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.

Endoscopic management of obesity: Impact of endoscopic sleeve gastroplasty on weight loss and co-morbidities at six months and one year.

INTRODUCTION: Endoscopic sleeve gastroplasty (ESG) is one of the new minimally invasive endoscopic treatments aimed at inducing weight loss. Its effectiveness in terms of weight loss is proven. Gastric volume reduction and delayed gastric emptying are the mechanisms that drive weight loss. However, potential benefits for co-morbidities in relation to weight loss after ESG are still being investigated. This study aims to evaluate the effect of ESG procedures on major obesity-associated co-morbidities, and on some biological parameters. PATIENTS AND METHODS: This is a series of consecutive cases from a prospective observational study carried out in a specialized center that follows a standardized care pathway for the multimodal management of obesity. Patients who have undergone ESG with endoscopic and laboratory follow-up at six and twelve months after this intervention were included in the study. Prospectively recorded data on weight loss, co-morbidities and laboratory parameters at six and twelve months after surgery was analyzed retrospectively. Changes in body mass index (BMI), absolute weight loss (AWL), percent of excess weight loss (%EWL) and percent total weight loss (%TWL) were assessed at six and twelve months. Reduction in various obesity-related co-morbidities (arterial hypertension [AHT], type 2 diabetes mellitus [T2DM], gastroesophageal reflux disease [GERD], obstructive sleep apnea syndrome [OSAS] and dyslipidemia was also evaluated at six and twelve months. Changes in blood glucose, liver function tests and lipid blood tests were also analyzed at six and twelve months. RESULTS: From October 2016 to July 2021, 99 of the 227 patients who underwent ESG in our unit (43.6%) subsequently underwent a complete endoscopic and laboratory follow-up at six and twelve months. The initial BMI was 42.7±7.8kg/m2 and age was 45±12.7 years. Seventy-four patients (74.8%) were female. Total weight loss (%TWL) and excess weight loss (%EWL) were 16.6±7.4% and 43.3±21.2%, respectively, at six months, 16.6±9.6% and 42.9±25.6%, respectively, at one year. At six and twelve month follow-up, a statistically significant reduction was observed for the rates of T2DM (30.8 and 32.7%), hypertension (18.4 and 22.1%), GERD (28 and 25.7%), OSAS (15.8 and 25.5%) and dyslipidemia (69.2 and 77.2%) (P<0.001). A statistically significant difference was found in the reduction in blood glucose between the pre-operative period and six months post-operatively (P<0.01) and between the pre-operative period and twelve months post-operatively (P<0.01). The reduction in triglycerides and total cholesterol between the pre-operative values and at six months was statistically significant (P<0.01) as was the reduction at twelve months (P<0.01) (P=0.017). For liver function tests, the reduction in AST was statistically significant at six and twelve months after ESG (P=0.048) (P=0.048) as was ALT (P<0.01) (P<0.01) respectively. From October 2016 to July 2021, of the 227 patients who underwent ESG, 99 (43.6%) had follow-up gastro-duodenoscopy at 6 and 12 months. %TWL and %EWL were respectively 16.6±7.4% and 43.3%±21.2 at 6 months, 16.6±9.6% and 42.9±25.6% at one year. Statistically significant reduction rates at 6 and 12 months were observed in T2DM (30.8 and 32.7%), AHT (18.4 and 22.1%), GERD (28 and 25.7%), OSAS (15.8 and 25.5%) and dyslipidemia (69.2 and 77.2%) (P<0.001). Moreover, glycemic levels were statistically significantly reduced between the pre-operative period and 6 months post-operative (1.11±0.22mg/L vs. 1.01±0.17mg/L, P<0.01), and between the pre-operative period and 12 months post-operative (1.11±0.22mg/L vs. 1.06±0.32mg/L, P<0.01). A statistically significant reduction was also observed in triglycerides and total cholesterol levels at 6 months (1.52±0.74mmol/L vs. 1.14±0.52mmol/L, P<0.01) (1.94±0.4mmol/L vs. 1.85±0.36mmol/L, P<0.01) and at 12 months (1.52±0.74mmol/L vs. 1.18±0.67mmol/L, P<0.01) (1.94±0.4mmol/L vs. 1.82±0.39mmol/L, P=0.017) and in AST (27.2±11.7 IU/L vs. 23.7 IU/L; P=0.048) (27.2±11.7 IU/L vs. 24.7±14.65 IU/L, P=0.048) and ALAT levels (34±21.32 IU/L vs. 22.3±10.4 IU/L, P<0.01 and 34±21.32 IU/L vs. 27.07±25 IU/L, P<0.01) at 6 and 12 months after ESG, respectively. CONCLUSION: ESG is a well-tolerated and safe surgical procedure that is effective in terms of weight loss and reduction of obesity-related co-morbidities at six months and one year. This procedure could thus be adopted on a broader clinical scale and be more widely promoted as an effective treatment for morbid obesity.

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.

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.

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.

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.

Cannabis-induced acute pancreatitis: a case report with comprehensive literature review.

OBJECTIVE: Cannabis is an illegal drug that has been under the spotlight in recent years, due to its vast array of effects on different biological systems. The role of cannabis has been investigated in the management of pain in acute pancreatitis (AP), even though some studies suggest that it may have a causative effect in this pathology and could be considered the underlying etiology in some cases of idiopathic AP. In this case report, we discuss the case of a young man who presented with three different episodes of AP, with apparently no significant history of alcohol and drug consumption, and with no evidence of a biliary, genetic or, autoimmune etiology. During the third episode, in which he had developed a voluminous pseudocyst, treated trough ultrasound (EUS)-guided drainage, he admitted consumption of cannabis daily. The Naranjo score resulted to be 6 (confirming the possible causality), and it was suggested to the patient to avoid cannabis consumption. Since then, he did not develop any other AP episodes. In summary, cannabis should be considered among the possible AP etiologies, as its causative identification and interruption may significantly improve the course of several idiopathic APs.

Beware of the dog - Capnocytophga Canimorsus septic shock: a case report.

Capnocytophaga canimorsus is a Gram-negative rods frequently isolated as commensal in the saliva of pets that can be transmitted to humans. We report a case of septic shock caused by this pathogen. A 78-year-old man affected by diabetes and hypertension was admitted for fever in our Emergency Department. He reported fever (37.7°C) with normal values of blood pressure, heart rate and saturation of oxygen. Laboratory studies showed increased values of procalcitonin and normal white-cell level. Blood cultures were collected and an empirical antibiotic therapy was started. He reported six days earlier a bite of a dog at the right hand. During the following days the patient presented a deterioration of clinical conditions with fever, asthenia and comparison of petechial lesions. C. canimorsus was isolated from blood cultures. He was treated with fluids and appropriate antibiotic therapy with a full recovery. Dog wounds are frequent minor injuries with an underestimated worldwide incidence because only few patients develop complications. C. canimorsus could be an emerging cause of sepsis, also in immunocompetent patients. The current understanding of risk factors for C. canimorsus associated sepsis and a prompt approach to anamnesis and treatment of early stage injuries, could have a considerable medical outcome.

Clinical assessment and management of severe acute pancreatitis: a multi-disciplinary approach in the XXI century.

Acute pancreatitis (AP) is the most common gastrointestinal disorder requiring hospitalization, with a high rate of morbidity and mortality. Severe AP is characterized by the presence of persistent organ failure involving single or multiple organs. Clinical evolution, laboratory and radiological assessment are necessary to evaluate the prognosis and inform the management of AP. The onset of severe AP may be classified in two principal phases. The early phase, during the first week, is characterized by the activation of the auto-inflammatory cascade, gut dysbiosis, bacterial translocation, and the down-regulation of immune responses. The late phase is characterized by the development of local and systemic complications. Several old paradigms have been amended in the management of AP patients, such as the indication of nutrition, the use of antibiotic therapy, pain control strategies, and even the use of surgery. Real world evidence has shown that in the majority of cases a step-up approach is most effective. In this review, we discuss the clinical assessment and improvements to the management of patients with severe AP in a high volume center where a multi-disciplinary approach is performed.

Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.

Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.

Inflammation as a mediator of the association between osteoporosis and hearing loss in older subjects: a population-based study.

OBJECTIVE: Due to the aging of populations, the prevalence of hearing loss and osteoporosis is increasing. Previous studies have found an association between these conditions. Nevertheless, the pathophysiologic pathway of such an association has not yet been established. The present study aimed at evaluating the association, if any, of hearing loss with osteoporosis in an older unselected population, and whether this association varied according to inflammatory status. PATIENTS AND METHODS: We assessed the association of osteoporosis with a self-reported hearing loss in all 310 subjects aged 75+ living in Tuscania (Italy), without exclusion criteria. Bone density was assessed by calcaneal quantitative ultrasound; osteoporosis was defined as a T-score ≤ -2.5 Standard Deviation. RESULTS: Hearing loss was associated with osteoporosis (OR = 1.84, 95% CI = 1.03-3.28; p = 0.40) in multivariable logistic regression analysis, after adjusting for potential confounders. Analysis of the interaction term indicated that this association varied according to the erythrocyte sedimentation rate, ERS (p = 0.030), and high-sensitivity C reactive protein, hs-CRP (p = 0.017) but not sex (p = 0.832). Of notice, this association was significant only for higher levels of inflammatory parameters (OR = 2.82; 95% CI = 1.15-6.90; p = 0.023 for the higher ERS tertile; and OR = 3.81; 95% CI = 1.36-10.63; p = 0.011 for the higher hs-CRP tertile vs. lower tertiles). CONCLUSIONS: Hearing loss is associated with osteoporosis in community dwelling elderly. Such an association seems to depend upon higher inflammation levels.

The association of pancreatic cystosis and IPMN in cystic fibrosis: case report and literature review.

Pancreatic cystosis is a rare presentation of cystic fibrosis involving pancreatic gland. To date, only very few cases of pancreatic cystosis have been described in literature. Pancreatic cystosis may begin during the second decade of life and is the rarest presentation of cystic fibrosis. This disease is characterized by the presence of multiloculated cysts without ductal system communication of different sizes in all the pancreatic tissue. Herein, we report a case of a young woman affected by cystic fibrosis that was admitted to our Pancreatic Centre to evaluate a picture of diffuse multiloculated pancreatic cysts. After magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) assessment, we perform the diagnosis of the concomitant presence of the rare condition of pancreatic cystosis with Branch Duct-Intraductal Papillary Mucinous Neoplasm (BD-IPMN). To our knowledge, this is the first reported case of a cystic fibrosis patient with the combination of pancreatic cystosis and IPMN.

Uptodate in the assessment and management of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal Papillary Mucinous Neoplasms (IPMNs) are the most common cystic tumors of the pancreas and are considered premalignant lesions. IPMNs are characterized by the papillary growth of the ductal epithelium with rich mucin production, which is responsible for cystic segmental or diffuse dilatation of the main pancreatic duct (MPD) and/or its branches. According to the different involvement of pancreatic duct system, IPMNs are divided into main duct type (MD-IPMN), branch duct type (BD-IPMN), and mixed type (MT-IPMN). IPMNs may be incidentally discovered in asymptomatic patients, particularly in those with BD-IPMNs, when imaging studies are performed for unrelated indications. The increase in their frequency may reflect the combined effects of new diagnostic techniques, the improvement of radiologic exams and progress in the recognition of the pathology. MD-IPMNs present a higher risk of malignant progression than BD-IPMNs; as a consequence, all the guidelines strictly suggest the need of surgery for MD- and MT- IPMNs with MPD > 10 mm, while the management of BD-IPMNs is still controversial and depends on several cysts and patients features. The choice between non-operative and surgical management depends on the distinction between benign and invasive IPMN forms, assessment of malignancy risk, patient's wellness and its preferences. This manuscript revises the different guidelines for the management of IPMNs that have been published in different world countries: the international (Sendai 2006 and Fukuoka 2012), the 2013 European, the 2014 Italian, and finally the 2015 American guidelines. In summary, this review will integrate the recent insights in the combination of diagnostic techniques, such as Magnetic Resonance Imaging (MRI) and endoscopic ultrasound (EUS), pathology classification, and management of IPMNs.

Enhancement patterns of intrahepatic mass-forming cholangiocarcinoma at multiphasic computed tomography and magnetic resonance imaging and correlation with clinicopathologic features.

OBJECTIVE: Incidence of intrahepatic mass-forming cholangiocarcinoma (IMCC) is increasing worldwide, especially in patients with chronic liver disease. The small and the histologically well-differentiated IMCCs in chronic liver disease could be arterially hypervascular lesions with/without washout on computed tomography (CT) and magnetic resonance imaging (MRI), mimicking typical hepatocellular carcinoma (HCC). The aim of this work is to evaluate contrast enhancement (CE) patterns of IMCCs at quadri-phasic multidetector CT (4-MDCT) and MRI, using imaging-clinicopathologic correlation. PATIENTS AND METHODS: The 4-MDCT and MR images of 56 histologically confirmed IMCCs were retrospectively evaluated for tumor morphology and enhancement features. Enhancement pattern was defined according to the behavior of the nodule in arterial (AP), portal venous (PVP) and equilibrium phases (EP), and dynamic pattern was described according to enhancement progression throughout the different phases. Arterial and dynamic enhancement patterns were correlated with chronic liver disease, tumor size and histological differentiation. RESULTS: Most of the nodules were peripherally hyperenhancing (50%) on AP, and partially hyperenhancing on PVP (67.9%) and EP (80.3%). Forty-six (82.1%) IMCCs showed progressive CE, 7 (12.5%) stable CE and 3 (5.4%) wash-out. In normal liver there were 34 nodules with progressive and 3 with stable CE, whereas in chronic liver disease there were 12 IMCCs with progressive, 4 with stable and 3 with washout pattern (p = 0.01); IMCCs with progressive CE were more differentiated than IMCCs with stable CE and wash-out (p = 0.02). CONCLUSIONS: The most prevalent enhancement pattern of IMCCs was arterial rim enhancement followed by progressive and concentric filling. The stable and the washout patterns were more frequent in poorly differentiated IMCCs. Contrast washout was observed only in IMCCs emerging in chronic liver disease with a risk of misdiagnosis with HCC.

Bone age progression during five years of substitutive therapy for the induction of puberty in thalassemic girls--effects on height and sitting height.

UNLABELLED: It is known that in thalassemic patients there is a disproportion between lower and upper segments whose causes have not yet been identified. We evaluated whether the administration of estrogens to induce puberty in hypogonadic thalassemic girls caused an inappropriate acceleration of bone maturation and whether this had a negative influence on final and sitting height. MATERIALS AND METHODS: Twelve thalassemic patients with spontaneous puberty (Group A) and seven patients with hypogonadism (Group B) were studied. The mutations of the beta gene were identified by DNA analysis. We took into account four observations, ranging from the onset of spontaneous puberty in group A or the start of substitutive therapy in group B, to 5 years later. At each observation we considered: chronological age (CA), bone age (BA), height (Ht) expressed in cm and as standard deviation score (HtSDS) calculated with respect to CA (HtSDSCA) and BA (HtSDSBA), growth spurt, sitting height, expressed as SDS (SH-SDS), and height gain (HG). The delta BA and delta CA were calculated between the first and the final observation values to evaluate the bone age acceleration (delta BA/delta CA). RESULTS: No acceleration of BA was noted. delta BA/delta CA was 0.98 +/- 0.1 in group A and 0.89 +/- 0.1 in group B (p > 0.05). All patients in group B had the most severe form (beta degree/beta degree) of thalassemia. During the final observation, SH-SDS was -1.43 +/- 1.2 and -2.9 +/- 0.6 in group A and B respectively (p < 0.002), while no difference between the two groups for HtSDSCA and HtSDSBA was observed. HG was greater in group A than in group B (17.7 +/- 5.4 cm vs 10.8 +/- 5.2 cm) (p < 0.002), such as the spurt 8.6 +/- 1.4 cm (group A) and 6.1 +/- 2.6 cm (group B) (p < 0.05). CONCLUSIONS: Girls with hypogonadism did not show an inappropriate acceleration of BA, as they reached near final height similar to girls with spontaneous puberty. The auxological parameters showed a more severe body disproportion with the prevalence of the lower segment in the hypogonadic girls. This could be explained by a higher degree of bone marrow hyperplasia related to the most severe form of thalassemia and a higher blood consumption. As a consequence, damage at the vertebral level might determine an inability of the bone tissue to respond to estrogens. We suggest beginning estrogen therapy earlier in order to obtain better truncal growth.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy.

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.

Longitudinal monitoring of bone mineral density in thalassemic patients. Genetic structure and osteoporosis.

The changes in bone mineral density (BMD) measured by single photon absorptiometry (SPA) using two observations conducted over a period of 2 years were examined in 54 thalassemic subjects [30 F(A) and 24 M(B)] with a chronological age ranging from 2.6 to 22.6 years and in 27 sex- and age-matched controls (C). Each category (A, B and C) was divided into three groups according to pubertal signs: pre-pubertal subjects (A1, B1 and C1); peri-pubertal subjects (A2, B2 and C2) and pubertal subjects from the first observation (A3, B3 and C3). Furthermore, each group of patients was divided into sub-groups on the basis of haematological phenotypes, those with a more severe form were called beta0/beta0 while those with other forms were called "others". The most significant findings were the following: the presence of a more severe reduction of the bone mineral density in patients with the beta0/beta0 phenotype than in patients with the "others" phenotype; patients with hypogonadism corresponded to the beta0/beta0 phenotype, while those with spontaneous puberty corresponded to the "others" phenotype. In conclusion, since puberty and the degree of bone mineral density are related to the haematological phenotype, puberty (spontaneous or induced) positively influences the bone mineral density only at the start of puberty, while subsequently, the degree of osteoporosis is the expression of widespread and chronic systemic damage due to the haematological phenotype.