Frequent Site Research Articles

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.

Five-year cancer survival rates in Monastir, Tunisia

Abstract Background Cancer is a major public health problem worldwide. To the best of our knowledge, there is no Tunisian population-based registry studies investigating cancer survival in Tunisia. The objectives of our study were to estimate the five-year cancer survival rates in the province of Monastir, Tunisia. Methods We performed a retrospective cohort study including patients originating from Monastir diagnosed with cancer between 2002 and 2014. Data were collected from the cancer register of the center. Patients were followed until December 2022. Results In total, 9318 cancer cases were identified of whom 5741 were included for the survival analysis. The 5-year cancer survival rate, all sites combined, was 46% (95% CI: 45-47.3). Among the 10 most frequent cancer sites in Monastir, cancers having the lowest 5-year survival rates were lung cancer in men (18.2% (95% CI: 15.6-20.7)) and stomach cancer in both sexes (32.1% (95% CI: 23.4-40.7) and 25.3% (95% CI: 16-34.5) in men and women respectively). The cancers with the highest 5-year survival rates among men were skin cancer (other than malignant melanoma) (64% (95% CI: 54.5-73.4)), prostate cancer (59.1% (95% CI:54.7-63.4)) and colon cancer (55.1% (95% CI: 47.7-62.4). In women, cervical cancer (70% (95% CI: 61.8-78.1), skin cancer (other than malignant melanoma) (66.2% (95% CI: 55.1-77.2) and breast cancer (63.8% (95% CI:58.8-67.7)) were those with the highest 5-year survival rates. Patients ≥ 65 years had the lowest 5-year survival rates for almost all cancer sites in both genders. Conclusions Our study has shown that cancer survival rates in Tunisia remain low compared to developed countries. The widespread implementation of cancer control programs including healthy lifestyle, education, screening and early detection are urgently needed. Key messages • The 5-year cancer survival rate, all sites combined, in Monastir was 46% (95% CI: 45-47.3). • Cancers with the lowest 5-year survival rates in Monastir were lung cancer in men and stomach cancer in both sexes.

CCR7 depletion alleviates bony growth imbalance following physeal injury in mice

Growth plates are the frequent sites of skeletal injury in children, leading to skeletal growth imbalances. Chemokines, including the receptor CCR7, play a crucial role in stem cell recruitment and cartilage homeostasis, with previous studies linking CCR7 to osteoarthritis progression. However, its role in growth plate cartilage remains unclear. We analyzed the role of CCR7 in the physeal cartilage repair process in mice model. Physeal injury was created in the proximal tibia in 3-week-old C57BL/6 mice (WT) and CCR7-knockout mice (CCR7−/−). Tibial length was measured macroscopically and sections of the physeal injury were analyzed histologically and immunohistochemically. Height and bone volume of the tibial growth plate and bone mineral density (BMD) of the subchondral area were measured by micro-CT. Mesenchymal stem cells (MSCs) were harvested and gene expression after osteogenic differentiation was analyzed using qRT-PCR. At 1, 3 and 5 weeks postoperatively, injured tibiae of CCR7−/− mice were less shortened than those of WT mice. Bone volume of the physeal bridge was significantly lower in CCR7−/− mice than in WT mice. In contrast, BMD of the subchondral area was comparable between CCR−/− and WT mice, and between sham and operated tibiae. In osteogenic differentiation, CCR7−/− mice showed significantly lowered expression of osteogenic markers such as Osterix, Runx2 and Type X collagen. We demonstrated CCR7 depletion in mice inhibited physeal bridge formation and ameliorated growth imbalances after physeal injury.

Clinical features of chronic tibial osteomyelitis: a single-center retrospective study of 282 cases in Xinjiang, China.

Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang. A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification. Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41-50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA. Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.

