bluuebunny/crossref_metadata_2025 huggingface dataset:
P-436 EndoTime: Non-categorical timing estimates for luteal endometrium
Authors: Mitchell A , Lipecki J , Muter J , Lucas E , Makwana K , Fishwick K , Odendaal J , Hawkes A , Vrljicak P , Brosens J , Ott S
Published: June 2022

Study question

Can expression measurements of a small panel of genes be used to develop a continuous, non-categorical model for the improvement of endometrial biopsy timing accuracy?

Summary answer

Measuring expression levels of six genes (IL2RB, IGFBP1, CXCL14, DPP4, GPX3, and SLC15A2) is sufficient to obtain and assess substantially more accurate timing estimates.

What is known already

Commercially available endometrial timing approaches based on gene expression require much larger gene sets and use a categorical approach that classifies samples as pre-receptive, receptive, or post-receptive.

Study design, size, duration

Gene expression was measured by RT-qPCR in different sample sets, comprising a total of 664 endometrial biopsies obtained 4 to 12 days after a self-reported positive home ovulation test. A further 36 endometrial samples were profiled by RT-qPCR as well as RNA-sequencing.

Participants/materials, setting, methods

A computational procedure, named ‘EndoTime’, was established that models the temporal profile of each gene and estimates the timing of each sample. Iterating these steps, temporal profiles are gradually refined as sample timings are being updated, and confidence in timing estimates is increased. After convergence, the method reports updated timing estimates for each sample while preserving the overall distribution of time points.

Main results and the role of chance

The Wilcoxon rank-sum test was used to confirm that ordering samples by EndoTime estimates yields sharper temporal expression profiles for held-out genes (not used when determining sample timings) than ordering the same expression values by patient-reported times (GPX3 : p < 0.005; CXCL14 : p < 2.7e-6; DPP4 : p < 3.7e-13). Pearson correlation between EndoTime estimates for the same sample set but based on RT-qPCR or RNA-sequencing data showed high degree of congruency between the two (p = 8.6e-10, R-squared = 0.687). Estimated timings did not differ significantly between control subjects and patients with recurrent pregnancy loss or recurrent implantation failure (p > 0.05).

Limitations, reasons for caution

Timing estimates are informed by glandular gene expression and will only represent the temporal state of other endometrial cell types if in synchrony with the epithelium. Additionally, methods that estimate the day of ovulation are still required as these data are essential inputs in our method.

Wider implications of the findings

Our method is the first to assay the temporal state of endometrial samples on a continuous domain, enabling accurate temporal profiling of any gene in luteal phase biopsies for a wide range of research applications and, potentially, clinical use. It is freely available, open-source software including supporting data sets.

Trial registration number

Not applicable
P-561 Long-read amplicon guided haplotype imputation enabling comprehensive preimplantation genetic testing in families with de novo pathogenic variants
Authors: Ayeb Y , Tsuiko O , Jatsenko T , Allemeersch J , Melotte C , Ding J , Denayer E , Legius E , Brems H , Vermeesch J , Dimitriadou E
Published: June 2022

Study question

Can we use comprehensive genome-wide haplotyping PGT for couples carrying de novo mutations, given the absence of phasing references to establish the disease-associated haplotype?

Summary answer

Targeted amplicon long-read sequencing represents a valuable approach for PGT workup that leverages comprehensive PGT application in families with de novo mutations.

What is known already

Preimplantation genetic testing (PGT) aims to select embryos devoid of inherited pathogenic variants. Current comprehensive genome-wide haplotyping PGT methods cannot be applied for couples where one of the partners carries a de novo mutation, as absence of affected close relatives restricts variant phasing to establish the disease-associated haplotype. For such families targeted approaches are currently used instead, thus missing genome-wide embryo analysis.

Study design, size, duration

To overcome the forementioned limitation, we developed a long-read amplicon guided haplotype imputation method. From January 2017 till June 2021 thirty-two couples were enrolled into the PGT program at the Centre for Human Genetics, UZ Leuven, in the context of a de novo variant causing a known monogenic disorder in one of the two partners.

Participants/materials, setting, methods

Genomic DNA from the partner carrying the variant (proband) and his/her parents was used for trio analysis via long-range PCR and long-read amplicon sequencing using the PacBio RSII and/or Oxford Nanopore platforms. Targeted haplotype phasing was then performed to impute the disease-associated allele.

Main results and the role of chance

The parental origin of the mutant allele was identified in 20 patients, resulting in the current 62.5% success rate. Most de novo mutations occurred on the paternal allele. In the remaining families, the region of interest either had no SNPs or had insufficient number of informative SNPs linked to mutation. From the successfully analyzed couples, eight have proceeded to PGT cycle and so far, three disease-free children have been born.

Limitations, reasons for caution

A costly family-specific work-up is required, allowing nevertheless the implementation of a generic genome-wide method at the embryo analysis stage. The sequencing cost itself is anticipated to decrease in time. To avoid non-informative results, the analysis of multiple amlpicons is recommended.

Wider implications of the findings

Current practices for the handling of couples with de novo variants are mostly targeted, require the combination of direct and indirect approaches and often require the multiple biopsies. Targeted amplicon long-read sequencing represents a valuable approach for PGT workup that leverages comprehensive PGT application in families with de novo mutations.

Trial registration number

not applicable
P-580 Cumulative live birth rate of oocyte in-vitro maturation with a pre-maturation step in women with polycystic ovary syndrome or high antral follicle count
Authors: Pham H , Le A , Nguyen A , Ha U , Nguyen T , Pham T , Ho T , Vuong L
Published: June 2022

Study question

What is the cumulative live birth rate (CLBR) at 24 months of women undergoing oocyte in vitro maturation (IVM) a with pre-maturation step (CAPA-IVM)?

Summary answer

The CLBR at 24 months with CAPA-IVM was 38.2%.

What is known already

IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM) improves the competence of oocytes matured in-vitro by sustaining meiotic arrest to allow the synchronization of cytoplasmic and genetic maturation of the oocytes. Results from a randomized controlled trial showed that CAPA-IVM resulted in a live birth rate after the first transfer of 35.2% which was non-inferior to IVF. There is a lack of data on cumulative live birth following CAPA-IVM.

Study design, size, duration

A multi-center, retrospective study, performed at IVFMD, My Duc Hospital and IVFMD Phu Nhuan, My Duc Phu Nhuan Hospital from 1 January 2017 to 31 December 2019.

Participants/materials, setting, methods

All women with polycystic ovary syndrome (PCOS) or high antral follicle count (AFC) treated with a CAPA-IVM cycle were recruited to the study. All embryos were frozen at day 3. Cumulative live birth was difined as at least one live birth resulting from initiated CAPA-IVM cycle. If the women did not return for embryo transfer, outcomes were followed up until 24 months from aspiration day. Logistic regression was performed to assess which factors predicted CLBR.

Main results and the role of chance

Between 1 January 2019 and 31 December 2019, there were 374 eligible women included in the study, among them, 368 patients had embryos for transfer (98.4%) and six patients had no embryo for transfer (1.6%). A total of 496 frozen embryo transfer (FET) cycles from 368 patients were performed. Mean age and body max index (BMI) were 29.5±3.21 years and 22.3±3.09, respectively. The maturation rate was 63.2%. The median number of embryos was 4.0 [2.00; 6.00]. The cumulative clinical pregnancy rate was 60.4%, cumulative ongoing pregnancy rate was 51.6%. At 24 months after starting the treatment, the CLBR of CAPA-IVM was 38.2%. Multivariate analysis showed that patient age and number of metaphase II oocytes were the predictive factors for cumulative live birth after CAPA-IVM.

Limitations, reasons for caution

The study limitation derives from its retrospective nature. The generalizability of the study may be limited due to the single ethnicity group.

Wider implications of the findings

In patients with PCOS or high AFC, CAPA-IVM was viable and resulted in acceptable CLBR. CAPA-IVM may be the first-line treatment for women with PCOS or high AFC requiring assisted reproduction.

Trial registration number

not applicable
P-583 PCOS patients got better IVF/ICSI outcomes with “higher” progesterone level on hCG day: a retrospective study of Ten years data
Authors: Yang S , Rong L , Xiumei Z , Lina W , Haiyan W , Caihong M , Ping L , Jie Q
Published: June 2022

Study question

We aimed to investigate whether serum Progesterone (P) on the day of hCG trigger can be used as a biomarker to predict the IVF/ICSI outcomes in PCOS patients.

Summary answer

PCOS patients got better IVF/ICSI outcomes with “higher” progesterone level (2.7-5.9mmol/L).

What is known already

There were several studies suggesting serum Progesterone (P) on the day of hCG trigger can be used as a biomarker to predict IVF outcomes, and to decide fresh cycle embryo transfer or frozen all. But there was few study focus on PCOS patients.

Study design, size, duration

This is a single-center retrospective cohort study in PCOS women undergoing the first transfer of an IVF cycle between January 1st 2010 and December 31th 2019. There were 141,539 oocyte retrieval cycles during the study period, and 97,189 cycles were their first IVF cycle. PCOS was diagnosed according to the Rotterdam criteria. Among them, 3,146 cycles full filled the inclusion and exclusion criteria, and all with two embryos transferred on Day 3.

Participants/materials, setting, methods

We compared the live birth rate of fresh embryo transfer, stratified for serum P level. We looked for interaction between serum P level and live birth rate of fresh cycles. The serum P level within normal range (< 6nmol/L) on the day of hCG trigger day was divided into 4 quartiles. The four quartiles were defined as ≤ 1.35 nmol/L (Q1), >1.35-1.93 nmol/L (Q2), >1.93-2.7 nmol/L (Q3), >2.7 nmol/L (Q4).

