bluuebunny/crossref_metadata_2025 huggingface dataset:
Children with medulloblastoma treated with modified ACNS0821 temozolomide, irinotecan, and bevacizumab: The Seattle Children’s Hospital experience
Authors: Ronsley Rebecca , Bradford Miranda C , Crotty Erin E , Vitanza Nicholas A , Runco Daniel V , Stevens Jeffrey , Hoeppner Corinne , Holtzclaw Susan L , Wein Amy R , Lee Amy , Cole Bonnie L , Ermoian Ralph , Leary Sarah E S
Published: November 2024

Background

Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children’s Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen.

Methods

Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan, and temozolomide, referred to as “TIB.” Each TIB cycle includes oral temozolomide (200 mg/m2/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose), and IV irinotecan (125 mg/m2/dose or 340 mg/m2) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response, and outcome were collected. The analysis included Kaplan–Meier estimates of 3-year overall survival (OS) and 3-year progression-free survival.

Results

Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21–23.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n = 1) and family preference (n = 1). The most common toxicities were thrombocytopenia (n = 7), neutropenia (n = 4), nausea (n = 5), vomiting (n = 5), and diarrhea (n = 3). Five patients required dose modification of one agent for toxicity. Median follow-up from TIB therapy start was 1.61 (0.47–7.66) years. Three-year OS was 48% (95% CI: 18%–74%) and 3-year event-free survival was 16% (95% CI: 1%–49%).

Conclusions

TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.
Computational model of a feeding copepod engaged in three modes of movement
Authors: Hachmeister Julian , Takagi Daisuke
Published: November 2024

Objectives: Copepods display distinct feeding modes to capture prey in the surrounding water. However, the mechanism and range of prey detection are not fully understood. Methods: Using the method of regularized Stokeslets, we constructed a mathematical model of the flow field around a copepod engaged in three modes of movement: sinking, swimming and hovering. The model assumes that the copepod is negatively buoyant with a simplified body and a pair of long antennae. We then introduced a rigid, neutrally buoyant sphere in the model to predict where potential prey items become detectable in theory. Key Findings: We find that the flow fields around the sinking and swimming models are generally unidirectional, while the flow around a hovering copepod has a significant cross-stream component. Our model shows that the volume of the surrounding fluid that is predicted to be inspected has distinctive shapes that resemble a thin sheet while sinking, a cylinder while swimming and a funnel while hovering. Conclusion: The results suggest that the most efficient mode of feeding depends on the distribution of prey items in the surrounding water.
The E3 ligase TaE3V-B1 ubiquitinates proteins encoded by the vernalization gene TaVRN1 and regulates developmental processes in wheat
Authors: Li Tian , Nagarajan Ragupathi , Liu Shujuan , Luzuriaga Juan C , Zhai Wenxuan , Cao Shuanghe , Jia Haiyan , Carver Brett F , Yan Liuling
Published: November 2024

In wheat (Triticum aestivum), early maturity is desired to avoid the hot and dry summer season, especially in view of climate change. Here, we report that TaE3V1, a C3H2C3 RING-type E3 ligase that interacts with TaVRN1, is associated with early development. Aside from its RING domain, TaE3V1 does not harbor any domains that are conserved in other RING-type or other E3 ligase proteins. TaE3V-B1b, encoded by the functional TaE3V1 allele, interacts with and ubiquitinates TaVRN1. In contrast, TaE3V-B1a, encoded by a natural nonfunctional TaE3V1 allele, neither interacts with TaVRN1 nor has E3 ligase activity. TaE3V-B1b activity decreases with plant age under warmer temperatures, but not under the low temperatures required for vernalization. We employed a gene editing method to simultaneously inactivate the 3 homoeologous TaE3V1 genes to validate their functions. Overall, our results suggest that the naturally mutated and edited TaE3V1 alleles can accelerate wheat development and aid adaptation to warming climates.
National Influences on Election Outcomes for State Executive Offices
Authors: King James D
Published: November 2024

Many argue that American elections at all levels of government are now national affairs. Yet to what extent are state executive election outcomes influenced by national factors? Individual election outcomes are used to test the relative influences of national, state, and individual factors in elections for governor and secondary executive offices. The results reinforce the federalist nature of American elections by indicating that individual and state factors exert greater influence than national factors on state executive elections, especially for high-profile offices and, to a somewhat lesser degree for other, lesser-profile offices. Similar outcomes in national and state elections appear to result from the partisan composition of the electorate rather than top-down influences. The analysis supports the view that American federalism is alive and well in the electoral arena.
A small molecule K-3 promotes PDX1 expression and potentiates the differentiation of pluripotent stem cells into insulin-producing pancreatic β cells
Authors: Yano Tatsuya , Shimaya Yukihiro , Enomoto Takayuki , Kiho Toshihiro , Komoriya Satoshi , Nakashima Ryutaro , Shiraki Nobuaki , Kume Shoen
Published: November 2024

Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for diabetes patients. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55,000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions. K-3 preferentially acts on stage 3 pancreatic progenitor cells and increases the population expressing high levels of PDX1. As a result, the ratios of the PSC-derived PDX1 / NKX6.1 double-positive endocrine progenitor and INS / NKX6.1 double-positive mono-hormonal endocrine cells were increased. K-3 enhances the expression of functional pancreatic β cell markers and affects biological processes concerning organ development. K-3 also increased the yield of endocrine cells at the end of stage 5. The novel compound is a beneficial new tool for efficiently generating PSC-derived insulin-producing cells with high functionality and differentiation efficiency.
Non‐lethal sonodynamic therapy inhibits high glucose and palmitate‐induced macrophage inflammasome activation through mtROS‐DRP1‐mitophagy pathway
Authors: Wang Jiayu , Shen Yicheng , Chen Heyu , Guan Jinwei , Li Zhitao , Liu Xianna , Guo Shuyuan , Wang Linxin , Yan Baoyue , Jin Chenrun , Li He , Guo Tian , Sun Yun , Zhang Weihua , Zhang Zhiguo , Tian Ye , Tian Zhen
Published: November 2024

Obesity plays a crucial role in the development and progression of type 2 diabetes mellitus (T2DM) by causing excessive release of free fatty acid from adipose tissue, which in turn leads to systemic infiltration of macrophages. In individuals with T2DM, the infiltration of macrophages into pancreatic islets results in islet inflammation that impairs beta cell function, as evidenced by increased apoptosis and decreased glucose‐stimulated insulin secretion. The present study aimed to investigate the effects of non‐lethal sonodynamic therapy (NL‐SDT) on bone marrow‐derived macrophages (BMDMs) exposed to high glucose and palmitic acid (HG/PA). These findings indicate that NL‐SDT facilitates the expression of DRP1 through the transient production of mitochondrial ROS, which subsequently promotes mitophagy. This mitophagy was shown to limit the activation of the NLRP3 inflammasome and the secretion of IL‐1β in BMDMs exposed to HG/PA. In co‐culture experiments, beta cells exhibited significant dysfunction when interacting with HG/PA‐treated BMDMs. However, this dysfunction was markedly alleviated when the BMDMs had undergone NL‐SDT treatment. Moreover, NL‐SDT was found to lower blood glucose levels and elevate serum insulin concentrations in db/db mice. Furthermore, NL‐SDT effectively reduced the infiltration of F4/80‐positive macrophages and the expression of CASP1 within islets. These findings provide fundamental insights into the mechanisms through which NL‐SDT may serve as a promising approach for the treatment of T2DM.
ALPK2 prevents cardiac diastolic dysfunction in heart failure with preserved ejection fraction
Authors: Yoshida Tatsuya , Yoshida Satoya , Inukai Kohei , Kato Katsuhiro , Yura Yoshimitsu , Hattori Tomoki , Taki Kentaro , Enomoto Atsushi , Ohashi Koji , Okumura Takahiro , Ouchi Noriyuki , Kawase Haruya , Wettschureck Nina , Offermanns Stefan , Murohara Toyoaki , Takefuji Mikito
Published: November 2024

Protein phosphorylation, controlled by protein kinases, is central to regulating various pathophysiological processes, including cardiac systolic function. The dysregulation of protein kinase activity plays a significant role in the pathogenesis of cardiac systolic dysfunction. While cardiac contraction mechanisms are well documented, the mechanisms underlying cardiac diastole remain elusive. This gap persists owing to the historical focus on systolic dysfunction in heart failure research. Recently, heart failure with preserved ejection fraction (HFpEF), an age‐related disease characterized by cardiac diastolic dysfunction, has emerged as a major public health concern. However, its underlying mechanism remains unclear. In this study, we investigated cardiac protein kinases by analyzing the gene expression of 518 protein kinases in human tissues. We identified alpha‐kinase 2 (ALPK2) as a novel cardiac‐specific atypical kinase and generated tamoxifen‐inducible, cardiomyocyte‐specific Alpk2‐knockout mice and Alpk2‐overexpressing mice. Alpk2 deficiency did not affect cardiac systolic dysfunction in the myocardial infarction model or the pressure‐overload‐induced heart failure model. Notably, cardiomyocyte‐specific Alpk2 deficiency exacerbated cardiac diastolic dysfunction induced by aging and in the HFpEF model. Conversely, Alpk2 overexpression increased the phosphorylation of tropomyosin 1, a major regulator that binds myosin to actin, and mitigated cardiac stiffness in HFpEF. This study provides novel evidence that ALPK2 represents a potential therapeutic target for cardiac diastolic dysfunction in HFpEF and age‐related cardiac impairments.
“Having Support at Work ‘Is Different’ and Important”: A Qualitative Study of Virtual Peer Discussion Groups With Medical School Faculty
Authors: Brazeau Chantal M.L.R. , Ayyala Manasa S. , Chen Ping-Hsin , Swarbrick Margaret
Published: November 2024

Purpose

In response to the need to support health care professionals during the COVID-19 pandemic, an innovative, peer-led discussion group program for medical school faculty, called CIRCLE (Colleague Involved in Reaching Colleagues through Listening and Empathy), was developed at Rutgers Health. This article describes results of a qualitative analysis of the participants’ experiences, explores virtual communication platform use during this peer support program, and identifies the program’s beneficial elements.

