Comprehensive Diagnostic Workup Research Articles

Diagnostyka nietypowego stanu gorączkowego u 55-letniego mężczyzny

BackgroundThe paper describes a diagnostically challenging case of recurrent fever with an atypical course in a 55-year-old man. The authors highlight the significant difficulty in reaching a correct diagnosis, as well as the doubts and problems associated with the diagnostics. They suggest considering brucellosis as a diagnosis based on the patient's history and the course of the disease characterized by fluctuating, intermittent, and nocturnal fever.ObjectiveThe aim of the study was to present an atypical and diagnostically challenging case of recurrent febrile episodes in a 55-year-old man.Material and methodsA comprehensive diagnostic workup, including laboratory tests, imaging, and specialist consultations, was conducted. The patient's medical history, physical examination, and various diagnostic tests were analyzed.ResultsIn a patient with recurrent episodes of fever, an infection with Brucella spp. was detected, which was effectively treated with long-term antibiotic therapy. Imaging and laboratory diagnostics, along with specialist consultations, helped rule out other potential causes of the symptoms. The patient achieved lasting improvement following the treatment.ConclusionsThere is a high probability that the patient was infected with Brucella bacteria. Diagnostic challenges and the rarity of the disease, considered non-existent in Poland, hinder prompt confirmation or exclusion of infection. The authors aimed to highlight the possibility of a higher frequency of brucellosis in Poland. They suggest that Brucella bacteria may still be present, causing chronic, unrecognized, recurrent fevers. Based on the case analysis, the authors indicate that the frequent occurrence of this disease in Poland might be higher than reported by statistics.

Management of Metastatic Spinal Disease - A Practical Approach.

Narrative review. This review presents a comprehensive approach to the management of spinal metastases. N/A. The wide spectrum of clinical presentation in spinal metastases necessitates a personalized approach to treatment planning. This includes a comprehensive diagnostic workup, oncological management, palliation of symptoms, and surgical intervention if appropriate. A systematic and multidisciplinary approach allows optimal shared decision making to reach an evidence-informed and value-congruent treatment plan for the patient. We highlight how advances in stereotactic body radiotherapy (SBRT) and separation surgery may be incorporated into clinical management from a spine surgeon's perspective. This review summarizes the approach and management of spinal metastases, its outcomes and complications.

Idiopathic male infertility – what are we missing?

ABSTRACT Couple’s infertility is a rising issue worldwide affecting approximately 15% of couples. In 50% of the couples, a male factor infertility can be identified. Moreover, 30% of the men exhibit reduced sperm quality without any identifiable reason, thereby delineating the condition of idiopathic male infertility (IMI). Despite numerous improvements in the diagnosis and treatment of male infertility over the last decades, idiopathic forms are still the most challenging clinical dilemmas. The aim of this article is to describe the comprehensive diagnostic work-up that each idiopathic infertile man should follow. Moreover, potential new pathophysiological mechanisms and suggested treatment options are discussed. A detailed medical history and an extensive physical examination are mandatory to investigate potential treatable causes of MFI. Similarly, standard semen analysis has been proven to be limited in capturing the fecundability of the spermatozoa itself, therefore more advanced examinations, such as sperm DNA fragmentation (SDF) and oxidative stress measurement, are becoming important in clinical practice for IMI. In terms of diagnostic tools, imaging and genetic investigations are useful to classify idiopathic infertile men, however, epigenetic changes have demonstrated to have a role in sperm production and a prognostic value in fertility outcomes. Antioxidant treatment for IMI has been found to be a valid option to counteract ROS action, while gonadotropins are used to improve sperm quality and SDF. Artificial intelligence is promising to better manage idiopathic infertile men in terms of diagnosis and treatment options.

The importance of the 'uterine factor' in recurrent pregnancy loss: a retrospective cohort study on women screened through 3D transvaginal ultrasound.

