Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

PURPOSE: Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. METHODS: We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. RESULTS: Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). CONCLUSION: Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Efficacy, feasibility and tolerability of ketogenic diet for the treatment of poor response to bariatric surgery.

PURPOSE: Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition. METHODS: A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated. RESULTS: A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected. CONCLUSION: Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.

Comparison of BACTEC™ blood culture media for the detection of fungemia.

The aim of the present study was to investigate whether addition of the BACTEC™ Mycosis bottle to the standard BACTEC™ aerobic and anaerobic bottles contributed to a higher detection rate and a faster time to detection (TTD) of fungi. This was a retrospective cohort study of all patients with a positive blood culture with Candida species delivered to the Department of Clinical Microbiology, Herlev and Gentofte Hospital, Denmark in the 8-year period 2006 through 2014. The patients had at least one BACTEC™ aerobic and one Mycosis bottle sampled at the same time and at least one of the bottles yielded growth of fungi. Among 184 patients included, 173 were examined using BACTEC™ aerobic, anaerobic and Mycosis bottles. The anaerobic vial generally had the lowest detection rate and the longest TTD. The detection rate of BACTEC™ aerobic plus anaerobic with the BACTEC™ Mycosis bottle was significantly higher than the detection rate of BACTEC™ aerobic plus anaerobic without BACTEC™ Mycosis bottle for all species after 1-5 days, and specially for Candida glabrata at 2, 3, 4 and 5 days. TTD for C. glabrata was significantly shorter for BACTEC™ Mycosis than TTD for BACTEC™ aerobic or anaerobic bottles after ½ to 4 days. When combining "first or only" detection, the BACTEC™ Mycosis bottle had a significantly higher detection as compared to the aerobic bottle. Addition of the BACTEC™ Mycosis bottle to the standard BACTEC™ aerobic and anaerobic bottles significantly contributed to a higher detection rate and a faster TTD of fungemia.

Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia.

Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment. The rareness of the infection makes it difficult to improve antibiotic treatment through randomized clinical trials. This observational study investigated clinical features and outcome of invasive L. monocytogenes infections including the efficacy of empiric and definitive antibiotic therapies. Demographic, clinical and biochemical findings, antibiotic treatment and 30-day mortality for all episodes of L. monocytogenes bacteraemia and/or meningitis were collected by retrospective medical record review in the North Denmark Region and the Capital Region of Denmark (17 hospitals) from 1997 to 2012. Risk factors for 30-day all-cause mortality were assessed by logistic regression. The study comprised 229 patients (median age: 71 years), 172 patients had bacteraemia, 24 patients had meningitis and 33 patients had both. Significant risk factors for 30-day mortality were septic shock (OR 3.0, 95% CI 1.4-6.4), altered mental state (OR 3.6, 95% CI 1.7-7.6) and inadequate empiric antibiotic therapy (OR 3.8, 95% CI 1.8-8.1). Cephalosporins accounted for 90% of inadequately treated cases. Adequate definitive antibiotic treatment was administered to 195 patients who survived the early period (benzylpenicillin 72, aminopenicillin 84, meropenem 28, sulfamethoxazole/trimethoprim 6, and piperacillin/tazobactam 5). Definitive antibiotic treatment with benzylpenicillin or aminopenicillin resulted in a lower 30-day mortality in an adjusted analysis compared with meropenem (OR 0.3; 95% CI 0.1-0.8). In conclusion, inadequate empiric antibiotic therapy and definitive therapy with meropenem were both associated with significantly higher 30-day mortality.

Association of autoimmune thyroid diseases, chronic atrophic gastritis and gastric carcinoid: experience from a single institution.

