Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance.

Purpose: This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods: We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results: The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion: Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.

Livedoid Vasculopathy with Severe Debilitating Neuropathy in a Prior Professional Athlete.

Livedoid vasculopathy (LV) can be a challenging diagnosis with an interesting pathophysiology. LV is an uncommon diagnosis that can be easily mistaken for more common skin conditions, especially in a person of color who may be underrepresented in pathology images used in medical education. LV has an average of five years from initial presentation to diagnosis, possibly due to providers not having it on their differential for lower extremity ulcerations. Prolonged time to diagnosis can potentially lead to life-changing complications. We present a case of a former professional sprinter who became debilitated by neuropathy secondary to complications from LV. He was seen multiple times and had an extensive work-up exploring a broad differential including autoimmune etiologies, hypercoagulable disorders, neuropathies, and other vascular disorders before reaching the diagnosis. This case emphasizes the importance of early diagnosis and treatment with a multidisciplinary team to help prevent the progression of these symptoms. We break down an extensive work-up that involves a multidisciplinary team including dermatology, hematology, neurology, rheumatology, and vascular surgery. This case will also highlight examples of LV in a patient with a dark skin complexion, which can be challenging to find in current literature. We additionally show images that demonstrate many of the classic pathologic findings associated with LV and how those can help lead to the diagnosis along with detailed descriptions of those findings. Classic physical exam findings including atrophic blanche and lower extremity ulcerations are highlighted. We also review LV's history, diagnosis, and treatment to help readers achieve a better understanding of the disease.

Garré's Sclerosing Osteomyelitis of the Tibia in a Hispanic Adult Male: A Case Report.

Sclerosing osteomyelitis of Garré is a rare inflammatory pathology characterized by cortical thickening and loss of the medullary canal. Typically, this pathology affects the mandible. However, the involvement of long bones, such as the femur and tibia, is also possible. This condition predominantly affects children and young adults, especially females, and commonly emerges before age 25, with an average onset age of 16 years. The disease is characterized by an insidious onset, causing local pain, distention of the affected bone, and a moderately increased erythrocyte sedimentation rate. We aim to report a unique case involving a 25-year-old Hispanic male presenting with a one-year insidious onset of left anterior lower leg pain. The patient's clinical course, laboratory findings, and imaging results are discussed. Despite a three-month trial of conservative management, symptomatic relief was elusive, prompting a left tibia core biopsy. Biopsy results revealed an inflammatory-reactive process with a xanthogranulomatous reaction. The continuation of conservative measures post-biopsy led to significant symptom resolution, highlighting the potential efficacy of histopathological examination. This case contributes to the limited literature on adult sclerosing osteomyelitis of Garré, particularly in long bones and among Hispanic individuals. Successful management through biopsy and conservative treatment provides valuable insights into therapeutic options for this rare condition.

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

Demodex folliculorum (Trombidiformes: Demodecidae) infestation in medical students with facial dermatoses and healthy groups.

Demodex folliculorum (Simon, 1842) has been associated with various dermatological conditions. This study aimed to assess the prevalence of Demodex infestation in medical students with facial dermatoses compared with healthy medical students serving as controls. A total of 250 participants were enrolled, including 150 individuals with facial dermatoses and 100 healthy controls. Sampling was performed based on the standardized skin surface biopsy method. Demographic characteristics, specifically gender and age, were not statistically different between the patient and control groups. Among the facial dermatosis patients, 25 out of 150 (16.6%) were found to have Demodex infestation, while only three out of the 100 healthy controls (3%) exhibited infestations. The only identified species was D. folliculorum. The rates of Demodex infestation were significantly higher in the patients compared to the control groups. These findings indicate a higher prevalence of Demodex infestation among medical students with facial dermatosis, particularly in those diagnosed with folliculitis, acne vulgaris, and inflammatory papule, when compared to healthy controls. A better understanding of the relationship between D. folliculorum infestation and these dermatological conditions may lead to improved diagnostic and treatment strategies in the future.

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection.

