respectively.

Conclusion:

Due to the increased cesarean sections, placental invasion may be increasing. The diagnosis of prenatal placental invasion is important to reduce maternal morbidity and mortality. Recent trends indicate an increased use of MRI to evaluate placental invasion as a complement to US. The most accurate imaging findings are using US for placental lacunae and MRI to detect the dark intraplacental band.
Evaluation of the Diagnostic Value of Bedside Transthoracic Ultrasonography (TTUS) and Lower Extremity Three-Points Compression Duplex in the Diagnosis of the Pulmonary Embolism
Authors: Golshani Keihan , Sharafsaleh Mohammad
Published: June 2020

Background:

The present study aimed at evaluating the diagnostic value of lung transthoracic ultrasonography (TTUS) and lower extremity sonography versus computed tomography pulmonary angiography (CTPA) in the diagnosis of pulmonary embolus (PE).

Materials and Methods:

This study was performed on 104 patients with clinically suspected PE. CTPA and D-dimer was performed on all patients. Wells’ deep vein thrombosis criteria (WDVTC) was evaluated and recorded at the patient’s admission. Finally, the results of adding venous and lung sonography scores to the WDVTC with and without the results of D-dimer test were analyzed for predicting the diagnosis of PE.

Results:

There were 104 patients clinically suspected of having a PE and enrolled in the study. A PE was confirmed in 37.5% of this cohort. WDVTC had a sensitivity and specificity of 94.87% and 80.00%, respectively, to predict PE. When adding D-dimer to the WDVTC for patients unlikely to have a PE (WDVTC≤4), the sensitivity and specificity of positive D-dimer in diagnosis of PE were 94.87% and 56.92%, respectively ( P < .001).

Conclusion:

According to these study results, the modification of the WDVTC along with the results of lung TTUS and lower extremity venous sonogram significantly increase the diagnostic power for PE.
An Invasive Molar Pregnancy: A Case Report With Associated Imaging
Authors: Levine Elliot M. , Fernandez Carlos M. , McElwee Angela
Published: June 2020

Human chorionic gonadotropin is generally used as a biomarker to identify invasive molar pregnancy. The extent of the disease (e.g., its staging) has not, however, relied on its sonographic description. A case is presented that can illustrate some diagnostically useful sonographic features of three-dimensional transvaginal sonography for this condition. The clinical imaging of this case initially suggested it to be a benign hydatidiform mole but ultimately was diagnosed as an invasive molar pregnancy, with human chorionic gonadotropin monitoring. Clinical imaging was used to help manage this patient, with the demonstration of trophoblastic invasion of the uterine wall. Although two-dimensional sonography is commonly used to diagnose molar pregnancy, three-dimensional sonography may offer a clinical advantage for the management of invasive molar pregnancy, which can occur in 15% of benign hydatidiform molar pregnancies.
Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis
Authors: Neveu Gaëlle , Richard Cyrielle , Dupuy Florian , Behera Prativa , Volpe Fiona , Subramani Pradeep Annamalai , Marcel-Zerrougui Benjamin , Vallin Patrice , Andrieu Muriel , Minz Aruna Mukti , Azar Nabih , Martins Rafael M. , Lorthiois Audrey , Gazeau Florence , Lopez-Rubio José-Juan , Mazier Dominique , Silva Amanda K. A. , Satpathi Sanghamitra , Wassmer Samuel C. , Verdier Frédérique , Lavazec Catherine
Published: June 2020

Plasmodium falciparum gametocytes, the sexual stage responsible for malaria parasite transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated. Here, we identify late erythroblasts as a new host cell for P falciparum sexual stages and show that gametocytes can fully develop inside these nucleated cells in vitro and in vivo, leading to infectious mature gametocytes within reticulocytes. Strikingly, we found that infection of erythroblasts by gametocytes and parasite-derived extracellular vesicles delay erythroid differentiation, thereby allowing gametocyte maturation to coincide with the release of their host cell from the bone marrow. Taken together, our findings highlight new mechanisms that are pivotal for the maintenance of immature gametocytes in the bone marrow and provide further insights on how Plasmodium parasites interfere with erythropoiesis and contribute to anemia in malaria patients.
Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition
Authors: Dzama Margarita M. , Steiner Marlene , Rausch Johanna , Sasca Daniel , Schönfeld Jonas , Kunz Kerstin , Taubert Martha C. , McGeehan Gerard M. , Chen Chun-Wei , Mupo Annalisa , Hähnel Patricia , Theobald Matthias , Kindler Thomas , Koche Richard P. , Vassiliou George S. , Armstrong Scott A. , Kühn Michael W. M.
Published: June 2020

