Despite a decline in incidence and mortality during the last decades,stomach cancer is one of the main health challenges worldwide.According to the GLOBOCAN 2020 estimates,stomach cancer caused approximately 800000 de...Despite a decline in incidence and mortality during the last decades,stomach cancer is one of the main health challenges worldwide.According to the GLOBOCAN 2020 estimates,stomach cancer caused approximately 800000 deaths(accounting for 7.7%of all cancer deaths),and ranks as the fourth leading cause of cancer deaths in both genders combined.About 1.1 million new cases of stomach cancer were diagnosed in 2020(accounting for 5.6%of all cancer cases).About 75%of all new cases and all deaths from stomach cancer are reported in Asia.Stomach cancer is one of the most lethal malignant tumors,with a five-year survival rate of around 20%.There are some well-established risk factors for stomach cancer:Helicobacter pylori infection,dietary factors,tobacco,obesity,and radiation.To date,the most important way of preventing stomach cancer is reduced exposure to risk factors,as well as screening and early detection.Further research on risk factors can help identify various opportunities for more effective prevention.Screening programs for stomach cancer have been implemented in a few countries,either as a national or opportunistic screening of high-risk individuals only.Generally,due to its high aggressiveness and heterogeneity,stomach cancer still remains a severe global health problem.展开更多
Helicobacter pylori(H. pylori) plays a role in the patho-genesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a mul...Helicobacter pylori(H. pylori) plays a role in the patho-genesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence:(1) eradication of the already present infection; and(2) immunization(prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.展开更多
Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to wa...Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋ ） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.展开更多
AIM： To determine risk factors for pulmonary embolism and estimate effects and benefits of prophylaxis. METHODS： We included 78 patients who died subsequently to a pulmonary embolism after major abdominal surgery fr...AIM： To determine risk factors for pulmonary embolism and estimate effects and benefits of prophylaxis. METHODS： We included 78 patients who died subsequently to a pulmonary embolism after major abdominal surgery from 1985 to 2003. A first, retrospective analysis involved 41 patients who underwent elective surgery between 1985 and 1990 without receiving any prophylaxis. In the prospectively evaluated subgroup, 37 patients undergoing major surgery between 1991 and 2003 were enrolled： all of them had received a prophylaxis consisting in lowmolecular weight heparin, given subcutaneously at a dose of 2850 IU AXa/0.3 mL （body weight 〈 50 kg） or 5700 IU AXa/0.6 mL （body weight ≥ 50 kg）. RESULTS： A higher incidence of thromboembolism （43.9% and 46.34% in the two groups, respectively） was found in older patients （〉 60 years）. The incidence of pulmonary embolism after major abdominal surgery in patients who had received the prophylaxis was significantly lower compared to the subjects with the same condition who had not received any prophylaxis （P 〈 0.001, OR = 2.825; 95% CI, 1.811-4.408）. Furthermore, the incidence of pulmonary embolism after colorectal cancer surgery was significantly higher compared to incidence of pulmonary embolism after other abdominal surgical procedures. Finally, the incidence of pulmonary embolism after colorectal cancer surgery among the patients who had received the prophylaxis （11/4316, 0.26%） was significantly lower compared to subjects undergoing a surgical procedure for the same indication but without prophylaxis （10/1562, 0.64%） （P 〈 0.05, OR = 2.522; 95% Ct, 1.069-5.949）. CONCLUSION： Prophylaxis with low molecular weight heparin is highly recommended during the preoperative period in patients with diagnosis of colorectal cancer due to high risk of pulmonary embolism after elective surgery.展开更多
AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A t...AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.展开更多
AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhos...AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.展开更多
Hepatitis B virus(HBV)infection is a major cause of acute and chronic hepatitis,and of its long-term complications.It is the most variable among DNA viruses,mostly because of its unique life cycle which includes the a...Hepatitis B virus(HBV)infection is a major cause of acute and chronic hepatitis,and of its long-term complications.It is the most variable among DNA viruses,mostly because of its unique life cycle which includes the activity of error-prone enzyme,reverse transcriptase,and the very high virion production per day.In last two decades,numerous research studies have shown that the speed of disease progression,reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus.It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools,thus making the monitoring for these mutations a necessity in proper evaluation of patients.The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen(HBsAg),which may lead to evasion of vaccine-induced immunity.However,the emergence of these mutations has not yet raised concern since it was shown that they develop slowly.Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade,particularly in regard to management of resistance to antiviral drugs.In the era of drugs with high genetic barrier for resistance,on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary.Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures,more proper planning of immunization programs and creating the most efficient therapeutic protocols.展开更多
Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating th...Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.展开更多
AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MA...AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages Ⅰ to Ⅳ) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.展开更多
Cystic dystrophy of the duodenal wall is a rare condition characterized by the development of cysts in heterotopic pancreatic tissue localized in the duodenal wall.A 38-year- old man was admitted to the hospital for a...Cystic dystrophy of the duodenal wall is a rare condition characterized by the development of cysts in heterotopic pancreatic tissue localized in the duodenal wall.A 38-year- old man was admitted to the hospital for abdominal pain and vomiting after food intake.The diagnosis of acute pancreatitis was initially suspected.Abdominal ultrasound examination revealed thickening of the second portion of duodenal wall within which,small cysts(diameter,less than 1 cm)were present in the vicinity of pancreatic head. The head of pancreas appeared enlarged(63 mm×42 mm) and hypoechoic.Upper endoscopy and barium X-ray series were performed revealing a severe circumferential deformation,as well as 4 cm long stenosis of the second portion of the duodenum.CT examination revealed multiple cysts located in an enlarged,thickened duodenal wall with moderate to strong post-contrast enhancement.We suspected that patient had cystic dystrophy of duodenal wall developed in the heterotopic pancreas and diagnosis was confirmed by endoscopic ultrasound(EUS).Endoscopic ultrasound(EUS)revealed circular stenosis from the duodenal bulb onwards.A twenty megahertz mini-prope examination further showed diffuse(intramural)infiltration of duodenal wall limited to the submucosa and muscularis propria of the second portion of duodenum with multiple microcysts within the thickened mucosa and submucosa.Patient was successfully surgically treated and pancreatoduodenectomy was performed.The pathological examination confirmed a diagnosis of cystic dystrophy of a heterotopic pancreas. Endoscopic ultrasonography features allow preoperative diagnosis of cystic dystrophy of a heterotopic pancreas in duodenal wall,with intralumina120 MHz mini probe sonography being more efficient in cases of luminal stenosis.展开更多
AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT met...AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.展开更多
Hepatocellular carcinoma(HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide,...Hepatocellular carcinoma(HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancerrelated deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the BarcelonaClinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized-based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease(chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative(surgical treatment and tumor ablation) or palliative(transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.展开更多
BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral dr...BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.METHODS:During a 3-year period,a total of 49 patients with hilar tumors(Bismuth-Corlette type II) were referred for endoscopic treatment,following the criteria of unresectability.Ultrasound,computed tomography scan and magnetic resonance cholangiopancreatography(MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography(ERCP).The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected.Mechanical bile duct dilation was performed,followed by plastic stent placement only in the liver lobe which was previously opacified.The procedures were performed under conscious sedation.The patients were followed up for the next 12 months with a stent exchange every 3 months.Primary outcome was assessed by patient survival in the first 12 months after the procedure.RESULTS:All 49 patients were treated with ERCP while 39(79.59%) had successful stent placement.Among these,32 had hilar cholangiocarcinoma(82%) and 7(18%) had gallbladder cancer.Two groups of patients had Bismuth II strictures:A,21 patients(54%) with unilateral contrast injection and drainage,and B,18(46%) with bilateral contrast injection and drainage.A total of 57 plastic stents were used(10 Fr,89%;11.5 Fr,11%).Group B showed a lower bilirubin level 7 days after the procedure(P=0.008).Early complications were cholangitis(3 patients,2 in group A and 1 in group B) and acute pancreatitis(2 patients,1 each in A and B) with no statistical difference between the groups.Late complications were stent migration(5 patients,1 in A and 4 in B) and stent clogging(6 patients,2 in A and 4 in B) showing a significant difference between the groups(P<0.01).The first stent replacement after 3 months was successful in 展开更多
Ulcerative colitis and Crohn’s disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The ...Ulcerative colitis and Crohn’s disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD. The involvement of structures the limbic system, such as the anterior cingulate cortex, the prefrontal cortex, and the amygdala, paves the way for the discovery of the mechanisms underlying depression depression, anxiety, alexithymia, personality traits, and other psychological impairments following the onset of IBD. Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy. Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects, and psychotropic medication can provoke the worsening of IBD symptoms. Thus, both approaches must be applied with awareness of the possibility of side effects. We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.展开更多
Background:As the result of dramatic political changes,civil wars,and a long-term refugee crisis from the end of the last to beginning of this century,the population of Serbia has experienced significant health proble...Background:As the result of dramatic political changes,civil wars,and a long-term refugee crisis from the end of the last to beginning of this century,the population of Serbia has experienced significant health problems.The aim of this study was to assess cancer mortality trends in Serbia.Methods:This nationwide study was carried out to analyze cancer mortality in Serbia during 1991-2015 using offi-cial data.The age-standardized mortality rates(per 100,000)were calculated by direct standardization,using the world standard population by Segi.The average annual percent change(AAPC)and corresponding 95%confidence interval(CI)were computed using joinpoint regression analysis.Age-period-cohort analysis was performed to address the possible underlying reasons for the observed temporal trends.Results:Over the 25-year study period,there were 466,075 cancer deaths(266,043 males and 200,032 females)in Serbia.Overall cancer mortality increased between 1991 and 2009 in both males(by+0.9%per year)and females(by+0.8%per year)and has been decreasing since then,by−0.9%annually in both sexes.For almost all major cancers except stomach cancer,cancer mortality in Serbia demonstrated upward trends during the study period.The largest increases were noted in lung cancer among females(AAPC=+3.7,95%CI 3.5-3.9)and prostate cancer in males(AAPC=+1.9,95%CI 1.4-2.3).Conclusions:After two decades of increase,cancer mortality rates are finally declining in Serbia.Despite this,these rates place Serbia among the countries with the highest cancer mortality in the world.展开更多
Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of m...Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups： focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liven Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients.展开更多
AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.
Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comor...Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. Aims To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. Methods People aged 18-65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected. Results A total of 3170 people with type 2 diabetes (56.2% women;with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%;however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. Conclusions Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.展开更多
文摘Despite a decline in incidence and mortality during the last decades,stomach cancer is one of the main health challenges worldwide.According to the GLOBOCAN 2020 estimates,stomach cancer caused approximately 800000 deaths(accounting for 7.7%of all cancer deaths),and ranks as the fourth leading cause of cancer deaths in both genders combined.About 1.1 million new cases of stomach cancer were diagnosed in 2020(accounting for 5.6%of all cancer cases).About 75%of all new cases and all deaths from stomach cancer are reported in Asia.Stomach cancer is one of the most lethal malignant tumors,with a five-year survival rate of around 20%.There are some well-established risk factors for stomach cancer:Helicobacter pylori infection,dietary factors,tobacco,obesity,and radiation.To date,the most important way of preventing stomach cancer is reduced exposure to risk factors,as well as screening and early detection.Further research on risk factors can help identify various opportunities for more effective prevention.Screening programs for stomach cancer have been implemented in a few countries,either as a national or opportunistic screening of high-risk individuals only.Generally,due to its high aggressiveness and heterogeneity,stomach cancer still remains a severe global health problem.
文摘Helicobacter pylori(H. pylori) plays a role in the patho-genesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence:(1) eradication of the already present infection; and(2) immunization(prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.
基金Supported by the Ministry of Science and Technological Development of the Republic Serbia and“Super-Intense Laser-Matter Interactions”-SILMI Project,European Scientific Foundation
基金supported by the Ministry of Science and Technological Development of the Republic of Serbia, Grant # 143038
文摘Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋ ） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.
文摘AIM： To determine risk factors for pulmonary embolism and estimate effects and benefits of prophylaxis. METHODS： We included 78 patients who died subsequently to a pulmonary embolism after major abdominal surgery from 1985 to 2003. A first, retrospective analysis involved 41 patients who underwent elective surgery between 1985 and 1990 without receiving any prophylaxis. In the prospectively evaluated subgroup, 37 patients undergoing major surgery between 1991 and 2003 were enrolled： all of them had received a prophylaxis consisting in lowmolecular weight heparin, given subcutaneously at a dose of 2850 IU AXa/0.3 mL （body weight 〈 50 kg） or 5700 IU AXa/0.6 mL （body weight ≥ 50 kg）. RESULTS： A higher incidence of thromboembolism （43.9% and 46.34% in the two groups, respectively） was found in older patients （〉 60 years）. The incidence of pulmonary embolism after major abdominal surgery in patients who had received the prophylaxis was significantly lower compared to the subjects with the same condition who had not received any prophylaxis （P 〈 0.001, OR = 2.825; 95% CI, 1.811-4.408）. Furthermore, the incidence of pulmonary embolism after colorectal cancer surgery was significantly higher compared to incidence of pulmonary embolism after other abdominal surgical procedures. Finally, the incidence of pulmonary embolism after colorectal cancer surgery among the patients who had received the prophylaxis （11/4316, 0.26%） was significantly lower compared to subjects undergoing a surgical procedure for the same indication but without prophylaxis （10/1562, 0.64%） （P 〈 0.05, OR = 2.522; 95% Ct, 1.069-5.949）. CONCLUSION： Prophylaxis with low molecular weight heparin is highly recommended during the preoperative period in patients with diagnosis of colorectal cancer due to high risk of pulmonary embolism after elective surgery.
文摘AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.
基金Supported by Ministry of Education,Science and Technological Development,Belgrade,Republic of Serbia,Project No.175036
文摘AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.
基金Supported by Ministry of Education,Science and Technological Development,Republic of Serbia,Grant No.175073
文摘Hepatitis B virus(HBV)infection is a major cause of acute and chronic hepatitis,and of its long-term complications.It is the most variable among DNA viruses,mostly because of its unique life cycle which includes the activity of error-prone enzyme,reverse transcriptase,and the very high virion production per day.In last two decades,numerous research studies have shown that the speed of disease progression,reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus.It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools,thus making the monitoring for these mutations a necessity in proper evaluation of patients.The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen(HBsAg),which may lead to evasion of vaccine-induced immunity.However,the emergence of these mutations has not yet raised concern since it was shown that they develop slowly.Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade,particularly in regard to management of resistance to antiviral drugs.In the era of drugs with high genetic barrier for resistance,on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary.Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures,more proper planning of immunization programs and creating the most efficient therapeutic protocols.
文摘Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain.
基金Supported by Ministry of Science, Project No. 145061
文摘AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages Ⅰ to Ⅳ) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.
文摘Cystic dystrophy of the duodenal wall is a rare condition characterized by the development of cysts in heterotopic pancreatic tissue localized in the duodenal wall.A 38-year- old man was admitted to the hospital for abdominal pain and vomiting after food intake.The diagnosis of acute pancreatitis was initially suspected.Abdominal ultrasound examination revealed thickening of the second portion of duodenal wall within which,small cysts(diameter,less than 1 cm)were present in the vicinity of pancreatic head. The head of pancreas appeared enlarged(63 mm×42 mm) and hypoechoic.Upper endoscopy and barium X-ray series were performed revealing a severe circumferential deformation,as well as 4 cm long stenosis of the second portion of the duodenum.CT examination revealed multiple cysts located in an enlarged,thickened duodenal wall with moderate to strong post-contrast enhancement.We suspected that patient had cystic dystrophy of duodenal wall developed in the heterotopic pancreas and diagnosis was confirmed by endoscopic ultrasound(EUS).Endoscopic ultrasound(EUS)revealed circular stenosis from the duodenal bulb onwards.A twenty megahertz mini-prope examination further showed diffuse(intramural)infiltration of duodenal wall limited to the submucosa and muscularis propria of the second portion of duodenum with multiple microcysts within the thickened mucosa and submucosa.Patient was successfully surgically treated and pancreatoduodenectomy was performed.The pathological examination confirmed a diagnosis of cystic dystrophy of a heterotopic pancreas. Endoscopic ultrasonography features allow preoperative diagnosis of cystic dystrophy of a heterotopic pancreas in duodenal wall,with intralumina120 MHz mini probe sonography being more efficient in cases of luminal stenosis.
基金Supported by the grant 143010 from the Ministry of Science and Environment Protection of the Republic of Serbia
文摘AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.
文摘Hepatocellular carcinoma(HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancerrelated deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the BarcelonaClinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized-based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease(chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative(surgical treatment and tumor ablation) or palliative(transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.
