bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, Safety, and Efficacy of Letermovir for Cytomegalovirus Prophylaxis in Adolescent Hematopoietic Cell Transplantation Recipients
Authors: Groll Andreas H. , Schulte Johannes H. , Antmen Ali Bülent , Fraser Christopher J. , Teal Valerie L. , Haber Barbara , Caro Luzelena , McCrea Jacqueline B. , Fancourt Craig , Patel Mayankbhai , Menzel Karsten , Badshah Cyrus 
Published: January 2024

Introduction:
Letermovir is a cytomegalovirus (CMV) terminase complex inhibitor approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients (R+). We report pharmacokinetics (PK), safety, and efficacy of letermovir in adolescent (12–18 years) allogeneic HCT recipients from an ongoing clinical study.

Methods:
In this phase 2b, multicenter, open-label study (NCT03940586), 28 adolescents received 480 mg letermovir [240 mg with cyclosporin A (CsA)] once daily orally or intravenously. Blood was collected for intensive (n = 14) plasma concentrations of letermovir. Intensive PK data were used for dose confirmation. Target exposure range 34,400–100,000 h × ng/mL for pediatric median exposures was based on model-predicted phase 3 population PK simulations in adult HCT recipients.

Results:
All participants were CMV-seropositive (body weight 28.7–95.0 kg). Of 12 PK-evaluable participants, 8 receiving 480 mg letermovir without CsA and 4 receiving 240 mg letermovir with CsA achieved exposures comparable to the adult exposure range. Exposure above the target but below the adult clinical program maximum was observed in 1 patient. Safety was consistent with previously described safety in adults. The proportion of participants with clinically significant CMV infection through week 24 post-HCT was comparable (24%) to that in the pivotal phase 3 study in adults (37.5%).

Conclusions:
Administration of adult letermovir doses in this adolescent cohort resulted in exposures within adult clinical program margins and was associated with safety and efficacy similar to adults. Results support a letermovir dose of 480 mg (240 mg with CsA) in adolescent allo-HCT recipients.
A Case of Enterococcal Patent Ductus Arteriosus-associated Endarteritis in a Preterm Neonate
Authors: Mayer Alessandra , Crippa Beatrice Letizia , Pietrasanta Carlo , Picciolli Irene , Ronchi Andrea , Raschetti Roberto , Bandera Alessandra , Colli Anna Maria , Mosca Fabio , Francescato Gaia , Pugni Lorenza 
Published: January 2024

Introduction:
The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics.

Case Presentation:
We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime.

Discussion:
IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.
Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review
Authors: Serbest Ceylanoglu Kubra , Guneri Beser Buse , Singalavanija Tassapol , Juntipwong Sarinee , Worden Francis Paul , Demirci Hakan 
Published: January 2024

Purpose:
To review the outcomes of targeted therapy and immunotherapy in advanced conjunctival tumors, including conjunctival squamous cell carcinoma, conjunctival melanoma, and conjunctival lymphoma.

Methods:
A Pubmed database systematic search was performed between January 1999 and December 2022. The literature search was limited to studies published in English.

Results:
This review included 142 patients with advanced malignant conjunctival tumors from 42 articles. In the conjunctival squamous cell carcinoma group, 2 cases of advanced conjunctival squamous cell carcinoma treated with epidermal growth factor receptor inhibitors showed significant tumor size improvement after 7.5 months of follow-up. Among 7 cases treated with systemic immunotherapy, 5 cases (72%) had complete response (CR), 1 case (14%) showed partial response (PR), and 1 case (14%) had stable disease (SD) after 16 months. In the conjunctival melanoma group, among 18 cases treated with combined v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated extracellular signal-regulated kinase inhibitors, 6 (33%) had CR, 5 (28%) had PR, 2 (11%) had SD, and 5 (28%) had progressive disease after 24.8 months of follow-up. Of 44 conjunctival melanoma cases treated with immunotherapy, 12 (28%) had CR, 9 (20%) had PR, 7(16%) had SD, and 16 (36%) had progressive disease after 14.2 months. Systemic Rituximab treatment for conjunctival lymphoma cases resulted in CR in 21 patients (63%), PR in 11 patients (33%), and SD in 1 patient (3%) after 20.5 months of follow-up. Intralesional Rituximab injections in 38 conjunctival lymphoma cases showed CR in 28 patients (75%), PR in 7 patients (19%), SD in 1 patient (2%), and progressive disease in 2 patients (4%) after 20.4 months of follow-up.

