Advanced Molecular Solutions for Cancer Therapy-The Good, the Bad, and the Ugly of the Biomarker Paradigm.

Identifying the most effective actionable molecules whose "smart" manipulation might selectively kill/slow down/stop the proliferation of cancer cells, with few side effects on the normal cells of the tissue, was for decades the single major objective of countless investigators [...].

Endotoxin Inflammatory Action on Cells by Dysregulated-Immunological-Barrier-Linked ROS-Apoptosis Mechanisms in Gut-Liver Axis.

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut-liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut-liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.

An Innovative Approach to a Potential Neuroprotective Sideritis scardica-Clinoptilolite Phyto-Nanocarrier: In Vitro Investigation and Evaluation.

The cutting-edge field of nanomedicine combines the power of medicinal plants with nanotechnology to create advanced scaffolds that boast improved bioavailability, biodistribution, and controlled release. In an innovative approach to performant herb nanoproducts, Sideritis scardica Griseb and clinoptilolite were used to benefit from the combined action of both components and enhance the phytochemical's bioavailability, controlled intake, and targeted release. A range of analytical methods, such as SEM-EDX, FT-IR, DLS, and XDR, was employed to examine the morpho-structural features of the nanoproducts. Additionally, thermal stability, antioxidant screening, and in vitro release were investigated. Chemical screening of Sideritis scardica Griseb revealed that it contains a total of ninety-one phytoconstituents from ten chemical categories, including terpenoids, flavonoids, amino acids, phenylethanoid glycosides, phenolic acids, fatty acids, iridoids, sterols, nucleosides, and miscellaneous. The study findings suggest the potential applications as a promising aspirant in neurodegenerative strategy.

Molecules at Play in Cancer.

Despite its wide range of incidence, cancer can spontaneously occur in any part of the body and invade regions other than the originally affected tissue [...].

Genomic Fabrics of the Excretory System's Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report, we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically removed right kidney and its metastasis in the chest wall from the perspective of the Genomic Fabric Paradigm (GFP). The GFP characterizes every single gene in each region by these independent variables: the average expression level (AVE), relative expression variability (REV), and expression correlation (COR) with each other gene. While the traditional approach is limited to only AVE analysis, the novel REV analysis identifies the genes whose correct expression level is critical for cell survival and proliferation. The COR analysis determines the real gene networks responsible for functional pathways. The analyses covered the pathways for aldosterone-regulated sodium reabsorption, collecting duct acid secretion, endocrine and other factor-regulated sodium reabsorption, proximal tubule bicarbonate reclamation, and vasopressin-regulated water reabsorption. The present study confirms the conclusion of our previously published articles on prostate and kidney cancers that even equally graded cancer nodules from the same tumor have different transcriptomic topologies. Therefore, the personalization of anti-cancer therapy should go beyond the individual, to his/her major cancer nodules.

Metabolic Deregulation in Pulmonary Hypertension.

The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in "Genes" by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid-derived 2-like 2 (Nfe2l2) in three standard PAH rat models. PAH was induced by subjecting the animals to hypoxia (HO), or by injecting with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with novel analyses of previously published transcriptomic datasets of the animal lungs from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and fructose and mannose pathways. According to the transcriptomic distance, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes, and replaced phosphomannomutase 2 (Pmm2) with phosphomannomutase 1 (Pmm1) in the center of the fructose and mannose metabolism. We also found significant regulation of key genes involved in PAH channelopathies. In conclusion, our data show that metabolic dysregulation is a major PAH pathogenic factor.

Calprotectin, Biomarker of Depression in Patients with Inflammatory Bowel Disease?

Background and Objectives: Calprotectin is a marker for intestinal inflammation. Recent research suggests a link between inflammation and depression. This study assessed the association between the levels of calprotectin in patients from South-Eastern Europe and the severity of depression, anxiety, and quality of life. Materials and Methods: This cross-sectional study included 30 confirmed patients with Crohn's disease (CD) and ulcerative colitis (UC) who were assessed using clinical interviews for determining the severities of mental disorders (i.e., depression severity-PHQ-9, anxiety-GAD-7) and the quality of life (EQ-5D). Stool samples were collected from all participants for measuring their levels of calprotectin. Results: The level of calprotectin is correlated with PHQ-9 (ρ = 0.416, p = 0.022) and EQ-5D (ρ = -0.304, p = 0.033) but not with GAD 7 (ρ = 0.059, p = 0.379). Calprotectin levels in patients with mild, moderate, and moderately severe depression were significantly higher than in patients with minimal depression (198 µg/g vs. 66,9 µg/g, p = 0.04). Calprotectin level was corelated with the following depressive symptoms: autolytic ideation (ρ = 0.557, p = 0.001), fatigue (ρ = 0.514, p = 0.002), slow movement (ρ = 0.490, p = 0.003), and sleep disorders (ρ = 0.403, p = 0.014). Calprotectin was an independent predictor of depression with an odds ratio of 1.01 (95%: 1.002-1.03, p < 0.01). An ROC analysis showed that a level of calprotectin of 131 µg/g or higher has a sensitivity of 82%, a specificity of 61%, and an accuracy of 70% for predicting depression. In this study, no significant correlations were found between calprotectin level and anxiety. Conclusions: Calprotectin levels are associated with the severity of depression, and checking for a calprotectin level of 131 µg/g or higher may be a potential accessible screening test for depression in patients with inflammatory bowel disease.

