bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of falling accident when carrying a thermos bottle in front of the body
Authors: Tatekawa Yukihiro , Tsuzuki Yukihiro , Fukuzato Yoshimitsu
Published: September 2024

Traumatic injury in children often involves traffic accidents, falls from height, bicycle accidents, abuse, and sports. We present our experience with a 6-year-old girl who bruised her abdomen by falling while running with a thermos bottle hanging diagonally across her neck and left shoulder, crossing in front of her body. After the injury, she was rushed to the hospital and plain abdominal computed tomography revealed free air, suggesting intestinal injury due to blunt trauma. She was transferred to our hospital, where abdominal examination revealed a bruise and redness at the umbilicus. There were signs of peritoneal irritation and guarding throughout the abdomen. Upright chest X-ray showed free air in the right subdiaphragmatic region. Laparoscopic inspection revealed one perforation and two serosal injuries. The damaged serosa was repaired, and the perforated intestine was resected and anastomosed. The patient was discharged on the 11th day following an uneventful postoperative course.
Nasopharyngeal and temporal bone abscess following necrotizing otitis externa: a case report
Authors: Alharthi Ahmad S , Almalki Zohour A , Alnafie Johara A , Althobaiti Hazem K , Ibrahim Mohamed M
Published: September 2024

Necrotizing otitis externa (NOE) is a severe infection primarily affecting the external auditory canal, seen mainly in immunocompromised individuals as patients with diabetes mellitus (DM). This case report highlights unusual complications of NOE: temporal bone and nasopharyngeal abscesses. These complications underscore the severity of NOE, particularly when caused by rare pathogens such as Klebsiella species. We detail the case of a 70-year-old male with uncontrolled DM who presented with severe right ear pain, purulent discharge, and significant postauricular swelling. Laboratory investigations revealed elevated inflammatory markers and poorly controlled diabetes. Cultures confirmed Klebsiella pneumoniae, and imaging showed diffuse edema and abscess formation in the temporal bone and nasopharynx. The patient was treated with intravenous Ceftazidime and ciprofloxacin for 6 weeks, followed by oral ciprofloxacin. Effective management of NOE necessitates a comprehensive, multidisciplinary approach. Early intervention, regular monitoring, and imaging are critical for promptly detecting and managing complications.
Rare confounder: benign multicystic peritoneal mesothelioma in a patient with mucinous colon adenocarcinoma
Authors: Patel Kruti K , Stinson Griffin P , Terracina Krista P , Nordenstam Johan F , Read Thomas E
Published: September 2024

Benign multicystic peritoneal mesothelioma (BMPM) is a rare condition, in which patients have multiple cystic lesions of the peritoneum. BMPM can mimic mucinous carcinomatosis and can thus create a diagnostic dilemma. We present the case of a 76-year-old woman who was referred for management of ascending colon adenocarcinoma and was noted to have several nonspecific cystic lesions in the abdomen and pelvis on preoperative computed tomography and diagnostic laparoscopy. Frozen section analysis suggested the lesions contained ‘mucin’. Due to concern for metastases, right colectomy was aborted. Final histologic analysis of the laparoscopic biopsies revealed mesothelial cysts, consistent with BMPM, unrelated to her colon adenocarcinoma. Laparoscopic right colectomy was performed 2 weeks later. BMPM can create diagnostic and therapeutic uncertainty in patients with known visceral malignancies when discovered incidentally. Frozen section analysis may not be accurate in differentiating the two, and final histologic confirmation should be sought prior to definitive treatment.
Deciphering the dynamic single-cell transcriptional landscape in the ocular surface ectoderm differentiation system
Authors: Zhang Canwei , Lin Zesong , Yu Yankun , Wu Siqi , Huang Huaxing , Huang Ying , Liu Jiafeng , Mo Kunlun , Tan Jieying , Han Zhuo , Li Mingsen , Zhao Wei , Ouyang Hong , Chen Xiangjun , Wang Li
Published: September 2024

The ocular surface ectoderm (OSE) is essential for the development of the ocular surface, yet the molecular mechanisms driving its differentiation are not fully understood. In this study, we used single-cell transcriptomic analysis to explore the dynamic cellular trajectories and regulatory networks during the in vitro differentiation of embryonic stem cells (ESCs) into the OSE lineage. We identified nine distinct cell subpopulations undergoing differentiation along three main developmental branches: neural crest, neuroectodermal, and surface ectodermal lineages. Key marker gene expression, transcription factor activity, and signaling pathway insights revealed stepwise transitions from undifferentiated ESCs to fate-specified cell types, including a PAX6 + TP63 + population indicative of OSE precursors. Comparative analysis with mouse embryonic development confirmed the model’s accuracy in mimicking in vivo epiblast-to-surface ectoderm dynamics. By integrating temporal dynamics of transcription factor activation and cell–cell communication, we constructed a comprehensive molecular atlas of the differentiation pathway from ESCs to distinct ectodermal lineages. This study provides new insights into the cellular heterogeneity and regulatory mechanisms of OSE development, aiding the understanding of ocular surface biology and the design of cell-based therapies for ocular surface disorders.
Rapid Loss of Nutritional Symbionts in an Endemic Hawaiian Herbivore Radiation Is Associated with Plant Galling Habit
Authors: Hansen Allison K , Argondona Jacob A , Miao Sen , Percy Diana M , Degnan Patrick H
Published: September 2024