Main results and the role of chance

The baseline characteristics with no different between groups, except BMI. The patients in Q4 group with lowest BMI, significantly higher number of oocytes retrieved and live birth rate (P < 0.05) . The Logistic regression analysis of the relative factors on live birth rate including BMI, basal LH and number of oocytes retrieved [P = 0.003, 0.030, 0.037 respectively, 95%CI (1.022, 1.111), (1.004, 1.076), (1.002, 1.082)].

Limitations, reasons for caution

Due to the retrospective nature of this study, a well-designed and matched large sample prospective study is needed. The definition of elevated P level and the method of hormonal assessments were different between studies, this limiting the comprehensive analysis of researches and the further verification of existing results.

Wider implications of the findings

PCOS patients who with normal range P level on hCG day, got better IVF/ICSI outcomes with “higher” progesterone level (2.7-5.9mmol/L). Weight control is important for PCOS patients accepting IVF treatment.

Trial registration number

NOT APPLICABLE
P-714 Visfatin and Silent Information Regulator 1 (SIRT1) in Pakistani infertile females
Authors: Alam F , Rehman R
Published: June 2022

Study question

What is the relationship of SIRT1 and oxidative stress markers with obesity among infertile Pakistani females?

Summary answer

Progressive decline in antioxidants with the increase in BMI suggests that obesity causes oxidative stress that consequently leads to infertility in females.

What is known already

Deficiency of Silent Information Regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, triggering obesity and associated metabolic disorders. SIRT1 expression levels are higher in endocrine system dysfunctions. Obesity has a potential risk for subfertility, infertility, deteriorated embryo quality, decreased endometrial receptivity, implantation failure and increased miscarriage rates. Visfatin increases in response to low levels antioxidants in obese, and its expression is negatively associated with the antioxidants produced. It disturbs glucose metabolism and promotes obesity, rendering it a powerful candidate as an OS marker.

Study design, size, duration

This cross-sectional study was conducted from August 2017 – July 2019, at Aga Khan Hospital in collaboration with Australian Concept Infertility Medical Centre (ACIMC) on 207 fertile and 135 infertile female subjects were recruited after ethical approval from of Aga Khan Hospital (AKU-ERC-2018-0557-601).

Participants/materials, setting, methods

kg)/height in meters (m2). Females were categorized by South-Asian criteria of BMI (normal-weight=18.0-22.9; overweight = 23-24.9; obese >25.0 kg/m2). Commercially available ELISA kits were used for estimation of serum Manganese Superoxide Dismutase (MnSOD), Glutathione Reductase (GR), visfatin and SIRT1. Pearson Chi-Square test and ANOVA were applied to compare the means within BMI groups. Association of variables was observed by Spearman correlation with significance at p < 0.05.

Main results and the role of chance

The mean BMI was 25.94 ± 5.1 kg/m2; 27.5% of females were normal-weight, 22.8% overweight, while 40.9% were obese. BMI was significantly high in infertile subjects (p < 0.001). MnSOD, visfatin and GR were lower in infertile females, decreasing from normal-weight to obese (p < 0.001). Increase in BMI was associated with a decrease in SIRT1 and antioxidants levels in both fertile and infertile females.

Limitations, reasons for caution

The small sample size was a limitation of the current study due to financial constraints, on the basis of which measurement of other non-enzymatic antioxidants such as malondialdehyde (MDA), glutathione, total antioxidant capacity (TAC), nitric oxide (NO) and reactive oxygen species could not be made possible.

Wider implications of the findings

SIRT1 is a fascinating target in various disease situations due to the promise of pharmacological and/or natural modulators of SIRT1 activity within the framework of endocrine and immune-related disease models.

Trial registration number

non applicable
P-720 Frequency of recessive genetic mutations in gamete donation program participants
Authors: Cullere M , Barbero S , Sanchez Sarmiento C
Published: June 2022

Study question

Is it possible to determine which are the most prevalent genetic diseases in our argentinian gamete donor population to develop a regional genetic panel and carry out correct pre-reproductive counseling?

Summary answer

We found the most frequent recessive genetic diseases in the gamete donor population, and determined the frequency of positives and negatives for all analyzed mutations.

What is known already

The access of the population with fertility problems to the gamete donation program is every day more frequent. The analysis of recessive genetic mutations of both recipients and gamete donors is essential to ensure the absence of some diseases in the offspring. There are different ways to study the carrier of monogenic diseases, one of them is the CGT® (CARRIER GENETIC TEST), which could be performed on individuals with no previous personal or family history of disease in order to have knowledge of the asymptomatic carrier status and to reduces the incidence of genetic abnormalities.

Study design, size, duration

Retrospective descriptive study. 586 blood samples obtained in Nascentis (Cordoba) from December 2016 to November 2019 were analyzed. Of these, 159 were from donors who belonged to the gamete donation program.

Participants/materials, setting, methods

CGT® results of 159 donors of both sexes were analyzed. A blood sample was drawn from each patient and the kit was sent to Igenomix® for the corresponding CGT® analysis. A complete list of mutations was obtained, the most frequent were identified and the frequency of each one was calculated. We also created the ranking of the fifteen most frequent mutations in the population of oocyte and sperm donors.

