AUTOANTIBODIES RELATED TO RHEUMATIC DISEASES AFTER COVID-19 INFECTION

BackgroundSARS-CoV-2(Severe acute respiratory syndrome coronavirus 2) has been circulating worldwide for three years. It mainly causes upper respiratory tract infection, which can manifest as pulmonary infection and even respiratory distress syndrome in severe cases. Different autoantibodies can be detected in patients infected with COVID-19.ObjectivesTo explore autoantibodies related to rheumatic diseases after COVID-19 infection.MethodsNinety-eight inpatients were tested for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens(ENA), anti-neutrophil cytoplasmic antibodies（ANCA), anticardiolipin antibodies,a-β2GPI (IgG/IgM). They were from a tertiary hospital in Guangzhou during the COVID-19 epidemic. Data were described statistically.ResultsNinety-eight hospitalized patients were tested for relevant antibodies. The average age was 50.64±19.54;67 (68.4%) were male, 64 (65.3%) were COVID-19 positive, 90 (90.9%) had rheumatic diseases, and 56 of them were COVID-19 positive patients with rheumatic diseases.There were 76 patients tested for antinuclear antibodies;29 （38.16%）were negative, 18 （23.68%）had a 1/80 titre, and 29（28.16%） had a titre greater than 1:80. The 31 covid patients were positive for ANA. In the high-titer group, 19 patients with rheumatic diseases were positive for COVID-19, and 12 patients had an exacerbation of the rheumatic diseases (6 of whom had previously had pulmonary fibrosis). Of 31 covid patients, only two were non-rheumatic patients, and both were elderly, aged 85 and 100, respectively.Fifty-six patients had ENA results, and 29 for positive antibodies, 8 for ds-DNA antibodies, 2 for anti-Sm antibodies, 6 for anti-nucleosome antibodies, 12 for anti-U1RNP antibodies, 2 for anti-Scl-70 antibodies, 12 for anti-SS-A antibodies, 3 for anti-mitochondrial M2 antibodies, 2 for anti-centromere antibodies, 1 for anti-Po antibodies, and one for anti-Jo-1 antibody. All 56 patients had rheumatic diseases, and no new patients were found.There were 62 patients with ANCA data. P-ANCA was positive in 12 cases(19.35%), and MPO-ANCA was positive in 2 cases. An 85-year-old non-rheumatic COVID-19 patient was P-ANCA positive. She had a history of hypertension, colon cancer, CKD3, coronary heart disease, and atrial flutter.In the anticardiolipin antibodies group, there were 62 patients;only 6 were positive, and 2 were rheumatic patients infected with COVID-19. Antiphospholipid antibodies were detected in 33 patients, and a-β2GPI was tested in one patient, an 82-year-old COVID-19 patient with gout, diabetes, and cerebral infarction in the past. We did not find a statistical difference in the above results.ConclusionWe have not found a correlation between SARS-CoV-2 and serum autoantibodies of rheumatic immune diseases. It needs large samples and an extended follow-up to research.AcknowledgementsThis work was supported by Scientific and Technological Planning Project of Guangzhou City [202102020150], Guangdong Provincial Basic and Applied Basic Research Fund Project [2021A1515111172], National Natural Science Foundation of China Youth Fund [82201998] and Third Affiliated Hospital of Sun Yat-Sen University Cultivating Special Fund Project for National Natural Science Foundation of China [2022GZRPYQN01].Disclosure of Interestsone declared.

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.

Reducing your risk cancer-focused health events to meaningfully engage the medically underserved and diminish future cancer disparities

