Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

We should be learning as much from failure as success

'You do not know what you will find, you may set out to find one thing and end up discovering something entirely different'-Alexander Fleming As the pace at which medicine is advancing continues to accelerate, haematologists will increasingly find themselves practising unfamiliar medicine and using novel treatments. Whilst most scientific breakthroughs hopefully lead to an overall improvement in quality of life and prognosis, it is imperative that enough attention is paid to the shortcomings of new treatments and adverse events. The recent COVID-19 pandemic is a stark reminder of the cyclical nature of history and the need for healthcare professionals to utilise lessons learnt by our predecessors. Fleming and the discovery of penicillin highlights how mistakes in practice can sometimes lead to unexpected but useful revelations. The use of thalidomide as a treatment for hyperemesis gravidarum in the 1960s devastatingly lead to birth defects in thousands of people. Today, the repurposing of thalidomide, through lateral thinking and further study, has contributed to significant improvements in the prognosis of patients with Multiple Myeloma.1 Mortality following allogenic stem cell transplant continues to decrease overtime as knowledge surrounding complications and how to manage these improves, despite the fact that patients receiving stem cell transplants are becoming increasingly complex.2 These examples from history demonstrate the merit in studying adverse events and undesired outcomes. National reviews of patient health records indicate that errors currently occur in 10% of hospital admissions.3 With new treatments and more complex patients this will likely increase. It is estimated that voluntary reporting by healthcare professionals of such events only occurs 70% of the time.3 History should be used to guide essential changes in attitudes towards error reporting and help to create an ethos where 'failings' are more willingly recognised as a tool to guide improvement and innovation.

Inflammatory biomarkers: Breast cancer survival and possible role in COVID-19 associated comorbidity

It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.

ECMO for the immunocompromised pediatric patient: Our experience

Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.

Importance of IP-10 as a biomarker of host immune response: Critical perspective as a target for biosensing

While the exploration into biomolecules for diagnostic and prognostic devices continues to develop, many molecules continue to be examined for individual diseases or treatments. Consequently, it can be difficult to fully understand the scope of one individual molecule's current and potential clinical utilization. The scope of this study aimed to assess the potential of Interferon Gamma-induced Protein 10 (IP-10) as a biomarker in a wide variety of diseases, both as a main and supplemental indicator of disease infection and progression. IP-10 is a chemokine secreted in response to IFN-gamma playing a major role in the activation and regulation of inflammatory and immune responses within the body. Currently, IP-10 has displayed potential application in diseases such as COVID-19, tuberculosis, sepsis, Kawasaki disease, cancer, and many more. Molecular assays developed for the detection of IP-10 take longer testing time, sophisticated instrument utilization, and need more sample volumes. These cannot be utilized for bedside patient monitoring during the illness state of the patient. Biosensing tools are alternative methods used at clinical sites due to their rapid results. Though many types of sensing mechanisms established for the detection of disease biomarkers such as optical, piezoelectric sensors, and electrochemical biosensors are far beyond the other sensing methods due to their ease of mechanism, rapid results, and portable nature. IP-10 has been a promising biomarker in different diseases, evaluation of IP-10 levels at different time points of treatments is necessary. To achieve this, current conventional methods cannot be used and thus a portable device that provides rapid results is in demand. Such point-of-care (POC) device development for IP-10 analysis is very crucial in the current scenario. Beyond this, the clarification of its physiological role in healthy and infected individuals could allow for more proper utilization in clinical diagnoses, prognoses, treatment monitoring, and more. Overall, this study was developed to summarize the associations currently created between levels of IP-10 and other biomolecules and diseases.Copyright © 2023 The Author(s)