Clinical and epidemiological characterization of infections in pediatric hemato-oncology patients with febrile neutropenia in the North of Mexico

Abstract Background Neutropenic fever is the most common complication in patients undergoing chemotherapy, where the choice of empirical antibiotic treatment should be based on the probable focus of infection, the predominant causative microorganisms, and the sensitivity of those organisms to antibiotics, which varies between each hospital and region. Over time, the spectrum of isolated microorganisms in different clinical syndromes of patients presenting during their infectious episode has changed. Our objective is to describe the prevalence of infectious etiology in pediatric patients with neutropenic fever, as well as the clinical characteristics of patients with documented infection. Methods The study design is ambispective, observational, and descriptive of a cohort type. Patients between 0 and 18 years old from the pediatric department of the “Dr. José E. González” University Hospital will be included from May 2019 to June 2023, with hematological-oncological disease during their febrile neutropenia infectious process with a complete medical record. Results A total of 326 episodes of febrile neutropenia were included, of which 15% had microbiological isolation (49 patients). The etiological classification during the events was as follows: bacteria 81%, viruses 14%, and fungi 4%. Five different infection sites were identified. Among these, bacteremia were the most frequent site of infection (10%), followed by gastrointestinal infections (2.4%), respiratory infections (1.5%), skin and soft tissue infections (1.2%), and lastly, urinary tract infections (1%). A total of 45 microorganisms were isolated from different infection sites. Among these, gram-negative bacteria (28 isolates, 62%) were more common and outnumbered gram-positive bacteria (14 isolates, 31%). Among gram-negatives, Escherichia coli (42%) was the most common isolate, followed by Pseudomonas aeruginosa (17%), and Klebsiella pneumoniae (14%). Among gram-positives, Streptococcus mitis (28%), Coagulase-negative Staphylococcus (21%), and Rothia mucilaginosa (14%) were identified. Conclusion Febrile neutropenia at the Hospital Universitario primarily affects 6-year-old males with ALL. The microbiological characterization suggests the intentional search for gram-negative bacteremia, allowing us to direct timely and targeted antibiotic therapy to influence clinical prognosis. It is worthwhile to continue the research line that allows us to identify susceptibility and resistance profiles to address these patients more effectively.

Longitudinal tooth fracture indicating a questionable prognosis for an endodontist

Introduction and Objectives: Longitudinal fracture or vertical fracture of a tooth occurs at any level in the root and extends vertically. It has a high incidence of occurrence in the first molars. The most frequent sites to occur are the buccolingual surface and proximal surfaces of teeth. The etiology of fracture involves different factors in endodontically treated and non-endodontically treated teeth. Longitudinal fractures become the most challenging to diagnose and treat. This paper reviews these aspects of challenges and discusses the advantages and limitations of dental materials used for the treatment. Review Methods: PubMed and Google Scholar databases were searched for articles on longitudinal tooth fractures between 2007 and 2022. The 16 current articles were selected. Brief Description of the State of Knowledge: As per the review of the literature, longitudinal fracture of the tooth is the most common fracture to occur due to excessive forces on the root canal-treated tooth. This occurs in endodontically treated teeth due to long-term application of calcium hydroxide, cracks caused during root canal preparation extended by the pressure of root canal obturation, and in non-endodontically treated teeth due to cyclic and heavy masticatory stress, and habitual chewing of hard food especially in males. Summary: Functional and esthetic outcomes following longitudinal fracture treatment are important considerations in the case of anterior teeth. Longitudinal fracture or vertical fracture of a tooth occurs mostly in the first molars. It is crucial to identify and manage actors for good prognosis, as restoration at a time can reduce fracture extension prevent microleakage.

Malignant Non-Odontogenic Tumors of the Oral Cavity – Single Institutional Retrospective Study of Three Decades

Abstract Malignant non-odontogenic tumors of the oral cavity remain understudied in India, despite their global prevalence. This retrospective analysis examined cases from a single institution in Maharashtra between 1990 and 2021, focusing on patient demographics, clinical presentations, and histopathological features. Oral squamous cell carcinoma (OSCC) emerged as the predominant malignancy, with epithelial malignancies accounting for 98.6% of cases. A slight male predominance was observed. Buccal mucosa was the most frequent site of occurrence, with tobacco chewing identified as the primary risk factor. This study underscores the need for increased attention to oral malignancies in routine medical examinations and calls for more comprehensive statistical analysis to inform clinical practice and public health strategies.