Main results and the role of chance

The 159 CGT® analysis allowed us to compile a list of a total of 63 diseases present in the sample. 78.3% of the donors presented one or more mutations. 69.4% of women and 78.5% of men were positive for at least one mutation. Among men, the most frequent mutation was phenylketonuria (18.1%). Among women, the most frequent were Usher syndrome (8%), Oculocutaneous albinism type 2, Glycine encephalopathy and cystic fibrosis (5%). Other frequent ones were Wilson's disease, central core congenital myopathy, and retinitis pigmentosa.

Limitations, reasons for caution

It is possible that an increase in the number of CGT® analyzed slightly modifies some of the positions in the ranking of diseases, so it is suggested to carry out studies with a larger sample size in order to obtain more comprehensive conclusions.

Wider implications of the findings

The analysis of recessive genetic mutations of the gamete donors represents a fundamental tool to avoid the appearance of diseases in the offspring. Each fertility center should know the frequency of occurrence of the most common and/or serious diseases in order to obtain safer results in each of their treatments.

Trial registration number

not applicable
P-758 Evaluating mismatch categories and true errors using an electronic witnessing system
Authors: Leisinger C , VerMilyea M
Published: June 2022

Study question

What are the types and frequency of errors occurring in the laboratory identified by an electronic witnessing system (EWS)?

Summary answer

Several types of mismatch categories were identified, and the rate of a potentially catastrophic true mismatch error was < 1%.

What is known already

Mix-ups in the IVF laboratory have been recently highlighted in the media. These errors can have devastating long-term consequences for the fertility clinics and families involved. Prevention of these errors should be paramount in the laboratory.

Study design, size, duration

A retrospective analysis was conducted using 15 months of electronic witnessing data from two IVF laboratories in the United States. A total of 11,357 witnessed procedures were evaluated to determine the type and frequency of mismatches that occurred.

Participants/materials, setting, methods

All procedure match and mismatch data was recorded by an EWS (Matcher, IMT International). The mismatch data from two laboratories was evaluated to determine the category and occurrence of mismatches taking place in the assisted reproductive technology (ART) laboratory.

Main results and the role of chance

The overall mismatch rate was 0.78% (89/11,357). The types of mismatches were identified as: 1) Program: duplicate barcodes scanned, barcode misread by program, non-Matcher barcode picked up during scan, connectivity issues; 2) Wrong patient selected; 3) Transcription error; 4) Cycle set up: treatment cycle not set up correctly, donor not linked to treatment cycle; 5) True error: dishes and/or tubes from two different patients were in the same workstation at the same time. Program error happened most frequently at 0.30% (34/11,357). The wrong patient selected and cycle set up errors occurred 0.18% (20/11,357), followed by transcription error at 0.11% (12/11,357). A true error occurred 0.03% (3/11,357) and was rectified in < 10 seconds meaning there was no time for actual mixing of gametes to occur. These findings agree with previously published reports worldwide where the occurrence of a true mismatch is < 1%.

Limitations, reasons for caution

The present study retrospectively analyzed mismatch data gathered over a 15-month period after implementation of EWS. Further investigation is warranted to determine if mismatches occur more or less frequently after long term use of an EWS.

Wider implications of the findings

Failure to identify a true mismatch error may lead to a catastrophic error. Continued evaluation of EWS may provide insight into how and why a true error occurs. This information can then be utilized to improve laboratory protocols and procedures for enhanced patient protection.

Trial registration number

Not applicable
P-759 Comparison of DNA methylation profiles of human embryo cultured in either uninterrupted or interrupted incubators
Authors: Zhu L , Li J , Huang G
Published: June 2022

Study question

Are there are differences in the DNA methylation profiles of human embryos cultured in Time-lapse imaging (TLI) and standard incubators (SI)?

Summary answer

The genome-wide DNA methylation landscape was globally similar between the SI and TLI groups.

What is known already

Early embryonic development is a special biological process, along with dynamic changes of DNA methylation. In vitro culturing ensured the successful development of human embryo, and is the most important step of ART cycle. TLI is one type of newly developed ART embryo culture systems, which allows for continuous assessment of embryonic development. Our previous study performed transcriptome analysis to compare SI and TLI and found that the global transcriptomic profiles were similar between the two groups. However, whether there are differences in the DNA methylation profiles of human embryos cultured in TLI and SI still unknown.

Study design, size, duration

This study was designed to explore the influence of SI and TLI incubator culturing on genome-wide DNA methylation of human eight-cell embryos. A total of 9 women who received IVF treatment, ≤ 30 years old (range: 20–30 years), without a history of genetic diseases or smoking were included in this study.

Participants/materials, setting, methods

Transvaginal oocyte retrieval was performed 36 h after HCG injection. Cumulus-enclosed oocytes were collected in 2.5 mL IVF medium and incubated in 5% O2, 6% CO2, and 37 °C incubators for insemination. The fertilized oocytes were transferred into pre-equilibrated Embryoslides. Then the embryoslides were cultured in either TLI or SI at 37 °C with 5% O2 and 6% CO2 until embryo transfer on Day 3. Samples were sequenced by the Illumina HiSeq 4000 with a 150-bp paired-end.

Main results and the role of chance

The genome-wide methylation patterns and CpG methylation levels in transposable elements and imprinting control regions of TLI-cultured embryos were similar to those of the SI-cultured embryos. However, a small number of differentially methylated regions (DMRs) were detected, and these DMRs mainly occurred in exons other than promoters. Functional annotation revealed that the genes in DMRs tended to execute functions such as cell cycle, DNA damage stimulus, histone modification, mitochondrial, glucose import, and MAPK signaling pathway.

Limitations, reasons for caution

Small sample size.

Wider implications of the findings

Evaluated the safety of TLI culture system from the perspective of DNA methylation at single-cell level, and provided an important reference for understanding the association between embryo culture condition and epigenetic regulation.

Trial registration number

not applicable
Hyperbaric Oxygen as Successful Monotherapy for a Severe Ulcerative Colitis Flare
Authors: Harlan Nicole P , Roberts Jane , Siegel Corey , Buckey Jay C
Published: June 2022

Lay Summary

This report presents a case of severe ulcerative colitis treated with hyperbaric oxygen as successful monotherapy.
A quality improvement initiative using peer audit and feedback to improve compliance
Authors: Fridrich Annemarie , Imhof Anita , Staender Sven , Brenni Mirko , Schwappach David
Published: June 2022

Background

The Surgical Safety Checklist (SSC) published by the WHO in 2009 is used as standard in surgery worldwide to reduce perioperative patient mortality. However, compliance with the SSC and quality of its application are often not satisfactory. Internal audits and feedbacks seem promising for improving SSC application.

Objective

The purpose of this study is to investigate whether an intervention consisting of peer observation and immediate peer feedback can be implemented with high fidelity and acceptance.

Method

Data were obtained from a national pilot programme that was initiated in Switzerland in 2018 to measure and improve compliance with the SSC using peer audit and feedback. A total of 11 hospitals with 14 sites implemented the full intervention. Each hospital formed an interprofessional project team that should perform at least 30 observations with feedback on SSC application documented in an observation tool developed specifically for this programme. Since the SSCs of the study hospitals differ greatly regarding checklist items, for each of the three SSC sections standard items were defined: four at Sign In, five at Team Time Out and two at Sign Out. Frequency analyses were performed for initiation characteristics, SSC application at item level, feedback characteristics and programme evaluation.

Results

The 11 hospitals documented 715 valid observations, and feedback on SSC application was provided for 79% of the observations. In 61%, all team members stopped their work for the SSC application, and in 71%, the items were read off from the checklist (instead of recalled from memory). On average, 86% of the standard items were read out by the checklist coordinator, whilst the two items at Sign Out were read out only in 60% and 74%. Additional visual checks with another source (e.g. patient wristband) took place in only 41%, and verbal confirmation of the items (by someone else other than the checklist coordinator) was obtained on an average of 76% across all three checklist sections. The surgical teams reacted positively in 64% to the peer feedback.

Conclusion

Both implementation fidelity and acceptability of the intervention were high—the present intervention seems suitable for regular monitoring of the quality of SSC application with internal resources. Peer observation facilitated identifying weaknesses regarding the SSC process and application at item level. Across all hospitals, the Sign Out section in general, visual control for item checks and lack of work interruption of all team members during SSC application showed up as the main areas of improvement.
Isolated infraspinatus musculotendinous junction tear treated with open repair and dermal allograft augmentation: a case report with 5-year outcome
Authors: Alben Matthew G , Gambhir Neil , Virk Mandeep S
Published: June 2022

We report the 5-year outcome of an isolated, atraumatic full-thickness infraspinatus myotendinous junction tear treated with open surgical repair. The index patient developed severe pain and weakness in external rotation strength following a subacromial corticosteroid injection. Magnetic resonance imaging and ultrasound of the shoulder demonstrated a full-thickness myotendinous junction tear with extensive muscle edema, mild atrophy and a spinoglenoid notch varix. Due to persistent, worsening pain and presence of ER weakness, the patient underwent primary infraspinatus muscle–tendon repair with allograft augmentation via an arthroscopic-assisted open posterior approach. The patient had an uneventful postoperative course with a resolution of pain and improvement in ER strength, which is maintained at the latest 5-year follow-up. This case report highlights a favorable long-term outcome of an isolated infraspinatus myotendinous junction tear treated with primary muscle–tendon repair and dermal allograft augmentation.
Treatment of COVID-19 Patients with Two Units of Convalescent Plasma in a Resource-Constrained State
Authors: Ipe Tina S , Ugwumba Blessing , Spencer Horace J , Le Tuan , Ridenour Terry , Armitage John , Ryan Stefanie , Pearson Shanna , Kothari Atul , Patil Naveen , Dare Ryan , Crescencio Juan C R , Venkata Anand , Laudadio Jennifer , Mohammad Khalid , Jamal Naznin , Thompson John , McNew Hailey , Gibbs McKenzie , Hennigan Steve , Kellar Stan , Reitzel Keith , Walser Brandon E , Novak Amanda , Quinn Brian
Published: June 2022

Importance

Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood.