Method

CIRCLE was inaugurated in October 2020 at Rutgers New Jersey Medical School and Rutgers Robert Wood Johnson Medical School using evidence-informed topics. The inaugural CIRCLE peer-led discussion groups included 50 physicians who met twice monthly in groups of 5 to 8 between October 2020 and April 2021. Deidentified transcript data were iteratively reviewed using conventional content analysis, including familiarization, thematic framework creation, indexing, charting, mapping, and interpretation. Themes were grouped into 4 conceptual framework categories based on social support theory in the context of work-related stress: emotional, appraisal, informational, and instrumental support.

Results

Themes emerged based on the framework: emotional support (connecting on a deeper level, importance of support at work, COVID-19 made virtual connections needed), relevant appraisal support (feeling “not alone,” safe space to connect and share), informational support (sharing self-care strategies), and instrumental support (incentives to join are helpful but connection leads to engagement, some structure but “not too much” is important, virtual modalities are convenient and conducive to connection).

Conclusions

Benefits of peer discussion groups include deeper connections at work, reduced isolation, safe sharing, and exchange of information on self-care. Connection and balancing structure and autonomy were important to engagement. Virtual modalities were viewed as feasible, convenient, and conducive to connection. This article highlights the benefits and convenience of virtual peer-led discussion groups for medical school clinical faculty and provides evidence for content development of these programs.
Individual and System-level Factors Contributing to Guideline Nonadherent Surgical Antibiotic Prophylaxis at a Tertiary Healthcare System: A Qualitative Analysis
Authors: Bardia Amit , Melnick Edward R. , McCall Terika , Zhao Xiwen , Lin Hung-Mo , Fisher Clark , Burg Matthew M. , Schonberger Robert B.
Published: November 2024

Background:

Antibiotics play a crucial role in preventing surgical site infections, yet adherence to Infectious Disease Society of America guidelines varies widely. This qualitative study aimed to explore factors influencing perioperative antibiotic administration and assess the potential impact of a clinical decision support tool on guideline adherence.

Methods:

In this qualitative study, perioperative personnel with diverse roles (surgeons, anesthesiologists, certified nurse anesthetists, trainees, and pharmacists) were interviewed using a semistructured interview format from September 2023 through April 2024. Interviews were then analyzed for codes, which were assigned to concepts using the constant comparison method for assessment of factors that were described as barriers or facilitators of guideline adherence.

Results:

After 3 piloting interviews, 9 sessions were conducted with a total of 17 participants: 7 attending anesthesiologists, 3 resident trainees, 2 perioperative pharmacists, 3 Certified Registered Nurse Anesthetists, and 2 attending surgeons. Key themes emerged: (1) limited familiarity with Infectious Disease Society of America antibiotic guidelines, (2) lack of standardization and optimization of antibiotic decision-making process, (3) challenges with managing β-lactam allergies, (4) difficulty optimizing vancomycin timing, and (5) perceived benefit of a clinical decision support tool in enhancing workflow and guideline adherence.

Conclusions:

Nonadherence to antibiotic guidelines in the perioperative setting often results from a lack of structured workflow. The interviews provide a foundation for developing a clinical decision support tool tailored to provider needs, aiming to improve user satisfaction and promote better adherence to perioperative antibiotic guidelines.
Predictors of Recurrence After Curative Surgery for Stage I Colon Cancer: Retrospective Cohort Analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group
Authors: Turri Giulia , Martinelli Luigi , Rega Daniela , Tamini Nicolò , Paiano Lucia , Deidda Simona , Bao QuocRiccardo , Lorenzon Laura , De Luca Raffaele , Foppa Caterina , Mari Valentina , Taffurelli Giovanni , Picciariello Arcangelo , Marsanic Patrizia , Siragusa Leandro , Bagolini Francesco , Nascimbeni Riccardo , Rizzo Gianluca , Vertaldi Sara , Zuolo Michele , Bianchi Giorgio , Rorato Lisa Marie , Reddavid Rossella , Gallo Gaetano , Crepaz Lorenzo , Di Leo Alberto , Trompetto Mario , Potenza Enrico , Santarelli Mauro , de’Angelis Nicola , Ciarleglio Francesco , Milone Marco , Coco Claudio , Tiberio Guido Alberto , Anania Gabriele , Sica Giuseppe S. , Muratore Andrea , Altomare Donato Francesco , Montroni Isacco , De Luca Maurizio , Spinelli Antonino , Simone Michele , Persiani Roberto , Spolverato Gaya , Restivo Angelo , de Manzini Nicolò , Braga Marco , Delrio Paolo , Verlato Giuseppe , Pedrazzani Corrado
Published: November 2024

Objective:

The aim of this study is to provide solid evidence to update the management of stage I colon cancer (CC) after surgery.

Background:

Given the low risk of recurrence of stage I CC, some international guidelines do not recommend intensive follow-up after surgery. However, data on the actual incidence, risk factors, and site of recurrences are scarce.

Methods:

This is a retrospective multicenter cohort study considering patients who underwent surgery at 25 Italian centers between 2010 and 2019, with a minimum follow-up of 24 months. A total of 1883 consecutive adult patients with stage I CC treated with curative surgery were considered, and 1611 fulfilled the inclusion criteria. The primary outcome was the rate of recurrence. Secondary outcomes included survival and risk factors for recurrence.

Results:

Eighty patients developed cancer recurrence (5.0%), of which 90% was systemic relapse. The event was more frequent in pT2 (6.0% vs 3.2%, P = 0.013), male patients (6.1% vs 3.6%, P = 0.021), in the presence of lymphovascular invasion (7.2% vs 3.6%, P = 0.01), and in cases of partial resection (11.1% vs 4.6%, P = 0.011). Also, preoperative carcinoembryonic antigen (P = 0.007) and tumor diameter (P < 0.001) were higher in the group who relapsed. Most patients had isolated cancer recurrence (90%). Recurrences peaked between 10 and 18 months after surgery and declined over time. Adjusted Cox regression analysis identified tumor diameter, carcinoembryonic antigen level, lymphovascular invasion, male gender, and less than 12 analyzed lymph nodes as significant risk factors for worse recurrence-free survival.

Conclusions:

This study showed that a not negligible rate of stage I CC recur after curative surgery. Most relapses occur at a single site within the first 3 years after surgery. This evidence could be used to optimize postoperative follow-up.
The Perioperative NonaGEnaRIan And cenTenarian suRgICal (GERIATRIC) Risk Stratification Tool
Authors: Weinberg Laurence , Lee Dong Kyu , Fletcher Luke , Ou Yang Bobby , Karp Jadon , Koshy Anoop N , Guha Ranjan , Slifirski Hugh , D’Silva Michael R , Bellomo Rinaldo , Churilov Leonid
Published: November 2024

Objective:

To develop age-appropriate nonaGEnaRIan And cenTenarian suRgICal (GERIATRIC) risk tool for classifying patients who may or may not develop postoperative complications or die within their index hospital admission.

Background:

There are no validated perioperative risk stratification tools for use in nonagenarian and centenarian patients—people aged 90 to 99 years and >100 years.

Methods:

In this retrospective observational study, nonagenarians and centenarians undergoing any surgical procedure were profiled. Surgery severity was stratified, and the incidence and grade of postoperative complications were recorded. Multivariable logistic regression analysis was performed on a training cohort, followed by calibration on a validation cohort, followed by performance evaluation on a testing cohort. The discriminative accuracy was compared to that of the age-adjusted Charlson Comorbidity Index for each outcome. The primary outcome was the ability of the risk stratification tool to effectively classify patients into those who may or may not experience a postoperative complications or mortality within their index hospital stay.

Results:

A total of 3085 patients were enrolled. The GERIATRIC risk tool had good discriminative accuracy for any postoperative complication [area under the receiver operating characteristic curves (AUROC), 0.857; 95% CI = 0.824–0.890] and any severe postoperative complication (AUROC, 0.833; 95% CI = 0.793–0.874), and fair discriminative accuracy for in-hospital mortality (AUROC, 0.780; 95% CI = 0.668–0.893).

Conclusions:

Compared to the age-adjusted Charlson Comorbidity Index, The GERIATRIC risk tool was accurate in classifying patients into those who may or may not experience severe complications or die during their index admission. The tool can be used to assist perioperative clinicians with shared decision-making and short-term prognostication.
Best Available Outcomes Evidence Informing Standard of Care
Authors: Comadoll Shea , Nguyen Mai P.
Published: November 2024

Although nonoperative management is the mainstay for rib fracture treatment, surgical stabilization of rib fractures is becoming more common. Recently, the number of high-quality studies on management of rib fractures has also increased. The primary purpose of this review is to analyze the currently available prospective randomized studies on the management of rib fractures. In addition, we will summarize both short-term and long-term outcomes of patients with rib fractures.
Discussion of Surgical Indications: The Black, White, and Gray
Authors: Weatherby David J.
Published: November 2024

Chest wall trauma is rapidly evolving and now represents a multidisciplinary field with incredible growth in research and surgical intervention; however, even with more than 800 publications on chest wall trauma to date, surgical indications are not black and white. Injury patterns need to be better defined and outcome measurements need to evolve for accurate longer term functional assessment of patients if this field of surgery is to move beyond historical indications for operative intervention. This essay will communicate what is known about operative indications in a way that stratifies the need for surgery.
Comparative Analysis of Full Endoscopic Interlaminar Lumbar Discectomy and Lumbar Microdiscectomy
Authors: Şerifoğlu Luay , Etli Mustafa Umut , Özdoğan Selçuk
Published: November 2024

Study Design:

Retrospective clinical study.

