Causes of hospitalisation before and after the 2009 L'Aquila earthquake.

On 6 April 2009, an earthquake struck L'Aquila. The San Salvatore Hospital was evacuated, and a field hospital was built. The study aimed to assess the epidemiologic impact of the earthquake through the analysis of patient population admitted to the field hospital during a 2-month period following the disaster. We retrospectively evaluated causes of hospitalisation and demographic data of patients admitted to (i) the Division of Internal Medicine and (ii) the Division of Emergency Medicine of the field hospital from 6 April, 2009 to 29 May, 2009. All data were compared with the admissions made at the same divisions of the San Salvatore Hospital during the same period of previous year. (i) Patient group (n = 102) and comparison group (n = 108). Mean patient age was higher, patients living in L'Aquila were more numerous, while mean length of stay was lower after than before the earthquake. Infectious diseases increased, while 'other' diseases decreased after the disaster both in admission and in discharge diagnoses. Gastroenterological diseases decreased with the earthquake but only in admission diagnoses. (ii) Patient group (n = 5255) and comparison group (n = 6564). Triage codes changed with the earthquake. Cardiovascular, psychiatric, gynaecological, infectious and chronic diseases increased, while pneumologic, gastroenterological, traumatic and 'other' diseases decreased after the quake. The number of hospitalised patients decreased with the tremor, while those discharged transferred to other hospitals and those who rejected hospitalisation increased. A natural disaster completely changes causes of hospitalisation in the Divisions of Internal and Emergency Medicine. These findings can be useful for the design of specific intervention programmes and for softening the detrimental effects of quakes.

Circadian rhythms of plasma atriopeptin, plasma renin activity and plasma aldosterone in patients with hepatorenal syndrome.

The etiology of hepatorenal syndrome (HRS) is still incompletely understood, but the atriopeptin-renin-aldosterone system plays an important role in its pathogenesis. Since this system presents a circadian rhythmicity, the aim of the study was to investigate the circadian rhythm in the circulating concentrations of atriopeptin (atrial natriuretic peptide, pANP), plasma renin activity (PRA) and plasma aldosterone (pA) in patients with HRS, compared with healthy controls. Venous blood samples were drawn during the span of a whole day and every two hours from a peripheral vein in 10 healthy subjects and in 10 patients with HRS. The circulating concentrations of pANP, PRA and pA were determined by radioimmunoassay. Statistical analysis was carried out by the "cosinor" method. The controls presented a significant (p < 0.05) circadian rhythm for each variable, whereas no rhythm (p > 0.05) was found in HRS patients. The pANP, PRA and pA rhythms were significantly (p < 0.05) different between the two groups, HRS patients having higher mean daily concentrations and larger circadian variations of pANP, PRA and pA than controls. Significant relations (p < 0.05) were demonstrated between the mean daily concentrations of pANP and PRA (r = 0.79), PRA and pA (r = 0.73) and PRA and pA (r = 0.76) in the controls; on the contrary, the HRS patients showed only a significant (p < 0.05) positive relation between pANP and PRA (r = 0.71). These results confirm the previous observation that the atriopeptin-renin- aldosterone system presents a well-defined circadian time structure in healthy subjects, while the HRS patients present a complete loss of the secretory sequentiality and of the circadian rhythm, with desynchronization of the whole system. This great upset in the temporal and functional organizations of the system could play an important role in promoting and/or in maintaining the hydro-electrolyte unbalance of HRS.

Plasma cell leukemia. A report on 11 patients and review of the literature.

OBJECTIVE: Plasma-cell leukemia (PCL) is considered the leukemic variant of multiple myeloma. The diagnosis is based on plasmocytosis exceeding 2,000/mm3 and any evidence of clonal plasma cell proliferation. There are two forms of PCL: the primary form occurring in patients without preceding multiple myeloma or monoclonal gammopathy of undetermined significance, and the secondary form arising as a late manifestation in patients with multiple myeloma. Aim of the study was to describe our series of PCL and to report the main clinical and laboratory findings from the largest series in the literature. METHODS: Review of all cases of PCL observed from 1976 to 1994 in our Medical Divisions. Med-line research of the largest (more than 5 cases reports) series of PCL from 1969 to 1994. RESULTS: Eleven cases of PCL were identified. We diagnosed 6 cases with primary PCL out of a total of 512 patients with monoclonal gammopathy (incidence, 1.2%), 4 cases of secondary PCL as terminal phase out of 220 patients with multiple myeloma (incidence, 1.8%), and 1 case of secondary PCL as evolution of monoclonal gammopathy of undertermined significance out of 226 cases (incidence, 0.4%). From our and literature review, that identified 203 cases of primary PCL and 157 cases of secondary PCL, the clinical and the laboratory features did not significantly differ between primary and secondary forms of PCL, whereas significant differences exist between the two forms regarding response to therapy and median survival. In our series, the mean survival was 14 months for primary PCL and 6.8 months for secondary PCL. Two of the 6 patients with primary PCL obtained a complete remission, with a duration of 28 and 23 months, respectively; only 1 patient with secondary PCL had a response to chemotherapy, with a remission of 6 months. CONCLUSION: Our observation and literature data indicate that PCL, both primary and secondary, is a very poor prognosis disease, that the response rate is higher with combination chemotherapy than single agents, and that primary PCL has a relatively better survival, since secondary plasma PCL usually shows resistance to any type of chemotherapy.

