Incidence of lower limb amputation in diabetic patients between 2010 and 2018 in Osijek-Baranja County

Introduction: Diabetic foot ulceration (DFU) is associated with high morbidity, mortality, and represents the leading cause of hospitalization in patients with diabetes. Peripheral arterial disease (PAD), present in half of patients with DFU, is an independent predictor of lower limb amputation (LLA) and can be difficult to diagnose in a diabetic population. Underdiagnosis and undertreatment of critical PAD are frequent.1-3 To our knowledge there is no data about LLA incidence in Croatia neither in diabetics nor in nondiabetics. Our aim was to determine the incidence of amputation in patients with diabetes mellitus in Osijek-Baranja County. Patients and Methods: This was a tertiary-care-based retrospective study involving adult patients in whom amputation were performed for reasons relating to complication of PAD and/or diabetes in the University Hospital Centre Osijek from 1st January 2008 to 31st December 2018. We calculated LLA rates using estimates of the population with diabetes derived from CroDiab registry and Croatian Institute for Public Health for Osijek-Baranja County. LLAs were further categorized by level of amputation as follows: minor (toe and foot) and major (above foot and below knee, and above knee). Results: There were 1551 LLAs in ten-year period. Smaller proportion of amputation was above foot (49.3% vs 59.3%). LLA rates per 1,000 adults with diabetes decreased 29% between 2010 and 2013 and then increased 76 % between 2014 and 2018 (Figure 1). We observed the same pattern in both minor and major LLA but rates of amputation above knee steadily increased 2.65 times between 2010 and 2018 (from 0.69 to 1.83 LLA per 1,000 patients). Conclusion: This study confirmed high rate of lower limb amputation in diabetic patients in Osijek- Baranja County which is representative for east Croatia region. After a decline of low limb amputations in diabetic patients between 2011 and 2013, LLA rates began to increase from 2014 to 2018. Reasons for that reversal trend are unclear. It can be due to poor management of CVD risk factors, poor glycemic control, and failure in early detection of PAD. It is also possible that change in health policy and organization of diabetes care together with socioeconomic factors could affect trends of LLA. Incidence rate of LLA in our population is important for further improvements in diabetes care and for decisions in health policy

Diabetes Mellitus and diabetic ketoacidosis associated with pembrolizumab

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus (DM) and is characterized by hyperglycemia, hyperketonemia and metabolic acidosis. With the increasing use of immune checkpoint inhibitors (ICIs), such as pembrolizumab in cancer therapy, it’s important tounderstand immune-related adverse events that comes with it

Connection between glycemic variability obtained using the UniGluko system and the quality of life people with type 1 diabetes

Research has shown that glycemic variability increases the risk of the development of acute and chronic complications with diabetes. Accordingly, the assessment of glycemic variability is of great importance to determine the quality of life for people suffering from diabetes. Objective: To examine the connection between glycemic variability and the quality of life for people with type 1 diabetes who use self-monitoring blood glucose devices. Respondents and methods: 42 respondents participated in the research with an average age of 39.6, who are treated with intensified insulin therapy. For the purpose of glycemic variability assessment, an innovative uniGluko system is used, which enables the display of glycemia in a unique graphic interface in the form of numeric values within the last three months from which a glycemic variability index was calculated as well as a general information survey, a survey on the quality of life from the World Health Organization (WHOQOL – BREF) and a short questionnaire regarding illness perception (Brief – IPQ). Results: By usage of standard deviation as a glyemic variability measure, statistically significant results have been obtained and they demonstrate that lower glycemic variability is connected to better quality of life (rs=-0.4571; p=0.0023), higher satisfaction with health (rs=-0.3186; p=0.0398) and reduced impact of disease on emotional life (rs=0.4097; p=0.,0071). Lower glucose variability implies reduced impact of disease on everyday life (rs=0.3091; p=0.0464), reduced incidence of symptoms (rs=0.3441; p=0.0255), and patients’ sense that they have more control over disease (rs=-0.5185; p=0.0004). Conclusion: The glycemic variability has a negative impact on life quality and health of patients with diabetes type 1

Magnesium, zinc and iron serum levels as potential parameters significant for effective glycemic control in children with type 1 diabetes

