Small Bowel Diverticulosis and COVID-19: Awareness Is the Key: A Case Series and Review of the Literature.

Small bowel non-Meckelian diverticulosis is a rare condition with only a few published cases despite being described over 200 years ago. In the midst of the COVID-19 pandemic, studies suggested that many patients may experience gastrointestinal manifestations. Intestinal symptoms could worsen the inflammation and infection associated with small bowel diverticulitis. Here we present three cases: one with inflammation and rupture in a COVID-19 patient and another as an asymptomatic detection. The third case involved recurrence after the first laparoscopic lavage approach. Furthermore, we provide a mini-review of the literature to emphasize the importance of considering this entity in the differential diagnosis of an acute abdomen. In the majority of cases involving small bowel diverticula, conservative management is the preferred approach. However, when complications arise, surgical intervention, including enteroctomy and primary anastomosis, may be necessary to achieve optimal outcomes.

Down-regulation of KLF2 in lung fibroblasts is linked with COVID-19 immunofibrosis and restored by combined inhibition of NETs, JAK-1/2 and IL-6 signaling.

Kruppel-like factor 2 (KLF2) has been linked with fibrosis and neutrophil-associated thromboinflammation; however, its role in COVID-19 remains elusive. We investigated the effect of disease microenvironment on the fibrotic potential of human lung fibroblasts (LFs) and its association with KLF2 expression. LFs stimulated with plasma from severe COVID-19 patients down-regulated KLF2 expression at mRNA/protein and functional level acquiring a pre-fibrotic phenotype, as indicated by increased CCN2/collagen levels. Pre-incubation with the COMBI-treatment-agents (DNase I and JAKs/IL-6 inhibitors baricitinib/tocilizumab) restored KLF2 levels of LFs to normal abolishing their fibrotic activity. LFs stimulated with plasma from COMBI-treated patients at day-7 expressed lower CCN2 and higher KLF2 levels, compared to plasma prior-to-treatment, an effect not observed in standard-of-care treatment. In line with this, COMBI-treated patients had better outcome than standard-of-care group. These data link fibroblast KLF2 with NETosis and JAK/IL-6 signaling, suggesting the potential of combined therapeutic strategies in immunofibrotic diseases, such as COVID-19.

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.

Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

A Comprehensive Analysis on Nutritional and Antioxidant Characteristics of a Traditional Roasted Maize Flour (Furniko) of Pontic Greeks: Comparative Study to Related Flour Products.

Furniko flour (FF) is a traditional roasted flour derived from a maize landrace, commonly consumed by Greeks of Pontic origin in the northern regions of Greece. Despite its perceived nutritional benefits, there is a lack of scientific data to support and highlight its value. This study aimed to compare the nutritional, physicochemical, anti-nutritional, functional, and antioxidant characteristics of FF with those of traditional and non-traditional types of maize flour. Furniko flour (FF) presented the highest values for protein (10.86 ± 0.36 g/100 g), fat (5.05 ± 0.08 g/100 g), K (539.93 mg/100 g), Mg (126.38 mg/100 g), P (296.4 mg/100 g), Zn (2.44 mg/100 g), and total phenolic content (TPC) (156 mg GAE/100 g). However, FF exhibited lower levels of Fe (3.83 mg/100 g), carbohydrates (70.55 ± 0.24 g/100 g), and antioxidant activity (0.27 ± 0.02 µmol of TE/g) than other types of flour examined. Furniko's functional properties make it an excellent source for porridges, while its low content of antinutrients reduces the possibility of low bioavailability of Fe, Zn, Mg, and Ca. Due to its significant and functional characteristics, Furniko flour could be considered an important material in the food industry, especially in bakery goods and health-oriented foods like energy bars, breakfast cereals, and gluten-free pasta. More research is needed, however, to thoroughly investigate its dietary potential and compatibility with other components.

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure.

Aiming to reduce mortality in COVID-19 with severe respiratory failure we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. Patients with PaO2/FiO2 < 100 mmHg were analysed. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n = 26) or SOC plus monotherapy with either IL-1-receptor antagonist anakinra (n = 19) or tocilizumab (n = 11). COMBI was significantly associated with lower in-hospital mortality and intubation rate, shorter duration of hospitalization, and prolonged overall survival after a median follow-up of 110 days. In vitro, COVID-19 plasma induced tissue factor/thrombin pathway in primary lung fibroblasts. This effect was inhibited by the immunomodulatory agents of COMBI providing a mechanistic explanation for the clinical observations. These results support the conduct of randomized trials using combined immunomodulation in COVID-19 to target multiple interconnected pathways of immunothrombosis.

Mental health well-being and functional adjustment in colorectal cancer patients: a prospective cohort study.