The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced. Combining menin-MLL inhibition with specific small-molecule kinase inhibitors of FLT3 phosphorylation resulted in a significantly superior reduction of phosphorylated FLT3 and transcriptional suppression of genes downstream of FLT3 signaling. The drug combination induced synergistic inhibition of proliferation, as well as enhanced apoptosis, compared with single-drug treatment in models of human and murine NPM1mut and MLL-r leukemias harboring an FLT3 mutation. Primary acute myeloid leukemia (AML) cells harvested from patients with NPM1mutFLT3mut AML showed significantly better responses to combined menin and FLT3 inhibition than to single-drug or vehicle control treatment, whereas AML cells with wild-type NPM1, MLL, and FLT3 were not affected by either of the 2 drugs. In vivo treatment of leukemic animals with MLL-r FLT3mut leukemia reduced leukemia burden significantly and prolonged survival compared with results in the single-drug and vehicle control groups. Our data suggest that combined menin-MLL and FLT3 inhibition represents a novel and promising therapeutic strategy for patients with NPM1mut or MLL-r leukemia and concurrent FLT3 mutation.
CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma
Authors: Ramkumar Poornima , Abarientos Anthony B. , Tian Ruilin , Seyler Meghan , Leong Jaime T. , Chen Merissa , Choudhry Priya , Hechler Torsten , Shah Nina , Wong Sandy W. , Martin Thomas G. , Wolf Jeffrey L. , Roybal Kole T. , Pahl Andreas , Taunton Jack , Wiita Arun P. , Kampmann Martin
Published: June 2020

Cancer cells commonly develop resistance to immunotherapy by loss of antigen expression. Combinatorial treatments that increase levels of the target antigen on the surface of cancer cells have the potential to restore efficacy to immunotherapy. Here, we use our CRISPR interference– and CRISPR activation–based functional genomics platform to systematically identify pathways controlling cell surface expression of the multiple myeloma immunotherapy antigen B-cell maturation antigen (BCMA). We discovered that pharmacologic inhibition of HDAC7 and the Sec61 complex increased cell surface BCMA, including in primary patient cells. Pharmacologic Sec61 inhibition enhanced the antimyeloma efficacy of a BCMA-targeted antibody-drug conjugate. A CRISPR interference chimeric antigen receptor T cells (CAR-T cells) coculture screen enabled us to identify both antigen-dependent and antigen-independent mechanisms controlling response of myeloma cells to BCMA-targeted CAR-T cells. Thus, our study shows the potential of CRISPR screens to uncover mechanisms controlling response of cancer cells to immunotherapy and to suggest potential combination therapies.
Venetoclax and hypomethylating agents (HMAs) induce high response rates in MDS, including patients after HMA therapy failure
Authors: Ball Brian J. , Famulare Christopher A. , Stein Eytan M. , Tallman Martin S. , Derkach Andriy , Roshal Mikhail , Gill Saar I. , Manning Benjamin M. , Koprivnikar Jamie , McCloskey James , Testi Rebecca , Prebet Thomas , Al Ali Najla H. , Padron Eric , Sallman David A. , Komrokji Rami S. , Goldberg Aaron D.
Published: June 2020

Key Points

Treatment-naive and relapsed/refractory MDS patients receiving venetoclax and HMAs have an ORR of 59% with 63% of responders proceeding to transplant. Allogeneic stem cell transplantation after treatment with venetoclax in combination with HMA is associated with prolonged survival.
Genetic and evolutionary patterns of treatment resistance in relapsed B-cell lymphoma
Authors: Rushton Christopher K. , Arthur Sarah E. , Alcaide Miguel , Cheung Matthew , Jiang Aixiang , Coyle Krysta M. , Cleary Kirstie L. S. , Thomas Nicole , Hilton Laura K. , Michaud Neil , Daigle Scott , Davidson Jordan , Bushell Kevin , Yu Stephen , Rys Ryan N. , Jain Michael , Shepherd Lois , Marra Marco A. , Kuruvilla John , Crump Michael , Mann Koren , Assouline Sarit , Connors Joseph M. , Steidl Christian , Cragg Mark S. , Scott David W. , Johnson Nathalie A. , Morin Ryan D.
Published: June 2020