Background. Various trace elements contribute to the development of diabetes and its complications through their roles in glucose metabolism and the oxidative stress response. The aim of this study was to ascertain the difference in serum magnesium, zinc and iron concentrations between healthy children and children with type 1 diabetes mellitus (T1DM). This study also aimed to determine whether serum concentrations of magnesium, zinc, and iron in children with T1DM correlated with the duration of the disease and the quality of glycemic control in this group. Material and methods. A total of 99 children with T1DM and 40 healthy children were included in this study. Magnesium, zinc and iron serum levels were assessed using the photometric method. Results. Significantly lower levels of magnesium and zinc (P < 0.001) were observed, between the T1DM group and the healthy control group but no statistically significant differences were found in iron levels (P = 0.13) between the two groups. While there were no statistically significant differences in serum concentrations with respect to the duration of disease, it was, however, discovered that children with poorer glycemic control had significantly lower serum zinc concentrations (P < 0.001) while magnesium and iron levels remained similar (P = 0.07 and 0.21 respectively). Conclusion. This study found that while there was no significant difference in iron serum levels in children with T1DM compared to healthy controls, children with T1DM did have more significantly decreased magnesium and zinc serum levels than the control group. Serum zinc levels in this study also directly correlated to poorer glycemic control. Further studies are required to explore whether magnesium and zinc supplementa­tion, or nutritional intake, could potentially be used to achieve better glycemic control in children with T1DM

Metabolic Syndrome – Community Nursing Evaluation and Intervention: the CroHort Study

This prospective study of 1277 participants investigated patient risk self-assessment, motivation for changes in main determinants of the metabolic syndrome and the impact of community nursing intervention on cardiovascular risk reduction. Observed values of metabolic syndrome determinants indicated an elevated cardiovascular risk. Participants showed greatest motivation for positive changes regarding blood pressure, (3.70±1.26) then hyperglycemia (3.55±1.28), hyperlipidemia (3.46±1.30), overweight and obesity (3.43±1.28), and physical activity habits (3.29±1.31). Changes in physical activity and nutritional habits were not related to self-reported motivation regardless of the age and sex (p>0.05). The most pronounced median improvements were observed in cholesterol (men 4.43%, women 4.89%) and triglycerides (men 3.41%, women 1.49%), with only slight changes in BMI (men 1.08%, women 1.18%) and no change in waist-to-hip ratio and glucose. This study revealed that, although aware and motivated, patients often do not succeed in changing habits. Concomitant changes of the environment and multisectoral prevention approach is necessary

Incidence of Lower Limb Amputation in Diabetic Patients in Osijek-Baranja County

Amputation of the lower limb (LLA) is one of the most feared adverse outcomes among diabetic patients. Our aim was to determine the incidence of amputation in diabetic patients in Osijek-Baranja County and to examine the possible correlationbetween clinical characteristics of the patients and the time elapsed before the first amputation. This was a tertiary-care-based retrospective study and included 925 diabetic patients who underwent non-traumatic lower limb amputation in the University Hospital Osijek from January 1st 2008 to December 31st 2018. Data on associated cardiovascular risk factors and clinical characteristics of the patients were collected from diabetic registry of the Department of diabetes and endocrinology. A total of 278 patients had all data for further analysis. There were 1551 LLAs over a ten year period. The incidence was 6.14 per 1,000 adults with diabetes. LLA rates per 1,000 adults with diabetes decreased by 29% between 2010 and 2013 and then increased by 76% between 2014 and 2018. In ten year period incidence of amputation in diabetic patients varied from 4 to 7.8 per 1000 persons-year. We observed the same pattern in both minor and major LLA but rates of amputation above knee steadily increased 2.7 times between 2010 and 2018 (from 0.69 to 1.83 per 1000 patients-year). The mean age of patients with LLA was 67.2 years, 66% were male, mean BMI was 29.6±4.8 kg/m2 and the mean duration of diabetes was 14.7±8.2 years. There was no association between smoking, arterial hypertension and hyperlipemia, ACE inhibitor use, statin use, antiplatelet use, CVD, neuropathy and duration of diabetes before first amputation. Only sulphonylurea and insulin therapy significantly prolonged the time before the first amputation (p = 0.00001, for each). In conclusion, our study confirmed high rate of lower limb amputation in diabetic patients in Osijek-Baranja County. Incidence rates of LLA in our population are important for further improvements in diabetes care and decisions in health care policy