What is the prevalence of congenital and acquired anomalies of the uterus in women with recurrent pregnancy loss (RPL) of unknown etiology examined using 3D transvaginal ultrasound (US)? Depending on the adopted diagnostic criteria, the prevalence of partial septate uterus varies between 7% and 14% and a T-shaped uterus is 3% or 4%, while adenomyosis is 23%, at least one of type 0, type 1 or type 2 myoma is 4%, and at least one endometrial polyp is 4%. ESHRE and the Royal College of Obstetricians and Gynaecologists guidelines on RPL recommend the adoption of the 3D transvaginal US to evaluate the 'uterine factor'. Nevertheless, there are no published studies reporting the prevalence of both congenital and acquired uterine anomalies as assessed by 3D transvaginal US and diagnosed according to the criteria proposed by the most authoritative panels of experts in a cohort of women with RPL. This was a retrospective cohort study including 442 women with at least two previous first-trimester spontaneous pregnancy losses (i.e. non-viable intrauterine pregnancies), who referred to the obstetrics and gynecology unit of two university hospitals between July 2020 and July 2023. Records of eligible women were reviewed. Women could be included in the study if: they were between 25 and 42 years old; they had no relevant comorbidities; they were not affected by infertility, and they had never undergone ART; they and their partner tested negative to a comprehensive RPL diagnostic work-up; and they had never undergone metroplasty, myomectomy, minimally invasive treatments for uterine fibroids or adenomyomectomy. Expert sonographers independently re-analyzed the stored 2- and 3D transvaginal US images of all included patients. Congenital uterine anomalies (CUAs) were reported according to the American Society for Reproductive Medicine (ASRM) 2021, the ESHRE/European Society for Gynaecological Endoscopy (ESGE) and the Congenital Uterine Malformation by Experts (CUME) criteria. Acquired uterine anomalies were reported according to the International Federation of Gynecology and Obstetrics (FIGO) and the Morphological Uterus Sonographic Assessment (MUSA) criteria. The partial septate uterus was diagnosed in 60 (14%; 95% CI: 11-17%), 29 (7%; 95% CI: 5-9%), and 47 (11%; 95% CI: 8-14%) subjects, according to the ESHRE/ESGE, the ASRM 2021, and the CUME criteria, respectively. The T-shaped uterus was diagnosed in 19 women (4%; 95% CI: 3-7%) according to the ESHRE/ESGE criteria and in 13 women (3%; 95% CI: 2-5%) according to the CUME criteria. The borderline T-shaped uterus (diagnosed when two out of three CUME criteria for T-shaped uterus were met) was observed in 16 women (4%; 95% CI: 2-6%). At least one of FIGO type 0, type 1, or type 2 myoma was detected in 4% of included subjects (95% CI: 3-6%). Adenomyosis was detected in 100 women (23%; 95% CI: 19-27%) and was significantly more prevalent in women with primary RPL and in those with three or more pregnancy losses. At least one endometrial polyp was detected in 4% of enrolled women (95% CI: 3-7%). The absence of a control group prevented us from investigating the presence of an association between both congenital and acquired uterine anomalies and RPL. Second, the presence as well as the absence of both congenital and acquired uterine anomalies detected by 3D US was not confirmed by hysteroscopy. Finally, the results of the present study inevitably suffer from the intrinsic limitations of the adopted classification systems. The prevalence of CUAs in women with RPL varies depending on the classification system used. For reasons of clarity, the US reports should always state the name of the uterine anomaly as well as the adopted classification and diagnostic criteria. Adenomyosis seems to be associated with more severe forms of RPL. The prevalence rates estimated by our study as well as the replicability of the adopted diagnostic criteria provide a basis for the design and sample size calculation of prospective studies. No specific funding was used. The authors have no conflicts of interest to declare. N/A.

Prostate cancer risk assessment and avoidance of prostate biopsies using fully automatic deep learning in prostate MRI: comparison to PI-RADS and integration with clinical data in nomograms.

