bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior Scleral and Limbal Inflammatory Necrosis After Adjuvant Miltefosine for Recalcitrant Acanthamoeba Keratitis
Authors: de la Presa Martin , Ibach Mitch , Berdahl John , Holland Edward J.
Published: September 2021

Purpose:

The purpose of this study was to report a retrospective case series of anterior scleral and limbal inflammatory necrosis after adjuvant miltefosine for recalcitrant Acanthamoeba keratitis (AK).

Methods:

A case series and literature review.

Result:

Four eyes of 3 patients with recalcitrant AK developed anterior scleral and limbal inflammatory necrosis with significant scleral-limbal thinning after treatment with miltefosine. The average age was 38 years, and the average duration of infection before miltefosine treatment was 239 days. All cases required urgent surgical intervention to either prevent or mitigate corneal–limbal perforation.

Conclusions:

Miltefosine has been observed to result in the resolution of AK when used as an adjunctive therapy. It may also lead to a consecutive inflammatory necrosis of the anterior sclera and limbus. This inflammatory response may be significant enough to cause rapid scleral-limbal thinning with subsequent perforation.
Diagnosis and management of postrefractive surgery ectasia
Authors: Hatch Kathryn M. , Ling Joseph J. , Wiley William F. , Cason John , Ciralsky Jessica B. , Nehls Sarah M. , McCabe Cathleen M. , Donnenfeld Eric D. , Thompson Vance
Published: September 2021

Postrefractive surgery ectasia is a serious, sight-threatening complication seen after the following procedures: laser in situ keratomileusis, photorefractive keratectomy, small-incision lenticule extraction, radial keratotomy, and/or arcuate keratotomy. Specific risk factors may include age, corneal thickness, degree of refractive error, corneal topographic changes including irregular astigmatism, percent tissue ablation, and residual stromal bed. Biomarkers may be a new option to help indicate who is at greatest risk for ectasia. Visual aids including spectacles or contacts lenses are often required to achieve optimal vision. Collagen crosslinking is the only treatment believed to stop progression of ectasia and prevent keratoplasty. Other surgical options may include topography-guided phototherapeutic keratectomy and intrastromal corneal ring segments. Ultimately, an “ounce of prevention is a pound of cure,” so careful preoperative screening and ultimately offering the safest and most effective treatments for patients is arguably the most important job of the refractive surgeon.
Home Coping Strategies for Fatigue Used by Patients With Lung Cancer Receiving Chemotherapy in Rural China: A Qualitative Study
Authors: DONG Xiaomeng , PENG Jianying , LI Xingxing , ZHAO Qiyuan , ZHANG Xiuwei
Published: September 2021

Background

Cancer-related fatigue, a distressing symptom, is frequently reported by patients with lung cancer as increasing in severity with the number of rounds of chemotherapy. Yet, patients and healthcare providers are challenged to control this fatigue. Thus, healthcare providers must have interventions to effectively enhance coping engagement in patients with lung cancer.

Purpose

The aims of this study were to explore how patients with lung cancer in a rural area of China undergoing chemotherapy cope with the fatigue at home and to summarize their strategies.

Methods

A descriptive qualitative research approach was used, and data were collected using semistructured interviews. Sixteen patients with lung cancer with chemotherapy-related fatigue living in rural communities were recruited from a large, tertiary teaching hospital in Huzhou in eastern China. The transcripts of the interviews were analyzed using content analysis.

Results

Coping strategies for cancer-related fatigue were delineated into the three themes of (a) psychological adjustment, (b) efforts to change lifestyles and act as a Chinese health practitioner, and (c) relying on social support.

Conclusions/Implications for Practice

The participants in this study provided information on a variety of approaches to reducing/alleviating cancer-related fatigue that were influenced by Chinese culture. Healthcare providers and patients may work together in clinical settings to identify appropriate, effective coping solutions and then to incorporate these into the regular care regimen to help patients transition between hospital and home.
In-vitro thromboelastographic characterization of reconstituted whole blood utilizing cryopreserved platelets
Authors: Christodoulides Alexei , Zeng Ziqian , Alves Nathan J.
Published: September 2021