Insect herbivores frequently cospeciate with symbionts that enable them to survive on nutritionally unbalanced diets. While ancient symbiont gain and loss events have been pivotal for insect diversification and feeding niche specialization, evidence of recent events is scarce. We examine the recent loss of nutritional symbionts (in as little as 1 MY) in sap-feeding Pariaconus, an endemic Hawaiian insect genus that has undergone adaptive radiation, evolving various galling and free-living ecologies on a single host-plant species, Metrosideros polymorpha within the last ∼5 MY. Using 16S rRNA sequencing, we investigated the bacterial microbiomes of 19 Pariaconus species and identified distinct symbiont profiles associated with specific host-plant ecologies. Phylogenetic analyses and metagenomic reconstructions revealed significant differences in microbial diversity and functions among psyllids with different host-plant ecologies. Within a few millions of years, Pariaconus species convergently evolved the closed-gall habit twice. This shift to enclosed galls coincided with the loss of the Morganella-like symbiont that provides the essential amino acid arginine to free-living and open-gall sister species. After the Pariaconus lineage left Kauai and colonized younger islands, both open- and closed-gall species lost the Dickeya-like symbiont. This symbiont is crucial for synthesizing essential amino acids (phenylalanine, tyrosine, and lysine) as well as B vitamins in free-living species. The recurrent loss of these symbionts in galling species reinforces evidence that galls are nutrient sinks and, combined with the rapidity of the evolutionary timeline, highlights the dynamic role of insect–symbiont relationships during the diversification of feeding ecologies. We propose new Candidatus names for the novel Morganella-like and Dickeya-like symbionts.
Acute heart failure with reduced ejection fraction following ozoralizumab in a patient with rheumatoid arthritis: A case report
Authors: Ito Takaaki , Miyoshi Yuji
Published: September 2024

Ozoralizumab (OZR), a novel next-generation tumor necrosis factor (TNF) inhibitor with variable heavy-chain domains of heavy-chain-only antibodies, named Nanobody®, was approved in September 2022 as the sixth TNF inhibitor in Japan. Other previous TNF inhibitors have been associated with various adverse drug reactions (ADRs), including heart failure (HF). The real-world data on these rare but clinically significant ADRs associated with OZR is lacking. Herein, we report a case of an 81-year-old female patient with rheumatoid arthritis who was insufficiently responsive to previous TNF inhibitors and developed HF with reduced ejection fraction (HFrEF) after the first OZR administration. Her condition improved after OZR discontinuation, suggesting that OZR may have precipitated the HF with reduced ejection fraction despite tolerance with previous TNF inhibitors. Further studies are warranted to elucidate the mechanism and incidence of OZR-associated HF.
A global assessment of kidney care workforce
Authors: Okpechi Ikechi G , Tummalapalli Sri Lekha , Chothia Mogamat-Yazied , Sozio Stephen M , Tungsanga Somkanya , Caskey Fergus J , Riaz Parnian , Ameh Oluwatoyin I , Arruebo Silvia , Damster Sandrine , Donner Jo-Ann , Jha Vivekanand , Levin Adeera , Nangaku Masaomi , Saad Syed , Tonelli Marcello , Ye Feng , Bello Aminu K , Johnson David W
Published: September 2024

Background

An adequate workforce is needed to guarantee optimal kidney care. We used the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to provide an assessment of the global kidney care workforce.

Methods

We conducted a multinational cross-sectional survey to evaluate the global capacity of kidney care and assessed data on the number of adult and paediatric nephrologists, the number of trainees in nephrology and shortages of various cadres of the workforce for kidney care. Data are presented according to the ISN region and World Bank income categories.

Results

Overall, stakeholders from 167 countries responded to the survey. The median global prevalence of nephrologists was 11.75 per million population (pmp) (interquartile range [IQR] 1.78–24.76). Four regions had median nephrologist prevalences below the global median: Africa (1.12 pmp), South Asia (1.81 pmp), Oceania and Southeast Asia (3.18 pmp) and newly independent states and Russia (9.78 pmp). The overall prevalence of paediatric nephrologists was 0.69 pmp (IQR 0.03–1.78), while overall nephrology trainee prevalence was 1.15 pmp (IQR 0.18–3.81), with significant variations across both regions and World Bank income groups. More than half of the countries reported shortages of transplant surgeons (65%), nephrologists (64%), vascular access coordinators (59%), dialysis nurses (58%) and interventional radiologists (54%), with severe shortages reported in low- and lower-middle-income countries.

Conclusions

There are significant limitations in the available kidney care workforce in large parts of the world. To ensure the delivery of optimal kidney care worldwide, it is essential to develop national and international strategies and training capacity to address workforce shortages.
Global structures, practices, and tools for provision of hemodialysis
Authors: Htay Htay , Cho Yeoungjee , Jha Vivekanand , See Emily , Arruebo Silvia , Caskey Fergus J , Damster Sandrine , Donner Jo-Ann , Levin Adeera , Nangaku Masaomi , Saad Syed , Tonelli Marcello , Ye Feng , Okpechi Ikechi G , Bello Aminu K , Johnson David W
Published: September 2024

Background

Hemodialysis (HD) is the most commonly utilized modality for kidney replacement therapy worldwide. This study assesses the organizational structures, availability, accessibility, affordability and quality of HD care worldwide.

