bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection Rates of Non-Cavitary Epithelioid Cell Granuloma by Gastrointestinal Biopsy in Patients with Treatment-Naïve Crohn’s Disease
Authors: Endo Katsuya , Kawakami Yoko , Yoshino Yuki , Kondo Shiho , Fukushi Daisuke , Takasu Atsuko , Kogure Takayuki , Hirota Morihisa , Murakami Kazuhiro , Satoh Kennichi
Published: October 2023

Introduction: Detecting non-cavitary epithelioid cell granuloma by gastrointestinal biopsy is important in the initial diagnosis of Crohn’s disease (CD). In the present study, we aimed to determine the rate of granuloma detection by gastrointestinal biopsy according to the number of biopsies performed. Methods: The present study included patients newly diagnosed with CD at our hospital between April 2017 and March 2023. During endoscopic examinations, biopsy specimens were taken from affected lesions. Initially, one section per biopsy was examined to detect granuloma. In cases where no granulomas were detected, step sections were additionally prepared and examined. The rate of granuloma detection by gastrointestinal biopsy was retrospectively examined. Results: A total of 30 patients with a new diagnosis of CD were included in this study. In total, 284 gastrointestinal biopsies were performed in 29 cases. The rate of granuloma detection by gastrointestinal biopsy per case was 58.6% (17 out of 29 cases). The rate of granuloma detection by gastrointestinal biopsy per biopsy was 6.0% (17 out of 284 biopsies) on initial histological examination and 11.6% (33 out of 284 biopsies) following examination of step sections. The rate of granuloma detection was significantly improved by performing histological examination of step sections compared with initial examinations (p < 0.05). Conclusion: The rate of granuloma detection per biopsy was 11.6%, even after histological examination of step sections. These results indicate that performing multiple intestinal biopsies and assessing for the presence of granuloma using multiple section examinations are required in the initial diagnosis of CD.
Clinical Differences between Posner-Schlossman Syndrome Patients with Intermittent Intraocular Pressure Elevation and Glaucomatous Damage
Authors: Wang Qian , Zeng Wen , Zeng Weijuan , Liu Yang , Ke Min
Published: October 2023

Introduction: Although there is abundant evidence that Posner-Schlossman syndrome (PSS) can lead to secondary glaucoma, data on the clinical differences between PSS patients with secondary glaucoma and those with intermittent intraocular pressure (IOP) elevation are sparse. Methods: This retrospective observational study included 52 patients (52 eyes) diagnosed with PSS and admitted to Zhongnan Hospital of Wuhan University between January 2019 and February 2022. Demographic characteristics and clinical features were gathered from admission records. Patients were divided into two groups: 27 cases with intermittent IOP elevation (group A) and 25 cases with secondary glaucoma (group B and C). Of the secondary glaucoma cases, 18 were further divided into the topical IOP-lowering medications group (group B) and 7 into the glaucoma surgery group (group C). Clinical characteristics of different groups were compared. Results: Compared to the intermittent IOP elevation group, PSS patients with secondary glaucoma had a longer course of disease, a higher incidence of iris depigmentation, lower best corrected visual acuity, lower endothelial cell density, and higher interferon-γ (IFN-γ) concentration and cytomegalovirus (CMV) deoxyribonucleic acid (DNA) copy number in the aqueous humor (all p < 0.05). Group C presented a higher CMV DNA copy number in the aqueous humor than groups A and B (p < 0.05). Compound trabeculectomy proved effective in group C, with a functional filter bleb and well-controlled IOP without disease progression after 1 year of follow-up. Conclusion: Distinctive characteristics existed between PSS patients with secondary glaucoma and those with intermittent IOP elevation. Compound trabeculectomy appears to be an effective treatment option when IOP cannot be controlled through topical medications.
Variation in Ischemic Stroke Payments in the USA: A Medicare Beneficiary Study
Authors: Etges Ana Paula Beck da Silva , de Souza Ana Claudia , Jones Porter , Liu Harry , Zhang Xiaoran , Marcolino Miriam , Polanczyk Carisi Anne , Martins Sheila Ouriques , Sampaio Gisele , Lioutas Vasileios Arsenios
Published: October 2023