Conducting in-vitro thrombosis research presents numerous challenges, the primary of which is working with blood products, whether whole blood or fractionated whole blood, that have limited functional shelf-lives. As a result, being able to significantly prolong the clotting functionality of whole blood via fractionation and recombination promises greater accessibility via resource minimization in the realm of thrombosis research. Whole blood with CPDA1 from healthy volunteers was fractionated and stored as frozen platelet-free plasma (PFP, -20°C), refrigerated packed red blood cells (pRBCs, 4°C) and cryopreserved platelets (-80°C). Subsequent recombination of the above components into their native ratios were tested via thromboelastography (TEG) to capture clotting dynamics over a storage period of 13 weeks in comparison to refrigerated unfractionated WB+CPDA1. Reconstituted whole blood utilizing PFP, pRCBs and cryopreserved platelets were able to maintain clot strength (maximum amplitude) akin to day-0 whole blood even after 13 weeks of storage. Clots formed by reconstituted whole blood exhibited quicker clotting dynamics with nearly two-fold shorter R-times and nearly 1.3-fold increase in fibrin deposition rate as measured by TEG. Storage of fractionated whole blood components, in their respective ideal conditions, provides a means of prolonging the usable life of whole blood for in-vitro thrombosis research. Cryopreserved platelets, when recombined with frozen PFP and refrigerated pRBCs, are able to form clots that nearly mirror the overall clotting profile expected of freshly drawn WB.
Comparison of therapeutic effects of different acupuncture and moxibustion therapies on irritable bowel syndrome
Authors: Guo Jialei , Yang Li , He Jing , Yang Zhengming
Published: September 2021

Background:

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with recurrent abdominal pain and changes in bowel habits. Many pieces of evidence show that acupuncture and moxibustion therapy has advantages in the treatment of IBS, but there are many acupuncture and moxibustion therapy options, each of which has different therapeutic effects. This study will evaluate the clinical efficacy of different acupuncture and moxibustion therapies in the treatment of IBS by means of a network meta-analysis.

Methods:

According to the retrieval strategy, we retrieved the randomized controlled trials of acupuncture and moxibustion treatment of IBS from China National Knowledge Infrastructure, Wanfang, VIP, Chinese biomedical databases, PubMed, Embase, Web of Science, and the Cochrane Library databases from the database establishment to July 2021. We assessed the quality of the studies using the Cochrane Risk Bias Assessment Tool and assessed the strength of the evidence using the Grading of Recommendation Assessment, Development, and Evaluation methodology. All data analyses were performed by RevMan5.3, Gemtc 0.14.3, and Stata 14.0.

Results:

This study evaluated the efficacy of different acupuncture and moxibustion therapies in the treatment of IBS by evaluating the clinical efficacy rate, symptom scores, quality of life scores, adverse reactions, etc, and further explore the mechanism of action of each therapy.

Conclusion:

This study will provide a reliable evidence-based basis for selecting the best acupuncture and moxibustion therapy for IBS.

Ethics and dissemination:

Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/3278Y
The postoperative choledochoscopy in the management of the residual hepatolithiasis involving the caudate lobe
Authors: Liang Li , Zhuang Donghai , Feng Xianguang , Zhang Kai , Zhi Xuting
Published: September 2021

To reveal the role of the postoperative choledochoscopy in treating the residual calculi in the caudate lobe (CL) of the liver.

We recruited 66 patients with T-tube/percutaneous transhepatic cholangioscopy tract who still had residual gallstones in the CL at least 6 weeks after the operation. Imaging examinations determined the gallstones’ locations in the patients, and all of them underwent the postoperative choledochoscopic examination through the T-tube/percutaneous transhepatic cholangioscopy tract for therapeutic intervention.

Among the 66 patients, the residual gallstones were mostly located in the Spiegel lobe (48/66, 72.7%), and the residual gallstones that located in the origin of the CL bile branches were successfully determined in the 57 patients (57/66, 86.4%), the remaining 9 patients were unclear because the proximal ducts were severely narrow or even atresia. The mean frequency of the postoperative choledochoscopy was 3.6 (range, 1–10) times. There were 9 patients with complications, and no mortality occurred. In the origin-proved 57 patients, 6 patients failed to remove the gallstones altogether, and the final residual gallstone clearance rate was 77.3% (51/66). There was no significant difference between the Spiegel lobe and the other parts of the CL in determining the bile duct's origins, gallstone clearance rate, and complications. However, the frequency of choledochoscopy in the other parts of the CL was more than in the Spiegel lobe.

The postoperative choledochoscopy, an essential method for treating the residual gallstones in the CL, commands high efficiency for calculi extraction and fewer complications. The main reasons for failing to remove the residual gallstones are that the bile duct's origins could not be determined, and the distal bile ducts are atretic in the CL.
Natural course of hemoglobin level after total knee arthroplasty and the benefit of tranexamic acid injection in the joint
Authors: Cho Myung Rae , Jun Chung Mu , Song Suk Kyoon , Choi Won Kee
Published: September 2021

We retrospectively investigated the natural course of hemoglobin (Hb) level after total knee arthroplasty (TKA) and identified the benefit of tranexamic acid injection at the operation field for unilateral TKA patients who have not received blood transfusions.