Methods

This cross-sectional study relied on desk research data as well as survey data from stakeholders (clinicians, policymakers and patient advocates) from countries affiliated with the International Society of Nephrology from July to September 2022.

Results

Overall, 167 countries or jurisdictions participated in the survey. In-center HD was available in 98% of countries with a median global prevalence of 322.7 [interquartile range (IQR) 76.3–648.8] per million population (pmp), ranging from 12.2 (IQR 3.9–103.0) pmp in Africa to 1575 (IQR 282.2–2106.8) pmp in North and East Asia. Overall, home HD was available in 30% of countries, mostly in countries of Western Europe (82%). In 74% of countries, more than half of people with kidney failure were able to access HD. HD centers increased with increasing country income levels from 0.31 pmp in low-income countries to 9.31 pmp in high-income countries. Overall, the annual cost of in-center HD was US$19 380.3 (IQR 11 817.6–38 005.4), and was highest in North America and the Caribbean (US$39 825.9) and lowest in South Asia (US$4310.2). In 19% of countries, HD services could not be accessed by children.

Conclusions

This study shows significant variations that have remained consistent over the years in availability, access and affordability of HD across countries with severe limitations in lower-resourced countries.
Effects of Nicotine Doses and Administration Frequencies on Mouse Body Weight and Adipose Tissues
Authors: Qin Runwen , Zhang Yi , Xu Shihua , Mei Yingwu , Jin Ge , Mi Yang , Zhang Haifeng
Published: September 2024

Introduction

This study investigates the effects of varying nicotine doses and administration frequencies on mouse body weight, adipose tissues, and liver.

Aims and Methods

Male C57BL6/J mice received subcutaneous nicotine doses (0.5, 1, or 2 mg/kg) once daily (qd), twice daily (bid), or four times daily (qid) for 4 weeks. Body weight, inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) weight and size, and UCP1 expression were assessed, along with liver fat deposition and morphology.

Results

Nicotine administration reduced body weight and decreased the weight and size of iWAT and eWAT compared to controls. The frequency of nicotine administration had a more significant impact on body weight and fat tissues than the dosage itself, with 2 mg/kg bid being optimal for weight reduction. Nicotine increased BAT cell numbers and amplified UCP1 expression in iWAT and BAT. It had minor effects on eWAT UCP1 expression and no substantial impact on liver fat deposition or morphology, except for a reduction in liver weight with doses exceeding 4 mg/kg.

Conclusions

Nicotine-induced weight reduction is frequency-dependent, with 2 mg/kg bid being the optimal regimen. The mechanisms may include reductions in iWAT and eWAT weights and cell sizes, induction of browning in iWAT, increased BAT quantity and UCP1 expression, and heightened energy expenditure in iWAT and BAT. Nicotine’s ability to induce eWAT browning is relatively weak, indicating diverse mechanisms of action across different adipose tissue types. These findings provide a foundation for further exploration of nicotine’s multifaceted functions and underlying mechanisms.

Implications

This study examines how different nicotine doses and administration frequencies affect mouse body weight and adipose tissues. It finds that administering nicotine bid (twice daily) at 2 mg/kg leads to optimal weight reduction. Nicotine induces browning in white adipose tissue, increases BAT quantity and UCP1 expression, and affects energy expenditure. The findings underscore nicotine’s nuanced effects across different adipose tissue types and lay the groundwork for further exploration of its mechanisms and therapeutic potential in weight management.
Dietary plasticity in small Arctic copepods as revealed with prey metabarcoding
Authors: Flo Snorre , Svensen Camilla , Præbel Kim , Bluhm Bodil Annikki , Vader Anna
Published: September 2024

Objectives

Small copepods (<2 mm) compose an important constituent of the Arctic marine food web, but their trophic interactions remain largely unexplored, partly due to methodological limitations.

Methods

We here characterize the prey of the abundant cyclopoid Oithona similis, harpacticoid Microsetella norvegica and calanoid Microcalanus spp. from the Arctic Barents Sea and Nansen Basin during four seasons using brute force prey metabarcoding of the 18S rRNA gene.

Key findings

Chaetognaths were unexpectedly the most consistently identified taxa and composed 47% of all prey reads. Some taxa were seasonally important, including diatoms in April–May (43%), dinoflagellates in December (15%) and March (17%), and urochordates in August (20%). Compositional differences among species were also discernible, and the M. norvegica diet was significantly different from both O. similis and Microcalanus spp. The diets varied nevertheless more with season than species despite the inherent trophic traits that distinguish the ambush-predator O. similis, chemosensoric particle-chaser M. norvegica and current-feeding Microcalanus spp.

Conclusions

Our results thus indicate that dietary plasticity is common in small Arctic copepods, regardless of their behaviors or strategies for finding sustenance. We further hypothesize that such plasticity is an important adaptation in systems where prey availability is highly seasonal.
R2C2 + UMI: Combining concatemeric and unique molecular identifier–based consensus sequencing enables ultra-accurate sequencing of amplicons on Oxford Nanopore Technologies sequencers
Authors: Deng Dori Z Q , Verhage Jack , Neudorf Celine , Corbett-Detig Russell , Mekonen Honey , Castaldi Peter J , Vollmers Christopher
Published: September 2024

The sequencing of PCR amplicons is a core application of high-throughput sequencing technology. Using unique molecular identifiers (UMIs), individual amplified molecules can be sequenced to very high accuracy on an Illumina sequencer. However, Illumina sequencers have limited read length and are therefore restricted to sequencing amplicons shorter than 600 bp unless using inefficient synthetic long-read approaches. Native long-read sequencers from Pacific Biosciences and Oxford Nanopore Technologies can, using consensus read approaches, match or exceed Illumina quality while achieving much longer read lengths. Using a circularization-based concatemeric consensus sequencing approach (R2C2) paired with UMIs (R2C2 + UMI), we show that we can sequence an ∼550-nt antibody heavy chain (Immunoglobulin heavy chain - IGH) and an ∼1,500-nt 16S amplicons at accuracies up to and exceeding Q50 (<1 error in 100,000 sequenced bases), which exceeds accuracies of UMI-supported Illumina-paired sequencing as well as synthetic long-read approaches.
Proxy Advisory Firms and Corporate Shareholder Engagement
Authors: Dey Aiyesha , Starkweather Austin , White Joshua T
Published: September 2024

We study how Institutional Shareholder Services (ISS) affect firms’ engagement with shareholders. Our analyses exploit a quasi-natural experiment using say-on-pay voting outcomes near a threshold that triggers ISS to review engagement activities. Firms receiving ISS treatment exhibit swift and substantive increases in extensive and intensive margins of engagement, especially when their boards have higher agency conflicts and directors are more likely to lose voting support from ISS. Increases in engagement persist over time, and shareholders appear to value the increased engagement. Collectively, we shed light on an unexplored channel through which ISS positively influences firms’ governance and information environments.
Circuit breakers and market runs
Authors: Bongaerts Dion , De Luca Sarah D , Van Achter Mark
Published: September 2024

Traders may run on financial markets merely out of fear of future liquidity shocks. We present a model that shows that adequately calibrated circuit breakers can prevent such coordination failures by curbing excessive trading. It suggests a novel, forward-looking circuit breaker that becomes most restrictive in cases when expected welfare losses of inefficient market runs are largest. The probabilities of current and future liquidity shortages are important determinants for such welfare-optimized circuit breakers. We empirically illustrate how to calibrate these parameters. We also determine under which economic conditions circuit breakers damage welfare and should not be implemented.
Extubation-Related Complications
Authors: Chaverra Kornerup Santiago , Parotto Matteo
Published: September 2024

Extubation represents an essential component of airway management. While being a common procedure in anesthesiology and critical care medicine, it is accompanied by a significant risk of morbidity and mortality. Safe extubation requires considerable skills, risk stratification and advanced planning. It is important to emphasize that intentional extubation is always an elective procedure, and as such should only be executed when conditions are optimal. The purpose of this review is to discuss the complications associated with planned extubation in the adult patient, including risk factors and management strategies, mainly focusing on the postoperative setting.
In the Nick of Time—Emergency Front-of-Neck Airway Access
Authors: Drew Thomas , Radwan Mohamad Atef , McCaul Conan Liam
Published: September 2024

Emergency front-of-neck access refers to all techniques that deliver oxygen into the airway lumen through the anterior neck structures and encompasses access both through the cricothyroid membrane and the tracheal wall. There has yet to be a universal agreement regarding the preferred technique. A surgical incision is currently the most common approach in prehospital and in-hospital care. This review intends to review and summarize the existing clinical, basic science, and societal guidelines for eFONA.
The Effectiveness of Growth Modulation Using Tension Band Plates in Children With Achondroplasia in Comparison to Children With Idiopathic Frontal Axial Deformities of the Knee
Authors: Hösl Matthias , Afifi Faik Kamel , Thamm Antonia , Göttling Lara , Holzapfel Boris M. , Wagner Ferdinand , Mohnike Klaus , Nader Sean
Published: September 2024

Background:

Achondroplasia is the most common form of rhizomelic dwarfism. Aside from disproportionally short extremities, frontal knee malalignments are common. We assessed the effectiveness of guided growth via tension band plates in children with achondroplasia in comparison to patients with idiopathic knee deformities using radiography.

Methods:

Twenty children with achondroplasia (8 valgus/31 varus knees) and 35 children with idiopathic knee malalignments (53 valgus/12 varus knees) which underwent temporary hemiepiphysiodesis at the distal femur and/or proximal tibia were retrospectively compared. Radiographic outcomes (mechanical lateral distal femoral angle, medial proximal tibial angle, and mechanical axis deviation) were compared before surgery and plate removal. Correction rates according to plate location were compared as change per implant duration and per growth in leg length.

