bluuebunny/crossref_metadata_2025 huggingface dataset:
A flux-based machine learning model to simulate the impact of pathogen metabolic heterogeneity on drug interactions
Authors: Chung Carolina H , Chandrasekaran Sriram
Published: July 2022

Drug combinations are a promising strategy to counter antibiotic resistance. However, current experimental and computational approaches do not account for the entire complexity involved in combination therapy design, such as the effect of pathogen metabolic heterogeneity, changes in the growth environment, drug treatment order, and time interval. To address these limitations, we present a comprehensive approach that uses genome-scale metabolic modeling and machine learning to guide combination therapy design. Our mechanistic approach (a) accommodates diverse data types, (b) accounts for time- and order-specific interactions, and (c) accurately predicts drug interactions in various growth conditions and their robustness to pathogen metabolic heterogeneity. Our approach achieved high accuracy (area under the receiver operating curve (AUROC) = 0.83 for synergy, AUROC = 0.98 for antagonism) in predicting drug interactions for Escherichia coli cultured in 57 metabolic conditions based on experimental validation. The entropy in bacterial metabolic response was predictive of combination therapy outcomes across time scales and growth conditions. Simulation of metabolic heterogeneity using population FBA identified two subpopulations of E. coli cells defined by the levels of three proteins (eno, fadB, and fabD) in glycolysis and lipid metabolism that influence cell tolerance to a broad range of antibiotic combinations. Analysis of the vast landscape of condition-specific drug interactions revealed a set of 24 robustly synergistic drug combinations with potential for clinical use.
Disparity in female and Asian representation amongst cardiology journal editorial boards members: a call for empowerment
Authors: Lim O Z H , Chen Y , Dimmeler S , Yong A W J , Singh H , Sim M L E , Kong G , Lim W H , Low T T , Park D -W , Chew N W S , Foo R
Published: July 2022

Background

While progress is evident in gender and ethnic representation in the workplace, this disparity remains prevalent in academic positions.

Objectives

We examined gender and Asian ethnic representation in editorial boards of cardiology journals.

Methods

A cross-sectional analysis was conducted using publicly available data on Cardiology and Cardiovascular medicine journals in the first quartile of the 2020 Scimago Journal & Country Rank indicator. The proportions of female and Asian editorial board members, associate editors and editors-in-chief were assessed. Subgroup analyses were conducted based on the journal’s geographical origin, subspecialty and demographic of the editor-in-chief.

Results

Seventy-six cardiology journals, involving 8915 editorial board members, were included. Only 19.6% of editorial board members were female, 20.8% Asians and 4.0% Asian females. There were less female representation amongst editors-in-chief (9.9%) compared to associate editors (22.3%). European (18.1%) and North American-based journals (21.1%) had higher female representation compared to Asian-based journals (8.7%). There was lower Asian representation in European (18.1%) and North American-based journals (19.9%) compared to Asian-based journals (72.3%). Females were underrepresented in interventional (14.5%) journals, while Asians were underrepresented in general cardiology (18.3%) and heart failure (18.3%) journals. Journals led by female editors-in-chief had significantly higher female representation compared to male-led ones, while journals with Asian editors-in-chief had greater Asian representation compared to non-Asian led ones.

Conclusion

This study highlights the female and Asian ethnic underrepresentation in academic roles in cardiology journal editorial boards. Further analysis is needed for other ethnicities, while the community pushes towards gender-balanced and ethnic diversity across editorial boards.
Mind your step: social cerebellum in interactive navigation
Authors: Li Meijia , Pu Min , Baetens Kris , Baeken Chris , Deroost Natacha , Heleven Elien , Van Overwalle Frank
Published: July 2022

The posterior cerebellum contributes to dynamic social cognition by building representations and predictions about sequences in which social interactions typically take place. However, the extent to which violations of prior social expectations during human interaction activate the cerebellum remains largely unknown. The present study examined inconsistent actions, which violate the expectations of desired goal outcomes, by using a social navigation paradigm in which a protagonist presented a gift to another agent that was liked or not. As an analogous non-social control condition, a pen was transported via an assembly line and filled with ink that matched the pen’s cap or not. Participants (n = 25) were required to memorize and subsequently reproduce the sequence of the protagonist’s or pen’s trajectory. As hypothesized, expectation violations in social (vs non-social) sequencing were associated with activation in the posterior cerebellum (Crus 1/2) and other cortical mentalizing regions. In contrast, non-social (vs social) sequencing recruited cerebellar lobules IV–V, the action observation network and the navigation-related parahippocampal gyrus. There was little effect in comparison with a social non-sequencing control condition, where participants only had to observe the trajectory. The findings provide further evidence of cerebellar involvement in signaling inconsistencies in social outcomes of goal-directed navigation.
Energy restriction and housing of pregnant beef heifers in mud decreases body weight and conceptus free live weight
Authors: Nickles Kirsten R , Garcia-Guerra Alvaro , Fluharty Francis L , Kieffer Justin D , Relling Alejandro E , Parker Anthony J
Published: July 2022

