Epidemiology of tuberculosis in immigrant patients hospitalised in Infectious Diseases Units in Italy: multicentric study

In order to retrospectively evaluate the prevalence of immigrant patients affected by active tuberculosis, we analysed the clinical data of 2255 immigrant patients hospitalised during 2002 in ordinary admission or in Day Hospital in 48 Clinics of Infectious Diseases. In all, 303 patients were affected by active tuberculosis (13.4% of the total immigrant hospitalised patients); 30 patients (9.9%) were also HIV-positive. There was a considerable male gender bias (62.5%); the mean age was 29.7 years; 144 patients were from Africa (47.5%), 72 (23.7%) from Asia, 47 (15.5%) from eastern Europe and 40 (13.2%) from South America. The clinical variants were: pulmonary (57.7%), lymph node (15.8%), meningitis (13.8%), intestinal (4.2%), bone (3.3%), pleurical (2.3%), peritoneal (2.3%) and renal (0.6%). We conclude that tuberculosis is a very frequent disease among immigrants, especially of African origin. The high percentage is due to several factors, such as no vaccine prophylaxis and poor, overcrowded living conditions. It is fundamental to focus on the need to provide better health support for all subjects by setting up screening plans to estimate the real incidence of this pathology and ensure medical treatment to prevent the spread of this infection among immigrants and the local host population.     

Anaphylaxis: a 7-year follow-up survey of 46 children.

BACKGROUND: Little is known about the frequency of and the features associated with recurrent anaphylaxis in pediatric populations. During 1994 to 1996, we enrolled 76 children affected by anaphylaxis in a prospective study to analyze their clinical and allergic features. OBJECTIVE: To undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis. METHODS: After a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study. RESULTS: A telephone interview was successfully completed in 46 (61%) of the 76 patients who had been enrolled in our 1994-1996 study. Of these 46 patients, 14 (30%) had experienced a recurrence of anaphylaxis. Children with atopic dermatitis either during 1994 to 1996 (64% vs 34%; P = .04) or at the time of the current study (43% vs 16%; P = .03) and those with urticaria-angioedema at the time of the current study (93% vs 31%; P = .0002) were found to be at a significantly higher risk for recurrent anaphylaxis. Furthermore, those children who were sensitive to at least 1 food allergen during 1994 to 1996 were more likely to have experienced a recurrence of anaphylaxis (93% vs 56%; P < .04). CONCLUSIONS: This study suggests that patients may have a greater risk of recurrence of anaphylaxis if they have atopic dermatitis, urticaria-angioedema, or at least 1 positive result of skin prick tests to food allergens.     

Clinical Features of Fatal Familial Insomnia: Phenotypic Variability in Relation to a Polymorphism at Codon 129 of the Prion Protein Gene

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1+ 1.1 months) or a prolonged (30.8 + 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mai seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.     

Cytomegalovirus infection after bone marrow transplantation in children

Cytomegalovirus (CMV) is a well-known cause of disease occurring after bone marrow transplantation (BMT). The manifestations of CMV range from asymptomatic infection, defined as active CMV replication in the blood in the absence of clinical manifestations or organ failure abnormalities, to CMV disease, characterized by CMV infection with clinical symptoms or organ function abnormalities. Diagnostic procedures to assess the viral load have improved greatly with the increased use of antigenemia, CMV DNA, and immediate early-messenger RNA. Many conditions concur in determining the risk of developing CMV reactivation or disease after bone marrow transplant with serologic status of donor and recipient, type of bone marrow transplant, presence of graft-versus-host disease being the most studied. However, time and quality of immune reconstitution seems to be the pivotal factors. Pneumonia and gastrointestinal involvement are the most frequently documented clinical pictures with late-onset CMV reactivation or disease representing a new challenge. CMV prophylaxis or pre-emptive therapy adopted during the last few years in allogeneic BMT recipients has changed the natural history of the disease, reducing the risk of CMV disease, CMV-associated death, transplant-related mortality, and has prolonged the period at risk. Specific studies on children are lacking, however, the clinical pictures and features seems to be similar both in children and adults.     

Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis

Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.     

Plasma protein haptoglobin modulates renal iron loading

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.     

A mouse model for infectious mononucleosis

Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpesvirus that establishes life-long latency and is associated with lymphoproliferative disorders and the development of several malignancies. EBV infection is frequently, but not always, associated with the development of a syndrome termed infectious mononucleosis. The recent isolation and characterization of a murine gamma-herpesvirus, MHV-68 (gammaHV-68) has provided the first small animal model for studying immunity and pathogenesis of a gamma-herpesvirus in its natural host. MHV-68 has important biological and genetic similarities with the human gamma-herpesviruses. Following intranasal infection of mice with MHV-68, an acute respiratory infection in the lung develops and is cleared, followed by the establishment of latency. Similar to EBV, MHV-68 latency is largely established in B cells, although other cell types can be latently infected. The establishment of latency correlates with a prominent splenomegaly, polyclonal B cell activation with associated autoantibody production, and CD8+ T cell-dominated peripheral blood lymphocytosis, in many aspects mirroring EBV-induced infectious mononucleosis. There are key differences in the MHV-68- and EBV-induced CD8+ T cell responses however. Whereas the expanded CD8+ T cells associated with EBV-induced mononucleosis are largely the outgrowth of T cells responding to lytic viral epitopes elicited during the acute phase of the response, the CD8+ T cell lymphocytosis associated with MHV-68-induced infectious mononucleosis is dominated by an oligoclonal population of T cells expressing Vbeta4+ T cell receptors that are not reactive to acute viral epitopes. The focus of this article will be to highlight the similarities and differences in the infectious mononucleosis syndrome associated with human and murine gamma-herpesviruses.     

Ultrastructural identification of the splenic follicular dendritic cells in the chicken

Background: There is a need to identify the follicular dendritic cells (FDC) of the chicken spleen at the ultrastructural level during a secondary immune response. Methods: The cells were identified after intravenous priming BSA and boosting with biotinylated BSA conjugated to colloidal gold particles. Monoclonal antibodies raised specifically either to chicken IgG or IgM were used to characterize these immune complex-trapping cells. Results: The FDC had an irregular morphology which varied through time, supporting the existence of two types of FDC in the chicken spleen, one showing filiform cell processes, the other provided with beaded dendrites. When the filiform dendrites were observed, the FDC bound the antigen on their surfaces. These dendrites showed an intrincate convoluted configuration, forming tightly wrapped networks near the cell body. The networks had the same features as those described in mammals as antigen retaining reticulum (ARR). In chickens, the ARR, which represents sites of antigen localization on FDC, reached maximum development on day 5 after the second injection of BSA and had disappeared by day 8. At this time FDC had beaded dendrites. Conclusions: Antigen is retained on FDC in the chicken spleen for long periods of time. © 1995 Wiley-Liss, Inc.     

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry

BackgroundObesity has been described as a protective factor in cardiovascular and other diseases being expressed as ‘obesity paradox’. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI).MethodsWe retrospectively collected data up to May 31^st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m²; n = 1110, 25?30 kg/m²; n = 1464, and >30 kg/m²; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed.ResultsThe rate of respiratory insufficiency was more recorded in BMI 25?30 kg/m² as compared to BMI < 25 kg/m² (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m² than BMI < 25 kg/m², respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m² and BMI > 30 kg/m² did not impact the mortality rate (HR 1.15, 95% CI: 0.889?1.508; p = 0.27) (HR 1.15, 95% CI: 0.893?1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m² is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538?1.004; p = 0.05).ConclusionsHOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.