Search Results (31)

Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study’s main endpoints. Statistical analysis was performed using MedCalc^® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22–116.99], HR: 12.54 [95% CI: 1.28–122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients’ clinical outcomes. Full article

Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide. Full article

Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin production. Telotristat use in patients with carcinoid syndrome and uncontrollable diarrhea under somatostatin analogs is approved, but its specific role in patients with CHD is still not clear. IN this context, we aimed to explore the effect of telotristat in heart fibrosis using a mouse model of serotonin-secreting metastasized neuroendocrine neoplasm (NEN). To this aim, four treatment groups (n = 10/group) were evaluated: control, monthly octreotide, telotristat alone, and telotristat combined with octreotide. Plasma serotonin and NT-proBNP levels were determined. Heart fibrosis was histologically evaluated after 6 weeks of treatment or when an individual mouse’s condition was close to being terminal. Heart fibrosis was observed in all groups. Non-significant reductions in primary tumor growth were observed in all of the treated groups. Feces volume was increased in all groups. A non-significant decrease in feces volume was observed in the octreotide or telotristat-treated groups, while it was significantly reduced with the combined treatment at the end of the study compared with octreotide (52 g reduction; p < 0.01) and the control (44.5 g reduction; p = 0.05). Additionally, plasma NT-proBNP decreased in a non-significant, but clinically relevant, manner in the octreotide (28.2% reduction), telotristat (45.9% reduction), and the octreotide + telotristat (54.1% reduction) treatment groups. No significant changes were observed in plasma serotonin levels. A similar non-significant decrease in heart valve fibrosis was observed in the three treated groups. In conclusion, Telotristat alone and especially in combination with octreotide decreases NT-proBNP levels in a mouse model of serotonin-secreting metastasized NEN, when compared with the control and octreotide, but its effect on heart valve fibrosis (alone and in combination) was not superior to octreotide in monotherapy. Full article

This work focused on the verification of the electrical parameters and the durability of side connectors installed in glass–glass photovoltaic modules. Ensuring the safe use of photovoltaic modules is achieved, among others, by using electrical connectors connecting the PV cell circuit inside the laminate with an external electric cable. In most of the cases for standard PV modules, the electrical connector in the form of a junction box is attached from the back side of the PV module. The junction box is glued to the module surface with silicone where the busbars were previously brought out of the laminate through specially prepared holes. An alternative method is to place connectors on the edge of the module, laminating part of it. In such a case, the specially prepared “wings” of the connector are tightly and permanently connected using laminating foil, between two glass panes protecting against an electrical breakdown. Additionally, this approach eliminates the process of preparing holes on the back side of the module, which is especially complicated and time-consuming in the case of glass–glass modules. Moreover, side connectors are desirable in BIPV applications because they allow for a more flexible design of installations on façades and walls of buildings. A series of samples were prepared in the form of PV G-G modules with side connectors, which were then subjected to testing the connectors for the influence of environmental conditions. All samples were characterized before and after the effect of environmental conditions according to PN-EN-61215-2 standards. Insulation resistance tests were performed in dry and wet conditions, ensuring full contact of the tested sample with water. For all modules, before being placed in the climatic chamber, the resistance values were far above the minimum value required by the standards, allowing the module to be safely used. For the dry tests, the resistance values were in the range of GΩ, while for the wet tests, the obtained values were in the range of MΩ. In further work, the modules were subjected to environmental influences in accordance with MQT-11, MQT-12, and MQT-13 and then subjected to electrical measurements again. A simulation of the impact of changing climatic conditions on the module test showed that the insulation resistance value is reduced by an order of magnitude for both the dry and wet tests. Additionally, one can observe visual changes where the lamination foil is in contact with the connector. The measurements carried out in this work show the potential of side connectors and their advantage over rear junction boxes, but also the technological challenges that need to be overcome. Full article