PURPOSE: Autoimmune polyendocrine syndromes (APS) type III are characterized by the association of autoimmune thyroid disease (ATD) with other autoimmune diseases such as diabetes, alopecia, pernicious anemia, vitiligo and chronic atrophic gastritis. A strong association between ATD and atrophic gastritis (AG) has been demonstrated. Moreover 10 % of patients affected by AG have a predisposition to develop gastric carcinoid and adenocarcinoma as a result of chronic hypergastrinemia caused by achlorhydria and subsequent ELC cells neoplastic transformation. METHODS: The aim of the study is to evaluate, in a consecutive series of patients followed for ATD in our outpatients clinic, the prevalence of AG. In the period 2004-2014, 242 patients with ATD underwent a screening performing APCA, Vitamin B12, ferritin, iron, and hemoglobin and red cells count measurements with subsequent gastroscopy in case of APCA positivity. RESULTS: We found 57/242 (23.5 %) patients with APCA positivity. Of these patients 33/57 (57.8 %), 31 F and 2 M, were affected by Graves disease; 24/57 (42.1 %) 21 F and 3 M by Hashimoto thyroiditis; 10/57 (17.5 %) presented with anemia, 14/57 (24.5 %) with vitamin B12 deficiency, 9/57 (15.7 %) with iron deficiency. In 2/57 a gastric carcinoid was found. CONCLUSIONS: Our data confirm the high association rate of AG in ATD which frequently is not an isolated disease but configure the picture of APS type III and need to be followed accordingly. An early diagnosis may be useful for diagnosis of gastric carcinoids and to explain and treat a gastric related L-thyroxine malabsorption and presence of chronic unexplained anemia.

Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection.

BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS: This was a double-blind randomized placebo-controlled intervention study of a single dose of 80 mg methylprednisolone versus saline on seroma formation after mastectomy. Patients were further classified according to the surgical axillary procedure: mastectomy with sentinel lymph node biopsy (M + SLNB) or mastectomy with level I-II axillary lymph node dissection (M + ALND). Treatments were administered into the wound cavity via the drain orifice following removal of the drain on the first day after surgery. The primary endpoint was seroma formation; secondary endpoints included the frequency of side-effects and complications. RESULTS: A total of 212 women scheduled for mastectomy for primary breast cancer were included. After M + SLNB, 32 (46 per cent) of 69 women developed a seroma in the methylprednisolone group, compared with 52 (78 per cent) of 67 in the saline group (P < 0.001). The mean cumulative seroma volume in the intention-to-treat population for the first 10 and 30 days was significantly lower in the methylprednisolone group (24 ml versus 127 ml in the saline group, and 177 versus 328 ml respectively) (P < 0.001). After M + ALND, similar proportions of patients developed a seroma in the methylprednisolone (35 of 37, 95 per cent) and saline (34 of 36, 94 per cent) groups, and methylprednisolone administration had no significant effect on seroma formation. No differences in infection rate were observed. CONCLUSION: Methylprednisolone administered into the wound cavity on the first day after M + SLNB exerted a highly significant preventive effect against seroma formation during the next 30 days. This effect was not seen in the M + ALND group. Future studies may clarify whether higher or repeated methylprednisolone doses increase the efficacy.

Evaluating antibiotic stewardship programs in patients with bacteremia using administrative data: a cohort study.

When introducing new antibiotic guidelines for empirical treatment of bacteremia, it is imperative to evaluate the performance of the new guideline. We examined the utility of administrative data to evaluate the effect of new antibiotic guidelines and the prognostic impact of appropriate empirical treatment. We categorized 2,008 adult patients diagnosed with bacteremia between 2010 and 2012 according to whether they received cephalosporins or fluoroquinolones (old regimen) or not (new regimen). We used administrative data to extract individual level data on mortality, readmission, and appropriateness of treatment, and computed adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 30-day mortality and post-discharge readmission by regimen and appropriateness of treatment. In total, 945 (47.1%) were treated by the old regimen and 1,063 (52.9%) by the new. The median length of stay (8 days) did not differ by regimen and neither did the proportion of those receiving appropriate empirical treatment (84.1% vs. 85.5%). However, fewer patients with the new regimen were admitted to the intensive care unit (ICU; 3.8% vs. 12.0%) and they had lower 30-day mortality (16.4% vs. 23.4%). The adjusted 30-day mortality HR for appropriate versus inappropriate treatment was 0.79 (95% CI 0.62-1.01) and 0.83 (95% CI 0.66-1.05) for the new versus the old regimen. The HR for 30-day readmission for appropriate versus inappropriate treatment was 0.91 (95% CI 0.73-1.13) and 1.05 (95% CI 0.87-1.25) for the new versus the old regimen. This study demonstrates that administrative data can be useful for evaluating the effect and quality of new bacteremia treatment guidelines.

