Modifiable risk factors associated with later gut decolonization of carbapenem-resistant Gram-negative bacteria in children: a prospective cohort study.

BACKGROUND: Nosocomial infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) are associated with increased mortality and prolonged hospitalization; thus, later CRGNB decolonization has significant clinical and public health implications. AIM: To investigate modifiable/non-modifiable risk factors for CRGNB later gut decolonization in children. METHODS: CRGNB carriers (aged from one day to 16 years) hospitalized in a tertiary level hospital (2018-2019) were included. Upon CRGNB carriage detection, rectal swab cultures were taken weekly, if patients were hospitalized, and monthly after discharge for 12 months. CRGNB decolonization was defined as three consecutive negative rectal-swab cultures obtained ≥1 week apart. Modifiable (treatment administered/medical devices) and non-modifiable (age/gender/comorbidities) risk factors were recorded. Cox regression for later CRGNB decolonization was performed. FINDINGS: One hundred and thirty CRGNB carriers were recorded. After 12 months, 5.4% remained carriers. Risk factors for later decolonization were immunosuppression (hazard ratio: 0.52; 95% confidence interval: 0.31-0.87), carbapenems (0.52; 0.30-0.91), proton pump inhibitors (PPIs) (0.39; 0.24-0.64) and their duration of use, duration of hospitalization (0.90; 0.81-0.92, per 10 days), number of readmissions (0.90; 0.86-0.96), abdominal surgery (0.33; 0.17-0.65), urinary catheter (0.42; 0.24-0.76), and duration of steroid administration per 10 days (0.86; 0.84-0.88). CONCLUSIONS: Carbapenems, PPIs and their duration of use, duration of steroids use, immunosuppression, urinary catheter, readmissions, duration of hospitalization, and abdominal surgery are associated with later CRGNB decolonization among children. Paediatric patients at risk of later decolonization should be under targeted screening and pre-emptive contact precautions. Known carriers at risk of later CRGNB decolonization should be under meticulously applied contact precautions for longer durations.

[Eosinophilic dermatoses]. / Eosinophile Dermatosen.

Eosinophilic dermatoses are a heterogeneous group of rare diseases that histopathologically display the defining pattern of an eosinophil-rich dermal infiltrate. In these eosinophilic dermatoses, a histopathologic pattern called flame figures, which result from degranulation of eosinophils in the tissue, can be observed. Although eosinophil granulocytes can also be detected in other dermatoses such as atopic dermatitis, urticaria, prurigo and bullous pemphigoid, the eosinophil-rich infiltrate is decisive for classic eosinophilic dermatoses. Accordingly, eosinophilic dermatoses include hypereosinophilic syndrome, eosinophilic fasciitis, granuloma faciale, pustular sterile eosinophilia, and angiolymphoid hyperplasia with eosinophilia. These eosinophilic dermatoses display clinical different patterns and are discussed in this article, as well as the interesting eosinophils and novel therapeutic options.

Prevalence of type 2 diabetes mellitus in a representative sample of Greek adults and its association with modifiable risk factors: results from the Hellenic National Nutrition and Health Survey.

OBJECTIVE: Diabetes mellitus is a disease associated with many complications leading to premature death. The aim of this study was to estimate prevalence of type 2 diabetes (T2D), and the proportion of the population unaware of the condition, in association with modifiable risk factors. STUDY DESIGN: Data from the Hellenic National Nutrition and Health Survey were used (n = 3773 adults, 40.8% men) and were obtained by trained personnel. METHODS: Diabetes mellitus disease status was categorized as per the International Classification of Diseases codes (10th version). A subsample from the two main metropolitan areas was used to assess T2D and impaired fasting glucose (IFG) (n = 990; 38.2% men) from plasma analysis. RESULTS: The prevalence of T2D in the population was 5.2% in total, reaching 13.7% in adults aged >60 years (no sex differences). IFG was observed in 27.3% of adults in the two metropolitan areas, and 40% were unaware of having T2D in this subsample. The likelihood of having T2D significantly increased with age and body weight, whereas it decreased with higher educational level and physical activity (P for all <0.001). CONCLUSION: The high T2D prevalence in adults, especially among the older age-groups, suggests a major public health problem in Greece.