Prognostic value of Pugh's modification of Child-Turcotte classification in patients with cirrhosis of the liver.

The Child-Turcotte classification, as modified by Pugh et al., was recorded on diagnosis in 598 completely followed patients with cirrhosis of the liver. The variables that comprise the Pugh classification are ascites, encephalopathy, serum albumin, serum total bilirubin, and prothrombin time. The Pugh score categorized in three classes (class A = score 5 or 6, class B = score 7 to 11, class C = score 12 to 15) separates the series into three groups of approximately equal size with significant differences in median survivals (p less than 0.005) and in survival curves (p less than 0.0001). The characteristics of simplicity, availability, low cost and good discrimination power make the Pugh classification a very useful method to estimate prognosis in patients with cirrhosis of the liver.

[Diagnostic value of gamma glutamyl transpeptidase and the mean corpuscular volume in chronic hepatitis of alcoholic etiology]. / Valore diagnostico della gamma-glutamiltranspeptidasi e del volume corpuscolare medio per l'etiologia alcolica in corso di epatopatia cronica.

In order to assess the diagnostic value of serum gamma-glutamyl-transpeptidase (GGT) and mean corpuscular volume (MCV) as markers of alcoholism in chronic liver diseases, 107 patients with non-alcoholic chronic liver disease and 192 patients with alcoholic liver disèases have been compared. GGT and MCV values were checked two times: the day of admission to hospital and 10 days after complete withdrawal from alcohol. The patients with alcoholic liver diseases present significantly higher values of GGT and MCV in respect with patients with non-alcoholic liver diseases. A significant (p < 0.05) decrease of about 50% in serum GGT levels and of about 3% in MCV was observed after alcohol withdrawal only in the group of alcoholic liver diseases whereas no changes were found in the other group of patients: For the diagnosis of alcoholism in chronic liver diseases, while the sensitivity and the specificity of the several markers vary from 50% to 86%, the positive predictive values of GGT and MCV at admission were 92.2% and 73.4%, and the negative predictive values were 40.2% and 75.7%, respectively. Moreover, the positive predictive values of GGT and MCV after 10 days of alcohol withdrawal were 95.3% and 85.9% and the negative predictive values were 31.8% and 46.7%, respectively. The contemporary decrease in GGT and MCV values does not seem to offer better informations than GGT decrease. These data suggest that, even if GGT and MCV do appear per se as weak indicators of alcoholism during chronic liver diseases, the early decrease in their values, especially in serum GGT, are good and specific markers of alcohol abuse and, consequently, of the alcoholic etiology of liver disease.

[Prognostic factors in IgG and micromolecular multiple myeloma. Retrospective analysis of 50 consecutive cases]. / Fattori prognostici nel mieloma multiplo IgG e micromolecolare. Analisi retrospettiva di 50 casi consecutivi.

Clinico-pathological findings in 50 consecutive previously untreated patients with IgG and micromolecular multiple myeloma were reviewed. The clinical factors related with a shorter survival were: Bence-Jones proteinuria, high level of serum creatinine and serum calcium, low level of haemoglobin, widespread bone lesions, and plasma cell percentage in bone marrow more than 20%. This factor is significantly correlated with survival. The staging systems proposed by Durie and Salmon and by Merlini et al. are a precious reference in the evaluation of survival and treatment.

[Assessment of gallbladder motility in patients with alcoholic hepatic cirrhosis after a fatty meal. A real-time ultrasonography study]. / Valutazione della motilità colecistica in pazienti con cirrosi epatica alcolica dopo pasto grasso. Uno studio ecografico a tempo reale.

