Clinical Management Of Patients Research Articles

Leveraging Generative AI to Accelerate Biocuration of Medical Actions for Rare Disease.

Structured representations of clinical data can support computational analysis of individuals and cohorts, and ontologies representing disease entities and phenotypic abnormalities are now commonly used for translational research. The Medical Action Ontology (MAxO) provides a computational representation of treatments and other actions taken for the clinical management of patients. Currently, manual biocuration is used to assign MAxO terms to rare diseases, enabling clinical management of rare diseases to be described computationally for use in clinical decision support and mechanism discovery. However, it is challenging to scale manual curation to comprehensively capture information about medical actions for the more than 10,000 rare diseases. We present AutoMAxO, a semi-automated workflow that leverages Large Language Models (LLMs) to streamline MAxO biocuration for rare diseases. AutoMAxO first uses LLMs to retrieve candidate curations from abstracts of relevant publications. Next, the candidate curations are matched to ontology terms from MAxO, Human Phenotype Ontology (HPO), and MONDO disease ontology via a combination of LLMs and post-processing techniques. Finally, the matched terms are presented in a structured form to a human curator for approval. We used this approach to process 4,918 unique medical abstracts and identified annotations for 21 rare genetic diseases, we extracted 18,631 candidate disease-treatment curations, 538 of which were confirmed and transferred to the MAxO annotation dataset. The results of this project underscore the potential of generative AI to accelerate precision medicine by enabling a robust and comprehensive curation of the primary literature to represent information about diseases and procedures in a structured fashion. Although we focused on MAxO in this project, similar approaches could be taken for other biomedical curation tasks.

Non-malarial febrile illness: a systematic review of published aetiological studies and case reports from China, 1980–2015

BackgroundRapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy.MethodsA systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980–2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ – Chinese Science Citation Database SM, The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection.ResultsA total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China.ConclusionsThis review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country.

Clinical characteristics and management of patient with portal hypertension at tertial level hospital in Tanzania

BackgroundPortal hypertension is a common diagnosis in Sub-Saharan African countries, with the majority of patients presenting late. This study aimed to understand Clinical characteristics, aetiology, the treatment offered in our setting, and factors associated with portal hypertension at a tertiary-level hospital, in Tanzania.MethodologyA prospective cross-sectional observational single hospital-based study was conducted at MNH, from May 2021 to April 2022. A minimum of 152 subjects were required with an error of less than 5% and a study power of 80% at a 95% confidence interval. A structured questionnaire was used to collect data. Ethical clearance was obtained from the MUHAS/MNH IRB.ResultsA total of 154 eligible participants consented and participated in this study. The mean age of participants was 42 ± 15.8 years (range 2–87). Most of the study participants were males 64.9% with a male-to-female (M: F) ratio of 1.8:1. Vomiting blood was the common symptom among the study participants 51.3%. Schistosomiasis 53.9% and viral infection 26.6% were the common etiologies followed by alcohol abuse 7.8%. Most were medically treated at 89.61% followed by radiological treatment at 8.44% while only 1.95% of patients received surgical treatment. There was a significant association between the grade of oesophagal varices and bleeding consequences (p-value < 0.01).ConclusionThe majority of patients were medically treated while patients who require surgical care are unable to assess it. We recommend the establishment of a transplant services program to counteract the unmet need and more retrospective research toward policy establishment.

Role of COVID-19 Vaccine in the Management of Gynecologic Oncology Lymphadenopathies.