Results:

Achondroplasia patients were younger (9±2 vs.12±2 y), femoral and tibial growth rate was 43.3% and 48.5% lower and implant duration lasted longer: 36.9±8.9 months in valgus knees and 23.0±14.3 months in varus knees versus 13.4±7.9 months in idiopathic valgus and 11.7±4.6 months in idiopathic varus knees. Significant improvements in joint orientation angles and mechanical axis deviation were achieved but femoral and tibial plates achieved slower correction per months in achondroplasia (P≤0.031). When normalized to bone growth, the rate of correction in joint orientation angles was no longer significantly different for the femur (P=0.241), with a trend for slower correction in the tibia (P=0.066). The corrections in MAD per leg growth (mm/mm) remained smaller (P=0.001). In achondroplasia, older age correlated with slower MAD correction (r=−0.36, P=0.022), femoral plates corrected faster than tibial (P=0.024) and treatment of valgus was less successful than varus involving longer treatments (P=0.009). More complications occurred in achondroplastic knees (P=0.012).

Conclusions:

Skeletally immature patients with achondroplasia can benefit from growth modulations, but they need longer treatments and face more complications. Their slower growth does not solely determine the more tenacious success.

Level of Evidence:

Therapeutic Level III—case-control study.
Treatment outcomes following partial shave biopsy of atypical and malignant melanocytic tumors in pediatric patients
Authors: Arjunan Akshaya , Wardrop Mary , Malek Marcus M. , Davit Alexander J. , Sargen Michael R. , Kirkwood John M. , Demanelis Kathryn , Seynnaeve Brittani K.N.
Published: September 2024

Pediatric melanoma is the most common skin cancer in children and treatment relies on accurate staging. The American Academy of Dermatology recommends excisional biopsy for suspicious skin lesions, however, partial shave biopsies are often performed, the impact of which is unknown in pediatric and adolescent/young adult (AYA) patients. The aim of this retrospective case series study was to evaluate the impact of the diagnostic biopsy method on staging, treatment, and treatment-related outcomes in pediatric/AYA patients with melanoma. Among 103 pediatric/AYA patients with atypical cutaneous melanocytic lesions, the most common biopsy method was partial shave (68/103, 66.0%) followed by punch (20/103, 19.4%), excisional (14/103, 13.6%), and incisional nonshave (1/103, 1%). Over half of all biopsies yielded a positive deep margin, reflecting compromised microstaging (56/103, 55.4%), the majority occurred following partial shave (52/56, 92.9%) compared with other techniques (P < 0.001). All 11 patients with wider surgical target margins of wide local excision and 8/9 patients with sentinel lymph node biopsy performed due to positive deep margin, underwent a partial shave biopsy (P = 0.05 and 0.32, respectively). Almost half of all patients who underwent partial shave biopsy had a clinically suspected abnormal melanocytic tumor prior to biopsy (31/68, 45.6%; P = 0.03). Of 56 patients who had compromised microstaging, 17 (30.4%) had a diagnosis of melanoma (P = 0.17). Pediatric/AYA patients frequently undergo partial shave biopsy, which is associated with more invasive definitive surgical treatment due to compromised microstaging. These results may help optimize care of patients with cutaneous melanocytic tumors.
Transcatheter Aortic Valve Implantation (TAVI) in Bicuspid Aortic Valve Disease: A Systematic Review
Authors: Goulden Christopher J. , Wright Kelly , Alim Samina , Patel Nikhil , Irfan Mahnoor , Onay Dilşat , Sabet Cameron , Nguyen Dang , Harky Amer
Published: September 2024

Transcatheter aortic valve implantation (TAVI) is effective and safe, but its outcomes for patients with bicuspid aortic valve (BAV) disease are relatively unclear. A comprehensive search of PubMed, Medline, and Google Scholar till November 2023 yielded studies evaluating TAVI in BAV patients. Inclusion criteria were applied, and data were extracted on clinical and procedural outcomes, including echocardiographic measures and complications. Statistical analyses included descriptive statistics, subgroup analysis, and sensitivity analysis. From the 29 studies covering 8045 BAV patients, the mean age was found to be 72.5 ± 10.35 years with a male predominance of 56.4% ± 7.9%. TAVI was significantly beneficial, decreasing the mean aortic gradient from 46.9 to 10.4 mm Hg postprocedure and increasing aortic valve area, evidencing improved hemodynamics. A high procedural success rate of 93.3% was noted, predominantly through femoral access. However, complications included pacemaker need (12.6%), minor bleeding, and acute kidney injury. All-cause mortality escalated from 3.7% perioperatively to 16.8% after 1 year. Hazard ratios and P values highlighted significant outcomes: perioperative hazard ratio for mortality at 3.7% (P < 0.05), reduction in perioperative versus postoperative gradients (P < 0.001), and increase in postoperative aortic valve area (P < 0.001). The need for postdilatation was less than predilatation (P < 0.05), and significant differences were noted in device sizes (P < 0.05). TAVI in BAV patients showed good perioperative outcomes but with moderate complication rates. Notably, there was a significant rise in 1-year mortality, underscoring the importance of careful patient selection and strict postoperative care. More studies are necessary to determine long-term results and refine procedures for this group.
Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection
Authors: Itohara Kotaro , Yamamoto Kazuhiro , Fujinaka Shunsuke , Hashimoto Mari , Tamura Naoki , Kitahiro Yumi , Omura Tomohiro , Fujioka Kazumichi , Yano Ikuko
Published: September 2024

Background:

Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed.