Gallbladder emptying after fatty meal administration was investigated by real-time ultrasonography in 10 patients with alcoholic cirrhosis of the liver, and 10 normal controls. Gallbladder volume was measured using the sum of cylinders method before and 5', 15', 20', 30', 60', 90', and 120' after fatty meal administration. Patients with liver cirrhosis presented the gallbladder volume significantly increased after 15' and 20', and significantly reduced after 60' and 90' in respect to controls. A significant difference was found between the groups in the two curves, patients showing a retarded contraction of gallbladder. The mechanism for sluggish gallbladder emptying in liver cirrhosis is unknown, however impaired emptying with bile stasis provides a potential pathophysiology basis for the high frequency of cholelithiasis in this disease.

[Prognostic evaluation in multiple myeloma. Relationship between immunological types, single prognostic factors, clinical staging systems, morphological classification systems and survival]. / La valutazione prognostica nel mieloma multiplo. Relazione tra tipi immunologici, singoli fattori prognostici, sistemi di stadiazione clinica, sistemi di classificazione morfologica e sopravvivenza.

The prognostic value of the multiple myeloma (MM) immunological type, of 20 different single prognostic variables, of 11 clinical staging systems, and of 6 morphological classification systems was evaluated in 121 patients (71 males and 50 females, 75 MM IgG, 26 MM IgA, and 20 MM micromolecular), who were followed from diagnosis to demise. The values of the prognostic variables related to diagnosis were correlated with survival by means of univariate analysis; multivariate analysis according to Cox's model was employed to select highly-significant parameters correlated with survival among these variables. Every patient was retrospectively staged according to each clinical and morphological system. Mean survivals were computed for each group on the basis of immunological type, mean value of each prognostic factor, clinical and morphological stage. Survival curves were computed and compared. All prognostic parameters showed a significant relationship with survival, even though p-value differed. Multivariate analysis according to Cox's model has indicated the following variables as significantly correlated with survival: bone marrow plasma cell percentage, degree of lytic bone lesions, hemoglobinemia value, and serum levels of beta 2-microglobulin. Each clinical and morphological staging system, as well as immunological types and mean value of single prognostic parameters, have divided patients into separate groups with significant differences in mean survival and in survival curves. All of these factors could be taken into account for correct prognostic evaluation, and, if they were applied in different steps of diagnosis and therapy, it would be possible to study the MM patient under different perspectives, in order to have a more complete picture of the disease and of the patient.

The natural history of monoclonal gammopathy of undetermined significance. A 5- to 20-year follow-up of 263 cases.

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum monoclonal component (M-component), but no evidence of multiple myeloma, macroglobulinaemia, amyloidosis or other plasma cell proliferative disease. A long-term follow-up study (median 11.5 years) has been carried out in 263 cases of MGUS, 159 males (60.5%) and 104 females (39.5%), aged 40-89 years (median 66.5 years). The actuarial probability for malignant transformation was 6.1, 15.4 and 31.3% at 5, 10 and 20 years, respectively. At the final evaluation, 157 patients (59.7%), 119 (45.3%) of whom with no increase and 38 (14.4%) with an increase in serum M-component, died of causes unrelated to MGUS and without development of any plasma cell proliferative disease; 47 patients (17.9%) were still alive without increase in M-component; 11 patients (4.1%) were still alive and at follow-up presented values of serum M-component > 30 g/l without any evidence of plasma cell proliferative or lymphoproliferative disease; 48 patients (18.3%) developed multiple myeloma (35 cases, 13.1%), solitary plasmacytoma of the bone (2 cases, 0.8%), macroglobulinaemia (4 cases, 1.6%), malignant lymphoma (3 cases, 1.2%), amyloidosis (2 cases, 0.8%), chronic lymphocytic leukaemia (1 case, 0.4%), and plasma cell leukaemia (1 case, 0.4%). The patients developing multiple myeloma, solitary plasmacytoma, macroglobulinaemia and plasma cell leukaemia had an increase in serum M-component, whereas no increase was found in malignant lymphoma, amyloidosis and chronic lymphocytic leukaemia. These findings and the data in the literature suggest that MGUS could be considered a preneoplastic condition; since no clinical and laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up indefinitely.

Tobacco smoking and risk of haematological malignancies in adults: a case-control study.

A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute nonlymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose-response effect, and the variation in risk according to the histological subtype of the malignancy.

Circadian rhythms of fibrinogen antithrombin III and plasminogen in chronic liver diseases of increasing severity.

Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma levels fluctuate during the day. The aim of this study was to investigate the circadian rhythms of these three factors in chronic liver disease. Five groups of subjects were considered: (A) 15 healthy controls: (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chronic active hepatitis; (D) 15 patients with compensated cirrhosis of the liver, and (E) 15 patients with decompensated cirrhosis with ascites. The levels of fibrinogen, antithrombin III and plasminogen were determined in blood samples drawn in each subject during the span of a day every 3 h starting from midnight. The time-related values were analyzed using the 'population-mean cosinor' method. Groups A and B presented a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithrombin III and groups D and E no significant (p > 0.05) circadian rhythms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by ANOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circulating levels of fibrinogen, antithrombin III and plasminogen in controls and suggest that liver disease is associated with progressive circadian modifications in the temporal structure of fibrinogen, antithrombin III and plasminogen, related to the stage of the liver disease. The rhythm derangements may be considered markers of evolution in liver disease.

Treatment of type C chronic active hepatitis with interferon-alpha 2a. Treatment duration does not influence biochemical remission but does decrease the relapse rate.

Few data are as yet available on the influence of interferon (IFN) treatment duration on biochemical remission and posttreatment relapse of chronic type C hepatitis. We investigated whether duration of recombinant IFN-alpha 2a treatment influences the remission and relapse rates in type C chronic active hepatitis (CAH). Sixty-two CAH patients were randomly assigned to receive 3 MU of i.m. recombinant IFN-alpha 2a three times per week for either 3 (group A, 32 patients) or 6 (group B, 30 patients) months. A complete biochemical remission was cumulatively observed in 62.5 and 63.3% of patients in groups A and B, respectively (p = NS). One and two patients in groups A and B, respectively, showed a biochemical relapse during treatment. In all cases biochemical remission was observed within the first 3 months of treatment. Among responders, 84.2 and 52.9% (p = 0.04) cumulatively had relapses in groups A and B, respectively. We conclude that IFN treatment duration does not influence the biochemical remission rate in type C CAH, but lowers the relapse rate of those who are treated for a longer period. The IFN treatment should be stopped if the patient is a nonresponder after 3 months of treatment. In responders, treatment should be continued for at least 6 months.

Circadian rhythm of arginine vasopressin in hepatorenal syndrome.

The etiology of hepatorenal syndrome is still incompletely understood, but the nonosmotic release of arginine vasopressin (AVP) seems to have an important role. Since AVP presents a well-defined daily periodicity in its production and secretion, the aim of the study was to investigate the circadian rhythm in its circulating plasma concentrations in patients with hepatorenal syndrome, compared with healthy controls. Venous blood samples were drawn during a 24 hour period at 2 hourly intervals from a peripheral vein in 10 healthy subjects and in 10 patients with hepatorenal syndrome for the determination of the circulating plasma levels of AVP by radioimmunoassay. Statistical analysis was carried out by the 'cosinor' method. The controls presented a significant (p < 0.002) circadian rhythm in the AVP circulating levels, whereas no rhythm (p > 0.05) was found in patients. The circadian rhythms were significantly (p < 0.005) different between the two groups, patients having higher mean daily concentration and lower circadian variation of AVP. These results confirm the existence of a well-defined circadian rhythm of AVP in healthy subjects, whereas the hepatorenal syndrome patients present a complete loss of the circadian rhythm. It could be hypothesized that primitive damage in circadian time-keeping regulates the circadian rhythm of vasopressinergic neurons, or has a secondary effect on the peripheral vasodilatation in the course of advanced liver disease. This great upset in the temporal and functional organization, together with that of the renin-angiotensin-aldosterone system, could play an important role in promoting and/or in the maintenance of the hydroelectrolyte imbalance that characterizes the hepatorenal syndrome.

[Serum levels of magnesium in hepatic cirrhosis]. / Livelli sierici di magnesio nella cirrosi epatica.

In a group of 50 patients with liver cirrhosis compared with a group of 50 clinically healthy subjects serum magnesium levels were determined. The patients were divided according the aetiology of liver cirrhosis and to the presence or not of ascite and cholestasis. The serum magnesium levels were related to the main laboratory tests used in liver cirrhosis. The patients present a significant decrease of serum magnesium levels in comparison to controls. The patients with alcoholic cirrhosis of the liver and with ascite have significant lower magnesium levels in comparison with the patients with post-hepatitis cirrhosis and with patients without ascite. There is a significant correlation between serum magnesium levels and serum levels of aldosterone, albumin, gamma-glutamyl transpeptidase and total pool of bile acids. Direct and indirect effects of alcohol, a secondary hyperaldosteronism, the use of diuretics, and hypoalbuminaemia could account for magnesium serum level decrease in liver cirrhosis.

Hepatic encephalopathy: lack of changes of gamma-aminobutyric acid content in plasma and cerebrospinal fluid.

The aim of the study was to verify the role of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic gamma-aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid gamma-aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symptoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy. The mean plasma and cerebrospinal fluid gamma-aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the gamma-aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy.