Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

Evaluation of CD10 expression as a diagnostic marker for colorectal cancer.

Aim: We aimed to determine the potential of CD10 as a marker for the early diagnosis of adenocarcinoma of the colon. Background: Adenocarcinoma is diagnosed in one out of 20 individuals in the USA and western European countries. Its prognosis and treatment depend largely on the severity of the disease at the time of diagnosis. Additional new biological markers are being sought that can help diagnose colon cancer at an early stage. One such marker present in both serum and tumor tissue is CD10. Methods: CD10 concentrations were tested by ELISA and immunohistochemistry in serum and tissue samples, respectively, from 113 patients diagnosed histopathologically and treated for adenocarcinoma of the colon. Additionally, the ROC curve with optimal cut-off point based on Youden's criterion was calculated for CD10. Results: Serum concentrations of CD10 and its tissue expression in patients diagnosed with adenocarcinoma of the colon correlate with cancer staging based on the Astler-Coller-Dukes classification. To ascertain the optimal cut-off point for CD10 as a predictor of belonging to the study group, ROC curve was prepared for CD10. Optimal cut-off point for CD10 was 0.57, with prediction of belonging to the study group for CD10 ≥ 0.57. Conclusion: CD10 can be a useful marker in the early diagnosis of adenocarcinoma of the colon.

Retroperitoneal hematoma in COVID-19 patients - case series.

COVID-19 patients, particularly those with severe pulmonary involvement, are at an increased thromboembolic risk related, among various causes, to the cytokine storm and excessive activation of the coagulation cascade and platelets. Different intensity of anticoagulation for them is proposed, mainly with low molecular weight heparins (LMWHs); in a confirmed pulmonary embolism (PE) the therapeutic dose of LMWH is routinely used. Some authors suggest that hemorrhagic complications in COVID-19 patients are rare. At the same time, one can find reports on internal bleeding, including retroperitoneal hematoma (RPH) and other abdominal hematomas. CASE REPORTS: The authors describe 5 cases (3 of those aged more than 80 years) with giant RPHs and with moderate/severe COVID-19 pneumonia, treated before RPH diagnosis with different enoxaparin doses. The therapeutic dose was given to the male with verified PE limited to the segmental/subsegmental pulmonary arteries and initially to the female in whom echocardiography was strongly suggestive of PE, yet this diagnosis was excluded on CT angiography. In one patient, the enoxaparin dose was escalated from 40 mg bd to 60 mg bd after the D-dimer increase. Two patients had bleeding complications despite the enoxaparin dose restricted to 40 mg/daily or bd. Two males had a coexistent psoas hematoma while in only one female there was a coexistent femoral hematoma. RPHs occurred between day 4 and 14 of hospitalization and all were treated conservatively. Three patients who died were particularly charged, so their deaths were not merely directly associated with RPH, which was closely analyzed in one autopsy performed. The authors underline that the choice of anticoagulation intensity in patients with COVID-19 pneumonia without venous thromboembolism seems sometimes difficult but recent publications indicate the low prophylactic enoxaparin dose as an optimal option. Anticoagulation dose escalation based only on the D-dimer level may not be appropriate for certain patients; moreover, the D-dimer increase is commonly observed during internal bleeding.

Relationship between stress and alexithymia, emotional processing and negative/positive affect in medical staff working amid the COVID-19 pandemic.

The psychological burden of the COVID-19 pandemic may have a lasting effect on emotional well-being of healthcare workers. Medical personnel working at the time of the pandemic may experience elevated occupational stress due to the uncontrollability of the virus, high perceived risk of infection, poor understanding of the novel virus transmission routes and unavailability of effective antiviral agents. This study used path analysis to analyze the relationship between stress and alexithymia, emotional processing and negative/positive affect in healthcare workers. The sample included 167 nurses, 65 physicians and 53 paramedics. Sixty-two (21.75 %) respondents worked in COVID-19-designated hospitals. Respondents were administered the Toronto Alexithymia Scale-20, Cohen's Perceived Stress Scale, Emotional Processing Scale, and the Positive and Negative Affect Schedule. The model showed excellent fit indices (χ2 (2)=2.642, p=0.267; CFI=0.999, RMSEA=0.034, SRMR=0.015). Multiple group path analysis demonstrated physicians differed from nurses and paramedics at the model level (X2diff (7)=14.155, p<0.05 and X2diff (7)=18.642, p<0.01, respectively). The relationship between alexithymia and emotional processing was stronger in nurses than in physicians (difference in beta=0.27; p<0.05). Individual path χ2 tests also revealed significantly different paths across these groups. The results of the study may be used to develop evidence-based intervention programs promoting healthcare workers' mental health and well-being.

Dysfunctional Coping Mediates the Relationship between Stress and Mental Health in Health-Care Staff Working amid the COVID-19 Pandemic.

OBJECTIVE: This cross-sectional study aimed to assess the stress outcomes in health-care staff working during the COVID-19 pandemic and to explore the role of coping in the relationship between stress outcomes and mental health dimensions with Preacher & Hayes's mediation analysis. SUBJECTS AND METHODS: One hundred seventy participants including physicians (n = 41; 24.1%), nurses (n = 114, 67.1%), and paramedics (n = 15, 8.8%) with a mean age of 37.69 ± 12.23 years and an average seniority of 14.40 ± 12.32 years were administered the Toronto Alexithymia Scale-20, Cohen's Perceived Stress Scale (PSS-10), the Emotional Processing Scale, and Positive and Negative Affect Schedule. The data were analyzed by estimation of simple correlation coefficients and a Preacher and Hayes's mediation procedure. RESULTS: Participants reported elevated levels of stress (7-8 sten on the sten scale developed for the PSS-10 questionnaire). Statistically significant differences in the stress levels between nurses, paramedics, and physicians could not be determined. In contrast, significant association between mental health outcomes and the occupational category could not be found. CONCLUSION: Our observations support the assumption about a controlling role of coping in the relationship between work-related stress, alexithymia, emotional processing loneliness and positive/negative affect in medical staff working amid pandemic.

The relationship between the symptom of fatigue and the functioning of patients with inflammatory bowel diseases after surgery.

INTRODUCTION: The occurrence of fatigue in patients suffering from inflammatory bowel diseases (IBD) is influenced by pain, frequent bowel movements, stress associated with symptoms and time of their occurrence reaction of surroundings, fear for their own health, sleep disturbances, side effects of pharmacological treatment, physical and mental exhaustion, hindered social contacts and difficulties at work. AIM: To evaluate the fatigue and the assessment of functioning of patients with IBD, who were treated surgically. MATERIAL AND METHODS: To evaluate the functioning of patients, a Polish version of the Inflammatory Bowel Disease Questionnaire was used. To evaluate the occurrence of fatigue in studied subjects, a Polish version of the Functional Assessment of Chronic Illness Therapy - Fatigue Scale was used. The activity of disease was evaluated with the use of the Crohn's Disease Activity Index for patients with Crohn's disease (CD) and the Clinical Activity Index for patients with ulcerative colitis (UC). RESULTS: Before surgery, there was no significant difference between CD and UC patients, with regard to the mean FACIT-F (28.76 for CD and 28.76 for UC, p = 0.72). Also, after surgery, there was no significant difference between CD and UC patients, with regard to the mean FACIT-F (14.8 for CD and 16.0 for UC, p = 0.71). The IBD patients who underwent surgery for CD and UC had significantly lower FACIT-F scores compared to the patients before the surgery (p = 0.001 and p = 0.0001, respectively). IBD patients who underwent surgery for CD and UC had significantly better functioning and higher IBDQ total scores compared to the patients before the surgery. CONCLUSIONS: Surgical treatment significantly reduces the fatigue symptom in patients with IBD. The severity of fatigue correlates with disease activity and functioning in the respective areas.

Takotsubo cardiomyopathy after intravenous epinephrine administration following cardiac arrest provoked by pneumoperitoneum - a case report.

In stress-induced takotsubo cardiomyopathy (TC) high levels of catecholamines, including epinephrine, may be detected in blood. On the other hand, administration of exogenous epinephrine may occasionally result in TC. A CASE REPORT: The authors describe a case of a 58-year-old, otherwise healthy female, with TC which occurred after intravenous injection of 1 mg of epinephrine against cardiac arrest provoked by pneumoperitoneum performed before planned laparoscopic cholecystectomy. She was admitted 3 days earlier due to biliary colic following a dietary mistake. Bradycardia followed by asystole took place immediately after carbon dioxide insufflation into the peritoneal cavity. Normal heart rhythm, with transient tachycardia, recurred after a short cardiac massage, intravenous atropine and epinephrine administration as well as pneumoperitoneum decompression. ECG after the episode showed nonspecific ST segment changes. Left ventricular dysfunction assessed in echocardiography as contractile abnormalities and decreased global longitudinal strain (GLS) represented an unusual type of TC - intermediate between mid-basal and focal one. These abnormalities, involving mainly the posterior wall, resolved rapidly within 24 hours without any specific treatment. The absence of coronary artery disease was confirmed by 128-row multidetector computed tomography. TC should be considered as a potential complication of epinephrine action; however, different factors related to laparoscopic procedure including general anesthesia, intubation, underlying disease and mental stress might have been also involved in TC triggering in the case presented.

Foreign body in the gastrointestinal tract leading to small bowel obstruction--case report and literature review.

The presence of a foreign body in the gastrointestinal tract constitutes a common pathology, considering surgical clinical practice. The management of the ingestion of a foreign body depends on many factors. The study presented a case of a 33-year-old female patient subjected to surgical treatment, due to deliberate swallowing of a balloon. The above-mentioned was the amateur equivalent of intragastric balloon insertion, inducing weight loss. This is a rare cause of a foreign body ingestion, seldomly found in literature data. The patient reported to the Emergency Department on the second day after ingestion with symptoms of mechanical subobstruction, and after initial diagnostics, was qualified for surgery. The postoperative period proved uneventful. The study illustrated the often unfavourable access to false data on the internet, which may stimulate towards the above-mentioned behaviour.

Transcriptional changes between uninflamed ulcerative colitis and familial adenomatous polyposis pouch mucosa can be attributed to an altered immune response.

A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and some patients with ulcerative colitis (UC). However, this surgical treatment is often associated with pouchitis, a long-term complication that occurs mostly in UC patients. The purpose of this study was to better define the molecular background of pouchitis. A microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients undergoing surgery for UC and FAP, respectively. There were 4,770 genes that significantly differentiated uninflamed from inflamed mucosal samples, and their functional features were represented mostly by metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed genes between UC and FAP samples, irrespective of mucosal inflammation status, revealed multiple pathways and terms that were linked to changes in immune response. Interestingly, the comparison of uninflamed UC and FAP samples identified a set of 29 altered probe sets, including an inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most distinct changes in gene expression profiles differentiating uninflamed UC and FAP pouch mucosal samples were attributed to the Gene Ontology category innate immune response. Our study confirmed that alterations in immune responses can be found between patients who underwent surgery for UC and FAP, independent of the pouch inflammation status. This observation may be important when managing IPAA patients.

Preliminary study with SprayShield™ Adhesion Barrier System in the prevention of abdominal adhesions.

INTRODUCTION: Peritoneal adhesions, the fibrotic bands that form between the surfaces in the peritoneal cavity following surgery, still pose a difficult clinical challenge. AIM: To evaluate the SprayShield™ Adhesion Barrier System (PEG ester amine solution and a buffer solution) in reducing post-operative adhesion formation. MATERIAL AND METHODS: This was a prospective, multi-center, randomized, single blind study. A total of 11 subjects diagnosed with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) were randomized: 8 to the SprayShield™ arm and 3 to the control arm. SprayShield™ was applied on the viscera directly under the midline peritoneal incision and at the site of ileostomy. During the follow-up surgery, the incidence, extent, and severity of post-operative adhesion formation were evaluated, as well as the time required to mobilize the ileal loop. RESULTS: In patients who received SprayShield™ the time required to mobilize the ileal loop at the ileostomy closure was slightly shorter and the incidence and severity of adhesions were somewhat lower vs. control subjects (NS). CONCLUSIONS: SprayShield™ was found to be easy to use, safe, and quick to apply, and performed well in adherence and conformity. The incidence and severity of adhesions were lower for SprayShield™ subjects vs. control subjects, but due to the limited number of patients there are not enough data to confirm the effectiveness of the SprayShield™ Adhesion Barrier System in prevention of adhesions.

Anti-inflammatory effect of sulodexide during acute peritonitis in rats.

BACKGROUND/AIMS: Peritonitis is one of the complications of peritoneal dialysis. We demonstrate the systemic and intraperitoneal anti-inflammatory action of sulodexide given systemically. METHODS: Dialysis was performed in male Wistar rats with acute peritonitis induced by addition of endotoxin to the fluid. Sulodexide (10 mg/kg b.w.) was used acutely as supplement to the dialysis fluid or chronically, during 7 days preceding the study by intramuscular (i.m.) injection. RESULTS: In rats given i.m. sulodexide the dialysate cell count was lower by 45% (p < 0.001) versus untreated rats with peritonitis. Dialysate elastase activity in i.m. sulodexide-treated rats was lower by 22% (p < 0.05) compared to peritonitis. In rats treated with i.m. sulodexide the increase of plasma tumor necrosis factor-alpha was reduced by 53% (p < 0.002). Pretreatment with i.m. sulodexide reduced transperitoneal loss of total protein and albumin during peritonitis by 26% (p < 0.002) and by 16% (p < 0.05), respectively. CONCLUSION: Sulodexide given systemically reduces the intraperitoneal and vascular inflammatory response during acute peritonitis in rats.

[Atypical clinical picture of strangulated obturator hernia]. / Nietypowy obraz kliniczny uwieznietej przepukliny zaslonowej.

Strangulated obturator hernia is a very rare condition found almost always in elderly, debilitated multiparas usually with concomitant severe chronic illnesses. The authors presented a case of a young, 35-years-old woman of normal constitution, nullipara, without previous abdominal surgery. This unusual clinical picture despite the symptoms of intestinal obstruction caused difficulties in the correct preoperative diagnosis. It is the youngest case of patient with strangulated obturator hernia described in Polish medical literature.

[Fenotypical characteristic of coagulase negative staphylococci isolated from patients hospitalized on burn ward and surgical ward]. / Fenotypowa charakterystyka gronkowców koagulazo-ujemnych izolowanych z ran od pacjentów hospitalizowanych na oddziale oparzeniowym i chirurgii urazowej.

The aim of the study was to analysis of the adhesion factors of coagulase-negative staphylococci (CNS) to intravenous catheter: ability to adhesion, slime production, hydrophobicity of surface of cells and susceptibility to antibiotics. The researches heve been done on CNS strains isolated from cardiosurgical patients. Slime production ability was evaluated using plate method according to Christensen and Congo Red Agar method. Adherence of bacterial strains to intravenous catheter (polytetrafluoroethylene) in vitro was determined using the method of Richards. Hydrophobicity of surface of cells was determined on the basis of agregattion in (NH4)2SO4 Susceptibility to antibiotics was determined using the disc-diffusion method. Out of the analyzed strains 19% were labeled as slime producing in the plate method and 14% in the Congo red Agar method. 43% of analyzed strains were found to have TTC reduction of 3+, 19% of 2+ and 28% of 1+. Among these 10% of the assesed strains did not reduce TTC.