This study aimed to evaluate the incidence of lymphadenopathies after COVID-19 vaccination and their impact on the clinical management of gynecologic oncology patients. A retrospective observational study was conducted involving patients who underwent abdominopelvic or thoracoabdominopelvic CT scans during diagnosis or follow-up. Patients were classified into a vaccinated group (Vac group) and a non-vaccinated group (NoVac group). The radiological appearance of lymphadenopathies was categorized as low or high risk of malignancy, and management strategies were recorded as standard management or additional assessment. 75 patients were included, with 44 in the Vac group and 31 in the NoVac group. The incidence of lymphadenopathies was similar between the groups: 34.1% in the Vac group and 32.3% in the NoVac group (p = 0.868). High-risk lymphadenopathies were observed in 20.4% of the Vac group and 22.6% of the NoVac group, while low-risk lymphadenopathies were seen in 13.6% of the Vac group and 9.7% of the NoVac group (p = 0.691). Standard management was the most common approach, used in 80.0% of the Vac group and 100.0% of the NoVac group (p = 0.25). COVID-19 vaccine does not increase the incidence of lymphadenopathies in imaging tests of gynecological cancer patients.

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

BackgroundA definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022.MethodsThe study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender.ResultWe studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs. 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs. VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010).ConclusionsAdministration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies.

Delphi consensus recommendations on treatment for advanced-stage marginal zone lymphoma in South Korea.

Due to the lack of treatment guidelines for the management of advanced-stage marginal zone lymphoma (MZL), only one chemoimmunotherapy-cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-is reimbursed in the first-line setting in South Korea. The aim of this study was to develop a consensus-based recommendation for the treatment of patients with advanced-stage MZL. Twelve hematologist oncologists participated in a two-round Delphi process to identify consensus on the management of patients with advanced-stage MZL in South Korea. Physicians rated their level of agreement with each statement on a four-point Likert scale. Statements were divided into two sections: definitions used in clinical practice and clinical management of patients with advanced-stage MZL. Consensus was reached for 23 of 33 (69.7%) and 5 of 13 statements (38.5%) in rounds 1 and 2, respectively. There was strong consensus (91.7%) that advanced-stage MZL subtypes are defined according to the Lugano staging system. First-line systemic treatment should be prescribed for patients with symptomatic advanced-stage MZL. Although there was unanimous agreement that R-CVP is the standard first-line treatment for advanced-stage MZL, physicians also agreed that bendamustine with rituximab (BR) has greater efficacy than R-CVP as first-line treatment (91.7%). For the treatment of relapsed/refractory advanced-stage MZL, BR and R-CVP can be repeated in patients with short (< 24 months) and long remission periods (≥ 24 months), respectively. This study provides insights on the management of patients with advanced-stage MZL in South Korea. This may enhance clinical decision-making, thus improving patient outcomes.

Comparison of gastrointestinal bleeding in patients with and without liver cirrhosis

Objectives Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics. Methods A retrospective study on cirrhotics hospitalized for GIB 2010–2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included. Results Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6–32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% (p = 0.002), less commonly gastric ulcer 13% vs. 31% (p < 0.001), duodenal ulcer 9% vs. 29% (p < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls (p < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls (p < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls (p < 0.001) Conclusions Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Genomic analysis of &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; strains virulence and antibiotic resistance