Conclusions:
Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.
Treatment of Thyroid Eye Disease-Associated Ophthalmopathy and Myopathy With Intraorbital Injection of 5-Fluorouracil and Triamcinolone Acetonide
Authors: Kupcha Anna C. , Law James J. , Mawn Louise A. 
Published: January 2024

Purpose:
The authors report a technique of local application of anti-metabolite and corticosteroid mixture in the orbit for treatment of thyroid orbitopathy with moderate-severe inflammation and muscle involvement.

Methods:
Patients of one orbital surgeon seen between March 2019 and May 2020 with active thyroid eye disease and restrictive strabismus were considered for local treatment of the myopathic component of the disease. A mixture of 1 ml 5-FU 50 mg/ml, 0.25 ml triamcinolone 40 mg/ml, and 1 ml lidocaine 2% is injected through the skin using a 25-gauge, 1.5-inch needle into the orbit adjacent to the affected extraocular muscle. Six patients were treated in the outpatient setting and 3 patients have been treated with this intervention intraoperatively at the time of orbital decompression. One was treated with the mixture reconstituted with hyaluronic acid (Healon GV) to address postoperative medial rectus fibrosis to the medial wall, this mixture was applied topically in the operative field and not injected.

Results:
All patients had subjective improvement in the eye movement limitation and 2 patients had a change in motility on exam that was temporally correlated to injections. One patient did not disclose high-dose aspirin intake before injection and experienced a retrobulbar hemorrhage immediately following injection which was successfully treated. No complications were noted as a result of the medication itself.

Discussion:
The combination of 5-fluorouracil and triamcinolone acetonide for orbital treatment may be a useful adjunct in treating patients with ongoing inflammatory activity, both in the office and in the operating room. The novel combination may optimize ophthalmic outcomes, modifying disease course in some patients.
Practice Patterns and Patient Experience of Care Among US Veterans with Prostate Cancer: A 10-Year Scoping Review
Authors: Patel Mital , Turner Erin , Edwards Natalie C. , Aworunse Olubiyi , Bhattacharyya Samir 
Published: January 2024

Purpose:
This study evaluated and synthesized the literature on prostate cancer practice patterns and patient experience of care within the US Veterans Affairs (VA) population.

Materials and Methods:
A scoping review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews standards. Search terms were prostate cancer, Veterans, treatment patterns, healthcare, resource, patient experience, quality of care, healthcare quality. The search was limited to human studies published in English in the past 10 years (2013-2022). Studies were included if they evaluated treatment patterns, health care resource use, and/or patient experience of care among US Veterans with prostate cancer.

Results:
Among 150 included studies, most were retrospective VA database evaluations (n = 119, 79.3%) or retrospective cohort studies (n = 8, 5.3%), with the remaining being prospective observational cohort studies (n = 16, 10.7%), randomized controlled trials (n = 5, 3.3%), a meta-analysis (n = 1, 0.7%), and a provider survey (n = 1, 0.7%). Sample sizes ranged from 11 to 214,649 patients. The most common topics were pharmacological therapies (n = 28), racial/ethnic disparities (n = 27), and definitive radiation therapy or radical prostatectomy (n = 24). Some studies indicated Veterans may not have access to the same quality of prostate cancer care compared with the general population. Opportunities for improvement in shared decision making remain.

Conclusion:
Some findings from this scoping review indicate that Veterans may not have access to the same quality of prostate cancer care compared with the US general population. Research is needed to confirm whether observed practice pattern differences are warranted given the potential negative care impact.
Dependence of Cochlear Duct Length Measurement on the Resolution of the Imaging Dataset
Authors: Spahn Bjoern , Ilgen Lukas , Neun Tilmann , Müller-Graff Franz-Tassilo , Schendzielorz Philipp , Hagen Rudolf , Althoff Daniel , Zabler Simon , Rak Kristen 
Published: January 2024

Hypothesis
Measurements of the cochlear duct length (CDL) are dependent on the resolution of the imaging dataset.

