Case Report on a Rare Malignancy: Anorectal Melanoma

Introduction: Melanoma of the rectum is an extremely rare disease. The median survival rate is 2-5 years. Current treatment for this aggressive cancer is resection if possible and consider adjuvant or neoadjuvant radiotherapy;immunotherapy in nonresectable cases. Given the rapid spread of disease due to its submucosal growth and metastasis pattern, there is low success rates with treatments. Case Description/Methods: An 84-year-old male presented to the emergency department with an acute COVID-19 infection. The patient was also found to have gram-negative septicemia on blood cultures, so a CT abdomen/pelvis was performed (Figure 1a). The CT showed rectal wall thickening. A flexible sigmoidoscopy was planned for a future outpatient visit after recovering from his acute infection. The patient, however, developed an acute onset of dyspnea and had a high probability V/Q scan while in the hospital. He was started on anticoagulation, and shortly after starting therapy the patient developed bright red rectal bleeding. Due to the new onset of rectal bleeding it was decided to expedite the sigmoidoscopy. The sigmoidoscopy was performed in the hospital showing an ulcerated partially black pigmented non- obstructing medium-sized mass that was partially circumferential involving one-third of the lumen (Figure 1b). A biopsy of the lesion was taken using cold-forceps. The pathology stained positive for S100 consistent with melanoma. The diagnosis of anorectal melanoma was made, and colorectal surgery was consulted. The patient was deemed not to be a surgical candidate secondary to age and active COVID-19 infection. Oncology was consulted, and it was decided to start the patient on radiation and immunotherapy with a PD-1 inhibitor. Discussion(s): The symptoms of anorectal melanoma can be subtle and in this case report completely asymptomatic. Symptoms to be aware of are rectal bleeding and tenesmus. Diagnosing melanoma on sigmoidoscopy can be challenging as most tumors are not pigmented. Biopsies should be taken and sent for immunohistochemical staining for S100, if positive the patient should have a PET scan. Treatment choices for the tumor are based on staging. In a resectable tumor sphincter-saving local excision with radiotherapy to the site of the tumor and the pericolic and inguinal lymphatics is recommended. For unresectable tumors or tumors with distant metastasis, immunotherapy with PD-1 inhibitors (nivolumab and ipilimumab) is an emerging treatment choice.

SEVERE MYOCARDITIS WITH CARDIOGENIC SHOCK IN ADULT-ONSET STILL'S DISEASE AFTER mRNA COVID-19 VACCINATION: A CASE OF ATYPICAL PRESENTATION

Background/Aims Adult-onset Still's disease is a systemic inflammatory disease of unknown aetiology. Post-COVID-19 vaccine adult-onset Still's disease has been reported and was associated with only mild myocarditis. Here we report the first case of adult-onset Still's disease after mRNA COVID-19 vaccination presenting with severe myocarditis with acute heart failure and cardiogenic shock. Methods We described the case history of the patient. Results A 72-year-old Chinese woman developed gradual onset of fever, shortness of breath, sore throat, generalised arthralgia, malaise and poor appetite 15 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. Physical examination revealed fever, bilateral ankle oedema and elevated jugular venous pressure. Significant investigation results are shown in Table 1. Extensive viral panel tests (including enterovirus, influenza and cytomegalovirus) were all negative. Echocardiography showed severely reduced left ventricular ejection fraction of 20%. The acute heart failure was complicated by cardiogenic shock requiring intensive care unit admission. Myocarditis was later diagnosed. Although the heart condition subsequently improved, there were persistent fever and arthralgia, as well as the development of generalised maculopapular skin rash. In view of that, series of investigations were performed, which revealed persistent neutrophilic leucocytosis, hyper-ferritinaemia and liver function derangement, while autoimmune panel was grossly unremarkable and septic/viral workup was negative (Table 1). Contrast PET-CT scan showed no features of malignancy. Adult-onset Still's disease was diagnosed, and the patient was treated with oral prednisolone 40mg daily. The patient's condition responded to the treatment;the fever subsided and the leucocyte count and inflammatory markers were normalised, and she was subsequently discharged. Three months after discharge, the patient was clinically well with prednisolone tapered down to 5mg daily. Reassessment echocardiogram showed full recovery with LVEF 60%. Conclusion Severe myocarditis with acute heart failure and cardiogenic shock is a possible initial presentation of adult-onset Still's disease after mRNA COVID-19 vaccination. After exclusion of more common aetiologies, it is important to consider adult-onset Still's disease as one of the differential diagnoses in the presence of compatible features following COVID-19 vaccination, such that appropriate and timely workup and treatment can be offered. (Table Presented).