There were 115 cases conducted by a surgeon who performed TKA without injecting tranexamic acid and 62 cases by another surgeon with injection. During 2-weeks of hospitalization, Hb level was checked on the day of surgery and 1, 2, 3, 5, 7, 11 days after surgery.

Regardless of whether whom the operator was and tranexamic acid was injected or not, the same natural course of Hb level after TKA was observed. The lowest value of Hb was shown at postoperative day 3, after which it tended to recover. In repeated measures analysis of variance test, mean difference from preoperative Hb level showed a statistically significant difference between tranexamic acid injected and noninjected groups (P = .01). In post hoc test, the differences from preoperative Hb levels were significantly lower at all measurements in surgeon with injection of tranexamic acid.

When deciding whether to transfuse after TKA, it should be noted that the patient tends to show the lowest Hb level on postoperative day 3. Also, the authors emphasize that tranexamic acid injection in the joint at the operation field is an effective method to reduce the loss of Hb after TKA.
Cardiopulmonary function findings of pediatric patients with patent ductus arteriosus
Authors: Huang Hung Ya , Wang Shang Po , Tuan Sheng Hui , Li Min Hui , Lin Ko Long
Published: September 2021

Transcatheter occlusion and surgical ligation are the treatments of choice for most patent ductus arteriosus (PDA) in children. Fifty-five children who had PDA completed a pulmonary function test and a symptom-limited treadmill exercise test from 2016 to 2018 at 1 medical center in southern Taiwan. The study group was divided into surgical ligation and catheterization groups, which were compared to a healthy control group matched for age, sex, and body mass index. Data about the performance on the exercise test, including metabolic equivalent at anaerobic threshold and peak, were analyzed. No differences in the pulmonary function and ventilatory parameters were observed between the surgery, catheterization, and control groups. Heart rate at peak and at anaerobic threshold significantly differed in the investigated groups. The post hoc analysis showed that the surgery group had a lower heart rate at peak and threshold compared to the catheterization and control groups (P = .02, P < .001, respectively). No significant difference was found between the catheterization group and the control group. A larger and younger group of patients were recruited, allowing for newer data about the cardiopulmonary function to be obtained. The findings suggest that patients with PDA could undergo physical training after intervention. The imposition of restrictions to limit sports activities should be avoided.
Pathogen distribution and bacterial resistance in children with severe pneumonia
Authors: Su De-Quan , Huang Hong-Lin , Zhuo Zhi-Qiang
Published: September 2021

To examine the etiological distribution of pathogens in pediatric patients with severe pneumonia and analyze the drug resistance of major pathogen species.

Nasopharyngeal secretion specimens were collected for bacterial culture from pediatric patients admitted to the Xiamen children's hospital who were diagnosed with severe pneumonia from January 2016 to December 2019. Pathogen species were detected by quantitative polymerase chain reaction, direct immunofluorescence, and bacterial culture and we examined the drug susceptibility of the bacterial pathogens.

At least 1 species of the pathogen was detected in 576 of 734 patients and a total of 444 bacterial samples were isolated, of which 284 were gram-negative and 160 were gram-positive. The most frequently detected bacteria were Haemophilus influenzae, Streptococcus pneumonia, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. In addition, we isolated 186 viral samples, of which the majority were respiratory syncytial virus (n = 90) and adenovirus (n = 70) as well as 142 Mycoplasma pneumonia samples.

Gram-negative bacteria are dominant among the pathogens causing severe pneumonia in pediatric patients and the major pathogen species are resistant to a variety of antibiotics. Appropriate antibiotic use has an important role in preventing the emergence of resistant strains.
Management of chronic myeloid leukemia presenting with isolated thrombocytosis and complex Philadelphia chromosome
Authors: Gao Lu , Ren Ming-qiang , Tian Zu-guo , Peng Zhi-yuan , Shi Genghui , Yuan Zhong
Published: September 2021

Rationale:

Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and pathological characteristics of CML patients, which were characterized by thrombocytosis and complex Philadelphia chromosome translocation. Moreover, we also introduced our therapeutic schedule for this patient as well as review relative literature.

Patient concerns:

A 24-year-old female presented with night sweating, fatigue, and intermittent fever for 1 month.

Diagnosis:

Fluorescence in situ hybridization results revealed that breakpoint cluster region (BCR)-Abelson (ABL) gene fusion in 62% of the cells and karyotyping showed a complex 3-way 46, XY, t(9;22;11) (q34;q11;q13) [19/20] translocation. This patient was diagnosed with CML complicated with thrombocytosis and complex Philadelphia chromosome translocation.

Interventions:

The patients received continuously oral imatinib mesylate tablets (400 mg) once a day.