Introduction: The growing cost of stroke care has created the need for outcome-oriented and cost-saving payment models. Identifying imbalances in the current reimbursement model is an essential step toward designing impactful value-based reimbursement strategies. This study describes the variation in reimbursement fees for ischemic stroke management across the USA. Methods: This Medicare Fee-For-Service claims study examines USA beneficiaries who suffered an ischemic stroke from 2021Q1 to 2022Q2 identified using the Medicare-Severity Diagnosis-Related Groups (MS-DRGs). Demographic national and regional US data were extracted from the Census Bureau. The MS-DRG codes were grouped into four categories according to treatment modality and clinical complexity. Our primary outcome of interest was payments made across individual USA and US geographic regions, assessed by computing the mean incremental payment in cases of comparable complexity. Differences between states for each MS-DRG were statistically evaluated using a linear regression model of the logarithmic transformed payments. Results: 227,273 ischemic stroke cases were included in our analysis. Significant variations were observed among all DRGs defined by medical complexity, treatment modality, and states (p < 0.001). Differences in mean payment per case with the same MS-DRG vary by as high as 500% among individual states. Although higher payment rates were observed in MS-DRG codes with major comorbidities or complexity (MCC), the variation was more expressive for codes without MCC. It was not possible to identify a standard mean incremental fee at a state level. At a regional level, the Northeast registered the highest fees, followed by the West, Midwest, and South, which correlate with poverty rates and median household income in the regions. Conclusions: The payment variability observed across USA suggests that the current reimbursement system needs to be aligned with stroke treatment costs. Future studies may go one step further to evaluate accurate stroke management costs to guide policymakers in introducing health policies that promote better care for stroke patients.
Spinal Dysraphism Presenting as Neuropathic Ulcers: A Case Report of a Delayed Diagnosis
Authors: Al-Luhaibi Razan S. , Khayyat Shahad T. , Al-Sayed Suha H. , Alhawsawi Waseem K. , Al Hawsawi Khalid A.
Published: October 2023

Spinal dysraphism (SD) refers to the abnormal fusion of dorsal midline structures during embryogenesis. It encompasses a variety of congenital spinal defects, ranging from an overt defect in which neural tissue is exposed with no overlying skin (open SD) such as myelomeningoceles to skin-covered malformations (closed or occult SD). A 13-year-old boy presented with recurrent multiple painless ulcers and erosions over the tips of the toes, mainly involving the right foot with hemorrhagic crusts for 5 years. A review of systems revealed back pain, urine incontinence, and numbness in his right knee. He was diagnosed with peripheral neuropathic ulcers and tethered cord syndrome secondary to SD and confirmed by MRI. He underwent cord detethering and lipoma resection as well as expectant therapy with satisfying outcomes. Physicians should consider early diagnosis of SD to avoid later neurological complications of SD (traction and/or pressure on the spinal cord) when infants are presented with such anomalies: MRI, close follow-up, and neurosurgical intervention may be recommended.
The Case for the Patient-Centric Development of Novel Digital Sleep Assessment Tools in Major Depressive Disorder
Authors: Peerenboom Nele , Aryal Suvekshya , Blankenship Jennifer M. , Swibas Tracy , Zhai Yaya , Clay Ieuan , Lyden Kate
Published: October 2023

Background: Depression imposes a major burden on public health as the leading cause of disability worldwide. Sleep disturbance is a core symptom of depression that affects the vast majority of patients. Nonetheless, it is frequently not resolved by depression treatment and may even be worsened through some pharmaceutical interventions. Disturbed sleep negatively impact patients’ quality of life, and persistent sleep disturbance increases the risk of recurrence, relapse, and even suicide. However, the development of novel treatments that might improve sleep problems is hindered by the lack of reliable low-burden objective measures that can adequately assess disturbed sleep in this population. Summary: Developing improved digital measurement tools that are fit for use in clinical trials for major depressive disorder could promote the inclusion of sleep as a focus for treatment, clinical drug development, and research. This perspective piece explores the path toward the development of novel digital measures, reviews the existing evidence on the meaningfulness of sleep in depression, and summarizes existing methods of sleep assessments, including the use of digital health technologies. Key Messages: Our objective was to make a clear call to action and path forward for the qualification of new digital outcome measures which would enable assessment of sleep disturbance as an aspect of health that truly matters to patients, promoting sleep as an important outcome for clinical development, and ultimately ensure that disturbed sleep will not remain the forgotten symptom of depression.
A Real-World Retrospective Study to Evaluate the Reliability of Cetuximab plus Capecitabine versus Capecitabine as Maintenance Therapy in Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer
Authors: Li Jun , Zhang Hang , Guo Xuli , Dong Shaoting , Li Yi , Huang Weizhen , Yuan Xia
Published: October 2023