Objectives:

The aim is to assess and contrast the results of full endoscopic lumbar discectomy (FELD) and lumbar microdiscectomy (LMD) for L5–S1 disc herniation, with a specific emphasis on postoperative pain reduction and surgical effectiveness.

Background:

Although minimally invasive spine operations are becoming more popular, there is still little research on the comparative effectiveness of FELD and LMD.

Materials and Methods:

The research had a total of 50 patients who received surgical intervention for L5–S1 disc herniation, with 25 patients getting full endoscopic interlaminar discectomy and the other 25 patients undergoing LMD. Clinical outcomes were assessed using the Visual Analog Scale for low back and leg pain, collected preoperatively and at the end of 1 week, 3 months, and 6 months postsurgery. Patient satisfaction was evaluated using Odoms criteria at the same intervals.

Results:

The study included 50 patients (26 men, 24 women), with a mean age of 51.11 ± 13.76 years. The groups had no significant differences in demographic data. Back and leg pain Visual Analog Scale scores decreased more significantly in the FELD group after 1 week of surgery (P < 0.001), although the declines at 3 months and 6 months were not significantly different between the two groups. According to Odoms criteria, patient satisfaction was favorable in both groups and significantly better in the FELD group than in the LMD group at 1 week postoperatively [excellent in 20 patients (80%) in the FELD group vs 9 patients (36%) in the LMD group (P = 0.025)]. However, patient satisfaction at 3 months and 6 months did not differ between the groups.

Conclusion:

This study demonstrates that FELD offers significant early postoperative advantages over LMD at the L5–S1 level when compared with pain and satisfaction scales.

Level of Evidence

Level III.
Revisiting the Consistency of Financial Disclosure Reporting by Authors at Annual Spine Conferences Show Inconsistent Improvements After 14 Years
Authors: Kim Lucas Y. , Grauer Jonathan N.
Published: November 2024

Study Design:

Cross-sectional study of presenter disclosures from the 2022 North American Spine Society (NASS), Scoliosis Research Society (SRS), and Cervical Spine Research Society (CSRS) annual research conferences.

Objective:

The current study aimed to evaluate the consistency of financial disclosures for authors presenting at multiple 2022 spine conferences and compared results to those previously reported in 2008.

Summary of Background Data:

Transparent reporting of financial relationships between physicians and industry is seen as an important way to limit/address potential bias. Thus, many research conferences require authors to disclose such relationships. Despite these requirements, variability in the financial disclosure reporting for matched speakers at 2008 major spine conferences was previously reported. Since then, the Sunshine Act mandated public financial relationships, potentially furthering attention and leading to improvements in financial disclosures.

Methods:

Disclosures of authors presenting at >1 of the three 2022 spine conferences were compiled from conference websites, and discrepancies were determined based on conference disclosure policies. For comparisons where both conferences required disclosure of all relationships, the discrepancy was identified if there was not a match. For comparisons where 1 conference required paper-specific relationships, and the other required all relationships, discrepancy was identified if the first was not a subset of the other. Results were compared with those reported from 2008.

Results:

NASS and SRS both required disclosure of all relationships, had 208 overlapping authors, and had 36.5% discrepancies. SRS and CSRS required all and paper-specific disclosures, had 37 overlapping authors, and had 29.7% discrepancies. NASS and CSRS required all and paper-specific disclosures, had 81 overlapping authors, and had 29.6% discrepancies. Overall, the average discrepancy for pairs of conferences in 2008 was 26%, and for 2022 was 32%, indicating a lack of improvement. Compared with 2008, discrepancies decreased more when disclosure requirements were the same for both conferences being considered.

Conclusions:

These findings demonstrate that significant variability remains in the reporting of financial conflicts of interest by authors presenting at 3 major spine conferences last year, despite previous scrutiny and the evolution of the Sunshine Act. These discrepancies may reflect the ambiguity caused by different disclosure policies and further attention is needed for this topic.
What Is in the Neuromuscular Junction Literature?
Authors: Lacomis David
Published: November 2024

This update starts with an interesting series of children and adults with congenital myasthenic syndrome with a DOK7 variant. The next section is on autoimmune myasthenia gravis (MG) epidemiology, cost of care, and hospitalizations. A number of studies on the newer treatments are discussed including a phase 2 trial of nipocalimab and recommendations for using some of these drugs. A large trial emphasizing the negative effects of pyridostigmine in muscle-specific kinase MG is covered. A study on the incidence of taste disorders and alopecia in MG follows. The update ends with the topic of the burden of disease in MG and Lambert–Eaton myasthenic syndrome.
A Case Series Examining Clinic, Laboratory, and Physical Function After Administration of Nusinersen in Adults With Spinal Muscular Atrophy, a Single-Center Study
Authors: Bertorini Tulio , Knickerbocker Janna , Anwar Hagar , Mays William , Carter Kimberly , Metter E. Jeffrey , Talbot Laura A.
Published: November 2024

Spinal muscular atrophy is an incurable inherited disease caused by lower motor neuron death from mutations of the survival motor neuron genes. Intrathecal therapy with the antisense oligonucleotide, nusinersen, has been demonstrated to be beneficial in children with this disease, but the experience in adults, particularly ambulatory patients, is limited. We present a prospective observational case series from a single center using nusinersen therapy where we categorize 6 adult patients with spinal muscular atrophy into 2 functional categories: ambulatory (n = 3) or nonambulatory (n = 3). All received therapy that was administered intrathecally every 4 months. We monitored the course and laboratory data for 1 year and observed for side effects. There was no significant deterioration for 1 year. There was some minor improvement particularly in subjective changes. The benefit seems to decrease after 3 months. No significant complications were observed.
A rare clinical manifestation of plexiform neurofibroma in the absence of neurofibromatosis-1: a case report
Authors: Rwomurushaka Evance Salvatory , Mremi Alex , Hussein Atiyya , Majaliwa Esther , Lodhia Jay
Published: November 2024

Plexiform neurofibroma is a benign tumor of peripheral nerves that occurs in up to 30% of patients with neurofibromatosis type-1 (NF-1). We present a case of a 15-year-old male patient without NF-1, with an 11-year history of a slow growing, painless mass on the left side of the back extending to the gluteal region, with no constitutional symptoms but with some scoliosis. Histology of the mass was compatible with a plexiform neurofibroma. Plexiform neurofibromas commonly occur in, but are not limited to the craniofacial region. The mainstay of treatment is surgical resection, but complete resectability is challenging due to their locally infiltrative growth pattern. This highlights the need for patient-specific management strategies, even when established guidelines are in place.
MACULAR NEURODEGENERATIVE AND VASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHIC ANGIOGRAPHY IN SICKLE CELL DISEASE ARE NOT RELATED TO ITS OCULAR AND SYSTEMIC COMPLICATIONS
Authors: Brandsen Rajani P. , Biemond Bart J. , Nasim Gulsum Z. , Nur Erfan , Schlingemann Reinier O. , Diederen Roselie M.H.
Published: November 2024

Purpose:

To evaluate macular abnormalities in sickle cell disease with optical coherence tomographic angiography and to determine associations with sickle cell retinopathy (SCR) and clinical and laboratory characteristics.

Methods:

Complete ophthalmic examination was performed in consecutive patients with sickle cell disease (HbSS, HbSC, HbSβ0, or HbSβ+ genotype), including fundoscopy and macular spectral-domain optical coherence tomography/optical coherence tomographic angiography scans. Sickle cell retinopathy stage was based on fundoscopic examination (without fluorescein angiography) instead of the Goldberg classification because fluorescein angiography was only used in case of tentative diagnosis. Medical/ophthalmological history and hematologic characteristics were retrieved from medical records.

Results:

Two hundred and forty-nine eyes of 137 patients were analyzed. The mean age was 33.3 ± 12.4 years (range 15–70 years). Nonproliferative SCR was present in 57 eyes (22.9%) and proliferative SCR in 36 eyes (14.5%). Macular thinning was present in 100 eyes (40.2%) and was associated with lower foveal vessel density of the superficial capillary plexus and deep capillary plexus and with enlargement of the foveal avascular zone area, perimeter, and acircularity index. Age and female sex were associated with lower (para)foveal vessel density in the superficial capillary plexus and deep capillary plexus. No associations were found between SCR presence/severity and macular thinning or vessel density.

Conclusion:

Macular abnormalities were common but did not result in visual impairment. No relation with SCR presence/severity was found. Although optical coherence tomographic angiography imaging is suitable for detecting maculopathy, it appears to have no diagnostic value in identifying patients at risk for SCR.
Guardian Knowledge in Primary Congenital Glaucoma
Authors: Alfaar Ahmad Samir , Hassan Doaa M. , Bawazir Mohammed , Elsanabary Zeinab , Ezzat Sameera , Elsayed Yasmine
Published: November 2024

Précis:

Guardian education level and frequency of surgical interventions are key determinants of knowledge in primary congenital glaucoma, highlighting the need for targeted educational strategies.

Objective:

Management of congenital glaucoma poses unique challenges, particularly concerning the patient guardians’ understanding of the condition, which is crucial for treatment adherence and follow-up compliance. This study aimed to assess guardians’ knowledge levels and identify the influencing factors.

Methods:

This cross-sectional study included 103 guardians of pediatric patients with primary congenital glaucoma. Participants with missing data were excluded from the study. The participants were assessed using a 20-question survey covering various aspects of glaucoma. Descriptive and inferential statistics were used for analysis.

