Treatment of fever and associated symptoms in the emergency department: which drug to choose?

OBJECTIVE: Fever is a frequent cause of admission to the Emergency Department (ED) worldwide. Although it can be caused by a wide range of conditions, the most effective treatment based on its etiology is still undetermined. PATIENTS AND METHODS: This prospective, single-center, observational study enrolled adult patients who accessed the ED for fever. Physicians were free to administer paracetamol 1,000 mg (P), the combination paracetamol 500 mg/ibuprofen 150 mg (PI) or Ibuprofen 600 mg (I). The primary endpoint was both 1-degree and 1-point reduction in body temperature for all associated symptoms on the Numerical Rating Scale (NRS) after 1 hour (T1). The secondary endpoint was the reduction of at least 2 points on the NRS after two hours (T2). Adverse events, the need for rescue therapy, and the response based on the underlying etiology (bacterial, viral, or immune/neoplastic) were also evaluated. RESULTS: 324 patients (170 males, mean age 71±6 years) were enrolled: 187 had bacterial, 80 viral, and 57 neoplastic/inflammatory fever. Fever was treated with Paracetamol 1,000 mg (P) in 189 patients and with Paracetamol/Ibuprofen 500/150 mg (PI) in 135 subjects, while none of the patients were primarily treated with I. Based on the fever etiology P was administered to 113 patients with bacterial fever (59.8%), 48 patients with viral fever (25.4%), and 28 subjects with neoplastic/inflammatory fever (14.8%). PI was administered to 74 patients with bacterial fever (54.8%), 32 patients with viral fever (23.7%), and 29 subjects with neoplastic/inflammatory fever (21.5%). The primary endpoint was achieved by 126 patients, 70 of them (37.0%) were treated with P and 56 (41.5%) with PI (p=0.418). The secondary endpoint was achieved by 295 patients, 171 (90.5%) of them treated with P and 124 (91.9%) treated with PI (p=0.669). No significant differences were found between groups treated with P and PI concerning rescue therapy (15 vs. 6 patients; p=0.893). Interestingly, PI was more effective than P in patients with bacterial fever at T1 (P 33.6% vs. PI 48.6%; p=0.040), while efficacy of P and PI was similar at T2 for all kind of fever. CONCLUSIONS: Paracetamol 1,000 mg represents the first choice for the treatment of fever in the ED, followed by Paracetamol/Ibuprofen 500/150 mg. Interestingly, Paracetamol/Ibuprofen combination resulted in being more effective in patients with bacterial fever one hour after its administration.

Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Patient safety recommendations and management in patients with COVID-19 pneumonia suspicion: a retrospective study.

OBJECTIVE: Since December 2019, new pneumonia of unknown aetiology broke out in Wuhan, Hubei province, China. Subsequently, a virus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of the disease. Currently, the epidemic has spread all over the world. The most common manifestations of COVID-19 are fever, fatigue and dry cough. At the moment, the nuclide acid test is the gold standard method for the diagnosis of this infection. METHODS: In the present paper, we report our experience with all patients who came to the Emergency Department from March 1 to April 1, 2020, with suggestive symptoms of COVID-19 infection. Patients: they all underwent a first oropharyngeal and nasopharyngeal swab in the emergency department and, if negative, a second one after at least 24 hours. RESULTS: Our study shows how the results obtained at time zero are usually identical to the ones obtained after 24 hours. We thus suggest, in patients with high suspicion of COVID19 and a negative result at the first swab, to repeat the test after at least 48 hours, during which patients with symptoms of COVID-19 pneumonia disease should be kept in isolation to avoid the risk of contagion. CONCLUSIONS: these measures and in particular the early identifica-tion of cases with consequent isolation will allow the containment of the spread of the virus, representing one of the fundamental measures to guarantee and strengthen the control of the infection to reduce hospital admissions, the overload of national health service and health costs.