Methods:

Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir.

Results:

Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration–time curve from 0 to 24 hours of 40–60 mcg·h·mL−1 of ganciclovir was calculated.

Conclusions:

The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.
Let’s Twist Again: Nasolabial Turnover Flap for Full-thickness Aesthetical Nasal Ala Reconstruction
Authors: Schonauer Fabrizio , D’Alessio Matteo , Cavaliere Annachiara , Razzano Sergio , D’Angelo Dario
Published: September 2024

Background:

The nasal ala has always been considered a difficult anatomical structure to restore, particularly when full-thickness reconstruction is needed. Although the forehead flap is considered the flap of choice, the nasolabial turnover flap, despite being a one-step surgical procedure, has been largely ignored for nasal ala reconstruction. We present our experience performing nasal ala full-thickness reconstruction with the nasolabial turnover flap, reporting on its advantages and comparing it with the most commonly used alternative techniques.

Methods:

Between 2017 and 2022, 48 patients presenting full-thickness defects of the nasal ala after skin cancer resection underwent reconstruction with a nasolabial turnover flap at two large regional plastic surgery units. Surgical technique was presented in detail, with particular attention in describing the complex three-dimensional movement of the flap.

Results:

All patients healed uneventfully, with good functional and cosmetic outcomes. No major complications were observed.

Conclusions:

The nasolabial turnover flap is a reliable and valuable option for achieving full-thickness nasal ala reconstruction. Satisfactory results in terms of function and cosmetic appearance can be obtained in a one-stage operation. Based upon our experience, the nasal turnover flap could be considered a viable reconstruction option, even for less-experienced surgeons.
Education in reproductive medicine
Authors: Kennedy Richard
Published: September 2024

The speciality of reproductive medicine encompasses several common disease processes contributing significantly to the global burden of disease. They include infertility, which affects 1 in 6 women and for which access to care falls well short of global need. Key to increasing access is the education and training of a capable, high-quality workforce. Education and training in medicine are undergoing a revolution catalyzed by the recent pandemic, which forced a rapid shift from face to face to virtual learning. This change came coincidental with other emerging trends in clinical education, driven by developments in information technology and Generation Y. The changes are broadly welcome but present significant challenges to educators who are grappling with evolving social educational trends, technical aspects, cyber threats, and the impact of AI. This short commentary discusses education and training in reproductive medicine in this context.
Corneal Clarity and Tomographic Patterns in Pseudoexfoliation Syndrome: A Severity-Based Investigation
Authors: Yilmaz Yusuf Cem , Hayat Serife Ciloglu , Ipek Sefik Can
Published: September 2024

Purpose:

The aim of the study was to investigate the corneal and anterior segment characteristics in pseudoexfoliation syndrome (PXS), depending on the severity of the disease.

Materials and methods:

This cross-sectional study was conducted at a tertiary care hospital, in the ophthalmology department, in Turkey. Pseudoexfoliation syndrome group was classified into three groups. Pseudoexfoliative material on the part of the pupillary border was classified as group 1, on the entire pupillary border was classified as group 2, and pseudoexfoliative material on the entire pupillary border and iris surface was classified as group 3. The control group was composed of age and gender-matched individuals who had undergone a completely normal ophthalmologic examination. Scheimpflug tomography was performed to record tomographical data.

Results:

The PXS groups 1, 2, and 3, along with the control group, consist of 29, 32, 33, and 42 participants, respectively. There was no significant difference in age–gender distribution between patients and the control group (P>0.05). Group 3 showed significant differences in central corneal thickness compared with the control group (P=0.001). In addition, anterior chamber angle was found to be significantly lower in group 3 than the control group (P<0.001). In corneal densitometry (CD) values, significant increases compared with the control group were observed in groups 2 and 3 across all anterior annuli (P<0.001). In group 1, significant increases observed in the anterior 6-10 mm and 10-12 mm annuli (P<0.001). In the middle 6-10 mm annuluses, only group 3 showed a significant increase compared with the control group (P<0.001). In the posterior 0-2, 2-6, and 6-10 mm annuli, significant increases compared with the control were observed only in groups 2 and 3 (P=0.001, P=0.001, P<0.001, respectively).

Conclusions:

Corneal densitometry values, even without an increase in intraocular pressure, have a tendency to increase in PXS depending on the severity of the disease. While minimal changes were observed in the middle layer, it was particularly noted that the effects of the disease were more prominent in the peripheral cornea.
Occupational Exposure to 50 ppm Isoflurane Impairs Sperm Parameters in Mice
Authors: Zanin Marina , Varela Junior Antonio Sergio , Bonel Acosta Izani , Anastacio da Silva Edenara , Bicca Dode Maria Eduarda , Gehrcke Martielo Ivan , Gobbo Braz Mariana , Dahl Corcini Carine
Published: September 2024

Objectives

The aims of the study are to assess the effect of occupational exposure to isoflurane on the sperm quality of mice and to investigate whether cessation of exposure can restore seminal quality.