Results:

The sample included 96 guardians, primarily females (80.2%). The children’s ages varied significantly, averaging ∼44 months (SD = 39.8). The guardians predominantly had secondary education (34.4%) and most were housewives (77.1%). There was a positive correlation between higher education levels and the overall knowledge score of guardians (P = 0.006). Similarly, the guardian’s locality showed a positive correlation with knowledge scores, with urban guardians having higher scores than rural guardians. In addition, there was a positive correlation between the number of surgical operations performed on the child and the guardians’ knowledge. For the subtotals, variables such as the child order among siblings and the age of the child showed significant positive correlations, emphasizing the multifaceted influences on guardians’ understanding. In the multivariate analysis, the guardian’s education level showed a significant positive correlation with the overall score, as did the number of operations performed on the patient.

Conclusions:

The study revealed gaps in guardian knowledge, irrespective of educational level or other demographic factors. Guardians’ education level and the number of operations performed on the child are critical determinants of guardians’ understanding of congenital glaucoma. Traditional approaches to educational interventions may require reevaluation, and there is a pressing need for targeted educational interventions.
Accuracy of thick and thin intraocular lens power formulas using paraxial vergence calculation
Authors: Næser Kristian , Nielsen Rasmus
Published: November 2024

Purpose:

To compare the prediction errors (PEs) of several thick intraocular lens (IOL) formulas with a thin lens approach using variations of the same paraxial vergence calculation formula.

Setting:

Department of Ophthalmology, Randers Regional Hospital, Denmark.

Design:

Prospective, noninterventional study.

Methods:

Optical low coherence reflectometry biometry was prospectively and consecutively performed in 132 eyes with subsequent phacoemulsification and insertion of the same aspheric IOL model. Clinical refraction was performed 2 months postoperatively. Retrospectively, the same paraxial vergence formula was used and only the methods were varied for calculating the postoperative IOL position, thickness, and curvatures to construct 4 formulas: Næser I formula based on thick lens calculation using the manufacturer's cutting card information, Næser II formula based on thick lens calculation using calculated IOL data from open sources, Næser III formula based on thick lens calculation and a fixed IOL thickness of 0.62 mm, and Næser IV formula based on thin lens calculation with fixed IOL position 0.31 mm anterior to the postoperative capsule. Each formula was optimized separately, hereby assuring a mean error of zero. The PE was defined as the difference between the measured and predicted spherical equivalent refraction.

Results:

Mean absolute error amounted to 0.30 ± 0.26 diopters for all 4 formulas with no statistically significant difference. PE averaged zero for short, normal, and long eyes.

Conclusions:

The additional optical information provided by thick IOL calculations seems insignificant compared with other sources of error, related to the accuracy of IOL manufacturing, crystalline lens refractive index, and postoperative refraction.
A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery
Authors: Chiu Yun-Ning , Kung Ching-Yun , Huang Kuo-Hung , Lin Shih-Chieh , Fang Wen-Liang , Chen Ming-Huang , Lo Su-Shun , Li Anna Fen-Yau , Wu Chew-Wun , Lan Yuan-Tzu
Published: November 2024

Background:

Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery.

Methods:

In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared.

Results:

Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p<0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K/Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival.

Conclusion:

Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.
Pretreatment plasma vitamin D and response to neoadjuvant chemotherapy in breast cancer: evidence from pooled analysis of cohort studies
Authors: Shu Chi , Yang Qian , Huang Jun , Xie Xuan , Li Hong , Wu Hong , Wang Xin , Chen Xin , Xie Yuping , Zhou Yanhong , He Yazhou , Xu Chuan
Published: November 2024

Background:

Biological evidence has revealed antitumor effect of vitamin D, but whether it could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients remains inconclusive. The aim was to investigate the association between pretreatment vitamin D level and response to NAC and subsequent survival outcomes in BC patients.

Materials and methods:

The authors systematically searched the Medline, Embase, Cochrane Library, and Web of Science databases and clinical trial registries to identify relevant articles from inception to 8 October 2024. Eligible studies investigating the associations between pretreatment plasma vitamin D and response to NAC in BC patients were selected according to the predefined criteria, with the study characteristics extracted by two reviewers. The primary outcome was pathological complete response (pCR), while overall pathological response and event-free survival (EFS) were adopted as secondary outcomes. Summary effect estimates of odds ratios (ORs) or hazard ratios (HRs) with 95% CIs were pooled using a random-effects model. Subgroup and sensitivity analyses were performed based on study characteristics and methodological quality.

Results:

Six retrospective cohort studies involving 1291 BC patients were included. The authors observed a significant association between pretreatment vitamin D deficiency and 50% increased odds of non-pCR after NAC (OR=1.50, 95% CI: 1.11–2.03, P=0.008) with no heterogeneity (I
2=0%). The authors also identified a significant association of vitamin D with the overall pathological response (OR=1.33, 95% CI: 1.01–1.75, P=0.046). A similar association with EFS (HR=1.27, 95% CI: 0.92–1.75, P=0.139) was also noted although the effect estimate was not statistically significant. Sensitivity analyses based on methodological quality showed consistent findings.

