A bronchoalveolar lavage-driven antimicrobial treatment improves survival in hematologic malignancy patients with detected lung infiltrates: A prospective multicenter study of the SEIFEM group

Bronchoalveolar lavage (BAL) is recommended for diagnosing lung infiltrates (LI) in patients with hematologic malignancy (HM). Prospective data on the impact of BAL on survival are still lacking. We conducted a prospective observational study on patients who performed BAL for LI among 3055 HM patients hospitalized from January to September 2018. The BAL was performed in 145 out of 434 patients who developed LI, at a median time of four days from LI detection. The median age was 60 (1-83). Most patients had an acute myeloid leukemia/myelodisplastic syndrome (81), followed by lymphoma (41), acute lymphoblastic leukemia (27), and other types of HM (36). A putative causal agent was detected in 111 cases (76%), and in 89 cases (61%) the BAL results provided guidance to antimicrobial treatment. We observed a significantly improved outcome of LI at day +30 in patients who could receive a BAL-driven antimicrobial treatment (improvement/resolution rate: 71% vs 55%; P = .04). Moreover, we observed a significantly improved outcome in 120-day overall survival (120d-OS) (78% vs 59%; P = .009) and 120-day attributable mortality (120d-AM) (11% vs 30%; P = 0.003) for patients who could receive a BAL-driven treatment. The multivariate analysis showed that BAL-driven antimicrobial treatment was significantly associated with better 120d-OS and lower 120d-AM. We did not observe any severe adverse events. In conclusion BAL allows detection of a putative agent of LI in about 75% of cases, it is feasible and well tolerated in most cases, demonstrating that a BAL-driven antimicrobial treatment allows improvement of clinical outcome and survival.     

Motor cortex excitability in vascular depression

The aim of this study was to evaluate excitatory/inhibitory intracortical circuit changes in patients with vascular depression, and whether there are any interhemispheric differences of motor cortical excitability.Fifteen vascular depressed elderly (VD), ten nondepressed subcortical vascular disease patients (SVD) and ten age-matched controls underwent bilateral motor threshold and paired-pulse studies. They were also assessed for their brain vascular burden at MRI and neuropsychological profile.Executive dysfunction and apathy were significantly higher in VD; we were unable to find significant differences in resting motor threshold, cortical silent period and paired-pulse curves between VD, SVD and controls, and between the two hemispheres in the VD group.Our findings might suggest that neurophysiological mechanisms underlying VD differ from those previously reported in Major Depression (reduced excitability in the left hemisphere) and seem to be similar to those of patients with SVD. Our findings also, support the “vascular depression” hypothesis, suggesting that in VD patients the depressive syndrome is not the primary disease but can be considered as one of the clinical manifestations in the wide symptom spectrum of the cerebral small vessel disease.     

Enhanced motor cortex facilitation in patients with vascular cognitive impairment-no dementia

Data on Transcranial Magnetic Stimulation (TMS) derived measures of cortical excitability and intracortical circuits in age-related white matter changes are scarce. We aimed to assess early changes of motor cortex excitability in nondemented elderly patients with subcortical ischemic vascular disease (SVD). Ten SVD elderly and ten age-matched controls underwent paired-pulse TMS for the analysis of intracortical inhibition (ICI) and facilitation (ICF). All subjects performed neuropsychological assessment and brain magnetic resonance imaging. SVD patients showed abnormal executive control function. No statistically significant differences were found for resting motor threshold, cortical silent period between SVD patients and controls or between the two hemispheres, in patients. A significant enhancement of mean ICF was observed in SVD patients. This study provides the first evidence of functional changes in intracortical excitatory neuronal circuits in patients with SVD and clinical features of vascular cognitive impairment-no dementia. Further studies are required to evaluate whether the observed change of ICF might predict cognitive and/or motor impairment in a population at risk for subcortical vascular dementia.     

Effect of a short-term treatment with alendronate on bone density and bone markers in patients with central diabetes insipidus.