13C urea breath test to identify Helicobacter pylori Infection in patients with upper gastrointestinal bleeding admitted to the Emergency Department.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a cause of Emergency Department (ED) visits. Peptic ulcer secondary to H. pylori (HP) infection and/or to the use of NSAIDs is the most frequent cause. The aim of the study is to evaluate directly in the ED the prevalence of HP infection through Urea Breath test (UBT) in patients admitted to the ED for UGIB. PATIENTS AND METHODS: We enrolled 87 patients (58M/29F) with a mean age of 63.8 + 11.7 yrs with an active UGIB who performed EGDS and UBT. RESULTS: 34.4% of patients performing EGDS and UBT resulted positive to HP. Peptic ulcer was present in 20/30 (66.7%) of HP+ compared to 20/57 (35.1%) of HP- (p<0.001), and also gastritis and/or duodenitis were mostly present in HP+ (23.3% vs. 15.8%) (p<0.05). A biopsy was performed in only 31% of patients with a positive rate of 33.3%. In 78% we obtained a correspondence between UBT and biopsy results. Compared to biopsy result, we obtained for UBT a positive predictive value (PPV) of 71% and a negative predictive value (NPV) of 80%. Taking the UBT as a gold standard, we obtained for biopsies a PPV of 69% and a NPV of 85%. CONCLUSIONS: Our study confirms that the use of UBT directly in ED in patients with UGIB allows for a rapid, reliable and non-invasive diagnosis of HP infection as a causative agent for bleeding, thus permitting a right etiological treatment.

Role of troponin in COVID-19 pandemic: a review of literature.

Acute SARS-CoV-2 respiratory disease is an infectious respiratory disease caused by the virus SARS-CoV-2 belonging to the coronaviridae family. A pandemic is still present as of May 2020. In addition to causing pneumonia, SARS-CoV-2 may induce a direct damage to the heart, causing myocarditis, with significant impairment of cardiac contractility, and/or pericarditis. Elderly patients and those with cardiovascular risk factors, such as hypertension and diabetes mellitus, are at increased risk of heart complications from COVID-19. In this review, we focused on the correlation between COVID-19 infection and the high sensitivity troponin T and I, and their significance in the development of myocarditis. Data emerging from the studies so far conducted indicate that a high value of high-sensitivity troponin represents a negative prognostic indicator when associated with heart damage on an infectious-inflammatory basis (i.e. myopericarditis). We should identify a safe and clear diagnostic algorithm, possibly combining patient clinical history, troponin levels and cardiac ultrasound findings that could help us in the prediction of myopericarditis.

Role of first aid in the management of acute alcohol intoxication: a narrative review.

OBJECTIVE: Acute alcohol intoxication is actually a common admission cause in the Emergency Department and represents an increasing public health burden, in particular among adolescents. It involves possible and significant illness and injury, which can quickly get worse and may need to be managed in the emergency room. MATERIALS AND METHODS: We conducted a narrative review of the literature regarding the effectiveness of first aid role of the Emergency Department setting. RESULTS: This review included eighteen studies about alcohol intoxication management in the Emergency Department; most of all highlights the emerging phenomenon in Europe and around the world of acute alcohol intoxication management in first aid. The treatment of acute alcohol intoxication depends on general clinical conditions of the patient, vital signs, hemodynamic stability, cognitive state, alcohol-related complications, which are closely related to the blood alcohol concentration. At the same time, symptoms could be extremely variable due to individual differences in alcohol metabolism. In case of mild-moderate intoxication (blood alcohol concentration < 1 g/L), no drugs are necessary. In case of severe intoxication (blood alcohol concentration > 1 g/L), it is necessary to support with intravenous fluids, treat hypoglycemia, hypotension, hypothermia and electrolyte imbalance, administer complex B and C vitamins and accelerate alcohol elimination from blood with metadoxine. Unlike adults, adolescents are more exposed to the toxic effect of alcohol (because of their immature hepatic alcohol dehydrogenase activity), and then, acute alcohol-related complications are more frequent and dangerous in young people than in adult population. In many cases, patients affected by acute alcohol intoxication referring to an Emergency Department have mild-moderate transitory symptoms that do not require the use of drugs; they can benefit from a clinical observation, with a clinical course often completed within 24 hours with a favorable outcome. Clinical observation with vital signs control is necessary also to evaluate the possible development of the alcohol withdrawal syndrome (that involves a specific treatment) and to evaluate also possible pathological complications of the organism, above all acute liver damage. CONCLUSIONS: Patients affected by acute alcohol intoxication are the best candidates to apply the rules of the Temporary Observation Unit in the Emergency Department, because of a clinical course often completed within 24 hours, a favorable outcome and without the need for hospitalization. In many cases, hospitalization could be not necessary, but the patient affected by Alcohol Use Disorder must be referred to an Alcohol Addiction Unit for the follow-up, to reduce the risk of alcohol relapse and complications related to alcohol abuse, and financial costs of hospitalization.

