Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.

Pancreatic adenocarcinomas (PDAC) often possess mutations in K-Ras that stimulate the ERK pathway. Aberrantly high ERK activation triggers oncogene-induced senescence, which halts tumor progression. Here we report that low-grade pancreatic intraepithelial neoplasia displays very high levels of phospho-ERK consistent with a senescence response. However, advanced lesions that have circumvented the senescence barrier exhibit lower phospho-ERK levels. Restoring ERK hyperactivation in PDAC using activated RAF leads to ERK-dependent growth arrest with senescence biomarkers. ERK-dependent senescence in PDAC was characterized by a nucleolar stress response including a selective depletion of nucleolar phosphoproteins and intranucleolar foci containing RNA polymerase I designated as senescence-associated nucleolar foci (SANF). Accordingly, combining ribosome biogenesis inhibitors with ERK hyperactivation reinforced the senescence response in PDAC cells. Notably, comparable mechanisms were observed upon treatment with the platinum-based chemotherapy regimen FOLFIRINOX, currently a first-line treatment option for PDAC. We thus suggest that drugs targeting ribosome biogenesis can improve the senescence anticancer response in pancreatic cancer.

Evaluation of personalized methylprednisolone therapy in critically ill COVID-19 patients: an observational comparative study using real-life data.

OBJECTIVE: Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support. PATIENTS AND METHODS: Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone. RESULTS: The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality. CONCLUSIONS: Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.

Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis.

Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis

@#Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Effect of physician-provided education on the quality of bowel preparation.

BACKGROUND AND STUDY AIMS: Inadequate bowel preparation in patients scheduled for colonoscopy is an important problem. In our study, we aimed to investigate the effect of physician-provided bowel preparation education on the quality of bowel preparation and process. PATIENTS AND METHODS: A total of 150 outpatients who were referred to Kocaeli University Medical Faculty Hospital Gastroenterology Unit for colonoscopy between May 2019 and October 2019 were enrolled in our prospective, endoscopist-blinded study. Patients were divided into two groups. Group 1 (education group) included 73 patients who received 10 minutes of verbal information from a physician in addition to a written information form. Group 2 (control group) included 75 patients who received information from a medical secretary in addition to a written information form. During colonoscopy, the quality of bowel preparation was assessed using the Boston bowel preparation scale (BBPS). A BBPS score = 5 was considered adequate bowel preparation. The mean BBPS score, polyp detection rate, cecal intubation rate and time, and procedure time were also evaluated. RESULTS: The rate of adequate bowel preparation (BBPS score = 5) was 90.4% and 74.7% in groups 1 and 2, respectively (p = 0.021). The odds ratio for having a BBPS score = 5 in the education group was 3.199 compared with the control group (95% confidence interval = 1.254-8.164; p = 0.015). The cecal intubation rates were 91.8% and 88% in groups 1 and 2, respectively (p > 0.05). The cecal intubation time, procedure time, and adenoma detection rates were similar between the groups. The relationships of age, education level, sex, diabetes mellitus, medicine use, procedure time, and intraabdominal surgery with inadequate bowel preparation were analysed using a logistic regression model. Univariate and multivariate analyses revealed no significant factors associated with inadequate bowel preparation. CONCLUSIONS: Patient education on the bowel preparation process via a physician improved the quality of bowel preparation.

The relationship among plasma copeptin, carboxyhemoglobin, and lactate levels in carbon monoxide poisoning.