Objective

Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP).

Method

This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for health care cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP.

Results

Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units.

Conclusion

The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.
SARS-CoV-2 Antibody Longitudinal Profile of Immune Globulin Preparations
Authors: Park Hyun J , Alcover Karl C , Wang Qing , Gada Satyen M
Published: June 2022

Introduction

Intravenous immunoglobulin (IVIG) preparations, used for the treatment of antibody deficiencies, provide a glimpse of the general population’s antibody profile as each preparation is generated from a pool of thousands of donors. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease 2019 (Covid-19) pandemic, and a vaccine for the prevention of Covid-19 was authorized for emergency use in December 2020. We completed a longitudinal analysis of SARS-CoV-2 antibody levels in commercial IVIG preparations.

Materials and Methods

We collected IVIG samples from our infusion clinic. IVIG product lot number, product name, and manufacturer information were recorded, with the date of preparation verified from the manufacturer. SARS-CoV-2 antibody titers as well as total immunoglobulin levels were measured using commercially available assays. The study received Institutional Review Board approval.

Results

We found no SARS-CoV-2 antibodies in preparations generated on or before January 2020. Overall, SARS-CoV-2 antibody levels in IVIG preparations tended to increase with progressing preparation date. We observed a dramatic and continual rise of SARS-CoV-2 antibody levels in IVIG preparations made in the beginning after January 2021, coinciding with the peak in incidence of confirmed cases and availability of Covid-19 vaccines in the United States.

Conclusion

SARS-CoV-2 antibody levels in IVIG mirror case prevalence, and vaccination resulted in a far more rapid rate of rise in antibody levels. IVIG preparations or serum repositories can provide an accessible way to model a population’s evolving novel pathogen exposure, immunity, and vaccine response.
The relic galaxy NGC 1277 rules out intermediate-age stellar populations origin of CO-strong absorptions in massive early-type galaxies
Authors: Eftekhari Elham , La Barbera Francesco , Vazdekis Alexandre , Beasley Michael
Published: June 2022

Massive early-type galaxies (ETGs) show several strong CO absorption features in their H- and K-band spectra that cannot be explained by state-of-the-art stellar population models. For many years, the disagreement has been attributed to the presence of intermediate-age stellar components that are dominated by stars in the asymptotic giant branch phase. However, no robust evidence of this scenario has been provided so far. One way to test this claim is by comparison of CO indices for ETGs and for relic galaxies. Lacking the intermediate-age stellar populations, relic galaxies provide us with a unique opportunity to address the origin of strong CO absorptions in ETGs. Here, we utilize the prototype relic galaxy NGC 1277 and compare the CO absorption features of this galaxy with the ones of a representative sample of massive ETGs. We show that the CO lines in both systems have similar strengths, significantly stronger than the predictions of stellar population synthesis models. We conclude that intermediate-age stellar populations in massive ETGs are not the culprit of the strong CO absorptions.
Disguised as Ovarian Tumor: A Rare Case of Uterine Abscess Due to Hypervirulent Klebsiella pneumoniae Infection
Authors: Kamau Edwin , Ranson Elizabeth L , Zakhour Mae , Mayo Mark S , Sakona Ashlyn N , Allyn Paul R , Yang Shangxin
Published: June 2022

Hypervirulent Klebsiella pneumoniae (hvKp) causes invasive infections in the community setting. We report a rare case of uterine abscess due to hvKp, which appeared as a large-sized ovarian tumor-like pelvic mass. A timely laboratory warning of possible hvKp prompted correct diagnosis and helped guide perioperative decision making, contributing to successful treatment.
The Price of Mathematical Scepticism
Authors: Levy Paul Blain
Published: June 2022

This paper argues that, insofar as we doubt the bivalence of the Continuum Hypothesis or the truth of the Axiom of Choice, we should also doubt the consistency of third-order arithmetic, both the classical and intuitionistic versions.

Underlying this argument is the following philosophical view. Mathematical belief springs from certain intuitions, each of which can be either accepted or doubted in its entirety, but not half-accepted. Therefore, our beliefs about reality, bivalence, choice and consistency should all be aligned.
Sleep well to perform well: the association between sleep quality and medical student performance in a high-stakes clinical assessment
Authors: Falloon Karen , Bhoopatkar Harsh , Moir Fiona , Nakatsuji Miriam , Wearn Andy
Published: June 2022

Study Objectives

To investigate medical students’ sleep quality and duration prior to a major clinical assessment, and their association with clinical performance.

Methods

Third year medical students were surveyed following the end of year Observed Structured Clinical Examination (OSCE) using a self-completed questionnaire. The questionnaire focussed on sleep in the month and night before the assessment. OSCE scores were linked to questionnaire data for analysis.