Lack of access to cancer prevention education, early screening, and timely treatment, particularly in low socioeconomic, underserved communities, are cited as substantial barriers to improving survivorship. Outreach educational efforts with on-site screenings offered in partnership with community groups are known to be valuable in encouraging community members' uptake of healthy behaviors and adherence to screening recommendation. To create more engaging events, a community-academic partnership, We Engage 4 Health (WE4H), co-created 11 unique 4-panel comic-style stories designed to be read aloud together as attendees visit each event table. These colorful stories are shared on boards that stand on each table and are offered in both English and Spanish at this time. Many tables also have an accompanying hands-on activity. Together, they lead to meaningful "low stakes" discussions which support understanding of seemingly complex health information. Story topics include the cause of cancer (Cells Gone Wrong), cancer risk factors (Reducing Your Risk), the role of primary care in cancer screening (Primary Care for Prevention), the purpose of research (short Research Ready) and details about specific cancer types (Combatting Colon Cancer, Blocking Breast Cancer, Looking for Lung Cancer, Silencing Skin Cancer, Hindering HPV, and Professional Prostate Protection) and COVID-19 (Take Your Best Shot FAQs). A health passport is used to facilitate table visitation and survey collection at each table enables meaningful evaluation of the event as well as provides the community hosts and their partners baseline cancer data to inform future programing. In 2022, WE4H and the University of Cincinnati Cancer Center partnered with three different communities to co-host pilot events that served over 100 adult residents. Community, research interns and university students volunteered to work the tables at the event and received training prior. Post event surveys and discussions indicated that community partners appreciated the different take on a health fair event. Most volunteers indicated that they would enjoy volunteering again. Attendees indicated that they liked the graphic-style story format used and most preferred it to text and text with graphics approaches. Taken together, the data indicates that Reducing Your Risk events are useful in meaningfully engaging hard to reach, at risk attendees. Additional in-person and virtual events are being planned for 2023 as an approach to reach the medically underserved throughout our region.

Viruses and the risk of lung cancer: prevention and treatment

Lung cancer is the most common cancer in males and the second most common among females both in Europe and worldwide. Moreover, lung cancer is the leading cause of death due to cancer in males. The European region accounts for 23% of total cancer cases and 20% of cancer-related deaths. Relationships have been described between a number of infectious agents and cancers, but our knowledge of the role of viruses, both respiratory and systemic, in the pathogenesis of lung cancer is still rudimentary and has been poorly disseminated. In this chapter, we review the available evidence on the involvement of HPV, Epstein-Barr virus, HIV, cytomegalovirus and measles virus in the epidemiology and pathogenesis of lung cancer.Copyright © ERS 2021.

Commencing colorectal cancer screening at age 45 years in U.S. racial groups.

Screening for colorectal cancer (CRC) is cost-effective for reducing its mortality among the average-risk population. In the US, CRC incidence and mortality differ among racial/ethnic groups, with non-Hispanic Blacks (NHB) and American Indian/Alaska Natives showing highest incidence and mortality and earlier presentation. Since 2005, some professional societies have recommended CRC screening for NHB to commence at 45 years or earlier; this was not implemented due to lack of recommendation from key groups that influence insurance payment coverage. In 2017 the highly influential U.S. Multi-Society Task Force for Colorectal Cancer recommended screening to commence at 45 years for NHB; this recommendation was supplanted by data showing an increase in early-onset CRCs in non-Hispanic Whites approaching the under-50-year rates observed for NHB. Subsequently the American Cancer Society and the USPSTF recommended that the entire average-risk population move to commence CRC screening at 45 years. Implementing screening in 45-49-year-olds has its challenges as younger groups compared with older groups participate less in preventive care. The US had made extensive progress pre-COVID-19 in closing the disparity gap for CRC screening in NHB above age 50 years; implementing screening at younger ages will take ingenuity, foresight, and creative strategy to reach a broader-aged population while preventing widening the screening disparity gap. Approaches such as navigation for non-invasive and minimally invasive CRC screening tests, removal of financial barriers such as co-pays, and complete follow up to abnormal non-invasive screening tests will need to become the norm for broad implementation and success across all racial/ethnic groups.

Cause-of-death statistics in 2020 in the Republic of Korea.