Human papillomaviruses in hand squamous cell carcinomas from Chilean patients

IntroductionCutaneous squamous cell carcinoma (SCC) accounts for 20% of all skin cancers and its incidence continues to increase globally. It represents 75% of non-melanoma skin cancer (NMSC) mortality. Risk factors include ultraviolet radiation (UVR) exposure, advanced age, chemical exposure, fair skin types, and immunosuppression. While most human papillomavirus (HPV) infections are associated with the development of warts, a subgroup is potentially implicated in the development of cutaneous SCC. The prevalence of alpha, beta, and gamma-HPV in Chilean patients with hand SCCs has not been previously addressed. The objective of this study was to evaluate the presence of HPV and genotyping in hand SCC from Chilean patients.Materials and methodsAn observational, cross-sectional, descriptive study was conducted. Alpha (α), beta (β) and gamma (γ)-HPV detection was performed by conventional polymerase chain reaction (PCR) in paraffin-embedded tissue samples from 52 patients diagnosed with hand SCC from Santiago, Chile. HPV genotyping was carried out via direct amplicon sequencing by Sanger method.ResultsThe most frequent carcinoma site was the dorsum of the hands (52.5%). α-HPV was not detected in these specimens, whereas β-HPV and γ-HPV were detected in 25% of the analyzed samples. The most frequent genotypes found were β-HPV 100 (38%) and γ-HPV 178 (15%). Additionally, γ-HPV 101, 162, HPV-mSK_016, HPV-mSK_083, HPV-mSK_213 and HPV-mSK249nr genotypes were detected, none of which had been previously described in cutaneous SCC.Conclusionβ-HPV and γ-HPV are detectable in 25% of hand SCCs from Chilean patients. It is important to conduct prospective studies to better elucidate the role of these viruses in the development of this disease.

Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study.

The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections. US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥72hours for a Gram-negative bacterial infection (November 2020-March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics. This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8-18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases. Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.

Atypical fractures at non-classical sites associated with anti-resorptive therapy: A Systematic Review.

Osteoporosis is common, affecting more than 20% of women and 6% of men globally over the age of 50 (1). Anti-resorptive drugs, bisphosphonates and denosumab, have been effective treatments for osteoporosis for more than 30years. Rare complications of anti-resorptive therapy include medication-related osteonecrosis of the jaw and atypical femur fractures (AFF). The American Society for Bone and Mineral Research (ASBMR) proposed a case definition for these atypical femoral fractures in 2010, which was updated in 2013. However, atypical fractures at non-classical sites have been increasingly described. We aimed to systematically identify atypical fracture cases, excluded from the ASBMR AFF case definition in patients receiving anti-resorptive medication for longer than three years. A structured search of electronic databases, including PubMed, Medline (Ovid), Embase (Ovid), Cochrane and Web of Sciences, and hand-searching of conference abstracts was undertaken. All full-text articles written in English describing an atypical fracture in patients (aged >18years) and receiving anti-resorptive medication for >3years were included, with data extracted and analysed by two independent reviewers. Sixty-six articles were identified, describing 151 cases of atypical fractures in 114 individuals. The most frequent fracture site was the ulna, followed by the tibia. All patients were taking anti-resorptive treatment prior to or at the time of fracture, most frequently alendronate monotherapy (44%). Most commonly, fractures were transverse in nature (95%), following minimal or no trauma (96%), non-comminuted (98%) with cortical thickening of the surrounding bone (69%). Anti-resorptive treatment was ceased following atypical fracture in the majority (89%). Atypical fractures are rare and should not deter physicians from appropriate anti-resorptive therapy for osteoporosis. However, clinicians should be alert to their presence, at additional sites to the femur. An update of the current ASBMR AFF case definition to include other skeletal sites could be timely.

Microbiology of Actinomyces Species Isolated From Patients With Invasive Disease and Contaminated Samples in a Comprehensive Cancer Center.

Actinomyces are mucous membrane commensals that infrequently cause invasive disease. Our goal was to define Actinomyces species prevalence, the predominant disease site and risk factors for actinomycosis. We retrospectively reviewed patients with growth of Actinomyces species from cultures in a single-cancer center from July 2007 to June 2020. Proven invasive actinomycosis was defined as the presence of compatible clinical syndrome and radiographic findings with histopathological confirmation or culture from a normally sterile site. Probable invasive actinomycosis was defined based on the same criteria but without histologic confirmation. Contaminants were defined as culture growth in the absence of clinical or radiological findings consistent with disease. Speciation of Actinomyces was performed by the bioMerieux VITEK 2 anaerobic and coryneform identification card. Of 235 patients, 179 (76.2%) had malignancy. Among 90 (38.3%) patients with invasive actinomycosis, A odontolyticus was isolated in 32 (35.6%), followed by A meyeri in 20 (22.2%), and A naeslundii in 17 (18.9%). Among 145 (61.7%) colonized patients, A odontolyticus was isolated in 67 (46.2%), followed by A naeslundii in 27 (18.6%). Abdominopelvic infection was the most common site for invasive actinomycosis documented in 54 patients (60.0%) followed by orocervicofacial in 14 (15.6%) and thoracic in 10 (11.1%). A odontolyticus, A meyeri, and A naeslundi were the most frequently isolated species causing invasive actinomycosis, and A odontolyticus and A nauslendii among colonizers. Abdominopelvic represented the most frequent site for invasive disease. Further studies are needed to investigate the epidemiology of Actinomyces species in this population.

Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.

Clinical, Histologic, and Therapeutic Pattern of Posterior Fossa Tumors in Children in Cameroon: A Cross-sectional Study.

Posterior fossa tumors are significant in pediatric neurooncological populations due to their frequency and morbimortality. We convey a 10-year experience managing pediatric posterior fossa tumors at two reference centers in Cameroon. We conducted a cross-sectional study with data collected retrospectively in the Neurosurgery Department of the Central and General Hospitals of Yaounde from January 2010 to December 2019. Included in the study were all patients aged 0-15 years who underwent surgery for posterior fossa tumors. We retained 43 pediatric posterior fossa tumor files, representing 47.89% of pediatric brain tumors. The male/female sex ratio was 0.86, with a mean age of 6.93 ± 4.345 years. The predominant clinical presentations were headaches + vomiting (97.7%), visual impairment (67.4%), and altered consciousness (14%). The vermis was the most frequent site affected (46.5%). Hydrocephalus was found to be associated with the tumor in 30 patients (69.8%). Tumor excision was total in 90.7% of cases, with cerebrospinal fluid diversion performed within the surgery in 83% of cases. Pilocytic astrocytomas represented 37.2%, medulloblastomas 30.25%, ependymomas 6.9%, and brainstem gliomas 4.6%. The postoperatory mortality rate was 20.9%. The survival rate at 5 years for medulloblastomas was 43%. Pediatric posterior fossa tumors are frequent. Pilocytic astrocytomas are the most common histologic type, followed by medulloblastomas. Radical surgery is the leading standard of care. Adjuvant treatment remains limited.

Intravitreal injection practice patterns among Chinese ophthalmologists.

To describe the practice patterns of intravitreal injections (IVIs) among ophthalmologists in China. This was a cross-sectional online survey. Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center, a hospital-based national network, to complete an anonymous, 24-question, internet-based survey. They were surveyed on practices in injection techniques, pre-, and post-injections procedures. A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey (50.68% response rate). The 91.29% of the respondents evaluated systemic risk factors by medical history, electrocardiogram (ECG) and blood test. All the respondents used pre-injection prophylactic antibiotics. Most checked intraocular pressure (IOP, 99.1%) and blood pressure (96.1%) before injections. A majority of the respondents performed injections in the operating room (98.8%), wore masks (99.7%), gloves (99.4%) and sterile surgical clothing (96.1%), performed topical anesthetics (97.9%), and applied povidone-iodine (95.8%) pre-injection. The 61.26% of the respondents dilated pupil. About half of the respondents (51.05%) performed bilateral injections in the same setting. Superior temporal quadrant (40.54%) was the most frequent site of injection. Around three quarters used 30-gauge needles. Most respondents (97.9%) measured the site of injection from limbus. More than half (53.45%) performed conjunctiva displacement prior to injection. The 32.43% of the respondents checked IOP post-injection and 87.99% physicians checked hand motion (HM) or counting fingers (CF) after injection, while 36.94% observed optic nerve perfusion. All participants used topical antibiotics post-injections. Most physicians (91.89%) reviewed patients on the following day. This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

A single-center retrospective review of metastatic prostate cancer on PSMA position emission tomography/computed tomography: Beyond lymph nodes and bones.