Results

The response rate was 76.6% (216/282). Poor sleep quality (Pittsburgh Sleep Quality Index > 5) was reported by 56.9% (123/216) and 34.7% (75/216) of students the month and night before the OSCE, respectively. Sleep quality the night before the OSCE was significantly associated with OSCE score (p = .038), but not sleep quality in the preceding month. The night before the OSCE, students obtained an average of 6.8 h sleep (median 7, SD 1.5, range 2–12 h). Short sleep duration (≤6 h) was reported by 22.7% (49/216) and 38.4% (83/216) of students in the month and the night before the OSCE, respectively. Sleep duration the night before the OSCE was significantly associated with OSCE score (p = .026), but no significant association was found between OSCE score and sleep duration in the preceding month. Use of medication to help with sleep was reported by 18.1% (39/216) of students in the preceding month and by 10.6% (23/216) in the night before the OSCE.

Conclusions

Medical students’ sleep quality and duration the night before a clinical assessment were correlated with their performance in that assessment.
Hypocholesterolaemia as a prognostic factor in venomous snakebite: a retrospective study from a single centre in Kerala, India
Authors: Menon Jaideep C , Joseph Joseph K , Jose Manoj P , Janakiram Chandrasekhar , Kumar K Dileep , Lakappa Dhananjaya B , Sudhakaran Perumana R , Oomen Oomen V
Published: June 2022

Background

Studies have suggested a association between serum cholesterol values and severity of envenoming. The objective of the study was to correlate the serum cholesterol levels with severity of envenoming in victims of snakebite, across snake species in our patient population.

Methods

Retrospective secondary data analysis of health records of a cohort of snakebite victims treated at Little Flower Hospital, Angamaly, Kerala during June 2006–January 2008 was performed. The cholesterol values were assessed in 205 consecutive patients admitted with snakebite envenoming, within 24 h of admission and 10 h of overnight fasting. Lipid fractions were estimated from fasting serum through the standard CHOD-PAP method on a Hitachi analyzer. The cholesterol level was compared between victims with mild and serious envenoming to assess the proportion among each category with a low cholesterol (defined as ≤150 mg/dl as per institutional criteria). In addition, low cholesterol as a marker of severity was compared with other laboratory parameters suggesting severe envenoming such as low fibrinogen, low platelet count, neutrophilia, elevated creatinine, d-dimer, hepatic transaminases and albuminuria.

Results

Of the 146 victims with serious degree of snakebite envenoming 116 (79%) had low cholesterol values ≤150 mg%, while 30 (21%) had values >150 mg%. Of the patients with low cholesterol, 116 (78%) had serious envenoming, while 22% had mild envenoming. By contrast, 30 patients (21%) had values >150 mg%. The risk of moderate-severe envenoming with low cholesterol was 2.7 times (170%) that of victims with normal or high cholesterol on admission.

Conclusions

A low cholesterol on admission in victims of snake envenoming suggested a more severe degree of envenoming and likelihood of complications.
Nutrient Elements Promote Disease Resistance in Tomato by Differentially Activating Immune Pathways
Authors: Gupta Rupali , Leibman-Markus Meirav , Anand Gautam , Rav-David Dalia , Yermiyahu Uri , Elad Yigal , Bar Maya
Published: June 2022

Nutrient elements play essential roles in plant growth, development, and reproduction. Balanced nutrition is critical for plant health and the ability to withstand biotic stress. Treatment with essential elements has been shown to induce disease resistance in certain cases. Understanding the functional mechanisms underlying plant immune responses to nutritional elements has the potential to provide new insights into crop improvement. In the present study, we investigated the effect of various elements—potassium (K), calcium (Ca), magnesium (Mg), and sodium (Na)—in promoting resistance against the necrotrophic fungus Botrytis cinerea and the hemibiotrophic bacterium Xanthomonas euvesicatoria in tomato. We demonstrate that spray treatment of essential elements was sufficient to activate immune responses, inducing defense gene expression, cellular leakage, reactive oxygen species, and ethylene production. We report that different defense signaling pathways are required for induction of immunity in response to different elements. Our results suggest that genetic mechanisms that are modulated by nutrient elements can be exploited in agricultural practices to promote disease resistance.
Rotational thromboelastometry in patients with type 2 diabetes and mild COVID-19 pneumonia: A pilot prospective study
Authors: Bolek Tomáš , Samoš Matej , Škorňová Ingrid , Schnierer Martin , Jurica Jakub , Bánovčin Peter , Staško Ján , Kubisz Peter , Mokáň Marián
Published: June 2022

Background:

It was repeatedly demonstrated that patients with severe COVID-19 pneumonia, as well as patients with type 2 diabetes (T2D) have higher risk of thromboembolic complications. Rotational thromboelastometry (ROTEM®) is a viscoelastic hemostatic assay which allows complex assessment of hemostasis in whole blood. The aim of this study was to compare changes in hemostasis measured by ROTEM® in diabetic and nondiabetic patients with mild COVID-19 pneumonia.