Background: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). Patients and Methods: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. Results: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4–12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8–8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. Conclusion: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients.
Factors of Effective Internal Audits for Patient Safety in Primary Health Care Centers of Taif, Saudi Arabia
Authors: Alshamrani Salwa Moeed
Published: October 2023

Introduction: Internal audit is one of the tools to ensure safety in patient care. Literature on the internal audit effectiveness (IAE) in patient safety is scarce in Saudi Arabia. This study therefore aimed to assess the factors which influence the IAE in patient safety. Methods: A cross-sectional study was conducted among primary healthcare centers’ general directors and medical directors in Taif, Saudi Arabia. Data were collected using a validated structured questionnaire in Arabic and English. The questionnaire besides sociodemographics characteristics collected data on support of management, interdepartmental coordination, independence, objectivity, competence, and IAE. Analysis was done on SPSS version 26.0. Pearson correlation was used to see the relationship between factors and the IAE in patient safety. Results: A total of 94 participants were included in the analysis. The mean scores in each of the domains on a scale of 5 were; support of management 4.04, interdepartmental coordination 3.95, independence 4.03, objectivity 4.20, and competence 4.46, while for the IAE the mean score was 4.36. Correlation analyses found that the IAE was significantly associated with all five factors. All the factors had moderate association except for objectivity which had a weak correlation with IAE. Conclusions: Overall, there were satisfactory scores for the factors which affect IAE with room for further improvement. All the factors studied were positively associated with the IAE, indicating a need for healthcare organizations to consider these factors while planning internal audit activities. Further research on large scale is required to provide robust and generalizable results.
A Case of Oropharyngeal Carcinoma with an Oblique Neck that Benefited from Transoral Robotic Surgery
Authors: Yamakura Tatsuya , Shimizu Akira , Okamoto Isaku , Okada Takuro , Tokashiki Kunihiko , Kishida Takuma , Ito Tatsuya , Tsukahara Kiyoaki
Published: October 2023

Transoral robotic surgery (TORS) and transoral videolaryngoscopic surgery (TOVS) are minimally invasive procedures for early-stage head and neck cancers. However, due to its unique nature, transoral resection often leads to skeletal and anatomical disorders. We describe a case in which TORS was used in a 71-year-old man with a skeletal disorder, spastic stridor, and a T2N1M0 stage I p16-positive oropharyngeal carcinoma. Prior to the procedure, he underwent right cervical dissection (levels II–IV). Although he had an oblique neck, the right side of his neck was naturally hyperextended because the dissection was performed on the right side. The right facial, lingual, and external carotid arteries were ligated in preparation for TORS. Postoperative pathological examination revealed no extranodal involvement of the metastatic lymph nodes. A two-stage TOVS procedure was performed for the oropharyngeal tumor, in which the surgeon was required to be positioned at the patient’s head to allow direct manipulation. This makes the neck and oral cavity more susceptible to the skeletal effects. In contrast, in TORS, the da Vinci insertion angle can be set to match the angle of the neck, allowing surgeons to operate with less skeletal influence. TORS is more useful in this setting.
Risk of Hospital-Acquired Acute Kidney Injury among Adult Opioid Analgesic Users: A Multicenter Real-World Data Analysis
Authors: Pi Mingjing , Nie Sheng , Su Licong , Li Yanqin , Cao Yue , Gao Peiyan , Lin Yuxin , Zha Yan , Shi Yongjun , Li Hua , Zhao Jiajun , Kong Yaozhong , Li Guisen , Hu Ying , Liu Huafeng , Wan Qijun , Chen Chunbo , Liu Bicheng , Yang Qiongqiong , Su Guobin , Zhou Yilun , Weng Jianping , Xu Gang , Xu Hong , Tang Ying , Gong Mengchun , Hou Fan Fan , Xu Xin
Published: October 2023