Prostate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT. All available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified. The most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement. Given the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.

Clinical Characteristics and Treatment Outcomes of Patients With Newly Diagnosed Takayasu Arteritis in Japan During the First 2 Years of Treatment - A Nationwide Retrospective Cohort Study.

This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

The role of 18FDG-PET imaging in VEXAS syndrome: a multicentric case series and a systematic review of the literature.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is characterized by heterogeneous clinical manifestations. Due to the inflammatory nature of this condition, 18-FDG-PET (18-fluorodeoxyglucose-positron emission tomography) might be used to diagnose and monitor the disease. However, no data are available about the most common findings of PET imaging in this disease. For this reason, we summarised all the available reports of patients with VEXAS who underwent at least one PET scan and described 8 additional patients' PET from our centres. Overall, we described 35 patients' PET findings. All patients were male, with a median age of 70years. The most frequent hypermetabolic sites on PET scans were the bone marrow (77.1%), lymph nodes (35.3%), lungs (28.6%), spleen and large vessels (22.9%), and cartilage (20%). Six patients underwent a PET scan 2.7 ± 1.5years before VEXAS diagnosis, showing nonspecific uptake in the bone marrow. Four patients had a follow-up PET scan, showing a decrease or a disappearance of the previously identified hypermetabolic areas. In conclusion, although no specific uptake site has been found for VEXAS syndrome, PET imaging could help detect inflammatory foci that are not clinically evident. In addition, high metabolic activity in bone marrow might precede the clinical onset of the disease, shedding light on the pathogenesis of VEXAS.

Clinical Outcomes of Carbon Ion Radiation Therapy for Malignant Peripheral Nerve Sheath Tumors

Purposeto investigate outcome and toxicity of patients affected by malignant peripheral nerve sheath tumors (MPNSTs) treated with high-dose carbon ion radiotherapy (CIRT). Patients and methodswe retrospectively analyzed the outcome of 23 patients with MPNST treated between July 2013 and December 2020. Out of these, 13 patients (56.5%) had incompletely resected tumors, 8 patients (34.7%) experienced recurrence after surgery, and 2 patients (8.7%) had unresectable tumors. Before CIRT treatment, 4 patients underwent a second surgery after the first local recurrence (LR), and 1 patient underwent a third surgery for the second local relapse of disease. Six (26%) of patients received neoadjuvant chemotherapy. The most frequent tumor site was brachial plexus (N=9; 39.1%). In five patients (21.7%) neurofibromatosis type 1 (NF1) disorder was found, while 4 patients (17, 4%) had radiation-induced MPNST. The median CIRT prescribed total dose was 69.8 Gy [RBE] (range, 54-76.8) delivered in a median of 16 fractions (range, 15-22). Eleven patients (47.82%) were treated according to a sequential boost protocol with a median prescribed dose to CTV-LR of 45 Gy[RBE] (range, 41.4 – 54). ResultsAfter a median follow-up time of 23 months (range 3-100 months), the OS rates at 1-year and 2-year were respectively: 82.38%, 61.51%. The 1-year and 2-year LRFS rates were respectively: 65.07%, 48.80%; the 1-year and 2-year PFS rates were respectively: 56.37%, 40.99%. No patients showed acute or late Grade 4 toxicity or any treatment-related deaths. Ten patients (43.48%) reported acute toxicities of Grade ≥2: dermatitis in 6 patients, mucositis in 2 patients, peripheral neuropathy in 4 patients. Eight patients (34.78%) reported late toxicities of Grade ≥2, mainly due to loco-regional neuropathy. Conclusionshigh dose CIRT shows favorable local effect with acceptable toxicities in patients with gross residual and LR after surgery, or unresectable malignant peripheral nerve sheath tumors. Advanced treatment modalities such as particle therapy should be considered for MPNSTs.