Liver injury caused by SARS-CoV-2 delta and omicron-variant in Taiwan

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has recently emerged and spread globally. An outbreak of coronavirus disease 2019 (COVID-19) caused by the Delta variant occurred in Southern Taiwan in June 2021 and has been eliminated [1]. However, in April 2022, there was an outbreak of the Omicron variant in Taiwan. Fifteen patients with Omicron variant were admitted to our hospital from April 26 to May 1, 2022. We compared the clinical characteristics of the patients with the Delta variant in June 2021 and the Omicron variant in April 2022 (Table 1). These laboratory data were the first laboratory data at admission, and no anti-COVID-19 therapy was prescribed before these data. There were no differences in age (59.9 vs. 57.1 years, P = 0.96), male gender (63.6 vs. 60.0%, P = 1.00), diabetes ratio (27.3 vs. 35.7%, P = 1.00), body mass index (25.0 vs. 26.0 kg/m2, P = 1.00), pneumonia ratio (18.2 vs. 40.0%, P = 0.40) between the Delta and Omicron variants. There were also no differences in serum levels of aspartate aminotransferase (AST) (40.1 vs. 25.8 IU/L, P = 0.24) and alanine aminotransferase (ALT) (26.3 vs. 27.2 IU/L, P = 0.64) between the two groups. All the patients with the Omicron variant were symptomatic. The most common symptoms were upper respiratory tract infections (60.0%) (Supplementary Table 1). Six patients developed pneumonia without mechanical ventilator support requirement during admission (40.0%). Remdesivir, Paxlovid, or Molnupiravir were prescribed to patients according to their clinical conditions. Among the patients with the Omicron variant, nine (60.0%) had past medical history of diabetes, four (26.7%) had hypertension, three had chronic kidney disease (20.0%), and three had malignancy history (20.0%). COVID-19 might cause liver injury and lead to a more unfavorable prognosis [2]. In this study, about one-fifth of the patients suffered from liver injury, which was similar to previous studies [3]. There was no difference in liver injury between the Delta and Omicron variants in our study, which echoes previous research [4]. COVID-19 vaccination might protect against symptomatic diseases caused by the Omicron variant [5]. Vaccination rates have increased since 2021. In the study, over ninety percent of the patients have received at least two doses of vaccination. In conclusion, we demonstrated no difference in liver injury ratio between the Delta and Omicron variants. To our knowledge, this is the first report that compares the Delta and Omicron variants in Taiwan.

Hepatocellular Carcinoma Presenting as a Clival Mass

Introduction: Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancer and has a poor prognosis. Clivus metastasis is rare with only a few reported cases in the medical literature. We report a case of a patient who presented with clival mass found to have metastatic HCC. Case Description/Methods: A 63-year-old woman presented for neurosurgical evaluation after she was found to have a skull base mass on computerized tomography (CT) of the head at an outside hospital. She endorsed dysphagia for three months, however denied headaches or visual disturbances. A magnetic resonance imaging (MRI) revealed a 5.4 cm by 2.9 cm by 3.6 cm mass in the clivus, which was deemed as the cause of dysphagia (Figure 1a). The patient subsequently underwent an endoscopic transsphenoidal resection of the clival mass. Histopathology from the tissue revealed a hepatoid carcinoma, concerning for metastatic HCC (Figure 1b and 2c). Immunohistochemical strains were positive for hepatocytic marker arginase-1 (Figure 1d). Laboratory studies revealed alpha fetoprotein (AFP) of 56,344 ng/mL, CA-125 of 376 ng/mL, normal B-HCG and carcinoembryonic antigen (CEA). Thereafter, a triple phase CT of the liver revealed two LI-RADS 5 lesions suggestive of HCC as the primary malignancy. Patient's case was discussed at multidisciplinary tumor board with recommendations for systemic immunotherapy with atezolimumab plus bevacizumab and radiation therapy to the clivus. Discussion(s): The incidence of HCC has almost tripled since the 1980s making it the fastest rising cause of cancer related deaths. Metastasis to the brain comprises 0.26% to 2.2% of cases and the skull base is the most rarely affected anatomical site. Although CNS presentation is rare, we may see more neurological manifestations of metastatic HCC with the persistence of chronic hepatitis infections, the rise of metabolic diseases such as NASH, and an increase in alcohol-related liver disease during the COVID-19 pandemic. Although exceedingly rare, metastasis to the clivus should be considered in the differential diagnosis of skull base masses. Despite detection and treatment, prognosis remains poor and emphasis should be placed on consistent HCC surveillance. This case emphasizes that skull masses must be evaluated diligently as they can be the first sign of underlying liver malignancy. Given the morbidity and mortality associated with HCC, recognition of atypical manifestations of HCC can lead to a prompt diagnosis and initiation of life-saving treatment. (Figure Presented).