Average temperatures in the Midwest, USA are predicted to increase 2–9°C by the end of the century; resulting in muddy pastures for spring calving beef heifers as they enter late gestation. The objective of this study was to evaluate the effects of muddy conditions on heifer body weight (BW), body condition score (BCS), conceptus free live weight (CFLW), and fetal growth when heifers were energy restricted during late gestation. Eighteen Angus heifers (n = 9/treatment) were paired based on initial BW. One heifer from each BW pair was randomly allocated to either the mud (MUD) or control (CON) treatment on day 196 of gestation. Pens in the CON treatment were bedded with wood chips, while pens in the MUD treatment were filled with mud (average depth of 19.5 ± 7.9 cm). Heifers were housed individually and fed the same diet that consisted of a limit-fed total mixed ration from day 196 to 266 of gestation that was formulated to meet 66% of the net energy for maintenance, growth, and gestation requirements. Requirements and the amount of the diet offered were adjusted weekly, and heifers were weighed and sampled for blood metabolites weekly. Data were analyzed as a randomized complete block design with repeated measurements. There was a treatment × day of gestation interaction, such that heifers had similar BW, BCS, and CFLW on day 196 of gestation. By day 266 of gestation; however, heifers in the MUD treatment weighed 43.5 kg less (P < 0.01) and were 1.8 BCS units less (P < 0.01) than heifers in the CON treatment. This is further supported by the treatment × day effects we observed for back fat (BF) and rump fat (RF) thickness, such that the MUD heifers had less BF (P = 0.02) and RF (P < 0.01) by day 266 of gestation. There was a marginally significant difference for gestation length (P = 0.06), such that heifers in the MUD treatment calved approximately 3.1 days before the heifers in the CON treatment. Though heifers in the MUD treatment decreased their BW and CFLW during the treatment period, we did not observe a difference in calf birth weight (P = 0.34), calf plasma IgG concentration (P = 0.37), or calf weaning weight (P = 0.63). Despite heifers in the MUD treatment having greater BW, CFLW, and BCS losses compared with the heifers in the CON treatment, the heifers in the MUD treatment seemed to prioritize fetal growth, as they mobilized their body tissues to meet the energetic demands of pregnancy.
Amygdala subnuclei volumes, functional connectivity, and social–emotional outcomes in children born very preterm
Authors: Mueller Megan , Thompson Benjamin , Poppe Tanya , Alsweiler Jane , Gamble Greg , Jiang Yannan , Leung Myra , Tottman Anna C , Wouldes Trecia , Harding Jane E , Duerden Emma G ,   PIANO Study Group
Published: July 2022

Children born very preterm can demonstrate social-cognitive impairments, which may result from limbic system dysfunction. Altered development of the subnuclei of the amygdala, stress-sensitive regions involved in emotional processing, may be key predictors of social-skill development. In a prospective cohort study, 7-year-old children born very preterm underwent neurodevelopmental testing and brain MRI. The Child Behavioral Checklist was used to assess social–emotional outcomes. Subnuclei volumes were extracted automatically from structural scans (n = 69) and functional connectivity (n = 66) was examined. General Linear Models were employed to examine the relationships between amygdala subnuclei volumes and functional connectivity values and social–emotional outcomes. Sex was a significant predictor of all social–emotional outcomes (P < 0.05), with boys having poorer social–emotional outcomes. Smaller right basal nuclei volumes (B = -0.043, P = 0.014), smaller right cortical volumes (B = -0.242, P = 0.02) and larger right central nuclei volumes (B = 0.85, P = 0.049) were associated with increased social problems. Decreased connectivity strength between thalamic and amygdala networks and smaller right basal volumes were significant predictors of greater social problems (both, P < 0.05), effects which were stronger in girls (P = 0.025). Dysregulated maturation of the amygdala subnuclei, along with altered connectivity strength in stress-sensitive regions, may reflect stress-induced dysfunction and can be predictive of social–emotional outcomes.
Wildfires
Authors: Haymond Reena , Jesrani Lena
Published: July 2022

Wildfire smoke can travel hundreds of miles from its source, resulting in poor air quality. Exposure to poor air quality has been associated with health risks. Nurses should be knowledgeable about such risks to provide appropriate care and education in affected communities.
Microtemporal Relationships in the Fear Avoidance Model
Authors: Kichline Tiffany , Cushing Christopher C. , Connelly Mark , Black William R. , Simons Laura E. , Friesen Craig , Schurman Jennifer V.
Published: July 2022

Objectives:

Current literature in pediatric pain evaluates the Fear Avoidance model (FAM) pathways at the trait (or macrotemporal) level, but it is unknown if these pathways also occur at the state (or microtemporal) level. Identifying microtemporal processes can improve our understanding of how the relationships within the Fear Avoidance constructs vary when specific Fear Avoidance variables wax and wane. We hypothesized that changes in FAM constructs would be associated with changes in the next variable in the sequence on a microtemporal level, including: (1) higher pain when there is more pain-related fear, (2) higher pain-related fear when there is more avoidance, and (3) higher avoidance when there is more reported disability.

Methods:

71 pediatric patients with chronic abdominal pain (M=13.34 y, SD=2.67 y) reported pain severity, pain-related fear, and avoidance via ecological momentary assessments over 14 days.

Results:

Our results indicated significant microtemporal relationships between Fear Avoidance constructs for pain predicting pain-related fear, pain-related fear predicting avoidance, and avoidance predicting disability.

Discussion:

The current study suggests that the ways in which the FAM is related to various aspects of pain functioning differs on a state-level, which adds new clinical and research opportunities.
No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone, and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty
Authors: Muñoz-Leyva Felipe , Jack James M. , Bhatia Anuj , Chin Ki Jinn , Gandhi Rajiv , Perlas Anahi , Jin Rongyu , Chan Vincent
Published: July 2022

Background

An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption.

Methods

In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events.

Results

Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], –5.6 mg [–2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010).

Conclusions

In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions—local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections—failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
A Cadaver Feasibility Study of Extradural Contralateral C7 Ventral Root Transfer Technique for Treating Upper Extremity Paralysis
Authors: Chang Jie , Wang Binyu , Yu Lipeng , Wang Tong , Sui Tao , Zhu Yi , Cao Xiaojian , Yang Kaixiang
Published: July 2022

Study Design.

A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study.

Objective.

The aim was to ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior.

Summary of Background Data.

Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, the authors established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior.

Methods.

In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical magnetic resonance imaging scans of 60 adults were used to measure the distance between the donor and recipient nerves.

Results.

Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm (P<0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root.

Conclusion.

Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function.

Level of Evidence.

5
Does Post-Operative Spine Infection Bacterial Gram Type Affect Surgical Debridement or Antibiotic Duration?
Authors: Karamian Brian A. , Lambrechts Mark J. , Sirch Francis , Gupta Sachin , D’Antonio Nicholas D. , Levy Hannah , Reiter David , Dolhse Nico , Khan Mahir , Mao Jennifer , Canseco Jose A. , Woods Barrett I. , Kaye I. David , Hilibrand Alan , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: July 2022

Study Design.

Retrospective cohort study

Objective.

To evaluate differences in readmission rates, number of debridements, and length of antibiotic therapy when comparing bacterial gram type following lumbar spinal fusion infections.

Summary of Background Data.

Surgical site infections (SSIs) after spinal fusion serve as a significant source of patient morbidity. It remains to be elucidated how bacterial classification of the infecting organism affects the management of postoperative spinal SSI.

Methods.

Patients who underwent spinal fusion with a subsequent diagnosis of SSI between 2013-2019 were retrospectively identified. Patients were grouped based on bacterial infection type (gram-positive, gram-negative, or mixed infections). Poisson’s regressions analyzed the relationship between the type of bacterial infection and the number of incision and debridement (I&D) reoperations, and the duration of IV antibiotic therapy. Significance was set at P<0.05

Results.

Of 190 patients, 92 had gram-positive (G+) infections, 57 had gram-negative (G-) infections, and 33 had mixed (M) infections. There was no difference in 30- or 90-day readmissions for infection between groups (both P=0.051). Patients in the M group had longer durations of IV antibiotic treatment (G+: 46.4 vs G-: 41.0 vs M: 55.9 d, P=0.002). Regression analysis demonstrated mixed infections were 46% more likely to require a greater number of debridements (P=0.001) and 18% more likely to require an increased duration of IV antibiotic therapy (P<0.001), while gram-negative infections were 10% less likely to require an increased duration of IV antibiotic therapy (P<0.001) when compared to G- infections.

Conclusion.

Spinal SSI due to a mixed bacterial gram type results in an increased number of debridements and a longer duration of IV antibiotics required to resolve the infection compared to gram-negative or gram-positive infections.

Level of Evidence.

3
Development and Validation of the Medical Emergency Team-Risk Prediction Model for Clinical Deterioration in Acute Hospital Patients, at Time of an Emergency Admission*
Authors: Allen Joshua , Currey Judy , Jones Daryl , Considine Julie , Orellana Liliana
Published: July 2022

OBJECTIVES:

To develop and validate a prediction model to estimate the risk of Medical Emergency Team (MET) review, within 48 hours of an emergency admission, using information routinely available at the time of hospital admission.

DESIGN:

Development and validation of a multivariable risk model using prospectively collected data. Transparent Reporting of a multivariable model for Individual Prognosis Or Diagnosis recommendations were followed to develop and report the prediction model.

SETTING:

A 560-bed teaching hospital, with a 22-bed ICU and 24-hour Emergency Department in Melbourne, Australia.

PATIENTS:

A total of 45,170 emergency admissions of 30,064 adult patients (≥18 yr), with an inpatient length of stay greater than 24 hours, admitted under acute medical or surgical hospital services between 2015 and 2017.

MEASUREMENTS AND MAIN RESULTS:

The outcome was MET review within 48 hours of emergency admission. Thirty candidate variables were selected from a routinely collected hospital dataset based on their availability to clinicians at the time of admission. The final model included nine variables: age; comorbid alcohol-related behavioral diagnosis; history of heart failure, chronic obstructive pulmonary disease (COPD), or renal disease; admitted from residential care; Charlson Comorbidity Index score 1 or 2, or 3+; at least one planned and one emergency admission in the last year; and admission diagnosis and one interaction (past history of COPD × admission diagnosis). The discrimination of the model was comparable in the training (C-statistics 0.82; 95% CI, 0.81–0.83) and the validation set (0.81; 0.80–0.83). Calibration was reasonable for training and validation sets.

CONCLUSIONS:

Using only nine predictor variables available to clinicians at the time of admission, the MET-risk model can predict the risk of MET review during the first 48 hours of an emergency admission. Model utility in improving patient outcomes requires further investigation.
An elevated platelet-to-lymphocyte ratio is associated with a higher risk of intracranial atherosclerotic stenosis
Authors: Huang Yanhua , Wang Zuoteng , Zhao Bing , Ma Yahui , Ou Yanan , Hu Hao , Hou Xiaohe , Yu Jintai , Tan Lan
Published: July 2022

Background:

Previous studies have shown that inflammation plays an important role in intracranial atherosclerotic stenosis (ICAS). The platelet-to-lymphocyte ratio (PLR) has recently emerged as a potential inflammatory biomarker. This study aimed to explore the association of the PLR with ICAS in a Chinese Han population.

Methods:

A total of 2134 participants (518 with ICAS, 1616 without ICAS) were enrolled in this study. ICAS was defined as atherosclerotic stenosis >50% or the occlusion of several main intracranial arteries. Multivariable logistic regression analyses were used to assess the association of the PLR with ICAS. Additional subgroup analyses were performed according to age (<60 vs. ≥60 years) and acute ischemic stroke.

Results:

Multivariate regression analysis showed that a high PLR was associated with a higher risk of ICAS in all participants (P < 0.001). Compared with the lowest quartile, the fourth PLR quartile was significantly associated with ICAS (OR 1.705, 95% confidence interval 1.278–2.275, P < 0.001). In the subgroups stratified by age, an association between the PLR and ICAS was found in the late-life group (P < 0.001), but not in the mid-life group (P = 0.650). In the subgroups stratified by acute ischemic stroke, the relationship between an elevated PLR and a higher risk of ICAS remained unchanged (stroke group, P < 0.001; non-stroke group, P = 0.027).

Conclusions:

An elevated PLR was associated with a higher risk of ICAS in a Chinese Han population. The PLR might serve as a potential biomarker for ICAS in the elderly population.
Robotic Surgery for the Ileal Pouch
Authors: Lynch A. Craig
Published: July 2022

BACKGROUND:

A robotic approach to total colectomy/proctectomy and ileal pouch reconstruction would seem to be a sensible use of the platform’s enhanced reach, visualization, and dexterity.

OBJECTIVE:

The study aimed to discuss current published data for robotic ileal pouch surgery.

STUDY SELECTION:

The study selection included a paucity of published data to date, representing early learning curves and case series with small numbers.

CONCLUSIONS:

Current robotic platforms may offer advantages, particularly in the low pelvis beyond what is found with a laparoscopic approach.
Complicated Facial Fillers: Management Algorithm
Authors: Ghareeb Fouad Mohamed , Hassan Medhat Sami Ali , El Nahas Mohamed Abdalla , Salem Mahmoud Sadek el Sayed
Published: July 2022

Background:

Various materials have been developed as skin fillers to correct wrinkles of the face. Dermal fillers are classified based on their biodegradability into bioresorbable versus nonbioresorbable. All dermal fillers have a potential risk of complications, which can be classified as early and late onset events. Among all the complications of filler injections, inflammatory nodules and granulomas are the most annoying and disfiguring. The purpose of the study was to provide a surgical treatment algorithm that allows us to deal with the complications of facial fillers through three surgical techniques.

Methods:

Thirty-one patients with complaints of facial contour abnormalities after filler injection, three surgical techniques were adopted according to the presenting case including face lift incision, needle aspiration and intraoral excision after preoperative preparation of the case with postoperative follow-up for 6 months.

Results:

Among our studied patients treated by these surgical techniques, dissection was difficult owing to the fibrosis and the granulomatous reaction post complicated filler injection. There were two cases of hematoma, 1 case of seroma, and 1 case of facial nerve injury that improved after 4 months, in which marked improvement of facial contour and skin quality was observed.

Conclusions:

The use of the facelift technique as a surgical treatment for post filler complication granuloma excision provides a useful and satisfactory method for patients complaining of major facial deformities following repeated complicated filler injections. Despite being more difficult than other techniques it is more satisfactory in facial rejuvenation post complicated facial fillers.
Refractive shifts due to belantamab mafodotin–associated corneal toxicity
Authors: Mittal Aman , Garg Sumit (Sam)
Published: July 2022

Introduction:

This report describes a case of belantamab mafodotin–associated corneal toxicity. The patient presented with refractive changes, which has not been previously reported with this condition.

Patient and Clinical Findings:

A 58-year-old man with refractory multiple myeloma and myopia presented for screening before the initiation of belantamab mafodotin (belamaf or Blenrep, an antibody-drug conjugate [ADC] with known corneal toxicity). After 1 infusion, he returned complaining of loss of uncorrected near vision and was found to have bilateral keratopathy with microcyst-like epithelial changes (MECs) in the midperipheral cornea.

Diagnosis, Intervention, and Outcomes:

A hyperopic refractive error was seen with manifest refraction, and central flattening was seen on corneal topography. The patient was diagnosed with corneal epithelial toxicity secondary to belamaf. The medication was discontinued, and the MECs migrated centrally causing a refractive shift and eventually resolving. The patient was ultimately happy with his visual outcome because his uncorrected vision returned to baseline.

Conclusions:

Any vision changes in patients on ADCs should be carefully worked up, including with manifest refraction and appropriate testing, because they may indicate early ocular side effects that can be treated. This case introduces evidence of hyperopic and myopic changes directly correlating with slitlamp examination findings and imaging of a patient with belamaf-induced MECs.
Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China
Authors: Wang Anzi , Su Dongyun , Chen Yanrong , Fu Yuhan , Tan Xiaoyan , Luo Jingyuan , Wang Jie , Li Yue , Chen Shu
Published: July 2022

The congenital factor VII deficiency (FVIID) is a rare autosomal recessive haemorrhagic disease caused by mutations in the F7 gene. The aim of this study was to identify the mutations causing FVII deficiency and explain the genotype–phenotype association in two unrelated Chinese patients. Mutation detection was conducted by sequencing the whole F7 gene coding exons, exon–intron boundaries and the untranslated regions of 3′ and 5′. Then, the genetic information was analyzed to predict the structures of the mutated proteins. A total of four different mutations were detected, including three missense mutations (c.64G>A, c.286A>G, and c.722C>A, predicting p.Gly22Ser, p.Arg96Gly, p.Thr241Asn, respectively) and one insertion mutation (c.204_205insCGGC, predicting p. Leu68Argfs∗37), among which two were reported for the first time (p.Arg96Gly, p.Leu68Argfs∗37). Multiple sequence alignments of FVII protein revealed that the residues p.Arg96 and p.Thr241 were highly conserved. The novel missense mutation p.Arg96Gly was determined as damaging with online software Polyphen-2 and SIFT. We investigated two asymptomatic patients diagnosed with severe FVII deficiency and identified two novel mutations (the mutation p.Arg96Gly and p.Leu68Argfs∗37). Identification of the F7 mutations was important for genetic counseling and accurate prediction of the inheritance pattern.
Evaluation of primary care physicians’ approaches to hemophilia and bleeding disorders: a questionnaire survey
Authors: Samur Bahadır M. , Samur Tuğba G. , Çiflikli Fatma-Ekin , Özcan Alper , Gök Veysel , Soykan Rabia , Soytürk Furkan , Kılıç Ömer , Kandur Mücahit , Kandemir Rabia , Zararsız Gözde , Karakükcü Musa , Patıroglu Turkan , Ünal Ekrem
Published: July 2022

Bleeding disorders are causes of great concern and panic for parents and primary care providers. Lack of knowledge and awareness on appropriate screening tests and factor product preparation contributed to potential diagnostic delays, increased complications, and economic costs. This study aimed to determine and compare the approach of primary care physicians (including general practitioners) and emergency physicians with a questionnaire including simulation-based cases on hemophilia. This simulation and two-stage questionnaire study was conducted with 244 participants. Before–after questionnaires, two case simulations, a brief presentation, and statistical analysis were performed. Participants mostly preferred tests, such as prothrombin time (PT) or partial thromboplastin time (PTT) to bleeding time for primary hemostasis (PT/PTT n: 192, 84.2%, bleeding time n: 94, 41.2%). Similar results were found for secondary hemostasis (bleeding time n: 144, 63.4%). There was a lack of knowledge in the management of simulation-based cases of acute hemorrhagic complications and factor product preparation (complication case: correct n: 100, 55.2%; initial doses correct n: 56, 43.4%, factor preparing correct n: 37, 49.3%, factor admission correct n: 36, 24.3%). All changed significantly, after the presentation (P = 0.000). Our study shows that there is probably a lack of knowledge of diagnostic investigations and appropriate factor product preparation with possible consequences for patients and economics.
Acute appendicitis in pregnant women: A Tunisian center experience
Authors: Mejri Atef , Arfaoui Khaoula , Trigui Emna
Published: July 2022

Acute appendicitis is the most common surgical pathology during pregnancy. It occurs in about 1 in 500 to 1 in 635 pregnancies per year,[1] and appendectomy is the gold standard in the treatment approach.[2] However, its diagnosis represents a challenge to both surgeons and obstetrician-gynecologists. In addition, the role of laparoscopy remains controversial.