Methods

Mice were exposed to 50 ppm of isoflurane for 5 hours per day over a 30-day period. Following this exposure, they were euthanized at predetermined postexposure intervals, and their sperm samples were analyzed for kinetics and viability parameters.

Results

Occupational exposure to isoflurane can adversely affect sperm at 50 ppm, a concentration deemed safe by international occupational health conventions in some countries. These effects are marked by oxidative stress, mitochondrial dysfunction, and genomic damage, alongside alterations in sperm kinetics and acrosomal integrity. Furthermore, cessation of exposure does not guarantee restoration of cellular quality.

Conclusions

Isoflurane at 50 ppm, previously deemed safe by some countries, impairs sperm kinetics and viability, potentially directing the spermatogenic process toward infertility and apoptosis.
Firefighter- and Fire Department–Level Barriers and Promoters of Physical Activity and Fitness Among Volunteer Firefighters
Authors: Shah Nimit N. , Wackowski Olivia A. , Jahnke Sara A. , Roy Jason , Hollerbach Brittany S. , Edwards Derrick L. , Caban-Martinez Alberto J. , Calkins Miriam M. , Austin Elena , Black Taylor M. , Awadalla Josephine , Grant Casey C. , Kubiel Brian S. , Graber Judith M.
Published: September 2024

Objective

To describe volunteer firefighters’ perspectives on how firefighter- and fire department–level factors influence their physical activity and fitness.

Methods

Firefighters (n = 28) were interviewed, stratified by their years of firefighting, using an interview guide. Thematic analysis and systematic coding were used to analyze the interview transcripts.

Results

Five themes were identified: (1) health and firefighting performance, (2) firefighter time and availability, (3) responsibility of the fire department to support volunteer members’ physical fitness, (4) fire training drills as a form of functional physical activity, and (5) fitness initiatives at the department. Interviewing by years of experience showed varied perspectives that converged toward similar conclusions.

Conclusions

Incorporating fitness discussions into department meetings and trainings and identifying fitness advocates within the department may contribute to overcoming barriers to physical fitness among volunteer firefighters.
Association Between Lifestyle Behavior and Health-Related Productivity Loss Among Korean Employees
Authors: Kang Young Joong , Kang Mo-Yeol
Published: September 2024

Objectives

To investigate factors associated with individual lifestyle influencing productivity reduction.

Methods

Data were collected using a Web-based questionnaire from January 6, 2020, to February 18, 2020. The study included 3890 wage workers across South Korea. Data on drinking, smoking, physical activity, and sleep were collected. This study measured health-related productivity loss (HRPL), using the Work Productivity and Activity Impairment Questionnaire: General Health version.

Results

Only nonoptimal sleep time was significantly associated with higher HRPL after adjusting for age, gender, education level, marital status, employment status, income level, weekly working hours, and occupation. This result was most derived from presenteeism than absenteeism. If the sleep disorder was diagnosed by a physician, the HRPL was even greater.

Conclusions

This study suggested that sleep is significantly associated with HRPL, particularly in men and manual workers.
Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials
Authors: de Oliveira Almeida Gustavo , Balieiro Caroline , Bertoli Edmundo Damiani , Moreira Maria Eduarda Liporaci , Silva Ana Laura Soares , Minucci Bárbara Silvestre , Zapparoli Isabella , Maluf Marcela Silva , Carvalho Henrique Champs Porfírio , dos Santos Borges Rafael , Pasqualotto Eric , Nienkötter Thiago , Alves Vinícius , Guida Camila Mota
Published: September 2024

Background

The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate.

Methods

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. The random-effects model was used to calculate the risk ratios with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3 (RStudio, PBC).

Results

Six RCTs comprising 20 574 patients with ACS were included, of whom 10 259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years, and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (risk ratio 0.93; 95% CI 0.90–0.97; P < 0.01) and nonfatal myocardial infarction (risk ratio 0.88; 95% CI 0.81–0.95; P < 0.01). There was no significant difference between groups for revascularization (risk ratio 0.94; 95% CI 0.90–1.00; P = 0.03), all-cause mortality (risk ratio 0.87; 95% CI 0.63–1.21; P = 0.42), or unstable angina (risk ratio 1.05; 95% CI 0.86–1.27; P = 0.64).

Conclusion

In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and nonfatal myocardial infarction, compared with statin monotherapy.
Current opinion in refractory and/or unexplained chronic cough
Authors: Misono Stephanie , Novaleski Carolyn K.
Published: September 2024

Purpose of review

Otolaryngologists are vital to successfully managing chronic cough in adults. This review presents updates regarding rapidly evolving concepts in chronic cough.

Recent findings

Significant growth is occurring in chronic cough research, strengthening the evidence of its major psychosocial impacts. Elucidation of the neural underpinnings of normal and abnormal cough within both the peripheral and central nervous systems highlight the previously underappreciated complexity of cough. Recent clinical practice recommendations emphasize personalized treatment approaches through addressing treatable traits of chronic cough. Investigations are ongoing to better distinguish chronic cough subgroups, and multiple types of important clinical outcome measures are being characterized. Newer research about chronic cough treatment encompasses pharmacologic and nonpharmacologic interventions, including oral and inhaled medications, superior laryngeal nerve blocks, and behavioral therapy.