Prognostic Value of Elevated Lipase in Pancreatitis versus Non Pancreatitis Hyperlipasemia (NPHL) due to Non-Malignant Causes

Introduction: While elevated lipase is typically used to diagnose acute pancreatitis, it has also been associated with other critical disease states including sepsis, COVID-19, bowel obstruction, and trauma. In this study we compared outcomes of patients with elevated lipase who had pancreatitis and NPHL. Method(s): Retrospective analysis was performed on all patients who presented to the Emergency Department between February 2016 and August 2020 with lipase >= 3x the upper limit of normal. Patient demographics and past medical history, including active cancer, were noted. Patient outcomes were followed through November 2021. If applicable, dates of death were also documented. Result(s): 414 total patients were included in this study. Upon initial evaluation, 305/414 (74%) were diagnosed with acute pancreatitis (AP) and 109/414 had NPHL. The age (54 617 vs. 58 618, p=0.0220), Sex (male 164/305 vs. 49/109, p=0.1194), and BMI (28.9 67.4 vs. 25.8 64.6, p=0.0066) were compared between the AP and NPHL groups. The serum lipase in the AP and NPHL group were respectively 1471 61070 vs. 605 6555 (p< 0.0001). The most common causes of NPHL were sepsis (10/109;9%) renal failure (7/109;6%), GI bleed (5/109;4%), and bowel obstruction (5/109;4%). The NPHL group had higher rate of malignancy (29/105;28%) compared to those with AP (35/305;11%, p< 0.0001). NPHL patients without malignancy had a higher mortality rate (63/80;80%) compared to those without malignancy in the AP group (17/270;6.3%, p< 0.0001). The most common malignancy in patients with AP was breast (6/35;17%, vs. 3/29;10%, p=0.4943). In NPHL, the most common malignancies were pancreatic (4/29;14%, vs. 3/35;9%, p=0.6920) and bowel malignancies (4/29;14%, vs. 4/35, 11% p51.0000). Conclusion(s): Patients with NPHL without malignancy have higher mortality than those with pancreatitis despite lower serum lipase levels. A limitation of our study is the difference between age and BMI of AP versus NPHL patients. Whether this impacts the prognostic relevance of NPHL on survival need to be explored in future studies.

An Evaluation of the Causes and Outcomes of Haemophagocytic Lymphohistiocytosis in Sheffield Teaching Hospitals: 2016 to 2021

Background/Aims Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines;treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH. Methods This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel. Results HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still's disease (n=5);antiphospholipid syndrome (n=2);JO1 dermatomyositis (n=1);SLE (n=1);and rheumatoid arthritis (n=1). Other causes included unknown (n=3);combined systemic JIA and sickle cell crisis (n=1);medication (alemtuzumab) (n=1);and primary HLH (n=1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%);after March 2020, the commonest trigger was infection (64%);COVID-19 explained 42% of cases. Mortality fell from 72% to 31%. Conclusion In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified;we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locallyagreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment. (Table Presented).

28th Italian Melanoma Intergroup National Congress

The proceedings contain 35 papers. The topics discussed include: germline variants and prognostic factors for cutaneous melanoma in children and adolescents;association between polygenic risk score and multiple primary melanoma;Porocarcinoma: an epidemiological, clinical, and dermoscopic 20-year study;primary cutaneous melanoma and COVID-19: a hospital-based study;atypical spitz tumors: an epidemiological, clinical and dermoscopic multicenter study with 16 years of follow-up;pediatric melanoma: an epidemiological, clinical and dermoscopic multicenter study;recurrence-free survival prediction in melanoma patients by exploiting artificial intelligence techniques on melanoma whole slide images;ultra-high frequency ultrasound and machine learning approaches for the differential diagnosis of melanocytic lesions;and genetic determinants of response to therapy in a real-world setting of advanced/metastatic melanoma patients: whole-exome sequencing and CFDNA analysis.