Polyomaviruses, particularly BK virus, are ubiquitous latent infections that may reactivate with immunosuppression during kidney transplantation, resulting in polyomavirus nephropathy (PVN). The levels of viruria and viremia serve as tools for screening and making a presumptive diagnosis of PVN, respectively, while a definitive diagnosis requires a kidney biopsy. There are histologic classifications of PVN based on the extent of tubular cell viral infection, interstitial fibrosis, and interstitial inflammation. These classifications correlate to some degree with graft function and loss, aiding in determining treatment efficacy and prognostication. PVN has histologic overlap with acute cell-mediated rejection, making the differential diagnosis challenging, although there are suggestive features for these different causes of graft dysfunction. This article reviews the diagnosis, histologic findings, and classifications of PVN, and discusses how to differentiate viral nephropathy from acute rejection.

Mistakes in utilising histopathology for the management of liver disease.

INTRODUCTION: Liver biopsy has become selective due to its invasiveness, potential adverse effects, patient acceptance and cost. Furthermore, the emergence of noninvasive tests (NITs) has challenged the necessity of liver biopsies in specific clinical situations. However, liver biopsy continues to play a crucial role in disease diagnosis, prognosis, and evaluating treatment compliance and response in selected patients. AREAS COVERED: In this narrative review, we discuss the errors and the shortcomings that can occur at various stages, from the initial patient selection for a liver biopsy to the final reporting phase, and strategies to address them. Clinicians and pathologists must take all necessary precautions to mitigate potential shortcomings that could compromise the value of liver biopsies. EXPERT OPINION: The increasing sophistication of NITs offers a safer, more convenient, and potentially more cost-effective approach to diagnosing chronic liver disease, especially for assessing the degree of liver fibrosis. As NITs continue to evolve, liver biopsy will likely transition to a more targeted role, ensuring optimal patient care in the ever-changing field of hepatology. However, liver biopsy will continue to have a pivotal role in assessing acute liver disease where the diagnostic yield of the liver biopsy still outweighs that of NITs.

Diagnostic Accuracy of Ultrasound Guided Percutaneous Pleural Needle Biopsy for Malignant Pleural Mesothelioma.

Background/Objectives: Ultrasound (US) has been progressively spreading as the most useful technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. Malignant pleural mesothelioma (MPM) represents the most common malignant pleural tumour. Thoracoscopy represents the gold standard for diagnosis, although conditions hampering such diagnostic approach often coexist. The Objective was to determine whether ultrasound-guided percutaneous needle biopsy (US-PPNB) has a high diagnostic accuracy and represents a safe option for diagnosis of MPM. Methods: US-PPNB of pleural lesions suspected for MPM in patients admitted from January 2021 to June 2023 have been retrospectively analyzed. An 18-gauge semi-automatic spring-loaded biopsy system (Medax Velox 2®) was used by experienced pneumologists. The obtained specimens were histologically evaluated and defined as adequate or non-adequate for diagnosis according to whether the material was considered appropriate or not for immunohistochemistry (IHC) analysis. The primary objective of the study was the diagnostic yield for a tissue diagnosis. Results: US-PPNB was diagnostic of MPM in 15 out of 18 patients (sensitivity: 83.39%; specificity: 100%; PPV: 100%). Three patients with non-adequate US-PPNB underwent thoracoscopy for diagnosis. We found significant differences in terms of mean pleural lesion thickness between patients with adequate and not-adequate biopsy (15.4 mm (SD: 9.19 mm) and 3.77 mm (SD: 0.60 mm), p < 0.0010. In addition, a significant positive correlation has been observed between diagnostic accuracy and FDG-PET avidity value. Conclusions: US-PPNB performed by a pneumologist represents a valid procedure with a high diagnostic yield and accuracy for the diagnosis of MPM, and may be considered as an alternative option in patients who are not suitable for thoracoscopy.

Frequency and Demographic Analysis of Odontogenic Tumors in Three Tertiary Institutions: An 11-Year Retrospective Study.