Personalized 3-Gene Panel for Prostate Cancer Target Therapy.

Many years and billions spent for research did not yet produce an effective answer to prostate cancer (PCa). Not only each human, but even each cancer nodule in the same tumor, has unique transcriptome topology. The differences go beyond the expression level to the expression control and networking of individual genes. The unrepeatable heterogeneous transcriptomic organization among men makes the quest for universal biomarkers and "fit-for-all" treatments unrealistic. We present a bioinformatics procedure to identify each patient's unique triplet of PCa Gene Master Regulators (GMRs) and predict consequences of their experimental manipulation. The procedure is based on the Genomic Fabric Paradigm (GFP), which characterizes each individual gene by the independent expression level, expression variability and expression coordination with each other gene. GFP can identify the GMRs whose controlled alteration would selectively kill the cancer cells with little consequence on the normal tissue. The method was applied to microarray data on surgically removed prostates from two men with metastatic PCas (each with three distinct cancer nodules), and DU145 and LNCaP PCa cell lines. The applications verified that each PCa case is unique and predicted the consequences of the GMRs' manipulation. The predictions are theoretical and need further experimental validation.

Extended Lymphadenectomy for Proximal Transverse Colon Cancer: Is There a Place for Standardization?

Background and Objectives: Complete mesocolon excision and high vascular ligation have become a standard procedure in the treatment of colon cancer. The transverse colon has certain embryological and anatomical particularities which require special attention in case of oncological surgeries. Proximal transverse colon cancer (TCC) can metastasize to the lymph nodes in the gastrocolic ligament. The aim of this study is to assess the tumor involvement of these lymph nodes and to determine the applicability of gastrocolic ligament lymph nodes dissection as the standard approach for proximal transverse colon cancer. Materials and Methods: this study analyzes the cases of patients admitted to the Surgery Department, diagnosed with proximal transverse colon cancer, with tumor invasion ≥ T2 and for which complete mesocolon excision with high vascular ligation and lymphadenectomy of the gastrocolic ligament (No. 204, 206, 214v) were performed. Results: A total of 43 cases operated during 2015−2020 were included in the study. The median total number of retrieved central lymph nodes was 23 (range, 12−38), that had tumor involvement in 22 cases (51.2%). Gastrocolic ligament tumor involvement was found in 5 cases (11.6%). The median operation time was 180 min, while the median blood loss was 115 mL (range 0−210). The median time of hospitalization was 6 days (range, 5−11). Grade IIIA in the Clavien-Dindo classification was noticed in 3 patients, with no mortality. Upon Kaplan−Meier analysis, tumors > T3 (p < 0.016) and lymph node ratio < 0.05 (p < 0.025) were statistically significant. Conclusions: lymph node dissection of the gastrocolic ligament in patients with advanced proximal transverse colon cancer may improve the oncological outcome in T3/T4 tumors, and therefore standardization could be feasible

Residual Gallbladder and Cystic Duct Stump Stone after Cholecystectomy: Laparoscopic Management.

Background: Cholecystectomy is the standard treatment for symptomatic gallstones, and the persistence of symptoms after surgery defines postcholecystectomy syndrome. Biliary causes of postcholecystectomy syndrome include subtotal cholecystectomy and remnant cystic duct stump stone; causes that are encountered with a low frequency, but which require diagnosis and provocative treatment. Laparoscopic management of such cases is recommended, but requires well-trained teams in laparoscopic surgery. Methods: This study is a retrospective analysis of patients who required surgical treatment for residual gallbladder and cystic duct stump stone after a cholecystectomy, hospitalized in the Surgery Department of Constanta County Hospital, who required completion of resection and were operated laparoscopically. Results: Between January 2010 and March 2020, 14 patients were hospitalized with residual gallbladder and cystic duct stump stone that required surgery. All patients underwent laparoscopic surgery. Symptomatology was dominated by recurrent biliary colic (50%). The period between the primary surgery and the surgery to complete the resection varied between 2-22 years. There were 4 cases of subtotal cholecystectomies, and 10 cases of remnant cystic duct stump stones. Intraoperative complications were encountered in only one case (7.14%), the number of days of hospitalization was on average 3 days. No patient showed any symptoms at 6-month postoperative follow-up. Conclusions: Postcholecystectomy syndrome is difficult to diagnose, symptomatic patients with remnant cystic duct stump stone/ subtotal cholecystectomy requiring surgery are difficult to manage. Laparoscopic surgery is preferred for the benefits that laparoscopic surgery brings, but requires an experienced surgeon in advanced laparoscopic techniques.