Povezanost polimorfizma gena za interleukin-10 (-1082g/a) s tipom 2 šećerne bolesti i mikrovaskularnim komplikacijama u hrvatskoj populaciji

Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the devel-opment and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in development of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity compared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.Smanjena sekrecija protuupalnog citokina interleukina (IL)-10 opisana je u debljini, metaboličkom sindromu i tipu 2 šećerne bolesti (T2ŠB). Međutim, nije utvrđeno može li intenzitet imunog odgovora tijekom kronične upale utjecati na razvoj i/ili progresiju dijabetesa kao i razvoj mikrovaskularnih komplikacija. Cilj ove studije bio je istražiti povezanost polimorfizma gena (SNP) -1082G/A za IL-10 s razvojem T2ŠB i kroničnih komplikacija. DNK za genotipizaciju se ekstrahirala iz krvnih stanica 240 adipoznih ispitanika koji su podijeljeni u dvije skupine: u eksperimentalnoj skupini bilo je 144 bolesnika s T2ŠB, a u kontrolnoj skupini 96 ispitanika usklađenih prema spolu i dobi. U skupini s T2ŠB nađene su više vrijednosti leukocita (p=0,012), fibrinogena (p=0,049) i inhibitora aktivacije plazminogena-1 (PAI-1) (p=0,009) te niže koncentracije albumina (p=0,001) nego u kontrolnoj skupini. Nije bilo statističke razlike u frekvencijama -1082G/A polimorfizma gena za IL-10 (p=0,654). Kada su se gledali ishodi za specifični genotip u svih ispitanika, ispitanici s homozigotnim genotipom (AA) imali su značajno više koncentracije glukoze natašte (p<0,000001), HbA1c (p<0,000001) i HOMA-IR (p=0,003632) te niži indeks HOMA-B (p=0,000178) u odnosu na ispitanike s genotipovima GG i GA. Nije bilo razlike u genotipovima polimorfizma IL-10 gena i razvoja nefropatije, retinopatije i polineuropatije. U zaključku, pretili bolesnici s T2ŠB imali su pojačanu upalnu aktivnost u usporedbi s pretilim ispitanicima bez šećerne bolesti. Nije utvrđena povezanost polimorfizma IL-10 i razvoja T2ŠB kao ni razvoja mikrovaskularnih komplikacija. Međutim, ishodi povezani s dijabetesom jasno su povezani s određenim genotipom IL-10

Syndrome of inappropriate antidiuretic hormone secretion as an adverse reaction of ciprofloxacin: a case report and literature review

Highlights Euvolemic patient with mild hyponatremia during ciprofloxacin treatment was evaluated No diuretic use; hypothyroidism and hypocortisolism were excluded as causes Our findings highlight ciprofloxacin\u27s potential role in inducing Syndrome of inappropriate antidiuretic hormone secretion Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Unsuppressed release of ADH leads to hyponatremia. This condition is referred to as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hereby, a case report is presented on ciprofloxacin-induced SIADH. A 67-year-old male patient was examined in the emergency room with symptoms of lethargy, headache, lack of attention, and a generally depressed mood lasting for three days. One week prior, empirical antimicrobial therapy involving ciprofloxacin for prostatitis was initiated. Laboratory analysis showed no relevant abnormalities except for hyponatremia (Na = 129 mmol/L). Chronic hyponatremia, thyroid dysfunction, and adrenal dysfunction were ruled out. Serum osmolality was 263 mOsmol/kg, urine osmolality was 206 mOsmol/kg, and urine sodium was 39 mmol/L. Given that all criteria for SIADH were met, ciprofloxacin was discontinued, and fluid restriction was advised. Four days later, the patient’s serum sodium concentrations nearly normalized (Na = 135 mmol/L), and all symptoms resolved. The Naranjo Scale yielded a score of 8, supporting the likelihood of a probable adverse reaction to ciprofloxacin. This case is presented to raise awareness among clinicians about the potential of ciprofloxacin to cause even mild hyponatremia

Imaging Features of Triple N Negative Breast Cancers – Mammography, Ultrasound and Magnetic Resonance Imaging

Breast cancer (BC) is a highly heterogeneous disease. Aim was to evaluate imaging features of triple negative breast cancers (TNBC) in comparison to non-TNBC. We reviewed data of 30 patients who had been diagnosed as having TNBC and 37 patients with non-TNBC (control group) using criteria described for mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) in Breast Imaging-Reporting and Data System (BI-RADS) lexicon for image interpretation. Age of patients, size of tumor, multifocality, histological type, tumor grade and status of lymph nodes were reviewed. TNBC were more often histological grade 3 and had significantly more positive lymph nodes at the time of diagnosis on pathology reports. On MMG, US and MRI TNBC mostly appeared as regularly shaped masses. On US as hypoechogenic masses with no posterior acoustic features and on MRI as masses with rim type of enhancement, fast wash-in and plateau type of curves. Most frequent category reported after MMG and US was BI RADS 4, and after MRI BI RADS 5. In conclusion, our study confirmed higher histological grade of TNBC, as well as more frequent lymph node involvement in comparation to the non-TNBC. TNBC showed tendency to affect younger women and to be larger than non-TNBC. Although, they most often presented as a mass on mammography and sonography, in a significant number of cases they remained miscategorized, due to the benign imaging features. All cases are recognized on MRI where they appear as rim enhancing masses

Interakcija između interleukina-6, C-reaktivnog proteina i interleukina-6 (-174) G/C polimorfizma u patogenezi Crohnove bolesti i ulceroznog kolitisa

Inflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn’s disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn’s disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn’s disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt’s severity index scale. C-reactive protein serum level was higher in Crohn’s disease patients without intestinal resection than in Crohn’s disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn’s disease and ulcerative colitis disease.Upalne bolesti crijeva predstavljaju multifaktorski poremećaj klinička manifestacija kojega ovisi o interakciji imunog odgovora te genetskih i okolišnih čimbenika. Rezultati više novijih istraživanja upućuju na ulogu citokina i polimorfizama gena u patogenezi bolesti u različitim populacijama, iako molekularni mehanizmi njihova singaliziranja i interakcije još nisu dovoljno poznati. Cilj ovoga istraživanja bio je ispitati učinke interleukina-6, C-reaktivnog proteina i interleukin-6 rs1800795 na razvoj Crohnove bolesti, ulceroznoga kolitisa i upalnih bolesti crijeva općenito te utvrditi razlike između skupine ispitanika oboljelih od upalnih bolesti crijeva i kontrolne skupine ispitanika. U istraživanje je uključeno ukupno 132 oboljela od upalnih bolesti crijeva i 71 zdravi davatelj krvi. Serumska koncentracija interleukina-6 određena je kemiluminiscentnom sekvencijskom imunometričnom, a koncentracija C-reaktivnog proteina imunoturbidimetrijskom metodom. Analiza polimorfizma rs1800795 provodila se na uređaju LightCyclerTM PCR 1.2 u stvarnome vremenu temeljem prijenosa energije uslijed fluorescentne rezonancije. Serumske koncentracije interleukina-6 i C-reaktivnoga proteina bile su povišene i u oboljelih od Crohnove bolesti i oboljelih od ulceroznoga kolitisa. Utvrđene su pozitivne korelacije između serumskih koncentracija C-reaktivnoga proteina i interleukina-6 i indeksa aktivnosti ulceroznoga kolitisa mjerenoga prema ljestvici MTWSI. Serumska koncentracija C-reaktivnog proteina bila je viša u oboljelih od Crohnove bolesti bez prethodne resekcije crijeva u usporedbi s oboljelima od Crohnove bolesti s prethodnom resekcijom crijeva. U oboljelih od ulceroznoga kolitisa serumske koncentracije interleukina-6 i C-reaktivnog proteina bile su statistički značajno više kod CC genotipa interleukina-6 u usporedbi s genotipom GG+GC. Analizom polimorfizma promotorske regije IL-6 rs1800795 nisu uočene razlike u učestalosti alela između oboljelih od Crohnove bolelsti, oboljelih od ulceroznoga kolitisa i kontrolne skupine ispitanika, ni razlike između kontrolne skupine ispitanika i oboljelih od upalnih bolesti crijeva općenito. Rezultati ove studije pružaju potencijalno važan uvid u ulogu signaliziranja interleukina-6 i C-reaktivnoga proteina te polimorfizma interleukina-6 u patogenezi Crohnove bolesti i ulceroznoga kolitisa