Diffuse large B-cell lymphoma (DLBCL) patients are typically treated with immunochemotherapy containing rituximab (rituximab, cyclophosphamide, hydroxydaunorubicin-vincristine (Oncovin), and prednisone [R-CHOP]); however, prognosis is extremely poor if R-CHOP fails. To identify genetic mechanisms contributing to primary or acquired R-CHOP resistance, we performed target-panel sequencing of 135 relapsed/refractory DLBCLs (rrDLBCLs), primarily comprising circulating tumor DNA from patients on clinical trials. Comparison with a metacohort of 1670 diagnostic DLBCLs identified 6 genes significantly enriched for mutations upon relapse. TP53 and KMT2D were mutated in the majority of rrDLBCLs, and these mutations remained clonally persistent throughout treatment in paired diagnostic-relapse samples, suggesting a role in primary treatment resistance. Nonsense and missense mutations affecting MS4A1, which encodes CD20, are exceedingly rare in diagnostic samples but show recurrent patterns of clonal expansion following rituximab-based therapy. MS4A1 missense mutations within the transmembrane domains lead to loss of CD20 in vitro, and patient tumors harboring these mutations lacked CD20 protein expression. In a time series from a patient treated with multiple rounds of therapy, tumor heterogeneity and minor MS4A1-harboring subclones contributed to rapid disease recurrence, with MS4A1 mutations as founding events for these subclones. TP53 and KMT2D mutation status, in combination with other prognostic factors, may be used to identify high-risk patients prior to R-CHOP for posttreatment monitoring. Using liquid biopsies, we show the potential to identify tumors with loss of CD20 surface expression stemming from MS4A1 mutations. Implementation of noninvasive assays to detect such features of acquired treatment resistance may allow timely transition to more effective treatment regimens.
Severe low cerebral oximetry in difficult cardiopulmonary bypass weaning of low body-weight infant: a case report and literature review
Authors: Hao Xuechao , Wei Wei
Published: June 2020

Background

For infants undergoing complex cardiac surgery, hemodynamic management after cardiopulmonary bypass (CPB) is challenging because of severe myocardial edema, vasomotor dysfunction and weak tolerance to a change in blood volume. More importantly, the lack of availability of equipment for advanced monitoring, such as transesophageal echocardiography or transthoracic echocardiography, restricts the accurate assessment of hemodynamics.

Case presentation

This is a case of severe hypotension and non-detectable pulse oxygen saturation (SpO2) after CPB in a low-weight infant who had normal blood pressure and oxygen saturation before surgery. Epinephrine and milrinone were administered with cerebral oximetry monitoring rather than blood pressure measurements because cerebral oximetry was more responsive to treatment than blood pressure. Under the guidance of cerebral oximetry, the infant was successfully weaned from CPB and recovered after surgery without adverse neurological events.

Conclusions

For infants who develop refractory hypotension and failure in SpO2 monitoring during the CPB weaning period, cerebral oximetry provides an index for assessing brain perfusion and valuable guidance for appropriate inotropic treatment.
Accuracy and trending abilities of finger plethysmographic blood pressure and cardiac output compared to invasive measurements during caesarean delivery in healthy women: an observational study
Authors: Omenås Ivar N. , Tronstad Christian , Rosseland Leiv Arne
Published: June 2020

Background

In women presenting for caesarean section under spinal anesthesia, continuous measurement of circulatory aspects, such as blood pressure and cardiac output, is often needed. At present, invasive techniques are used almost exclusively. Reliable non-invasive monitoring would be welcome, as it could be safer, less uncomfortable, and quick and easy to apply. We aimed to evaluate whether a non-invasive, finger plethysmographic device, the ccNexFin monitor, can replace invasively measured blood pressure in the radial artery, and whether cardiac output measurements from this device can be used interchangeably with measurements from the mini-invasive LiDCO monitor currently in use at our institution.

Methods

Simultaneous invasive measurements were compared to ccNexFin in 23 healthy women during elective caesarean section under spinal anesthesia. We used Bland Altman statistics to assess agreement, and polar plot methodology to judge trending abilities with pre-defined limits.

