Tall stature and gigantism in transition age: clinical and genetic aspects-a literature review and recommendations.

PURPOSE: Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many studies have described the main aspects of this condition during puberty, but an analysis of the characteristics that the physician should consider in the differential diagnosis of gigantism-tall stature secondary to a pituitary tumour-during the transition age (15-25 years) is still lacking. METHODS: A comprehensive search of English-language original articles was conducted in the MEDLINE database (December 2021-March 2022). We selected all studies regarding epidemiology, genetic aspects, and the diagnosis of tall stature and gigantism during the transition age. RESULTS: Generally, referrals for tall stature are not as frequent as expected because most cases are familial and are usually unreported by parents and patients to endocrinologists. For this reason, lacking such experience of tall stature, familiarity with many rarer overgrowth syndromes is essential. In the transition age, it is important but challenging to distinguish adolescents with high constitutional stature from those with gigantism. Pituitary gigantism is a rare disease in the transition age, but its systemic complications are very relevant for future health. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life and prevent comorbidities of individual patient in this age range. CONCLUSION: The aim of our review is to provide a practical clinical approach to recognise adolescents, potentially affected by gigantism, as early as possible.

Hepatitis C diagnosis and treatment in people who use drugs: mind the gap in the linkage to care.

OBJECTIVE: The objective of this study is to identify a simplified rapid screening and linkage-to-care model for HCV among PWUD. PATIENTS AND METHODS: The study stems from a collaborative project bringing together two local Italian Centers for Drug Addiction and the Hepatology-Infectious Diseases Department of Lazzaro Spallanzani. A research physician analyzed the available medical records seeking to identify HCV and HIV infected patients in care in the addiction centers. Between March 2018 and January 2020 subjects were selected from among a cohort of 720 PWUD in the two Centers' care. The study comprises three steps: first, screening for HCVAb; second, the linkage to care; third, clinical assessment to treatment. The research physician recruited patients for the first two steps directly in their local addiction center. The third step was conducted in the Spallanzani. The characteristics of those subjects who adhered to the three-step study program were then compared to those of the non-adhering PWUD. RESULTS: 194 were known HCVAb positive patients. Of the 505 PWUD in the care of the two Centers eligible for screening, 364 were enrolled in the study. 144 resulted HCVAb positive. 269 were tested for HCVRNA. 101 underwent a full assessment. 96 patients started antiviral therapy with DAA. Patients who refused first step screening were older patients and mainly heroin users; in the second step, almost all the HIV/HCV co-infected patients agreed to a viremia test; in the third step all the HIV/HCV co-infected patients refused HCV treatment. CONCLUSIONS: The study suggests an on-site specialist approach conducted directly in the addiction centers themselves starting from screening; it can bring the goal of HCV PWUD microelimination closer.

Severe EBV hepatitis treated with valganciclovir.

We describe the case of an 18-year-old immunocompetent male patient with severe hepatitis during primary Epstein-Barr virus infection, treated with oral valganciclovir. During the initial therapy with corticosteroids, the patient's clinical condition and liver function worsened, so we decided to add oral valganciclovir for its good bio-availability and previous encouraging experiences in different clinical settings, with rapid resolution of the symptoms.

Cryptococcal lymphadenitis as a manifestation of immune reconstitution inflammatory syndrome in an HIV-positive patient: a case report and review of the literature.

Cryptococcus neoformans infections are typically associated with T-cell deficiencies, including acquired immunodeficiency syndrome (AIDS). Although highly active antiretroviral therapy (HAART) has strongly reduced AIDS-related opportunistic infections, the restoration and reactivation of CD4+ cells can induce an immune reconstitution inflammatory syndrome (IRIS), consisting in a deregulated inflammatory response to latent infectious pathogens and/or to their residual antigens. Cryptococcal lymphadenitis has occasionally been documented in IRIS. Here we report a case of histology- and culture-negative cryptococcal lymphadenitis associated with IRIS in an adult AIDS patient with a history of disseminated cryptococcosis, after the start of fully adherent HAART. Appropriate diagnosis was established on nested-PCR and sequence analysis of the interspacer region 2 of C. neoformans ribosomal DNA, and detection of slow-growing blastospores in enrichment cultures of fine-needle lymph node aspirate. Review of recent literature and our case findings suggest that IRIS-associated cryptococcal lymphadenitis is more likely the flare up of a latent infection rather than an immunopathological response to residual antigen of unviable cryptococci.

Clearance of human herpesvirus 8 from blood and regression of leukopenia-associated aggressive classic Kaposi's sarcoma during interferon-alpha therapy: a case report.

A human immunodeficiency virus-negative woman with severe classic Kaposi's sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposi's sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.