Recently, Klebsiella pneumoniae strains have become widespread both in community-acquired infectious processes and in nosocomial infections. There are two pathotypes of K. pneumoniae: classical (cKp) and hypervirulent (hvKp). Representatives of any pathotype are prone to acquire and further transmit genetic factors of antibiotic resistance and virulence. This combination accounts for severity of the infectious process. Therefore, information about whether the strain belongs to either pathotype can help in prescribing proper therapy. Since there is no consensus upon hypervirulence marker, we attempted to find the most significant combinations of genetic markers of virulence and antibiotic resistance in K. pneumoniae strains. The study was aimed to conduct a genomic analysis of virulence and antibiotic resistance of K. pneumoniae clinical isolates. Materials and methods. There were examined 85 strains of K. pneumoniae isolated from diverse clinical material samples from patients in large St. Petersburg hospitals. In our work, we used classical bacteriological methods, including determination of the hypermucoviscous type using the “string test”, the mass spectrometric method (MALDI-ToF MS) for identifying bacteria, molecular methods for studying markers of virulence and antibiotic resistance (multilocus sequence typing, genome sequencing of K. pneumoniae strains). Results. Among the studied K. pneumoniae strains, the most common carbapenemase genes were OXA-48 (18.7%) and NDM-1 genes — 17.3% of strains; in 6.7% of strains, NDM-1 and OXA-48 genes were found simultaneously. The percentage of strains with β-lactamase genes CTX-M-15 was 54.7%, OXA-1 — 17.3%, TEM-1D — 13.3%, and in 17.3% of cases the OXA-1 and TEM-1D genes were simultaneously present in bacterial strains. Quinolone resistance genes were found in 68.4% of strains. The most common genes were qnrS1 (40% of strains) and qnrB1 (22.7%). Phenotypic antimicrobial susceptibility testing showed that 23.5% and 64.7% strains were resistant to colistin and carbapenems, respectively. 32.9% K. pneumoniae strains, isolated in patients with phlegmon, pneumonia, sepsis, and peritonitis, had a hypermucoid phenotype. The most common sequence types were: ST395 (24.3%), ST23 (17.6%) and ST512 (9.5%). 8% and 25.3% of strains belonged to capsule types K1 and K2, respectively. The polyketide synthesis locus ybt, which characterizes virulent strains, was detected in 69.3% isolates, and the clb locus was present in 10.7% of strains. In 73.3% and 14.7% strains, the plasmid-associated virulence loci iuc and iro were identified, which encode the biosynthesis of the siderophores aerobactin and salmochelin. We described 44 cases (58.7% of strains) of genotypic convergence of virulence and antibiotic resistance, as shown by simultaneously detected the aerobactin (iuc) locus and β-lactamase or carbapenemase genes. Thus, identification of hypervirulence may provide valuable information for the clinical management of patients with hvKp infections. Therefore, it is is obviously necessary to develop comprehensive diagnostic test for simultaneous screening of multidrug-resistant hypervirulent K. pneumoniae strains.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. 68Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Prevalence of cardiovascular autonomic neuropathy in an admixed population of patients with type 1 diabetes. Lessons from a pioneer multicentre study in Brazil

AIMSTo evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) and its associated factors in Brazilian patients with type 1 diabetes (T1D). MethodsThis cross-sectional, multicentre study was conducted in 14 public clinics in ten Brazilian cities. From 1760 patients, 1712 were included (97.3 %): 953 females (55.7 %), 930 (54.3 %) Caucasians, aged 29.9 ±11.9 years and with diabetes duration of 15.4 ± 9.2 years. CAN was evaluated using cardiovascular autonomic reflex tests. ResultsThe prevalence of CAN was 23.4 %. Multivariable hierarchical logistic regression showed CAN associated with age, smoking, lower socioeconomic status, higher yearly medical appointments, insulin therapeutic regimens, higher levels of HbA1c, total cholesterol, uric acid, diastolic blood pressure and heart rate, presence of retinopathy, diabetic kidney disease and a tendency to be associated with severe hypoglycemia. Lower health-related quality of life was also found in univariate analysis in these patients. ConclusionsPatients with T1D presented an important prevalence of CAN that was associated with other diabetes-related chronic complications, and also with demographic, clinical and laboratorial traditional risk factors. Considering lack of formal policy, our data could be used for guiding public health approach to awareness and CAN’s screening, diagnosis and clinical management in patients with T1D in Brazil.

Hybrid FDG-PET/MRI for Diagnosis and Clinical Management of Patients with Suspected Perihilar Cholangiocarcinoma: A Feasibility Pilot Study

Hybrid FDG-PET/MRI for Diagnosis and Clinical Management of Patients with Suspected Perihilar Cholangiocarcinoma: A Feasibility Pilot Study

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers

ObjectiveThe present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and MethodsFifty-six patients (age: 18–80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student’s t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC

Factors Influencing the Self-Management Stages of Older Patients With Chronic Pain: A Cross-Sectional Study

PurposeTo investigate the current status and related influencing factors of self-management stages in older patients with chronic pain. DesignA cross-sectional study. MethodsA total of 326 older patients with chronic pain were selected as the study subjects in five city districts from December 2022 to June 2023. We used a general information survey form, a numerical rating scale, a pain stages of change questionnaire, a health literacy assessment instrument for patients with chronic pain, and a psychological inflexibility in pain scale to collect relevant information from participants. Univariate analysis and multiple ordinal logistic regression analysis were conducted to identify the relevant influencing factors of the self-management stages. ResultsThe self-management stages of older patients with chronic pain were as follows: precontemplation stage (n = 52; 16.0%), contemplation stage (n = 103; 31.6%), action stage (n = 62; 19.0%), and maintenance stage (n = 109; 33.4%). Regression results showed that average monthly household income, smoking history, pain duration, health literacy, and psychological inflexibility were the influencing factors for the self-management stages of older patients with chronic pain. ConclusionsIn this study, the self-management stages of older patients with chronic pain still needed to be improved. Suitable personalized pain self-management strategies should be developed based on identified factors affecting patients to improve their self-management stages. Clinical ImplicationsNursing professionals can use research survey findings to identify patients at low levels of self-management stage and develop personalized intervention strategies based on various influencing factors. For example, nurses can provide practical smoking cessation guidance to assist older chronic pain patients in improving their lifestyle. Nurses can also seek support from family members to collectively offer better medical care and nursing services for the patient if financially feasible. Secondly, as our study has demonstrated, patients' health literacy and psychological flexibility were poor. Nurses can utilize available clinical resources to offer educational materials, such as portable handbooks and online videos, covering pain-related knowledge, managing pain medication, and coping strategies like massage and exercise. Combining this approach with mental health education, such as relaxation therapy, can help patients better understand their pain and actively participate in their self-management. In addition, nursing staff should pay more attention to the self-management stages of older chronic pain patients, and the assessment of self-management stages can be included in clinical pain management for patients. Regular assessment will help track more patients needing attention and make timely adjustments to their pain management plans.

Evaluating the role of sarcopenia and [18F]FDG PET/CT parameters in prognosis of pancreatic ductal adenocarcinoma

This study investigates the relationship between 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters, clinicopathological characteristics, and sarcopenia in patients with pancreatic ductal adenocarcinoma (PDAC) and evaluates their prognostic roles. Material and methodsThe primary tumor's maximum standard uptake (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values, as well as clinicopathological factors, were evaluated retrospectively. Computed tomography (CT) was used to assess the skeletal muscle index (SMI). Sarcopenia was defined based on SMI calculated at the third lumbar vertebra (L3). SMI cut-off values ​​for sarcopenia were accepted as 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. The primary endpoint was the overall survival (OS). OS data were analyzed by the Kaplan-Meier method and compared using the log-rank test. To identify predictive factors for sarcopenia, multivariable logistic regression was used following univariable logistic regression. Cox proportional hazards regression analyses were used to find predictors of OS. ResultsOf the 86 patients included in the study, 37 (43%) were diagnosed with sarcopenia. Compared with non-sarcopenic patients, sarcopenia was observed in older patients (P=0,028) and patients with lower body mass index (BMI) (p=0,001). Age and BMI independently predicted sarcopenia. Univariate analysis identified sarcopenia, advanced stage, and higher primary tumor TLG as significant predictors of overall survival. Multivariate Cox regression analysis revealed that the advanced tumor stage (p=0.017) and higher TLG (p=0,042) independently predicted OS. The median OS was 9.4 months in non-sarcopenic patients and 5.0 months in sarcopenic patients (p=0,021). ConclusionIn this study cohort, advanced-stage disease and higher primary tumor TLG were identified as independent predictors of OS in patients with PDAC. Additionally, we emphasize the importance of incorporating [18F]FDG PET/CT-derived sarcopenia assessments into the prognostic evaluation and clinical management of PDAC patients. While sarcopenia was associated with shorter OS in univariate analysis, it was not an independent predictor in multivariate analysis.