Results

Mean arterial and systolic pressures showed biases (invasive – ccNexFin) of − 4.3 and 12.2 mmHg, with limits of agreement of − 15.9 – 7.4 and − 11.1 – 35.6, respectively. The ccNexFin trending abilities were within the suggested limits for mean pressure but insufficient for systolic pressure compared to invasive measurements. Cardiac output had a small bias of 0.2 L/min, but wide limits of agreement of − 2.6 – 3.0. The ccNexFin trending abilities compared to the invasive estimated values (LiDCO) were unsatisfactory.

Conclusions

We consider the ccNexFin monitor to have sufficient accuracy in measuring mean arterial pressure. The limits of agreement for systolic measurements were wider, and the trending ability compared to invasive measurements was outside the recommended limit. The ccNexFin is not reliable for cardiac output measurements or trend in pregnant women for caesarean delivery under spinal anesthesia.

Trial registration

Registered May 23, 2013, at ClinicalTrials.gov under number NCT01861132.
Combined sodium Dimercaptopropanesulfonate and zinc versus D-penicillamine as first-line therapy for neurological Wilson’s disease
Authors: Zhang Jing , Xiao Lulu , Yang Wenming
Published: June 2020

Background

Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson’s diseases (WD), the current treatment options available for WD are still limited, especially for WD patients with neurological symptoms. This study is intended to compare the therapeutic approaches for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy, and identify the more effective therapeutic approach.

Methods

The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients treated with intravenous DMPS + Zinc and in combination with oral zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS) and Barthel index. The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed.

Results

Ninety-three patients in Group 1, displayed decreased GAS scores and increased Barthel indexes consistently in comparison with the baseline (P < 0.01). Among them, 82 patients (88.2%) exhibited significant neurological improvement after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) exhibited neurological improvements, while 17 patients (26.2%) experienced neurological deterioration after 1-year follow up. Six patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio (P < 0.01) and lower worsening ratio of the neurological symptoms for the patients (P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and blood cell counts remained stabilized in group1.

Conclusions

This study indicates that the combined therapeutic approach of DPMS and zinc may be a preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA.
The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: a systematic review
Authors: Baron Ruth , Taye Meron , der Vaart Isolde Besseling-van , Ujčič-Voortman Joanne , Szajewska Hania , Seidell Jacob C. , Verhoeff Arnoud
Published: June 2020

Background

Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever.

Methods

Pubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18 years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively.

Results

(1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02–1.24) to OR 3.19 (1.52–6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08–1.16) to OR 3.21 (1.89–5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed.

Conclusions

This review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.
Clinical and Genetic Study on a Chinese Patient with Infantile Onset Epileptic Encephalopathy carrying a PPP3CA Null Variant: a case report
Authors: Yang Sai , Shen Xiang , Kang Qingyun , Kuang Xiaojun , Ning Zeshu , Liu Shulei , Liao Hongmei , Cao Zhenhua , Yang Liming
Published: June 2020

Background

PPP3CA gene encodes the catalytic subunit A of a calcium-dependent protein phosphatase called calcineurin. However, two distinct mechanisms in PPP3CA deficiency would cause two clinically different diseases. Gain-of-function mutations in the autoinhibitory domain at the C-terminus would cause ACCIID that stands for arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development. While loss-of-function mutations in PPP3CA would cause infantile or early childhood onset epileptic encephalopathy1, named as IECEE1. IECEE1 is a severe epileptic neurodevelopmental disorder and mainly characterized by psychomotor delay. Here, we report a Chinese patient who was clinically and genetically diagnosed as IECEE1. We also extensively analyzed electroencephalogram (EEG) features of the patient in this study.

Case presentation

A 2-year-old Chinese patient who had recurrent polymorphic seizures was clinically and genetically diagnosed as IECEE1. A frameshift variant c.1283insC (p.T429NfsX22) was identified in this case. Multiple types of abnormal features were observed in the EEG, comparing with the previous reports.

Conclusions

These findings could expand the spectrum of PPP3CA mutations and might also support the diagnosis and further study of IECEE1.
Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity
Authors: Bachman Thomas E. , Iyer Narayan P. , Newth Christopher J. L. , Ross Patrick A. , Khemani Robinder G.
Published: June 2020

Background

Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited.

Methods

This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50–80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels.

Results

Neonates were categorized by postmenstrual age: < 33 (n = 155), 33–36 (n = 192) and > 36 (n = 1031) weeks.

