Recommendations For Clinical Management Research Articles

Impact of repeated low-level red-light therapy on axial length, refraction, and macular retinal blood flow density in adolescents with mild to moderate myopia.

In order to evaluate the effectiveness of repeated low-level red-light (RLRL) therapy on stabilizing axial elongation and refractive changes in adolescents with mild to moderate myopia. In addition, we also examined whether RLRL therapy affects retinal blood flow density in the macular region, a factor previously unstudied in this context. Conducted at a single clinical site, this retrospective, single-arm study followed participants over six months, with assessments at baseline, 1 month, 3 months, and 6 months. The primary outcomes included axial length and spherical equivalent refraction (SER) changes. Secondary assessments included retinal blood flow density (superficial and deep macular layers), white-to-white corneal diameter, central corneal thickness, intraocular pressure (IOP), corneal curvature, light sensitivity, and peripheral retinal thickness. There were 32 enrolled participants (mean age = 11.5 ± 1.72) in the current study. The spherical equivalent (SER) remained relatively stable over the first three months, but it significantly improved at six months, changing from -2.39 ± 2.21 D at baseline to -2.01 ± 2.12 D (P < 0.05). However, the axial length also showed minimal variation across follow-up visits, indicating stable eye growth with no substantial elongation throughout the study period. Furthermore, RLRL therapy resulted in stable measurements across primary and secondary outcomes (all P > 0.05), with no significant changes over the six months. There were no obvious side effects following the treatment. Low-energy red light therapy shows promise as a non-invasive approach for stabilizing myopia in adolescents, with no observed compromise to retinal blood flow density. Further longitudinal research is needed to validate these findings and support clinical recommendations for myopia management.

Thyroid Nodules with Indeterminate Cytology and Negative Molecular Profile: Prevalence of Malignancy and Practice Paradigms for Surveillance.

Background: In the era of molecular testing, thyroid nodules with indeterminate cytology are increasingly being managed nonoperatively. The false-negative rates of these molecular tests, and therefore missed malignancies, are not well defined in real-world clinical practice. Methods: This retrospective study of patients undergoing fine needle aspiration (FNA) biopsy at our health system between November 2017 and March 2022 included nodules with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) III and IV cytology and negative, currently negative, or negative but limited ThyroSeq version 3 (TSv3) results. Surgical pathology of resected nodules, as well as details of ultrasound (US) surveillance practices, was recorded. A range of prevalence of malignancy (PoM) estimates were calculated based on all nodules (PoM low) and surgically resected nodules (PoM high). Results: The study cohort consisted of 556 nodules. TSv3 results were distributed as 443 (80%) negative, 85 (15%) currently negative, and 28 (5%) negative but limited. Overall, 75 nodules were resected: 54 nodules (9.7%) had immediate surgery, and 21 nodules (3.8%) had delayed surgery after surveillance imaging. Currently negative and negative but limited nodules were more likely to undergo immediate surgical resection compared with negative nodules (20%, 18%, and 7%, respectively, p < 0.001). The PoM in molecularly benign TBSRTC III and IV thyroid nodules ranged between 3% and 23% depending on the inclusion of all versus resected nodules. TBSRTC IV molecularly benign nodules had a higher PoM than TBSRTC III (PoM low 7.3% vs. 1.6%, p < 0.001; PoM high 48% vs. 13%, p = 0.0013). In the 90% of nodules that were managed nonoperatively, 63% had at least one surveillance US. Timing of initial surveillance US ranged from 3 to 60 months (median 13 months, interquartile [IQR] 11-19 months). Median follow-up duration was 25 months (IQR 17-34 months). Nodule growth occurred in 24% of nodules; only a minority (7%) underwent repeat FNA. Conclusions: Negative subtype of TSv3 should be considered in clinical management recommendations. For negative but limited samples, repeat FNA should be performed. Optimal surveillance strategy for nonresected negative and currently negative nodules remains unknown. Until further real-world data are available, surveillance ultrasonography is recommended for TSN and TSCN nodules, similar to the ATA guidelines for TBSRTC II nodules.

Patients with Darier disease have an increased risk of keratinocyte carcinoma: a Swedish registry-based nationwide cohort study.