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways.

The genetic causes of the differentiated, highly treatable, and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully understood. The mostly accepted PTC etiology blames the altered sequence or/and expression level of certain biomarker genes. However, tumor heterogeneity and the patient's unique set of favoring factors question the fit-for-all gene biomarkers. Publicly accessible gene expression profiles of the cancer nodule and the surrounding normal tissue from a surgically removed PTC tumor were re-analyzed to determine the cancer-induced alterations of the genomic fabrics responsible for major functional pathways. Tumor data were compared with those of standard papillary and anaplastic thyroid cancer cell lines. We found that PTC regulated numerous genes associated with DNA replication, repair, and transcription. Results further indicated that changes of the gene networking in functional pathways and the homeostatic control of transcript abundances also had major contributions to the PTC phenotype occurrence. The purpose to proliferate and invade the entire gland may explain the substantial transcriptomic differences we detected between the cells of the cancer nodule and those spread in homo-cellular cultures (where they need only to survive). In conclusion, the PTC etiology should include the complex molecular mechanisms involved in the remodeling of the genetic information processing pathways.

Romanian Wild-Growing Chelidonium majus-An Emerging Approach to a Potential Antimicrobial Engineering Carrier System Based on AuNPs: In Vitro Investigation and Evaluation.

Novel nanotechnology based on herbal products aspires to be a high-performing therapeutic platform. This study reports the development of an original engineering carrier system that jointly combines the pharmacological action of Chelidonium majus and AuNPs, with unique properties that ensure that the limitations imposed by low stability, toxicity, absorption, and targeted and prolonged release can be overcome. The metabolite profile of Romanian wild-grown Chelidonium majus contains a total of seventy-four phytochemicals belonging to eight secondary metabolite categories, including alkaloids, amino acids, phenolic acids, flavonoids, carotenoids, fatty acids, sterols, and miscellaneous others. In this study, various techniques (XRD, FTIR, SEM, DLS, and TG/DTG) were employed to investigate his new carrier system's morpho-structural and thermal properties. In vitro assays were conducted to evaluate the antioxidant potential and release profile. The results indicate 99.9% and 94.4% dissolution at different pH values for the CG-AuNPs carrier system and 93.5% and 85.26% for greater celandine at pH 4 and pH 7, respectively. Additionally, three in vitro antioxidant assays indicated an increase in antioxidant potential (flavonoid content 3.8%; FRAP assay 24.6%; and DPPH 24.4%) of the CG-AuNPs carrier system compared to the herb sample. The collective results reflect the system's promising perspective as a new efficient antimicrobial and anti-inflammatory candidate with versatile applications, ranging from target delivery systems, oral inflammation (periodontitis), and anti-age cosmetics to extending the shelf lives of products in the food industry.

The Clinicopathological Differences of Colon Cancer in Young Adults Versus Older Adults.

Purpose: Colon cancer is the third-most common and fatal cancer, with a mean age of onset >65 years. In recent years, there has been an increase in the number of cases of colon cancer in young (CCY) patients. This study investigates the biological behavior and epidemiological features of CCY and older adults in our area. Methods: Eighty-one patients (19 young adults <40 years old and 62 older adults ≥40 years old) were admitted to the General Surgery Clinic of the Constanta Emergency Hospital for colon cancer between January and December 2018. The biological behavior and epidemiological characteristics of the two groups were compared. Results: The group of young patients was characterized by finding the diagnosis on an average of 6-9 months after the onset of the first symptom, in a more advanced stage of the disease (73.69%); the onset of symptoms being nonspecific (diarrhea 26.32%, weight loss 21.05%, constipation 21.05%, and bloating 21.05%) and initially treated in a benign context, without the recommendation of additional specific explorations. The time between the onset of symptoms and the diagnosis established in the category of patients ≥40 years of age was on an average of 3-6 months, with most patients being diagnosed in the early stages of the disease (62.9%). Conclusions: Improving health education through colon cancer information programs should be implemented with information on alert symptoms and indications on the steps that a symptomatic patient should follow and no longer ignore his or her symptoms, because health is not necessarily the prerogative of youth.

TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population.

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/ß-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058-4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.

Depression in Central and Eastern Europe: How Much It Costs? Cost of Depression in Romania.

OBJECTIVE: The present study aims to estimate the public cost of depression in Romania during a seven-year time span to complement existing papers with data from Central and Eastern Europe and to identify and propose measures that allow efficient use of funds. METHODS: We used data collected from the National Health Insurance System to analyze the main components of the cost. FINDINGS: Indirect costs exceed direct costs. Within the direct costs, hospitalization and medicines still have an important share but are decreasing due to the intervention of outpatient services such as psychiatrists and psychotherapists. CONCLUSION: Since the goal is mental health, it is necessary to act early and quickly to decrease the burden in the long run. Annually, the mean direct cost of depression per patient is EUR 143 (part of it is represented by hospitalization, i.e., EUR 67, and psychotherapy, i.e., EUR 5), the mean cost of sick leaves per patient is EUR 273, and the total cost per patient is EUR 5553. Indirect costs (cost of disability and lost productive years) represent 97.17% of the total cost. An integrated approach to early diagnosis, effective treatment, monitoring, and prevention as well as included economic and social programs are needed to optimize indirect costs.

Risk factors in non­surviving patients with infection with carbapenemase­producing Enterobacterales strains in an intensive care unit.

Carbapenemase-producing Enterobacterales (CPE) are Gram-negative bacteria that belong to the Enterobacterales family and produce enzymes known as carbapenemases, which inhibit carbapenems, cephalosporins and penicillins. Carbapenem-resistant Enterobacterales (CRE) are resistant to carbapenems, cephalosporins and penicillins via mechanisms that may or may not produce carbapenemases. The identification of carbapenems is critical for the initiation of proper antibiotic therapy. The present case-control, retrospective study included 64 patients with CPE strains admitted to an intensive care unit between September, 2017 and October, 2021; of these, 34 patients with CPE succumbed and 30 control patients with CPE strains survived. CPE strains in the deceased patients were caused by Klebsiella spp. in 31 cases (91.2%) and Escherichia coli in 3 cases (8.8%). The univariate analysis revealed that the predictive factors associated with mortality in patients with CPE were admission with coronavirus disease 2019 (COVID-19) (P=0.001), invasive mechanical ventilation (P=0.001), and treatment with corticosteroids (P=0.006). The multivariate analysis revealed that admission with COVID-19 [odds ratio (OR), 16.26; 95% confidence interval (CI), 3.56-74.14; P≤0.05] and invasive mechanical ventilation (OR, 14.98; 95% CI, 1.35-166.22; P≤0.05) were associated with mortality as independent risk factors. Admission with COVID-19 increased the risk of mortality 16.26-fold and invasive mechanical ventilation increased the risk of mortality by 14.98-fold. On the whole, the present study demonstrates that the length of hospital duration in patients who acquired CPE did not influence mortality, whereas infection with COVID-19 increased and invasive mechanical ventilation were associated with an increased risk of mortality.

Associated factors for bacterial colonization in patients admitted to the intensive care unit of the Clinical Hospital of Infectious Diseases.

Introduction: This study aimed to identify isolates from colonization and assess the risk factors for bacterial colonization and the risk of death in patients admitted to the intensive care unit (ICU) of the Constanta County Infectious Diseases Hospital between September 2017 and September 2019. Methods: This was a retrospective case-control study in a single center that included all patients admitted to the ICU in Constanta, Romania, who underwent bacteriological screening upon admission and 7 days after admission, between September 2017 and September 2019. In total, 253 patients were included in this study. The nasal exudate, pharyngeal exudate, and rectal swab samples were screened. Results: In this study, 253 patients were screened bacteriologically, of which 53 had bacterial colonization and 200 did not. Among the bacterial strains, Klebsiella spp. (43.39%) was the most frequently isolated. The predominant resistance mechanism detected in the bacterial isolates was extended-spectrum ß-lactamase (ESBL). Multivariate analysis identified a Carmeli score of 3 as an independent risk factor for acquiring bacterial colonization in the ICU. The mortality rate of patients with bacterial colonization was 11.32% and 6% for the patients without colonization (p>0.05). Conclusions: Our study revealed an increased prevalence of Enterobacterales colonization in the ICU. Risk factors for acquiring bacterial colonization differed depending on the type of bacterial colonization, such as ESBL, carbapenemases, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). An independent risk factor for acquiring bacterial colonization was the Carmeli score of 3.

Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

BACKGROUND AND AIMS: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). METHODS: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 µg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. RESULTS: Mean fecal calprotectin was 1540±890 µg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. CONCLUSIONS: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.