Introduction: Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. Methods: This multicenter, retrospective real-world study analyzed 255,265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. The primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. Results: As compared to dezocine, the most commonly used opioid analgesic for treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio: 1.56, 95% confidence interval: 1.40–1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesic users with mild-to-moderate pain after adjusting for confounders. Conclusion: The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.
Preventive Transoral Endoscopic Thyroidectomy by Vestibular Approach in 6-Year-Old Patient with the High-Risk RET C634R Germline Mutation
Authors: Panaseykin Yury , Polkin Vyacheslav , Severskaya Nataliya , Isaev Pavel , Iliyn Aleksey , Plugar Alisa , Kupriyanova Ekaterina , Ivanov Sergey , Kaprin Andrey
Published: October 2023

Aggressiveness and age of manifestation of medullary thyroid cancer depend on the risk level of germline RET mutations. For high-risk mutations, preventive thyroidectomy is recommended at young age. In recent years, endoscopic operations for thyroid cancer were introduced in clinical practice. But such experience in pediatrics is very limited. We present a case report of a male patient, 6-year-old with the high-risk germline mutation С634R in RET gene. Close relatives (mother, cousin, and native sister) of the proband, were treated for medullary thyroid cancer. Also, his grandmother on the maternal line and her native brother died at the age of 38 and 37 years because of medullary thyroid cancer progression. Since 3 years old, our patient was under regular exams. At the age of six, calcitonin level was 8 ng/mL, and no evidence of pathology on ultrasound. According to recommendations of American Thyroid Association from 2015 (ATA 2015), preventive thyroidectomy was planned. This operation was performed by transoral vestibular approach. Oral nutrition started on the first day after the operation and the patient was discharged from the hospital. No major complications were observed. Transitory paresthesia and slight edema of the submental compartment were noticed. Consider this, endoscopic operation on the thyroid gland can be performed, as a preventive procedure, for RET gene germline mutation carriers in young age. This method helps avoid scars on the skin of the anterior neck.
EVI1 Disruption Post Neuroblastoma Treatment: A Case Analysis of Treatment-Associated Acute Myeloid Leukemia in a Pediatric Patient
Authors: Zhang Xin
Published: October 2023

In recent years, there has been an increasing focus on understanding the long-term consequences of pediatric cancer treatments, particularly the emergence of secondary malignant neoplasms (SMNs). Here, we present a case study highlighting the aftermath of treatment, where a pediatric patient, initially treated for neuroblastoma, developed treatment-related acute myeloid leukemia (tAML) 6 years later. Our investigation emphasizes the crucial role of EVI1 disruption in accelerating the progression of secondary tumors. This case underscores the significant risk of SMNs following pediatric cancer therapy. By analyzing genetic anomalies, we identified variations in the PTPN11 and KMT2C genes, suggesting a complex interplay between genetic susceptibility and chemotherapy-induced mutagenesis in tAML development. Furthermore, our exploration of the involvement of topoisomerase II inhibitors in tAML provides insights into potential future therapeutic approaches. Reporting this case is vital for deepening our understanding of the mechanisms driving SMNs after pediatric cancer treatments. Through a comprehensive analysis of genetic anomalies and treatment variables, we can offer more precise clinical diagnoses and treatment strategies. This approach holds the potential to reduce the occurrence of secondary tumors and improve the long-term prognosis for pediatric patients.
Refractory Intestinal Behçet-Like Disease Associated with Trisomy 8 Myelodysplastic Syndrome Resolved by Parenteral Nutrition
Authors: Takahashi Ryo , Matsubara Yasuo , Takahashi Satoshi , Yokoyama Kazuaki , Ahyoung Lim Lay , Koga Michiko , Sakamoto Hiroyuki , Boku Narikazu , Shida Dai , Yotsuyanagi Hiroshi
Published: October 2023

Intestinal Behçet disease (BD), associated with myelodysplastic syndrome (MDS), is often refractory to treatment. An 80-year-old man with trisomy 8 MDS (refractory anemia) developed intermittent fever. Despite investigations to exclude infectious disease, autoimmune disease, and malignancy as the cause of the fever, the etiology could not be determined. A colonoscopy revealed several shallow round ulcers in the ileocecal region and ascending colon, and the biopsy specimens showed nonspecific inflammation. Thereafter, the patient experienced abdominal pain and diarrhea. Other than an oral aphthous ulcer, the patient did not show symptoms to meet the diagnostic criteria for BD. The patient was diagnosed with intestinal ulcers (intestinal BD-like disease) with MDS and trisomy 8. After treatment failure with 5-aminosalicylic acid, steroid, colchicine, and azacitidine, cerebral infarction occurred. Eating was difficult because of the patient’s impaired consciousness; hence, total parenteral nutrition (TPN) was commenced. The fever and abdominal symptoms improved with bowel rest over approximately 1 month. Small amounts of food were orally administered to the patient following recovery from the after-effects of the cerebral infarction, but diarrhea and fever repeatedly flared up. Therefore, TPN was continued at home. The patient has not experienced any further intestinal BD symptoms for approximately 1 year with bowel rest. Nutritional therapy, including bowel rest, may be an effective treatment option for intestinal BD with MDS, and might be used as an induction therapy of remission or a supportive therapy for other treatments.
Novel LAGE3 Pathogenic Variants Combined with TRPC6 and NUP160 Variants in Galloway-Mowat Syndrome: A Case Report
Authors: Huang Limin , Zhang Xiaojing , Zhang Yingying , Wang Yanfei , Mao Jianhua
Published: October 2023

Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies in children. Researchers studying GAMOS reported the first pathogenic variant identified was the WDR73 gene, and more recently, four new pathogenic genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. In the present study, we report a new mutation of c.290T>G (p.L97R) LAGE3 in a 4-year-old boy with specific urological and nephrological complications. The patient presented with early-onset proteinuria, brain atrophy, delayed language and motor development, and axial hypotonia. This patient also had mutations in two other genes: TRPC6 and NUP160, make the clinical presentation of this patient more diverse. Our novel findings add to the spectrum of pathogenic variants in the LAGE3 gene. In addition, early genetic diagnosis of GAMOS is essential for genetic counseling and prenatal care.
New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus
Authors: Mahmud Hussen Bashdar , Noori Majid , Sayad Babak , Ebadi Fard Azar Maryam , Sadri Nahand Javid , Bayat Mobina , Babaei Farhad , Karampour Romina , Bokharaei-Salim Farah , Mirzaei Hamed , Moghoofei Mohsen , Bannazadeh Baghi Hossein
Published: October 2023

Introduction: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. Methods: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. Results: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. Conclusion: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.
Retrospective Case-Control Study of REGEN-COV (Casirivimab and Imdevimab) Therapy for Patients with COVID-19 and Cancer Using the United States MarketScan® Database
Authors: Takemoto Kazue
Published: October 2023

Introduction: Patients with cancer may be at a higher risk of experiencing severe complications from coronavirus disease 2019 (COVID-19) than are patients without cancer. This study evaluated the efficacy of REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, for treating COVID-19 in patients with cancer in the USA. Methods: Using the MarketScanⓇ database, de-identified data of patients with a COVID-19 diagnosis between November 1, 2020, and November 30, 2021, were analyzed. In the preliminary study, patients with COVID-19 were divided into two groups: those with and without cancer within 1 year prior to a COVID-19 diagnosis. In the main study, patients with COVID-19 with cancer were divided into two groups: those with and without REGEN-COV treatment. Patient outcomes, such as COVID-19-derived hospitalization, hospitalization duration, and medical costs, were assessed between these two groups by propensity score matching. Results: Within the first 30 days of a COVID-19 diagnosis, the group treated with REGEN-COV had fewer hospitalizations (3.2% vs. 13.3%; p < 0.001), fewer mean hospitalization days (0.2 vs. 1.1 days; p < 0.001), and a lower mean-associated medical payment (2,709 vs. 8,120 USD; p < 0.001) than the group not treated with REGEN-COV. Patients with specific cancer types, including non-Hodgkin’s lymphoma, leukemia, and lung cancer, had higher hospitalization rates than those with other cancer types. Conclusion: Patients with cancer treated with REGEN-COV experienced a decreased risk for hospitalization, hospitalization duration, and total COVID-19-related costs. Patients with cancer were at a higher risk of being hospitalized for COVID-19 than were those without cancer. The use of neutralizing antibody therapy may reduce the risk of severe COVID-19 infection for patients with cancer with an otherwise high risk. Future replication studies should be conducted using other databases that include Medicaid users and other insured persons for comparison and validation.
Effect of a Group-Based Narrative Language Training in Typically Developing Turkish-Dutch Children
Authors: Daelman Julie , Alighieri Cassandra , Van Lierde Kristiane , Simon Ellen , Altinkamis Feyza , Baudonck Nele , D'haeseleer Evelien
Published: October 2023

Introduction: Due to the heterogeneity in language trajectories and differences in language exposure, a lot of bilingual children could use some extra support for the acquisition of the school language to reduce the risk of language problems and learning difficulties. Enhancing bilingual children’s narrative abilities in the school language could be an efficient approach to advance the general school language abilities as well. Therefore, this study aimed to investigate whether a narrative intervention could improve both general and narrative school language abilities of typically developing bilingual (Turkish-Dutch) children. Methods: Nineteen Turkish-Dutch bilingual children (6–9.9 years) were enrolled in this single-arm early efficacy study. The intervention procedure was administered in the school language (Dutch) and based on a test-teach-retest principle with two baseline measurements. At baseline 1, the expressive, receptive, and narrative language abilities were determined. The second baseline measurement consisted of a second measurement of the narrative abilities. Subsequently, a weekly 1-h group-based intervention was implemented during 10 sessions. After the intervention phase, the expressive, receptive, and narrative language abilities were tested again. Results: After the intervention, the children produced significantly more story structure elements compared to both baseline measurements. No significant differences were found for microstructure narrative measures. The participants had significantly higher scores on the expressive and receptive language measurements post-intervention. Conclusion: These findings suggest that the intervention could be an efficient approach to stimulate the second language development of bilingual children.
Usefulness of an Easy, Structured, and Home-Based Exercise Program to Improve Physical Performance and Quality of Life in a Patient’s Cohort with Obesity
Authors: López-López Carlos Omar , Montes Castillo María de la Luz , Aguilar-Serralde Claudia Angélica , Torres-Cruz Mónica Nohemí , Rojas-Stevenson Andrea , Bólivar-Tellería Isabel
Published: October 2023

Introduction: The benefits of exercise in patients with obesity are clear; physical performance and quality of life improve after exercise programs in patients with obesity. Our aim was to evaluate the usefulness of an easy, structured, and home-based exercise program to improve physical performance and quality-of-life in patients with obesity. Methods: A cohort of patients with obesity (BMI ≥30 kg/m2) was recruited during 2017–2020. Patients who met the inclusion criteria were invited and those who accepted signed informed consent. Patients were evaluated by the same team of physicians who performed the 6-min walking test and collected the clinical and biochemical variables, also applied quality-of-life questionnaire at baseline and 3 months after starting the exercise program that was divided in two levels: level 1: active mobilization of four limbs (15 min) + cardiovascular exercise (15 min walking), 5 days/week; level 2: eight strengthening exercises for upper and lower limbs with an elastic band + cardiovascular exercise (15 min walking), 5 days/week. This study used means (SD), frequencies (percent), Student's t test, and Pearson correlation test. Results: We included 151 patients, mostly women (81.5%), age 46.3 ± 9.8 years old, BMI 40.3 ± 8.56 kg/m2, 34.4% performed some type of exercise, and the most frequents comorbidities were dyslipidemia and diabetes. After 3 months, 86 patients (57%) remained in the study and attended the final evaluation. Evident changes in physical performance were reported (distance traveled, speed walking and VO2max); however, improvement in quality of life was remarkable. Conclusion: An easy, structured, and home-based exercise program improves physical performance and quality of life in patients with obesity, without losing its benefits for the health.
A Genealogy of Gestures: On the Nature and Emergence of Forms of Gestural Communication within Shared Routines
Authors: Carpendale Jeremy I.M. , Kettner Viktoria A. , Guevara de Haro Irene
Published: October 2023

Communicative development can be better understood by examining the diversity of gestures and how various forms of gestures are interlinked in their developmental origins – their genealogy. To draw attention to the differences and interrelations among forms of gestures, we group gestures into three families based on their developmental origins: (1) action-based gestures that develop from infants’ spontaneous actions that others respond to; (2) conventional gestures; and (3) iconic gestures. Although these diverse gestures are acquired through somewhat different developmental pathways, we argue that they develop in the context of shared experiences within social routines. What differs is the relative role of the caregiver and child in initiating the routine. In viewing communicative development in this way, we show the importance of basing our investigations on an adequate conception of meaning in order to recognize the similarity in the underlying processes involved in early communicative development.
Assessing the Acceptability of Less Invasive Caries Removal Techniques for treating Deep Carious Lesions: A Conjoint Survey among Dentists Practicing in a Midwestern American State
Authors: Ortega-Verdugo Paula , Warren John J. , Gaeth Gary J. , Carter Knute , Kateeb Elham , Kolker Justine L. , Shane Dan M.
Published: October 2023