Odontogenic tumors (OTs) are distinct conditions that develop in the jawbones, exhibiting diverse histopathological features and variable clinical behaviors. Unfortunately, the literature on this subject in Saudi Arabia remains sparse, indicating a pressing need for more comprehensive data concerning the frequency, demographics, treatment modalities, and outcomes of OTs. OBJECTIVES: The study aims to evaluate the frequency, demographic features, treatment, and outcomes of OTs across three tertiary medical centers. METHODS AND MATERIAL: OT cases were identified in King Abdulaziz Medical City (KAMC), King Fahad Medical City (KFMC), and Prince Sultan Military Medical City (PSMMC) from January 2010 to December 2021. RESULTS: Ninety-two OT cases were identified from the anatomical pathology laboratories of three tertiary hospitals. KFMC contributed the highest number of cases (43.5%), followed by KAMC (30.4%) and PSMMC (26.1%). The median age of OT patients was 29 years (range: 5-83), with males representing more than half of the patients (56.5%). The mandible was the most frequent site of OT occurrence (72.5%), with ameloblastoma being the predominant OT (63.0%), followed by odontoma (19.5%). Among the treatment modalities, bone resection was employed the most (51.0%), followed by enucleation (25.6%). Notably, 11.5% of OT cases with available follow-up data exhibited recurrence, with ameloblastoma accounting for eight recurrent cases. CONCLUSIONS: Although OTs are relatively common in the jaws, they are rare in anatomical pathology laboratories and the general population. This study contributes valuable insights into the epidemiology characteristics, treatment trends, and recurrence rates of OTs in Saudi Arabia.

Primary Cardiac Intimal Sarcoma: Multi-Layered Strategy and Core Role of MDM2 Amplification/Co-Amplification and MDM2 Immunostaining.

Primary cardiac tumours are relatively uncommon (75% are benign). Across the other 25%, representing malignant neoplasia, sarcomas account for 75-95%, and primary cardiac intimal sarcoma (PCIS) is one of the rarest findings. We aimed to present a comprehensive review and practical considerations from a multidisciplinary perspective with regard to the most recent published data in the specific domain of PCIS. We covered the issues of awareness amid daily practice clinical presentation to ultra-qualified management in order to achieve an adequate diagnosis and prompt intervention, also emphasizing the core role of MDM2 immunostaining and MDM2 genetic analysis. An additional base for practical points was provided by a novel on-point clinical vignette with MDM2-positive status. According to our methods (PubMed database search of full-length, English publications from January 2021 to March 2023), we identified three studies and 23 single case reports represented by 22 adults (male-to-female ratio of 1.2; male population with an average age of 53.75 years, range: 35-81; woman mean age of 55.5 years, range: 34-70) and a 4-year-old child. The tumour-related clinical picture was recognized in a matter of one day to ten months on first admission. These non-specific data (with a very low index of suspicion) included heart failure at least NYHA class II, mitral regurgitation and pulmonary hypertension, acute myocardial infarction, ischemic stroke, obstructive shock, and paroxysmal atrial fibrillation. Awareness might come from other complaints such as (most common) dyspnoea, palpitation, chest pressure, cough, asthenia, sudden fatigue, weakness, malaise, anorexia, weight loss, headache, hyperhidrosis, night sweats, and epigastric pain. Two individuals were initially misdiagnosed as having endocarditis. A history of prior treated non-cardiac malignancy was registered in 3/23 subjects. Distant metastasis as the first step of detection (n = 2/23; specifically, brain and intestinal) or during follow-up (n = 6/23; namely, intestinal, brain and bone, in two cases for each, and adrenal) required additional imagery tools (26% of the patients had distant metastasis). Transoesophageal echocardiography, computed tomography (CT), magnetic resonance imagery, and even 18F-FDG positronic emission tomography-CT (which shows hypermetabolic lesions in PCIS) represent the basis of multimodal tools of investigation. Tumour size varied from 3 cm to ≥9 cm (average largest diameter of 5.5 cm). The most frequent sites were the left atrium followed by the right ventricle and the right atrium. Post-operatory histological confirmation was provided in 20/23 cases and, upon tumour biopsy, in 3/23 of them. The post-surgery maximum free-disease interval was 8 years, the fatal outcome was at the earliest two weeks since initial admission. MDM2 analysis was provided in 7/23 subjects in terms of MDM2-positive status (two out of three subjects) at immunohistochemistry and MDM2 amplification (four out of five subjects) at genetic analysis. Additionally, another three studies addressed PCISs, and two of them offered specific MDM2/MDM2 assays (n = 35 patients with PCISs); among the provided data, we mention that one cohort (n = 20) identified a rate of 55% with regard to MDM2 amplification in intimal sarcomas, and this correlated with a myxoid pattern; another cohort (n = 15) showed that MDM2-positive had a better prognostic than MDM2-negative immunostaining. To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10-20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy.

A Review of Endobronchial-Ultrasound-Guided Transbronchial Intranodal Forceps Biopsy and Cryobiopsy.

