Coronary atherosclerotic lesions in human immunodeficiency virus–infected patients: a histopathologic study

BackgroundStudies suggest human immunodeficiency virus–positive (HIV+) patients have an increased risk of coronary artery disease (CAD), yet little is known about the histopathology, severity, or distribution of lesions.MethodsThe coronary arteries of 66 deceased AIDS patients and 19 HIV controls (age <55) were dissected and graded for percent luminal stenosis by intimal lesions, percent of intima involved with lipid, and extent of intimal calcification on a scale of 0 to 3. Medical histories, antiretroviral therapies, and CAD risk factors were reviewed.ResultsHIV+ patients were older than controls (P=.06), and more were male (P=.02). Thirty-five percent of HIV+ patients had stenosis ≥75% of at least one artery. Compared to controls, HIV+ patients had three times greater odds of stenosis ≥75%, controlling for age and sex (one-sided P=.03). Older age and male sex were also risk factors (one-sided P<.001). HIV seropositivity was associated with increased plaque lipid content (one-sided P=.02) and calcification (one-sided P=.08). Duration of HIV infection, antiretroviral therapy, and immune status did not predict severe disease in multivariate analyses. Previously unreported patterns of dystrophic calcification were observed in HIV+ patients and older controls.ConclusionsYoung to middle-aged patients dying from advanced AIDS have atherosclerotic CAD that may result in luminal narrowing, heavy calcification, and high plaque lipid content. The pattern of disease, location of lesions, and plaque composition are typical of atherosclerosis in HIV-negative patients. No relationship between antiretroviral therapies and atherosclerosis was seen in this small study of heavily treated patients.     

Relationship between cytomegalovirus infection and procoagulant changes in human immunodeficiency virus‐infected patients

Cytomegalovirus is associated with hypercoagulability, and is reported to increase the risk of venous thrombosis in human immunodeficiency virus (HIV)‐infected patients. Progression to AIDS, however, is also associated with hypercoagulability and venous thrombosis, and may result in more comorbidities, such as reactivation of cytomegalovirus. It is therefore unknown whether active cytomegalovirus in HIV infection results in a procoagulant state or whether hypercoagulability is the result of HIV infection itself. In this cross‐sectional study of 104 consecutive HIV‐infected patients, active cytomegalovirus infection was associated with hypercoagulability independently of stage of HIV disease. This finding may deserve attention in preventative recommendations for use of thromboprophylaxis in HIV‐infected patients.     

Iron supplementation during human immunodeficiency virus infection: a double-edged sword?

Although iron supplementation is considered beneficial for groups at risk for anemia, concern has been raised that it could be harmful during human immunodeficiency virus (HIV) infection. Studies suggest: (1) faster HIV disease progression in thalassemia major patients receiving inadequate doses of iron-chelating drug; (2) higher mortality among patients receiving iron supplementation with dapsone compared with aerosolized pentamidine for prophylaxis against Pneumocytis carinii pneumonia; (3) higher iron stores and mortality among patients with haptoglobin Hp 2-2 phenotype; and (4) shorter survival among patients with high bone marrow iron deposition. These studies largely involved men in developed countries. Among HIV-infected pregnant women in Africa with a high prevalence of iron deficiency, no relationship was found between indicators of iron status and HIV disease severity. The available data do not contraindicate the current practice of iron supplementation in developing countries where there is a high prevalence of both HIV infection and iron deficiency.     

Can immune-related genotypes illuminate the immunopathogenesis of cytomegalovirus disease in human immunodeficiency virus–infected patients?

Most human immunodeficiency virus (HIV) patients are seropositive for cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This observation may reflect variations in genes affecting inflammatory and natural killer cell responses. DNA samples were collected from 240 HIV-infected patients followed at the University Hospitals/Case Medical Center (Cleveland, OH) between 1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37) experienced CMV disease. Genotypes were determined using allele-specific fluorescent probes or multiplex polymerase chain reaction sequence-specific primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease in African American patients (p = 0.04 and p = 0.02, respectively). IL10-1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were associated with low nadir CD4(+) T cell counts in African American patients (p = 0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA-1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In general, polymorphisms associated with CMV disease and CD4(+) T cell counts were distinct in Caucasian and African American patients in the United States. The LILRB1 I142T polymorphism was associated with both CMV disease and low nadir CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir CD4(+) T cell count in African American patients was DARC T-46C.     

Chronic delta hepatitis: Is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections?

Eighty-six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection. Patients were classified into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases). All but 14 patients were asymptomatic at presentation. Liver histology showed chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During follow-up, 52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and 1 received a liver transplant. Among the 28 patients who died, 4 had HDV infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and was unrelated to liver disease in 2 (8%) cases. There results demonstrate that chronic delta hepatitis is a severe disease, especially among drug users with HIV and HCV infection. The high morbidity and mortality of chronic delta hepatitis justifies the use of antiviral therapy to modify the natural course of the disease. © 1996 Wiley-Liss, Inc.     

Low blood zinc concentrations in patients with poor clinical outcome during SARS-CoV-2 infection: is there a need to supplement with zinc COVID-19 patients?

Among 275 patients with COVID-19, we found that median blood zinc level was significantly lower in patients with poor clinical outcome (N = 75) as compared to patients with good clinical outcome (N = 200) (840 μg/L versus 970 μg/L; p < 0.0001), suggesting that zinc supplementation could be useful for patients with severe COVID-19.     

What is the clinical relevance of respiratory syncytial virus bronchiolitis?: findings from a multi-center, prospective study

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children <24?months of age who presented with <4?days duration of AB. Subjects were divided into the following groups: “only RSV,” “also RSV,” “no RSV,” and “no pathogen.” The clinical severity score on admission as well as the overall severity of disease was assessed. RSV was the most common cause of AB (77.5?%). “Only RSV” or “also RSV” patients had a higher clinical score on admission compared to those with “no RSV,” p?<?0.001 and p?<?0.02, respectively. “Only RSV” and “also RSV” patients had a higher disease severity score when compared to patients with “no RSV,” 5.9?±?1.4 vs. 5.1?±?1.5, p?<?0.001, and 5.6?±?1.4 vs. 5.1?±?1.5, p?<?0.02, respectively. Disease severity did not vary as a function of transfer to the pediatric intensive care unit (PICU) or duration of supplemental oxygen, yet, “only RSV” was associated with a longer length of stay (LOS) than “no RSV,” p?<?0.02. “Only RSV”-related AB was associated with a more severe initial clinical presentation and a longer LOS. There appears to be little immediate clinical benefit to diagnosing RSV AB to the individual patient, but the application of these diagnostic methods may have significant cost-saving implications and, thus, deserves consideration by medical professionals and health policy analysts.     

Developmental change associated with human immunodeficiency virus infection in school‐age children with hemophilia

This study was designed to examine (a) developmental change associated with human immunodeficiency virus (HIV) infection in hemophilic boys ages 6 to 16 years and (b) whether age at infection was a critical variable in developmental change for children with HIV disease. Of the 11 subjects, 5 were HIV‐seronegative (HIV‐), and 6 were HIV‐seropositive (HIV+). The HIV+ children were asymptomatic at entry, but by the end of the study, one child had received a diagnosis of AIDS. All subjects were medically well at each time of assessment Standardized measures of general intelligence, academic achievement, neurological development, and problem behaviors were administered to each child every 6 months for 2 years. Both the HIV‐ and HIV+ children performed within age expectations at each time of assessment, and their parents reported very few behavior problems, indicating that the children were adjusting well to chronic illness. Both groups obtained lower achievement test scores than expected for their level of general intellectual ability. Differences were found in the pattern of retest effects for the two groups. There were improvements in Wechsler intelligence test performance over time for the HIV‐ children, but the HIV+ children demonstrated subtle declines in performance on measures of verbal and perceptual abilities. The HIV+ children infected at a younger age (M = 3 years, 11 months) performed more poorly on measures of perceptually related skills and demonstrated more deficient retest effects generally on tasks requiring visual‐motor coordination and perceptual organization than those infected at an older age (M = 9 years, 4 months). In addition, they exhibited more frequent signs of neurological problems than those infected later in life. The findings are discussed in terms of percolation theory, and implications for the children's educational planning are considered.     

Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co‐infection: Clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.     

Palivizumab prophylaxis for respiratory syncytial virus in infants with cystic fibrosis: is there a need?

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study’s objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged <?2 years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ² and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B)?=?0.23 [0.11–0.49], p?<?0.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; t?=?2.39 [df?=?7], p?=?0.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (t?=?3.52 [df?=?15], p?=?0.003) and hospital LOS (t?=?2.11 [df?=?52], p?=?0.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups.     