From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24–28) n = 2603; 34 (33–35) n = 2501; and 38 (37–39) n = 21,058. The chance of normoxemia (65, 95%-CI 64–67%) was similar across the SpO2 range of 88–95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21–29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18–33%), for infants 33–36 weeks at 97% SpO2 (24, 95%-CI 14–25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17–22%).

Conclusions

The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.
Comparison between minimally invasive deltoid-split and extended deltoid-split approach for proximal humeral fractures: a case-control study
Authors: Wang Ji-Qi , Lin Chui-cong , Zhao You-Ming , Jiang Bing-Jie , Huang Xiao-Jing
Published: June 2020

Background

With the rapid aging of the population, the incidence of proximal humeral fracture (PHF) has increased. However, the optimal method for open reduction and internal fixation (ORIF) remains controversial.

Methods

We performed a retrospective analysis of patients with PHF who underwent locking plate internal fixation at our institution from January 2016 to December 2018. Patients were divided into two groups based on the surgical approach used: an expanded deltoid-split approach group (ORIF group) and minimally invasive deltoid-split approach group (minimally invasive percutaneous plate osteosynthesis, [MIPPO] group). The groups were compared in terms of demographic and perioperative characteristics, and clinical outcomes.

Results

A total of 115 cases of PHF were included in our study, of which 64 cases were treated using the minimally invasive deltoid-split approach and 51 using the extended deltoid-split approach. Fluoroscopy was performed significantly less frequently in the ORIF group and the surgical duration was shorter. However, the postoperative visual analogue scale (VAS) pain score and duration of postoperative hospital stay were significantly higher compared to the MIPPO group. Moreover, secondary loss was significantly less extensive in the ORIF group compared to the MIPPO group, while there was no significant group difference in fracture healing time, Constant shoulder score, or complications at the last follow-up visit.

Conclusions

The clinical outcomes associated with both the minimally invasive and extended deltoid-split approaches were satisfactory. The data presented here suggest that the extended deltoid-split approach was superior to the minimally invasive deltoid-split approach in terms of operational time, fluoroscopy, and secondary loss of reduction, while the minimally invasive approach was superior in terms of postoperative pain and hospital stay. Accordingly, neither procedure can be considered definitively superior; the optimal surgical procedure for PHF can only be determined after full consideration of the situation and requirements of the individual patient.
Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma
Authors: Zhang Peng-Fei , Gao Chao , Huang Xiao-Yong , Lu Jia-Cheng , Guo Xiao-Jun , Shi Guo-Ming , Cai Jia-Bin , Ke Ai-Wu
Published: June 2020

Objective

Natural killer (NK) cells play a critical role in the innate antitumor immune response. Recently, NK cell dysfunction has been verified in various malignant tumors, including hepatocellular carcinoma (HCC). However, the molecular biological mechanisms of NK cell dysfunction in human HCC are still obscure.

Methods

The expression of circular ubiquitin-like with PHD and ring finger domain 1 RNA (circUHRF1) in HCC tissues, exosomes, and cell lines was detected by qRT-PCR. Exosomes were isolated from the culture medium of HCC cells and plasma of HCC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit and then characterized by transmission electronic microscopy, NanoSight and western blotting. The role of circUHRF1 in NK cell dysfunction was assessed by ELISA. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the molecular mechanisms of circUHRF1 in NK cells. In a retrospective study, the clinical characteristics and prognostic significance of circUHRF1 were determined in HCC tissues.

Results

Here, we report that the expression of circUHRF1 is higher in human HCC tissues than in matched adjacent nontumor tissues. Increased levels of circUHRF1 indicate poor clinical prognosis and NK cell dysfunction in patients with HCC. In HCC patient plasma, circUHRF1 is predominantly secreted by HCC cells in an exosomal manner, and circUHRF1 inhibits NK cell-derived IFN-γ and TNF-α secretion. A high level of plasma exosomal circUHRF1 is associated with a decreased NK cell proportion and decreased NK cell tumor infiltration. Moreover, circUHRF1 inhibits NK cell function by upregulating the expression of TIM-3 via degradation of miR-449c-5p. Finally, we show that circUHRF1 may drive resistance to anti-PD1 immunotherapy in HCC patients.

Conclusions

Exosomal circUHRF1 is predominantly secreted by HCC cells and contributes to immunosuppression by inducing NK cell dysfunction in HCC. CircUHRF1 may drive resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for patients with HCC.