High levels of mid-regional proadrenomedullin in ARDS COVID-19 patients: the experience of a single, Italian Center.

OBJECTIVE: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores. PATIENTS AND METHODS: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score). RESULTS: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%. CONCLUSIONS: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.

Case report of COVID-19 in an elderly patient: could SARS-CoV2 trigger myositis?

Though the exact etiology of autoimmune diseases still remains not completely known, there are various factors which are known to contribute to be trigger of autoimmune diseases. Viral infection is known to be among the other. It is known as the infection from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) can be an autoimmune trigger, so, we suppose that SARS-Coronavirus (SARS-CoV-2) could be as well. Several authors have highlighted the temporal consequence between SARS-CoV-2 and autoimmune diseases. In this case report we described a patient admitted for COVID-19 pneumonia with completely negative autoimmunity at admission who developed major pulmonary interstitial disease. During the hospitalization the weaning difficulties from oxygen led us to the repetition of autoimmunity pattern which became positive (both during hospitalization then after two months from dismission) with marked positivity for specific antibodies for myositis even after the patient's infectious healing. In the follow-up, the patient continued to have asthenia and muscle weakness despite steroid therapy. She is still in follow-up and will be further evaluated over time. Can we therefore think that in this case the development of autoimmunity can persist beyond the infectious phase and determine over time the development of a real autoimmune myositis?

Isolated immune thrombocytopenic purpura in a young adult Covid-19 patient.

OBJECTIVE: Patients with Covid-19 can have different symptoms, ranging from asymptomatic patients to various grades of respiratory failure, caused by typical interstitial pneumonia, cardiac involvement or neurological symptoms. PATIENTS AND METHODS: In April 2020, we focused our attention on a young woman with diffused purpura on her lower extremities, with no respiratory, cardiac or neurological symptoms. A complete blood analysis showed us a severe thrombocytopenia. We excluded other possible causes of thrombocytopenic purpura such as hematological (lymphocyte subsets), hepatological disease or splenomegaly. On autoimmune screening, we found Isolated immune thrombocytopenic purpura in a young adult Covid-19 patient positivity of anti-nuclear antibody (ANA) with a centrosome pattern and extractable nuclear antigens (ENA) and connective tissue disease screen resulted positive but none of the included specific antigens results positive, probably due to an aspecific antibody reaction. The wide variability of COVID disease presentation may be due to a personal different immune response to the virus. CONCLUSIONS: The immune response against the virus is crucial in the evolution and understanding of COVID-19 disease but it has still to be fully understood.

The first case of systemic lupus erythematosus (SLE) triggered by COVID-19 infection.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, SARS-CoV-2. The acute phase may be followed by a second phase actually not yet completely understood but probably associated to an autoimmune activation. At the moment is not possible to clearly define an association between immunological findings and pathological symptoms, however, this case report describes the case of a patient who following COVID-19 infection development autoimmune antibodies who persist in time longer than viral phase. Those antibodies can be responsible for the multi pathological clinical picture showed from our patient that, according to EULAR 2019 criteria, could be classified as systemic lupus erythematosus (SLE). SLE is probably one of the possible chronic rheumatologic diseases triggers by COVID-19 and this is the first case of SLE with vasculitis actually described in literature.

Severe acute dried gangrene in COVID-19 infection: a case report.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) related coagulopathy may be the first clinical manifestation even in non-vasculopathic patients and is often associated with worse clinical outcomes. CASE PRESENTATION: A 78 years old woman was admitted to the Emergency Unit with respiratory symptoms, confusion and cyanosis at the extremity, in particular at the nose area, hands and feet fingers. A nasal swab for COVID-19 was performed, which resulted positive, and so therapy with doxycycline, hydroxychloroquine and antiviral agents was started. At admission, the patient was hemodynamically unstable requiring circulatory support with liquids and norepinephrine; laboratory tests showed disseminated intravascular coagulation (DIC). During hospitalization, the clinical condition worsened and the cyanosis of the nose, fingers, and toes rapidly increased and became dried gangrene in three days. Subsequently, the neurological state deteriorated into a coma and the patient died. DISCUSSION: In severe cases, COVID-19 could be complicated by acute respiratory disease syndrome, septic shock, and multi-organ failure. This case report shows the quick development of dried gangrene in a non-vasculopathic patient, as a consequence of COVID-19's coagulopathy and DIC. CONCLUSIONS: In our patient, COVID-19 related coagulopathy was associated with poor prognosis.

Incidence, clinical features and management of acute allergic reactions: the experience of a single, Italian Emergency Department.

OBJECTIVES: Few data on the incidence, aetiology, clinical features and management of patients with acute allergic reactions presenting to the Emergency Department are currently available. The aim of the study was to report the annual experience of a single Italian adult Emergency Department about anaphylaxis. PATIENTS AND METHODS: This is a retrospective, case-based study of adult patients attending the Emergency Department in Alessandria, Italy, during the years 2009-2010. We evaluated the medical records of patients satisfying diagnostic codes involving acute allergic reactions. Incidence, demographic data, causative agents, clinical features, management and outcome were reported. RESULTS: 390 patients with acute allergic reactions were evaluated during the year, corresponding to 0.7% of all Emergency Department visits. Causative agents were recognized in 55.1% of patients and more commonly included drugs (26.9%), insects (14.8%) and foods (8.9%). Cutaneous features were the single most common clinical presentation although two or more clinical features were frequently reported (17.7%). Anaphylaxis was diagnosed in 4.6% of patients. After therapy and a period of monitoring, 92.8% of patients were discharged directly from the Emergency Department, 7.0% were admitted and one patient died, corresponding to a fatality rate of 0.2%. CONCLUSIONS: Acute allergic reactions are common diseases referring to our Emergency Department. In the half of cases a precipitant agent was identified and cutaneous and/or mucosal changes were often the first feature. Most patients were definitely treated and discharged but about 7.0% of patients required hospitalisation. Observation Unit and Intermediate Care Unit were essential for clinical management of these patients.

Diagnostic and prognostic significance of high sensitive troponin in chest pain.

BACKGROUND AND OBJECTIVES: Chest pain is one of the most frequent presenting complaints among patients arriving to the Emergency Department. In this population, the prevalence of acute coronary syndrome is about 25% instead that of acute myocardial infarction ranges from 5 to 15%. The diagnostic challenge for the emergency physician is the early rule-in or rule out of acute myocardial infarction within first few hours after chest pain presentation, particularly in those patients with normal or not significant electrocardiogram. EVIDENCE AND INFORMATION SOURCES: The current review is based on an analysis of most important clinical trials on this topic. STATE OF THE ART: The universal current guidelines established that the term "myocardial infarction" should be used when there is evidence of myocardial necrosis of ischemic origin, as documented by an increase of myocardial necrosis markers. Actually, cardiac troponins are considered the standard biomarkers for acute myocardial infarction diagnosis, because are more superior in sensitivity and specificity to the other available markers. PERSPECTIVES: More recently, high sensitive troponin assays have been developed, permitting the early measurement of very low concentrations. CONCLUSION: In this review, we analyzed the diagnostic and prognostic significance of these new high sensitive troponins in Emergency Department chest pain management.

The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: randomized trial.

BACKGROUND: Lactase enzyme supplements and probiotics with high beta-galactosidase activity may be valid treatment options for the lactose intolerance. Aim of this study was to assess whether supplementation with tilactase or Lactobacillus reuteri when compared to placebo affects hydrogen breath excretion and gastrointestinal symptoms in lactose intolerant patients during lactose breath test (H,-LBT). METHODS: Sixty lactose intolerant patients participated in the study and were randomized to three 20 patients-treatment groups: tilactase group (tilactase 15 minutes before control H2-LBT); placebo group (placebo 15 minutes before control H2-LBT); Lactobacillus reuteri group (LR) (LR b.i.d. during 10 days before control H2-LBT). The outcomes were LBT normalization rate, and influences of treatments on both mean maximum hydrogen concentration and clinical score. RESULTS: LBT normalization rate was significantly higher in tilactase and LR groups with respect to placebo. Tilactase was significantly more effective than LR in achieving LBT normalization (p <0.01). Both significant reduction of mean peak H2 excretion and improvement of the mean clinical score were observed in tilactase and LR groups after treatment with respect to placebo (p <0.0001). Tilactase was significantly more effective than LR in reducing both mean peak hydrogen excretion and mean clinical score. CONCLUSIONS: In lactose intolerants, tilactase strongly improves both LBT results and gastrointestinal symptoms after lactose ingestion with respect to placebo. Lactobacillus reuteri also is effective but lesser than tilactase. This probiotic may represent an interesting treatment option for lactose intolerance since its use is simple and its effect may last in the time after stopping administration.

Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole.

BACKGROUND AND OBJECTIVES: Few controlled trials on antibiotic therapy for small intestinal bacterial overgrowth are available at present. Aim of the study was to assess efficacy, safety and tolerability of rifaximin with respect to metronidazole for the treatment of small intestinal bacterial overgrowth. MATERIAL AND METHODS: We enrolled 142 consecutive patients with diagnosis of small intestinal bacterial overgrowth. Diagnosis of small intestinal bacterial overgrowth based on the clinical history and the positivity of glucose breath test. Patients were randomised to two 7-day treatment groups: rifaximin 1200 mg/day and metronidazole 750 mg/day. Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated. RESULTS: One drop-out was observed in rifaximin group. Five drops-out occurred in metronidazole group. The glucose breath test normalization rate was significantly higher in the rifaximin with respect to the metronidazole group (63.4% versus 43.7%; p < 0.05; OR 1.50, 95% CI 1.14-4.38). The overall prevalence of adverse events was significantly lower in rifaximin with respect to metronidazole group. DISCUSSION: Rifaximin showed an higher SIBO decontamination rate than metronidazole at the tested doses, both with a significant gain in terms of tolerability. Either the present study or recent evidencies suggest that rifaximin represents a good choice for the management of patients affected by SIBO.

Prevalence of small intestinal bacterial overgrowth in children with irritable bowel syndrome: a case-control study.

OBJECTIVE: To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in children affected by irritable bowel syndrome (IBS). STUDY DESIGN: Consecutive children affected by IBS according to Rome II criteria (n = 43) were enrolled at the Gemelli Hospital, Catholic University of Rome. The control population (n = 56) consisted of healthy subjects without IBS symptoms, similar to patients for age, sex, and social background. All subjects underwent lactulose/methane breath test (LBT) to assess small intestinal bacterial overgrowth. RESULTS: The prevalence of abnormal LBT result was significantly higher in patients with IBS (65%, 28/43) with respect to control subjects (7%, 4/56; OR 3.9, 95% CI 7.3-80.1, P < .00001). Patients with abnormal LBT showed a trend toward a worse visual analog scale score with respect to children with IBS without SIBO, but a significant statistical difference was observed only for bloating. CONCLUSIONS: Results from this study suggest a significant epidemiologic association between SIBO and IBS in childhood. Placebo-controlled interventional studies with antibiotics used to treat bacterial overgrowth are warranted to clarify the real impact of the disease on IBS symptoms.

New insights into the pathophysiology of IBS: intestinal microflora, gas production and gut motility.

Irritable bowel syndrome (IBS) is a complex disorder clinically characterized by abdominal pain and altered bowel habit. Its pathogenetic mechanisms are still incompletely known; genes, psychosocial factors, changes in gastrointestinal motility and visceral hypersensitivity are traditionally thought to play a crucial role in symptom generation. Recent studies have identified new additional factors that can interact with the established mechanisms. Dysregulation of brain-gut axis, gastrointestinal infection, low-grade infiltration and activation of mast cells in the intestinal mucosa with consequent release of bioactive substances, and altered serotonin metabolism are the emerging factors of IBS pathogenesis. Finally, modification of small bowel and colonic microflora and altered gas balance may be of relevance in at least some subgroups of IBS patients. New therapies can be developed only on the basis of a better understanding of the heterogeneous picture of the pathophysiology of IBS.

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome.

BACKGROUND: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. AIM: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. METHODS: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001). CONCLUSIONS: The present case-control study showed an epidemiological association between irritable bowel syndrome and small intestinal bacterial overgrowth. Placebo-controlled small intestinal bacterial overgrowth-eradication studies are necessary to clarify the real impact of small intestinal bacterial overgrowth on irritable bowel syndrome symptoms.

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. RESULTS: A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). CONCLUSIONS: In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth.

BACKGROUND: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. AIM: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. METHODS: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. RESULTS: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. CONCLUSIONS: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.

Sacroileitis and peripheral arthropathy associated with ulcerative colitis: effect of infliximab on both articular and intestinal symptoms.

Infliximab has been proven to be an effective therapy in a miscellany of rheumatic diseases and has been approved for the treatment of moderate-to-severe Crohn's disease with an inadequate response to conventional therapy and for the management of enterocutaneous fistulas. Data about the role of infliximab in ulcerative colitis are still controversial. Here, we report a case of a patient with sacroileitis and peripheral arthropathy associated with left-sided ulcerative colitis who achieved a sustained clinical remission after infliximab therapy.