Unexpected macrophage activation syndrome in a healthy young woman: a case report.

Macrophage activation syndrome (MAS) is a life-threatening condition and a medical emergency with a high-risk of mortality. It belongs to a group of diseases known as "hemophagocytic lymphohistiocytosis", characterized by a cytokine storm, with secretion of tumor necrosis factor, interleukins and interferon-gamma, and an inappropriate activation of macrophages and T-lymphocytes. Some inflammatory and systemic autoimmune diseases, such as systemic juvenile idiopathic arthritis, Still's disease and systemic lupus erythematosus, can develop into macrophage activation syndrome. This is the first episode of macrophage activation syndrome (MAS) in a young healthy woman. She arrived at the Emergency Department complaining of four days of weakness and fever not responsive to paracetamol. She had no significant past medical history, her mother suffered from rheumatoid arthritis. In the Emergency Department, we performed laboratory exams, autoimmune and infectious disease screening, bone marrow biopsy. The final diagnosis was of macrophage activation syndrome. Macrophage activation syndrome, in extremely rare cases, can arise independently years before the manifestation of an autoimmune disease. Persistent fever, high level of inflammatory markers and pancytopenia should raise suspicion in healthy people, especially when associated with a family history of autoimmune disease. Early diagnosis and consequent early treatment are fundamental to avoid progressive tissue damage that can lead to organ failure and death.

Acute uncomplicated diverticulitis: key points for early management. A single-centre retrospective study.

OBJECTIVE: Acute uncomplicated diverticulitis is an important clinical condition usually managed in clinical practice with antibiotic therapies and hospitalization in ward. In this setting, recent papers and guidelines suggest to limit the use of antibiotics in selected cases and encourage an early discharge in low-risk patients. The purpose of this retrospective study is to identify serological inflammatory markers and CT findings of acute uncomplicated diverticulitis (AUD) at the onset of the disease and the correlation with the need for in-patient or out-patient management. PATIENTS AND METHODS: It was used a database drawn from the collection of the patients admitted to our Emergency Room from January 2016 to 2019 and undergoing urgent abdominal CT-scan for suspicious of acute diverticulitis. For each patient we considered biochemical and radiological parameters at the onset of the disease and if patients were managed as in-patients (hospitalization in ward) or as out-patient (early discharged or after observation in Short Stay Unit). RESULTS: Among patients with early diagnosis of AUD, 108 (65%) were hospitalized in ward with mean time of in-stay of 6.94 days, while only 58 (35%) patients with same diagnosis were managed as out-patient and early discharged from emergency room or after observation in short stay unit with a mean time of in-stay significantly shorter (3.39 days, p-value 0.0007). Higher levels of C reactive protein and the length of colon involved considered as percentage (%) in comparison with the entire colon were significantly related to the need for hospitalization (p-value 0.03). CONCLUSIONS: Biochemical parameters and a more advanced radiological evaluation, as the length (%) of colon involved, could allow a stratification of patients with diagnosis of AUD at the admission and help physicians in the early management.

The role of gut microbiota in mediating obesity and diabetes mellitus.

OBJECTIVE: This review inspects the relations between the microbiota and the intestinal immune system in the advancement of metabolic illnesses, such as obesity and diabetes mellitus. The role of the microbiota in intestinal immune defense and the control of metabolism are subject to examination. MATERIALS AND METHODS: In type 1 diabetes, the adhesion proteins prompt inside the intestinal epithelium prompt a more significant immune response that may result in the destruction of pancreatic ß cells by CD8+ T-lymphocytes, as well as increased articulation of interleukin-17, which is associated with autoimmunity. Studies suggest that the beginning of metabolic ailments and certain co-morbidities can be viewed in light of the protection between the gut microbiota and the intestinal immune system. The gut microbiota is analyzed as a key regulator of metabolic ailments. Research demonstrates that obese patients with type 2 diabetes have a certain gut microbiota and that the microbiota is translocated from the gut to the tissues in conjunction with the illness, which instigates inflammation. RESULTS: Research in animals and people suggests that a probiotic supplement may regulate the gut microbiota, thereby improving the prognosis for diabetes. CONCLUSIONS: The mechanism underlying this phenomenon relates to a decrease in the inflammatory reaction and oxidative stress, as well as a decrease in leaky gut. Such reactions increase insulin sensitivity and reduce autoimmune responses.

Atypical presentation of acute pancreatitis: a single center case-match analysis of clinical outcomes.

OBJECTIVE: Acute pancreatitis (AP) may present an aspecific clinical picture without abdominal symptoms (atypical AP). We compared clinical outcomes between typical and atypical AP. PATIENTS AND METHODS: Thirty out of 1163 patients (2.6%) presented an atypical AP. Demographic, clinical data, laboratory and radiological findings, management type, length of hospital stay (LOS) and mortality rate were retrospectively reviewed. A case match analysis 2:1 was performed. The final groups comprised 50 typical APs (TAP group) and 25 atypical APs (AAP group). RESULTS: The AAP patients presented fever (36%), syncope (32%) and dyspnea (16%) as the most frequent symptoms. Laboratory values showed similarity between the two groups. We noted a comparable edematous AP rate in both groups (p=0.36). Ten (20%) TAP and 3 (12%) AAP patients needed ERCP, respectively (p=0.38). Cholecystectomy was similarly performed in both cohorts (p=0.81). One TAP patient underwent a percutaneous drainage and subsequent surgical necrosectomy compared to none in the AAP cohort (p=0.47). LOS and mortality rate were comparable (p=0.76 and 0.3, respectively). CONCLUSIONS: Similar outcomes have been reached in the two groups. Routine evaluation of the serum amylase values fundamentally contributed to early diagnosis and appropriate treatment.

The efficacy of a mix of three probiotic strains in reducing abdominal pain and inflammatory biomarkers in acute uncomplicated diverticulitis.

OBJECTIVE: Acute Uncomplicated Diverticulitis (AUD) is defined as the inflammation of a colon diverticulum, often involving colic wall and pericolic fat. Conventional treatment of AUD includes antibiotics, usually ciprofloxacin and metronidazole, fasting, and fluid therapy. The aim of this study was to test the efficacy of a mix of three probiotic strains (Bifidobacterium lactis LA 304, Lactobacillus salivarius LA 302, Lactobacillus acidophilus LA 201; Lactibiane Iki®, Biocure [PiLeJe Groupe], Italy/PiLeJe Laboratoire, France) in association with conventional antibiotics in treating AUD compared to conventional antibiotics used alone. PATIENTS AND METHODS: We enrolled 84 (25M/59F mean age 61.5 ± 11.5 years) consecutive patients who came to the Emergency Department of the Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy, with a diagnosis of AUD confirmed by CT scan. After routine blood test and dosage of C-reactive protein (C-RP), patients were randomly divided into two groups: Probiotic group (42 patients, 10M/32F mean age 32.23 ± 10.3 years) was treated with ciprofloxacin 400 mg twice a day and metronidazole 500 mg three times a day for one week and simultaneously supplemented with the probiotic mix, 1 sachet twice a day for 10 days. Control group (42 patients, 15M/27F mean age 59.01 ± 11.3 years) received the same antibiotic treatment without the probiotic mix. All patients filled a daily Visual Analog Scale (VAS) for assessment of abdominal pain, with a range value from 0 (asymptomatic) to 10, and CRP value was determined on admission and at discharge. RESULTS: As regards abdominal pain, on Day 3, Group A showed a significant decrease of 4.06 points (51.4%) in VAS score compared to a decrease of 2.79 points (34.9%) in Group B. On Day 5 the decrease was of 6.3 points (80%) in Group A and of 4.85 points (61%) in Group B. VAS score was reduced by 7.59 points (96%) in Group A and 6.1 points (76%) in Group B on Day 7 +, and by 7.8 points (99%) in Group A and 7.2 points (90%) in Group B on Day 10. About inflammation, Group A showed a decrease in C-RP value of 64%, compared to a decrease of only 35% in Group B. We also observed that the duration of hospitalization was significantly shorter for patients in Group A: 89 h (3.7 days) in Group A vs. 101 h (4.2 days) in Group B (p=0.03). CONCLUSIONS: Our results indicated showed that the supplement with the probiotic mix of Bifidobacterium lactis LA 304, Lactobacillus salivarius LA 302, and Lactobacillus acidophilus LA 201 in combination with the standard antibiotic therapy for AUD reduced abdominal pain and inflammation significantly more than antibiotic treatment used alone. These findings could be due to the anti-inflammatory activity of the probiotic mix. Larger studies are needed to validate its use in the clinical practice.

Intestinal permeability in physiological and pathological conditions: major determinants and assessment modalities.

Intestinal permeability is the property that allows solute and fluid exchange between intestinal lumen and intestinal mucosa. Many factors could have major impact on its regulation, including gut microbiota, mucus layer, epithelial cell integrity, epithelial junction, immune responses, intestinal vasculature, and intestinal motility. Any change among these factors could have an impact on intestinal homeostasis and gut permeability. Healthy condition is associated to normal intestinal permeability whereas several intestinal and extra intestinal disease, like inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease among others, are associated to increased intestinal permeability. This review aims to synthesize determinants on intestinal permeability and to report methodologies useful to the measurement of intestinal permeability in clinical practice as well as in research settings.

Microbes and Alzheimer' disease: lessons from H. pylori and GUT microbiota.

OBJECTIVE: the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations. RESULTS: all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance. CONCLUSIONS: Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aß into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

Effect of Lactobacillus reuteri (DSM 17938) on methane production in patients affected by functional constipation: a retrospective study.

OBJECTIVE: Constipation is a common symptom affecting up to 30% of the Western population and is strongly associated with the presence of intestinal methanogens, which may directly inhibit motor activity. Two recent studies performed on adult and children affected by chronic constipation showed that the supplementation with L. reuteri significantly improved bowel movements. Whether its action is related to a decreasing of methane (CH4) production has never been tested. We have therefore designed a study aimed at testing this hypothesis. PATIENTS AND METHODS: Data of 20 adults (12 females, mean age 36.2 ± 13.7) affected by functional constipation, treated with the probiotic L. reuteri (DSM 17938) for 4 weeks who performed a H2/CH4 lactulose breath test (LBT) in our institution showing a CH4 production higher than 5 ppm were retrospectively analyzed from March to June 2015. Data recorded in their stool diary, reporting the frequency of defecations and stool consistency were also analysed, as well as the result of the LBT performed at the end of the treatment with L. reuteri. RESULTS: Four weeks of L. reuteri administration was associated with a significant decrease of mean CH4 production determined by LBT (from 20.8 ± 15 to 8.9 ± 8.6; p < 0.0001 CI 95%) and of AUC value (from 5101.5 ± 3571.13 to 2128.4 ± 2110.8; p < 0.0001 CI 95%). Moreover, a total disappearance of CH4 production (< 5 ppm at LBT) was observed in 11 patients, while, we did not observe any significant decrease of H2 production (from 13.2 ± 8.8 to 11.4 ± 7.3, CI 95%, n.s.). CONCLUSIONS: This study highlights for the first time the beneficial effect of Lactobacillus reuteri (DSM 17938) on chronic constipation, via a significant decrease of CH4 production.

Safety and efficacy of low doses of diclofenac on acute pain in the emergency setting.