Outcomes:

After treatment with imatinib for 3 months, the BCR/ABLIS was less than 0.1% and achieved major molecular response. Moreover, the BCR/ABLIS of this patient achieved major molecular response. The BCR/ABLIS values at 6 months and 12 months were less than 0.01% and 0.0032%, respectively. And no BCR/ABL fusion was detected in the next 2 years follow-up period.

Lessons:

Imatinib might represent a preferred therapeutic option for CML patients with rare thrombocytosis and complex chromosomal translocation. In addition, BCR/ABL fusion gene examination in patients with thrombocytosis might represent an effective strategy to avoid the misdiagnosis of this specific CML population.
Anaphylactic shock in a patient with severe aortic stenosis treated with adrenaline and landiolol for circulatory management
Authors: Yokoyama Akihiro , Sekino Motohiro , Ichinomiya Taiga , Ishizaki Hironori , Ogami-Takamura Keiko , Egashira Takashi , Yano Rintaro , Matsumoto Sojiro , Higashijima Ushio , Hara Tetsuya
Published: September 2021

Rationale:

We present the first case of a patient with severe aortic stenosis who developed anaphylactic shock and was successfully treated with adrenaline and landiolol, a highly selective β1-receptor blocker, to prevent disruption of the myocardial oxygen supply–demand balance caused by tachycardia.

Patient concerns:

An 86-year-old woman was scheduled for simultaneous anterior–posterior fixation for a burst fracture of the 12th thoracic vertebra; 200 mg sugammadex, a neuromuscular blocking agent antagonist, was administered postoperatively, and she was extubated without complications. However, 6 min after extubation, her blood pressure decreased abruptly to 55/29 mm Hg, and her heart rate increased to 78 bpm. Then, we intervened with fluid loading, an increased dose of noradrenaline, and phenylephrine administration. However, her blood pressure did not increase.

Diagnoses:

A general observation revealed urticaria on the lower leg; thus, we suspected anaphylactic shock due to sugammadex administration.

Interventions:

We carefully administered 2 doses of 0.05 mg adrenaline and simultaneously administered landiolol at 60 μg/kg/min to suppress adrenaline-induced tachycardia. Adrenaline administration resulted in a rapid increase in blood pressure to 103/66 mm Hg and a maximum heart rate of 100 bpm, suppressing excessive tachycardia.

Outcomes:

The patient's general condition was stable after the intervention, and circulatory agonists could be discontinued the following day. She was discharged from the intensive care unit on the fourth postoperative day.

Lessons:

Landiolol may help control the heart rate of patients with aortic stenosis and anaphylactic shock. The combined use of landiolol and adrenaline may improve patient outcomes; however, their efficacy and risks must be evaluated by studying additional cases.
Comparison of corneal endothelial cell changes after phacoemulsification between type 2 diabetic and nondiabetic patients
Authors: Joo Jin-Ho , Kim Tae Gi
Published: September 2021

The aim of this study is to compare the endothelial cell density (ECD) and morphology between diabetic mellitus (DM) and nondiabetic patients at 1 year after phacoemulsification in operated eyes and nonoperated eyes.

Evaluation was performed in 28 patients (56 eyes) with type 2 diabetes and 37 patients (74 eyes) without diabetes who underwent 1-year interval cataract surgery. Using a noncontact specular microscope and Scheimpflug rotating camera, corneal parameters were analyzed before and 1 year after surgery. Subgroups analysis was performed based on a disease duration 10 years and HbA1c concentration 7% and Pearson correlation analysis was performed.

The mean change in ECD at 1 year after surgery was 13.28% in the DM group and 11.40% in the control group. In the fellow nonoperated eyes, the mean change was 4.47% and 3.63% in the DM and control groups, respectively. There was no significant difference in postoperative ECD, coefficient of variance, hexagonality, and central corneal thickness between 2 groups. In the subgroup analysis, the long disease duration DM group (≥10 years) had a significantly greater ECD loss than the control and short disease duration DM groups (<10 years). Blood urea nitrogen (BUN) showed a significant correlation with postoperative ECD change (r = −0.474, P = .011).

The diabetic group with a longer disease duration showed significantly greater ECD decrease compared to the nondiabetic group and BUN correlated with ECD changes after phacoemulsification. Postoperative ECD loss may be high if the disease duration is long or if the BUN level is high.
Hypertension, cholesterol and diabetes medication adherence, health care utilization and expenditure in a Medicare Supplemental sample
Authors: Campbell Patrick J. , Axon David R. , Taylor Ann M. , Smith Karen , Pickering Matthew , Black Heather , Warholak Terri , Chinthammit Chanadda
Published: September 2021

Limited evidence exists regarding the relationships between adherence, as defined in Pharmacy Quality Alliance (PQA) medication adherence measures, health care utilization, and economic outcomes. PQA adherence measures for hypertension, cholesterol, and diabetes are of particular interest given their use in Medicare Star Ratings to evaluate health plan performance.