Validation of Artificial Intelligence in the Classification of Adolescent Idiopathic Scoliosis and the Compairment to Clinical Manual Handling.

The accurate measurement of Cobb angles is crucial for the effective clinical management of patients with adolescent idiopathic scoliosis (AIS). The Lenke classification system plays a pivotal role in determining the appropriate fusion levels for treatment planning. However, the presence of interobserver variability and time-intensive procedures presents challenges for clinicians. The purpose of this study is to compare the measurement accuracy of our developed artificial intelligence measurement system for Cobb angles and Lenke classification in AIS patients with manual measurements to validate its feasibility. An artificial intelligence (AI) system measured the Cobb angle of AIS patients using convolutional neural networks, which identified the vertebral boundaries and sequences, recognized the upper and lower end vertebras, and estimated the Cobb angles of the proximal thoracic, main thoracic, and thoracolumbar/lumbar curves sequentially. Accordingly, the Lenke classifications of scoliosis were divided by oscillogram and defined by the AI system. Furthermore, a man-machine comparison (n = 300) was conducted for senior spine surgeons (n = 2), junior spine surgeons (n = 2), and the AI system for the image measurements of proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L), thoracic sagittal profile T5-T12, bending views PT, bending views MT, bending views TL/L, the Lenke classification system, the lumbar modifier, and sagittal thoracic alignment. In the AI system, the calculation time for each patient's data was 0.2 s, while the measurement time for each surgeon was 23.6 min. The AI system showed high accuracy in the recognition of the Lenke classification and had high reliability compared to senior doctors(ICC 0.962). The AI system has high reliability for the Lenke classification and is a potential auxiliary tool for spinal surgeons.

Kidney failure amongst Irish Travellers.

The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

Factors influencing healthcare workers' and health system preparedness for the COVID-19 pandemic: A qualitative study in Ghana.

Adequate preparedness of health systems, particularly healthcare workers (HCWs), to respond to COVID-19 is critical for the effective control of the virus, especially in low- and middle-income countries where health systems are overburdened. We examined Ghanaian HCWs' perceived preparedness to respond to the pandemic and the factors that shaped their preparedness and that of the health system. Semi-structured in-depth interviews were conducted with n = 26 HCWs responsible for the clinical management of COVID-19 patients and three administrators responsible for developing and implementing COVID-19 policies at the facility level. Interviews were conducted over the phone in English, transcribed, and analyzed using a thematic analysis approach. Generally, HCWs felt inadequately prepared to contain the spread of COVID-19 due to resource shortages and inadequate training. HCWs, similarly, perceived the health system to be unprepared due to insufficient clinical infrastructure and logistical challenges. The few who felt prepared identified readiness in managing high consequence infectious disease cases and pre-existing protocols as enablers of HCW preparedness. The health system and HCWs were unprepared to manage the COVID-19 pandemic due to inadequate training, logistical challenges, and weak clinical infrastructure. Interventions are urgently needed to improve the health system's preparedness for future pandemics.

Effects of Corticosteroid Treatment on Olfactory Dysfunction in LATY136F Knock-In Mice.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients. LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons. Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group. Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.

Clinical value of liquid biopsy in FGFR2 fusion-positive cholangiocarcinoma patients during targeted therapy.

FGFR2 fusions occur in 10%-15% of intrahepatic cholangiocarcinoma (iCCA) patients, potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. We conducted a retrospective study on 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of circulating tumor DNA (ctDNA) are linked to clinical benefits from targeted therapy and result in improved progression-free survival and (PFS) overall survival (OS). Higher concentrations of cell-free DNA (cfDNA) before FGFRi treatment were linked to worse OS, correlating with impaired liver function, and indicating compromised cfDNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared to standard radiological imaging methods. VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiological progression, offering valuable guidance for the clinical management of patients with iCCA.

SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.