Correlation between enzyme-linked immunosorbent assay and immunofluorescence assay with lytic antigens for detection of antibodies to human herpesvirus 8.

The purpose of this study was to evaluate, in Kaposi's sarcoma patients, the correlation between antibody titers to the lytic antigens of human herpesvirus 8, as assessed by immunofluorescence assay, and values obtained by an enzyme immunoassay. The methods showed a stringent correlation, r = 0.625 (P<0.001).

Decay of HIV type 1 DNA and development of drug-resistant mutants in patients with primary HIV type 1 infection receiving highly active antiretroviral therapy.

The present study was aimed at describing the effect of highly active antiretroviral therapy (HAART) in 10 patients with primary HIV infection (PHI). Clearance rates of HIV RNA and HIV DNA in peripheral blood as well as the preexistence and the emergence of drug-resistant strains of HIV were determined over 52 weeks of treatment. The data indicate that HAART is able to induce a suppression of plasma viral load together with a significant decrease, but not a suppression, of peripheral blood mononuclear cell-associated proviral DNA in PHI subjects. Analysis of drug-resistant strains revealed that three PHI patients, showing a complete virologic response, developed mutations in the pol gene, thus suggesting that a persistent residual virus replication exists despite a sustained suppression of plasma viremia.

Metabolic and morphologic disorders in patients treated with highly active antiretroviral therapy since primary HIV infection.

UNLABELLED: Our objective was to describe morphologic and metabolic disorders in patients treated with highly active antiretroviral therapy (HAART) since primary HIV infection (PHI). Our method was prospective evaluation of patients with PHI initiating HAART at the time of diagnosis. Outcome measures were: development of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and of body shape abnormalities indicative of lipodystrophy, assessed through self-reported questionnaires and physical examination. RESULTS: From May 1997 to April 2001, 41 patients (35 males) with PHI presented at the National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy. A protease inhibitor-including regimen was started in 30 patients, and a nonnucleoside reverse transcriptase-inhibitor in 11. Median interval between enrollment and treatment initiation was 30 days (mean 39, range 10-150). Median HAART duration was 19 months (mean 21.2, range 3-47). Thirty-eight patients had undetectable (less than 80 cp/mL) HIV RNA after a median of 3 months (mean 4.1, range 1-15). Mean CD4 cells count increased from 632/mmc at baseline to 936/mmc at the last follow up. No cases of hyperglycemia (glucose level greater than 110 mg/dL) were observed. After a median of 6 months on HAART, 10 patients developed beyond grade 2 (greater than 240 mg/dL) hypercholesterolemia, 5 developed beyond grade 2 (greater than 400 mg/dL) hypertrygliceridemia, and two developed both. Body mass index did not change significantly. Five patients (12.2%) developed lipodystrophy after a median of 14.5 months (mean 15.3, range 2-30), with an incidence of 7.3 per 100 patient-years. CONCLUSIONS: Dyslipidemia and lipodystrophy can occur in patients treated with HAART since PHI. This risk of should be taken into account when considering this early antiretroviral treatment of HIV infection.

Pathogenesis II: fungal responses to host responses: interaction of host cells with fungi.

Most of our knowledge concerning the virulence determinants of pathogenic fungi comes from the infected host, mainly from animal models and more recently from in vitro studies with cell cultures. The fungi usually present intra- and/or extracellular host-parasite interfaces, with the parasitism phenomenon dependent on complementary surface molecules. Among living organisms, this has been characterized as a cohabitation event, where the fungus is able to recognize specific host tissues acting as an attractant, creating stable conditions for its survival. Several fungi pathogenic for humans and animals have evolved special strategies to deliver elements to their cellular targets that may be relevant to their pathogenicity. Most of these pathogens express surface factors that mediate binding to host cells either directly or indirectly, in the latter case binding to host adhesion components such as extracellular matrix (ECM) proteins, which act as 'interlinking' molecules. The entry of the pathogen into the host cell is initiated by fungal adherence to the cell surface, which generates an uptake signal that may induce its cytoplasmic internalization. Once this is accomplished, some fungi are able to alter the host cytoskeletal architecture, as manifested by a rearrangement of microtubule and microfilament proteins, and this can also induce epithelial host cells to become apoptotic. It is possible that fungal pathogens induce modulation of different host cell pathways in order to evade host defences and to foster their own proliferation. For a number of pathogens, the ability to bind ECM glycoproteins, the capability of internalization and the induction of apoptosis are considered important factors in virulence. Furthermore, specific recognition between fungal parasites and their host cell targets may be mediated by the interaction of carbohydrate-binding proteins, e.g., lectins on the surface of one type of cell, probably a parasite, that combine with complementary sugars on the surface of host-cell. These interactions supply precise models to study putative adhesins and receptor-containing molecules in the context of the fungus-host interface. The recognition of the host molecules by fungi such as Aspergillus fumigatus, Paracoccidioides brasiliensis and Histoplasma capsulatum, and their molecular mechanisms of adhesion and invasion, are reviewed in this paper.

Immune-derived cytokines in the nervous system: epigenetic instructive signals or neuropathogenic mediators?

The investigation of the effects of inflammatory cytokines (IC) on the growth and differentiation of neural cells has provided new insights on the role of such soluble mediators in nervous system development and/or plastic remodeling as well as in the pathogenesis of inflammatory neurodegenerative disorders, which are characterized by chronic IC dysregulation in the central nervous system (CNS). Thus, the study of the interaction between CNS and immune-derived soluble signals in physiological or pathological conditions is of increasing interest. This review first discusses experimental evidence supporting the instructive/permissive role of immune-derived cytokines on CNS development and plasticity. Next, we focus on human neurological disease states such as multiple sclerosis and the neurodegeneration associated to the acquired immune deficiency syndrome in which different inflammatory cytokines have been proposed as potential neuropathogenic mediators.

gamma-Interferon production in peripheral blood mononuclear cells and tumor infiltrating lymphocytes from Kaposi's sarcoma patients: correlation with the presence of human herpesvirus-8 in peripheral blood mononuclear cells and lesional macrophages.

Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (gamma-interferon [gamma IFN]) and Th2 (interleukin-4 [IL-4] cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TIL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. gamma IFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent gamma IFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (i.e., Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent gamma IFN production may be in response to or elicited by HHV-8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.

Kaposi's sarcoma cells express the macrophage-associated antigen mannose receptor and develop in peripheral blood cultures of Kaposi's sarcoma patients.

The mannose receptor (MR) is a surface 175-kd C-type lectin expressed by macrophages and dendritic cells. MR is involved in removal of effete cells, phagocytosis of mannose-coated particles, pinocytosis, and antigen presentation. Expression of MR was investigated in 17 biopsies of Kaposi's sarcoma (3 AIDS KS, 13 classical KS, and 1 transplant-associated KS) using three anti-MR monoclonal antibodies (3.29, D547, and PAM1). Immunostaining for MR was detected in 94 +/- 7% KS cells with spindle morphology. In normal tissues, MR was expressed by sinus-lining cells of spleen and lymph nodes, but it was not detected in endothelial cells lining normal hematic and lymphatic vessels, hemangioma, hemangioendothelioma, and lymphangioma. Expression of MR in KS cells prompted us to investigate the possibility that they derive from a circulating precursor cell. Peripheral blood mononuclear cells from 16 patients with KS (10 classical, 1 transplanted, and 5 AIDS) were cultured in PHA-conditioned medium for 10 to 14 days. Confluent monolayers of adherent spindle cells were detected in 8 of 11 classical KS, in 5 of 5 AIDS KS patients, and in 0 of 34 control patients. Peripheral-blood-derived KS-like cells were characterized by co-expression of macrophage and endothelial antigens being positive for CD45 (60%), CD68 (98%), MR (70%), CD14 (25%), VE-cadherin (70%), and von Willebrand factor (10%). When the immunophenotype of peripheral-blood-derived adherent cells was compared with that of KS spindle cells of tissue biopsies, it was found that both cell types are VE-cadherin+/MR+/CD68+, that peripheral-blood-derived spindle cells are CD34- and are less frequently stained for CD31 and von Willebrand factor, and that lesional KS cells do not express the leukocyte markers CD45 and CD18. Our findings are consistent with the possibility that KS lesions derive from tissue accumulation and local proliferation of a special subset of macrophages with endothelial features the normal counterpart of which are the sinus-lining cells of spleen and lymph nodes.

[Clinical use of a new absorbable suture material in general surgery]. / Impiego clinico di un nuovo materiale di sutura assorbibile in chirurgia generale

Results with a new, completely absorbable synthetic suture material made of polyglycolic acid (Dexon) in abdominal and anorectal surgery are reported. It is considered that this material can usefully be employed in the place of known absorbable materials and, under certain conditions, non-absorbable materials. No complications due to inflammation and mucosa ulceration following transparietal migration of stitches in the sero-serous or seromuscular layer of the intestine were noted. The results obtained when stitches were left in situ in 37 intradermal sutures, on the other hand, were not so satisfactory and some scars were judged cosmetically poor after 6 months. These results are felt to be caused by Dexon's long absorption time. In cases of this kind, therefore, it should only be used in the form of removable, single stitches.