SARS-CoV-2 spike S1 mediated lung tumor regression in a mouse model

Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.

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.

THE IMPACT OF THE SARS-COV-2 PANDEMIC ON THE EPIDEMIOLOGICAL PICTURE AND CHARACTERISTICS OF COLORECTAL CANCER - A RETROSPECTIVE ANALYSIS OF THE DEPARTMENT OF ONCOLOGY AND RADIOTHERAPY, UH of SPLIT, FOR THE YEAR 2020 IN COMPARISON TO PRE PANDEMIC 2017

Introduction: Colorectal cancer is the third most common cause of cancer in the world, after lung and breast cancer, while in Croatia is the most common malignant disease. Among the EU members, Croatia ranks ninth in terms of the incidence of colon cancer and a high second place by mortality. Since 2007, Croatia has had a National Colon Cancer Early Detection Program, but the response rate is still very low - 36% (25-52% depending on county and year).2 Despite the prevention program, approximately 13% of patients in Croatia is initially diagnosed with metastatic disease.1 According to the results of the CONCORD 3 study3, Croatia is at the bottom of the five-year survival (48%) compared to some other western countries (up to 71%) in the world. Method(s): A retrospective analysis was conducted at the Clinic of Oncology and Radiotherapy, CHC Split. Patients with newly diagnosed colorectal adenocarcinoma enrolled in the clinic from January 1, 2020 to December 31, 2020 were processed. The data were analyzed using descriptive statistics methods, with the use of Microsoft Excel tools. Result(s): A retrospective analysis of the medical history identified 269 patients (compared to 387 in 2017) presented at the multidisciplinary team (MDT) of CHC Split who were diagnosed with colorectal adenocarcinoma in 2020. All patients were presented to the MDT before starting the treatment. The median age of patients was 66 years, and the youngest patient was 22 years old. Patients from other counties who did not undergo the entire treatment/monitoring in our institution were excluded from the analysis. 52 patients (19.3%) were diagnosed in the metastatic stage of the disease, in stage 0 4 patients (1.5%), in stage I 32 (12%), in stage II 91 (34%), and in stage III 88 (33%). In 2 patients, the stage couldn't be precisely determined. There is a significant decrease in the number (81 in 2017 and 52 in 2020) but no percentage wise (20.9% in 2017 and 19.3% in 2020) of patients diagnosed with de novo metastatic colorectal cancer compared to the previous analysis from 2017, when 81 of them were detected. Patients diagnosed with metastatic disease were mostly in good general condition: ECOG 0 status 21 patients (40.3%), ECOG 1 24 patients (46.2%), ECOG 2 7 patients (13.5%), while no patient was ECOG status 3 or 4. 32 (57.7%) patients had a left-sided tumor, while 20 (42.3%) patients had a right-sided tumor. Conclusion(s): The results of our retrospective analysis showed a significant decrease in the number of patients compared to previous years. The effect of the smaller number of newly diagnosed patients will be analyzed and the real consequences will be seen, however, the appearance of patients in the later stages of the disease is to be expected.

The Magnitude of Covid-19 Effect on Melanoma Diagnosis, Histopathologic Features and Stage of the Disease in University Hospital of Split

Introduction: Due to the COVID-19 pandemic, some planned medical activities have been postponed, for both national directives and out of concern of the patients who were afraid to go to hospitals. Skin cancers, especially melanomas, diagnosed during lockdown also differed from pre-lockdown tumors in several notable ways, such as number of newly diagnosed patients and histopathologic features. The primary tumor thickness (mm), ulceration (%), anatomic localization, and regional lymph node involvements are important elements for determining the melanoma staging and prognosis. Aim(s): The aim of this report was to investigate the difference in number of newly diagnosed melanoma patients, histopathological features and melanoma TNM-staging between comparable pre-pandemic (March 2019 until March 2020) and pandemic periods (March 2020 until March 2021). Method(s): We collected the data from hospital clinical and pathohistological databases on the total number of newly diagnosed patients with melanoma in University Hospital of Split. Comparative analyses were performed in a pre-pandemic and a pandemic cohort. Result(s): Comparing the first year of the pandemic (N=57) with the same period one year before (N=69), 17,4% decrease of melanoma cases was observed. Cohort analysis showed no differences in the distribution of age and sex. The median age of the melanoma patients in a pre-pandemic cohort was 66 years (29-86), and in pandemic cohort 68 years (31-88). The male gender predominated among melanoma patients. In a pre-pandemic cohort, 63,8% of melanoma patients were man, and in pandemic cohort 68,4%. Cohort analysis showed differences in the primary localization of skin melanoma. In pre-pandemic cohort, primary localization of melanoma were head and neck in 17 patients (25%), trunk in 26 patients (38%), upper extremities in 13 patients (19,1%), lower extremities in 10 patients (14.7%) and unknown primary site in 2 patients (2,9%). In pandemic cohort, primary localization of melanoma were head and neck in 10 patients (17,5%), trunk in 32 patients (56,1%), upper extremities in 8 patients (14%), lower extremities in 5 patients (8,8%) and unknown primary site in 2 patients (3,5%). Cohort analysis showed no differences in the pathohistological subtypes. The most common pathohistological subtypes in both cohorts were superficial spreading subtype (21,7% vs 25,8%), unclassified (21,7% vs 17,5%) and nodular subtype (14,5% vs 17,5%). In pandemic cohort we diagnosed patients with increased tumor thickness and positive lymph nodes. In pre-pandemic cohorts we had more patients with thickness less than 1 mm (40,6% vs 31,6%). We found more patients with tumor thickness between 1 to 2 mm (17,5% vs 4,3%) and more than 4 mm (25% vs 20%) in pandemic. Accordingly, in pandemic cohort we found more patients with positive lymph nodes then in pre-pandemic (22,9% vs 5,9%), and more patients with initially metastatic disease (22,8% vs 15,9%). We did not observed any differences in presence of ulceration among the studied cohorts (26% vs 28%). Conclusion(s): In the analysis conducted in University Hospital of Split, we observed a marked decrease of newly diagnosed melanoma patients in the first year of the pandemic compared to the same period before the pandemic. We observed increased tumor thickness, more patients with lymph nodes involvements and initially metastatic disease in post-lockdown period. These findings may be the result of delays in diagnosis due to the disruptions in routine dermatologic and oncologic care during Covid-19 pandemic. The further analyses are needed to fully understand the impact of the Covid-19 pandemic on melanoma outcomes.

Impact of Covid 19 Pandemic on Elective Rectal Cancer Surgery - Single Institution Experience

Introduction: Surgical treatment of rectal cancer depends on clinical stage, size and location of primary tumor. A sphincter preserving technique such as low anterior resection (LAR) is the preferred method if negative distal margin can be achieved. If an adequate distal margin cannot be obtained, an abdominoperineal resection (APR) is required. A proctosigmoidectomy (Hartmann's procedure) is performed in patients with potentially curable obstructing rectal cancer after neoadjuvant chemoradiotherapy, or as a palliative treatment for locally advanced rectal cancer. Aim(s): The aim of this retrospective study was to investigate the impact of COVID 19 pandemic on the number and type of surgeries performed for the treatment of rectal cancer in UHC Zagreb, Department of Surgery. Material(s) and Method(s): Collected data were extracted from medical records of the patients who underwent surgery at the Department of Surgery from 1st of January 2016 to 31st of December 2022 with prior Ethics Committee approval. Total of 688 patients were included. Retrospective analysis of number and type of surgery was done consecutively by years for the period of interest. Result(s): In 2016 total of 75 patients underwent elective surgery for rectal cancer. LAR was performed in 64% (N=48) of patients, Hartmann's procedure in 20% (N=15), and APR in 16% (N=12). In 2017, 94 surgeries were performed. LAR accounted for 64% (N=60), Hartmann's procedure 17% (N=16), and APR 19% (N=18). In 2018, 115 surgeries were performed. LAR accounted for 69% (N=79), Hartmann's procedure 10% (N=12), and APR 21% (N=24). In 2019, 80 surgeries were performed. LAR accounted for 67% (N=54), Hartmann's procedure 9% (N=80), and APR 24%. In 2020, 78 surgeries were performed. LAR accounted for 59% (N=46), Hartmann's procedure 14% (N=11), and APR 27% (N=21). In 2021, 124 surgeries were performed. LAR accounted for 66% (N=82), Hartmann's procedure 14% (N=17), and APR 20% (N=25). In 2022, 122 surgeries were performed. LAR accounted for 64% (N=78), Hartmann's procedure 15% (N=18), and APR 21% (N=26). Conclusion(s): Our results show steady growth in numbers of performed surgeries in the years prior to the pandemic, with exception of the year 2019 when our department underwent organizational changes. In 2020, significant decrease in number of surgeries was observed as a result of restrictive epidemiological measures established to reduce the spread of COVID 19 infection. COVID 19 pandemic measures also resulted in delayed diagnosis and treatment of rectal cancer which is indirectly shown through the increasing share of Hartmann's procedure. In the years following the relaxation of measures, significant increase in number of performed surgeries that exceeded all the pre-pandemic years was recorded. Constant elevated share of Hartmann's procedure was noted as possible consequence of post COVID delay in diagnosis and confirmation of rectal cancer in more advanced stages of disease.

Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen

Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

Real world experience of the burden of infection in myeloma

The treatment landscape in myeloma has rapidly changed over the last few years with the advent of an ever increasing number of funded novel therapies. At the same time, the COVID-19 pandemic has caused a paradigm shift in the burden of infection within the community. Clinical trials often exclude older and more comorbid patients and so there is a paucity of data of the effect of infection on patients with myeloma in the 'real world'. We performed a restrospective audit of all patients with myeloma admitted with infection to our level 2b haematology centre over a 3-year period from November 2019 to November 2022. We collected data on patient demographics and characteristics, infection status, microbiology results, length of stay and outcome of admission. During the audit period there were 87 admissions from 52 patients. The median number of admissions per patient was 1 (range 1-6). The median age at admission was 72 (range 41-90). Patients had a median of two major comorbidities (range 0-8). Performance status was <2 in 63% of patients (33/52). In terms of disease characteristics, International Staging Score (ISS) was stage 1 in 12% of patients, stage 2 in 38%, stage 3 in 38% and unavailable in 12%. Revised ISS (R-ISS) was stage 1 in 2% of patients, stage 2 in 44%, stage 3 in 17% and unavailable in 37%. The median line of treatment was 2 (range 0-6). Respiratory tract infection was the most common site of infection in 51% of admissions. Microbiology was negative in over half of infection admissions (50/87). Fifteen per cent (13/87) had a positive COVID-19 PCR. A positive blood culture result was identified in 8% (7/87). The median length of stay was 9 days (range 1-58). The mortality rate of admissions with infection was 17% (15/87). Overall, our real-world results show the continuing burden of infection in myeloma in the era of modern treatment. Despite the omnipresence of the COVID-19 pandemic over the last 2 and a half years, this contributed to only a small number of admissions. Infections happened in patients of all ages and many patients had good performance status, limited comorbidities and intermediate risk disease. The mortality rate of our cohort was surprisingly high at 17%. In summary, infection remains a major complication of myeloma. Given our results we now plan a trial of prophylactic antibiotics for patients on active treatment.

Automatic Sleep Staging Using BiRNN with Data Augmentation and Label Redirection

Sleep staging has always been a hot topic in the field of sleep medicine, and it is the cornerstone of research on sleep problems. At present, sleep staging heavily relies on manual interpretation, which is a time-consuming and laborious task with subjective interpretation factors. In this paper, we propose an automatic sleep stage classification model based on the Bidirectional Recurrent Neural Network (BiRNN) with data bundling augmentation and label redirection for accurate sleep staging. Through extensive analysis, we discovered that the incorrect classification labels are primarily concentrated in the transition and nonrapid eye movement stage I (N1). Therefore, our model utilizes a sliding window input to enhance data bundling and an attention mechanism to improve feature enhancement after label redirection. This approach focuses on mining latent features during the N1 and transition periods, which can further improve the network model's classification performance. We evaluated on multiple public datasets and achieved an overall accuracy rate of 87.3%, with the highest accuracy rate reaching 93.5%. Additionally, the network model's macro F1 score reached 82.5%. Finally, we used the optimal network model to study the impact of different EEG channels on the accuracy of each sleep stage.