Functional substrate in patients with atrial fibrillation is predictive of recurrences after catheter ablation

BackgroundEnhanced characterization of the atrial electrical substrate may lead to better comprehension of atrial fibrillation (AF) pathophysiology. ObjectiveWith the use of high-density substrate mapping, we sought to investigate the occurrence of functional electrophysiologic phenomena in the left atrium and to assess potential association with arrhythmia recurrences after catheter ablation. MethodsSixty-three consecutive patients with AF referred for ablation were enrolled. Analysis of conduction abnormalities relied on 2 acquired left atrial electroanatomic maps (sinus and atrial paced rhythm). We classified conduction abnormalities as fixed (if these were present in both rhythms) or functional rhythm dependent (if unmasked in 1 of the 2 rhythms). Esophagus and aorta locations were recorded to check the correspondence with abnormal conduction sites. ResultsThere were 234 conduction abnormalities detected, of which 125 (53.4%) were functional rhythm dependent. The most frequent anatomic site of functional phenomena was the anterior wall, followed by the posterior wall, in sinus rhythm and the pulmonary venous antra in paced rhythm. Sites of functional phenomena in 82.6% of cases corresponded with extracardiac structures, such as sinus of Valsalva of ascending aorta anteriorly and the esophagus posteriorly. Most (88%) areas with functional phenomena had normal bipolar voltage. After pulmonary vein ablation, the number of residual functional phenomena is an independent predictor of AF recurrence (hazard ratio, 2.539 [1.458–4.420]; P = .001) with a risk of recurrences at multivariable Cox analysis. ConclusionDual high-density mapping (during sinus and paced rhythms) is able to unmask functional, rhythm-dependent phenomena that are predictive of AF recurrences during follow-up.

562. COMPARATIVE ANALYSIS OF THE OUTCOMES OF GASTRECTOMY VS. ENDOSCOPIC SUBMUCOSAL DISSECTION FOR THE TREATMENT OF GASTRIC TUBE CANCER AFTER ESOPHAGECTOMY

Abstract Background Although multimodal treatment and minimally invasive surgery for esophageal cancer have improved therapeutic outcomes for esophagectomy, this improvement has led to many reports of metachronous cancers following esophagectomy. After esophagectomy for esophageal cancer, the locations where metachronous cancers occur most frequently are the oropharynx, hypopharynx, and larynx, followed by the gastric tube. Due to a paucity of reports, much remains unknown about gastric tube cancer, such as the site of common occurrence, pattern of metastasis, treatment method. This study investigated the clinical characteristics of patients with gastric tube cancer and to examine the outcomes of gastrectomy versus endoscopic submucosal dissection. Methods Of 49 patients who underwent treatment for gastric tube cancer that developed 1 year or more after esophagectomy, 30 patients underwent subsequent gastrectomy (Group A), and 19 patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) (Group B). The characteristics and outcomes of these two groups were compared. Results The interval between esophagectomy and diagnosis of gastric tube cancer ranged from 1 to 30 years. The most common location was the lesser curvature of the lower gastric tube. When the cancer was detected early, EMR or ESD was performed, and the cancer did not recur. In advanced tumors, gastrectomy was performed but the gastric tube was difficult to approach and lymph node dissection was difficult; two patients died as a result of the gastrectomy. In Group A, recurrence occurred most often as axillary lymph node, bone, or liver metastases; in Group B, no recurrence or metastases were observed. Conclusion In addition to recurrence and metastasis, gastric tube cancer is often observed after esophagectomy. The present findings highlight the importance of early detection of gastric tube cancer after esophagectomy and that the EMR and ESD procedures are safe and have significantly fewer complications compared with gastrectomy. Follow-up examinations should be scheduled with consideration given to the most frequent sites of gastric tube cancer occurrence and the time elapsed since esophagectomy.