Introduction: The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial. Aim: To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3). Method: A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors. Results: 413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21–34) months, and tumor size was 1.0 (0.8–1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31–102) months, median tumor size 2 (1.2–3.4) cm, median Ki-67 index 5 (3–10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6–46) months, median tumor size 4.2 (2.6–7.0) cm, Ki-67 index 17 (9–64)%, the median disease-specific survival was 22 (6–75) months—99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors. Conclusion: Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection. Full article

Background: Parenteral nutrition (PN) is needed to avoid the development of malnutrition when enteral nutrition (EN) is not possible. Our main aim was to assess the current use, complications, and nutrition delivery associated with PN administration in adult critically ill patients, especially when used early and as the initial route. We also assessed the differences between patients who received only PN and those in whom EN was initiated after PN (PN-EN). Methods: A multicenter (n = 37) prospective observational study was performed. Patient clinical characteristics, outcomes, and nutrition-related variables were recorded. Statistical differences between subgroups were analyzed accordingly. Results: From the entire population (n = 629), 186 (29.6%) patients received PN as initial nutrition therapy. Of these, 74 patients (11.7%) also received EN during their ICU stay (i.e., PN-EN subgroup). PN was administered early (<48 h) in the majority of patients (75.3%; n = 140) and the mean caloric (19.94 ± 6.72 Kcal/kg/day) and protein (1.01 ± 0.41 g/kg/day) delivery was similar to other contemporary studies. PN showed similar nutritional delivery when compared with the enteral route. No significant complications were associated with the use of PN. Thirty-two patients (43.3%) presented with EN-related complications in the PN-EN subgroup but received a higher mean protein delivery (0.95 ± 0.43 vs 1.17 ± 0.36 g/kg/day; p = 0.03) compared with PN alone. Once adjusted for confounding factors, patients who received PN alone had a lower mean protein intake (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.18–0.47; p = 0.001), shorter ICU stay (HR: 0.96; 95% CI: 0.91–0.99; p = 0.008), and fewer days on mechanical ventilation (HR: 0.85; 95% CI: 0.81–0.89; p = 0.001) compared with the PN-EN subgroup. Conclusion: The parenteral route may be safe, even when administered early, and may provide adequate nutrition delivery. Additional EN, when possible, may optimize protein requirements, especially in more severe patients who received initial PN and are expected to have longer ICU stays. NCT Registry: 03634943. Full article

Data on the possible connection between circulating adipokines and PanNENs are limited. This novel study aimed to assess the serum levels of leptin and adiponectin and their ratio in patients with PanNENs and to evaluate the possible relationship between them and PanNEN’s grade or stage, including the presence of metastases. The study group consisted of PanNENs (n = 83), and healthy controls (n = 39). Leptin and adiponectin measurement by an ELISA assay was undertaken in the entire cohort. The serum concentration of adiponectin was significantly higher in the control group compared to the study group (p < 0.001). The concentration of leptin and adiponectin was significantly higher in females than in males (p < 0.01). Anincreased leptin–adiponectin ratio was observed in well-differentiated PanNENs (G1) vs. moderatelydifferentiated PanNENs (G2) (p < 0.05). An increased leptin–adiponectin ratio was found in PanNENs with Ki-67 < 3% vs. Ki-67 ≥ 3% (p < 0.05). PanNENs with distal disease presented lower leptin levels (p < 0.001) and a decreased leptin–adiponectin ratio (p < 0.01) compared with the localized disease group. Leptin, adiponectin, and the leptin–adiponectin ratio may serve as potential diagnostic, prognostic, and predictive biomarkers for PanNENs. Leptin levels and the leptin–adiponectin ratio may play an important role as predictors of malignancy and metastasis in PanNENs. Full article