Utilization of blood cultures in Danish hospitals: a population-based descriptive analysis.

This national population-based study was conducted as part of the development of a national automated surveillance system for hospital-acquired bacteraemia and ascertains the utilization of blood cultures (BCs). A primary objective was to understand how local differences may affect interpretation of nationwide surveillance for bacteraemia. From the Danish Microbiology Database, we retrieved all BCs taken between 2010 and 2013 and linked these to admission data from the National Patient Registry. In total, 4 587 295 admissions were registered, and in 11%, at least one BC was taken. Almost 50% of BCs were taken at admission. The chance of having a BC taken declined over the next days but increased after 4 days of admission. Data linkage identified 876 290 days on which at least one BC was taken; 6.4% yielded positive results. Ten species, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Enterococcus faecium, Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae and Klebsiella oxytoca, accounted for 74.7% of agents for this purpose classified as pathogenic. An increase in BCs and positive BCs was observed over time, particularly among older patients. BCs showed a seasonal pattern overall and for S. pneumoniae particularly. A predominance of male patients was seen for bacteraemias due to S. aureus, E. faecium and K. pneumoniae. Minor differences in BCs and positive BCs between departments of clinical microbiology underpin the rationale of a future automated surveillance for bacteraemia. The study also provides important knowledge for interpretation of surveillance of invasive infections more generally.

Incidence, clinical characteristics and 30-day mortality of enterococcal bacteraemia in Denmark 2006-2009: a population-based cohort study.

Enterococci currently account for approximately 10% of all bacteraemias, reflecting remarkable changes in their epidemiology. However, population-based data of enterococcal bacteraemia are scarce. A population-based cohort study comprised all patients with a first episode of Enterococcus faecalis or Enterococcus faecium bacteraemia in two Danish regions during 2006-2009. We used data collected prospectively during clinical microbiological counselling and hospital registry data. We determined the incidence of mono- and polymicrobial bacteraemia and assessed clinical and microbiological characteristics as predictors of 30-day mortality in monomicrobial bacteraemia by logistic regression analysis. We identified 1145 bacteraemic patients, 700 (61%) of whom had monomicrobial bacteraemia. The incidence was 19.6/100 000 person-years (13.0/100 000 person-years for E. faecalis and 6.6/100 000 person-years for E. faecium). The majority of bacteraemias were hospital-acquired (E. faecalis, 45.7%; E. faecium, 85.2%). Urinary tract and intra-abdominal infections were the predominant foci for the two species, respectively. Infective endocarditis (IE) accounted for 25% of patients with community-acquired E. faecalis bacteraemia. Thirty-day mortality was 21.4% in patients with E. faecalis and 34.6% in patients with E. faecium. Predictors of 30-day mortality included age, co-morbidity and hospital-acquired bacteraemia. In addition, intra-abdominal infection, unknown focus and high-level gentamicin resistance were predictors of mortality in E. faecalis patients. E. faecium was associated with increased risk of mortality compared with E. faecalis. The study emphasizes the importance of enterococci both in terms of incidence and prognosis. The frequency of IE in patients with E. faecalis bacteraemia emphasizes the importance of echocardiography, especially in community-acquired cases.

Linezolid as rescue treatment for left-sided infective endocarditis: an observational, retrospective, multicenter study.

The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE. The objective of this study is to report our experience with linezolid from a large consecutive cohort of IE patients. In a retrospective cohort study, data on 550 consecutive IE patients were collected at two tertiary University Hospitals in Copenhagen, Denmark. The main endpoints were differences in the in-hospital and 12 months post-discharge mortality between IE patients receiving linezolid for a part of the treatment and IE patients receiving conventional treatment. Of the 550 patients enrolled in the study, 38 patients received linezolid treatment and 512 received conventional treatment. Reasons for adding linezolid were antibiotic intolerance (n = 13), nephrotoxicity (n = 5), pharmaceutical interactions (n = 1), inadequate clinical response (n = 14), or inadequate microbial response (n = 5). No significant differences in the cure rate (74 % vs. 71 %, p > 0.05), in-hospital mortality (13 % vs. 14 %, p > 0.05), or post-discharge mortality at 12 months follow-up (26 % vs. 26 %, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics.