The Initial Response of Nuclear Medicine to the COVID-19 Pandemic

Objectives: COVID-19 posed profound challenges to nuclear medicine (NM) practice and education on an international scope. Initial lessons learned may be useful in understanding and optimizing dissemination of critical information during global disasters. To better understand the pandemic's initial manifold impact and responses that were in turn enacted, we systematically reviewed relevant articles published during the 2020 calendar year. Method(s): A librarian experienced in systematic reviews performed a rapid scoping review of the English language literature indexed in PubMed, Embase and Web of Science by crossing NM and COVID terms;445 citations were returned. Duplicate, extraneous, non-English and non-full text articles were excluded leaving 248 articles which were analyzed by origin, topic, design, and imaging details. Result(s): An array of topics, techniques, journals and countries of origin were encountered. 158 articles appeared in primary NMjournals, 26 appeared in generic radiology journals and 65 in non-imaging journals. Most frequent countries represented were USA (55), Italy (33), France (19) and UK (17), reflecting the hard-hit countries early during the pandemic. 118 clinical articles were case reports or small series of which 80 featured FDG-PET/CT. There were 36 observational studies. Among non-clinical topics, articles focused on safetymeasures (102), economics and recovery (23), remote reading (17) and education (8). There were 17 surveys. Society-based guidelines (47) and individual-group best practices (79) were published relating to cardiology (33), lung scintigraphy (12), andmultiple topics (48). Systematic (10) and narrative reviews (61) were less frequent than opinion articles (75). Frequent modalities discussed were FDG PET (156), nuclear cardiology (56) and lung scintigraphy (35). Conclusion(s): The medical literature has memorialized a robust response of information sharing during the initial challenges the COVID-19 pandemic relating to patient care, operations and education. Through scoping review, we have analyzed the nature of information disseminated. Opinions and single group best practices dominated the literature. Clinical reports during the first year were primarily case reports or small series, frequently FDG-PET/ CT. The nature of the literature matured as the year progressed, and sources of information broadened as the epidemic spread.

INTERIM RESULTS OF THE PML-16, PML-19 PROTOCOLS FOR PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA THERAPY

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Novel Ga-68-FAPI PET/CT offers oncologic staging without COVID-19 vaccine-related pitfalls

Ziel/Aim The global SARS-CoV-2 vaccination campaign brought attention to a recent pitfall in tumor staging by PET/CT. Several publications reported a non-specific F-18-FDG tracer uptake in axillary lymph nodes after COVID-19 vaccination. Ga-68-FAPI PET/CT is a new oncologic imaging tool that may overcome this limitation. Methodik/Methods For this purpose, we compared the tracer uptake in a head-to-head and same-day F-18-FDG and Ga-68-FAPI PET/CT study. 11 patients from our prospective database (NCT04571086) were included showing vaccine-related tracer uptake in axillary lymph nodes up to 6 weeks after COVID- 19 vaccination. Ergebnisse/Results Among the total of 11 patients, all (n = 11) showed visual positive uptake in the lymph nodes ipsilateral to the injection side on F-18-FDG PET. None (n = 0) of the included patients showed significant tracer uptake on Ga-68-FAPI PET. Follow-up imaging confirmed reactive nodal uptake in all patients. The tumor detection efficacy for these patients was 73 % for F-18-FDG and 94 % for Ga-68-FAPI. Schlussfolgerungen/Conclusions In our case series, Ga-68-FAPI demonstrated resistance to vaccine-related pitfalls while presenting superior tumor detection.