Coexistence of Constitutional Mismatch Repair Deficiency syndrome and Lynch syndrome in a family of seven : MSH6 mutation and childhood colorectal cancer - a case series.

PURPOSE: To present a case series of two fraternal twin girls who passed away from brain and colorectal cancers attributed to Constitutional Mismatch Repair Deficiency syndrome (CMMRD). A review of literature for CMMRD-related pediatric malignancies is also presented. METHODS: The two girls were diagnosed with cancer at the age of 11 and 13 respectively. The early onset of multiple malignancies in the family raised clinical suspicion for a potential genetic mutation. The presence of café-au-lait spots at clinical examination led to further investigations for neurofibromatosis. RESULTS: Neurofibromatosis type 1 testing was negative in both children. Genetic analysis turned out positive for biallelic MSH6 mutations in the two girls, leading to CMMRD syndrome diagnosis. Both parents and two out of three alive siblings were diagnosed with Lynch syndrome. CONCLUSIONS: Colorectal cancer is a very rare finding in childhood and should raise suspicion for CMMRD syndrome and should be followed by regular screening.

Ocular nonsteroidal inflammatory drugs: where do we stand today?

Since their first introduction in ophthalmology, the use of NSAIDs (nonsteroidal anti-inflammatory drugs) has been exponentially expanded, with numerous therapeutic applications. Despite their controversial history, they have proven their efficacy as anti-inflammatory agents in a variety of diseases. Nowadays, NSAIDs are part of surgical protocols of the most commonly performed ophthalmic operations, such as cataract or ocular surgery. They are universally implicated in the management of conjunctivitis, retinal and choroidal disease and miscellaneous inflammatory diseases. Moreover, although linked with serious adverse events and toxicities, their therapeutic magnitude in Ophthalmology should not be affected. This review systematically portrays the variety of ocular NSAIDs available to date, along with their differences in their way of action, indications and potential side effects in various ophthalmologic conditions.

Neurological disorders are associated with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease with an increased incidence particularly among the elderly. Several studies have recently reported an association between BP and neurological disorders. OBJECTIVE: To evaluate the association between BP and neurological disorders in a single centre in Germany. METHODS: We retrospectively assessed 183 patients with BP (diagnosed between 2011 and 2015) and 348 age- and sex-matched controls for neurological disorders. The latter were confirmed either by a neurologist or psychiatrist. RESULTS: Overall, there was a highly statistically significant association between BP and neurological disorders (P < 0.0001). These included dementia (P < 0.0001), Parkinson`s disease (P = 0.0434), stroke (P = 0.0015) and other neurological disorders but not Alzheimer's diseases, which was more common among patients in the control group. CONCLUSION: Our cohort of bullous pemphigoid and neurological disorders demonstrates a significant association between bullous pemphigoid and neurological disorders, including dementia, Parkinson's disease and stroke. These observations support the need for future studies in order to elucidate the immunological mechanisms responsible for these comorbidities.

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial.

BACKGROUND/OBJECTIVES: The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). SUBJECTS/METHODS: In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m2), IGT-B (n=20, BMI: 32.5±5kg/m2) or T2D (n=12, BMI: 32.2±5.2kg/m2) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. RESULTS: Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P<0.001 vs P=0.02, respectively). The 6-meal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P<0.05). There were no differences in HOMA-IR or plasma lipids between interventions. CONCLUSION: Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects.

[Update on the cutaneous neurobiology of pruritus]. / Aktuelles zur kutanen Neurobiologie von Pruritus.