Early infections in patients undergoing high-dose treatment with stem cell support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma.

BACKGROUND: Infections are life-threatening complications in patients undergoing high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious pathogens is essential to make a safe outpatient setting. METHODS: We conducted a retrospective study of 208 patients treated with HDT. The population included non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received prophylactic antibacterial treatment. RESULTS: Pathogens were isolated from 44% of all patients. MM patients more frequently had multiple pathogens in blood cultures (38% versus 25%). Transplantation related mortality was similar between the groups. CONCLUSION: The frequency of isolated pathogens, positive blood cultures, and the diversity of pathogens were higher in MM patients as compared to NHL patients. However, this did not translate into higher transplantation-related mortality, probably because broad-spectrum antibiotic treatment could be initiated immediately. A safe outpatient setting with prophylactic antibiotic treatment is dependent on continuous collection and registration of microbiological findings.

Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5).

AIMS: We previously demonstrated the presence of two different populations among adult-onset autoimmune diabetes (latent autoimmume diabetes of adults; LADA) having high or low titre of antibodies to glutamic acid decarboxylase (GADA). The transcription factor 7-like 2 (TCF7L2) gene has been recognized as the major gene associated with Type 2 diabetes. The aim of the present study was to evaluate whether the phenotypic heterogeneity of LADA based on GADA titre is associated with TCF7L2 polymorphisms. METHODS: Two hundred and fifty patients identified as LADA, divided into two subgroups with low (< or = 32 arbitrary units) or high (> 32 units) GADA titre, 620 subjects with Type 2 diabetes [from the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study cohort of 5330 subjects] in addition to 551 consecutive cases of Type 1 diabetes and 545 normoglycaemic subjects were analysed for the rs12255372 and rs7903146 polymorphisms of the TCF7L2 gene using Taqman. RESULTS: The genotype and allele distributions of the two polymorphisms revealed similar frequencies in subjects with low GADA titre and Type 2 diabetes. High GADA titre, Type 1 diabetes and controls also showed comparable frequencies. A significant increase of GT/TT genotypes of the rs12255372 single-nucleotide polymorphism (SNP) and CT/TT genotypes of the rs7903146 SNP was observed in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and controls (P < or = 0.04 for both comparisons). The risk alleles of both variants were increased in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and control subjects (P < 0.02 for all comparisons). CONCLUSIONS: TCF7L2 common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients.

Healing of chronic necrobiosis lipoidica lesions in a type 1 diabetic patient after pancreas-kidney transplantation: a case report.

Necrobiosis lipoidica (NL) is a degenerative disease of dermal connective tissue of unknown etiology characterized by erythematous plaques preferentially localized to distal extremities. Skin lesions show a chronic relapsing nature. NL is often associated with diabetes mellitus and satisfactory treatment options are lacking. We describe the spontaneous healing of NL lesions after pancreas and kidney transplantation in a Type 1 diabetic patient with chronic NL recalcitrant to a variety of standard treatments. The 31-yr-old male patient had experienced NL lesions for more than 15 yr; despite various systemic and topical treatments, the skin lesions had pregressively enlarged. Because of end-stage renal disease, a simultaneous pancreas and kidney transplantation was performed and immunosuppressive therapy with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone was started. Pancreatic transplantation maintained satisfactory metabolic control with no need of exogenous insulin. After transplantation, skin lesions slowly healed without any specific treatment, leaving residual areas of fibrotic scars. A skin biopsy confirmed the absence of typical NL lymphocytic and histiocytic inflammatory response. Clinical remission of NL lesions may probably be explained by the concomitant effect of multiple-drug regimen for immunosuppression (TAC, MMF, and prednisone) and improved skin microcirculation secondary to the good metabolic control provided by pancreas transplantation.