OBJECTIVE: The aim of our study is to determine whether there is a change in the plasma levels of copeptin and there is a relationship among the plasma levels of carboxyhemoglobin (COHb), lactate, and copeptin levels in patients presenting to the emergency department with carbon monoxide (CO) poisoning. METHODS: Fifty-seven patients admitted to the emergency department with CO poisoning were included in the study. The blood samples of the patients were collected on arrival 0th, 6th, and 12th hours for copeptin, lactate, and COHb levels. Data were analyzed using SPSS-17 statistical software. RESULTS: Arrival serum copeptin levels of the patients were compared to copeptin levels of healthy individuals and a statistically significant difference was found between them (p = 0.008). There was a statistically significant difference between the arrival levels of copeptin and 6th-hour (p = 0.006) and 12th-hour (p = 0.001) levels of copeptin. There was no significant difference between 6th-hour and 12th-hour copeptin levels (p = 0.51). In terms of serum lactate levels, there was a significant difference between arrival and 6th h (p < 0.001), arrival and 12th h (p < 0.001), and 6th and 12th h (p < 0.001). Likewise, in terms of serum COHb levels, there was a significant difference between arrival and 6th h (p < 0.001), arrival and 12th h (p < 0.001), and 6th and 12th h (p < 0.001). There was a positive correlation between COHb and lactate levels on arrival (r = 0.52; p = 0.001). CONCLUSION: Copeptin as a stress hormone can be used in the diagnosis and monitoring of patients with CO poisoning. However, the copeptin level was not superior to COHb and lactate levels.

The effects of dexmedetomidine on human internal mammary artery and saphenous vein grafts under hypothermia and normothermia.

OBJECTIVES: The purpose of this study was to determine the effects of hypothermia and normothermia on the isolated human saphenous vein (SV) and internal mammary artery (IMA) responses to dexmedetomidine. METHODS: The response of human IMA and SV strips with (E+) and without (E-) endothelium subjected to cumulative concentrations of (10-9, 0-6 M) dexmedetomidine were recorded at 37 °C and at 28 °C. OnE-way ANOVA was used for analysis. A p < 0.05 was considered significant. RESULTS: At 37˚C dexmedetomidine resulted in similar significant concentration-dependent contractions in both E+ and E- SV strips (p < 0.05). At 37 °C dexmedetomidine resulted in significant concentration-dependent contractions in E+ IMA strips, these contractions were significantly lower at all concentrations of dexmedetomidine in E- compared to E+ IMA strips (p < 0.05). When results between similar groups of SV and IMA strips were compared, the contractions were significantly higher in the IMA strips in E+ and E- at 37 °C and also E- 28 °C groups compared to SV (p < 0.05). CONCLUSION: In conclusion, dexmedetomidine causes in vitro vasoconstriction in human IMA and SV grafts. These contractions are greater in IMA compared to SV grafts. Endothelium-derived pathways are possibly involved in the contractile responses of IMA. Moderate hypothermia augments vasoconstriction in SV grafts (Fig. 3, Ref. 27).

Epidemiological profiles of otorhinolaryngological disorders in adults admitted to the emergency room of a tertiary university hospital.

BACKGROUND: The incidence of otorhinolaryngological emergencies has been steadily increasing. With the increasing number of patients admitted to the emergency room, numerous challenges in healthcare have become more prevalent. This study aimed to evaluate the epidemiological profile of otorhinolaryngological disorders in adults admitted to the emergency department of a tertiary university hospital. MATERIALS AND METHODS: A total of 7028 adult patients with otorhinolaryngological disorders admitted to the emergency department of a tertiary hospital from January 1 to December 31, 2016, were enrolled in the study. Each patient underwent a comprehensive clinical evaluation by the physicians of the emergency department and was consulted by an otorhinolaryngologist. Age, sex, time of visits, and cost of each patient due to healthcare insurance were recorded. RESULTS: In total, 3098 patients were male (36.6 ± 16.4 years; 44.1%) and 3930 were female (35.4 ± 16.2 years; 55.9%). The most common otorhinolaryngological disorders were pharyngitis (n = 2713; 38.6%), followed by tonsillitis (n = 1302; 18.5%) and rhinitis (n = 1161; 16.5%). These three infectious diagnoses constituted 73.6% of all otorhinolaryngological disorders. The highest number of medical visits due to otorhinolaryngological disorders was in January, whereas the lowest number of visits was in July. When we excluded the three infection-based diagnoses, otorhinolaryngological disorders were stable at approximately 150 patients per month. The main reason for the increase in the number of visits per month due to otorhinolaryngological disorders appeared to be a result of these three infection-based diagnoses. CONCLUSION: More than 80% of otorhinolaryngological disorders in adults admitted to the emergency department were not truly emergencies requiring attendance at a tertiary hospital emergency room. New policies should be instituted to reduce the workload of the emergency services and to allow more effort to be spent on real emergencies.