Risk calculators (RCs) improve patient selection for prostate biopsy with clinical/demographic information, recently with prostate MRI using the prostate imaging reporting and data system (PI-RADS). Fully-automated deep learning (DL) analyzes MRI data independently, and has been shown to be on par with clinical radiologists, but has yet to be incorporated into RCs. The goal of this study is to re-assess the diagnostic quality of RCs, the impact of replacing PI-RADS with DL predictions, and potential performance gains by adding DL besides PI-RADS. One thousand six hundred twenty-seven consecutive examinations from 2014 to 2021 were included in this retrospective single-center study, including 517 exams withheld for RC testing. Board-certified radiologists assessed PI-RADS during clinical routine, then systematic and MRI/Ultrasound-fusion biopsies provided histopathological ground truth for significant prostate cancer (sPC). nnUNet-based DL ensembles were trained on biparametric MRI predicting the presence of sPC lesions (UNet-probability) and a PI-RADS-analogous five-point scale (UNet-Likert). Previously published RCs were validated as is; with PI-RADS substituted by UNet-Likert (UNet-Likert-substituted RC); and with both UNet-probability and PI-RADS (UNet-probability-extended RC). Together with a newly fitted RC using clinical data, PI-RADS and UNet-probability, existing RCs were compared by receiver-operating characteristics, calibration, and decision-curve analysis. Diagnostic performance remained stable for UNet-Likert-substituted RCs. DL contained complementary diagnostic information to PI-RADS. The newly-fitted RC spared 49% [252/517] of biopsies while maintaining the negative predictive value (94%), compared to PI-RADS ≥ 4 cut-off which spared 37% [190/517] (p < 0.001). Incorporating DL as an independent diagnostic marker for RCs can improve patient stratification before biopsy, as there is complementary information in DL features and clinical PI-RADS assessment. For patients with positive prostate screening results, a comprehensive diagnostic workup, including prostate MRI, DL analysis, and individual classification using nomograms can identify patients with minimal prostate cancer risk, as they benefit less from the more invasive biopsy procedure. The current MRI-based nomograms result in many negative prostate biopsies. The addition of DL to nomograms with clinical data and PI-RADS improves patient stratification before biopsy. Fully automatic DL can be substituted for PI-RADS without sacrificing the quality of nomogram predictions. Prostate nomograms show cancer detection ability comparable to previous validation studies while being suitable for the addition of DL analysis.

Life-threatening airway obstruction by Riedel's thyroiditis: a rare presentation and diagnostic dilemma.

Riedel's thyroiditis is the rarest form of thyroiditis, occasionally resulting in rapid thyroid enlargement and potential tracheal obstruction. Here, we detail the case of an 81-year-old woman with a medical history including Hodgkin lymphoma, Hashimoto's thyroiditis, and multinodular goiter. She presented to the emergency room with stridor, cervical swelling, and breathing difficulties for over 2 days. CT scans revealed substantial thyroid enlargement causing significant glottal and tracheal compression, to a minimum tracheal diameter of 7 mm. Due to the severity of the compressive symptoms, orotracheal intubation and mechanical ventilation were deemed necessary. Surprisingly, despite the initial suspicion of malignancy given the rapid growth in the elderly, subsequent cytological and histological evaluations indicated a benign form of invasive fibrous thyroiditis - Riedel's thyroiditis. Although surgical intervention was advised, the patient declined and opted for endobronchial treatment with a prosthetic stent and subsequent treatment with systemic glucocorticoids. Following successful treatment, she was discharged within a week and resumed normal activities without respiratory distress. This case is noteworthy for its rapid benign mass growth, rare emergent presentation, and the patient's advanced age. The rapid enlargement of the thyroid gland in elderly patients poses a diagnostic challenge, stemming from the higher occurrence of aggressive thyroid carcinomas. Despite the clinical presentation, a comprehensive diagnostic workup, including fine-needle aspiration and core-needle biopsy, is crucial for accurately distinguishing between benign and malignant causes of thyroid nodule enlargement. This case report illustrates diverse treatment options for Riedel's thyroiditis, and the importance of individualized treatment plans based on the degree of airway obstruction, patient preferences, and response to initial interventions. Clinicians should contemplate the inclusion of glucocorticoids in the therapeutic regimen for Riedel's thyroiditis, particularly in cases where surgical intervention is not feasible or declined by the patient.

Primary left atrial rhabdomyosarcoma in a 42-year-old patient: an unusual cardiac tumor presentation

Left atrial rhabdomyosarcoma is an extremely rare and often overlooked form of primary cardiac malignancy that primarily affects the atria of the heart. The aggressive nature of atrial rhabdomyosarcoma necessitates early recognition, a comprehensive diagnostic workup, and prompt intervention to achieve the best possible outcomes. In this case report, we present the clinical details of a 42-year-old female diagnosed with left atrial rhabdomyosarcoma, who exhibited symptoms of recent pulmonary edema, weight loss, and alternating flushing. Diagnosis, surgical treatment, and the iatrogenic atrial septal defect complication due to interatrial septum invasion were discussed.