This study identified factors that influence dentists’ decisions regarding less invasive caries removal techniques such as stepwise removal (SW) and selective removal (SE) using a marketing research technique, conjoint analysis. A survey was sent to 1,434 dentists practicing in Iowa. Dentists were randomly assigned to receive a questionnaire to rate the likelihood they would use either SW/SE in hypothetical clinical scenarios. The scenarios were carefully created by conjoint design and included three relevant attributes: depth of lesion, hardness of carious dentin, and patient age. Descriptive and conjoint analyses were performed to assess trade-offs between these attributes, using SPSS. The study revealed that depth of lesion was the most important factor in the dentists’ decisions (49 importance value) when choosing a SW to treat a deep carious lesion, followed by hardness of carious dentin and patient age (21 importance value). For the SE group, depth of the lesion was also the predominant factor when selecting a treatment. The study also identified that a high proportion of dentists (24.9%) indicated they would never consider using SW or SE under any circumstances. Our survey showed that depth of lesion was the most important reason to select a less invasive caries removal method. The high proportion of dentists indicating they would never consider selective caries removal (SE) techniques suggests that these less invasive options are underutilized.
Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents
Authors: Levy Yurkovski Ilana , Tadmor Tamar
Published: October 2023

Background: Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to “accelerated CLL” (A-CLL) or to “Richter transformation” (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations. Summary: A-CLL is a rare and underdiagnosed entity that probably stands in the “gray zone” between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials. Key Messages: The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of “unmet need” and require further studies to identify the best diagnostic approach and a more effective treatment.
Review of the Role of Rituximab in the Management of Adult Minimal Change Disease and Immune-Mediated Focal and Segmental Glomerulosclerosis
Authors: Aslam Ahsan , Koirala Abbal
Published: October 2023

Background: Minimal change disease and primary FSGS are podocytopathies but are also immune-mediated diseases. Rituximab acts via multiple mechanisms by tilting the balance between autoreactive B and T cells in favor of regulatory B and T cells. The consequences are decreased production of cytokines, chemokines, and permeability factors by these cells. In the past decade, we have seen the discovery of autoantibodies mediating nephrotic syndrome (anti-annexin A2 antibody, anti-UCHL1 antibody, and anti-nephrin antibody), and rituximab decreases their production. Rituximab also binds to podocyte SMPDL3b and has direct podocyte actions. Summary: Rituximab’s role in managing these primary podocytopathies has been discussed in this brief review. Rituximab has been used extensively in children and adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, rituximab is not very promising in adult steroid-resistant nephrotic syndrome. Although ofatumumab would cause prolonged B-cell depletion and is fully humanized, it is unclear if it is superior to rituximab in preventing relapse of nephrotic syndrome. Key Messages: Rituximab therapy can induce prolonged remission in adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, no good data exist on using rituximab in steroid-resistant nephrotic syndrome.
Corneal Endothelial Cell Cultures from Organotypic Preservation of Older Donor Corneas Are Suitable for Advanced Cell Therapy
Authors: Aloy-Reverté Caterina , Bandeira Francisco , Otero Nausica , Rebollo-Morell Aida , Nieto-Nicolau Nuria , Gomes José Álvaro P. , Güell José L. , Casaroli-Marano Ricardo P.
Published: October 2023