Diclofenac is the most widely prescribed non-steroidal anti-inflammatory drug worldwide. Data collected during the last 10 years reported a dose-duration dependent increasing of cardiovascular risk associated with the use of diclofenac, supporting the evidence of a close association with the degree of COX-2 inhibition achieved in vivo. Nevertheless, the amplitude of cardiovascular risk associated with the administration of diclofenac at low doses and for the short-term duration is still poorly defined. Indeed, data did not show a clear and strong increasing of the risk for daily doses of 75 and of 50 mg. Concerning duration, while the identification of a safe temporal window is less defined, some studies reported an absence or a very low risk when the exposure is shorter than 30 days. Today, new low-dosage diclofenac formulations are available, allowing to reduce the systemic exposure, the degree of COX-2 inhibition and possibly the risk of occurrence of cardiovascular events. This is the reason why those new formulations may represent the ideal drug for the management of pain in the emergency setting.

Helicobacter pylori infection is associated with high methane production during lactulose breath test.

OBJECTIVE: Despite a growing interest toward the interplay between H. pylori and gastric microbiota, few data are available about this correlation. The aim of this study was to explore the relationship between H. pylori infection and gas production during lactulose breath test. MATERIALS AND METHODS: Data of patients undergoing both 13C-urea breath test (UBT) and lactulose breath test (LBT) under standard conditions in our GI unit were retrospectively analyzed. GI symptoms, such as dyspepsia, bloating, abdominal pain/discomfort, and epigastric pain on an eleven-point scale were also analyzed and correlate with the results of those tests. H2 and CH4 were calculated using the trapezoidal rule; a considerable CH4 production was defined by AUCCH4 ≥1200 ppm*4h. Statistical analyses were performed with Fisher's exact test and independent samples Mann-Whitney test. RESULTS: Data of 136 patients during a period of time of 3 months were analyzed. 36 patients (26.5%) showed a positive UBT. We do not find any difference as regards age, sex, symptom complaints, and small intestinal bacterial overgrowth between HP negative and positive patients. A greater methane production was observed in infected rather than non-infected patients (47.2% vs. 26% respectively, p=0.02). Furthermore, 25% infected and 10% non-infected produced greater amounts of CH4 compared to H2, resulting in a AUCCH4/AUCH2 ratio >1 (p=0.046). CONCLUSIONS: This study shows for the first time, a significant association between H. pylori infection and methane production, suggesting that H. pylori might influence gut microbiota composition. Further studies are needed to clarify mechanisms underlying this phenomenon.

High dose amoxicillin-based first line regimen is equivalent to sequential therapy in the eradication of H. pylori infection.

OBJECTIVE: Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy. PATIENTS AND METHODS: We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed. RESULTS: Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (p<0.01), while no significant differences were observed in HD-LCA group compared to LACT (p=ns). Compliance and occurrence of adverse effects were similar among groups. CONCLUSIONS: High-dose amoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage.

A bedside test for Clostridium Difficile infection: an Emergency Department use. Preliminary results.

OBJECTIVE: Clostridium Difficile (CD) infection is a severe cause of diarrhea in patients with prolonged hospitalization and/or previously treated with antibiotics. CD's A and B toxins are responsible for either diarrhea or septical status as well as other complications including toxic megacolon. Toxins isolation, usually performed by a central microbiological laboratory (CML), is mandatory for the final diagnosis of the disease. The clinical suspect of CD infection (CDI) results in the isolation of the patients, until the fecal test does not exclude the disease. Positive patients need to maintain isolation and start a specific antibiotic therapy. The aim of this study was to verify the sensitivity and specificity of a rapid test for the diagnosis of CDI. PATIENTS AND METHODS: We enrolled 20 (13F/7M, mean age 70 ± 12 yrs) consecutive pts who accessed the Emergency Department (ED) with diarrhea and a clinical suspect of CDI. An immune-enzymatic bedside test (Beta Dignostici, Messina, Italy) for the detection of GDH, toxin A and B of CD was used. The results of this test were then compared to the CML one's, on the same patient. RESULTS: 6 patients resulted positive to the bedside test compared to 7 of CML test (86% of concordance). In this patient, the bedside test showed a strong positivity for GDH without signs of toxin, meanwhile the CML test revealed the toxins. Possibly, the lower toxins concentration in this patient was responsible for such discordance. Both tests showed a full concordance for negative patients. Another interesting finding is that the bedside test provides results in only 5 minutes, compared to several hours (even 48) of CML test. CONCLUSIONS: The bedside test is a rapid and affordable tool for rapid diagnosis of CD infection especially in a ED where the positivity of the test affects either hospitalization or treatment.