Darier disease is a genodermatosis which manifests as hyperkeratotic papules and superficial erosions mainly in seborrheic skin areas. This retrospective registry-based cohort study aimed to estimate the association between Darier disease and skin cancer. Patients diagnosed with Darier disease were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) in 2016-2020. The local cohort included 13 patients. Verification of Darier disease diagnosis in the National Patient Registry showed positive predictive value of more than 90%. National Patient Registry was searched for Darier disease in 2001-2020, Swedish Cancer Registry for cancers and Prescribed Drug Register for medications. The national cohort included 770 patients and tenfold matched control cohort. Patients with Darier disease had an increased relative risk of keratinocyte carcinoma (basal cell carcinoma and cutaneous squamous cell carcinoma combined) (hazard ratio [HR], 1.6, 95% confidence interval [CI], 1.0-2.5, P = 0.036). The risk increase was significant for basal cell carcinoma (HR, 1.8, 95% CI, 1.1-2.9, P = 0.012), whereas there was a trend for cutaneous squamous cell carcinoma, (HR, 1.9, 95% CI, 0.9-4.1, P = 0.086) and cutaneous melanoma (HR, 2.4, 95% CI, 0.9-6.2, P = 0.083). Standardized incidence ratio for keratinocyte cancers was 2.9 (95% CI, 2.4-3.3. The results were consistent in two subgroup analyses adjusting for use of retinoid and/or immunosuppressive drugs. Patients with Darier disease have an increased risk of skin cancer, particularly keratinocyte carcinoma. This risk was consistent even when known risk modifiers for keratinocyte carcinoma were excluded in sensitivity analyses. The results support previously proposed molecular links between Darier disease and skin cancer, but further investigations are needed. Additional studies are also required to develop clinical management recommendations for Darier disease. In the meantime, dermatologists should be aware of the cancer risk in these patients and remain vigilant, as detecting cancer can be challenging in hyperkeratotic and/or eroded skin.

Pseudo-Worsening of Kidney Function Due to Inhibition of Renal Creatinine Secretion: Quality of Information Provided in Prescribing Information/SmPC.

Determination of serum creatinine concentrations and subsequent calculation of estimated glomerular filtration rates (eGFR) is a cornerstone of clinical medicine. Crucial clinical decisions such as drug treatment discontinuations are based on eGFR calculated from serum creatinine measurements. However, creatinine is not only filtered in the kidneys, but also actively secreted into urine. Creatinine transporters such as OCT2, OCT3, MATE1, MATE2-K, and OAT2 expressed in proximal tubular cells are responsible for active renal secretion of creatinine. Multiple drugs (e.g., oral antitumor drugs) inhibit these transporters thereby causing a pseudo-worsening of kidney function with an increase in serum creatinine concentrations and a decrease in eGFR while other methods for eGFR determination (e.g., by cystatin C) reveal normal kidney function. Since US Prescribing Information (PI) and European Summaries of Product Characteristics (SmPCs) are the most relevant source of information for physicians, we investigated the quality of information in US PI/German SmPCs of drugs with clear evidence for pseudo-worsening of kidney function. 514 drugs putatively interacting with creatinine transporters were identified. For 149 of those drugs, an increase in serum creatinine concentrations has been described. Available data confirmed the existence of pseudo-worsening of kidney function for 30 of those drugs, for the remaining 119 drugs existing data are insufficient. Only 23.5% (12/51) of the 30 drugs' PI/SmPCs contained unambiguous statements on this proven pseudo-worsening of kidney function and gave clear recommendations for clinical management. Taken together, inadequate information provided in PI or SmPCs on the pseudo-worsening of kidney function poses patients at unnecessary risks.

Innovation in cancer pharmacotherapy through integrative consideration of germline and tumor genomes.