Background
Previous research has shown highly precise cochlear measurements using 3D-curved multiplanar reconstruction (MPR) and flat-panel volume computed tomography (fpVCT). Thus far, however, there has been no systematic evaluation of the imaging dataset resolution required for optimal CDL measurement. Therefore, the aim of this study was to evaluate the dependence of CDL measurement on the resolution of the imaging dataset to establish a benchmark for future CDL measurements.

Methods
fpVCT scans of 10 human petrous bone specimens were performed. CDL was measured using 3D-curved MPR with secondary reconstruction of the fpVCT scans (fpVCTSECO) and increasing resolution from 466 to 99 μm. In addition, intraobserver variability was evaluated. A best-fit function for calculation of the CDL was developed to provide a valid tool when there are no measurements done with high-resolution imaging datasets.

Results
Comparison of different imaging resolution settings showed significant differences for CDL measurement in most of the tested groups (p < 0.05), except for the two groups with the highest resolution. Imaging datasets with a resolution lower than 200 μm showed lower intraobserver variability than the other resolution settings, although there were no clinically unacceptable errors with respect to the Bland-Altman plots. The developed best-fit function showed high accuracy for CDL calculation using resolution imaging datasets of 300 μm or lower.

Conclusion
3D-curved MPR in fpVCT with a resolution of the imaging dataset of 200 μm or higher revealed the most precise CDL measurement. There was no benefit of using a resolution higher than 200 μm with regard to the accuracy of the CDL measurement.
Hearing Impairment and Severe Attention Deficit/Hyperactivity Disorder: A Nationwide Study
Authors: Tsur Nir , Zloof Yair , Rittblat Mor , Reuven Yonatan , Simchoni Maya , Derazne Estela , Yitzchaki Ziv , Adler Lior , Shlaifer Amir , Manuva Omer , Beer Zivan 
Published: January 2024

Background
The association between hearing impairment and attention-deficit/hyperactivity disorder (ADHD) is unclear. Therefore, we aimed to assess this association in Israel's national sample of over 1.1 million adolescents.

Methods
We conducted a nationwide, population-based, cross-sectional study of all Israeli adolescents (n = 1,175,534, 58% males; mean age, 17 yrs) who were examined before mandatory military service during 2004 to 2020. Board-certified specialists confirmed diagnoses of hearing impairment and severe ADHD.

Main Outcomes and Measures
We compared the prevalence of severe ADHD in adolescents with and without hearing impairment. Associations were analyzed using logistic regression models and sensitivity analyses accounting for hearing impairment type (sensorineural vs. conductive) and severity.

Results
Of the 8,769 adolescents with hearing impairment, 57 were diagnosed with severe ADHD (prevalence = 0.65%). Of the 1,166,765 adolescents without hearing impairment, 3,936 were diagnosed with severe ADHD (prevalence = 0.29%). We found a significant association between hearing impairment and severe ADHD (odds ratio = 1.93 [95% confidence interval, 1.47–2.49]), which persisted in a multivariable model adjusted to age, sex, socioeconomic status, educational status, cognitive performance, and immigration status (odds ratio = 1.70 [95% confidence interval, 1.29–2.20]). The association also persisted when stratified by hearing impairment type (sensorineural vs. conductive) and severity.

Conclusions
Adolescents with hearing impairment had 70% increased odds of severe ADHD. Study findings suggest that active screening of patients with hearing impairment for ADHD should be considered.
Immunomodulatory Response of the Middle Ear Epithelial Cells in Otitis Media
Authors: Leffers David , Penxova Zuzana , Kempin Thorge , Därr Markus , Fleckner Jonas , Hollfelder Daniela , Ryan Allen F. , Bruchhage Karl-Ludwig , Kurabi Arwa , Leichtle Anke 
Published: January 2024

Hypothesis
The middle ear (ME) epithelium transforms because of changed immunomodulation during infection.