Long-term risk assessment in athletes with ventricular arrhythmias: the key roles of arrhythmia morphology, complexity, and substrate

Abstract Background Ventricular arrhythmias (VAs) are an important source of concern among athletes. Purpose To determine the prognostic role of non-invasive and invasive diagnostic assessments among athletes with complex VAs. Methods We included 215 athletes (83% male; 28 [19-43] years) with complex VAs in a prospective, multi-center cohort study. At baseline, each athlete underwent a prespecified comprehensive diagnostic workup, which included cardiac magnetic resonance (CMR) in 202 subjects, and electrophysiology study (EPS)/electroanatomical mapping (EAM) in 190. The primary study endpoint was the occurrence of sudden death or sustained VAs during long-term follow-up. Results During a median follow-up of 6.2 (4.4-8.1) years, 16 (7%) athletes had a primary outcome event, including one sudden cardiac death. In univariable Cox models, sustained VAs at presentation (p&amp;lt;0.001), uncommon VA morphology(p=0.004), syncope(p=0.005), abnormal ECG (p=0.003), VAs induction/persistence at exercise testing(p=0.021), late gadolinium enhancement (LGE;p=0.006), low-voltage areas (p=0.003) and late potentials (p&amp;lt;0.001) at EAM, and sustained VA induction by EPS (p&amp;lt;0.001) were all associated with increased risk of primary outcome events. The association of late potentials and EPS inducibility with primary outcome events was confirmed after controlling for all non-invasive predictors at univariable analysis, and the incorporation of findings of invasive tests allowed improved prediction of primary outcome events over clinical/non-invasive findings in isolation (log-likelihood ratio for nested models, p=0.043). Younger age (p=0.032), being a professional athlete (p=0.006), and absence of LGE (p=0.029) were independently associated with higher odds of uninterrupted competitive sports practice until last follow-up. Conclusions A comprehensive diagnostic assessment integrating clinical/ECG findings with CMR and EPS/EAM in selected cases may provide important prognostic information among athletes with complex VAs.

Arrhythmic mitral valve prolapse with versus without prior mitral valve repair: clinical profiles, electrophysiological substrates, and long-term clinical outcomes

Abstract Background Arrhythmic mitral valve prolapse (AMVP) is characterized by an arrhythmogenic left ventricular substrate, with high prevalence of myocardial scar. Whether patients with prior mitral valve repair for mitral valve prolapse (MVP) and new-onset complex ventricular arrhythmias (VAs) after cardiac surgery have different electroanatomical substrate and arrhythmic outcomes compared with AMVP patients without prior mitral valve surgery is currently unknown. Purpose We sought to compare the electroanatomical substrate and long-term clinical outcomes of patients with new-onset complex VAs after mitral valve surgery to AMVP patients without prior surgery. Methods We conducted a multicenter, prospective, observational study, enrolling MVP patients with prior mitral valve repair and new-onset complex VAs (&amp;gt;1000 premature ventricular contractions [PVCs]/day, nonsustained ventricular tachycardia [NSVT], and sustained VT) after cardiac surgery (group A,n=9), and patients with MVP, complex VAs and no prior surgery (group B,n=20). Each patient underwent a comprehensive diagnostic workup, including left ventricular electroanatomical mapping. Clinical-imaging data, as well as the location and segmental extension of both low-voltage areas and late potentials were assessed and compared between the two groups. The primary outcome was the occurrence of sustained VT or ventricular fibrillation(VF) during follow-up. Results In group A, complex VAs were first diagnosed after a median of 30(8-56) months following mitral valve repair. The characteristics of patients from the two study groups are presented in the Table. Patients from group A were older, sustained VT was nonsignificantly more common at baseline, the PVC count nonsignificantly higher, and LVEF nonsignificantly lower. Mitral annular disjunction was never observed in group A, while it was found in 7 patients from group B (p=0.066). At LV electroanatomical voltage mapping, bipolar and unipolar low-voltage areas (LVAs) were equally common in the two groups overall, and typically involved basal perimitral regions. However, patients from group B had concomitant bipolar and unipolar LVAs 50% of times, with larger unipolar LVAs, while patients from group A mostly showed isolated bipolar LVAs. Over a median follow-up of 15 (12-41) months, patients from group A (n=3, 33%) had slightly higher incidence of sustained VT or VF (HR: 1.91; 95% CI, 1.06-42.65; log-rank p=0.02, Figure) than patients from group B (n=2, 10%). Conclusion Compared to patients with AMVP and no prior cardiac surgery, patients with new-onset complex VAs after mitral valve repair for MVP have a slightly different clinical profile and electroanatomical substrate, characterized by predominant bipolar LVAs in the perimitral region. The long-term risk of major ventricular arrhythmias appears slightly higher in MVP patients with prior mitral valve surgery, mandating at least an equally careful risk assessment in both groups.

The expectations and experiences of patients regarding the diagnostic workup at a specialized memory clinic: An interview study.

Because of the shift towards earlier diagnosis of dementia and/or Alzheimer's disease (AD), increasing numbers of individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are seen in memory clinics. Yet, evidence indicates that there is room for improvement when it comes to tailoring of the diagnostic work-up to the needs of individual patients. To optimize the quality of care, we explored patients' perspectives regarding the diagnostic work-up at a specialized memory clinic. This interview study was conducted at Karolinska University Hospital (Sweden). The comprehensive diagnostic work-up for dementia at the memory clinic in Solna is conducted within 1 week. A sample of 15 patients (8 female; mean age = 61 years [range 50-72]; 11 SCD, 1 MCIand 3 AD dementia) was purposively selected for a series of three semistructured interviews, focussing on (1) needs and expectations (during the week of diagnostic testing), (2) experiences (within 2 weeks after test-result disclosure)and (3) reflections and evaluation (3 months after disclosure). Transcribed audio-recorded data were analyzed using thematic content analysis (using MaxQDA software). Three key themes were identified: (1) the expectations and motivations of individuals for visiting the memory clinic strongly impacted their experience; (2) the diagnostic work-up impacted individuals psychosocially and (3) the diagnostic work-up provided an opportunity to motivate individuals to adopt a healthier lifestyle. Our findings underscore the importance of enquiring about the expectations and needs of individuals referred to a specialized memory clinic, allowing for expectation management and personalization of provided information/advice, and potentially informing the selection of patients in need of a comprehensive diagnostic work-up. Structural guidance might be needed to support those with SCD and MCI to help them cope with uncertainty, potentially resolve their issues, and/or stimulate brain health. We gathered the perspectives of 15 individuals who had been referred to the memory clinic at three different time points through semistructured interviews, and these interviews were the primary data source.

Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation

Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

(193) Bilateral Onco-TESE and Placement of Bilateral Testicular Prostheses

Abstract Introduction Here we present the case of a 36-year-old male who underwent bilateral Onco-TESE (oncologic testicular sperm extraction) and insertion of bilateral testicular prostheses in the setting of bilateral testicular masses and refractor testicular pain. Preoperative evaluation revealed the presence of non-obstructive azoospermia and Klinefelter syndrome. Objective To demonstrate the effectiveness and feasibility of bilateral Onco-TESE as a therapeutic option for the patient with bilateral testicular masses, refractory bilateral testicular pain, non-obstructive azoospermia, and Klinefelter syndrome while attempting to preserve future fertility. Methods A comprehensive diagnostic workup was performed preoperatively including physical examination, scrotal ultrasound, hormonal evaluation, semen analysis, and genetic testing. Informed consent for the procedure and its filming was obtained from the patient prior to undergoing bilateral Onco-TESE and insertion of bilateral testicular prostheses. Results Pathologic analysis of testicular masses revealed Multinodular Leydig cell hyperplasia. The extracted testicular tissue yielded no viable sperm. The patient’s testicular pain resolved after the immediate postoperative period with an excellent cosmetic result. Conclusions This case presentation highlights a unique indication for bilateral Onco-TESE and insertion of bilateral testicular prostheses in a patient with bilateral testicular masses, bilateral testicular pain, Klinefelter syndrome, and desired future fertility. Disclosure No.

Frequency and Prognostic Value of Circulating Tumor Cells in Cancer of Unknown Primary.

Cancer of unknown primary (CUP) is defined as a primary metastatic malignancy, in which the primary tumor remains elusive in spite of a comprehensive diagnostic workup. The frequency and prognostic value of circulating tumor cells (CTCs), which are considered to be the source of metastasis, has not yet been systematically evaluated in CUP. A total of 110 patients with a confirmed diagnosis of CUP according to the European Society for Medical Oncology (ESMO) guidelines, who presented to our clinic between July 2021 and May 2023, provided blood samples for CTC quantification using CellSearch methodology. CTC counts were correlated with demographic, clinical, and molecular data generated by comprehensive genomic profiling of tumor tissue. CTCs were detected in 26% of all patients at initial presentation to our department. The highest CTC frequency was observed among patients with unfavorable CUP (35.5%), while patients with single-site/oligometastatic CUP harbored the lowest CTC frequency (11.4%). No statistically significant association between CTC positivity and the number of affected organs (P = 0.478) or disease burden (P = 0.120) was found. High CTC levels (≥5 CTCs/7.5 mL; 12/95 analyzed patients) predicted for adverse overall survival compared to negative or low CTC counts (6-months overall survival rate 90% vs 32%, log-rank P < 0.001; HR 5.43; 95% CI 2.23-13.2). CTC dynamics were also prognostic for overall survival by landmark analysis (log-rank P < 0.001, HR 10.2, 95% CI 1.95-52.9). CTC frequency is a strong, independent predictor of survival in patients with CUP. CTC quantification provides a useful prognostic tool in the management of these patients.

Shining a Light on Hidden Thyroids: A Case Exploring the Potential of Technetium Imaging for Lingual Thyroid Diagnosis

Ectopic thyroid, the presence of thyroid tissue in locations other than the normal anterior neck region between the second and fourth tracheal cartilages, is the most common form of thyroid dysgenesis. A 32-year-old female patient sought medical attention at the Otolaryngology Department with a foreign body sensation in her throat. To ensure an accurate diagnosis, hereby, the authors conducted a comprehensive diagnostic work-up, which included Technetium-99 (Tc-99m) scanning. Remarkably, the scanning results revealed radiotracer uptake in the base of the tongue while indicating an absence of uptake in the thyroid bed. By shedding light on present captivating case, the present report offers valuable insights into the usage of Technetium imaging in diagnosing doubtful Lingual Thyroid (LT) cases.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

Exploring Regional Challenges and Solutions to Appropriate and Equitable Care for Patients with Chronic Lymphocytic Leukemia

Background: For patients with chronic lymphocytic leukemia (CLL)-the most common form of leukemia in older adults-equitable access to care is particularly challenging, as the disease is often diagnosed in community cancer centers encumbered by regional disparities. Therefore, identifying and understanding regional barriers to care is essential. In 2020, the Association of Community Cancer Centers (ACCC) developed a heat map detailing the incidence rate of CLL diagnoses across the country (Fig.1), overlayed with the locations of CLL “expert” providers, revealing the areas in the US most in need of additional CLL clinical expertise (Fig. 2). In 2022, these incidence rates were stratified by race, ethnicity, and metropolitan statistical area to identify disparities Building on these maps, ACCC set out to identify specific regional challenges to appropriate, equitable care for patients with CLL. Methods: As part of an independent education program, ACCC initiated conversations with providers about the regional barriers that patients with CLL face. Through 4 webinars in February 2023, participants from 4 regions-Northeast (New York and Maine), Northwest (Montana and Idaho), Midwest (Wisconsin, Illinois, and Iowa), and Southwest (Texas)-shared insights on challenges and exchanged ideas on strategies to improve care for patients with CLL. In addition, ACCC interviewed 3 regionally diverse cancer programs (from the US Northwest, South, and Southwest regions) that are effectively overcoming regional challenges to reach their patient populations and provide equitable care. These interviews highlighted barriers and challenges, showcased effective outreach campaigns, and explored how the outreach improved the patient journey. Findings: The following themes emerged as key challenges and potential solutions throughout all regions studied: (1) Comprehensive Diagnostic Work-up Before Treatment Initiation: A key component in caring for patients with CLL is identifying certain disease related criteria prior to formulating a treatment plan. This includes determining the disease burden, disease-related symptoms, and if the patient meets certain active disease criteria (eg, Binet Stage C or Rai Stage III or IV). Further, by utilizing genetic testing, such as the TP53 gene mutation and IGHV mutation tests, physicians can estimate time to treatment and choice of specific novel targeted therapies. (2) Understanding Patient Population Needs: Cancer programs must understand the needs of their unique patient populations to effectively address them. For example, in the Northwest, as mountainous passes can make travel dangerous at times, one local program utilizes near-campus housing/hotel space for patients for the duration of their intensive treatment. In the Southwest, addressing health insurance coverage, low health literacy, language barriers, patient-provider mistrust, and culturally competent care for undocumented individuals presents challenges to equitable care delivery. Therefore, cancer programs in this region have implemented protocols to utilize community and social services to help support these patients. (3) Developing Community Partnerships: As the median age of diagnosis with CLL is approximately 70 years old, barriers such as transportation availability, caregiver support and financial constraints could be magnified. Building trust, particularly among vulnerable communities, also presents a significant challenge. By partnering with community outreach organizations, programs can help address these issues through community resources such as ride share programs, transportation vouchers, and financial assistance programs. (4) Provider Education and Learning: Because many patients are diagnosed in community cancer programs and smaller practices where physicians do not often have experience with CLL, nationally available provider education on new developments in testing and treatments is key. Conclusions: ACCC identified regional challenges and solutions to appropriate and equitable care for patients with CLL, including the importance of comprehensive diagnostic work-up before treating, understanding the regional needs of patient populations (particularly underserved populations), building community partnerships, and engaging in targeted provider education.

Bleeding Disorders in Women- a Unique Challenge Requiring a Unique Approach

Introduction: Bleeding disorders in women, particularly in developing countries, have been largely neglected due to various factors such as social stigma, limited access to comprehensive laboratory facilities, and the misconception of physiological bleeding during menstruation. Heavy menstrual bleeding (HMB) is a common symptom in women, and a significant percentage of cases may be associated with inherited bleeding disorders. However, the underreporting and underdiagnosis of these conditions remain prevalent, partly due to the stigma surrounding menorrhagia, leading to delayed medical care seeking. This study aims to explore the clinical and laboratory profiles of females with bleeding disorders who presented to our institute. Methods: A consecutive series of female patients referred to our advanced coagulation laboratory for complete workup with bleeding manifestations or abnormal screening coagulogram over a 59-month period (September 2018 to July 2023) were assessed. Patients with liver disease, chronic inflammation, or on anticoagulation therapy were excluded. Data on age at presentation and diagnosis, ISTH BAT score, annual bleeding rate, family history, hospitalizations, surgical interventions, and follow-up were retrospectively retrieved from our database. Heavy menstrual bleeding was subjectively defined based on specific criteria. Various laboratory parameters were analyzed for all patients. Data were presented using median/range and percentage. Missing data were not imputed, and MS Excel 2016 was used for analysis. Results: Over the study duration, 1019 patients were evaluated at our institute, with 488 females (47.9%) and 531 males (52.1%). Among the 235 patients (23%) diagnosed with bleeding disorders, 87 (37%) were women. The median age at diagnosis was 29 years (range: 9 months-84 years), while the median age of first symptom was 15 years (range: 7 days-81 years). The median time interval between presentation and diagnosis was 8 years (range: 6 months-30 years). The most common presenting symptom was HMB (34.4%), followed by ecchymotic patches (17.2%) and epistaxis (16%). Significant ISTH BAT scores (&amp;gt;6) were found in 17 patients (19.5%). A family history of bleeding was observed in 4.5% of patients, with 3 of them born to consanguineous parents. Incidentally detected abnormal screening coagulogram was present in 12.6% of patients. The most common bleeding disorder diagnosed was VWD (35.6%), followed by Factor VII deficiency (13.8%), Vitamin K dependent coagulation factor deficiency (9.2%), and Acquired Haemophilia A (9.2%). Intracranial bleeding (4.5%) was primarily associated with specific deficiencies. No carriers were detected in the study. Conclusion: Addressing bleeding disorders in women requires specific attention. The ISTH BAT score proved to be a user-friendly yet powerful tool, with 19.5% of patients showing significant scores that prompted comprehensive diagnostic workup. This study highlights the long latent period between the age of first symptom and the age of diagnosis, emphasizing the need to raise awareness among patients and primary physicians, especially gynaecologists. Menorrhagia starting from menarche was the most common bleeding symptom, emphasizing the importance of prompt and accurate diagnosis to prevent life-threatening bleeds. The consideration of acquired hemophilia A is crucial in cases of unexplained postpartum hemorrhage. Developing countries face additional challenges due to limited specialized laboratories, leading to outsourcing and increased testing costs. To improve diagnosis and care, early identification of female bleeders is essential, facilitated by outreach programs and advanced coagulation testing centers.

Unmasking Hypoglossal Nerve Schwannomas Mimicking Submandibular Salivary Gland Tumors: Case Report of a Rare Presentation and Surgical Management

Background: Schwannomas are solitary neurogenic tumors originating from the myelin-producing cells of the neural sheath. Hypoglossal nerve schwannomas are exceedingly rare, particularly those extracranially originating and mimicking a submandibular salivary gland tumor. Methods: We report the case of a 31-year-old female who presented to our ENT department with a painless swelling in her left submandibular region that has persisted for approximately five months. Discussion: Due to the rarity of these tumors and their unique nature, a comprehensive diagnostic workup is imperative for accurate diagnosis. Surgical excision remains the gold standard treatment. Conclusions: Extracranial hypoglossal nerve schwannomas represent a rare clinical entity requiring a thorough diagnostic process for precise identification. The preferred treatment strategy for managing hypoglossal gland schwannomas involves complete tumor excision while preserving the facial nerve.

FRI459 Sperm-Carried IGF2: Towards The Discovery Of The Spark That Gives Rise To Life

Abstract Disclosure: R. Cannarella: None. O.J. Rando: None. S. Chamayou: None. S. La Vignera: None. R.A. Condorelli: None. A.E. Calogero: None. Background. Infertility is a public health problem affecting 15% of couples of childbearing age. In half of the cases, the male factor is a primary or contributing cause. Unfortunately, despite a comprehensive diagnostic workup, the causes of male infertility remain unclear in a large percentage of cases, thus suggesting the urgent need for further research. Spermatozoa have now been shown to carry key RNAs that may play critical roles in the development of the embryo. In this contest, a potential key growth regulator is insulin-like growth factor 2 (IGF2) whose gene is highly conserved and paternally imprinted. The gene encoding for IGF2 is involved in growth and proliferation and we have already demonstrated that it is expressed in human spermatozoa (DOI: 10.3389/fendo.2022.1010796). Aim. To evaluate the impact of sperm-carried IGF2 on early embryo growth kinetics and gene expression. Materials and methods. Patients undergoing intracytoplasmic sperm injection (ICSI) for idiopathic or male factor infertility were enrolled. Couples with female factor infertility were excluded. Following clinical practice, an aliquot of the left-over semen samples used for ICSI was used to analyze the IGF2 mRNA levels. The kinetic parameters of each embryo development were recorded and correlated with the amount of IGF2 mRNA measured in the same swim-up spermatozoa used for ICSI. Transcriptome analysis of blastocyst obtained from parthenotes collected from twelve-week-old superovulated mice was performed after incubation with recombinant human IGF2 (rhIGF2) protein (Group 1, n=40) or vehicle (Group 2, n=40) or injection with Igf2 plus Gfp (encoding for a fluorescent protein) mRNAs (Group 3, n=20) or Gfp mRNA only (Group 4, n=20). Results. In total, 16 patients were enrolled and 131 embryos were collected. We found a significant negative correlation between sperm IGF2 mRNA levels and pronucleus fading time (tPN) (r= -0.2572, p= 0.0078, n=106 embryos) and between sperm IGF2 mRNA and time of 2-cell embryo (t2) (r= -0.2368, p= 0.0145, n=106 embryos). In contrast, sperm IGF2 mRNA levels did not correlate with t3, t4, t5, t6, t7, t8, t9, t morula (tM), t blastocyst (tB), and time of expanded blastocyst (tEB). On transcriptome analysis, 501 and 101 genes were differentially expressed between Group 1 and Group 2, and between Group 3 and Group 4, respectively. Pathway enrichment analysis revealed several differentially expressed genes that trigger embryo growth and development, endoderm and mesoderm differentiation, angiogenesis, and sustaining proliferative signaling. Conclusions. Sperm-carried IGF2 triggers the expression of genes involved in early embryo development and improves embryo kinetics. This evidence may shed light on the etiology of apparently idiopathic couple infertility, since low sperm-carried IGF2 levels may be responsible for the impairment of early embryo growth and development. Presentation Date: Friday, June 16, 2023

DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues

Identifying the primary site of metastatic cancer is critical to guiding the subsequent treatment. Approximately 3–9% of metastatic patients are diagnosed with cancer of unknown primary sites (CUP) even after a comprehensive diagnostic workup. However, a widely accepted molecular test is still not available. Here, we report a method that applies formalin-fixed, paraffin-embedded tissues to construct reduced representation bisulfite sequencing libraries (FFPE-RRBS). We then generate and systematically evaluate 28 molecular classifiers, built on four DNA methylation scoring methods and seven machine learning approaches, using the RRBS library dataset of 498 fresh-frozen tumor tissues from primary cancer patients. Among these classifiers, the beta value-based linear support vector (BELIVE) performs the best, achieving overall accuracies of 81-93% for identifying the primary sites in 215 metastatic patients using top-k predictions (k = 1, 2, 3). Coincidentally, BELIVE also successfully predicts the tissue of origin in 81-93% of CUP patients (n = 68).