Precision cancer medicine is widely established, and numerous molecularly targeted drugs for various tumor entities are approved or in development. Personalized pharmacotherapy in oncology has so far been based primarily on tumor characteristics, e.g., somatic mutations. However, the response to drug treatment also depends on pharmacological processes summarized under the term ADME (absorption, distribution, metabolism, and excretion). Variations in ADME genes have been the subject of intensive research for more than five decades, considering individual patients' genetic makeup, referred to as pharmacogenomics (PGx). The combined impact of a patient's tumor and germline genome is only partially understood and often not adequately considered in cancer therapy. This may be attributed, in part, to the lack of methods for combined analysis of both data layers. Optimized personalized cancer therapies should, therefore, aim to integrate molecular information about the tumor and the germline, taking into account existing PGx guidelines for drug therapy. Moreover, such strategies should provide the opportunity to consider genetic variants of previously unknown functional significance. Bioinformatic analysis methods and corresponding algorithms for data interpretation need to be developed to consider PGx data in interdisciplinary molecular tumor boards, where cancer patients are discussed to provide evidence-based recommendations for clinical management based on individual tumor profiles. Significance Statement The era of personalized oncology has seen the emergence of drugs tailored to genetic variants associated with cancer biology. However, full potential of targeted therapy remains untapped due to the predominant focus on acquired tumor-specific alterations. Optimized cancer care must integrate tumor and patient genomes, guided by pharmacogenomic principles. An essential prerequisite for realizing truly personalized drug treatment of cancer patients is the development of bioinformatic tools for comprehensive analysis of all data layers generated in modern precision oncology programs.

Evaluating text and visual diagnostic capabilities of large language models on questions related to the Breast Imaging Reporting and Data System Atlas 5th edition.

This study aimed to evaluate the performance of large language models (LLMs) and multimodal LLMs in interpreting the Breast Imaging Reporting and Data System (BI-RADS) categories and providing clinical management recommendations for breast radiology in text-based and visual questions. This cross-sectional observational study involved two steps. In the first step, we compared ten LLMs (namely ChatGPT 4o, ChatGPT 4, ChatGPT 3.5, Google Gemini 1.5 Pro, Google Gemini 1.0, Microsoft Copilot, Perplexity, Claude 3.5 Sonnet, Claude 3 Opus, and Claude 3 Opus 200K), general radiologists, and a breast radiologist using 100 text-based multiple-choice questions (MCQs) related to the BI-RADS Atlas 5th edition. In the second step, we assessed the performance of five multimodal LLMs (ChatGPT 4o, ChatGPT 4V, Claude 3.5 Sonnet, Claude 3 Opus, and Google Gemini 1.5 Pro) in assigning BI-RADS categories and providing clinical management recommendations on 100 breast ultrasound images. The comparison of correct answers and accuracy by question types was analyzed using McNemar's and chi-squared tests. Management scores were analyzed using the Kruskal- Wallis and Wilcoxon tests. Claude 3.5 Sonnet achieved the highest accuracy in text-based MCQs (90%), followed by ChatGPT 4o (89%), outperforming all other LLMs and general radiologists (78% and 76%) (P < 0.05), except for the Claude 3 Opus models and the breast radiologist (82%) (P > 0.05). Lower-performing LLMs included Google Gemini 1.0 (61%) and ChatGPT 3.5 (60%). Performance across different categories of showed no significant variation among LLMs or radiologists (P > 0.05). For breast ultrasound images, Claude 3.5 Sonnet achieved 59% accuracy, significantly higher than other multimodal LLMs (P < 0.05). Management recommendations were evaluated using a 3-point Likert scale, with Claude 3.5 Sonnet scoring the highest (mean: 2.12 ± 0.97) (P < 0.05). Accuracy varied significantly across BI-RADS categories, except Claude 3 Opus (P < 0.05). Gemini 1.5 Pro failed to answer any BI-RADS 5 questions correctly. Similarly, ChatGPT 4V failed to answer any BI-RADS 1 questions correctly, making them the least accurate in these categories (P < 0.05). Although LLMs such as Claude 3.5 Sonnet and ChatGPT 4o show promise in text-based BI-RADS assessments, their limitations in visual diagnostics suggest they should be used cautiously and under radiologists' supervision to avoid misdiagnoses. This study demonstrates that while LLMs exhibit strong capabilities in text-based BI-RADS assessments, their visual diagnostic abilities are currently limited, necessitating further development and cautious application in clinical practice.

Specific persistent symptoms of COVID-19 and associations with reinfection: a community-based survey study in southern China.