Introduction
The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa. Our goal is to depict the specific immune response of epithelial cells after infection at the molecular level.

Methods
The investigations were carried out on healthy and inflamed ME tissue, removed during surgical interventions in mouse and human models, and in a human in-vitro cell model in human ME epithelial cell line. We determined the epithelial localization of the protein expression of Toll- and NOD-like immune receptors and their associated signaling molecules using immunohistochemistry. In addition, we examined growth behavior and gene expression due to direct stimulation and inhibition.

Results
We found clinically and immunobiologically confirmed transformation of the inflamed ME epithelium depending on their origin, as well as differences in the distribution of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors in the epithelial cell lining. Dysregulated gene and protein expression of the inflammatory and apoptotic genes could be modulated by stimulation and inhibition in the epithelial cells.

Conclusions
The local ME mucosal tissue is believed to modulate downstream immune activity after pathogen invasion via intrinsic cellular mechanism. Using translation approaches to target these molecular pathways may offer more reliable clinical resolution of otitis media in the future.
Efficacy and safety of Buzhongyiqi decoction combined with acupoint application for functional constipation in elderly people: A systematic review and meta-analysis
Authors: Chen Yanjie , Luo Shu , Luo Min 
Published: January 2024

Purpose:
This study aimed to evaluate the efficacy and safety of Buzhongyiqi decoction combined with acupoint application in the treatment of functional constipation in elderly people.

Methods:
(1) Four Chinese databases (China National Knowledge Infrastructure, China Science Periodical Database, Chinese Citation Database, China Biology Medicine) and 4 foreign databases (PubMed, Web of Science, Cochrane Library, Embase) were searched, excluded, and included in randomized controlled trials of Buzhongyiqi decoction combined with acupoint application for the treatment of functional constipation in elderly people. (2) Systematic evaluation and meta-analysis using the RevMan 5.3 software. (3) Harbord linear regression and sensitivity analyses were conducted to evaluate publication bias using Stata 14.0. (4) Reliability of the conclusion assessment by sequential test analysis in TSA0.9 software. (5) Quality of evidence evaluation of outcome indicators was evaluated using Gradepro 3.6 software.

Results:
Eight randomized controlled trials including 658 case sample sizes were included. Compared with the control group, the intervention group showed improved clinical cure rate and effective rate of functional constipation in elderly people, reduced recurrence rate, and efficacy regulated the levels of defecation-related indices and indices of gastrointestinal function. In addition, trial sequential analysis indicated that the total clinical efficacy rate was conclusive, which showed that the therapeutic efficacy of the intervention group was superior to that of the control group. However, the incidence of adverse effects in intervention group was comparable to that of control group, and trial sequential analysis suggests that this result needs to be supported by additional research.

Conclusion:
Buzhongyiqi decoction combined with acupoint application has potential value in the treatment of functional constipation in elderly people. Currently, there is insufficient clinical evidence to objectively evaluate safety grades for this combination therapy.
Meta-analysis of risk factors for posttraumatic stress disorder in myocardial infarction
Authors: Liu Jingyu , Wang Lingyu , Wang Yimu , Fang Haiyan , Wang Xiang 
Published: January 2024

Background:
The aim of this study was to identify the risk factors for posttraumatic stress disorder in patients with myocardial infarction.

Methods:
Cohort, case-control, and cross-sectional studies on posttraumatic stress disorder (PTSD) in patients with myocardial infarction were searched from PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and Technology Journal database. The Newcastle-Ottawa Quality Assessment Scale was used to score the quality of the included literature in the cohort and case-control studies, and the cross-sectional studies were scored using the American Agency for Health Care Quality and Research cross-sectional study quality evaluation criteria. The literature was screened independently by 2 researchers, and if there was no consensus, the inclusion was decided by a third party. The extraction content included first author, publication year, sample size, PTSD assessment tool, PTSD assessment time, PTSD incidence, influencing factors, and study type. Meta-analysis of data was performed using Stata17.0 software.