Background: This study analyzed the causes of death in the Korean population in 2020. Method(s): Cause-of-death data for 2020 from Statistics Korea were examined based on the Korean Standard Classification of Diseases and Causes of Death, 7th revision and the International Statistical Classification of Diseases and Related Health Problems, 10th revision. Result(s): In total, 304,948 deaths occurred, reflecting an increase of 9,838 (3.3%) from 2019. The crude death rate (the number of deaths per 100,000 people) was 593.9, corresponding to an increase of 19.0 (3.3%) from 2019. The 10 leading causes of death, in descending order, were malignant neoplasms, heart diseases, pneumonia, cerebrovascular diseases, intentional self-harm, diabetes mellitus, Alzheimer disease, liver diseases, hypertensive diseases, and sepsis. Cancer accounted for 27.0% of deaths. Within the category of malignant neoplasms, the top 5 leading organs of involvement were the lung, liver, colon, stomach, and pancreas. Sepsis was included in the 10 leading causes of death for the first time. Mortality due to pneumonia decreased to 43.3 (per 100,000 people) from 45.1 in 2019. The number of deaths due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 950, of which 54.5% were in people aged 80 or older. Conclusion(s): These changes reflect the continuing increase in deaths due to diseases of old age, including sepsis. The decrease in deaths due to pneumonia may have been due to protective measures against SARS-CoV-2. With the concomitant decrease in fertility, 2020 became the first year in which Korea's natural total population decreased.Copyright © Korean Medical Association.

Developing Contemporary Survivorship Clinic for Recipients of Hematopoietic Cell Transplantation: A Single Center Experience

Introduction: Survival after hematopoietic cell transplantation (HCT) has improved tremendously over the last few decades. HCT survivors are at increased risk of long-term complications and secondary cancers. This poses unique challenges to the HCT-related healthcare system given the growing need for survivorship care. Developing a HCT survivorship program with a dedicated clinic to survivors ensures equitable access to care and ongoing patient education. Herein, we describe our program survivorship model and our initial experience. Method(s): The Moffitt Cancer Center (MCC) survivorship clinic (SC) planning committee was initiated in September 2019. The SC was launched in January 2021 with the mission to provide high-quality, comprehensive, and personalized survivorship care and to empower patients and community health care providers with education and a roadmap for screening for late effects. The SC initially focused on allogeneic (allo) HCT patients and later opened to autologous (auto) HCT recipients in February 2022. HCT patients are referred by primary HCT team after HCT with an emphasis on preferred timeframe of initial SC visit no earlier than 3 months but less than 12 months from HCT. SC is located at 2 physical locations: main campus and satellite, with virtual visit options to account for the distance from MCC and COVID considerations. SC applies a consultative model. SC is staffed by dedicated advanced practice professional (APP), supervised by SC faculty. The scope of SC care includes but is not limited to prevention of infections (education, vaccinations), surveillance of late effects (endocrine, pulmonary function, cardiac, bone health), and general cancer screenings (breast, colon, skin cancer). Patients' clinical data from SC inception to August 2022 were reviewed. Result(s): From January 2021 to August 2022, a total of 138 patients were seen in SC. The majority were seen in person (62% in clinic, 38% by virtual visit). Median age was 58 years (range, 19-82). Median time to first SC visit was 21 months (range, 3-1464) after HCT. Allo HCT was the most common type of HCT seen in clinic (87%, n=120). Most common diagnoses were acute myeloid leukemia (43%, n=59), myelodysplastic syndrome (17%, n=23), and acute lymphoblastic leukemia (10%, n=14). Only 17 patients (12%) were seen in 2021 but the volume increased significantly in 2022. Currently there are more than 10 patients seen in SC per month. Conclusion(s): We report successful experience in launching a contemporary HCT SC despite the challenges of an ongoing COVID pandemic. As a stand-alone cancer center, we serve a wide geographical location with subspecialty and primary care providers dispersed throughout the community. Our consultative model and experience could provide a useful guide for other programs. In 2023, we plan to expand our SC to a broader population of patients receiving other cellular immunotherapies.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Current status of probiotic and related health benefits

This review is aimed to explore the health beneficial effects of probiotics which are live microorganisms that provide a positive health influence on humans when taken in sufficient quantity. Lactic acid bacteria, bifidobacteria, and yeast are frequently used as probiotics. These health-beneficial bacteria could compete with pathogens and modulate the gut microbiota, and exhibit immunomodulatory, anti-obesity, anti-diabetic, and anti-cancer activities which are discussed in this review. Moreover, recent studies showed that probiotics could neutralize COVID-19 infections. Hence, probiotics have become an alternative to several drugs including antibiotics. In addition, probiotic efficacy also depends on the delivery system as the delivery agents help the bacteria to survive in the harsh environment of the human gut. Considering these health benefits of probiotics, now it has been applied to different food materials which are designated as functional food. This review explored a portrait of the beneficial effects of probiotics on human health.Copyright © 2022 The Author(s)