A Successful Treatment of a Critically Patient with SARS-CoV2

Background: The role of inflammatory cytokines is known in the pathogenesis of organ damage and is also confirmed in the context of COVID-19 disease. The modulation of the cytokine storm seems to determine endothelial protection, which can translate into a reduction of the "capillary leak syndrome", and, consequently, in a better control of the formation of edema and pulmonary infiltrates. CytoSorb stands in this context as a cartridge capable of adsorbing cytokines and allowing a better clinical course. Case Report: A 69 years-old woman with a history of arterial hypertension, diabetes mellitus and CKD, was admitted to ICU for SARS Cov 2 related critical illness staged with chest CT, blood gas analysis and PCR. At the admission, the patient presented with ubiquitous interstitial pneumonia, PaO2 60 mmHg with 90% Airvo2 and PCR 36.67. Therefore, in order to remove inflammatory cytokines, the patient underwent hemoperfusion treatment with the CytoSorb adsorbent cartridge. Method(s): The protocol used is approved by the FDA for the treatment of covid patients and consists of the use of 4 cartridges 12h, 12h, 24h, 24h with measurement for each cycle of PCR, PaO2 and chest CT control. Result(s): During the hemoperfusion whit CytoSorb, respiratory failure improved until the patient was discharged from the ICU on the tenth day, with oxygen support via simple facial mask. Below the progressive values of the PCR, PaO2 and the chest CT control on the twelfth day. Conclusion(s): The hemoperfusion treatment with the CytoSorb adsorbent cartridge proved to be a valid adjuvant therapy in determining a better clinical course both in terms of the need for invasive mechanical ventilation and survival.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma extent at FDG PET/MR staging: The NPCOVIPET study.

BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) pandemic on disease extent in patients with nasopharyngeal carcinoma (NPC) using 18 fuorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: This retrospective cohort study included biopsy-proven, newly diagnosed NPC patients using whole-body FDG PET/MR staging in two selected intervals: 1 May 2017 to 31 January 2020 (Group A, the pre-COVID-19 period), and 1 February 2020 to 30 June 2021 (Group B, the COVID-19 period). RESULTS: Three-hundred and ninety patients were included. No significant difference was observed in terms of T classification, N classification, overall stage, N stations, and M stations between the two groups (p > 0.05). For the involved neck node levels, more patients had developed level Vc metastasis in the group B (p = 0.044). CONCLUSION: Although the overall stage was not affected, more patients with NPC had developed level Vc metastasis in the era of COVID-19.

Examining Colorectal Cancer (CRC) Stage at Initial Diagnosis Before and During the COVID-19 Pandemic in the United States

Introduction: Colorectal Cancer (CRC) is on the rise, prompting the need for earlier screening in the United States (U.S.) population. The American Cancer Society now recommends screening for CRC in patients with average risk at the age of 45. Further complicating this picture, the COVID-19 pandemic has disrupted the routine screening process for CRC, which we hypothesize has impacted the stage at which CRC is detected. We sought to determine the extent to which the COVID-19 pandemic has affected colorectal cancer diagnosis trends at a large urban community hospital. Method(s): We performed a retrospective analysis of patients, comparing two time periods: pre-pandemic (1/1/2019-1/31/2020) and during COVID pandemic (2/1/2020-9/29/21). Data was extracted from the electronic medical record (EMR) to compile a database of patients diagnosed with CRC during these time periods. Patients included in this study had a new diagnosis of colorectal cancer and either followed with colorectal specialists at the hospital or had undergone tissue biopsy analysis by the Department of Pathology. The primary outcome was determining the stage at which CRC was detected and the modality utilized for CRC screening in that patient. Additional variables collected were as follows: age, pathological findings (grade, presence of tumor mutations, or microsatellite instability), gender, race, and insurance. Result(s): Data was collected from a total of 380 patients, which included 190 patients diagnosed with CRC within the timeframe defined as pre-pandemic and 190 diagnosed with CRC within the timeframe defined as during the pandemic. CRC diagnosis was analyzed in terms of TNM stage at time of diagnosis (Stages 0 through IV). Stage III and IV were grouped together and categorized as a late-stage diagnosis, whereas Stages 0, I, and II were grouped together and categorized as an early-stage diagnosis. Late-stage diagnosis was found in 34.7% (66/190) of patients in the pre-pandemic group. In comparison, late-stage diagnosis was found in 46.3% (88/190) of patients in the during pandemic group. Conclusion(s): Our results suggest that the COVID-19 pandemic did produce delays in care and work-up for CRC. We believe this is why CRC stage at the time of initial diagnosis was later for patients diagnosed during the pandemic than for patients diagnosed prior to the pandemic. In the future, we hope to evaluate if the impact of COVID-19 is reflected in tumor grade and genetic mutations at the time of diagnosis, and determine race and gender disparities.