BACKGROUND: Colorectal cancer significantly affects the quality of life of patients, while at the same time contributing to the development of symptoms of psychopathology. The aim of this prospective study, is to investigate the role of the disease in the quality of life of patients with colon cancer and in the appearance of symptoms of anxiety and depression, as well as the connection of the above characteristics during the recovery process, given the distress symptoms experienced by the patients. METHODS: In the present study, HADS, FACT - C, well as the DT are use, in a sample of 118 patients of an average age of 70.5 ± 8.5 years, which were submitted to partial or total colectomy surgery. RESULTS: Moderate levels of anxiety (M = 8.25, SD = 3.87) and low levels of depression (M = 6.90, SD = 2.97) and distress (M = 5.84, SD = 2.60) emerged preoperatively, while the improvement was significant of patients' quality of life level 6 months after surgery. At the same time, a significant negative effect of the patients' distress level preoperatively on their quality of life, during the recovery process was observed. CONCLUSION: Preoperative anxiety is not considered to be an element that affects the functionality and the psychological and physical adaptation to the disease of patients with colon cancer. On the contrary, the feelings of distress they experience can be a predictive factor of their quality of life after the partial or total colectomy surgery.

The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality.

BACKGROUND: Activins are members of the transforming growth factor-ß superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology. METHODS: Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters. Optimal scaling with ridge regression was used to screen variables and establish a prediction model. RESULT: The activin/follistatin axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a scoring system incorporating follistatin, activin-A, activin-B, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, and D-dimers, efficiently predicted fatal outcome (area under the curve [AUC], 0.951; 95% confidence interval, .919-.983; P <10-6). Two validation cohorts indicated similar AUC values. CONCLUSIONS: This study demonstrates a link between activin/follistatin axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.

The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study.

BACKGROUND: Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS: This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS: A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS: The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.

Estimated glomerular filtration rate independently predicts outcome of azacitidine therapy in higher-risk Myelodysplastic syndromes. Results from 536 patients of the Hellenic National Registry of Myelodysplastic and Hypoplastic syndromes.

Higher-risk Myelodysplastic syndromes (MDS) patients undergoing treatment with 5-azacytidine (AZA) are typically elderly with several comorbidities. However, the effect of comorbidities on the effectiveness and safety of AZA in real-world settings remains unclear. We analyzed data from 536 AZA-treated patients with higher-risk MDS, Myelodysplastic/Myeloproliferative neoplasms and low blast count Acute Myeloid Leukemia enrolled to the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes. Multivariate analysis adjusted also for the International Prognostic Scoring System (IPSS), its revised version (IPSS-R) and the French Prognostic Scoring System (FPSS), demonstrated independent associations of overall and leukemia-free survival with estimated glomerular filtration rate (eGFR) <45 mL min-1 /1.73 m2 (P = .039, P = .023, respectively), ECOG performance status <2 (P = .015, P = .006), and presence of peripheral blood blasts (P = .008, P = .034), while secondary MDS also correlated with significantly shorter leukemia-free survival (P = .039). Addition of eGFR <45 mL min-1 /1.73 m2 , in IPSS-R and FPSS increased the predictive power of both models. Only FPSS ≤2 and eGFR <45 mL min-1 /1.73 m2 predicted worse response to AZA in multivariate analysis, whereas eGFR <45 mL min-1 /1.73 m2 correlated significantly with death from hemorrhage (P = .003) and cardiovascular complications (P = .006). In conclusion, in the second largest real-world series of AZA-treated MDS patients, we show that an eGFR <45 mL min-1 /1.73 m2 is an independent predictor of worse response and survival. This higher cut-off, instead of the commonly used serum creatinine >2 mg/dL, can be utilized as a more precise indicator of renal comorbidity during AZA therapy. Incorporation of eGFR in the prognostic assessment of AZA-treated MDS patients may prove useful not only in routine practice, but also for the appropriate patient stratification in clinical trials with AZA combinations.

Ultrafast, low-power, PCB manufacturable, continuous-flow microdevice for DNA amplification.

The design and fabrication of a continuous-flow µPCR device with very short amplification time and low power consumption are presented. Commercially available, 4-layer printed circuit board (PCB) substrates are employed, with in-house designed yet industrially manufactured embedded Cu micro-resistive heaters lying at very close distance from the microfluidic network, where DNA amplification takes place. The 1.9-m-long microchannel in combination with desirably high flow velocities (for fast amplification) challenged the robustness of the sealing that was overcome with the development of a novel bonding method rendering the microdevice robust even at extreme pressure drops (12 bars). The proposed fabrication methods are PCB compatible, allowing for mass and reliable production of the µPCR device in the established PCB industry. The µPCR chip was successfully validated during the amplification of two different DNA fragments (and with different target DNA copies) corresponding to the exon 20 of the BRCA1 gene, and to the plasmid pBR322, a commonly used cloning vector in E. coli. Successful DNA amplification was demonstrated at total reaction times down to 2 min, with a power consumption of 2.7 W, rendering the presented µPCR one of the fastest and lowest power-consuming devices, suitable for implementation in low-resource settings. Detailed numerical calculations of the DNA residence time distributions, within an acceptable temperature range for denaturation, annealing, and extension, performed for the first time in the literature, provide useful information regarding the actual on-chip PCR protocol and justify the maximum volumetric flow rate for successful DNA amplification. The calculations indicate that the shortest amplification time is achieved when the device is operated at its enzyme kinetic limit (i.e., extension rate). Graphical abstract.

Quality of life, distress and psychological adjustment in patients with colon cancer.

PURPOSE: The purpose of this study was to investigate the relationships between distress, psychological adjustment, and quality of life in patients with colon cancer. METHOD: This study employed a cross-sectional design and included 104 colon cancer patients treated at AHEPA Hospital, Thessaloniki, Greece. The assessment tools used encompassed the Distress Thermometer, MINI-MAC scale, and FACT-C to evaluate distress, psychological adjustment, and quality of life. Statistical analysis, conducted in SPSS software, encompassed correlation tests and linear regression to explore the interplay between these variables in colon cancer patients. RESULTS: Correlation tests revealed that patients' quality of life is positively correlated with a fighting spirit (r = 0.719, p < 0.001), cognitive avoidance (r = 0.634, p < 0.001), and fatalism (r = 0.518, p < 0.001), and negatively with helplessness and hopelessness (r = -0.756, p < 0.001), and anxious preoccupation (r = -0.679, p < 0.001). OLS regression findings verified these results partially for a significance level of 5% but indicated no statistically significant effect of cognitive avoidance and fatalism on quality of life, which was further found unaffected by total distress. CONCLUSIONS: The intricate links between quality of life, distress, and psychological adjustment in colon cancer patients call for deeper investigation. A personalized approach in psycho-oncology care is essential for comprehensive treatment. These findings highlight the significance of addressing the psychological and emotional needs of colon cancer patients, as observed in the study's results.

An overview of immune checkpoint inhibitor toxicities in bladder cancer.

Bladder cancer is the tenth most prevalent malignancy worldwide, with a significant mortality burden. Urothelial carcinoma (UC) is the most common histological subtype, and treatment options are guided by whether the disease is muscle-invasive (MIBC) or non-muscle-invasive (NMIBC), with subsequent risk group stratification. The growing popularity of immune checkpoint inhibitors (ICIs) to treat MIBC and NMIBC as either monotherapy or combined with intravesical agents, may radically change the treatment paradigm of UC. Current treatments for NMBIC includes intravesical chemotherapy after trans-urethral resection of the bladder tumour, intravesical bacillus Calmette-Guerin (BCG) or radical cystectomy. Cisplatin-based chemotherapy is widely regarded as the first-line treatment for metastatic UC due to its beneficial response and survival rates when compared to alternative therapies. However, up to 70 % of metastatic UC patients are ineligible, and the prognosis of these patients remains poor, with a median survival of 13-16 months. For NMIBC and MIBC, ICIs provide a promising alternative for cisplatin-ineligible patients. In UC, ICIs including atezolizumab, nivolumab, avelumab, and pembrolizumab are Food and Drug Administration (FDA)-approved for monotherapy, and have demonstrated promising results, particularly in those who cannot receive cisplatin-based chemotherapy, and as a second-line treatment option for recurrent UC following platinum-based chemotherapy. It is important to consider that some patients may experience adverse events (AEs) with limited clinical benefit. Infusion-related reactions and immune-mediated AEs (imAEs) such as colitis, endocrinopathies, hepatitis, pneumonitis, interstitial lung disease, renal dysfunction, nephritis, cutaneous and neurological toxicities must be monitored for. Currently, there is no clear consensus on the role of a 'two-year stopping rule' in reducing the risk of imAEs, with further research on the optimal treatment duration of ICIs required. With increased ICI use, vigilance regarding their side effects is imperative. This review aims to provide an updated overview of ICI toxicities in bladder cancer, to assist clinicians in their therapeutic decision-making, with consideration of patient characteristics and the clinical context.

Large Language Models in Oncology: Revolution or Cause for Concern?

The technological capability of artificial intelligence (AI) continues to advance with great strength. Recently, the release of large language models has taken the world by storm with concurrent excitement and concern. As a consequence of their impressive ability and versatility, their provide a potential opportunity for implementation in oncology. Areas of possible application include supporting clinical decision making, education, and contributing to cancer research. Despite the promises that these novel systems can offer, several limitations and barriers challenge their implementation. It is imperative that concerns, such as accountability, data inaccuracy, and data protection, are addressed prior to their integration in oncology. As the progression of artificial intelligence systems continues, new ethical and practical dilemmas will also be approached; thus, the evaluation of these limitations and concerns will be dynamic in nature. This review offers a comprehensive overview of the potential application of large language models in oncology, as well as concerns surrounding their implementation in cancer care.

Survival after vascular resections in patients with borderline resectable or locally advanced pancreatic head cancer: A systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, and the most common cause of cancer-related deaths. In the past, vascular infiltration of the tumor rendered the disease unresectable. However, today, venous or arterial involvement of a PDAC is classified as borderline resectable (BR) or locally advanced (LA) disease. Pancreaticoduodenectomy (PD) with vascular resections is a promising intervention intended for complete resection of BR- and LA-PDAC. This study aims to assess the overall survival of patients undergoing PD with vascular resections, compared to those without. A PubMed search was conducted for cohort studies that included patients with BR- or LA-PDAC treated with vascular resections. The retrieved publications were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The study protocol was registered at the International Prospective Register for Systematic Reviews (PROSPERO). Sixteen cohort studies were included in our systematic review. Fourteen of them included patients undergoing PD with venous-only resections for PDAC. The 5-year overall survival rates ranged from 8.0% to 22.2% for vascular resection patients, and 4.0% to 24.3% for standard PD patients. Three cohorts included patients with PDAC and arterial and/or venous involvement who were treated with arterial resections. Their median overall survival ranged from 13.7 to 17.0 months, similar to that of patients who did not undergo vascular resections. PD with vascular resections in patients with BR- and LA-PDAC could lead to similar overall survival to that after standard PD.

Pseudomyxoma Peritonei: A Challenging Clinical Diagnosis. Case Report and Review of the Literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical entity of subtle onset abdominal pain, ascites, and distention associated with characteristic imaging. In most cases, laparoscopic exploration will give the definitive diagnosis and histopathologic verification. However, usually there are difficulties in the diagnosis of this disease. Case Report: Herein, we present a case of a 51-year-old female who developed ascites over 5 months. An investigational laparotomy established the diagnosis of PMP, after the discovery of a mucinous, grey-brown tumor that was CK20 positive and CK7 negative. Subsequently, chemotherapy with oxaliplatin combined with 5-FU (FOLFOX4 regimen), was initiated and the patient survived for 30 months. We also present a comprehensive review of the English literature concerning the different symptoms and radiological findings of this rare entity. According to the literature review, 35 cases of PMP with different clinical and radiological findings have been described. In the majority of the cases, ultrasound, computed tomography or magnetic resonance imaging was orientating towards a proper diagnosis before a diagnostic laparotomy. Conclusion: The combination of a clinical picture with the characteristic imaging findings enables a prompt diagnosis of PMP, making prognosis more favorable.

The Effects of Sarcopenia on Overall Survival and Postoperative Complications of Patients Undergoing Hepatic Resection for Primary or Metastatic Liver Cancer: A Systematic Review and Meta-Analysis.

Background: Colorectal cancer is the third most common cancer worldwide, and 20-30% of patients will develop liver metastases (CRLM) during their lifetime. Hepatocellular carcinoma (HCC) is also one of the most common cancers worldwide with increasing incidence. Hepatic resection represents the most effective treatment approach for both CRLM and HCC. Recently, sarcopenia has gained popularity as a prognostic index in order to assess the perioperative risk of hepatectomies. The aim of this study is to assess the effects of sarcopenia on the overall survival (OS), complication rates and mortality of patients undergoing liver resections for HCC or CRLM. Methods: A systematic literature search was performed for studies including patients undergoing hepatectomy for HCC or CRLM, and a meta-analysis of the data was performed. Results: Sarcopenic patients had a significantly lower 5-year OS compared to non-sarcopenic patients (43.8% vs. 63.6%, respectively; p < 0.01) and a significantly higher complication rate (35.4% vs. 23.1%, respectively; p = 0.002). Finally, no statistical correlation was found in mortality between sarcopenic and non-sarcopenic patients (p > 0.1). Conclusions: Sarcopenia was significantly associated with decreased 5-year OS and increased morbidity, but no difference was found with regard to postoperative mortality.

Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.

T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+ patients compared to PreI- patients (not reached vs. 321 days, respectively; p = 0.014). PreI+ patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+ cells and lower percentages of immunosuppressive Tregs compared to PreI- patients. Additionally, patients with PreI+ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens.