The pathology spectrum of AIDS-related non-Hodgkin's lymphoma

Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk of developing non Hodgkin's lymphomas (NHL). Current estimates indicate that 5-10% of HIV-infected individuals develop AIDS-related NHL (AIDS-NHL). AIDS-NHL share several clinical features, including frequent extranodal presentation, aggressive clinical course and poor outcome. However, AIDS-NHL are a heterogeneous group of malignancies. They traditionally included systemic and primary brain lymphomas, but nowadays their updated clinicopathologic spectrum also comprises two novel entities, namely primary effusion lymphoma and plasmablastic lymphoma of the oral cavity. In the last few years, several studies have shown that the pathologic heterogeneity of AIDS-NHL correlates with the heterogeneity of the molecular lesions associated with these lymphomas. However, despite their pathologic and molecular heterogeneity, AIDS-NHL have a common B-cell origin, although the precise stage of B-cell differentiation reflected by the different tumor types has not been clarified yet.     

Enzyme- and immunohistochemical study of a case of histiocytic necrotizing lymphadenitis

Summary A combined morphological, immunohistological, and enzyme histochemical analysis was performed on frozen and fixed lymph node tissue in a case of histiocytic necrotizing lymphadenitis (HNL) using conventional histology, a panel of monoclonal and polyclonal antibodies, and a series of common haematological enzyme reactions. Histology showed multiple paracortical necrotizing foci which, in a prominently necrobiotic background devoid of granulocytes, contained large numbers of foamy histiocytes and macrophages intermingled with cells resembling degenerating plasmacytoid T-cells. Most of the histiocytes were alpha₁-antichymotrypsin positive and foamy cells were also distinctly Leu-M1 positive. Strong granular acid phosphatase (AP) positivity was present in the cytoplasm of the macrophages and histiocytes. The cells with plasmacytoid features showed weaker and homogeneously diffuse AP staining. Alpha-naphthyl acetate esterase (ANAE) activity was much less striking than AP in the necrotizing foci and most of the ANAE negative cells corresponded to those with plasmacytoid features. No cells with B-cell lineage markers were present within the necrotizing foci; most of the occasional T-cells (Leu-1⁺, Leu-4⁺) present in the foci were Leu-2a⁺ (OKT8⁺) whereas OKT10⁺ lymphoid cells were abundant and appeared to correspond with the cells with plasmacytoid features. Our combined data confirm that the special type of necrosis found in HNL develops within foci of plasmacytoid T-cells undergoing regressive changes and apparently exhibiting distinct immunohistological and enzyme histochemical features.This study was supported in part by Grant n. 84.00525.44 from Consiglio Nazionale delle Ricerche Progetto Finalizzato Oncologia, Roma and by the Associazione Italiana per la Ricerca sul Cancro, Milano     

KSHV/HHV-8 associated Kaposi's sarcoma in lymph nodes concurrent with Epstein-Barr virus associated Hodgkin lymphoma

BACKGROUND: The unusual occurrence of a metastatic Kaposi's sarcoma (KS) in a lymph node affected by Hodgkin lymphoma (HL) was originally reported when knowledge of the specific virological features of these tumours was lacking. AIM: To re-evaluate this case by assessing whether the simultaneous presence of the two tumours was linked with common aetiopathogenetic factors. METHODS: The presence of EBV was investigated by in situ hybridisation, whereas KS associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) was detected by immunohistochemistry. Both viruses were analysed in the case reported, in 30 lymph nodes from patients with classic HL, and in 22 skin biopsies from patients with KS. RESULTS: Consistent with the findings in the HL and KS cases analysed, in the case showing features of both HL and KS in the same lymph node, EBV was detectable only in Reed-Sternberg (RS) cells, but not in KS spindle cells, whereas KSHV/HHV-8 was detectable only in KS spindle cells, and not in RS cells. CONCLUSION: It is probable that the development of KS and HL was related to two independent aetiological cofactors-KSHV/HHV-8 and EBV, respectively-and that the occurrence of the two malignancies in the same patient was merely fortuitous.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by ¹H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg⁻¹ i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.     

Effects of a Mediterranean Diet,Dairy, and Meat Products on Different Phenotypes of Dyslipidemia: A Preliminary Retrospective Analysis

Background: Dyslipidemia is one of the major causes of atherosclerotic cardiovascular disease (ASCVD) and a Mediterranean Diet (MD) is recommended for its prevention. The objectives of this study were to evaluate adherence to an MD at baseline and follow-up, in a cohort of dyslipidemic patients, and to evaluate how different food intakes can influence lipid profile, especially how different sources of saturated fatty acids impact lipid phenotype. Methods: A retrospective analysis was conducted on 106 dyslipidemic patients. Clinical characteristics, lipid profile, and food habits data were collected at baseline and after three months of follow-up with counseling. Adherence to an MD was evaluated with a validated food-frequency questionnaire (MEDI-LITE score). Results: The cross-sectional analysis showed that higher consumption of dairy products correlated independently with higher levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) and with lower triglycerides (TG) levels. Instead, lower HDL-C and TG levels and higher TC levels were independently associated with higher consumption of meat products. Adherence to an MD significantly improved after the follow-up period, from a mean value of 10 ± 3 (median 10, IQR 8–12) to 13 ± 2 (median 14, IQR 12–15), p < 0.0001. Conclusions: Dyslipidemic patients benefit from counseling for improving their adherence to an MD. The high intake of dairy products was associated with less atherogenic hyperlipidemia, which was characterized by higher levels of TC and HDL-C as compared withs the intake of an excessive amount of meat products, which was associated with higher levels of TC and TG and lower levels of HDL-C.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

A Cross-Country Network Analysis of Adolescent Resilience

PurposeIn situations of adversity, young people draw on individual, relational, and contextual (community and cultural) resources to foster their resilience. Recent literature defines resilience as a capacity that is underpinned by a network of interrelated resources. Although empirical studies show evidence of the value of a network approach, little is known regarding how different country contexts influence which resources are most critical within a resource network and how resources interact for adolescent resilience.MethodsNetwork analysis was conducted with data from studies that had used the Child and Youth Resilience Measure. Regularized partial correlation networks of 17 resources were estimated for 14 countries (Botswana, Canada, China, Colombia, Equatorial Guinea, India, Indonesia, Italy, Jordan, New Zealand, the Philippines, Romania, South Africa, and Syrian refugees living in Jordan). The sample size was 18,914 (mean age = 15.70 years, 48.8% female).ResultsWe observed mostly positive associations between the resources of interest. The salience and strength of associations between resources varied by country. The most central resource across countries was having supportive caregivers during stressful times because this resource had the most and strongest positive associations with other resources.ConclusionsThis study gives first empirical evidence from multiple countries that an interplay of social–ecological resources (such as individual skills, peer, caregiver and community support, and educational aspirations and opportunities) matter for adolescent resilience. Across countries, caregiver support appears to be most central for adolescent resilience. Future resilience interventions might apply this network approach to identify important, contextually relevant resources that likely foster additional resources.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).