Value of the 24 hour intraoesophageal pH monitoring in children.

Twenty four hour oesophageal intraluminal pH probe studies were performed in 114 children (range age: one month-12 years) referred for symptoms or signs compatible with gastroesophageal reflux. Forty five patients had reflux disease alone, 69 had evidence of oesophagitis which was assessed endoscopically and histologically. Recordings were also performed in 63 control patients. The occurrence of reflux was analysed for the total study period and particularly while awake, asleep, fasting, and during postcibal periods. Oesophageal acid exposure time and the number of reflux episodes lasting greater than five minutes during the total study period provided the best discrimination between patients and controls; however, 20% and 30% of all reflux patients had both normal (with 2 SD of control) acid exposure time and number of long lasting reflux episodes, respectively. Patients with oesophagitis had significantly more acid reflux than those with simple uncomplicated disease during postcibal, fasting, awake periods, but not during sleep; however, increasing severity of oesophagitis was not associated with increasing acid exposure. The ability of the intraluminal oesophageal pH test to discriminate patients with various degrees of reflux disease decreased if only postprandial pH variables were taken into account. We conclude that: (1) the 24 hour intraoesophageal pH monitoring may present false negative results that limit overall sensitivity of the test; (2) the presence of oesophagitis does not seem to be associated with increased oesophageal acid exposure during sleep; (3) limiting the pH recording to postprandial periods reduces the discriminatory power of the test.     

Efficacy of Combined Treatment with Lanreotide and Cabergoline in Selected Therapy-Resistant Acromegalic Patients

The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60–90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day).All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments.After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT+CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9±4.3 vs. 70.3±5.6%, p<0.01) and IGF-I suppression (54±4.4 vs. 45.3±5.7, p<0.01) and decrease of the nadir of GH (8.5±1.2 vs. 14.6±1.9 ng/ml, p<0.01) and IGF-I (400.9±32.8 vs. 462.1±45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15–30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3±6.3%) and IGF-I (43.9±4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1±2.1%) and IGF-I (57.5±2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN+CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN+CAB treatment.In conclusion, the treatment with dopaminergic drugs such as CV and CAB, significantly increased the efficacy of somatostatin analogs, and can be used in combined therapy in poorly responsive patients.     

Effect of growth hormone (GH) and/or testosterone replacement on the prostate in GH-deficient adult patients

The prostate is a target organ of the GH and IGF-I axis because prostate hypertrophy is found in acromegaly, reduced prostate size is found in GH deficiency (GHD) patients, and additionally, IGF-I is reported to be a positive predictor factor of prostate cancer. To investigate whether GH replacement therapy in adult patients with GHD has adverse effects on the prostate, we studied the effect of 12-month GH or GH plus testosterone replacement on prostate pathophysiology in 24 adult patients with GHD (11 euandrogenemic and 13 hypoandrogenemic), compared with 24 age-matched healthy controls. At study entry, GHD patients had lower prostate volume than controls (19.4 +/- 1.7 vs. 24.9 +/- 1.7 ml; P = 0.03). After 12 months of treatment, all hypoandrogenemic patients achieved normal testosterone levels, and prostate volume increased in the patients to the same level as controls (25.0 +/- 1.9 ml). The percentage increase in prostate volume was greater in hypoandrogenemic patients receiving both GH and testosterone replacement (51 +/- 11%) than in those receiving GH replacement alone (15 +/- 3%; P < 0.0009). At baseline, prostate volume was similar in GHD patients below or above 60 yr of age (16.8 +/- 1.3 vs. 23 +/- 3.6 ml; P = 0.08), whereas after treatment it was higher in the latter patients (21.8 +/- 1.2 vs. 29.5 +/- 3.9 ml; P = 0.04). Prostate-specific antigen (PSA) and free PSA did not change, whereas PSA density was significantly reduced after treatment in hypoandrogenemic patients; there was also no change in calcifications, cysts, or nodules. In conclusion, GH replacement restores prostate size to normal in both young and elderly patients, with no increase in prostate abnormalities. Because the simultaneous treatment with GH and testosterone induces an increase of prostate size by 50% of baseline on average, care is suggested in elderly patients with prostate hyperplasia to avoid any risk of prostate symptoms. In these cases, GH replacement might be performed sequentially to reduce the hypertrophic effect of combining GH and testosterone.     

Cardiac Abnormalities in Acromegaly

Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.     

Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4·8%), 149 (10%), 200 (13·2%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo-γ) and normal Ig levels (γ-normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment-free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels.     

Metals in Honeys from Different Areas of Southern Italy

The aim of the study was to quantify the cadmium (Cd), lead (Pb), chromium (Cr) and arsenic (As) contents in ninety honey samples from nine areas of southern Italy. Results showed that As content was below the detection limit, while Cd, Pb, and Cr contents were below the recommended maximum acceptable levels. Mean Cd, Pb, and Cr contents were 0.013, 0.289 and 0.707 mg kg^?1, respectively. The metal contents in honey varied greatly depending on considered area. Correlations between the metals were statistically significant (p < 0.05), suggesting that polluting sources involve the simultaneous presence of metals in honey.     

Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM⁺ and IgM⁻ plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.