Methane intestinal production and poor metabolic control in type I diabetes complicated by autonomic neuropathy.

AIM: At the state of art it's unknown the correlation between diabetes and lower gastrointestinal disorders. Some studies show a significantly higher prevalence of small intestinal bacterial overgrowth in patients with type I diabetes in particular complicated by autonomic neuropathy. No data exists about gastrointestinal methane production in patients with diabetes and autonomic diabetic neuropathy. The aim of this paper was to evaluate the correlation of small intestinal bacterial overgrowth and gastrointestinal methane production with metabolic control and daily insulin requirements in patients with type 1 diabetes and. autonomic diabetic neuropathy. METHODS: Thirty subjects with type 1 diabetes and autonomic diabetic neuropathy were underwent hydrogen and methane lactulose breath test (LBT) to evaluate the presence of small intestinal bacterial overgrowth (double peak of hydrogen) and methane production. The metabolic control was evaluated through the glycated hemoglobin and the daily insulin requirement (calculated as ratio between total insulin units in a day and body weight). Methane producers were treated with metronidazole (500 mg bid for 10 days) and perform a LBT 8 weeks after the end of therapy RESULTS: Eight over thirty patients (26.6%) met the diagnostic criteria for small intestinal bacterial overgrowth. 11/30 patients (36%) were methane-producers (mean baseline value 16.37 ± 13.01 ppm; mean peak 26.62 ± 11.41 ppm); interestingly this subset of patients showed a worse glycemic control (mean HbA1c 8.16 ± 0.9% vs. 7.49 ± 0.8%, P<0.05). After metronidazole therapy 7/11 (63.3%) reduced CH4 production and they showed a mean HbA1c significantly lower than corresponding value before antibiotic therapy (7.63 ± 0.7% vs. 8.25 ± 0.8%). CONCLUSION: Our study showed for the first time a possible role of CH4 production in metabolic control. In particular, the most interesting data is that an increased values of HbA1c seems to be related to a gut CH4 production as confirmed by its significant improvement after eradication therapy. We are not yet able to determine whether poor glycemic control is the cause or the consequence of the selection of methanogenic flora.

cDNA-microarray analysis as a new tool to predict lymph node metastasis in gastric cancer.

BACKGROUND: The aim of the present study was to investigate whether microarray gene expression analysis can be used to predict lymph node status in gastric cancer. METHODS: Twenty-nine patients undergoing gastrectomy for cancer were enrolled and subdivided according to the pathologic nodal involvement of their disease (N+ vs. N0). Molecular profiling was performed by cDNA microarray on tumor tissue and healthy mucosa. Data were processed to identify differently expressed genes. Selected genes were categorized with gene ontology. RESULTS: Compared to healthy gastric mucosa, 52 genes were differently expressed in N+ patients, and 50 genes in N0 patients. Forty-five genes were similarly regulated in N+ and N0 patients, whereas 12 genes were differently expressed between N+ and N0 patients. Seven genes were exclusively expressed in N+ patients: Egr-1 was upregulated; Claudin-18, AKR1C2, Cathepsin E, CA II, TFF 1, and progastricsin were downregulated. Five genes were exclusively expressed in N0 patients: Complement C5 receptor 1, PLA2/VII, and MMP- 9 were upregulated; MAO-A and ID-4 were downregulated. CONCLUSIONS: Microarray analysis could be a valuable tool to identify genes associated with lymph node metastasis in gastric cancer. This technique could improve the selection of patients with locally advanced disease who are candidates for extended lymph node dissection, multimodal treatment options, or alternative therapeutic strategies.