The relationship between neutrophil/lymphocyte and platelet/lymphocyte ratios with oxidative stress in active Crohn's disease patients.

BACKGROUND: This study investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values with oxidative stress in active Crohn's disease (CD) patients. We investigated whether these parameters were useful for follow-up assessments of CD activity. METHODS: Forty-nine patients with a confirmed diagnosis of CD (24 active and 25 inactive) and 38 control subjects were enrolled in the study. We measured serum activity of superoxide dismutase (SOD) using an enzyme-linked immunosorbent assay (ELISA) and malondialdehyde (MDA) levels using a spectrophotometric method. Neutrophil, lymphocyte and platelet counts were recorded, and the NLR and PLR values were calculated from these parameters. RESULTS: Patients with active CD exhibited significantly higher serum levels of MDA (p =0.007), NLR (p =0.034), and PLR (p =0.026) than inactive CD patients. Receiver operating characteristic (ROC) curve analysis demonstrated that the optimum cut-off values of MDA, NLR, and PLR based on the differences between active and inactive patients were 0.14 µmol/L, 2.58, and 192.26, respectively. The NLR value increased in active patients with elevated MDA levels as a dependent variable (B: 0.422, p =0.029). CONCLUSIONS: We suggest the use of MDA, PLR, and NLR values as a noninvasive test to evaluate disease activity in CD patients. NLR values may also reflect the presence of oxidative stress, and this value may be efficient and useful in determining CD activity. Hippokratia 2016, 20(4): 268-273.

3', 4'-dihydroxyflavonol attenuates tissue damage in unilateral testis ischemia-reperfusion in rats.

The purpose of this study was to determine the effect of 3',4'-dihydroxyflavonol (DiOHF) on oxidative damage and antioxidant system in experimental testicular torsion-detorsion.The study included 60 male Wistar albino rats. Study groups were formed as follows: 1. Control; 2. Sham; 3. 720° - 4 hours torsion; 4. 720° - 4 hours torsion + 4 hours detorsion; 5. 720° - 4 hours torsion + DiOHF; 6. 720° - 4 hours torsion + DiOHF + 4 hours detorsion; 7. 720° - 4 hours torsion + 24 hours detorsion; 8. 720° - 4 hours torsion + DiOHF + 24 hours detorsion. Testis were collected for the analysis of glutathione peroxidase (GPx), nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and xanthine oxidase (XO).GPx in the Group 8 were higher than the values in the other groups (p < 0.001). Concerning NO, the groups 3, 4, and 7 were found to have higher values than other groups (p < 0.001). MDA levels were higher in the groups 3, 7, and 8, when compared to the levels in other groups (p < 0.001). When tissue GSH levels were examined, the Group 5 had the highest GSH values (p < 0.001).With regard to XO values, the groups 3, 4, and 7 had the highest XO values (p < 0.001). The results of the study indicated that intraperitoneal DiOHF inhibited increased lipid peroxidation in testis ischemia-reperfusion injury in rats (Tab. 5, Ref. 46).

A new technique for endoscopic treatment of gastric phytobezoars: fragmentation using guidewire.