The pathogenesis of chronic and acute pruritus is not yet completely understood. Interactions of neurons with resident and nonresident skin cells seem to play an important role in the regulation of pruritus. Neuronal cells which express specific receptors and are capable of releasing neuromediators play an active role in this interaction. Furthermore, released neuromediators can activate immune cells including mast cells and eosinophils, which are increased in the inflammatory infiltrate of many pruritic skin diseases. Mast cells and eosinophils express receptors for neuromediators themselves. In addition, they can release neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and cytokines including interleukin (IL)-31 which correlate with disease activity in patients with inflammatory skin diseases including atopic dermatitis and induce neuronal outgrowth. In part, a correlation of these mediators has also been described with pruritus. Although the interplay between transient and resident cells in the skin with peripheral nerves, mast cells, and eosinophils plays an important role in the mutual activation, the neurobiological mechanisms that lead to pruritus are not completely clear yet.

Childhood atopic dermatitis-Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity.

Several studies have shown that neurotrophins including brain-derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner.

Pirfenidone-induced severe phototoxic reaction in a patient with idiopathic lung fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5-year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64-year-old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability. OBJECTIVE: In this report, we noted a severe phototoxic reaction under treatment with pirfenidone which underlies the potential phototoxic effect of this drug besides the already reported photosensitivity. METHODS: Routine laboratory tests and a skin biopsy were performed. RESULTS: Laboratory tests indicated increased markers of inflammation. The skin biopsy showed a perivascular lymphocytic inflammatory infiltrate, ballooning of keratinocytes with increased apoptosis. These findings were most consistent with a severe phototoxic reaction to pirfenidone which had been directly discontinued. The patient was started on oral methylprednisolone 100 mg/day which was gradually tapered off along with topical corticosteroids (mometasone furoate 0.1% cream) and oral antihistamines. This treatment led to a slow but complete resolution of the skin lesions within 20 days. CONCLUSION: To our knowledge, this is the first reported case of a severe phototoxic reaction during treatment with pirfenidone. Our aim by presenting this case is to increase the awareness of clinicians for severe phototoxic effects of oral pirfenidone.

Effect of meal frequency on glucose and insulin levels in women with polycystic ovary syndrome: a randomised trial.

BACKGROUND/OBJECTIVES: The aim of the study was to compare the effect of two-meal patterns (three vs six meals per day) on glucose and insulin levels in women with polycystic ovary syndrome (PCOS). SUBJECTS/METHODS: In a randomised, crossover, 24-week study, 40 women with PCOS, aged 27±6 years, body mass index 27±6 kg/m(2), followed a weight maintenance diet (% carbohydrates:protein:fat, 40:25:35), consumed either as a three- or a six-meal pattern, with each intervention lasting for 12 weeks. Anthropometric measurements, diet compliance and subjective hunger, satiety and desire to eat were assessed biweekly. All women underwent an oral glucose tolerance test (OGTT) with 75 g glucose for measurement of plasma glucose and insulin at the beginning and end of each intervention. HaemoglobinA1c (HbA1c), blood lipids and hepatic enzymes were measured at the beginning and end of each intervention. RESULTS: Body weight remained stable throughout the study. Six meals decreased significantly fasting insulin (P=0.014) and post-OGTT insulin sensitivity (Matsuda index, P=0.039) vs three meals. After incorporation of individual changes over time, with adjustment for potential confounders, the only variable that remained significant was the Matsuda index, which was then used in multivariate analysis and general linear models. Six meals improved post-OGTT insulin sensitivity independently of age and body weight vs three meals (P=0.012). No significant differences were found between six and three meals for glucose, HbA1c, blood lipids, hepatic enzymes, subjective desire to eat and satiety. CONCLUSIONS: Six meals had a more favourable effect on post-OGTT insulin sensitivity in women with PCOS compared with isocaloric three meals.

Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting.

BACKGROUND: Inhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment. METHODS: Ninety-one drug naïve patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit. RESULTS: HbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % ± 1.60 to 7.52 % ± 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c ≤ 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = -0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea. CONCLUSIONS: Vildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment.

The role of acetic acid on glucose uptake and blood flow rates in the skeletal muscle in humans with impaired glucose tolerance.

BACKGROUND/OBJECTIVES: Previous studies support the glucose-lowering effect of vinegar. However, the effect of vinegar on muscle glucose metabolism and endothelial function has not been studied in humans. This open, randomized, crossover, placebo-controlled study aims to investigate the effects of vinegar on muscle glucose metabolism, endothelial function and circulating lipid levels in subjects with impaired glucose tolerance (IGT) using the arteriovenous difference technique. SUBJECTS/METHODS: Eight subjects with IGT (4 males, age 46±10 years, body mass index 30±5) were randomised to consume 0.50 mmol vinegar (6% acetic acid) or placebo before a mixed meal. Plasma samples were taken for 300 min from the radial artery and the forearm vein for measurements of glucose, insulin, triglycerides, non-esterified fatty acids (NEFAs) and glycerol. Muscle blood flow was measured with strain gauge plethysmography. Glucose flux was calculated as the arteriovenous difference of glucose multiplied by the blood flow rates. RESULTS: Vinegar compared with placebo: (1) decreased arterial plasma insulin (Poverall<0.001; P75 min=0.014, ß=-42), (2) increased forearm blood flow (Poverall<0.001; P240 min=0.011, ß=1.53; P300 min=0.023, ß=1.37), (3) increased muscle glucose uptake (Poverall<0.001; P60 min=0.029, ß=2.78) and (4) decreased arterial plasma triglycerides (Poverall=0.005; P240 min<0.001, ß=-344; P300 min<0.001, ß=-373), without changing NEFA and glycerol. CONCLUSIONS: In individuals with IGT, vinegar ingestion before a mixed meal results in an enhancement of muscle blood flow, an improvement of glucose uptake by the forearm muscle and a reduction of postprandial hyperinsulinaemia and hypertriglyceridaemia. From this point of view, vinegar may be considered beneficial for improving insulin resistance and metabolic abnormalities in the atherogenic prediabetic state.

A randomized investigator-blind parallel-group study to assess efficacy and safety of azelaic acid 15% gel vs. adapalene 0.1% gel in the treatment and maintenance treatment of female adult acne.

BACKGROUND: Growing numbers of post-adolescent females are suffering from treatment-resistant or relapsing adult acne forms, therefore requiring the definition of safe and effective treatment options for this burdening disease. OBJECTIVES: To assess the efficacy of azelaic acid 15% gel (AzA) vs. no treatment during maintenance therapy of female adult acne and to compare its efficacy and safety vs. adapalene 0.1% gel (AD) during a 9-month period (3-month treatment and 6-month maintenance treatment). METHODS: A total of 55 women between 18 and 45 years with adult acne were included in this investigator-blind trial and randomized into three groups receiving AzA gel b.i.d. for 9 months (AzA9M, n = 17) or AzA gel b.i.d. for 3 months followed by a 6-month observational phase (AzA3M, n = 19) or AD gel once daily for 9 months (AD9M, n = 19). Parameters of efficacy, safety and patient-related factors were analysed. RESULTS: The reduction in lesion counts, severity and Dermatology Life Quality Index score was significant (P < 0.05) and comparable between groups during the treatment phase, while dryness and scaling were significantly lower (P < 0.05) in group AzA9M vs. AD9M. During maintenance, AzA9M was superior to AzA3M in the control of inflammatory lesions (P = 0.008) and total lesions (P = 0.014) at week 24. From week 12 to week 36, a mild relative increase in inflammatory lesions could be observed in all groups. In AzA3M, this increase exceeded that of AzA9M by 23.1% (P = 0.109), while the difference of total lesions diverged to 30.8% (P = 0.038). No significant differences could be detected between AzA9M and AD9M. Group AzA9M was non-inferior to AD9M (non-inferiority margin of 50% for the confidence limit for the relative effect) in the control of inflammatory acne lesions. CONCLUSIONS: AzA15% gel is a safe and effective treatment and maintenance treatment of female adult acne with non-inferior efficacy to AD 0.1% gel in the control of inflammatory acne.