Autoimmune Enteropathy (AIE) in a Patient Diagnosed with Thymoma: A Case Report

Introduction: Autoimmune enteropathy (AIE) is a very rare immune disorder that mainly attacks the gastrointestinal tract by T-cell. The full pathology mechanism is not clear. Typically, characterized by intractable diarrhea and nutritional malabsorption with extra-intestinal manifestations. The proposed diagnostic criteria include small bowel villous atrophy not responding to diet restriction, circulating gut epithelial cell autoantibodies (GECA), and lack of immunodeficiency. We describe a case of AIE with extensive GI involvement, presenting in a 60-year-old patient diagnosed with Type AB thymoma. Case Description/Methods: Our gentleman with a history of Covid-19 complicated with pulmonary embolism and an incidental finding of malignant thymoma. A CT-guided biopsy was consistent with undifferentiated malignant thymoma supported by immunohistochemistry staining. Subsequently, complicated severe diarrhea erupted with significant weight loss. Conservative management, antibiotics, and diet restriction were ineffective. Diagnostic work-up was unremarkable except for anti-enterocytes antibodies (AEA) and anti-goblet cells antibodies (AGA). Bowel biopsy revealed villous blunting, loss of Paneth cells, and minimal intraepithelial lymphocytosis with no evidence of crypt abscesses. Corticosteroid and Octreotide have helped the patient's diarrhea. Thoracoscopy thymectomy performed with radiation therapy due to local and lymphovascular invasion. Discussion(s): AIE characterized by severe villous blunting with the absence of goblet cells and Paneth cells, intraepithelial lymphocytosis, and increased crypt apoptosis. In comparison, graft vs host disease lack crypt abscesses, celiac disease shows increase in the intraepithelial lymphocytosis with intact goblet and Paneth cells, whereas inflammatory bowel disease has intact goblet and Paneth cells, and CVID characterized by absence of plasma cell in the lamina propria. The presences of the GECA are nonspecific but it may help in confirming the diagnosis or may predict the prognosis and recurrence. Only AGA has been reported in IBD. Neither has been observed in celiac disease. The low incidence of AIE and the limited existing literature available on the optimal guidance in management. Oral nutritional supplementation as well as total parenteral nutrition is helpful. The target is to control diarrhea and optimize the nutritional status before surgery. The main treatment is thymectomy.

Ablation for hepatocellular carcinoma (HCC)

Ablation includes ethanol injection, radiofrequency ablation (RFA), microwave ablation (MWA), etc. Ablation can be potentially curative, minimally invasive and easily repeatable for recurrence. RFA has been the most widely used ablation technique for liver tumors. The new-generation MWA system incorporating antenna cooling and high-power generation has attracted attention. It can create a more predictable ablation zone and a larger ablation volume in a shorter procedure time. Many high-volume centers have introduced new-generation MWA in Japan. However, many studies failed to show that new-generation MWA is superior to RFA in terms of local control and overall survival. In MWA, clinical data have been insufficient compared with those of RFA. There has been keen competition between surgical resection and ablation for almost 40 years since the era of ethanol injection. In 2021, SURF trial revealed that overall survival and recurrence-free survival were not significantly different between surgical resection and RFA. SURF trial was a multicenter randomized controlled trial in which 49 major centers in Japan enrolled patients with good hepatic function (Child-Pugh scores <= 7) and primary HCC of largest diameter <= 3 cm, and <= 3 nodules during the 6-year period of 2009-2015. The registered patients were followed for at least 5 years. As the result of SURF trial and other comparative studies, the revised Japanese clinical practice guidelines in 2021 treats hepatic resection and ablation equally for patients with <= 3 lesions, <= 3 cm in diameter. Recently, the combination of systemic and locoregional therapies has been attracting much attention. Systemic therapy using molecular targeted agents or immune checkpoint inhibitors is used for advanced HCC which cannot be treated by surgery or ablation. On the other hand, some locoregional therapies, such as hepatectomy and ablation, are potentially curative, but they cannot be indicated for advanced HCC. Combination of both therapies is an approach to improve the prognosis of advanced HCC, which is not indicated for curative treatment. Systemic therapy is used to shrink the tumor, and then locoregional therapies are performed to eradicate it. The combination may build a new strategy for advanced HCC. Ablation is highly operator-dependent. The skills and outcomes are very different from operator to operator. Before the pandemic of COVID-19, we held domestic and international training programs for intermediate and advanced doctors and hands-on seminars for young doctors. These were activities to exchange knowledge and experience and standardize the procedure. During the pandemic, we cannot get together. Since August 2020, we have conducted Japan Ablation Webinar 8 times with a total of 1,566 participants. We have also conducted International Ablation Webinar 4 times with a total of 1,272 participated doctors. Education is important to acquire skills and knowledge for successful ablation. We have established Japan Academy of Tumor Ablation (JATA) this year. There are two triggers. One is that SURF trial revealed that there is no difference between hepatectomy and ablation. The other is that ablation for lung, bone and soft tissue and kidney cancers has become reimbursed with health insurance since this September.