Hepatitis C: is there a case for universal screening in pregnancy?

Hepatitis C (HCV) is not routinely screened for antenatally in all maternity hospitals. Most hospitals adopt a policy of targeted screening. The policy in the Coombe Women and Infants University Hospital in Dublin changed from targeted screening in 2006 to universal screening in 2007. We audited the two consecutive years. The prevalence of HCV in our antenatal population was 1.4% for 2006 (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when universal screening came into affect. One woman in 2007 would not have been detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We conclude that there were similar detection rates for HCV in 2006 and 2007 and that universal screening is not required if inclusive criteria for selective screening are employed but is of use in research context.     

Treatment of bleeding in patients with platelet disorders: is there a place for recombinant factor VIIa?

The mechanism of action of recombinant factor VIIa (rFVIIa), i.e. increased thrombin generation on the membrane of activated platelets, as well as the results from in vitro and ex vivo models of thrombocytopenia or inherited thrombocytopathia may support some potential of rFVIIa in thrombocytopenia/thrombocytopathia. rFVIIa was reported as effective to stop or to decrease bleeding in few patients with severe thrombocytopenia resistant to platelet transfusions; however data are still scarce and clinical studies are really needed to define efficacy/safety ratio as well as optimal treatment regimen in this potential indication. Some data in patients with Glanzmann thrombasthenia (GT) may support the use of rFVIIa outside its primary indication in the cases in which there is no real treatment alternative (GT patients with antibodies to GP IIb-IIIa or with platelet refractoriness).     

Helicobacter pylori infection and atherosclerosis: is there a causal relationship?

For many years, the coexistence of Helicobacter pylori (H. pylori) infection and atherosclerotic diseases in a disproportional number of patients has inspired the presumption that a causal relationship exists between the conditions. This presumption was evidenced by the simultaneously declining epidemics of duodenal ulcer and coronary artery diseases in the United States in the past 40 years, and was further evidenced by the detection of H. pylori and their DNA in atherosclerotic plaques. Suggested mechanisms underlying this possible causality include intensified inflammatory stress, dyslipidemia, abnormal glucose metabolism, arterial stiffness, increased blood pressure and malnutrition. However, a causal relationship was disproved by results from other studies, which indicated that common risk factors shared by H. pylori infection and atherosclerosis, such as aging, cigarette smoking, disadvantageous socioeconomic status and high salt intake, may predestine their coexistence. Understanding the nature of the relationship between H. pylori infection and atherosclerosis is of vital importance, because a causality may indicate a possible strategy for preventing and treating atherosclerosis by eradicating H. pylori infection in selected individuals. This review assessed current evidence for and against a causal relationship between H. pylori infection and atherosclerosis.     

Haemorrhaging lesion in the breast: is there a role for embolisation?

Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.     

Ligands for Viscum album agglutinin and galectin-1 in human lung cancer: is there any prognostic relevance?

Viscum album agglutinin (VAA) is an extract component of mistletoe. It belongs to the plant lectin family and exerts various biological effects such as cytotoxic properties for tumor cells in culture. VAA as well as galectin-1, an endogenous lectin, possess galactose-specific surface-binding sites. We therefore investigated 159 cases of lung cancer for their capacity to bind VAA and galectin-1 and for Lewis antigen reactivity. Three different methods were used for detection of VAA: a two-step method with biotinylated VAA; an immune complex three-step method, and a four-step method. The most sensitive results were obtained with the four-step method utilising VAA, a goat-anti-VAA antibody and a biotinylated rabbit-anti-goat antibody. Intensity and distribution of staining were assessed using an immunoreactive score index (0-12). Approximately 70% of all tumors exhibited moderate to strong binding capacity for VAA. Adenocarcinomas and bronchiolo-alveolar carcinomas were more frequently labeled than squamous carcinomas. No relationship between expression of binding sites for VAA and galectin-1 as well as of Lewis antigens was found. Moreover, there was no correlation between VAA-binding capacity and survival, whereas expression of galectin-1-binding sites was of prognostic significance. Patients showing expression of galectin-1-binding sites revealed a better prognosis than those lacking binding sites or showing a weak reactivity (P = 0.0257 log rank test of Kaplan-Meier statistics).