The objective of this study was to assess the relationship between adherence and utilization and cost among Medicare Supplemental beneficiaries included in the aforementioned PQA measures over a 1-year period.

Retrospective cohort study.

Three cohorts (hypertension, cholesterol, and diabetes) of eligible individuals from the Truven Health MarketScan Commercial Claims and Encounters Research Databases (2009–2015) were used to assess associations between adherence and health care expenditure and utilization for Medicare Supplemental beneficiaries.

Generalized linear models with log link and negative binomial (utilization) or gamma (expenditure) distributions assessed relationships between adherence (≥80% proportion of days covered) and health care utilization and expenditure (in 2015 US dollars) while adjusting for confounding variables. Beta coefficients were used to compute cost ratios and rate ratios.

Adherence for all 3 disease cohorts was associated with lower outpatient and inpatient visits. During the 1-year study period, adherence was associated with lower outpatient, inpatient, and total expenditures across the cohorts, ranging from 9% lower outpatient costs (diabetes cohort) to 41.9% lower inpatient costs (hypertension cohort). Savings of up to $324.53 per member per month in total expenditure were observed for the hypertension cohort.

Our findings indicate adherence is associated with lower health care utilization and expenditures within 1 year.
Mesonephric adenocarcinomas in female genital tract
Authors: Xie Chuan , Chen Qiuhe , Shen Yangmei
Published: September 2021

Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.

We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients’ clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.

A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.

Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.
Incidence and computed tomography findings of lenvatinib-induced pancreatobiliary inflammation
Authors: Kurokawa Ryo , Inui Shohei , Tanishima Tomoya , Nakaya Moto , Kurokawa Mariko , Ishida Masanori , Gonoi Wataru , Amemiya Shiori , Nakai Yousuke , Ishigaki Kazunaga , Tateishi Ryosuke , Koike Kazuhiko , Abe Osamu
Published: September 2021

In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.

We included 78 patients (mean ± standard deviation, 69.8 ± 9.4 years, range: 39–84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016–September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.

PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.

Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.
Endoscopic simulators: training the next generation
Authors: Dolan Russell D. , Ryou Marvin
Published: September 2021

Purpose of review

To provide a review of current evidence evaluating endoscopic simulators as teaching platforms in gastroenterology training, with emphasis on upper gastrointestinal anatomy.

Recent findings

Endoscopic simulators have leveraged mechanical, virtual reality and ex-vivo or live animal platforms to deliver training in both general and therapeutic endoscopy. Simulators have demonstrated their greatest utility in training novice endoscopists. Intermediate and expert endoscopists may additionally benefit from simulator exposure when learning advanced therapeutic techniques including large tissue resection or natural orifice transluminal endoscopic surgery.

Simulator-based learning offers promise to complement conventional endoscopic training modalities for novice trainees. Nevertheless, additional evidence demonstrating a clear benefit is required for simulators to become an integral part of gastroenterology training. As novel advanced endoscopic therapies are developed, endoscopic simulators may assume a larger role in training prior to clinical practice.
The role of biomarkers in risk stratification, treatment and outcome in acute GVHD
Authors: Kaviany Saara , Kitko Carrie L.
Published: September 2021

Purpose of review

Graft-versus-host disease (GVHD) following hematopoietic cell transplant (HCT) has a significant impact on morbidity and mortality among recipients. Predicting the long-term outcomes at the time of diagnosis of GVHD or even after response to up-front therapy can be challenging and only has modest accuracy. With biomarkers available to help guide decision-making, the landscape of GVHD is evolving.

Recent findings

Several acute GVHD biomarkers have been identified, with some better able to categorize patients based on their GVHD severity and potential for refractory disease than standard clinical staging or response criteria.

Biomarkers are now being incorporated into the clinical trial design for both high and low-risk GVHD. These findings will likely impact how clinical care is delivered in the future as improved risk stratification has the potential to improve outcomes by providing individualized treatment plans for affected patients.
Change of RBC Deformability During Hematopoietic Stem Cell Transplantation
Authors: Kim Yu Kyung , Lee Jae Min
Published: September 2021