Gastrointestinal stromal tumors in elderly patients

Background: Gastrointestinal stromal tumors (GISTs) account for 1 to 3% of all primary malignant tumors of the gastrointestinal tract. The global incidence of GISTs varies in the range of 7-15 cases per 1 million people per year. In about 95% of cases, the incidence is sporadic. Despite the fact that some success has been achieved in the treatment of this pathology, the problem of GISTs treatment is urgent, especially in elderly and senile patients in particular. The aim of the study: To study the age-related characteristics of GISTs development in patients of older age groups. Material(s) and Method(s): A retrospective analysis of 56 clinical cases of GISTs in patients of different age groups according to the WHO classification was carried out in the study. Result(s): The most common variant of the immunohistochemical structure was the spindle cell one 62.5%. In most cases, tumors were localized in the stomach 82.2%. Elderly patients had larger tumor sizes compared with young and middle-Aged patients. In patients of older age groups, the disease was most often detected at stage II. In most cases, a comorbid pathology was detected, most often a combination of several diseases of the cardiovascular system. Conclusion(s): In patients of older age groups, the spindle cell structure of the GISTs is most common, the tumor was most often localized in the stomach (77.4%), most often the tumor was localized along the lesser curvature. In most cases, the tumor was up to 10.0 cm in diameter. On average, the disease was detected at stage II. Comorbid pathology occurred in 87.3% of cases. In 2020-2021, the disease was detected more often, the of tumors sizes were smaller, due to an increase in the number of CT scans of the chest for the diagnosis of the new coronavirus infection.Copyright © 2022 AME Publishing Company. All rights reserved.

Opportunities for providing surgical care to cancer patients during the COVID-19 pandemic.

It is now known that patients with chronic diseases, including those with cancer, are at an increased risk for a severe course of and death from COVID-19. This is due both to systemic immunosuppression caused by the tumor process and to the consequences of antitumor treatment. To provide surgical care to cancer patients during a pandemic is a challenging task. Perioperative SARS-CoV-2 infection is accompanied by a high risk for respiratory complications;however, a delay in surgical treatment for ma-ny cancers has a negative impact on cancer prognosis in the patient. Therefore, it becomes apparent that there is a need for strict selection of patients, in whom the benefits of surgical treatment outweigh the potential risk of severe complications;moreover, ways should be developed to provide the safest possible elective surgical care under the existing conditions. The P.A. Herzen Moscow Oncology Research Institute, Branch, National Medical Radiology Research Center, has not stopped providing care to cancer patients during the pandemic conditions.Copyright © 2021.

Competitive cause of death in elderly breast cancer survivors

Background: Breats cancer is a major health problem in elderly ( >= 70 years) women. Increase incidence with age and the progressive increase in life expectancy mean that the numbers in elderly breast cancer diagnosis are increasing. These patients do not always receive the proper treatment and despite this the survival of this population is not always depends on cancer, there are other competing causes of death typical of the aging population. Method(s): A retrospective observational analysis of women >= age 70 diagnosed with breast carcinoma in HUPHM between 2014 and 2020 was made. Clinical, pathological data and stages at diagnosis were analyzed. We checked our patients with the national death center (official national registry) thus obtaining an exact date of death and the cause of death. Data updated in January 2023 , ensuring a minimum follow-up of 24 months. We excluded deaths from Covid or of unknown cause to avoid bias. Result(s): A total of 421 patients were analyzed, mean age of 78.6 years and median follow-up of 48 months. 28% of patients had died at the time of analysis, 11% due to cancer and 17% from other causes. If we analyze the population deceased by cancer, no deaths are detected in patients diagnosed with carcinoma in situ (4% of the population), in stage I (30% of the population) the cumulative incidence of cancer death at 5 years is 3%, 7% In stage II (30% of the population), 15% in stage III (16%) and 70% in stage IV (12%). Death by other causes are more frequent in early breast cancer, the cumulative incidence at 5 years are 10% in stage I, 22% in stage II, 44% in satge III and just 10% in stage IV. The most frequent causes of death in this population were caridovascular events and infections. There are no differences in 5-year mortality according to histological subtypes 20%, 12%, 25% and 12% for triple negative, Rh+/HER2-, RH+/her2+ and RH-/HER2+ respectively. Conclusion(s): Although elderly patients do not receive optical treatments, mortality from cancer in early stages is incidental at 5 years, a different scenario is seen in metastatic disease in which the patient's prognosis depends mainly on the oncological disease, Therefore, an effort should be made in the treatment of these patients with metastatic breast cancer since adequate treatments can have a clearly positive impact on the survival of patients. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023

Impact of COVID-19 on breast cancer screening in the Brazilian Unified Health System (SUS)

Objectives: investigating the impact of the pandemic on breast cancer screening in the Unified Health System, in addition to comparing the data obtained from other countries. Method(s): a quantitative cross-sectional observational study was carried out, with references from the Cancer Information System - SISCAN on the number of mammograms performed from 2014 to 2022 by women in Brazil. Result(s): data regarding mammography in the high-risk population showed a drop of 38, 39% from 2019 to 2020. While in screening mammography, the decline was slightly more significant, at 39.18% in the same period. Regarding diagnostic mammography, the reduction was 33.15%, and in target population mammography, the peak was in 2019 with 2.721.075. On the other hand, the performance of mammography in patients already treated had a smaller decrease of 9.35%. Conclusion(s): there was a significant reduction in the number of mammograms performed in 2019 and 2020, which might lead to a late diagnosis of the disease and a worse prognosis.Copyright © 2023 Faculdade de Medicina de Ribeirao Preto - U.S.P.. All rights reserved.

Treating Lymphoma in the Pandemic Era: What We Learned from Our Experience at Fondazione Irccs Istituto Nazionale Dei Tumori

From March 2020 to May 2022, when SARS-CoV2 pandemic started spreading in Italy, 15 consecutive patients with non-Hodgkin Lymphoma (NHL) have been treated at the Pediatric Unit of Fondazione IRCCS Istituto Nazionale dei Tumori. Three of 15 patients developed COVID19 while on treatment [1 Burkitt lymphoma (BL), 1 anaplastic large cell lymphoma, 1 lymphoblastic T-cell lymphoma (T-LL)] and one patient at diagnosis [gray zone lymphoma (GZL), previously misdiagnosed as Hodgkin lymphoma]. Median age at diagnosis was 12 years;3 were male. Median positivity time of the nasal swab was 58 days (range 9-107 days). All patients remained asymptomatic or paucisymptomatic (flu-like symptoms) while positive. The first positive patient with T-LL, was in the induction phase of the Euro-LB-02 protocol guidelines: he succeeded in completing the whole treatment during the 107 days of swab positivity, experiencing mild toxicities (grade 2 transaminases and grade 3 lipase increase, both reversible) without significant delays. For this reason, we reduced the total dose of the first HD-MTX (protocol M) and administer the subsequent doses in 6 hours infusion instead of 24 with no further toxicities. After this first experience, all the subsequent patients have been treated accordingly, without major deviations from the established protocols. Minor precautions: the patient with refractory GZL received IEP course instead of IGEV as second-line treatment to avoid severe subsequent immunosuppression;the patient with BL omitted the fourth course of Rituximab during the period of swab positivity. Overall, we did not observe outstanding toxicities except for a toxic MTX level with subsequent reversible acute renal failure. Main teaching from these pilot experiences, which may translate into guidelines: 1) SARS-CoV2 infection is not an absolute contraindication to the oncological treatments. This is of main importance for the patients affected by lymphoma whose dose-intensity has a prognostic value. 2)We need to pay caution during HD-MTX treatment;indeed, we observed unexpected similar toxicities in other patients treated with HD-MTX for other solid malignancies. 3) The clearance of SARS-CoV2 might be exceptionally prolonged with persistent positivity of the nasal swabs for a longer time than the matched healthy population due to the immunosuppression characterizing lymphoma patients. For this reason and given the importance of maintaining the dose-intensity, specific treatments aiming at speeding up the clearing process are warmly suggested. (Figure Presented) Figure 1: (: 091) ITHACA study design and blood sampling time points. (OHT = Orthotopic Heart Transplant).Copyright © 2022 Elsevier Ltd. All rights reserved.

Prognosis Score for Overall Survival with CAR-T Therapy in Aggressive Lymphoma

Background: Despite the transformative potential of chimeric antigen receptor T (CAR-T) therapy, more tools to assist with identifying patients with increased likelihood of benefitting from this therapy will be helpful, particularly given the logistical complexity and socio-economic demands for CAR-T relative to other therapies. Health care resource restriction during the COVID-19 pandemic highlights the need for these tools. We present a simple survival score that uses 3 readily available clinical labs: platelet (plt), absolute lymphocyte count (ALC), and Lactate dehydrogenase (LDH), to predict the risk of dying within 6 months of CAR-T therapy in patients with aggressive lymphoma. Method(s): We conducted a retrospective chart review of patients with aggressive non-Hodgkin lymphoma (NHL) who received FDA-approved CAR-T between Jan 2018 to Jan 2022 at Mayo Clinic Rochester.(Table Presented)Results: Among a total of 110 pts who received CAR-T, 27 (25%) pts died within the first 6 months post CAR-T infusion (OS <= 6 months). Disease progression was the main cause of death (18/25, 72%), followed by infection (4/25, 16%), CAR-T related (HLH/MAS, 2/25, 8%), second primary malignancy (1/25, 4%) and unknown (2/25, 8%).Baseline demographics were comparable between the OS>6months and <=6months groups (Table 1). Patients' ECOG, Karnofsky performance status and 11 labs at the time of evaluation for CAR-T therapy (initial eligibility assessment, prior to leukapheresis) were compared between those who died from any cause within 6 months of CAR-T infusion and those who did not. Hemoglobin, plt, ALC, absolute monocyte count, CRP, ferritin, and LDH were selected as clinically and/or statistically significant variables for multivariate testing. Multivariate regression with boot-strap testing identified plt, ALC, and LDH as the most predictive variables with 80.9+/-11.7% accuracy for predicting death within 6 months of CAR-T infusion. Patients were scored 0-3 using these 3 labs, with 1 point assigned for plt <= 100 X109/L, ALC <= 0.4 X109/L, or LDH > 222 U/L (upper limit of normal). OS by this survival score is shown in Figure 1.(Figure Presented)Discussion: Due to the curative potential of CAR-T, patients with broader characteristics than those treated on registration studies have been treated in standard of care practice. While an estimated 5%-10% risk of CAR-T associated deaths in the first 3 months is seen across all patients in clinical trials, predictors for early death after CAR-T in real-world patient populations can provide additional context for pts and providers when selecting treatment. This survival score is important proof of concept that a simple model using readily accessible clinical labs at the time of CAR-T evaluation could provide additional context to help with additional clinical decision-making. Multicenter prospective studies will help define and validate the definitive survival scoring system.Copyright © 2023 American Society for Transplantation and Cellular Therapy