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.

Resiliency among Older Adults Receiving (Roar) Lung Cancer Treatment: A Feasibility Study

PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.

A Case Series of Kodamaea Ohmeri Infection: The Hidden Threat Unleashed

Intro: Kodamaea ohmeri, previously known as Pichia ohmeri, is an ascomycetous yeast that has emerged as an important cause of fungemia in immunocompromised patients. During the anamorphic stage this organism is also known as Candida guillermondii var. membranaefaciens. Method(s): We report five cases of Kodamaea ohmeri encountered from multicenter in Malaysia. Antifungal agent of choice will be discussed based on literature review. Finding(s): The cases were: (1) a contaminated peritoneal fluid in an adult patient on peritoneal dialysis;(2) a 60-year-old man with infected diabetic foot isolated K. ohmeri from a bone sample. Both cases discharged well without active antifungal fungal therapy. We observed fatality cases involving (3) an old man with underlying gastric adenocarcinoma who complicated with catheter- related bloodstream infection caused by K. ohmeri;(4) a patient with ventilator- associated pneumonia and septicaemic shock secondary to perforated terminal ileum;(5) and a severely ill COVID-19 stage 5b patient who passed away due to systemic fungaemia caused by K. ohmeri. Discussion(s): All three fatal cases received either amphotericin B or caspofungin as active antifungal agent. Literature evidence has shown that 40% of patient met demise despite on active antifungal agent, suggesting that currently no definitive antifungal agent proven to be a superior treatment option for K. ohmeri infection. Removal of indwelling medical device combined with antifungal therapy has favorable clinical outcome. Conclusion(s): Therefore, K. ohmeri infection in severely ill patients should be considered as a critical condition. Potential of alternative antifungal combinations need to be explored for an effective treatment option.Copyright © 2023

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.

American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting Abstracts

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

Introduction: Hyperthyroidism is known to increase catabolism of vitamin-K-dependent clotting factors (II, VII, IX, X) and increase the response of vitamin K antagonists, usually warfarin. Primary biliary cirrhosis (PBC) has been associated with thyroid dysfunction (TD), especially with autoimmune thyroid disease. In the below case, a patient with known PBC on warfarin is found to have severely elevated INR related to new-onset hyperthyroidism with clinical consequences of hemorrhage including upper GI bleed. Case Description/Methods: A 64-year-old female with PBC and antiphospholipid antibody syndrome on warfarin was admitted for hemorrhagic epiglottitis requiring emergency intubation and supratherapeutic INR. Her PBC was diagnosed as stage II on biopsy 23 years ago and has remained clinically stable on ursodiol therapy. On presentation, the patient was tachycardic, tachypneic, and had O2 saturations <90% on HFNC prior to intubation. Physical exam significant for larger goiter with diffuse upper airway swelling. She was admitted and found to have COVID-19 infection, INR .16.0 and PT>200.0 (limit of lab), WBC of 22.8, and lactate of 2.5. LFTs WNL aside from albumin of 2.0. TSH was <0.0017 (limit of lab) and free T4 of 3.4, free T3 of 5.3. TSH receptor antibody (TRAB) and thyroid stimulating immunoglobulin (TSI) levels were normal. Her last TSH was normal a year ago. CTA chest found a 5.7cm heterogeneous, partially calcified superior mediastinal mass consistent with multinodular thyroid goiter. Patient was initially given prothrombin complex concentrate and vitamin K with correction of INR over the following few days. She was extubated and started on methimazole. During the hospital course, she was found to have coffee ground emesis for which an EGD was done with findings of non-bleeding gastric ulcer (Forrest Class IIc) and LA Grade D esophagitis with adherent clot and bleeding for which hemostatic spray was applied. Patient was discharged a few days later following resumption of warfarin and on pantoprazole and methimazole. Discussion(s): The above case demonstrates a rare case of PBC and new-onset hyperthyroidism due to multinodular thyroid goiter causing significantly elevated INR in the setting of warfarin use with hospital course complicated by GI bleed. PBC is associated with TD - hyperthyroidism, hypothyroidism, and thyroid cancer. Hyperthyroidism is less commonly associated with PBC compared to other TDs but should be considered especially with a finding of elevated INR.

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.