A Diagnostically Challenging Case of Primary Pancreatic Lymphoma

Introduction: Primary Pancreatic Lymphoma (PPL) is the exceedingly rare instance of extranodal Non-Hodgkin's Lymphoma developing mainly in the pancreas.We report a diagnostically challenging case of a patient presenting with a rapidly growing pancreatic mass, found to have PPL. Case Description/Methods: A 48-year-old female with past history of tobacco use presented with several months of cramping abdominal pain following COVID-19 infection. She denied weight loss, fevers, or night sweats. Her physical exam, CBC, CMP, lipase, LDH, and CA 19-9 were unremarkable. An abdominal ultrasound revealed a 2.8 x 1.9 x 3 cm cystic mass of the pancreatic head, most congruent with a pseudocyst. Worsening abdominal pain prompted repeat ultrasound one month later, which showed a doubling in size. Endoscopic ultrasound (EUS) with fine needle aspiration of the cystic mass and surrounding lymph nodes yielded cystic contents and reactive lymphadenopathy. Two months later, her abdominal pain worsened and repeat imaging showed further doubling in size with encasement of the celiac plexus. A second FNA performed via EUS redemonstrated cystic contents. An ultrasound-guided core needle biopsy of the mass revealed necrotic CD301 diffuse large B cell lymphoma (DLBCL). PET scan was suggestive of stage IV PPL (Figure). Imaging also identified an inguinal lymph node that returned as CD101 BCL61 high grade follicular lymphoma, which was thought to be a distinct lesion. She was started on R-CHOP. Her clinical course was complicated by the formation and subsequent rupture of a splenic artery pseudoaneurysm, gastrointestinal bleeding, anuric kidney injury, and intestinal ischemia. She ultimately transitioned to comfort care. Discussion(s): Primary pancreatic lymphoma comprises 0.6% of extranodal lymphomas and 0.2% of primary pancreatic tumors. The clinical presentation is often vague and includes abdominal pain, B symptoms, jaundice, or bowel obstruction. The diagnostic criteria according to the WHO requires that the (1) majority of tumor burden be localized to the pancreas and (2) existing nearby and distant lymph node involvement should be secondary to pancreatic presentation. A biopsy is required to diagnose PPL, which is histologically most often DLBCL. Our case highlights the challenges associated with diagnosing PPL despite two EUS with FNA. Although rare, one should proceed with a high index of suspicion for PPL in any patient presenting with a rapidly enlarging pancreatic mass.

Hypermetabolic ipsilateral supraclavicular and axillary lymphadenopathy: Optimal time point for performing 18F-FDG PET/CT after COVID-19 vaccination

Ziel/Aim We aimed at evaluating the incidence of SARS-CoV2 vaccine-related axillary and supraclavicular hypermetabolic lymphadenopathy (HLA) and evaluate which timepoint produces the least number of false-positive findings in HLA. Methodik/Methods For this retrospective, multi-center imaging study patients with any form of SARS-CoV2 vaccination prior to 18F-FDG-PET/CT between January 2021 and December 2021 were included. Patients were divided into six groups according to the timepoint of vaccination prior to 18F-FDG-PET/CT imaging: Group 1 (0-6 Days), Group 2 (7-13 Days), Group 3 (14-20 Days), Group 4 (21-27 Days), Group 5 (28-34 Days) and Group 6 (35-80 Days). As reference SUVmax of mediastinal blood pool (MBP) and SUVmax contralateral reference lymph node (RL) were determined. For each group, the following parameters were assessed. A) absolute SUVmax of HLA B) incidence of HLA [defined as the ratio of SUVmaxHLA/ SUVmax Mediastinal Blood Pool (rHLA/MBP)] greater than 1,5 C) rHLA/MBP D) ratio SUVmax HLA vs. SUVmax contralateral reference lymph node (rHLA/RL). Ergebnisse/Results HLA showed the highest incidence in Group 1(day 0-6) 16/23 (70 %). Similarly, SUVmax HLA and rHLA/MBP were highest in this group, SUVmax 4.97 +/- 4.1 and 2.58 +/- 2.1 respectively. The incidence of HLA, SUVmax HLA, and rHLA/MBP were higher in Group 3 (14-20 days) than in Group 2 (7- 13days);57 % vs 44 %;5.05 +/- 4.33vs 3.9 +/- 2.81 (p = 0.723 and 2.32 +/- 1.8 vs 1.83 +/- 1.38(p = 0.788). All parameters for HLA dropped markedly after at least 21 days of vaccination. There were no significant differences in SUVmax HLA, rHLA/MBP and rHLA/RL in group 4 (21-27 days), group 5 (28-34 days) and group 6 (35-80 Days). [1] Schlussfolgerungen/Conclusions It is crucial for diagnostic physicians to assess the recent history of COVID-19 vaccination prior to FDG-PET/CT scan to reduce the risk of false-positive calls. If feasible, FDG PET should be postponed by at least 3 weeks after SARS-CoV2 vaccination especially if an accurate evaluation of axillary status is required.

Novel role of 18F- FDG PET/CT in rhinosinonasal mucormycosis in the era of covid-19 infection

Objectives: In the Covid-19 era, there was a surge in the cases of a life-threatening infection of rhinosinonasal mucormycosis. Mucormycosis, popularly known as black fungus, is an infection caused by mycetes mucorales, an aseptate hyphae. Presently, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used imaging modalities for the management of patients with rhinosinonasal mucormycosis. The present study was aimed to evaluate the role of 18F- FDG PET/CT in the detection of recurrent or residual disease in post-surgical or post antifungal therapy in these patients for further management. Method(s): A total of 10 patients were included in this pilot study of Covid-19 positive patients and histologically proven mucormycosis (by KOH mount). 18F- FDG PET/CT was performed to assess the disease status in 6 postoperative/ post debridement patients and response to antifungal therapy in 4 patients, at an interval of 40 (range = 27-66) days post intervention. Result(s): The mean age of the patients was 45.0 +/- 11.65 years. The male: female ratio was 9:1. The common clinical presentation was ipsilateral facial or orbital pain and swelling. Covid-19 infection was positive in all the patients except one who had CT finding with HRCT score of 10/25 and hence was considered as post Covid-19 infection. Six out of 10 patients were diabetic on oral hypoglycaemic agents or insulin. All patients had a baseline CT/MRI for staging the initial extent of the disease. Surgical debridement was done in 6 out of the 10 patients followed by antifungal therapy (Liposomal Amphotericin B and Pozaconazole). Remaining four patients were treated with antifungal therapy. PET/CTwas performed after an average of 40 days of surgical/medical intervention, in whom clinical symptoms persisted or worsened even on antifungal therapy. 18F-FDG PET/CT showed metabolically active residual disease in all the patients with a mean SUVmax of 9.78 +/- 4.03. Conclusion(s): In the era of ongoing Covid-19 infection, black fungus has been a debilitating disease with high mortality and morbidity. Present study demonstrated that 18F-FDG PET/CT can be an efficient imaging tool for an early surgical/ medical treatment response assessment and restaging.

Esophageal Squamous Cell Carcinoma: An Unfavorable Complication of Achalasia

Introduction: Achalasia is a motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. It is a rare condition with an annual incidence of 0.5-1.2 per 100,000 individuals. The etiology of primary achalasia is unknown, however secondary achalasia can be attributed to malignancy, infections or systemic diseases such as amyloidosis. An infrequent complication of achalasia is esophageal squamous cell carcinoma which has a prevalence of 26 in every 1,000 cases. We present a case of interval locoregionally advanced esophageal squamous cell carcinoma only 2 years after a normal upper endoscopy. Case Description/Methods: A 67-year-old female with known achalasia and previous pneumatic dilation in her 30s presented to our outpatient clinic in 2019 with complaints of worsening chronic dysphagia. EGD was performed which revealed a significantly dilated esophagus with candida esophagitis. Despite completing antifungal therapy, she continued to experience dysphagia to solids and liquids. Barium swallow demonstrated absent peristalsis with pooling of contrast within the esophagus. High-Resolution Manometry testing demonstrated absent peristalsis. She opted for surgical myotomy, however due to COVID restrictions, the procedure was delayed. Repeat EGD was performed in 2022 for pre-surgical evaluation and showed a large obstructing friable esophageal mass in the lower third of the esophagus. Pathology was consistent with invasive poorly differentiated squamous cell carcinoma. PET scan showed locoregional disease with FDG-avid esophageal and gastrohepatic node lesions. She was started on chemoradiation with Paclitaxel and Carboplatin (Figure). Discussion(s): The risk of esophageal squamous cell carcinoma in achalasia has significantly increased with incidence of approximately 1 in 300 patients. The presumed mechanism of malignancy in achalasia is poor emptying resulting in food stasis, bacterial overgrowth and inflammation leading to dysplasia and development of carcinoma. Given the relatively low incidence, there are currently no guidelines on routine endoscopic screening to assess for malignancy in patients with achalasia. Survival rates are poor as patients are often diagnosed at advanced stages. This case aims to illustrate the importance and need for interval screening in individuals with long standing achalasia to improve outcomes.

Comprehensive Program of Neurotherapy for a Visual Artist with Post-Covid-19 Syndrome Following Sars-Cov-2 Infection and Severe Course of Covid-19 Treated in Long-Term Pharmacologically Induced Coma

Background: Case study: Conclusion(s): The purpose of the study was twofold: (1) to present post-COVID-19 syndrome, which involves a variety of ongoing neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders resulting from SARS-CoV-2 infection followed by a severe course of COVID-19 treated in long term pharmacologically induced coma in a visual artist, which impacted on her artwork;(2) to present QEEG/ERP results and neuropsychological testing results in the evaluation of the effectiveness of a comprehensive neurotherapy program, with individualized EEG-Neurofeedback, and art-therapy in the reduction of post-COVID-19 syndrome in this artist. Ms. G., 42, a visual artist, portraitist, with good health, became ill in May 2022. Allegedly flu symptoms appeared first. After a few days, shortness of breath joined in. The PCR test for SARS-CoV-2 was positive. The patient was hospitalized, referred to the ICU, put on a respirator and treated over 11days of a pharmacologically induced coma. Two months after leaving hospital the patient developed post-COVID-19 syndrome. She was diagnosed by an interdisciplinary team: a neurologist, neuropsychiatrist and neuropsychologist. A PET scan of her brain revealed extensive changes involving a loss of metabolism in various brain areas. The presence of complex post-COVID, neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders was found and a neuropsychiatrist suggested a diagnosis of post-COVID schizophrenia. She was refered to the Reintegration and Training Center of the Polish Neuropsychological Society.We tested the working hypothesis as to the presence of schizophrenia and there was no reduction in the difference of ERPs waves under GO/NOGO task conditions, like in the reference group with schizophrenia (see also Pachalska, Kaczmarek and Kropotov 2021). The absence of a functional neuromarker for schizophrenia allowed us to exclude this diagnosis and to propose a new disease entity, that being post-COVID-19 syndrome. She received a comprehensive two-component program of neurotherapy: (1) program A consisting in goal-oriented neuropsychological rehabilitation, including art therapy (see also: Pachalska 2008;2022b), and (2) program B, based on the most commonly used form of EEG-Neurofeedback: frequency/ power EEG-Neurofeedback, using 2 bipolar surface electrodes, with the protocols written for her specific needs (see also Thompson & Thompson 2012;Kropotov 2016). The comprehensive neurotherapy program lasted 10 weeks, EEG Neurofeedback and art therapy classes were conducted 3 times a week for 45 minutes each. We found that after the completion of the comprehensive neurotherapy program there was a statistically significant reduction in high beta activity compared to the normative HBI database, which is associated with a reduction of anxiety. Also, we observed the improvement of neurocognitive functioning in neuropsychological testing (a significant reduction of anxiety and a noticeable improvement in neurocognitive functions). It should be stressed that the artist was happy that she had regained the ability to create, and even sells her artwork, although her style of painting had changed. Almost all the neurological, psychiatric, neurocognitive, emotional and behavioral disturbances, were reduced in their severity. The artist showed marked improvement and was able to return to painting. The artwork she produced after her illness is in high demand with art collectors. It can be also helpful in the reintegration of the Self System, and the improvement in her quality of life. Human Brain Index (HBI) methodology might be very useful in diagnosing and developing therapies for patients with post-COVID-19 syndrome.Copyright © 2023, MEDSPORTPRESS Publishing House. All rights reserved.