BACKGROUND AND STUDY AIMS: Bezoars result from accumulation of indigestible materials in the gastrointestinal tract and often occur in the stomach. In this study, we evaluated the use of guidewires in patients with gastric phytobezoars (PBs) as a new method for PB removal and examined the safety of the procedure. PATIENTS AND METHODS: Between February 2009 and January 2013, we analyzed data from 11 patients with gastric PBs. We fitted a transparent cap to a standard endoscope (EG450WR5, Fujinon), and a 0.025 inch guidewire was passed through the standart endoscope. PBs were surrounded by a loop in the guidewire and destroyed. After 2 weeks of treatment, patients were re-evaluated for effectiveness. RESULTS: PB fragmentation time was 5-11 minutes. In five patients with a history of gastric surgery, we needed an additional 16-28 minutes for removal of the fragments. In six patients additionally treated with enzymatic degradation after the breaking procedure, PBs completely disappeared within 2 weeks. There were no complications during the procedure. CONCLUSIONS: The guidewire and fragmentation procedure for PBs is an efficient and reliable method. When combined with enzymatic degradation, PBs can be managed quickly and effectively.

The effects of intrathecal morphine on patient-controlled analgesia, morphine consumption, postoperative pain and satisfaction scores in patients undergoing gynaecological oncological surgery.

OBJECTIVE: Gynaecological oncological surgery (GOS) includes a wide variety of surgical procedures and postoperative pain is a major concern. This study compared the impact of intrathecal morphine (ITM) plus patient-controlled analgesia (PCA) with PCA alone on morphine consumption, pain relief and patient satisfaction after GOS. METHODS: Sixty women undergoing GOS under general anaesthesia were randomized to receive either 0.3 mg ITM or placebo. On arrival at the postanaesthesia care unit each patient received a morphine PCA pump. The three primary outcome measures were pain, patient satisfaction scores evaluated using a 100-mm visual analogue scale and cumulative PCA morphine consumption. RESULTS: No significant differences were observed in the demographic data. Cumulative PCA morphine consumption was significantly lower in the ITM group compared with the control group. Fatigue scores were lower in the ITM group compared with the control group but did not reach statistical significance. Pain, sedation and patient satisfaction scores, and the rate of side-effects were similar for the two groups. CONCLUSIONS: Administering ITM in GOS could improve postoperative analgesia and reduce morphine consumption without serious side-effects.

Successful surgical treatment of Nicolau's syndrome combined with intravenous iloprost.

A 4 year-old boy was admitted to our clinic with symptoms of pain and ecchymosis in his right leg and foot after injection of benzathine penicilline. There was a localized gangrenous area at the femoral injection site. Doppler ultrasonography showed no arterial flow in the femoral artery and clear evidence of acute thrombosis of the superficial femoral and popliteal veins. Femoral arterial and venous thrombectomy and fasciotomy were performed immediately. After surgery the boy was treated by Iloprost infusion and enoxaparine. One week later necrotic changes had regressed, fasciotomies were closed and only the distal phalanx of the third toe needed amputation. Early surgical intervention and standard management combined with Iloprost infusion may help in healing the lesions by increasing extremity perfusion and may prevent extremity loss.

The preventive effect of diphenhydramine on bacterial growth in propofol: a laboratory study.

BACKGROUND AND OBJECTIVE: Diphenhydramine has local anaesthetic and antimicrobial activity and may be used to prevent intravenous propofol injection pain. We studied the effect of adding diphenhydramine to propofol emulsions for preventing bacterial growth. METHODS: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans cultures were inoculated into the following solutions: 1% propofol, 0.05% diphenhydramine + 1% propofol, 0.1% diphenhydramine + 1% propofol, 0.2% diphenhydramine + 1% propofol, 0.3% diphenhydramine + 1% propofol, 1% diphenhydramine and 0.1% lidocaine + 1% propofol. A 100-microL of inoculum suspension adjusted for each of the micro-organisms was added separately to each tube and left at 20 degrees C. A 10-microL aliquot of each mixture was inoculated onto blood agar medium at 5 and 24 h. These plates were incubated at 35 degrees C for 24 h. Each plated medium was read, and the number of colony-forming units were counted and recorded (n = 2). Analysis of variance (ANOVA) with a post hoc Tukey HSD test and paired t-tests were used for data analysis. P < 0.05 was considered as significant. RESULTS: Diphenhydramine inhibited bacterial growth in propofol solutions in a dose-dependent manner. It was more effective than 0.1% lidocaine at similar concentrations in preventing bacterial growth for all organisms. CONCLUSION: Diphenhydramine had a significant inhibitory effect on bacterial growth in propofol.