Methods:

We performed a pilot, prospective, observational study and enrolled 33 consecutive patients (14 with T2D and 19 nondiabetic ones) admitted to regular ward with mild COVID-19 pneumonia. The control group consisted from 11 healthy, nondiabetic blood donors. Blood samples were tested with ROTEM® using INTEM® and EXTEM® reagents.

Results:

We detected significant differences in EXTEM® clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) comparing patients with mild COVID-19 pneumonia and healthy donors. However, there were no significant differences in EXTEM®, INTEM®, and HEPTEM® parameters (CT, CFT, and MCF) according to diabetes status.

Conclusions:

Our study demonstrated hypercoagulation in patients with mild COVID-19 pneumonia. T2D did not affected ROTEM® parameters in patients with mild COVID-19 pneumonia.
Surgical outcomes of laparoscopic total extraperitoneal (TEP) inguinal hernia repair compared with Lichtenstein tension-free open mesh inguinal hernia repair: A prospective randomized study
Authors: Shah Mohammed Yunus , Raut Pratik , Wilkinson T.R.V. , Agrawal Vijay
Published: June 2022

Inguinal hernia repair is one of the most frequently performed surgery. The ideal procedure for inguinal hernia repair remains controversial. Open Lichtenstein tension-free mesh repair (LMR) is one of the most preferred open techniques with satisfactory outcomes. Laparoscopic approach in inguinal hernia surgery remains controversial, especially in comparison with open procedures. In this study, we have reported a comparison of laparoscopic total extraperitoneal (TEP) inguinal hernia repair with LMR. Postoperative pain, operative time, complications like seroma, wound infection, chronic groin pain, and recurrence rate were parameters to evaluate the outcome.

One hundred seventy-four patients were included in the study by consecutive randomized prospective sampling. The patients were divided into 2 groups: group A, laparoscopic TEP inguinal hernia repair, and group B, LMR. The procedures were performed by experienced surgeons. The primary outcomes were evaluated based on postoperative pain and recurrence rate. Secondary outcomes considered for evaluation were operative time, complications like seroma, infection, and chronic groin pain.

Severe pain was reported in group A (7.9%) compared to group B (15.1%), which was statistically significant (P < .001). Moderate pain was reported more in group B (70.9%) compared to group A (29.5%) (P < .001). The mean operative time in group A was 84.6 ± 32.2, which was significantly higher than that in group B, 59.2 ± 14.8. There was no major complication in both groups. The chronic pain postoperatively was significantly in higher number of patients in group B vs group A (22.09% vs 3.4%). The postoperative hospital stay period was significantly lesser for group A vs for group B (2.68 ± 1.52 vs 3.86 ± 6.16). Time duration taken to resume normal activities was significantly lower in group A (13.6 ± 6.8) vs (19.8 ± 4.6) in group B (P < .001).

Although there is definite evidence of longer operative time and learning curve, laparoscopic TEP has added advantages like less postoperative pain, early resumption of normal activities, less chronic groin pain, and comparable recurrence rate compared to open Lichtenstein repair. Laparoscopic TEP can be performed with acceptable outcomes and less postoperative complications if performed by experienced hands.
Home Oxygen Therapy
Authors: Fields Bronwyn E. , Whitney Robin L. , Bell Janice F.
Published: June 2022

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home. Nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses.
Building Blocks of Biofilms – an engaging and hands-on microbiology outreach activity for school children and the general public
Authors: Pincott Hayley , Hughes Megan , Cummins Thomas , Morse Daniel James
Published: June 2022

Biofilms are naturally occurring communities of microorganisms, attached to a surface and often embedded in a matrix of self-produced polymeric substances. Biofilms are widely implicated in human infections, particularly on prostheses and medical implants. Such biofilms are difficult to eradicate, often leading to replacement of the prosthesis and resulting in a significant burden to healthcare. 
Here we present a fun and engaging interactive activity targeted toward primary school/early secondary school children, introducing the concept of natural and healthcare-associated biofilms, using dental plaque as an archetypal example. Dental plaque forms as a result of poor oral/dental hygiene, and develops according to a typical series of defined stages: attachment and adherence to the surface, followed by colonisation and maturation of the biofilm structure, and eventually, dispersal. This activity uses dental disclosing tablets to visualise real biofilms (plaque) on the participants teeth, and uses interlocking building-blocks to represent microorganisms, where children build three-dimensional ‘biofilms’ of varying shapes and structural integrities. Each of the stages of development are discussed in detail, and after building the biofilms, balls of different shapes, sizes and weights can be used as ‘antimicrobials’ to disrupt the biofilm structure.
The outcomes of the activity are to enhance knowledge and general understanding of biofilms; their ubiquitous presence in the natural environment, development, implications in healthcare, and challenges of treatment. The various ‘antimicrobial’ balls also provide a basis to introduce and discuss drug selection for infections, and the importance of using the correct antimicrobial for different infections to avoid development of resistance.