Ultra-sensitive Detection of Alzheimer's Biosmarkers Using Plasmonic Optical Fiber Sensors

The emergence of the Covid-19 pandemic has drawn great attention to vulnerable people affected by major diseases. Among them, Alzheimer's disease (AD) is the most prevalent disease. However, a long-standing challenge is to achieve early diagnosis of AD by detecting biomarkers such as amyloid beta (Aβ42), thus avoiding the labor of specialized hospital personnel and the high cost of imaging examinations using positron emission tomography. In this paper, we report a straightforward approach to realize a non-invasive lab-around fiber (LaF) optical sensor for AD biomarker detection, which is based on a tilted fiber Bragg grating (TFBG) combined with a nanoscale metallic thin film. We successfully demonstrated the detection of Aβ42 in complex biological matrices with a detection limit of 5 pg/mL. Therefore, our TFBG-SPR biosensor platform enables large-scale early disease screening and has great potential for clinical applications in early AD diagnosis. © 2022 IEEE.

COVID-19 vaccination-related [18F]FDG-avid lymph node in a patient with marginal zone B-cell lymphoma

The [18F]FDG PET/CT is a crucial tool in the diagnostic process and monitoring of neoplastic diseases. Currently, during the global program of vaccination against COVID-19 and the possibility of axillary lymphadenopathy after this injection, the correct interpretation of PET/CT images is vitally significant and may create some difficulties. We present a case of increased uptake of [18F]FDG in an axillary lymph node in a PET/CT scan performed 2 days after the Pfizer BioNTech COVID-19 vaccine in a 48-year-old patient newly diagnosed with marginal zone B-cell lymphoma.Copyright © 2023 Via Medica.

Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial

Introduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB- 3111-214;NCT03846427);here, the final MAGNOLIA analysis is presented. Method(s): This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (>=1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomography (PET)-based Lugano criteria for IRC-confirmed fluorodeoxyglucose (FDG)-avid disease at baseline;non-avid disease was assessed by computed tomography (CT)-based criteria. Result(s): As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95];>=75 y=27.9%). MZL subtypes included extranodal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6);32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were efficacy- evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, (Figure Presented)(Figure Presented)ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade >=3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each;none led to treatment withdrawal. One pt (1.5%) had a Grade 3 gastrointestinal hemorrhage while receiving rivaroxaban. None of the pts required dose reduction. Conclusion(s): In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observedCopyright © 2023 American Society for Transplantation and Cellular Therapy

INTERIM RESULTS OF THE PML-16, PML-19 PROTOCOLS FOR PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA THERAPY.