Conclusion:

Pretreatment vitamin D deficiency is associated with an inferior response to NAC in BC patients. Our meta-analysis advocates further prospective studies with large sample sizes before vitamin D supplementation could be administered to improve NAC response and subsequent prognosis of BC patients.
Why protein-energy wasting leads to faster progression of chronic kidney disease
Authors: Narasaki Yoko , Rhee Connie M. , Kalantar-Zadeh Kamyar , Rastegar Mandana
Published: November 2024

Purpose of review

Protein-energy wasting (PEW) is increasingly more prevalent as chronic kidney disease (CKD) progresses to more advanced stages. There is a global recognition of the importance of preventing and mitigating PEW in the CKD population not on dialysis given the goal of extending dialysis-free time and delaying dialysis initiation and growing evidence of the clinical consequences of PEW which include the risk of death, hospitalization and clinical conditions such as infections. We reviewed the association of PEW and the malnutrition characteristics indicative of PEW on CKD progression.

Recent findings

Studies show the association between low serum albumin levels, low BMI, and diets with inadequate dietary energy and protein intake and CKD progression. Limited studies suggest low muscle mass impacts CKD progression. Optimizing nutrition by dietary management, including a moderately low protein (0.6–0.8 g/kg/day) and plant-based (>50% of protein source, known as PLADO) diet and as needed with supplementation [e.g. during acute kidney injury (AKI) event] administrated orally, enterally, or parenterally are the basis for the prevention and treatment of PEW in CKD and delaying CKD progression. Furthermore, other therapeutic methods such as treating or avoiding comorbidities and AKI, ensuring appropriate exercise and incremental transition to dialysis treatment may help ameliorate and prevent PEW development in CKD patients.

Using tailored precision nutrition approaches and nutritional supplementation with or without other beneficial strategies may help prevent and treat PEW and its consequent occurrence of CKD progression.
Incremental hemodialysis transition in veterans and nonveterans with kidney failure
Authors: Rhee Connie M. , Kovesdy Csaba P. , Unruh Mark , Crowley Susan , Geller David , Goldfarb David S. , Kraut Jeffrey , Rastegar Mandana , Rifkin Ian R. , Kalantar-Zadeh Kamyar
Published: November 2024

Purpose of review

Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients’ residual kidney function (RKF), comorbidities, and preferences.

Recent findings

Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD.

Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.
Molecular matching tools for allocation and immunosuppression optimization. Ready for primetime?
Authors: Niemann Matthias , Matern Benedict M.
Published: November 2024

Purpose of review

Molecular matching continues to be an important topic in organ transplantation. Over the years, several studies – larger and smaller – supported correlations of molecular incompatibility loads and clinical outcomes. However, their practical utility for clinical decision making remains controversial and there is no consensus on the context in which they should be used.

Recent findings

The recent literature on molecular matching can be divided into four main areas of research: several groups present improvements of the algorithmic pipelines (1), increasing the robustness of previous findings. Further clinical evidence is reported (2) in various cohorts and other organ transplant domains, such as liver and lung transplantation. Consideration is given to the application of molecular matching in the allocation of deceased organs (3), suggesting options to improve allocation equity and utility. Furthermore, evidence is provided for personalized immunosuppression based on immunological risk (4), including infection and post graft failure management.

There is ample evidence that current molecular matching algorithms add value to immunologic risk stratification for organ transplant recipients. First studies on how to translate these insights into patient management with respect to organ allocation and personalized medicine are underway and require further support.
Impact of Statin Use on Survival in Patients With Unresectable Pancreatic cancer Receiving Gemcitabine Plus Nab-Paclitaxel
Authors: Saito Kei , Nakai Yousuke , Sasaki Takashi , Takeda Tsuyoshi , Ueno Makoto , Tezuka Shun , Isayama Hiroyuki , Tomishima Ko , Kojima Yasushi , Yamamoto Natsuyo , Ito Yukiko , Oyama Hiroki , Toda Nobuo , Takagi Kaoru , Matsubara Saburo , Mohri Dai , Sato Tatsuya , Fujishiro Mitsuhiro
Published: November 2024

Purpose

The aim of this multicenter retrospective study was to evaluate the impact of statin use on clinical outcomes in patients with unresectable pancreatic cancer (PC) receiving gemcitabine plus nab-paclitaxel (GnP) in a large Japanese cohort.

Materials and Methods

We retrospectively reviewed the medical records including data on the use of concomitant medications in patients with unresectable PC receiving GnP between January 2015 and January 2019 at 10 hospitals. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were evaluated.

Results

A total of 1682 patients were included in the analysis; of which 322 patients (19%) received statins and 1360 (81%) did not receive statin. The median PFS and OS were 7.5 versus 7.3 months (P = 0.87) and 15.1 versus 14.4 months (P = 0.48) in cases with and without statin use. The use of statin was not associated with PFS (hazard ratio, 1.01; 95% confidence interval, 0.85–1.18, P = 0.93) or OS (hazard ratio, 1.05; 95% confidence interval, 0.91–1.21, P = 0.47) in the multivariable analyses. PFS and OS did not significantly differ by liposolubility of statins, either.

Conclusions

Stain use was not associated with PFS or OS in patients with unresectable PC receiving GnP.