Introduction: The purpose of this work was to evaluate the in vitro growth capacity and functionality of human corneal endothelial cells (hCEC) expanded from corneas of elderly (>60 years) donors that were preserved using an organotypic culture method (>15 days, 31°C) and did not meet the clinical criteria for keratoplasty. Methods: Cell cultures were obtained from prior descemetorhexis (≥10 mm) and a controlled incubation with collagenase type I followed by recombinant trypsin. Cells were seeded on coated plates (fibronectin-albumin-collagen I) and cultures were expanded using the dual supplemented medium approach (maintenance medium and growth medium), in the presence of a 10 μm Rho-associated protein kinase inhibitor (Y-27632). Cell passages were obtained at culture confluency (∼2 weeks). A quantitative colorimetric WST-1 cell growth assay was performed at different time points of the culture. Morphometric analysis (area assessment and circularity), immunocytochemistry (ZO-1, Na+/K+-ATPase α, Ki67), and transendothelial electrical resistance (TEER) were performed on confluent monolayers. Results: There was no difference between the cell growth profiles of hCEC cultures obtained from corneas older than 60 years, whether preserved cold or cultivated organotypic corneas. Primary cultures were able to maintain a certain cell circularity index (around 0.8) and morphology (hexagonal) similar to corneal endothelial mosaic. The ZO-1 and Na+/K+-ATPase pump markers were highly positive in confluent cell monolayers at 21 days after isolation (passage 0; P0), but significantly decreased in confluent monolayers after the first passage (P1). A weak expression of Ki67 was observed in both P0 and P1 monolayers. The P0 monolayers showed a progressive increase in TEER values between days 6 and 11 and remained stable until day 18 of culture, indicating a state of controlled permeability in monolayers. The P1 monolayers also showed some functional ability but with decreased TEER values compared to monolayers at P0. Conclusions: Our results indicate that it is possible to obtain functional hCEC cultures in eye banks, using simplified and standardized protocols, from older donor corneas (>60 years of age), previously preserved under organotypic culture conditions. This tissue is more readily available in our setting, due to the profile of the donor population or due to the low endothelial count (<2,000 cells/mm2) of the donated cornea.
Increased Glucagon Immunoreactivity in a Rat Model of Diet-Induced Obesity following Sleeve Gastrectomy
Authors: Al-Sabah Suleiman , Jamal Mohammad H. , Al-Khaledi Ghanim , Dsouza Carol , AlOtaibi Fatemah , Al-Ali Waleed , Cherian Preethi , Al-Khairi Irina , Ali Hamad , Abu-Farha Mohamed , Abubaker Jehad , Al-Mulla Fahd
Published: October 2023

Objective: Bariatric surgery is currently the most effective treatment for obesity, and procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy (SG) also result in rapid improvements in insulin sensitivity and glucose tolerance. In addition, these procedures cause changes in the secretion of various gut-derived hormones. The role these hormones play in the mechanism of the beneficial effects of bariatric surgery is still debated, but nonetheless, their importance provides inspiration for novel obesity-targeted pharmacotherapies. Methods: Male Sprague-Dawley rats were fed either regular chow or a cafeteria diet to induce obesity. A sub-group of the obese animals then underwent either sham surgery or SG. Results: Following a 4-week recovery period, SG rats weighed significantly less than obese or sham-operated rats. Improvements in glucose tolerance and insulin sensitivity also occurred in the SG group, but these were not always statistically significant. We measured the intracellular lipid content of liver samples and found that obese rats showed signs of non-alcoholic fatty liver disease, which were significantly ameliorated by SG. There were significantly higher glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide responses to a standard mixed meal in the SG group, as well as paradoxically higher glucagon secretion. Conclusion: These data highlight the need for more specific anti-glucagon antibodies to characterize the changes in proglucagon-derived peptide concentrations that occur following SG. Further studies are required to determine whether these peptides contribute to the therapeutic effects of SG.
Locoregional Therapy: From Mastectomy to Reconstruction, Targeted Surgery, and Ultra-Hypofractionated Radiotherapy
Authors: Banys-Paluchowski Maggie , Hartmann Steffi , Ditsch Nina , Krawczyk Natalia , Kühn Thorsten , de Boniface Jana , Banys-Kotomska Joanna , Rody Achim , Krug David
Published: October 2023

Background: The past 3 decades have seen an unprecedented shift toward treatment de-escalation in surgical therapy of breast cancer. Summary: Radical mastectomy has been replaced by breast-conserving and oncoplastic approaches in most patients, and full axillary lymph node dissection by less radical staging procedures, such as sentinel lymph node biopsy and targeted axillary dissection. Further, attempts have been made to spare healthy tissue while increasing the probability of removing the tumor with clear margins, thus improving cosmetic results and minimizing the risk of local recurrence. In this context, modern probe-guided localization techniques have been introduced to guide surgical excision. This progress was accompanied by the development of targeted systemic therapies. At the same time, radiotherapy for breast cancer has undergone significant changes. The use of hypofractionation has decreased the typical length of a treatment course from 5–6 weeks to 1–3 weeks. Partial breast irradiation is now a valid option for de-escalation in patients with low-risk features. Axillary radiotherapy achieves similar recurrence rates and decreases the risk of lymphedema in patients with limited sentinel node involvement. Key Messages: Taken together, these advances are important steps toward individualization of locoregional management strategies. This highlights the importance of interdisciplinary approaches for de-escalation of locoregional therapies.