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

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

Application of Neoaortoiliac System For Contained Rupture of Mycotic Infrarenal Aortic Aneurysm

Funding: None. Synopsis: 61-year-old male who initially presented to an outside facility with streptococcal pneumoniae meningitis and bacteremia. Of note, he had history of COVID-19 pneumonia a month prior. On hospital day 15, he reported sudden onset lower back pain prompting imaging which demonstrated a contained rupture of an infrarenal aortic aneurysm that had significantly evolved in comparison to admission imaging where his infrarenal aorta had the largest dimension measuring 2.9cm. We present the successful application of neoaortoiliac system (NAIS). Method(s): Proceeding with midline laparotomy we encountered dense adhesive disease due to his history of surgery for colon cancer. After adhesiolysis, we exposed the aorta and aneurysm with severe surrounding inflammatory changes. 20cm of femoral vein was harvested, reversed, and joined for a span of 4cm using an Endo GIA 45mm vascular load to create our neoaorta. Proximal and distal clamp zones were developed. Upon entering the aneurysm, a foul smell was encountered, revealing that the noxious process had destroyed the posterior wall of the aorta and paraspinal tissues. Our neoaorta was anastomosed in end-to-end fashion to the infrarenal aorta and subsequently to the common iliac arteries. Flow was initially restored to the hypogastric arteries and then the external iliac arteries. The retroperitoneum was closed over our repair and covered with omentum. Result(s): On post-operative day 2, he had hematochezia;intraoperatively, the IMA was noted to be 1mm in size, though had brisk back-bleeding and was ultimately ligated. A flexible sigmoidoscopy revealed ischemic sloughing of the sigmoid colon near his previous anastomosis from his colon cancer resection though no transmural necrosis. He remains on high-dose ceftriaxone to complete a 6-week course and metronidazole for 10 days due to his sigmoid mucosal ischemia per infectious disease recommendations. He is now post-operative day 10 and remains in the ICU. Conclusion(s): Mycotic aortic aneurysms constitute 1-1.8% of aortic aneurysms. The standard of treatment is aggressive debridement of involved aortic wall and periaortic tissue, in-situ or extra-anatomic reconstruction, coverage with an omental flap and long-term antibiotic therapy. NAIS is resistant to infection and aneurysmal dilation, however, is a time-consuming procedure with a mean completion time of 8 hours. Dorweiler et al. demonstrated that vascular reconstruction with femoral vein in infected aortoiliofemoral fields has a mortality of 9-10% with negligible rate of late complications (graft stenosis, thrombosis, and dilation) and that venous morbidity after femoral vein harvest is well tolerated. Clagett et al. demonstrated that NAIS fashioned from greater saphenous vein had a failure rate requiring intervention of 64% compared to 0% for those constructed with deep femoral vein. Lastly, it is important to note that our patient was previously COVID-19 positive. This case demonstrates that the sequela of COVID-19 may have been a significant factor in our patient's pathophysiology. As we continue to learn about the effects of COVID-19 on vascular pathology, we must keep a large repertoire of operative techniques at hand in order to treat complex presentations of vascular emergencies. [Formula presented] [Formula presented] [Formula presented] Institution: Orlando Health, Orlando, FLCopyright © 2022

Unplanned Delay in Time to Operation is Associated With Reduced Recurrence-Free Survival in Colon but Not Rectal Cancer Patients