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Post-COVID-19 Sydenham Chorea: A Case Report

Background: Sydenham chorea, or rheumatic chorea, is a movement disorder that is more prevalent among young people, with a mean age at symptom onset between 8 and 9 years. The condition is more common in females. Sydenham chorea is associated with rheumatic fever and is considered the most common cause of acute chorea in children. We believe that the present case is worth reporting since the occurrence of Sydenham chorea as a post-COVID-19 sequela has not been described in Brazil. Case Presentation: We report here the case of a 14-year-old girl with symptoms of acute chorea that emerged 15 days after treatment resolution of COVID-19 (SARS-CoV-2 or severe acute respiratory syndrome coronavirus 2). Brain computed tomography (CT) and magnetic resonance imaging scans showed no changes, and the laboratory tests revealed no signs of an active infectious process. In contrast, neurological positron-emission tomography/CT showed mild glycolytic hypometabolism in the bilateral mesial frontal region. Administration of an oral anticonvulsant resulted in a marked improvement in her symptoms. Conclusion(s): Despite major efforts of the scientific community for discovering treatments, preventive methods, mechanisms of action, and possible sequelae of SARS-CoV-2, there is still a long way to go to better understand this devastating pathological agent that has affected the global population.Copyright © 2023 Camargo and Morcillo.

The Role of Cardiac PET in Diagnosis and Prognosis of Ischemic Heart Disease: Optimal Modality Across Different Patient Populations.

PURPOSE OF REVIEW: Despite single-photon emission computerized tomography (SPECT) being the most used nuclear imaging technique for diagnosis of coronary artery disease (CAD), many now consider positron emission tomography (PET) as a superior modality. This review will focus on the advances of cardiac PET in recent years and its advantages compared to SPECT in diagnosis and prognosis of CAD. RECENT FINDINGS: PET's higher resolution and enhanced diagnostic accuracy, as well as lower radiation exposure, all help explain the rationale for its wider spread and use. PET also allows for measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which aids in several different clinical scenarios, such as diagnosing multivessel disease or identifying non-responders. PET has also been shown to be useful in diagnosing CAD in various specific populations, such as patients with prior COVID-19 infection, cardiac transplant, and other comorbidities.

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.

Right atrial thrombus in a patient after COVID-19 pneumonia

Background: Significant coagulopathy and hyperinflamation are found in patients with coronavirus disease 2019 (COVID-19). Case report: 44-year-old male patient was admitted to the Infective Clinic with a severe form of pneumonia COVID-19.The disease is complicated, with sub-segmental embolization of the lungs and pneumothorax, which are confirmed with laboratory and computed tomography (CT) lung with angiography. On the third day of hospitalization, an echocardiogram is performed, which shows global hypocontractility of the left ventricular walls with a reduced ejection fraction EF 45%. The right ventricle was borderline. After the applied therapy, the patient's condition improves and he is discharged home with anticoagulant therapy. An echocardiography (Figure 1) performed as part of a cardiology examination one months after discharge from the hospital diagnosed a mass in the right atrium (35x27mm), which could correspond to a thrombus. Calcifications were visualized in the mass. The patient is readmitted to the Cardiology Clinic and intravenous heparin is indicated. Perform transesophageal echocardiography (Figure 2) and confirm the presence of a mass consistent with thrombus. Cardiac CT (Figure 3) shows mass in right atrium extending into the inferior vena cava, and CT of the abdomen shows thrombosis of the inferior vena cava. Cardiac magnetic resonance (Figure 4) showed a mass in the right atrium, which, corresponds to a thrombus adherent to the interatrial septum. After application of contrast, focal zones of higher intensity are visualized, zones of fibrosis on interventricular septum, anterior l and inferior and lateral wall of subepicardial and intramyocardial localization, which correspond to the sequelae of the inflammatory process, with ejection fraction 45%. The right ventricle has normal dimensions. After unsuccessful therapy with unfractionated heparin, the thrombus was successfully surgically extracted. Conclusions: Cardiac imaging modalities, including transthoracic or transesophageal echocardiography, cardiac magnetic resonance, cardiac computed tomography, and 18Ffluorodeoxyglucose positron emission tomography have a complementary and reinforcing role for the evaluation of cardiac masses. [ FROM AUTHOR] Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)