A ten-year (1989-1998) perspective study of the incidence of Type 1 diabetes in the district of Catania (Sicily) in a 0-14 year age group.

The aim of this report was to evaluate the incidence of Type 1 diabetes mellitus (T1DM) in the district of Catania (eastern Sicily) in children under 15 yr of age over a ten-yr period (01/01/1989 - 31/12/1998) in relation to age, sex, monthly-seasonal variability, calendar yr and spatial clustering. The estimated completeness of our register was 99.2%. The overall incidence rate was 12.38 per 100,000 during the period of the study. Twenty-four percent of cases were 0-4 yr at diagnosis, 42% were 5-9 yr and 34% were 10-14 yr. More males (no. 148) than females (no. 125) were newly diagnosed with a male/female ratio similar to the base population ratio in the range 0-14 yr and within age groups. The study revealed a non-random spatial distribution of T1DM incidence in children not accounted for by known demographic factors. A significant seasonal pattern and temporal trend of incidence were also detected.

[The value of vaginal swabs]. / Vaerdien af vaginalpodninger.

INTRODUCTION: The use of culture of vaginal secretions by physicians and their use of microscopy of vaginal secretions were assessed. METHODS: The study was conducted partly as a registration of all microbiological requests and reports from the Department of Clinical Microbiology in a selected period, and partly as a questionnaire sent to all general practitioners (GPs) and specialists in obstetrics and gynaecology in the county of Arhus. RESULTS: In only 19% of 1,354 vaginal swabs received in a month could the findings lead to a specific antimicrobial treatment; 48% of these cases could be diagnosed by microscopy of vaginal secretions alone. Sixty-four per cent of the physicians returned the questionnaire. Half of the specialists and 60% of the GPs performed microscopy. Twenty-five per cent of the physicians treated patients solely on the basis of clinical symptoms. DISCUSSION: General culture of vaginal secretions has a limited clinical value. The diagnosis in patients complaining of vaginal discharge can often be made by microscopy. There is, however, a need for training GPs in microscopy, as well as specialists.

Association between colonization with group B streptococci during pregnancy and preterm delivery among Danish women.

OBJECTIVE: We studied the relationship between group B streptococcal colonization and preterm delivery. STUDY DESIGN: In this prospective study at a single hospital in Odense, Denmark, cervicovaginal cultures were obtained at < or = 24 weeks' gestation from all the women, at delivery from women with preterm deliveries, and from a random sample of women delivering at term. RESULTS: In 2846 singleton births, there was no significant association between group B streptococcal colonization at

[Incidence of methicillin-resistant Staphylococcus aureus among Kosovar-Albanian refugees at the refugee-center in Randers]. / Forekomst af methicillinresistent Staphylococcus aureus blandt kosova-albanske flygtninge på Flygtningecenter Randers.

INTRODUCTION: With the emergence of the war in Kosova, Europe faced a massive problem dealing with the refugees. The Danish quota was 3,000 refugees. Their health care was organised by the Danish Red Cross in collaboration with the District Hospital of Randers (DHR), the University Hospital of Arhus, and the Psychiatry Unit of the County of Arhus. The aim of the present retrospective study was to describe the prevalence of MRSA in this group of refugees. MATERIALS AND METHODS: Nasal screening culture for MRSA was performed on the first 50 refugees arriving at Randers. On admission to the DHR, the Kosovar-Albanian refugees were isolated until the MRSA culture showed negative. RESULTS: MRSA causing serious nosocomial infections has become a major problem in hospitals worldwide, with a higher incidence in the southern part of Europe than in Denmark. The initial nasal screening revealed no MRSA positive cultures. During the course of the subsequent 14 months, we found eight Kosovar-Albanian refugees infected with/colonised by MRSA (Table 1). We observed no spread of MRSA to other patient groups. CONCLUSION: We conclude that 1) the results of the initial screening of 50 refugees did not predict the succeding high incidence of MRSA; 2) the usual treatment with mupirocin nasal ointment and chlorhexidine wash did not prevent either reinfection or spread of MRSA in the refugee centre; 3) the rigorous isolation and screening strategy at DHR prevented the spread of MRSA to other patients and staff.