The aim of this open prospective randomized study was to evaluate the effect of a 6-month treatment with alendronate on the bone mineral density (BMD) at lumbar spine in patients with central diabetes insipidus. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered this study. At study entry, all subjects underwent BMD assessment at the lumbar spine and measurement of serum osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (Ntx). Thereafter, 9 of the 18 patients were randomized to receive treatment with alendronate at a dose of 10 mg, orally, once daily for 6 months (group 1), whereas the remaining 9 patients did not receive any treatment affecting bone status during this period (group 2). After 6 months, bone metabolism and bone density study were repeated in all patients. At baseline, lumbar BMD values (0.86+/-0.03 vs. 1.01+/-0.02 g/cm2; P<0.001) and serum OC levels (4.7+/-0.3 vs. 7.9+/-0.2 microg/L; P<0.001) were significantly lower, whereas urinary Ntx levels were significantly higher [72.0+/-1.9 vs. 64.6+/-1.7 nmol bone collagen equivalents (BCE)/nmol creatinine (Cr); P<0.01] in patients than in controls. After randomization, no difference in lumbar BMD, serum OC, or urinary Ntx was found between patients of group 1 and group 2. At the 6 month follow-up, no difference in serum OC levels was found compared to baseline evaluation in patients of both group 1 and group 2. By contrast, a significant decrease in urinary Ntx levels was found in patients of group 1 (70.3+/-3.0 vs. 75.4+/-2.1 nmol BCE/nmol Cr; P<0.05), but not in patients of group 2 (68.8+/-3.3 vs. 68.5+/-3.0 nmol BCE/nmol Cr; P = NS). A significant increase in lumbar BMD values was found in patients of group 1 (0.88+/-0.04 vs. 0.83+/-0.04 g/cm2; P<0.05), whereas a significant decrease in lumbar BMD values was found in patients of group 2 (0.86+/-0.05 vs. 0.89+/-0.05 g/cm2; P<0.05). Lumbar BMD increased 7.0+/-1.5% in patients of group 1 and decreased 4.2+/-1.8% in patients of group 2 (P<0.001). In conclusion, this study demonstrated that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. Therefore, alendronate treatment could be used in patients with central diabetes insipidus with documented osteopenia or osteoporosis.     

The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study

In 100 patients with hypopituitarism and 80 sex- and age-matched healthy subjects, we correlated the severity of cardiac impairment to the severity of GH deficiency (GHD). By the GH peak after arginine plus GHRH test (normal > 16.5 microg/liter), the patients were classified as severe GHD (n = 56), partial GHD (n = 27), and non-GHD (n = 17). Compared with controls, decreased left ventricular ejection fraction at rest was found only in severe GHD patients (55.0 +/- 8.8 vs. 63.4 +/- 4.5%, P < 0.001); decreased left ventricular ejection fraction response on effort in severe (-4.6 +/- 17.4 vs. 15.2 +/- 9.1%, P < 0.001) and partial GHD patients (3.6 +/- 6.6 vs. 14.6 +/- 8.3%, P < 0.001); decreased diastolic filling at rest in severe (2.53 +/- 0.68 vs. 3.01 +/- 0.48 end-diastolic volume per second, P < 0.001) and partial GHD (2.61 +/- 0.45 vs. 2.89 +/- 0.54 end-diastolic volume per second, P = 0.004) patients; and decreased exercise duration and capacity in all the patient groups. A normal systolic performance on effort was found in 21.4% of severe GHD, 55.6% of partial GHD, all non-GHD, and 93.7% of controls. A normal diastolic filling at rest was found in 57.1% of severe GHD, 74.1% of partial GHD, 76.5% of non-GHD, and 90% of controls. In conclusion, cardiac performance is correlated with the GH status because significant impairment was found in patients with severe and partial GHD but not in non-GHD hypopituitary patients.     

High sensitivity of flow cytometry improves detection of occult leptomeningeal disease in acute lymphoblastic leukemia and lymphoblastic lymphoma

Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM^pos/CC^pos) and CC negative-FC positive (CC^neg/FCM^pos), respectively. The remaining 24 (63 %) samples were double negative (CC^neg/FCM^neg) (p?=?0.001). CC^neg/FCM^pos patients showed a significantly shorter overall survival (OS) compared to CC^neg/FCM^neg ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p?=?0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.     

Increased prevalence of thyroid autoimmunity in patients successfully treated for Cushing's disease

BACKGROUND: Cushing's disease is characterized by abnormalities of immune function. OBJECTIVE: To evaluate the prevalence of autoimmune thyroid diseases in patients with Cushing's disease (CD), after successful treatment and the possible association between previous nodular goitre or positive thyroid autoantibodies during the active phase of CD and the subsequent development of autoimmune thyroid diseases after cure. SUBJECTS AND METHODS: Twenty patients with CD and 40 sex- and age-matched healthy controls were considered for the study. In CD patients, thyroid ultrasonography and measurement of circulating free thyroxine (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH), antithyroglobulin (anti-Tg) and antithyroperoxidase (anti-TPO) antibodies were performed at diagnosis and 6 months after disease cure while in controls they were performed only at study entry. RESULTS: Serum fT3, and fT4 levels were similar in patients, either during the active phase or after cure of the disease, and controls. Conversely, in the patients, serum TSH levels were significantly lower during active disease (0. 4 +/- 0.05 mU/l, P = 0.001) and significantly higher after disease cure (4.7 +/- 0.1 mU/l, P < 0.001) than in controls (2.3 +/- 0.4 mU/l). Four patients (20%) and 11 controls (27.5%) had positive anti-Tg and/or anti-TPO titre at study entry, while eight patients (40%) developed positive anti-Tg and/or anti-TPO titre after disease cure. The prevalence of positive antithyroid antibodies titre in cured CD patients was significantly higher than that observed in the same patients during the active disease (P = 0.008) and in controls (P = 0.031). A significantly higher prevalence of autoimmune thyroiditis was found in patients cured from CD (35%) than in patients with active CD (0%) (P = 0.016) and in controls (10%) (P = 0.031). A significant association was found between the presence of autoimmune thyroiditis after CD cure and the presence of a previous nodular goitre (P = 0.017) or positive thyroid autoantibodies titre (P = 0.007) during the active phase of the disease. CONCLUSION: Patients successfully treated for Cushing's disease have an increased prevalence of thyroid autoimmunity and autoimmune thyroiditis as compared to a control population. Therefore, patients with hypercortisolism need an accurate evaluation of thyroid function after remission of the disease in order to prevent the eventual onset of subclinical or overt post-thyroiditis hypothyroidism.     

Prospective assessment of body weight and body composition changes in patients with psoriasis receiving anti-TNF-α treatment

Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine associated with psoriasis pathogenesis. Anti-TNF-α therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti-TNF-α agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti-TNF-α therapies according with disease phenotype. Forty patients affected with psoriasis were followed up for 24 weeks and divided into two groups: psoriasis vulgaris (PsO) and psoriatic arthritis (PsA). Anthropometric, blood biochemical, body composition parameters, resting metabolic rate, and disease activity indexes were measured at baseline and at week 24. After 24 weeks of anti-TNF-α administration, the disease activity indexes and concentration of inflammatory markers were significantly decreased. Seventy-five percent of PsO and 60% of PsA patients had an increase in body weight. Weight changes correlated with fat mass gain in the PsO group, and with fat and lean mass gain in the PsA group. In the present study, we demonstrated that a blockage of TNF-α bioactivity is related with fat and lean mass gain in both PsO and PsA subjects. The anti-TNF-α therapies could play a key role in the cross talk between adipose tissue and skeletal muscle, mediated by the reduction of TNF-α and interleukin-6 production.