The red blood cell (RBC) deformability test is the measurement of the ability of RBCs to adapt their shape to the flow conditions. The major determinants of RBC deformability include cell shape, composition of the cell membrane and cytoskeleton, and internal viscosity (mean cell hemoglobin concentration). RBC deformability is primarily regulated by the composition and arrangement of the cell membrane. In cancer patients, chemotherapy and hematopoietic stem transplantation (HSCT) affect the bone marrow microenvironment, which may alter RBC production and deformability. We aimed to evaluate the change in RBC deformability during HSCT. Blood samples were obtained from patients who underwent HSCT. Eleven children were enrolled in this study. RBC deformability was measured with a microfluidic ektacytometer (RheoScan-D, RheoMeditech, Seoul, Korea). All analyses were completed within 24 hours after blood collection. The elongation index of the erythrocytes was measured. The elongation index of RBCs gradually increased from day 5 to day 30 after HSCT. RBC deformability may reflect the bone marrow microenvironment of the patient during HSCT. Further studies investigating the correlation between RBC deformability and the prognosis of HSCT are needed.
Prevalence of COVID-19 in Egyptian Children With Hemoglobinopathies and Inherited Anemias
Authors: Ismail Ahlam M. , Mahmoud Nagwa M.S. , Ghazawy Eman R. , Mousa Suzan O.
Published: September 2021

Since the World Health Organization (WHO) announced coronavirus disease-2019 (COVID-19) to be a pandemic, children’s COVID-19 cases were generally less severe than adults. The aim of the study was to determine the prevalence of COVID-19 cases among children with hemoglobinopathies and other inherited anemias living in El-Minya Governorate, Egypt, who are at high risk of exposure to infection. This cross-sectional study evaluated data from 258 children with hemoglobinopathies and inherited anemias. A questionnaire was used to collect data about COVID-19 symptoms coupled with appropriate investigations (complete blood count, d-dimer, anti-COVID antibodies, chest computed tomography scans, and polymerase chain reaction). We found 38 of 258 (14.7%) children had mild to moderate COVID-19, while there were no cases with severe form of COVID-19. COVID-19 cases were significantly older (8.63±3.37 vs. 6.71±3.56 y, P=0.01), noncompliant to iron chelators (63.2% vs. 11.8%, P=0.01), had higher serum ferritin (2639.47±835.06 vs. 1038.95±629.87 ng/mL, P<0.0001) and serum iron levels (803.68±261.36 vs. 374.18±156.15 µg/dL, P<0.0001) and more frequently had undergone splenectomy (78.9% vs. 25.5%; P<0.0001) than non-COVID-19 cases. In conclusion, only 14.7% of children with hemoglobinopathies and inherited anemias were recorded to have contracted mild to moderate COVID-19, with no reported severe cases.
Utilization of Thiopurine Metabolites and Allopurinol in Pediatric Acute Lymphoblastic Leukemia: Consideration for an Algorithmic Approach
Authors: Mosher Nichole , Torkildson Joseph , Golden Carla , Raphael Robert , Beach Barbara , Michlitsch Jennifer , Feusner James H. , Agrawal Anurag K.
Published: September 2021

Persistently elevated absolute neutrophil counts during maintenance for acute lymphoblastic leukemia is a risk factor for relapse and may be related to wild-type thiopurine methyltransferase activity and overly efficient shunting of 6-mercaptopurine to hepatotoxic metabolites (6-methylmercaptopurine nucleotides), leading to low 6-thioguanine nucleotides. 6-mercaptopurine is also metabolized by xanthine oxidase, and therefore allopurinol, an inhibitor of xanthine oxidase, allows for increased 6-thioguanine nucleotides and decreased 6-methylmercaptopurine nucleotide. Here, we report our experience with allopurinol for persistently elevated absolute neutrophil count or hepatotoxicity and suggest an algorithmic approach for checking thiopurine metabolites and initiating allopurinol in acute lymphoblastic leukemia maintenance.
Outcomes of Lymphoma Among American Adolescent and Young Adult Patients Varied by Health Insurance—A SEER-based Study
Authors: Huang Congyang , Hu Honglian , Jia Li , Liu Hanshan , Hu Suyun
Published: September 2021

Introduction:

Impacts of health insurance status on survival outcomes among adolescent and young adult (AYA, 15 to 39 years of age) patients with lymphoma in the United States are insufficiently known. This study aimed to clarify associations between health insurance status and overall survival (OS) estimates in this population.

Materials and Methods:

We examined 18 Surveillance, Epidemiology, and End Results registries in the United States and analyzed American AYA patients with lymphoma diagnosed during January 2007 and December 2016. Health insurance status was categorized, and Kaplan-Meier and multifactor Cox regressions were adopted using hazard ratio and 95% confidence interval. Probable baseline confounding was modulated by multiple propensity score.

Results:

A total of 21,149 patients were considered; ~28% were 18 to 25 years old, and 63.5% and 7.5% had private and no insurance, respectively. Private insurance rates increased in the 18 to 25 age group (60.1% to 6.1%, P<0.001) following the 2010 Patient Protection and Affordable Care Act (ACA), and lymphoma survival rates improved slightly 1 to 5 years postdiagnosis. Five-year OS rates decreased with age (93.9%, 90.4%, and 87.0% at 15 to 17, 18 to 25, and 26 to 39, respectively) and differed among insurance conditions (81.7%, 79.2%, 89.2%, and 92.0% for uninsured, Medicaid, insured, and insured/no specifics, respectively). Risk of death was significantly higher for those with Medicaid or no insurance than for those with private insurance in multiple propensity score-adjusted models (hazard ratio [95% confidence interval]=1.07 [1.03-1.12]), independent of stage at diagnosis.