Benign and malignant mediastinal lesions are not infrequently encountered in clinical practice. Mediastinoscopy has long been considered the gold standard in evaluating mediastinal pathology. Since its introduction into clinical practice, endobronchial-ultrasonography-guided transbronchial fine needle aspiration (EBUS-TBNA) has replaced mediastinoscopy as the initial procedure of choice to evaluate mediastinal lesions and to stage lung cancer. Its diagnostic yield in benign mediastinal lesions and less common malignancies, however, has remained limited. This has led different proceduralists to investigate additional procedures to improve the diagnostic yield of EBUS-TBNA. In recent years, different published reports concluded that the addition of EBUS-guided intranodal forceps biopsy (IFB) and transbronchial cryobiopsy (TBCB) to EBUS-TBNA increases the diagnostic yield especially in benign mediastinal lesions and uncommon mediastinal malignancies. The purpose of this review is to describe how EBUS-IFB and EBUS-TBCB are performed, to compare their diagnostic yields, and to discuss their limitations and their potential complications. In addition, the review will conclude with a proposed algorithm on how to incorporate EBUS-IFB and EBUS-TBCB into clinical practice.

COVID-19 mRNA Vaccination-Induced Myopericarditis in an Otherwise Healthy Young Male: An Evidence-Based Approach to Differentiating From Perimyocarditis.

A 29-year-old male, otherwise healthy with no past medical history, presented to the hospital after a two-day history of pleuritic chest pain with a fever. He had received his first dose of the mRNA-1273 coronavirus disease (COVID-19) vaccine (Moderna) two months prior without any adverse reactions. He received his second dose approximately 24 hours before symptom onset and hospital presentation. Work-up was unremarkable for respiratory, autoimmune, and rheumatological etiologies. The patient was found to have electrocardiogram features and symptoms in keeping with pericarditis, C-reactive protein elevation, and a peak high-sensitivity troponin level of 9,992 ng/L suggestive of a component of myocarditis. A dilemma arose regarding whether this patient should be diagnosed with perimyocarditis or myopericarditis, terms often used interchangeably without proper reference to the primary pathology, which can ultimately affect management. A subsequent echocardiogram was unremarkable, with a normal left ventricular systolic function, but cardiac resonance imaging revealed myocardial edema suggestive of myocarditis. Without convincing evidence for an alternative explanation after an extensive work-up of ischemic, autoimmune, rheumatological, and infectious etiologies, this patient was diagnosed with COVID-19 mRNA vaccine-induced myopericarditis. The patient fully recovered after receiving a treatment course of ibuprofen and colchicine. This case explores how the diagnosis of COVID-19 vaccine-induced myopericarditis was made and treated using an evidence-based approach, highlighting its differentiation from perimyocarditis.

A hospital-based study of prostate biopsy results in Indian males.

Introduction: The prostate is a gland belonging to the male reproductive system. Aging results in the dysfunction of the prostate that may present as inflammation, enlargement, and cancer. Additionally, the diseases of the prostate including cancers are slow in progression, and therefore, it is difficult to diagnose them early. Hence, it is increasingly important for physicians to recommend histopathological examination of the prostate gland to identify, manage, and treat prostate cancers. This study was conducted to assess prostate diseases among biopsy specimen collected from patients with signs of prostate diseases. Materials and Methods: This prospective study was conducted in the Department of Pathology, Deccan College of Medical Sciences, Owaisi Hospital, Hyderabad, between June 2012 and September 2014. All gross specimens (n = 300) of the prostate such as the needle biopsies of the prostate, transurethral resection of the prostate (TURP) chips, and excised specimens of the prostate were included in the study. Histopathological examinations of the biopsies were performed for nuclear size, chromatin material, nucleoli, membrane thickness, irregularity, cytoplasmic granularity, staining, and cell border conspicuity. The biopsies were also assessed for lobule formation, secretions, polymorphonuclear leukocytes, lymphocytes, macrophages, connective tissue stromal cells, their arrangements, and acellular connective tissue material. Results: Of 300 total prostatic biopsies performed, 56 (18.66%) were identified as inflammatory lesions of the prostate (prostatitis), 98 (32.66%) revealed benign prostatic lesions (benign prostatic hyperplasia (BPH)), 112 (37.33%) were identified as BPH with premalignant lesions, and 34 (11.33%) were revealed as malignant tumors of the prostate. Chronic prostatitis (67.85%) was the common inflammatory lesion. The majority (91.42%) revealed epithelial lesions compared to stromal lesions (08.58%). BPH was predominantly (28.00%) noticed among patients in the age group of 61-70 years. Prostatic intraepithelial neoplasia (PIN) was observed majorly (53.35%) in the age group of 61-70 years. Most of the prostatic cancers were identified as adenocarcinomas. However, three variants were also categorized as small cell carcinoma, signet ring cell carcinoma, and transitional cell carcinomas. Conclusions: The results reveal that prostatic adenocarcinomas are predominant among the study population. Additionally, prostatic diseases including cancer are commonly noticed among people belonging to the age group of 61-70 years. More than one-third of patients showed BPH with premalignant lesions, and a majority of the study population showed evidence of chronic prostatitis.