Surveillance remains fundamental to understanding the changes in epidemiological patterns regarding post-COVID conditions and reinfections. Persistent symptoms and reinfection in previously infected individuals are increasing being reported in many countries, but their associations among general populations were seldomly reported. Understanding the association with persistent symptoms of COVID-19 reinfection is essential to develop strategies to mitigate the long-term health and socio-economic impacts of the post-COVID conditions. This study aimed to investigate the incidence of COVID-19 persistent symptoms among previously infected Chinese community residents and explore associations of specific COVID-19 persistent symptoms with reinfection and other factors. A community-based survey was conducted in a southern city of China with about 20 million residents from August 3 to 24, 2023. Face-to-face questionnaires were distributed to a total of 1,485 residents to collect their information about COVID-19 infection, reinfection, specific ongoing persistent symptoms, and other COVID-19 related information. Multivariable logistic regression analysis was used to examine the association between specific persistent symptoms and reinfection of COVID-19, along with age, gender, and educational level. Of the 1,485 participants, 1,089 (73.3%) reported they had been infected with COVID-19. Among them, 89.1% reported having ongoing persistent symptoms and 14.2% reported had two or more times of infection. About 20% participants were infected 1 year or more since their initial infection. Fatigue, cough, and headaches were the top 3 symptoms being reported. Participants with reinfection were associated with a higher probability of reporting headaches (OR: 1.54, 95% CI: 1.06-2.25), loss of or change in smell and/or taste (OR: 1.90, 95% CI: 1.27-2.83), impaired sleep (OR: 1.55, 95% CI: 1.02-2.35), and brain fog (OR: 1.76, 95% CI: 1.12-2.76). Participants aged 45 and above and who had a bachelor's or higher degree were more likely to report chest tightness or shortness of breath, impaired sleep, and brain fog. During the post-emergency period of COVID-19 pandemic, the incidence of ongoing persistent symptoms among Chinese residents remains high. Individuals whose initial infection was longer than 1 year have the highest probability of reporting having multiple symptoms. Reinfection may increase the risk of reporting headaches, loss of or change in smell and/or taste, impaired sleep, and brain fog. It is important to maintain routine syndromic surveillance among previously infected people and provide recommendations for clinical management of individuals with multiple ongoing symptoms.

Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned.

In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university-affiliated practice sites across Indiana. The overarching goal of this PGx implementation program was to facilitate the sustainable adoption of genotype-guided prescribing into routine clinical care. To accomplish this goal, we pursued the following specific objectives: (i) to integrate PGx testing into existing healthcare system processes; (ii) to implement drug-gene pairs with high-level evidence and educate providers and pharmacists on established clinical management recommendations; (iii) to engage key stakeholders, including patients to optimize the return of results for PGx testing; (iv) to reduce health disparities through the targeted inclusion of underrepresented populations; (v) and to track third-party reimbursement. This tutorial details our multifaceted PGx implementation program, including descriptions of our interventions, the critical challenges faced, and the major program successes. By describing our experience, we aim to assist other clinical teams in achieving sustainable PGx implementation in their health systems.

Recommendations for 46,XY Disorders/Differences of Sex Development Across Two Decades: Insights from North American Pediatric Endocrinologists and Urologists

Clinical decision-making for individuals with 46,XY disorders/differences of sex development (DSD) remains unsettled and controversial. The North American DSD Clinician Survey examines the recommendations of a large group of clinical specialists over the last two decades. Active members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology were invited to respond to a web-based survey at three different timepoints: 2003–2004 (T1), 2010–2011 (T2), and 2019–2020 (T3). Data from 429 participants in T1, 435 in T2, and 264 in T3 were included in this study. The participants were presented with three XY newborn clinical case scenarios—micropenis, partial androgen insensitivity syndrome, and iatrogenic penile ablation—and asked for clinical management recommendations. The main outcomes assessed included the recommended gender of rearing, surgical decision-maker (parent or patient), timing of genital surgery, and age at which to disclose medical details and surgical history to the patient. For all scenarios, the overwhelming majority recommended rearing as male, including a significant increase across timepoints in those recommending a male gender of rearing for the infant with penile ablation. The proportions recommending female gender of rearing declined significantly across timepoints. In general, most recommended parents (in consultation with the physician) serve as surgical decision-makers, but these proportions declined significantly across timepoints. Recommendations on the timing of surgery varied based on the patient’s gender and type of surgery. There has been a shift in recommendations away from the “optimal gender policy” regarding gender of rearing and surgical interventions for patients with XY DSD.

Expert Consensus Recommendations for the Management of Ocular Surface Inflammation in Patients With Glaucoma.

We have developed through a consensus process 24 clinical recommendations for the comprehensive management of ocular surface inflammation in glaucoma patients, including diagnostic criteria, prevention measures, and treatment strategies according to ocular surface disease severity. To obtain expert consensus on the diagnosis, prevention, and management of ocular surface inflammation (OSI) in patients with glaucoma. An international steering committee of glaucoma and/or ocular surface disease (OSD) experts and a wider faculty of members from the Educational Club of Ocular Surface and Glaucoma (ECOS-G) collaborated to develop clinical recommendations on best practice in the management of OSI in glaucoma patients using a nonanonymous interactive quasi-Delphi process. Clinical recommendations were formulated by the steering committee based on an analysis of the recent literature to determine unmet needs, together with a web-based interactive survey of faculty members' opinion in seven identified areas of OSI management in glaucoma. Topics included (1) diagnosis of OSD, (2) diagnosis of OSI, (3) causes of OSI, (4) impact of OSD/OSI, (5) prevention of OSI, (6) treatment of OSI, and (7) inflammation and the deep structures of the eye. Faculty members were invited to vote on the clinical recommendations, and the steering committee then determined whether consensus had been achieved. Consensus was obtained on 24 clinical recommendations by 80%-100% of faculty members. There was consensus that OSI should be investigated in all glaucoma patients. The main prevention measure in glaucoma patients with pre-existing OSD was the elimination/minimisation of preserved medications, especially BAK-preserved eye drops. A subtractive treatment strategy rather than an additive strategy is recommended according to OSI/OSD severity to improve the ocular health and/or before glaucoma surgery. These recommendations for the management of OSI in glaucoma should be useful to guide decision-making in clinical practice.

Recommendations on cutaneous and hematological manifestations of Sjögren’s disease by the Brazilian Society of Rheumatology

Sjogren’s disease (SjD) is an autoimmune disease that is characterized not only by the sicca symptoms it causes but also by its systemic nature, which is capable of several and not yet fully understood extraglandular manifestations. To gain a clearer understanding of these manifestations as well as a better practical approach, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of the extraglandular manifestations present in ESSDAI (EULAR Sjogren´s syndrome disease activity index), followed by a voting panel with recommendations for clinical practice. This publication is complementary to others already published and covers cutaneous and hematological manifestations, with prevalence data generated by a meta-analysis of 13 clinical or laboratory manifestations and 6 clinical management recommendations.

Dynamic spinal orthoses self-reported effects in patients with back pain due to vertebral fragility fractures: A multi-center prospective cohort study.

Vertebral fragility fractures (VFFs) commonly result from low bone mass and microarchitecture deterioration of bone tissue. spinal orthoses are common non-pharmacological options for managing vertebral fracture pain. However, the effects of spinal orthoses on pain, physical functioning, and quality of life (QoL) are still debated. This survey aimed to investigate the patients-reported outcomes of a dynamic spinal orthosis prescribed in the routine clinical practice of VFFs management. This multi-center national-wide prospective cohort study assessed older patients (aged > 60years) diagnosed with acute VFFs and prescribed with a dynamic spinal orthosis (Spinfast®). A survey questionnaire was realized and included sections on patient characterization, osteoporosis characterization, spinal orthosis, clinical outcomes, pain medications, and osteoporosis medications. The questionnaire was administered at baseline and after three months. A total of 68 patients completed the questionnaire at three months. Most patients had one or two VFFs and were treated with pain medications and osteoporosis medications. Compliance and tolerability of the spinal orthosis were assessed, and clinical outcomes such as pain intensity, physical functioning, and QoL were measured. The results showed no significant differences in outcomes between age subgroups. Italian physical medicine and rehabilitation physicians were commonly involved in the management of VFFs patients. Sixty-six patients completed the questionnaire. The results showed that pain intensity, physical functioning and QoL improved after three months of spinal orthosis wearing (p< 0.0001). The correct management of VFFs is mandatory to improve pain and reduce disability, and our findings suggested a positive role of dynamic spinal orthosis to improve the comprehensive management of VFFs patients. However, high-quality research trials are warranted to provide clear recommendations for the correct clinical management of VFF.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Australasian Recurrent Pregnancy Loss Clinical Management Guideline 2024 Part I.

Guidelines for the investigation and management of recurrent pregnancy loss (RPL) have been developed in Europe, USA and UK, but there is currently no Australasian guideline. The Australasian Certificate of Reproductive Endocrinology and Infertility Consensus Expert Panel on Trial Evidence group has prepared a two-part guideline to provide guidance on the management of RPL. In Part I chromosomal, anatomical, and endocrine factors are outlined along with relevant recommendations for clinical management, levels of evidence and grades of consensus. In Part II thrombophilia, autoimmune factors, infective, inflammatory, and endometrial causes, environmental and lifestyle factors, male factor and unexplained causes will be outlined.

IMG-07. PEDIATRIC CRANIAL INCIDENTALOMAS: A SYSTEMATIC REVIEW UTILIZING MACHINE LEARNING

Abstract BACKGROUND The use of diagnostic neuroimaging in the care of pediatric patients continues to increase, leading to a rise in incidentally discovered lesions. The understanding of appropriate assessment and management of these findings is critical to providing comprehensive and timely care. This review aims to analyze the current literature to characterize diagnostic and prognostic characteristics of incidentally found brain tumors in pediatric patients. METHODS Using the guidelines under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), Pubmed and Medline (NCBI) databases were searched using selected keyword combinations and machine learning-assisted software. Case reports, case series, and retrospective cohort studies published up to December 2023 were included. RESULTS A total of 20 studies encompassing 627 patients were included in the review. The most common indications for imaging were headache (204; 33%), seizures (96; 15%), and trauma (78; 12%). Of studies providing information regarding localization, lesions were found in the supratentorial region in 327 (52%) cases and infratentorial region in 190 (30%). Of studies reporting imaging characteristics, T1 hypointensity (183/302; 61%), T2 hyperintensity (410/497; 82%), and no contrast enhancement (58/97; 60%) were the most common findings. Four hundred and thirty (68%) patients were observed after diagnosis, 83 (13%) patients underwent surgical intervention at diagnosis, and 40 (6%) patients underwent surgery after observation. Of 91 patients with histopathology data available, pilocytic astrocytoma (19; 21%) was most commonly reported. CONCLUSION In this study, we provide a review of diagnostic characteristics of incidentally discovered brain tumors in the pediatric population. Management of such lesions has changed greatly over the past several decades, and risks of surgical intervention should be weighed against a more conservative management and interval monitoring approach. These results may help guide discussions regarding disclosure of findings and recommendations for additional clinical management.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years

PurposeThe Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including...

Interpretation of Chinese guideline for the clinical management of patients with unruptured intracranial aneurysms (2024)

With the popularization of cerebrovascular imaging technology, the clinical detection rate of unruptured intracranial aneurysm (UIA) is increasing. UIA has a low risk of rupture, but once ruptured, it can seriously affect human health. The treatment of UIA is highly controversial and has attracted widespread clinical attention. The Society of Neurosurgery of the Chinese Medical Association, the Society of Cerebrovascular Surgery of the Chinese Stroke Association, the National Center for Neurological Diseases, and the National Center for Clinical Research on Neurological Diseases jointly formulate "Chinese guideline for the clinical management of patients with unruptured intracranial aneurysm management (2024)", which adopts a modular format, highlighting management recommendations and indicating current research deficiencies and future research directions. It provides comprehensive clinical management recommendations on UIA epidemiology, population screening, clinical imaging and diagnosis, rupture risk assessment, treatment decisions and choices, postoperative follow-up, and long-term management. The evidence sources are divided into the Chinese population and other populations, which helps guide clinical practice in China.

Smoking and pathogenic germline variants in patients with lung cancer.

8040 Background: Few studies have investigated the correlation of smoking history with pathogenic germline variants (PGVs) in patients diagnosed with lung cancer. With emerging opportunities for PGVs in DNA damage-repair (DDR) genes to inform precision therapies, we investigated the prevalence of PGVs in patients with lung cancer, stratified by smoking status. Methods: Germline genetic testing (GGT) (Invitae Corp.) and insurance claims (Komodo Healthcare MapTM) data were reviewed for 14,317 patients with an ICD code for lung cancer from 2015-2023 and hereditary cancer GGT of ≥ 10 genes. PGV rates were assessed overall, in DDR genes and in lung cancer related genes. Smoking history was defined by ICD codes. Number of genes tested varied per ordering clinician preference. Clinically actionable PGVs were defined as those associated with clinical management recommendations or trial eligibility per current standard of care guidelines. Chi-square tests were used with significance set to p &lt; 0.05. Results: The cohort was predominantly female (70.9%), white (65.7%), and over half had a history of smoking (57.1%). PGVs in 73 known cancer-risk genes were identified in 1,804/14,317 (12.6%) patients. Frequencies of PGV were 12.6% (1,026/8,175) in patients with smoking history compared to 12.7% (778/6,142) in those with no reported smoking history. There was no statistically significant difference in DDR gene, TP53, or EGFR PGV rates for patients with or without smoking history (p &gt; 0.05). Mean (SD) age of lung cancer diagnosis was significantly younger for patients with a history of smoking and DDR PGVs (61 (11)) compared to those with negative results (62 (12), p = 0.005). There was no significant difference in age of diagnosis between patients with no smoking history and DDR PGVs (60 (12)) and those with negative results (59 (13), p = 0.888). PGV rates by clinician-reported ancestry: Black/African-American, 9%; Asian or Pacific Islander, 11%; Hispanic, 12%; White, 13%. Among genes with &gt; 1,000 patients tested, PGVs were most common in BRCA2 (2.2%), CHEK2 (2.0%), ATM (1.6%), SPINK1 (1.6%), and BRCA1 (1.2%). Conclusions: In 14,317 patients with lung cancer, 12.6% had PGVs. There was no significant difference in enrichment of PGVs in DDR genes when patients were stratified by reported smoking history, suggesting the enrichment of these genes is independently associated with lung cancer. The age of onset for patients with DDR gene PGVs varied with smoking history, suggesting that risk conferred by these PGVs could be additive to smoking risk. These data reinforce prior studies supporting consideration of GGT for all patients with lung cancer, independent of age or reported smoking history.

A Guide to the Clinical Management of Vipera Snakebite in Italy.

The genus Vipera encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of Vipera snakebite tailored for Italian clinicians. It includes taxonomic keys for snake identification, insights into viper venom composition, and recommendations for clinical management. Emphasis is placed on quick and reliable identification of medically relevant snake species, along with appropriate first aid measures. Criteria for antivenom administration are outlined, as well as indications on managing potential side effects. While the protocol is specific to Italy, its methodology can potentially be adapted for other European countries, depending on local resources. The promotion of comprehensive data collection and collaboration among Poison Control Centres is advocated to optimise envenomation management protocols and improve the reporting of epidemiological data concerning snakebite at the country level.

The clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in patients with lung adenocarcinoma

BackgroundThe treatment of non-small cell lung cancer (NSCLC) patients can be complicated by the presence of the EGFR-T790M mutation. Although primary or secondary EGFR-T790M mutations have been extensively studied worldwide, there are few reports on the clinicopathological characteristics and physiological mechanisms of lung adenocarcinoma (LUAD) with only the EGFR-T790M primary mutation. MethodsThe clinical data of all LUAD patients with only the EGFR-T790M primary mutation were collected. Immunohistochemical staining was performed on cell cycle-related proteins, targeted therapy indicators, and prognosis-related proteins in the specimens obtained from puncture biopsies or surgeries. ObjectivesThe aim of this study is to analyze the clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in LUAD, and to offer recommendations for clinical management. ResultsTwo patients who have only the T790M de novo mutation were both female (2/12,928, 0.02%). β-catenin and Cyclin D1 were both highly expressed. In case 1, IHC results showed a positive Ki67 and mutant P53 and there was a significant increase in serum CYFRA 21–1. Third-generation of EGFR TKIs resulted in a partial response (PR) time of less than 8 months in case 1. In case 2, the patient underwent surgical resection and adjuvant chemotherapy, resulting in a progression-free survival (PFS) time of 25 months. ConclusionThe results suggest that abnormal activation of the Wnt signaling pathway may be specifically associated with the EGFR-T790M primary mutation in LUAD. Furthermore, it has been observed that patients with significant Ki67, mutant P53, and CYFRA 21–1 expression tend to have a poor prognosis.