Conclusions:

No or insufficient insurance was linked to poor OS in our sample in exposure-outcome association analysis. Insurance coverage and health care availability may enhance disparate outcomes of AYAs with cancer. The ACA has improved insurance coverage and survival rates for out sample. Nevertheless, strategies are needed to identify causality and eliminate disparities.
Treatment Individualization Using Pharmacokinetic Studies and Joint Ultrasound Imaging in Pediatric Patients With Hemophilia
Authors: Adramerina Alkistis , Teli Aikaterini , Symeonidis Symeon , Gelsis Ioannis , Gourtsa Vaia , Economou Marina
Published: September 2021

Hemophilia is characterized by bleeding diathesis, primarily affecting the joints. Prophylactic use of missing factor aims at limiting the number of bleeds and, in the long term, the risk of permanent joint damage. However, standard prophylactic regimens are usually applied empirically, not adjusting for variations in bleeding phenotype or drug metabolism. Aim of the present study was to evaluate the need for individualizing prophylaxis, with guidance of pharmacokinetic (PK) studies and joint ultrasound in a setting of everyday clinical practice. To evaluate adequacy of applied regimens, joint status was assessed using the Hemophilia Joint Health Score as well as ultrasound imaging, while PK studies were performed using the Web-Accessible Population Pharmacokinetic Service—Hemophilia. Imaging results were consistent with early joint damage in a large proportion of pediatric patients, whereas PK measures were indicative of inadequate prophylaxis in many cases—despite the limited number of bleeds reported by patients. The study revealed the need for prophylaxis adjustment in the majority of patients. Real world data confirm that traditional prophylaxis is often unable to achieve therapeutic goals, while an individualized approach, guided by the use of novel modalities, may be of great benefit to young hemophilia patients.
Efficacy of the Motivational Interviewing–Walk Intervention for Chemotherapy-Induced Peripheral Neuropathy and Quality of Life During Oxaliplatin Treatment
Authors: Kanzawa-Lee Grace A. , Ploutz-Snyder Robert J. , Larson Janet L. , Krauss John C. , Resnicow Kenneth , Lavoie Smith Ellen M.
Published: September 2021

Background

Oxaliplatin-induced peripheral neuropathy (OIPN) is prevalent among gastrointestinal cancer survivors and often impairs quality of life (QOL).

Objective

This pilot randomized controlled trial aimed to explore the effect of an 8-week home-based brisk walking (the “MI-Walk”) intervention on (1) OIPN severity and (2) QOL at 8 weeks, compared with physical activity (PA) education alone in oxaliplatin-receiving adults with gastrointestinal cancer.

Interventions/Methods

Participants (N = 57) recruited from 5 infusion sites received PA education at their second oxaliplatin visit, followed by phone assessments of adverse events over 8 weeks. Half (n = 29) received additional MI-Walk intervention motivational supports (eg, a Fitbit Charge 2 and motivational enhancement therapy sessions). Self-reported OIPN, QOL, and PA were measured before and after intervention.

Results

The intervention compared with the control condition had no effect on sensory OIPN (mean difference [

] = −0.01; P > .99), motor OIPN (

=2.39; P = .17), and QOL (

= −1.43; P > .99). Eight-week sensory (

=11.48 ± 0.38) and motor OIPN severities (

= 7.48 ± 0.36) were mild but higher than baseline (P ≤ .01). Self-reported PA level increased over time in both groups (

=44.85; P = .01). Averaging ≥225 moderate to vigorous PA minutes per week led to less sensory OIPN, particularly finger/hand tingling (

= −26.35; P = .01).

Conclusions

This study failed to detect beneficial effects of the MI-Walk intervention; however, the findings suggest that aerobic walking may blunt but not completely prevent OIPN. Further research is necessary.

