bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Melanocytic Nevus and Nevus Sebaceus: A Case Series and Review of the Literature
Authors: Schroedl Liesl M. , Lullo Jenna J. , de Luzuriaga Arlene M. Ruiz , Shea Christopher R. 
Published: April 2024

Abstract:
Nevus sebaceus is a rare congenital hamartoma with clinical and histopathological features that change with puberty. It has been associated with a number of secondary neoplasms, most of which are thought to derive from follicular germ cells. In this article, the authors describe a total of 3 cases of combined melanocytic nevus and nevus sebaceus to highlight this rare finding.
A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy
Authors: Chaudhari Advaita S. , McFadden Jason R. , Bentz Jessica , Evans Rebecca H. , Selim Maria A. , Sriharan Aravindhan 
Published: April 2024

Abstract:
Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non–neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she “does not always remember to apply” clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.
Richter Syndrome Presenting as Subcutaneous Nodules and a Dermal Plaque
Authors: Nickles Melissa , Hunt Samantha , Turcios-Escobar Saul , Babwah Amaara , Mobayed Nisreen , Murga-Zamalloa Carlos , Bain Michelle , Quigley John , Rubinstein Paul , Galvez Carlos 
Published: April 2024

Abstract:
Richter syndrome (RS) describes a phenomenon in which a patient with chronic lymphocytic leukemia (CLL) develops an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). Reports of cutaneous RS remain exceedingly rare. We report a 61-year-old woman with relapsed/refractory CLL presenting with several subcutaneous nodules on her arms and legs and a single dermal plaque on her abdomen. Skin biopsy revealed a diagnosis of DLBCL, ABC-type, and her clinical status rapidly deteriorated following diagnosis. We review the variety of clinical presentations of cutaneous RS, its association with CLL, risk factors for RS development in CLL patients, and the distinctive histopathologic and immunophenotypic features of DLBCL. We hope to highlight the importance of prompt skin biopsy in patients with CLL presenting with progressive skin lesions and increase awareness of this aggressive clinical syndrome.
Apocrine Hidrocystoma of the Nail: A Unique Case
Authors: Salah Haneen , Duran Juanita , Russell Mark A. , Gru Alejandro A. 
Published: April 2024

Abstract:
Apocrine hidrocystomas are benign, cystic neoplastic lesions resulting from the apocrine secretory component of the sweat gland. They most commonly occur on the head and neck, with predilection to the periorbital area. Less frequent sites include the axilla, nipple, external auditory canal, foreskin, conjunctiva, lower lip, and fingers, among others. The authors report a unique case of a nail bed hidrocystoma in a 55-year-old woman, a site not previously described.
Influence of Tacrolimus Intrapatient Variability on Allograft Rejection Frequency and Survival Following Liver Transplantation
Authors: Soares Maria Eduarda , Costa Gabriela , Guerra Laura , Morais Maria Clara , Vaz Nayana , Codes Liana , Bittencourt Paulo Lisboa 
Published: April 2024

Background:
Tacrolimus is the primary calcineurin inhibitor used in immunosuppressive regimens to prevent allograft rejection (AR) after organ transplantation. Recent studies have linked intrapatient variability (IPV) of tacrolimus with AR occurrence and reduced survival, especially in kidney transplant recipients. However, limited data are available on the impact of tacrolimus IPV on adverse outcomes after liver transplantation (LT).

Aims:
The aim of this study was to assess the association between tacrolimus IPV using various methodologies with acute AR and long-term patient survival after LT.

Methods:
All patients who underwent LT from January 2010 to July 2021 were retrospectively evaluated. Tacrolimus IPV was calculated for each patient using the mean and SD, mean absolute deviation (MAD), coefficient of variation (CV), and time in therapeutic range (TTR). These measures were then compared with AR within the first 24 months after LT and to long-term survival.

Results:
Out of 234 patients, 32 (13.7%) developed AR and 183 (78.2%) survived, with a mean follow-up of 101 ± 43 months. Tacrolimus IPV, assessed by mean, SD, MAD, and CV, was 8.3 ± 2.1, 2.7 ± 1.3, 32.0% ± 11.7%, and 39.4% ± 15.4%, respectively. There was no statistically significant correlation between Tacrolimus IPV and AR or survival post-LT.

Conclusions:
In a large cohort of patients from diverse racial backgrounds, tacrolimus IPV was not associated with clinically relevant outcomes such as AR and survival after LT.
Factors Influencing Serum Posaconazole Concentrations in Patients With Hematologic Malignancies Receiving Delayed-Release Tablets
Authors: Yamada Takaaki , Belabbas Tassadit , Suetsugu Kimitaka , Hirota Takeshi , Mori Yasuo , Kato Koji , Akashi Koichi , Egashira Nobuaki , Ieiri Ichiro 
Published: April 2024

Background:
Posaconazole (PCZ) plays a crucial role in the prophylaxis and treatment of invasive fungal infections in hematologic malignancies. PCZ concentrations reportedly vary among patients receiving delayed-release tablets (DRT). However, the factors influencing these concentrations remain insufficiently elucidated. Therefore, this study aimed to evaluate the factors influencing PCZ concentrations and their effect on the probability of target attainment (PTA) using a population pharmacokinetic (PPK) approach. We also explored the relationship between PCZ exposure and hepatotoxicity.

Methods:
This retrospective study included adult patients with hematologic malignancies who received PCZ DRT. A PPK model was developed based on observational data for 130 concentrations in 28 patients. Simulation analyses were performed to assess the PTA at standard doses of 0.7 and 1.0 mg/L for prophylaxis and treatment, respectively. Estimated concentrations were used to evaluate the correlation between PCZ exposure and hepatotoxicity.

Results:
Significant factors influencing PCZ concentrations included body weight, serum total protein levels, and diarrhea. Diarrhea correlated with decreased PCZ concentrations resulting in up to 26% lower PTA compared with that without diarrhea. Moreover, PTA declined markedly as the total protein levels decreased from 6.6 g/dL to 4.4 g/dL. The incidence of hepatotoxicity was 17.4% (4/23); no significant relationship could be established between the PCZ concentrations and hepatotoxicity (P = 0.188).

Conclusions:
We identified the factors affecting PCZ exposure, which could not be detected by PPK analysis using data from clinical trials. Our results suggest that the generally recommended dose of PCZ causes underexposure in patients with hematologic malignancies characterized by high body weight, hypoproteinemia, or concurrent diarrhea. Therapeutic drug monitoring for DRT may be recommended, especially in patients with these risk factors.
Retrospective Analysis of Steady-State Sodium Valproate Plasma Concentrations in Chinese Patients With Bipolar Disorder: Impact of Demographic and Clinical Characteristics
Authors: Qiming Qian , Ping Zheng , Huiqi Li , Leyu Xu , LIren Li , Ming Lei 
Published: April 2024

Background:
This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes.

Methods:
In total, 164 patients met the inclusion criteria and were included in the analysis. The patient age ranged from 13 to 60 years, with a median age of 25.71 years. Most patients (89%) received a daily dose of 1 g valproic acid. Co-administered psychiatric medications included aripiprazole, quetiapine, and lorazepam. Laboratory test results, such as hemoglobin and transaminase levels, were also collected as part of the study.

Results:
The average plasma valproic acid plasma concentration was 79.8 mg/L. The dose significantly affected valproic acid concentrations, as a higher percentage of measurements exceeded the therapeutic range at a daily dose of 1 g. Furthermore, females exhibited significantly higher valproic acid concentrations compared with males at the same dose (P < 0.05). However, different age groups showed no statistically significant differences in valproic acid concentrations (P > 0.05). The co-administered antipsychotic and antidepressant medications significantly affected valproate concentrations, as reflected in the multiple regression model (P < 0.01).

Conclusions:
This study offers valuable insights into the demographic and clinical characteristics of patients undergoing valproic acid therapy. It highlights the influence of dose, sex, and concomitant medications on plasma valproic acid concentrations. Overall, these findings can help guide dose adjustments and implement personalized treatment strategies in valproic acid therapy.
Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology
Authors: Alsoud Dahham , Moes Dirk Jan A. R. , Wang Zhigang , Soenen Rani , Layegh Zohra , Barclay Murray , Mizuno Tomoyuki , Minichmayr Iris K. , Keizer Ron J. , Wicha Sebastian G. , Wolbink Gertjan , Lambert Jo , Vermeire Séverine , de Vries Annick , Papamichael Konstantinos , Padullés-Zamora Núria , Dreesen Erwin 
Published: April 2024

Background:
Infliximab, an anti–tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research.

Methods:
The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement.

Results:
Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record–integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration.

Conclusions:
Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.
An Analysis of ChatGPT4 to Respond to Glaucoma-Related Questions
Authors: Kerci Suleyman G. , Sahan Berna 
Published: April 2024

Précis:
In recent years, ChatGPT has been widely used as a source of information. In our study, it was revealed that ChatGPT gives accurate information about glaucoma.

Purpose:
We examined the knowledge of ChatGPT about glaucoma.

Materials and Methods:
Frequently asked questions about glaucoma found on websites of ophthalmology associations and hospitals, and social media applications were assessed. Evidence-Based Recommendations in the European Glaucoma Society Terminology and Guidelines for Glaucoma, Fifth Edition were evaluated. Using the ChatGPT-4, each question was asked twice on different computers to assess the reproducibility of answers. The answers provided were recorded and 2 specialist ophthalmologists evaluated them independently, assigning scores ranging from 1 to 4.

Results:
The answers to all questions about glaucoma resulted in 88.7% completely correct, 7.5% correct but insufficient, and 3.8% misleading information and correct information. No question was answered completely incorrectly. While 85.8% of the general knowledge questions were answered correctly, 91.7%, 86.6%, and 91.7% of questions about diagnosis, treatment, and prevention were answered correctly, respectively. The number of questions prepared based on the European Glaucoma Society Terminology and Guidelines for Glaucoma was 16. The rate of completely correct answers to these questions was 75.0% (12). While 3 (18.8%) answers were correct but insufficient, 1 response (6.3%) contained false information and correct information.

Conclusions:
Our study revealed that ChatGPT answered 9 out of 10 questions about general information, diagnosis, treatment, and preventive and follow-up about glaucoma with acceptable and satisfactory accuracy rates. In addition, 3 of 4 answers given by ChatGPT were completely correct according to Terminology and Guidelines for Glaucoma.
Smoking Intensity is Associated With Progressive Optic Nerve Head Vessel Density Loss in Glaucoma
Authors: Nishida Takashi , Weinreb Robert N. , Tansuebchueasai Natchada , Wu Jo-Hsuan , Meller Leo , Mahmoudinezhad Golnoush , Gunasegaran Gopikasree , Adelpour Mohsen , Moghimi Sasan 
Published: April 2024

Précis:
A lifetime history of greater smoking consumption was associated with faster vessel density loss over time. Smoking intensity should be considered when assessing the risk of glaucoma progression, as well as its management.

Purpose:
To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients.

Methods:
In this longitudinal study, patients with POAG who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity.

Results:
One hundred sixty-four eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss [−0.11 (−0.23 to 0.00)] %/year per 10 pack-year higher; P=0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked <22.2 pack-years during their lifetime.

Conclusions:
A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.
Using machine learning to identify key subject categories predicting the pre-clerkship and clerkship performance: 8-year cohort study
Authors: Huang Shiau-Shian , Lin Yu-Fan , Huang Anna YuQing , Lin Ji-Yang , Yang Ying-Ying , Lin Sheng-Min , Lin Wen-Yu , Huang Pin-Hsiang , Chen Tzu-Yao , Yang Stephen J. H. , Lirng Jiing-Feng , Chen Chen-Huan 
Published: April 2024

Background:
Medical students need to build a solid foundation of knowledge to become physicians. Clerkship is often considered the first transition point, and clerkship performance is essential for their development. We hope to identify subjects that could predict the clerkship performance, thus helping medical students learn more efficiently to achieve high clerkship performance.

Methods:
This cohort study collected background and academic data from medical students who graduated between 2011 and 2019. Prediction models were developed by machine learning techniques to identify the affecting features in predicting the pre-clerkship performance and clerkship performance. Following serial processes of data collection, data preprocessing before machine learning, and techniques and performance of machine learning, different machine learning models were trained and validated using the 10-fold cross-validation method.

Results:
Thirteen subjects from the pre-med stage and 10 subjects from the basic medical science stage with an area under the ROC curve (AUC) >0.7 for either pre-clerkship performance or clerkship performance were found. In each subject category, medical humanities and sociology in social science, chemistry, and physician scientist-related training in basic science, and pharmacology, immunology-microbiology, and histology in basic medical science have predictive abilities for clerkship performance above the top tertile. Using a machine learning technique based on random forest, the prediction model predicted clerkship performance with 95% accuracy and 88% AUC.

Conclusion:
Clerkship performance was predicted by selected subjects or combination of different subject categories in the pre-med and basic medical science stages. The demonstrated predictive ability of subjects or categories in the medical program may facilitate students’ understanding of how these subjects or categories of the medical program relate to their performance in the clerkship to enhance their preparedness for the clerkship.
Incidence, epidemiology, and outcomes of acute allograft rejection following liver transplantation in Australia
Authors: Tang Lauren C.Y. , Chetwood John D. , Lai Mandy S.M. , Yip Terry C.F. , Cao Rena , Powter Elizabeth , Salimi Shirin , Wu Rodger , Coulshed Andrew , Bowen David G. , Strasser Simone I. , Valliani Talal , Crawford Michael , Pulitano Carlo , McKenzie Catriona , Kench James , McCaughan Geoffrey W. , Liu Ken 
Published: April 2024

Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology, and outcomes of acute rejection have not been well described in Australia. We retrospectively studied consecutive adults who underwent deceased donor LT at a single center between 2010 and 2020. Donor and recipient data at the time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed, and only a graft’s first instance of biopsy-proven acute rejection was analyzed. During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p=0.11). The median time to the first episode of rejection was 71 days after LT: 2.2% hyperacute, 50.4% early (≤90 d), and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI: 0.97–1.00, p=0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI: 1.27–5.09, p<0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI: 0.08–0.58, p<0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI: 2.21–4.42, p<0.001) and patient survival (aHR 3.42, 95% CI: 2.35–4.98, p<0.001). In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant, while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.
Comparison of 1-stage and 2-stage Managements for Common Bile Duct Stones and Gallstones (CBDS)
Authors: Zhou Jie , Chen Ye , Yu Songlin , Wang Hui , Wang Yufeng , Chen Quanning 
Published: April 2024

Objective:
The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS).

Methods:
This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups.

Results:
Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05).

Conclusions:
Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.