This article describes a method of immunity testing for commercial unmanned aircraft vehicles relative to a variable near-lightning electric field component. The research focuses on one of the components of the electromagnetic field generated during a lightning discharge: the electrical component. Studies are proposed showing the influence of only this one factor on overvoltages arising in the drone. So far, no one has analyzed such an impact from emerging disturbances, because previous studies in the area have largely considered the impact of the entire electromagnetic field. This is justified practically, but not scientifically—it is necessary to determine the impact of each component separately. Selected electronic components are tested here. For that purpose, two types of pulses are used: Wave Form 4 (WF4–6.4/69 μs from DO-160 standard) and Voltage waveform 1.2/50 μs (PN-EN 61000-4-5:2014-10). The testing object is centrally placed in a capacitor between two parallel plates of dimensions 2 m by 2 m to provide a homogeneous electric field. The results (from a Rigol 1054Z oscilloscope) are saved in *.CSV files (for further analysis). The research shows that the greatest overvoltages are in active parts of the drone (higher-than-supply voltage level), such as the RF antenna or semiconductors. This emphasizes the need to pay special attention to the protection of these elements against a pulsed electromagnetic field, especially the electric component (e.g., lightning discharge). Full article

To enhance the extraction of methane gas from coal beds, hydraulic fracturing technology is used. However, stimulation operations in soft rocks, such as coal beds, are associated with technical problems related mainly to the embedment phenomenon. Therefore, the concept of a novel coke-based proppant was introduced. The purpose of the study was to identify the source coke material for further processing to obtain a proppant. Twenty coke materials differing in type, grain size, and production method from five coking plants were tested. The values of the following parameters were determined for the initial coke: micum index 40; micum index 10; coke reactivity index; coke strength after reaction; and ash content. The coke was modified by crushing and mechanical classification, and the 3–1 mm class was obtained. This was enriched in heavy liquid with a density of 1.35 g/cm³. The crush resistance index and Roga index, which were selected as key strength parameters, and the ash content were determined for the lighter fraction. The most promising modified coke materials with the best strength properties were obtained from the coarse-grained (fraction 25–80 mm and greater) blast furnace and foundry coke. They had crush resistance index and Roga index values of at least 44% and at least 96%, respectively, and contained less than 9% ash. After assessing the suitability of coke material for proppants in the hydraulic fracturing of coal, further research will be needed to develop a technology to produce proppants with parameters compliant with the PN-EN ISO 13503-2:2010 standard. Full article

With the level of development of the smart city, there are more and more research sub-areas in which the latest material and technological solutions are used, enabling the proper management and functioning of these cities. On the one hand, the introduced materials and technologies are designed to facilitate the functioning of residents both in the urban space and at home; on the other hand, the implemented solutions strive to be consistent with the principles of sustainable development. As shown in this article, reports on new technical and technological solutions and their positive and negative effects are strongly emphasized in publications on the development of smart cities. The most highlighted materials research in the smart city area concerns smart materials and their characteristics and applications. A research gap in this area is in the presentation of material solutions, particularly materials intended for the load-bearing structures of vehicles (electric vehicles, flying vehicles) or infrastructure elements (buildings, shelters, etc.) designed to increase the durability of the structure while reducing its weight. This paper aims to comprehensively present the most important research areas related to the functioning of smart cities in light of previous research, with particular emphasis on new material solutions used for thin-walled load-bearing structures in smart cities made of AHSS (advanced high-strength steel). These solutions are very essential for smart cities because their use allows for the installation of additional devices, sensors, transmitters, antennas, etc., without increasing the total weight of the structure; they reduce the number of raw materials used for production (lighter and durable thin structures), ensure lower energy consumption (e.g., lighter vehicles), and also increase the passive safety of systems or increase their lifting capacity (e.g., the possibility of transporting more people using transports at the same time; the possibility of designing and arranging, e.g., green gardens on buildings; etc.). AHSS-welded joints are usually characterized by too-low strength in the base material or a tendency to crack. Thus, the research problem is producing a light and durable AHSS structure using welding processes. The research presented in this article concerns the possibility of producing welded joints using the Metal Active Gas (MAG) process. The test methods include the assessment of the quality of joints, such as through visual examination (VT); according to the requirements of PN-EN ISO 17638; magnetic particle testing (MT); according to PN-EN ISO 17638; and the assessment of the selected mechanical properties, such as tensile strength tests, bending tests, and fatigue strength checks. These methods enable the selection of the correct joints, without welding defects. The results have a practical implication; advanced production technology for obtaining AHSS joints can be used in the construction of the load-bearing elements of mobile vehicles or parts of point infrastructure (shelters, bus stops). The obtained joint is characterized by adequate strength for the production of the assumed structures. The originality of the manuscript is the presentation of a new, cheaper, and uncomplicated solution for obtaining an AHSS joint with good mechanical properties. The application of the presented solution also contributes to sustainable development (lower fuel and material consumption use by mobile vehicles) and may contribute to increasing the load capacity of mobile vehicles (the possibility of transporting more people). Full article

Type I gastric neuroendocrine neoplasms (gNENs) are associated with atrophic gastritis and have a high recurrence rate, which means frequent endoscopies are required. The objective of this study was to identify factors predicting the local recurrence of type I gNENs. The clinical course and the pathological and biochemical data of patients with type I gNENs treated at Bnai Zion Medical Center between 2006 and 2022 were analyzed retrospectively. Twenty-seven type I gNENs were evaluated. The follow-up period was 41 months (range: 11–288 months). Recurrence of the tumor occurred in 13/27 (48%) patients after 35 months (median (M), interquartile range (IQR): 21–67.5). Serum gastrin levels were significantly higher in patients with recurrent disease versus patients with non-recurrent disease (788 vs. 394 ng/L; p = 0.047), while the Ki-67 index was significantly lower in patients with recurrent disease versus patients with non-recurrent disease (1% vs. 3.5%; p = 0.035). Tumor size, mitotic count, and serum chromogranin A levels did not correlate with recurrence. The present study emphasizes the role of gastrin in the pathogenesis of gNEN recurrence and highlights the debate regarding the ability of the Ki-67 index to predict the clinical course of this disease. Full article

Pancreatic neuroendocrine neoplasms (pNEN) are rare and heterogeneous tumors. Previous investigations have shown that autophagy can be a target for cancer therapy. This study aimed to determine the association between the expression of autophagy-associated gene transcripts and clinical parameters in pNEN. In total, 54 pNEN specimens were obtained from our human biobank. The patient characteristics were retrieved from the medical record. RT-qPCR was performed to assess the expression of the autophagic transcripts BECN1, MAP1LC3B, SQSTM1, UVRAG, TFEB, PRKAA1, and PRKAA2 in the pNEN specimens. A Mann–Whitney U test was used to detect differences in the expression of autophagic gene transcripts between different tumor characteristics. This study showed that G1 sporadic pNEN have a higher expression of autophagic genes compared to G2. Lymphatic and distant metastasis occurred significantly more often in pNEN with a decreased expression of the autophagic genes. Within sporadic pNEN, the insulinomas express higher levels of autophagic transcripts than gastrinomas and non-functional pNEN. MEN1-associated pNEN show a higher expression of autophagic genes than sporadic pNEN. In summary, a decreased expression of autophagic transcripts distinguishes metastatic from non-metastatic sporadic pNEN. The significance of autophagy as a molecular marker for prognosis and therapy decisions needs to be further investigated. Full article

The study of the R&D in this paper is to determine the range of essential oils (EOs) in the raw materials of species of the genus Thymus of the natural flora in the Carpathian region and their antimicrobial activity. It was found that the component range of EO in species of the genus Thymus depends on the microclimatic conditions of the population. The range of essential oils in the raw material of Th. Serpyllum and Th. Pulegoides is 7–9 mL and Th. Marschallianus is 3.5 mL. The research found that the plants Th. Serpyllum and Th. Pulegoides that grow in sunny habitats have an aromatic mono- and bicyclic monoterpenoid chemotype (K/α-T-neol/ G/p-C/B), with total dominance of carvacrol and p-cymene. The populations of Th. Serpyllum, which grow on the edges of sparse pine forests, and populations of Th. Pullegioide, with denser plant cover and which grow in meadows, have an acyclic and bicyclic monoterpene chemotype (G/α-T-neol/B/K). Plants that grow in the communities of meadow-steppe vegetation have the following chemotypes: Th. Serpyllum—L/K/G with 63% of linalool, Th. Pullegioides—G/α-T-neol/L/B, and Th. Marschallianus—α-T-neol/K/L/α-T-nen/G/B. Of these, the dominant chemotypes are α-terpineol and carvacrol (28:6.5%). A wide spectrum of antimicrobial activity was registered in samples of Th. Pullegoides and Th. Serpyllum that have an aromatic-monoterpenoid chemotype. Essential oils of Th. Pullegoides were dominated by carvacrol, and p-cymene had the highest fungicidal action (41.00 ± 1.0%). Plant populations of Th. Pullegoides and Th. Serpyllum with the aromatic-monoterpenoid chemotype are suggested by R&D to be of use in the pharmaceutical industry. They have high contents of natural components, which are effective in a wide spectrum of antimicrobial activity. The EO of Th. Marschallianus had the lowest influence on the inhibition of bacterial and fungal reproduction. Full article

Background: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. Methods: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. Results: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. Conclusion: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available. Full article

Background: Across a variety of solid tumors, prognostic implications of nutritional and inflammation-based risk scores have been identified as a complementary resource of risk stratification. Methods: In this retrospective study, we performed a comparative analysis of several established risk scores and ratios, such as the Glasgow Prognostic Score (GPS), in neuroendocrine neoplasms of the gastro–entero–pancreatic (GEP-NEN) system with respect to their prognostic capabilities. Clinicopathological and treatment-related data for 102 GEP-NEN patients administered to the participating institutions between 2011 and 2021 were collected. Scores/ratios significantly associated with overall or progression-free survival (OS, PFS) upon univariate analysis were subsequently included in a Cox-proportional hazard model for the multivariate analysis. Results: The median age was 62 years (range 18–95 years) and the median follow-up period spanned 51 months. Pancreatic or intestinal localization at the initial diagnosis were present in 41 (40.2%) and 44 (43.1%) cases, respectively. In 17 patients (16.7%), the primary manifestation could not be ascertained (NNUP; neuroendocrine neoplasms of unknown primary). Histological grading (HG) revealed 24/102 (23.5%) NET/NEC (poorly differentiated; high grade G3) and 78/102 (76.5%) NET (highly or moderately differentiated; low–high grade G1–G2). In total, 53/102 (51.9%) patients presented with metastatic disease (UICC IV), 11/102 (10.7%) patients presented with multifocal disease, and 56/102 (54.9%) patients underwent a primary surgical or endoscopic approach, whereas 28 (27.5%) patients received systemic cytoreductive treatment. The univariate analysis revealed the GPS and PI (prognostic index), as well as UICC-stage IV, HG, and the Charlson comorbidity index (CCI) to predict both the PFS and OS in GEP-NEN patients. However, the calculation of the survival did not separate GPS subgroups at lower risk (GPS 0 versus GPS 1). Upon the subsequent multivariate analysis, GPS was the only independent predictor of both OS (p < 0.0001; HR = 3.459, 95% CI = 1.263–6.322) and PFS (p < 0.003; HR = 2.119, 95% CI = 0.944–4.265). Conclusion: In line with previous results for other entities, the present study revealed the GPS at baseline to be the only independent predictor of survival across all stages of GEP-NEN, and thus supports its clinical utility for risk stratification in this group of patients. Full article