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Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder characterized by a defective NADPH oxidase complex leading to an impaired respiratory burst and defective killing of pathogens by phagocytes. The most common type of CGD is caused by hemizygous mutations of the CYBB gene on the X chromosome encoding the gp91phox subunit. It usually affects males, yet heterozygous females may rarely manifest clinical signs of the disease due to skewed X chromosome inactivation in leukocytes . Despite advances in gene therapy, hematopoietic stem cell transplantation (HSCT) remains the main definitive treatment. Older patients, however, are at greater risk of HSCT-related complications and mortality and may require a specific approach.

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.

Purpose This study was intended to determine whether a simulation-based education addressed to physicians was able to increase the proportion of hospitalized elderly with atrial fibrillation prescribed with oral anticoagulants (OACs) compared with the usual practice. Methods We conducted a cluster randomized trial (from April 2015 to September 2018) on 32 Italian internal medicine and geriatric wards randomized 1:1 to intervention or control arms. The physicians of wards randomized to intervention received a computer-based e-learning tool with clinical scenarios (Dr Sim), and those of wards randomized to control received no formal educational intervention. The primary outcome was the OAC prescription rate at hospital discharge in the intervention and control arms. Results Of 452 patients scrutinized, 247 were included in the analysis. Of them, 186 (75.3%) were prescribed with OACs at hospital discharge. No difference was found between the intervention and control arms in the post-intervention phase (odds ratio, 1.46; 95% confidence interval [CI], 0.81-2.64). The differences from the pre- to post-intervention phases in the proportions of patients prescribed with OACs (15.1%; 95% CI, 0%-31.5%) and with direct oral anticoagulants (DOACs) (20%; 95% CI, 0%-39.8%) increased more in the intervention than in the control arm. Conclusions This simulation-based course did not succeed in increasing the rate of elderly patients prescribed with OACs at hospital discharge compared with the usual practice. Notwithstanding, over time there was a greater increase in the intervention than in the control arm in the proportion of patients prescribed with OACs and DOACs. Trial Registration ClinicalTrials.gov identifier: NCT03188211.

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This is the first study investigating the effect of oxycodone in polytrauma patients. The management of pain in polytrauma patients has become a very relevant issue. Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most used drugs in polytrauma patients, even though their use is associated with an increased hemorrhagic risk. Previous studies have demonstrated the efficacy of oxycodone for the treatment of acute pain. The aim of this study was to assess the efficacy of oxycodone administration in polytrauma patients, with minor injuries.15 polytrauma patients (10 males, mean age 40 +/- 13 years; 5 females, mean age 49 +/- 26 years) were admitted to the Emergency Department of the Catholic University, A. Gemelli Hospital in Rome, Italy. All patients underwent physical examination, FAST ultrasound, total body CT scanning and blood tests. Three patients had multiple costal fractures, three had pelvic fracture, two had tibial fracture, five had vertebral fractures, one patient had clavicle fracture and ulnar fracture, one patient a severe trauma of the left leg, which required amputation. Five patients also reported minor head trauma, with a Glasgow Coma Score (GCS) 15. All patients reported abdominal trauma, while none of them had severe thoracic or kidney damage. Patients with head trauma also underwent a second CT head scanning 12 hours after admission, which excluded the occurrence of cerebral damage. All patients were then treated with oral administration of oxycodone 10 mg two times per day (bid) for 3 days. Pain intensity, before and after the administration of oxycodone, was evaluated using a scale ranging from 0 to 10.The mean pain score at admission was 8 +/- 0.7. All patients reported significant pain improvement after the administration of oxycodone (8 +/- 0.7 vs 1.8 +/- 0.9; p0.0001). A dosage increase of oxycodone from 20 to 40 mg bid was required in only one patient with a clavicle fracture. The main side effects were light-headache (5 patients), constipation (4 patients) and nausea (3 patients).These data indicate that oxycodone is a safe and effective drug for pain relief in polytrauma patients without severe thoracic, kidney or brain damage.

Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion. Wernicke's encephalopathy has a causative association with alcoholism but recently there has been an increased prevalence also in other clinical conditions. In literature potentially fatal Wernicke's encephalopathy onset in an advanced achalasia has been previously reported only once. We describe for the first time an improvement of achalasic symptoms in a young patient affected by end-stage achalasia and anorexia nervosa (coming from ineffective Heller-Dor myotomy) after vitamin B1 supplementation. This case report suggest a potential positive impact of B1 supplementation on end-stage achalasic patients and requires systematic studies to confirm this observation.

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.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.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 (p0.01), 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.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.

Aims of the study were to assess the effects of rifaximin treatment on small intestinal bacterial overgrowth (SIBO) prevalence and gastrointestinal symptoms.Fifty (50) irritable bowel syndrome (IBS) children were consecutively enrolled. All subjects underwent lactulose hydrogen/methane breath test (LBT) to assess SIBO before and one month after the treatment with rifaximin 600 mg daily for one week. All IBS patients filled out a Visual Analogic Scale (VAS) to assess and score gastrointestinal symptoms (abdominal pain, constipation, diarrhoea, bloating, flatulence) at baseline and one month after treatment.The prevalence of abnormal LBT in patients with IBS was 66% (33/50). LBT normalization rate was 64% (21/33). Compliance was excellent, and no relevant side-effects were observed during treatment. VAS score was significantly higher in IBS patients with abnormal LBT than SIBO negatives, and strongly improved after successful treatment.Rifaximin was effective and safe in SIBO treatment and IBS symptoms improvement in childhood. Double blind placebo-controlled interventional studies are warranted to verify the real impact of SIBO on gastrointestinal symptoms in children with IBS.

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.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.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%; p0.05; 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.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.

Several studies have demonstrated that Helicobacter pylori (H. pylori) eradication does not affect metabolic control in diabetic patients. The prevalence of H. pylori infection and reinfection rate in adult diabetic patients seems to be higher than in controls.To evaluate the reinfection rate of H. pylori three years after a standard eradicating treatment and the late effect of eradication upon metabolic control in young diabetic patients.We enrolled 75 diabetic patients and 99 controls, from previous our studies in which we had evaluated H. pylori infection. In all subjects we re-evaluated the presence of H. pylori by means of 13C-Urea Breath Test, metabolic control and the prevalence of gastrointestinal symptoms. The effect of age, sex and socio-economic factors on H. pylori reinfection were also evaluated.The prevalence of H. pylori infection was higher in diabetic patients (17/69, 24%) than in dyspeptic controls of similar age, gender and socio-economical status after three years of follow-up. The reinfection rate was higher in diabetic patients than in controls. Multivariate analysis confirmed that age and socio-economical status were independently associated with H. pylori reinfection.Young patients with diabetes present a higher risk of H. pylori gastric reinfection than controls. In addition, age and mean annual income are associated with reinfection.

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).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.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 (p0.01). 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 (p0.0001). Tilactase was significantly more effective than LR in reducing both mean peak hydrogen excretion and mean clinical score.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.

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N=221), errors in the prescribed doses were the most frequent cause of inappropriate use (N=55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

Background/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence of celiac disease in patients with a positive H2-lactose breath test compared to a control group. Methods: This retrospective study included 54 patients (15 males/39 females; mean age 37.8 ± 7 years) from southern Italy, referred to the Gastroenterology Unit for bloating and diarrhea after the introduction of milk or dietary lactose. They had a positive H2-lactose breath test and a negative H2-glucose breath test. 50 blood donors were drawn from a similar population, matched for sex and age, and enrolled as a control group. All patients were screened for possible celiac disease by measuring the serum level of IgA antibodies to endomysium, anti-transglutaminase and total IgA. Patients positive for at least one of these markers were submitted to upper gastrointestinal endoscopy. Results: None of the patients had a IgA deficiency. 24% of the patients showed positivity of celiac disease antibodies compared to 2% in the control group (p < 0.001). Histologic samples of these patients showed villous atrophy (53.8% Marsh type IIIa, 38.4% Marsh IIIb, and 7.6% with Marsh type IIIc) confirming the celiac disease, while in the control subjects duodenal biopsies were normal. Conclusions: A high prevalence of celiac disease was observed in patients with a positive H2-lactose breath test compared to healthy controls. In these subjects lactase deficiency seems to be the only manifestation of celiac disease. We suggest serologic screening for celiac disease in all patients with a positive H2-lactose breath test before beginning a milk-exclusion diet.

Background: During winter 2009 we treated with prolonged corticosteroid infusion eight consecutive patients affected by H1N1-virus infection and severe pneumonia. The most severe patient was a previously healthy 30-year-old man admitted to hospital because of bilateral pneumonia and severe acute respiratory failure. Method: H1N1-virus infection was detected by broncho-alveolar lavage performed on day 1. After some days following admission the patient was still in a life-threatening state, not responding to oseltamivir, protective mechanical ventilation and veno-arterial extracorporeal membrane oxygenation (ECMO). Results: The addition of methylprednisolone infusion at a stress dose (1 mg/kg/24 h) as rescue therapy significantly and rapidly improved the clinical condition. Weaning from ECMO and invasive mechanical ventilation was possible within a relatively few days. Conclusion: According to the literature reports more than 34% of H1N1-virus severe infections were treated with corticosteroids. This report and our experience may suggest a possible life-saving use of corticosteroids at a stress dose in severely ill patients with an H1N1-virus infection that is not responding to the most advanced treatments.