A Novel KCNQ2 Variant in a Patient with a Combined Tremor Syndrome.

Background: Tremor disorders have various genetic causes. Case report: A 60-year-old female with a family history of tremor presented a combined tremor syndrome, transient episodes of loss of contact and speech disturbances, as well as distal painful symptoms. Genetic screening revealed a novel heterozygous missense variant in the KCNQ2 gene. Discussion: The KCNQ2 protein regulates action potential firing, and mutations in its gene are associated with epilepsy and neuropathic pain. The identified variant, although of uncertain significance, may disrupt KCNQ2 function and also play a role in tremor pathogenesis. This case highlights the importance of genetic screening in combined tremor disorders.

Explorative cost-effectiveness analysis of colorectal cancer recurrence detection with next-generation sequencing liquid biopsy in Spain, France, and Germany.

Background: Next-generation sequencing liquid biopsy (NGS-LB) for colorectal cancer (CRC) detection and surveillance remains an expensive technology as economies of scale have not yet been realized. Nevertheless, the cost of sequencing has decreased while sensitivity has increased, raising the question of whether cost-effectiveness (CE) has already been achieved from the perspective of European healthcare systems. Objectives: This health economic (HE) modeling study explores the CE of NGS-LB for CRC based on direct treatment costs compared to standard care without liquid biopsy in Spain, France, and Germany. Methods: A structured literature search was used to collect evidence from 2009 to 2020 on the stage-dependent quality of life (quality-adjusted life-years, QALY), efficacy, and total direct treatment costs (TDC) of NGS-LB. A decision-analytic Markov model was developed. Over the remaining lifetime, cumulative life expectancy (LE), TDC, and QALYs were calculated for 60-year-old men and women in CRC stage III with different assumed effects of NGS-LB of 1% or 3% on improved survival and reduced stage progression, respectively. Results: The use of NGS-LB increases LE by 0.19 years in Spanish men (France: 0.19 years, Germany: 0.13 years) and by 0.21 years in Spanish women (France: 0.21 years, Germany: 0.14 years), respectively. The 3% discounted cost per QALY gained was 35,571.95 € for Spanish men (France: 31,705.15 €, Germany: 37,537.68 €) and 35,435.71 € for Spanish women (France: 31,295.57 €, Germany: 38,137.08 €) in the scenario with 3% improved survival and reduced disease progression. Compared to the other two countries, Germany has by far the highest TDC, which can amount to >80k euros in the last treatment year. Conclusion: In this explorative HE modeling study, NGS-LB achieves generally accepted CE levels in CRC treatment from the health system perspective in three major European economies under assumptions of small improvements in cancer recurrence and survival. Confirmation of these findings through clinical trials is encouraged.

Is it worthwhile to use next generation liquid biopsy for cancer recurrence detection on patients with colorectal cancer? Colon cancer is common. Worldwide, almost one million people die from it every year. Next Generation Sequencing Liquid Biopsy is a very sensitive technology for detecting cancer cells and their genetic information in the blood. Therefore, it is a good way to detect cancer and to detect early recurrence of a previously treated tumor. This test procedure is not yet used very often. Therefore, it is still expensive. Furthermore, there are still no studies that have demonstrated that and how liquid biopsy can aid doctors and patients after initial treatment. The research team of this study has developed an analytical model to investigate what performance liquid biopsy should have to demonstrate an affordable patient benefit in terms of quality of life, survival and cost per additional quality-adjusted life year gained. To do this, they studied the existing medical literature and many cost studies on colorectal cancer for the countries of Spain, France and Germany to feed their model. Then, they made different assumptions about the performance of liquid biopsy and did calculations. In the process, they also particularly examined the significance of specific influencing factors such as costs or disease progression in so-called sensitivity analyses. As a result, the authors found that there are large differences in treatment costs for colorectal cancer between the three countries Spain, France and Germany. Furthermore, even small improvements in the progression of cancer and the survival of cancer patients lead to the economic efficiency of liquid biopsy for the health care system. However, these are still thought experiments, so the research team of this study says that there should be further clinical trials to assess the impact of liquid biopsy on cancer progression and patient survival by using this technology. By this, one could confirm or contradict the authors' educated assumptions and possibly pave a new way towards medical progress for people with colorectal cancer.

B-cell Lymphoblastic Lymphoma Presenting as a Sinonasal Mass: A Case Report.

B-cell lymphoblastic lymphoma (B-LBL) is an abnormal proliferation of lymphocyte precursor cells located primarily outside of the bone marrow and peripheral blood, typically in the mediastinum or other lymph nodes. It is often a disease of childhood that presents with lymphadenopathy, fatigue, pallor, bone pain, and weight loss with laboratory findings of anemia and thrombocytopenia. Initial presentations prompted by head and neck manifestations are exceedingly rare. A five-year-old girl with no significant past medical history presented with right facial swelling and mild proptosis on ophthalmologic evaluation. She was referred to a tertiary care facility by her local otolaryngologist for further management after computed tomographic imaging revealed right maxillary sinus opacification and erosion of the anterior maxillary bone. Her symptoms were initially responsive to prednisone and amoxicillin-clavulanate, and only right unilateral nasal discharge persisted with a near-complete resolution of other sinonasal symptoms. Notably, laboratory values, including complete blood count, were within normal limits. Given concern for the etiology of the bony erosion, the patient presented for a second opinion, where imaging and biopsy resulted in flow cytometry findings consistent with B-ALL/LBL. After a bone marrow biopsy, the ultimate diagnosis was Murphy's stage III B-cell lymphoblastic lymphoma. Malignant neoplasms of the sinonasal region are rare in children, where primary sinonasal B-LBL is a unique occurrence. Clinical features of sinonasal B-LBL in the paranasal sinuses may masquerade as pathologies such as acute sinusitis, orbital cellulitis, and benign tumors or polyps that can lead to a confounding diagnosis. In this case presentation, an initial response to steroids and antibiotics should not provide false reassurance when other features and signs, such as maxillary bone erosion, may suggest the presence of malignancy.

High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.

Rationale and design of the Innsbruck Diabetic Kidney Disease Cohort (IDKDC)-a prospective study investigating etiology and progression of early-stage chronic kidney disease in type 2 diabetes.

Background: The development of chronic kidney disease (CKD) in about 20%-40% of patients with type 2 diabetes (T2D) aggravates cardiovascular morbidity and mortality. Pathophysiology is of increasing relevance for individual management and prognosis, though it is largely unknown among T2D patients with CKD as histologic work-up is not routinely performed upon typical clinical presentation. However, as clinical parameters do not appropriately reflect underlying kidney pathology, reluctance regarding timely histologic assessment in T2D patients with CKD should be critically questioned. As the etiology of CKD in T2D is heterogeneous, we aim to assess the prevalence and clinical disease course of typical diabetic vs atypical/non-specific vs non-diabetic vs coexisting kidney pathologies among T2D patients with mild-to-moderate kidney impairment [KDIGO stage G3a/A1-3 or G2/A2-3; i.e. estimated glomerular filtration rate (eGFR) 59-45 mL/min irrespective of albuminuria or eGFR 89-60 mL/min and albuminuria >30 mg/g creatinine]. Methods: The Innsbruck Diabetic Kidney Disease Cohort (IDKDC) study aims to enroll at least 65 T2D patients with mild-to-moderate kidney impairment to undergo a diagnostic kidney biopsy. Six-monthly clinical follow-ups for up to 5 years will provide clinical and laboratory data to assess cardio-renal outcomes. Blood, urine and kidney tissue specimen will be biobanked to identify diagnostic and prognostic biomarkers. Conclusions: While current risk assessment is primarily based on clinical parameters, our study will provide the scientific background for a potential change of the diagnostic standard towards routine kidney biopsy and clarify its role for individual risk prediction regarding cardio-renal outcome in T2D patients with mild-to-moderate kidney impairment.