INTRODUCTION: Patient often experience delays in operative care due to access issues, comorbidities, and other personal reasons. However, during the recent COVID pandemic, hospital resources were severely limited and all patients were forced to endure unprecedented delays, including colon and rectal cancer patients. The oncologic implications of these delays are unknown. METHOD(S): Adult patients who underwent surgery for colon and rectal cancer between January and September of 2020 were retrospectively reviewed. Patients with stage 4 disease were excluded. Patients were categorized as regular or extended interval if time to operation was less than or greater than 40 days for colon cancer and 80 days for rectal cancer. RESULT(S): A total of 186 patients were included, 123 colon cancer and 63 rectal cancer. In the colon cancer group, there were 65 regular interval and 58 prolonged interval patients. There were no significant differences in post-operative, 30-day, or 90-day post-operative outcomes between the two interval groups. During the follow up period (regular vs prolonged: 468.7 +/- 238.3 vs 414.2 +/- 235.5, p = 0.005) there was a higher rate of recurrence in the prolonged group (4.6% vs 17.2%, p = 0.023). Cox regression controlling for disease stage, procedure performed, and resection score demonstrated a significant difference in recurrence-free survival (HR = 7.544, p = 0.007). In the rectal cancer group, there were 48 regular interval and 15 prolonged interval patients. There were no significant differences in postoperative, 30-day, or 90-day outcomes between the two interval groups. During the follow up period (regular vs prolonged: 574.0 +/- 237.3 vs 569.3 +/- 252.2, p = 0.687) there was no difference in recurrence (16.7% vs 26.7%, p = 0.389), but recurrence-free survival was significantly longer in the regular interval group (543.9 +/- 241.6 vs 493.1 +/- 237.4, p = 0.009). However, Cox regression controlling for disease stage, neoadjuvant chemotherapy, procedure performed, resection score demonstrated no difference in recurrence-free survival (HR = 1.403, p = 0.662). CONCLUSION(S): A prolonged time to surgery, greater than 40 days, was associated with decreased recurrence-free survival for color cancer patients. In rectal cancer, no significant reduction in recurrence-free survival was observed despite a longer time to surgery interval in the prolonged group. In events when resources are limited, colon cancer patients may benefit from prioritized treatment and rectal cancer patients may be able to tolerate longer delays without significant impacts on recurrence-free survival.

Phytochemistry and Pharmacology of Indian Traditional Plant Hyssop (Hyssopus officinalis L.): A Review

Hyssopus officinalis is a traditional medicinal plant that belongs to the family Lamiaceae, which has been used for centuries for various purposes like carminative, expectorant, and cough reliever. It has been used for the treatment of numerous diseases in patients such as ulcers, asthma, jaundice, leprosy, dropsy, bronchitis, COPD, diabetes, AIDS, bacterial and fungal infections as an herbal remedy due to its fewer side effects and is more efficacies than other traditional medicine. Major classes of chemical compounds found in H. officinalis essential oil are bicyclic monoter-penes, monoterpenoids, acyclic monoterpenes, phenolic monoterpenoids, monocyclic monoterpenes, monocyclic sesquiterpenes, tricyclic sesquiterpenes, bicyclic sesquiterpenes, tricyclic sesquiterpe-noids, straight chain saturated hydrocarbons. Some of the major chemical constituents present in the H. officinalis are beta-pinene, alpha-pinene, 1, 8-cineole, apigenin, diosmin, caffeic acid, rosmarinic acid, cis-pinocamphone, trans-pinocamphone, iso-pinocamphone, pinocarvone, which are responsible for its various pharmacological activity. Various studies have been performed on the pharmacological activity of its extract, such as antioxidant, antimicrobial, anti-diabetic, anticancer, antiviral, anti-inflammatory, analgesic, anti-leishmanial, anthelmintic, anti-protozoal, and anti-anxiety. Recently, it is used as an anticancer agent and has been demonstrated by studying its cytotoxic and apoptotic effects on breast cancer and colon cancer cells. It is used as a potent antibacterial and antifungal agent being studied on the antibiotic-resistant bacterial and fungal strains recently, which can be further useful in developing herbal medicine against AMR. It is an excellent natural antioxidant due to the presence of polyphenolic compounds, and H. officinalis is used in various food industries as a source of natural antioxidants, which has minimum side effects as compared to artificial antioxi-dants. Furthermore, the pharmacological activity of these individual chemical constituents in H. officinalis extract still needs to be investigated for identifying the effectiveness of this plant in the natural treatment of various diseases. This review aims to collect various data regarding the traditional herbal plant hyssop (Hyssopus officinalis), including its photochemistry, chemical structures of the phyto-constituents and pharmacological profile, along with all the pharmacological models. This plant has significant importance in the health industry, so further studies are required on its effective usage against various emerging health problems, including COVID-19, cancer, diabetes, AMR.Copyright © 2023 Bentham Science Publishers.

Linitis plastica of the rectum secondary to prostate carcinoma.

Linitis plastica is an intramural carcinoma that may occur in any hollow organ. Rectal linitis plastica (RLP) is a morphological variant cancer that may occur as a primary form of cancer or secondary as a metastasis of a primary malignancy. We report the case of a man in his 70s with RLP secondary to prostate carcinoma who was initially suspected to have an obstructing rectal adenocarcinoma. During colonoscopy a segment of cobblestone mucosa was seen in the distal rectum. Subsequent imaging showed enhancement of all wall-layers of the rectum and diffuse retroperitoneal fat infiltration with traction on both ureters. A prostate-specific membrane antigen scan confirmed RLP secondary to a prostate carcinoma mimicking the clinical and radiological signs of an obstructing rectal carcinoma with retroperitoneal fibrosis.This case emphasises the possible pitfalls in the diagnosis of RLP and the importance of advanced imaging techniques, such as MRI, as well as appropriate histological samples. The patient underwent androgen deprivation therapy to which RLP responded well and neither systemic chemotherapy or surgery was necessary.

When and How to Use Covariate Adjustment to Improve Precision in Randomized Trials

Background In May 2021, the US Food and Drug Administration (FDA) released a revised draft guidance for industry on ''Adjustment for Covariates in Randomized Clinical Trials for Drugs and Biological Products.'' This guidance discusses adjustment for covariates in the statistical analysis of randomized clinical trials in drug development programs. It specifically focuses on the use of prognostic baseline factors to improve precision for estimating treatment effects. The impact depends on the specifics of the trial, but typical sample size reductions range from 5-25% (at no cost). Despite regulators such as the FDA and the European Medicines Agency recommending covariate adjustment, it remains highly underutilized leading to inefficient trials in many disease areas. This is especially true for binary, ordinal, and time-to-event outcomes, which are quite common in COVID-19 trials and are, moreover, prevalent as primary outcomes in many disease areas (e.g. Alzheimer's disease and stroke). Research and guidance on this topic could therefore not be more timely. In response to the FDA draft guidance on covariate adjustment, this session invites experts who represent a variety of viewpoints, coming from academia and Pharmaceutical industry. The aim of this session is to provide insight into the state-of-the-art methods at a high level and from a practical perspective. We moreover want to discuss the main obstacles that lead to the underutilization of covariate adjustment, all of which we aim to surmount in this session. Finally, we want to discuss the connections of the different talks to the FDA draft guidance and provide options for better practice. Talk by Min Zhang ''Covariate adjustment for randomized clinical trials when covariates are subject to missingness.'' One practical issue that may have limited the use of covariate adjustment is that covariates are often subject to missingness. Existing statistical methodologies often ignore this issue and assume covariates are completely observed. We discuss conditions under which robust covariate adjustment can be achieved when the missingness of covariates is present. We study various methods for handling missing data and compare their performances in terms of robustness and efficiency through comprehensive simulation studies. Recommendations on strategies for handling missing covariates to achieve robust covariate adjustment are provided. Talk by Mark van der Laan on ''Targeted Learning of causal effects in randomized Trials with continuous time-to-event outcomes.'' Targeted maximum likelihood estimation (TMLE) provides a general methodology for estimation of causal parameters in the presence of high-dimensional nuisance parameters. Generally, TMLE consists of a twostep procedure that combines data-adaptive nuisance parameter estimation with semi-parametric efficiency and rigorous statistical inference obtained via a targeted update step. In this talk, we demonstrate the practical applicability of TMLE for standard survival and competing risks settings where event times are not confined to take place on a discrete and finite grid. We demonstrate TMLE updates that simultaneously target point-treatment-specific survival curves and treatmentcause- specific subdistributions in the competing risk setting, across treatment and time points. We consider the case that we only observe baseline covariates as well as the case that we also track time-dependent covariates that potentially inform censoring/drop-out. This results in estimates that are not only fully efficient, but also respect the natural monotonicity of survival functions and cause-specific subdistributions. It moreover makes sure that the sum of subdistributions and survival equals 1. We propose a super-learner for the causespecific conditional hazards that incorporate many possible Cox models as well as a variety of highly adaptive Lasso estimators. Asymptotic theoretical guarantees are given and finite-sample robust performance is demonstrated with simulations. We illustrate the usage of the considered methods for a ovo Nordisk Leader study as well as for publicly available data from a trial on adjuvant chemotherapy for colon cancer. Talk by Kelly Van Lancker on ''Combining Covariate Adjustment with Information Monitoring and Group Sequential Designs to Improve Randomized Trial Efficiency'' In this talk, we focus on the knowledge gap in statistical methodology that leads to the underutilization of covariate adjustment. A first obstacle is the uncertainty of its efficiency gain and corresponding sample size reduction at the design stage;an incorrect projection of a covariate's prognostic value risks an over- or underpowered future trial. A second open problem is the incompatibility of many covariate-adjusted estimators with the commonly used group sequential, information-based designs (GSDs). To overcome these challenges, we suggest combining covariate adjustment with information monitoring and continuing the trial until the required information level is surpassed. Since adjusted estimators typically have smaller variance than standard estimators, the information accrues faster leading to faster trials. Building on this, we propose a new statistical method that orthogonalizes estimators in order to (1) have the independent increments property needed to apply GSDs and (2) simultaneously improve (or leave unchanged) the variance at each analysis. Such a method is needed in order to fully leverage prognostic baseline variables to speed up clinical trials without sacrificing validity or power. We prove that this method has properties such as the independent increments, consistency, asymptotic normality, and correct type I error and power, and evaluate its performance in simulations and data analyses. Discussion by Frank Bretz This talk will discuss connections between the three previous presentations in the session and recommendations in the May 2021 FDA revised draft guidance for industry document on ''Adjustment for Covariates in Randomized Clinical Trials for Drugs and Biological Products.'' It will moreover touch on the broad impact of covariate adjustment for the pharmaceutical industry and provide advice on better practice.