基金supported by the Ministry of Education and Science of the Republic of Serbia(175054)
文摘BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.METHODS:During a 3-year period,a total of 49 patients with hilar tumors(Bismuth-Corlette type II) were referred for endoscopic treatment,following the criteria of unresectability.Ultrasound,computed tomography scan and magnetic resonance cholangiopancreatography(MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography(ERCP).The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected.Mechanical bile duct dilation was performed,followed by plastic stent placement only in the liver lobe which was previously opacified.The procedures were performed under conscious sedation.The patients were followed up for the next 12 months with a stent exchange every 3 months.Primary outcome was assessed by patient survival in the first 12 months after the procedure.RESULTS:All 49 patients were treated with ERCP while 39(79.59%) had successful stent placement.Among these,32 had hilar cholangiocarcinoma(82%) and 7(18%) had gallbladder cancer.Two groups of patients had Bismuth II strictures:A,21 patients(54%) with unilateral contrast injection and drainage,and B,18(46%) with bilateral contrast injection and drainage.A total of 57 plastic stents were used(10 Fr,89%;11.5 Fr,11%).Group B showed a lower bilirubin level 7 days after the procedure(P=0.008).Early complications were cholangitis(3 patients,2 in group A and 1 in group B) and acute pancreatitis(2 patients,1 each in A and B) with no statistical difference between the groups.Late complications were stent migration(5 patients,1 in A and 4 in B) and stent clogging(6 patients,2 in A and 4 in B) showing a significant difference between the groups(P<0.01).The first stent replacement after 3 months was successful in
文摘Ulcerative colitis and Crohn’s disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD. The involvement of structures the limbic system, such as the anterior cingulate cortex, the prefrontal cortex, and the amygdala, paves the way for the discovery of the mechanisms underlying depression depression, anxiety, alexithymia, personality traits, and other psychological impairments following the onset of IBD. Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy. Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects, and psychotropic medication can provoke the worsening of IBD symptoms. Thus, both approaches must be applied with awareness of the possibility of side effects. We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.
基金supported by Ministry of Education,Science and Technological Development,Republic of Serbia,2011-2016(Contract No.175042).
文摘Background:As the result of dramatic political changes,civil wars,and a long-term refugee crisis from the end of the last to beginning of this century,the population of Serbia has experienced significant health problems.The aim of this study was to assess cancer mortality trends in Serbia.Methods:This nationwide study was carried out to analyze cancer mortality in Serbia during 1991-2015 using offi-cial data.The age-standardized mortality rates(per 100,000)were calculated by direct standardization,using the world standard population by Segi.The average annual percent change(AAPC)and corresponding 95%confidence interval(CI)were computed using joinpoint regression analysis.Age-period-cohort analysis was performed to address the possible underlying reasons for the observed temporal trends.Results:Over the 25-year study period,there were 466,075 cancer deaths(266,043 males and 200,032 females)in Serbia.Overall cancer mortality increased between 1991 and 2009 in both males(by+0.9%per year)and females(by+0.8%per year)and has been decreasing since then,by−0.9%annually in both sexes.For almost all major cancers except stomach cancer,cancer mortality in Serbia demonstrated upward trends during the study period.The largest increases were noted in lung cancer among females(AAPC=+3.7,95%CI 3.5-3.9)and prostate cancer in males(AAPC=+1.9,95%CI 1.4-2.3).Conclusions:After two decades of increase,cancer mortality rates are finally declining in Serbia.Despite this,these rates place Serbia among the countries with the highest cancer mortality in the world.
文摘Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. It is characterized by a cystic dilatation of the lumen with stasis of mucus inside it. Histopathologically mucocele is divided into three groups： focal or diffuse mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This condition is often associated with other neoplasia, especially adenocarcinoma of the colon and ovaries. We here describe a 57 year old male patient who presented with abdominal discomfort, constipation, fresh blood in stool and frequent urination. He had a big cystadenoma of the appendix associated with adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The patient underwent right haemicolectomy, sigmoid colon resection and segmental resection of the liven Now 3 years later he has no evidence of disease relapse. According to this, we stress the need of accurate preoperative diagnosis and intraoperative exploration of the whole abdomen in these patients.
文摘AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.
文摘Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. Aims To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. Methods People aged 18-65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected. Results A total of 3170 people with type 2 diabetes (56.2% women;with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%;however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. Conclusions Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.