Comparison of diphenhydramine and lidocaine for prevention of pain after injection of propofol: a double-blind, placebo-controlled, randomized study.

BACKGROUND AND OBJECTIVE: Pain on injection is still a problem with propofol. The purpose of the study was to compare the effectiveness of diphenhydramine and lidocaine on pain caused by propofol at the site of injection. METHODS: One hundred and eighty ASA I-II adults undergoing elective surgery were randomly assigned into three groups of 60 each. Group I (placebo) received 2 mL normal saline, Group II received 2 mL (40 mg) 2% lidocaine and Group III received 2 mL (20 mg) diphenhydramine intravenously (i.v.) during a 1-min venous occlusion, followed by propofol into a cephalic forearm vein of the antecubital fossa. Pain assessment was made immediately after propofol injection. RESULTS: In the placebo group 25 (41.7%) patients experienced pain during propofol injection as compared to 2 (3.3%) and 3 (5.0%) in the lidocaine and diphenhydramine groups, respectively. The prevalence of pain and pain score were significantly less in both the lidocaine and diphenhydramine groups than in the placebo group (P = 0.00). No difference was found between the diphenhydramine and lidocaine groups (P = 0.60). CONCLUSION: Previous injection of diphenhydramine with venous occlusion can be considered as an alternative to lidocaine for reducing the prevalence of pain caused by injection of propofol into peripheral veins.

Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.

We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.

Demographic, socioeconomic and educational aspects of obesity in an adult population.

Obesity as a disease is a yet-unidentified sum of genetic and environmental factors. Risky eating behavior and lifestyle may bring the disease. The aim of the study was to find out risk factors for obesity factors influencing definition of obesity. Participants (n = 1500) who filled out a questionnaire about eating habits are grouped according to their body mass indices as normal weight, overweight and obese (n = 500 in each group). According to our results, the prevalence of having obese first-degree relatives is significantly higher in obese individuals (p < 0.001). Sixty-two of normal weighing subjects were university graduates, whereas this ratio was only 31% in the obese group (p < 0.001). Incidence of obesity was higher in married participants when compared to the single or divorced/widowed persons (p < 0.001). Multinomial logistic regression analysis gave the following results: risk of obesity was 57% less in participants lacking a family history of obesity when compared to the ones with a positive family history (p = 0.005). Being married increases the risk of obesity 2.5 times; being a primary school graduate increases the risk about 1.5 times. Lower educational level, unemployment and lack of counseling seem to be risk factors associated with obesity. Diverging patterns of sociodemographic features, lifestyles and perception were evident even between overweight and obese populations.

NSAID-related upper gastrointestinal bleeding: are risk factors considered during prophylaxis?

The purposes of this study were to evaluate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on acute nonvaricose upper gastrointestinal bleeding (ANUGIB) and establish whether the NSAID-prescribing physicians take precautions to prevent or reduce GI ulcerations. Clinical characteristics, causes of bleeding and clinical outcomes of patients hospitalised in our gastroenterology clinic with ANUGIB were recorded prospectively over a 1.5-year period. NSAIDs, including aspirin, were used by 127 of 168 patients (73%). Among the NSAID users, 100 patients (78%) had at least one risk factor for serious adverse GI events related to NSAIDs. Only two patients were using proton pump inhibitors and one patient was using H2 receptor blocker of the high-risk group for GI side effects of NSAIDs. NSAIDs have an important effect on GI bleeding, and it seems that risk factors are underestimated by physicians.