As knowledge about chronic cough in adults continues to expand in both research and clinical practice, otolaryngologists can continue to raise awareness of the role of the larynx in cough and promote ongoing multidisciplinary collaborations. In the coming years, more pharmacologic options and personalized treatment approaches will likely emerge for chronic cough.
Non-invasive central nervous system stimulation to improve bladder and pelvic floor function in the aging population
Authors: Chen Annie , Hwang Kuemin , Khavari Rose
Published: September 2024

Purpose of review

The literature was reviewed for all noninvasive central nervous system (CNS) stimulation techniques, which includes transcranial brain or trans-spinal stimulation, in the aging population. Given the rising ubiquity of this technology, noninvasive nature, and low side-effect profile reported, this technology can have a big impact on the aging population. As patients afflicted with neurogenic disorders are living longer lives, a special emphasis is placed on the aging neurogenic population.

Recent findings

Noninvasive CNS stimulation techniques have been applied to major bladder and pelvic floor disorders such as voiding dysfunction, chronic pelvic pain, urgency and urge incontinence, lower urinary tract dysfunction, and situational urge incontinence in both the idiopathic and neurogenic populations. Overall, these noninvasive technologies demonstrate effectiveness for the treatment of these conditions with some studies showing effectiveness with longer-term follow-up suggesting lasting CNS remodeling.

Most manuscripts had a generally small number of patients and an even smaller number of geriatric patients represented. No studies were specifically designed to investigate geriatric outcomes. It is the hope of this systematic review to help model future studies according to existing literature, but with a focus on the geriatric population as they stand to gain the most from noninvasive technologies with limited adverse events.
“More Areas of Grey”
Authors: Sofronas Marianne , Wright David Kenneth , Macdonald Mary Ellen , Bitzas Vasiliki , Carnevale Franco A.
Published: September 2024

Neuropalliative care as a clinical speciality aims to address the unique end-of-life needs and concerns of patients with neurologic disease. Although literature has outlined clinical hurdles, a more nuanced understanding of how neuropalliative care was experienced, conceptualized, and enacted could provide context and depth to better outline practice and research priorities. This article presents findings from an ethnographic study of neuropalliative care conducted in a university-affiliated, tertiary care neurological hospital in Canada with a dedicated neuropalliative consultation service. Specifically, this article examines how clinical hurdles outlined in the neuropalliative literature were experienced and addressed by multiple stakeholders, including patients, families, and clinicians. These clinical hurdles include locating the scope of neuropalliative care, ascertaining the impact of prognostic uncertainty and poor recognition of the dying patient, and navigating the tensions between curative and palliative philosophies. In the discussion, the implications of these clinical hurdles are addressed, concluding with reflections on the role of ethnography, palliative care in the context of functional changes, and broadening approaches to uncertainty.
Reassessment of Plurihormonal Pituitary Adenomas/PitNETs
Authors: Kleinschmidt-DeMasters B. K. , Turin Christie G.
Published: September 2024

Plurihormonal pituitary adenomas/neuroendocrine tumors express multiple pituitary hormones and/or transcription factors, as determined by immunohistochemistry (IHC). Three types exist based on Endocrine WHO 2022 classification: mature plurihormonal PIT1 (pituitary-specific POU-class homeodomain factor-1), immature PIT1-lineage tumors, and a third type with unusual combinations of pituitary hormones and/or transcription factors. However, since then, “somatogonatotroph”/“multilineage” tumors with PIT1/SF1 (steroidogenic factor 1) co-expression have been described, possibly confounding this classification. We performed a database search, from 2018 to 2023, to identify and reclassify tumors, correlating with neuroimaging and endocrinological features at presentation. We identified 22 cases: M 9:F 13, mean age at surgery 51±16 years. The most common symptoms at initial presentation were headaches and/or vision changes (6/22) and acromegaly (5/22). All tumors were macroadenomas, mean diameter of 25±17mm; 11/22 (50%) had cavernous sinus invasion. More than 70% of tumors clinically secreted at least 1 hormone, and 27% tumors secreted at least 2 different hormones. Four patients underwent >1 surgical intervention. Reclassification by IHC yielded almost exclusively 2 types: immature PIT1-lineage (9/22) and “somatogonadotroph”/“multilineage tumors” with PIT1/SF1 co-expression (12/22), the latter replacing mature plurihormonal tumors. One true unusual plurihormonal tumor was identified. The extent of growth hormone, prolactin, thyroid stimulating hormone, PIT1, and SF1 IHC was variable, but immunopositivity for follicle-stimulating hormone and/or luteinizing hormone was nearly confined to co-expressors, distinguishing these from immature PIT1-lineage tumors. In conclusion, tumor size, invasiveness, and endocrinopathies do not distinguish PIT1/SF1 co-expressing tumors from immature PIT1-lineage tumors preoperatively; only full IHC pituitary workup allows distinction.