Results:
Ten studies were included, including 2 cohort studies, 7 cross-sectional studies, and 1 case-control study, with a total sample size of 2371 patients, including 26 influencing factors. The results of meta-analysis showed that the prevalence of PTSD in patients with myocardial infarction was 21.2%. Statistically significant influencing factors were gender (odd ratio [OR] = 3.124), neuroticism score (OR = 2.069), and age (OR = 0.913).

Conclusions:
The prevalence of PTSD in patients with myocardial infarction in China is higher than that in other countries. Female and neurotic personality are risk factors for developing PTSD in patients with myocardial infarction, and old age is protective factor for developing PTSD in patients with myocardial infarction. Targeted measures should be taken to prevent and reduce the occurrence and development of PTSD in patients with myocardial infarction in the future.
The second cutaneous anthrax infection diagnosed by metagenomic next-generation sequencing: A case report
Authors: Zheng Cuiying , Ye Jiaqing , Song Minghui , Guo Yumei , Gao Weili , Hao Jiahao , Feng Zhongjun , Zhang Lijie 
Published: January 2024

Rationale:
Anthrax is a severe zoonotic infectious disease caused by Bacillus anthracis. Most reported cases were traditionally diagnosed through culture and microscopy. We reported here the second case of cutaneous anthrax diagnosed by metagenomic next-generation sequencing (mNGS).

Patient concerns:
A 63-year-old man had a history of contact with an unwell sheep, developing local redness and swelling on wrist. The dorsal side of the left hand and forearm, with tension blisters on the back of the left.

Diagnosis:

B anthracis was detected from culturing and mNGS of tension blisters.

Interventions:
On the second day of admission, the patient was administered 3.2 million units of penicillin every 6 hours, and isolated and closely observed.

Outcomes:
The patient improves and is discharged.

Lessons:
Traditional bacterial cultures are time-consuming, while mNGS offers the advantage of accurate, quick, high-throughput, unbiased sequencing of all genetic material in a sample, which is a good technical tool for assisting in the diagnosis of rare pathogen infections.
Long-term survival in a patient with multiple metastatic gastric cancer treated with PTX plus emvolimab and disitamab vedotin: case report and treatment experience: A case report
Authors: Zhou Yongjin , Zhang Meifeng , Dai Li , Yan Zhiqiang , Wang Haibin , Yang Hongxin , Jin Xiangren , Wang Qian 
Published: January 2024

Rationale:
Most Chinese patients with locally advanced gastric cancer at diagnosis have an overall 5-year survival rate of <50%. Surgical resection alone is not suitable for patients with locally advanced gastric cancer. Currently, comprehensive treatment is the focus of locally advanced gastric cancer.

Patients concerns:
The patient, a 56-year-old female, was admitted to the hospital because of “4 + months of double hydronephrosis found during a physical examination.” Who was admitted for computer tomography and gastroscopy examinations, and take pathological tissue specimens during endoscopic examination.

Diagnoses:
Computed tomography assessment indicated ulcerative gastric cancer with an abdominal implant, bladder, and bone metastases. An endoscopic examination revealed that the ulcer of the gastric angle was huge, and through relevant auxiliary examinations, the diagnosis of this disease is gastric cancer complicated with multiple metastases to bladder, rectum, lumbar spine, and peritoneum. Clinically diagnosed as cT4bN3M1.

Interventions:
The patient is currently undergoing first, second, and third line neoadjuvant therapy, combined with immunotherapy, targeted therapy, neoadjuvant intraperitoneal systemic chemotherapy, nutritional support, and other treatment plans.

Outcomes:
After 15 cycles of treatment, the progression-free survival had reached 15 months. The patient had an NRS2002 score of 1, an ECOG score of I, a quality of life score of 55, albumin of 35.27 g/L, and a decrease in abdominal and pelvic fluid accumulation and exudation compared to before.

Lessons:
We demonstrated high survival of almost 3 years in a patient with gastric cancer that was complicated by bone, peritoneal, rectal, and bladder metastases. The combination of immunotherapy, targeted therapy, and neoadjuvant intraperitoneal systemic chemotherapy, along with the maintenance of nutritional status and CTCs could be a valuable modality for the subsequent treatment and observation of similar patients.