5th ECOP, European Conference of Oncology Pharmacy

The proceedings contain 130 papers. The topics discussed include: frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy;simple approach to enhance green tea epigallocatechin gallate stability in aqueous solutions and it bioavailability: experimental and theoretical approaches;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;impact of the 2019 coronavirus pandemic on cancer treatment in the Calabria Region, Italy;Palbociclib associated neutropenia in clinical practice;successful introduction of a point mutation into the genome of a primary colon cancer cell line using CRISPR base editing technology;incidence of cisplatin-induced nephrotoxicity and associated risk factors: single-center experience;real world data of alk-inhibitors in patients with advanced or metastic non-small cell lung cancer;pembrolizumab in non-small-cell lung cancer: a systematic review of real life data in Spain;gynecomastia in a male after imatinib treatment for chronic myeloid leukemia;and results after discontinuation of pembrolizumab in metastatic melanoma or lung cancer patients: real-word experience.

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic.

AIM: This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. METHOD: This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. RESULTS: From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58-14.06), postoperative SARS-CoV-2 (16.90, 7.86-36.38), male sex (2.46, 1.01-5.93), age >70 years (2.87, 1.32-6.20) and advanced cancer stage (3.43, 1.16-10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). CONCLUSION: Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks.

Original Article Evaluation of clinical outcomes, laboratory and imaging data of patients with solid tumor infected with COVID-19 infection

Background: COVID-19 is associated with higher mortality rates in patients with cancer. In this study, we aimed to evaluate the clinical outcomes, and laboratory and imaging data of patients with solid tumor infected with COVID-19 infection. Method(s): This is a cross-sectional retrospective study performed in 2020-2022 on 85 patients with a previous diagnosis of solid tumors infected with COVID-19. We included all patients with tumors of solid organs that were diagnosed with COVID-19 infection and required hospitalization those patients previously hospitalized for treatments and were infected with COVID-19 during hospitalization. Demographic data of patients were collected using a checklist. We collected data regarding clinical outcome (discharge, hospitalization or death), duration of hospitalization, requiring ICU admission, duration of hospitalization divided by received drugs and type of tumor and mean survival time. Furthermore, we collected laboratory data from all patients. The radiologic characteristics of patients were also extracted from their data. Result(s): Breast cancer was the most common solid tumor (34.9%), followed by lung cancer (19.3%). The mortality rate was 24.1% (20 patients). The highest mortality rate in this study was for metastatic intestinal cancer to the lung (100%, one patient), followed by metastatic prostatic cancer to lung (50%, three patients). The highest hospitalization duration was for patients with glioblastoma multiform (GBM) (30 days). The mean survival time among patients with mortality was 19.15+/-1.80 days. The mean CT severity score of all patients was 27.53+/-22.90. Patient's most common radiologic sign was air space consolidation (89.1%). The highest CT severity score was found in patients with stomach cancer (46.67+/-5.77). Conclusion(s): The mortality rate in this study was 24.1%. Based on the results of our study and previous research, special care should be provided to patients with solid tumors during the COVID-19 pandemic and in infected cases.Copyright © 2022, E-Century Publishing Corporation. All rights reserved.

Seven bacterial response-related genes are biomarkers for colon cancer.

BACKGROUND: Colon cancer (CC) is a common tumor that causes significant harm to human health. Bacteria play a vital role in cancer biology, particularly the biology of CC. Genes related to bacterial response were seldom used to construct prognosis models. We constructed a bacterial response-related risk model based on three Molecular Signatures Database gene sets to explore new markers for predicting CC prognosis. METHODS: The Cancer Genome Atlas (TCGA) colon adenocarcinoma samples were used as the training set, and Gene Expression Omnibus (GEO) databases were used as the test set. Differentially expressed bacterial response-related genes were identified for prognostic gene selection. Univariate Cox regression analysis, least absolute shrinkage and selection operator-penalized Cox regression analysis, and multivariate Cox regression analysis were performed to construct a prognostic risk model. The individual diagnostic effects of genes in the prognostic model were also evaluated. Moreover, differentially expressed long noncoding RNAs (lncRNAs) were identified. Finally, the expression of these genes was validated using quantitative polymerase chain reaction (qPCR) in cell lines and tissues. RESULTS: A prognostic signature was constructed based on seven bacterial response genes: LGALS4, RORC, DDIT3, NSUN5, RBCK1, RGL2, and SERPINE1. Patients were assigned a risk score based on the prognostic model, and patients in the TCGA cohort with a high risk score had a poorer prognosis than those with a low risk score; a similar finding was observed in the GEO cohort. These seven prognostic model genes were also independent diagnostic factors. Finally, qPCR validated the differential expression of the seven model genes and two coexpressed lncRNAs (C6orf223 and SLC12A9-AS1) in 27 pairs of CC and normal tissues. Differential expression of LGALS4 and NSUN5 was also verified in cell lines (FHC, COLO320DM, SW480). CONCLUSIONS: We created a seven-gene bacterial response-related gene signature that can accurately predict the outcomes of patients with CC. This model can provide valuable insights for personalized treatment.

Management of colorectal cancer screening backlog due to the COVID-19 pandemic: A retrospective analysis of the use of a colorectal cancer screening clinical-decision support tool in Argentina.

BACKGROUND: The COVID-19 pandemic created a backlog in colorectal cancer (CRC) screening and surveillance colonoscopies. The real impact in Argentina is not fully known. GOAL: To estimate the impact of the COVID-19 pandemic on CRC prevention by comparing the number of CRC screening and surveillance consults in a clinical decision support-tool used in Argentina before, during and after pandemic lockdown. METHODS: We analyzed data from May 2019 to December 2021 from CaPtyVa, a clinical decision support tool for CRC screening and surveillance. Queries were divided in pre-pandemic (May 2019 to March 2020), lockdown (April 2020 to December 2020), and post-lockdown (January 2021 to December 2021). The number of CRC monthly screening and surveillance visits were compared among the three periods and stratified according to CRC risk. RESULTS: Overall, 27,563 consults were analyzed of which 9035 were screening and 18,528 were surveillance. Pre-pandemic, the median number of screening consults was 346 per month (IQR25-75 280-410). There was a decrease to 156 (80-210)/month (p<0.005) during lockdown that partially recovered during post-lockdown to 230 (170-290)/month (p=0.05). Pre-pandemic, the median number of surveillance consults was 716 (560-880)/month. They decreased to 354 (190-470)/month during lockdown (p<.05) and unlike screening, completely recovered during post-lockdown to 581 (450-790)/month. CONCLUSIONS: There was a >50% decrease in the number of CRC screening and surveillance consults registered in CaPtyVa during lockdown in Argentina. Post-lockdown, surveillance consults recovered to pre-pandemic levels, but screening consults remained at 66% of pre-pandemic levels. This has implications for delays in CRC diagnoses and patient outcomes.