This study discusses the diagnostic approach and reviews the appropriate surgical approach while evaluating the part of laparoscopy.

This is a retrospective descriptive analysis reviewing 36 patients who underwent surgery for acute appendicitis during pregnancy at the “Surgery Department of Jendouba Hospital from January 1, 2005 to December 31, 2019. Data include age, comorbidities, previous abdominal surgery, symptoms, physical examination findings, complementary exams results, operative treatment details, the emergency status of the procedure, associated medical treatment, antibiotics and tocolysis, the pathology reports, and follow-up.

The mean age of patients was 27 years. Twenty-one patients (58, 33%) were in the second trimester of pregnancy, 6 patients (16, 66 %) were in the first trimester, and 9 (25%) in the third one. The physical examination reported a right iliac fossa tenderness in 27 patients (75%). The abdominal ultrasound was performed in all cases and guided the diagnosis in 24 cases (66, 66%). 18 patients (50%) underwent laparoscopy, 12 patients (33, 33%) underwent laparotomy. The remaining 6 patients (16, 66%) required a conversion from laparoscopic to open surgery.

The clinical presentation of appendicitis in pregnancy is often misguiding. Therefore, an abdominal ultrasound should be performed for all pregnant patients having abdominal pain. The difficulty of operating under laparoscopy increases with the pregnancy term, leading to a higher risk of conversion, which increases the operating time and the doses of anesthetics, causing a maternal and fetal risk.
Effectiveness of acupuncture for irritable bowel syndrome: Protocol for a scoping review of systematic reviews and meta-analyses
Authors: Li Yachen , Peng Sike , Liang Fangyuan , Liu Suzhen , Li Jia
Published: July 2022

Background:

Irritable bowel syndrome (IBS) is a common functional bowel disorder. Many systematic reviews/meta-analyses indicate that acupuncture and related therapies are effective for IBS. However, the robustness of the results in the systematic reviews and meta-analyses has not been evaluated. This scoping review aims to ascertain the credibility of current evidence of acupuncture therapy for IBS, to provide clinical research investigators with reliable information.

Methods:

Searches of China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), China Biology Medicine disc (CBMdisc), and Wanfang Database since the establishment of the database to February 2022. Study selection and data extraction will be conducted by 2 reviewers, and the quality will be assessed by 2 trained reviewers. We will use Assessment of Multiple Systematic Reviews-2 (AMSTAR2) for methodological quality assessment, Preferred Reporting Items for Systematic Reviews and Meta-Analyses for report quality assessment, Grading of Recommendations, Assessment, Development, and Evaluation for the quality of evidence assessment, and the Risk of Bias in Systematic Reviews for the bias assessment.

Results:

The results will be published in a peer-reviewed journal.

Trial registration number:

INPLASY202210117.

Conclusion:

This scoping review will provide comprehensive evidence of acupuncture for patients with irritable bowel syndrome.

Ethics and dissemination:

This scoping review does not require ethical approval as it is a secondary assessment of available literature.
De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report
Authors: Ding Yingying , Dong Hongliang , Li YongCheng , Liu Lei , Cai Ying , Wang Ying , Tian Shengya , Dai Chengtao
Published: July 2022

Introduction:

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) mutations are the most common accurate gene targets. However, the lack of case reports or cohort studies on the exceptionally rare mutations limit the acquisition of deeper insights.

Patient concerns:

A 76-year-old female nonsmoker presented to our hospital with a one-week disease history of cough accompanied by shortness of breath.

Diagnosis:

Contrast-enhanced CT scan showed right pleural effusion with scattered inflammation and consolidation in the right upper lung. Tumor marker display showed obvious increased. Histopathology of the pulmonary mass combined with Immunohistochemical staining indicated lung adenocarcinoma. Contrast-enhanced magnetic resonance imaging suggested brain metastases. ECT scan showed bone metastasis. The patient was thus diagnosed as right lung adenocarcinoma of stage IV (cT3N3M1c). Next generation sequencing was performed to profile the mutation status of known oncogenic driver mutations, and only EGFR-D761Y in exon 19 (allelic frequency, AF: 0.53%) mutation was found.

Interventions:

The patient was accordingly treated with the third generation EGFR-Epidermal growth factor receptor tyrosine kinase inhibitor (TKI) Osimertinib (80 mg, qd). Accompanied with whole brain radiotherapy (DT3000c Gy/10f) for brain metastases, technetium methylene diphosphonate injection was performed for bone metastases.

Outcomes:

The efficacy of the first-line Osimertinib treatment for 1 month was assessed as PR per RECIST version 1.1. The NSCLC patient harboring EGFR-D761Y mutation detected prior to the EGFR L858R mutation was benefited from the third-generation EGFR-TKI Osimertinib and had a worse prognosis than with other EGFR mutations according to data from previous case reports.

Conclusions:

This case reported a NSCLC patient with de novo mutation of EGFR-D761Y responding to third generation TKI Osimertinib.
Influence of the COVID-19 pandemic on regular clinic visits and medication prescriptions among people with diabetes: Retrospective cohort analysis of health care claims
Authors: Maeda Toshiki , Nishi Takumi , Harada Masataka , Tanno Kozo , Nishiya Naoyuki , Asayama Kei , Okuda Nagako , Sugiyama Daisuke , Yatsuya Hiroshi , Okayama Akira , Arima Hisatomi
Published: July 2022

The aim of this study was to investigate the effect of the COVID-19 pandemic on regular clinic visits among people with diabetes and to elucidate the factors related to visit patterns among these patients during the pandemic.

This was a longitudinal study using anonymized insurance claims data from the Joint Health Insurance Society in Tokyo from October 2017 to September 2020. First, we identified patients with diabetes who were fully enrolled in the health plan from fiscal year 2017 until September 2020 and who were regularly receiving glucose-lowering medications (every 1–3 months) from October 2017 to September 2018. We divided follow-up into the pre-pandemic period (October 2018 to March 2020) and the pandemic period (April 2020 to September 2020). A multilevel logistic regression model was used to determine the risks of delayed clinic visits/medication prescriptions (i.e., >3 months after a previous visit/prescription) during the pandemic period.

We identified 1118 study participants. The number of delayed clinic visits/medication prescriptions during the pre-pandemic and pandemic periods was 188/3354 (5.6%) and 125/1118 (11.2%), respectively. There was a significant increase in delayed clinic visits during the pandemic (adjusted odds ratio 3.68 (95% confidence interval 2.24 to 6.04, P < .001), even after controlling for confounding factors. We also found a significant interaction between sex and delayed visits; women had significantly fewer clinic visits during the COVID-19 pandemic than men.

We clarified the relationship of the COVID-19 pandemic with delays in regular clinic visits and medication prescriptions among people with diabetes. The response to the COVID-19 pandemic differed between men and women.
Centrilobular zonal necrosis is a unique subtype of autoimmune hepatitis: A cohort study
Authors: Ueda Kaoru , Aizawa Yoshio , Kinoshita Chika , Nagano Tomohisa , Ishida Jinya , Saeki Chisato , Oikawa Tsunekazu , Harada Toru , Hokari Atsushi , Saruta Masayuki
Published: July 2022

Backgrounds:

Centrilobular zonal necrosis (CZN) is described as a histological feature present in a small number of autoimmune hepatitis (CZN-AIH) patients. CZN may be detected in the absence of significant interface hepatitis, which is the most important histological finding of AIH. The clinical and histopathological spectra of CZN-AIH were not homogeneous, and the concept of CZN-AIH as a distinctive subtype of AIH remains controversial, due to the rarity of CZN-AIH and the ambiguous definition of CZN.

Methods:

To elucidate the clinical and immunogenetic features of CZN-AIH, a total of 102 biopsy samples of AIH, obtained at The Jikei University Katsushika Medical Center and Jikei University Hospital from 2000 to 2018, were reviewed. The 32 patients whose biopsies showed CZN were selected as the CZN-AIH group, and the remaining 70 were grouped as the non-CZN-AIH controls (control AIH). Data on clinical, histopathologic, and immunogenetic features were statistically compared between the CZN-AIH and the control AIH group. Additionally, the impact of the onset pattern (acute or chronic) and coexistent significant interface hepatitis in CZN-AIH was determined.

Results:

In CZN-AIH, the frequency of acute-onset cases was significantly higher than that in control AIH (56.2% vs 32.9%; P < .05), and the number of cases with moderate-to-severe interface hepatitis in liver histology was significantly lower (37.5% vs 87.1%; P < .001). Compared to the control AIH, cases of CZN-AIH had lower immunoglobulin G level (P < .001), lower antinuclear antibodies titer (P < .001), and lower AIH score (P < .001). The immunogenetic disproportionate distribution of HLA-DR phenotypes in control AIH (increased HLA-DR4 and decreased HLA-DR9) was not found in CZN-AIH. Moreover, CZN-AIH was less frequently relapsed (P < .05). For the acute-onset CZN-AIH cases, the clinical features were hardly indistinguishable from the chronic CZN-AIH cases. Similarly, the existence of interface hepatitis did not influence on the pathophysiology of CZN-AIH. Moreover, the acute-onset CZN-AIH cases is clinically distinguishable from acute-onset control AIH

Conclusion:

CZN can characterize as a distinct AIH subtype, regardless of onset-pattern or coexistence of significant interface hepatitis. To further strengthen this hypothesis, collection of more CZN-AIH cases is needed.
Clinical, radiological, and magnetic resonance imaging characteristics of axial spondyloarthritis with late onset
Authors: Chung Ho Yin , Huang Jin Xian , Chan Shirley Chiu Wai , Lee Kam Ho , Tsang Helen Hoi Lun , Lau Chak Sing
Published: July 2022

We aimed to investigate the clinical, diagnostic, and imaging features of patients with late onset axial spondyloarthritis (SpA) with initial symptom manifestation aged over 45 years.

Participants with axial SpA were consecutively recruited. Clinical, demographic, blood, and imaging parameters were compared between the groups with early (≤45 years) and late onset (>45 years) at a cross-sectional level. Logistic regressions were used to determine the independent associations with axial SpA with late onset.

A total of 455 participants were recruited. Among them, 70 (15.4%) had late onset disease. Multivariate analyses showed that axial SpA with late onset was associated with higher C-reactive protein based ankylosing spondylitis disease activity index (ASDAS-CRP) (B = 0.10; P = .04), higher intensity of spinal inflammation as measured by maximum apparent diffusion coefficient (spinal ADC max) (B = 0.27; P = .03) and mean ADC (spinal ADC mean) (B = 0.30; P = .004), lower modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (B = –0.12; P = .02), more tender joint count (B = 0.12; P = .02), and fewer inflammatory back pain (IBP) (OR = 0.26; P < .001).

Axial SpA with late onset had higher clinical disease activity, higher intensity of spinal MRI inflammation, less radiographic damage, and more tender joint count. There was also less inflammatory back pain, which could make the diagnosis more difficult.
The prognostic factors of Ewing sarcoma/peripheral primitive neuroectodermal tumor: A retrospective analysis of 67 patients at a single center
Authors: Peng Jing , Han Xing Min
Published: July 2022

To investigate the characteristics and factors that impact the prognosis of Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) patients. We retrospectively analyzed ES/pPNET patients diagnosed at our hospital from January 2011 to December 2020. We used 1-way analysis of variance to investigate whether the age differences between different subgroups were statistically significant and used the Kaplan–Meier method and Cox regression model for the survival analysis. Of the 67 included patients, 13 had central nervous system PNET, and 54 had ES/pPNET. The median survival time of the 54 ES/pPNET patients was 18 months; the 1-year, 3-year and 5-year progression-free survival rates were 37.0% and 9.3% and 1.9%, respectively; and the 1-year, 3-year and 5-year overall survival (OS) rates were 66.7%, 27.8%, and 7.4%, respectively. The 1-way analysis of variance results showed no statistically significant age difference between the different subgroups (P = .127 between the central nervous system PNET and ES/pPNET groups, P = .764 between different subgroups within the ES/pPNET group). The univariate survival analysis showed that metastasis at diagnosis and the treatment method were independent factors affecting the OS rate of ES/pPNET patient (P = .003 and 0.000, respectively). The multivariate survival analysis also showed that the treatment method and metastasis at diagnosis were related factors affecting OS (P = .025 and 0.001, respectively). The prognosis of patients with primitive neuroectodermal tumors is poor. The treatment method and metastasis at the time of diagnosis influences ES/pPNET patient survival time, but there is no significant tumor site-dependent correlation with patient age or sex.
Preventing nausea and vomiting after gynecological laparoscopic surgery by patient-controlled intravenous analgesia with a naloxone admixture: A randomized controlled trial
Authors: Yang Haihong , Gu Xuedong , Xu Meiling , Yang Guan , Rao Yunju , Gao Liang , Gong Gu , He Siyi
Published: July 2022

Background:

Opioid-induced nausea and vomiting are common side effects of patient-controlled intravenous analgesia (PCIA). This study aimed to explore the inhibitory effect of a naloxone admixture on the incidence of sufentanil-induced postoperative nausea and vomiting (PONV).

Methods:

A total of 132 Uyghur American Society of Anesthesiologists I and II patients scheduled to undergo elective gynecological laparoscopic surgery were recruited; among these, 120 patients were enrolled and randomly allocated into 4 groups: patients receiving PCIA but no naloxone were included in the control group (group A); patients receiving PCIA with a low-dose naloxone admixture at 0.2 μg·kg−1·h−1 were included in group B; patients receiving PCIA with naloxone admixture at 0.4 μg·kg−1·h−1 were included in group C; patients receiving PCIA with naloxone admixture at 0.6 μg·kg−1·h−1 were included in group D. All patients were administered sufentanil at 0.04 kg−1·h−1, butorphanol at 2 kg−1·h−1, and dexmedetomidine at 0.08 kg−1·h−1 using a PCIA device within 2 days of surgery. The occurrence of nausea and vomiting, visual analogue scores for pain intensity, mean arterial pressure, heart rate, oxygen saturation, pruritus, lethargy, respiratory depression, etc, was recorded at 2, 8, 12, 24, and 48 hours postoperatively.

Results:

There was a significant difference in the PONV scores between the groups at 8, 12, and 24 hours after surgery (P < 0.01). At 8 and 12 hours, the score of group C/D was significantly lower than that of group A/B (P < 0.01). At 24 hours after surgery, the PONV score of group B/C/D was significantly lower than that of group A (P < 0.01). No significant difference was observed in the general data and visual analogue scores for postoperative pain between the 4 groups.

Conclusion:

Naloxone admixture administered at 0.4 to 0.6 μg·kg−1·h−1 can exert an effective inhibitory effect on the incidence and intensity of PONV in gynecological laparoscopic surgery.