Implications for Practice

Although the effectiveness of brisk walking in reducing OIPN is unclear, this study supports prior evidence that moderate to vigorous PA is beneficial and safe during chemotherapy treatment.
Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability
Authors: Luck Marisa E. , Li Xiaoling , Herrnreiter Caroline J. , Choudhry Mashkoor A.
Published: September 2021

Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. In particular, intoxication at the time of burn injury leads to compromised intestinal T cell responses, which can diminish intestinal immunity and promote bacterial translocation, allowing for increased secondary infections in the injured host and associated sequelae, such as multiple organ failure and sepsis. Regulatory T cells (Treg) have been identified as important mediators of suppressing effector T cell function. Therefore, the goal of this study was to assess the effects of ethanol intoxication and burn injury on Treg populations in small intestinal immune organs. We also evaluated the suppressive capability of Tregs isolated from injured animals. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a ∼12.5% total body surface area scald burn. One day after injury, we identified a significant increase in Tregs number in small intestine Peyer's patches (∼×1.5) and lamina propria (∼×2). Tregs-producing cytokine IL-10 were also increased in both tissues. Finally, Tregs isolated from ethanol and burn-injured mice were able to suppress proliferation of effector T cells to a greater degree than sham vehicle Tregs. This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol + burn Tregs compared with sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues 1 day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn-injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.
Exploring the Obesity Paradox in A Murine Model of Sepsis: Improved Survival Despite Increased Organ Injury in Obese Mice
Authors: Lewis Erick D. , Williams Holden C. , Bruno Maria E.C. , Stromberg Arnold J. , Saito Hiroshi , Johnson Lance A. , Starr Marlene E.
Published: September 2021

Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Results from preclinical sepsis studies have not been able to replicate these findings. The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. Male C57BL/6 mice were provided high-fat (HFD) or low-fat (LFD) diets for 20 weeks. HFD-fed mice experienced higher rates of survival compared to LFD-fed mice after septic challenge induced by CS injection (66% vs. 25%, P = 0.01, survival assessed for 14 days). Despite the survival advantage, HFD-fed mice had higher rates of positive bacterial cultures and increased markers of kidney injury. Circulating levels of IL-6, IL-1β, TNFα, and IL-23 were equivalent 24 h after CS-injection; however, IL-17A was uniquely increased in HFD-fed mice. While LFD-fed mice maintained euglycemia, HFD-fed mice were hyperglycemic 6 and 12 h after CS-injection. Stable isotope resolved metabolomics analysis of liver tissue showed diverging pathways of glucose utilization during sepsis, with LFD-fed mice significantly upregulating glycolytic activity and HFD-fed mice decreasing glucose entry into the TCA cycle. This murine study corroborates clinical data that obesity confers a survival benefit in sepsis, albeit at the expense of more significant organ injury. The mechanisms promoting survival in the obese remain unknown; however, this model appears to be well-poised to begin answering this question. Differences in glucose utilization are a novel target to investigate this paradox.
Diagnosis of Acute Promyelocytic Leukemia After Presentation to Neuro-Ophthalmology
Authors: Paxton Andrew B. , Micieli Jonathan A.
Published: September 2021

Background:

Acute promyelocytic leukemia (APML) is a medical emergency that can initially present with neuro-ophthalmologic signs. Early recognition is crucial, and immediate treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) can be life-saving. The goal of this study was to describe patients who first presented to neuro-ophthalmology and were subsequently diagnosed with APML.

Methods:

We retrospectively reviewed consecutive patients seen at a tertiary neuro-ophthalmology centre. Patients with an unknown diagnosis of APML at presentation who subsequently went on to receive this diagnosis were included. Clinical characteristics, neuro-ophthalmologic findings, and outcome were retrieved.

Results:

A total of 3 patients (2 women and 1 men) with a mean age of 30.7 (range 24–33) years were included in the study. Neuro-ophthalmologic diagnoses at presentation were severe hemorrhagic papilledema related to dural venous sinus thrombosis, hemorrhagic bilateral optic disc edema, and left homonymous hemianopia related to an occipital lobe hemorrhage. At diagnosis, the average hemoglobin was 83.7g/L (range 78–104), and the platelet count was 39.3 × 109/L (range 15–77). All patients were treated with ATRA and ATO. One patient developed papilledema and sixth nerve palsies related to this treatment, which resolved with acetazolamide. Clinical follow-up ranged from 6 to 12 months, and all patients were in clinical remission about systemic APML.

Conclusion:

Neuro-ophthalmologic symptoms may be the first manifestations of APML, and a complete blood count is an essential test in patients presenting with optic disc edema, especially if hemorrhagic.
Establishing the Minimum Intensity of Transcranial Magnetic Stimulation Superconditioning Pulses to Effect Inhibition and Facilitation of Motor Evoked Potentials
Authors: Calancie Blair M. , Chin Stella , Wang Dongliang
Published: September 2021

Purpose:

Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses—a superconditioning (SC) train—when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles.

Methods:

We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalized to test input responses and were compared within and between subjects.

Results and conclusions:

For inhibition, the minimum intensity of SC pulses needed to influence the follow-on MEP was found to be 60% of the target muscle's resting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse—often reported as 80% of the single-pulse threshold—typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.