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.     

Characterization of drug resistance mutations in naïve and ART-treated patients infected with HIV-1 in Yaounde, Cameroon

Currently the prevalence of HIV‐1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV‐1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV‐1 genetic diversity and to characterize HIV‐1 mutations conferring drug resistance among antiretroviral therapy (ART)‐naïve and ART‐treated patients. A cohort of 239 patients infected with HIV were followed‐up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV‐1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first‐line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second‐line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721–727, 2012. © 2012 Wiley Periodicals, Inc.     

JAK inhibitors and psoriatic arthritis: A systematic review and meta-analysis

BackgroundDespite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, additional drugs are needed to improve care of this disease. JAK inhibitors (JAKinhibs) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA. Tofacitinib and Upadacitinib were recently approved for the treatment of PsA. Our aim was to assess the efficacy and safety of JAKinhibs for the treatment of PsA.MethodsA systematic review of the literature was performed to identify RCTs by electronic search of MEDLINE and EMBASE database until April 2021. RCTs were considered eligible if included only patients with PsA treated with JAKinhibs. The pooled efficacy and safety outcomes were calculated by meta-analysis and expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I² statistic.ResultsFive RCTs for a total of 3293 PsA patients treated with different JAKinhibs or placebo were included (2 phase III studies on Tofacitinib, 1 phase II study on Filgotinib and 2 phase III studies on Upadacitinib). All the studies were judged at low risk of bias according to Cochrane criteria. JAKinhibs showed a significantly higher ACR20 response rate compared to placebo (OR 3.78, 95% CI 2.72–5.24, I^2 = 57%, random effect model).and were associated with a non-statistically significant higher risk of serious adverse events (OR 1.12, 95% CI 0.14–2.82, I^2 = 46%, random effect model).ConclusionsThis is the first systematic review that performed a comprehensive evaluation of the efficacy and safety of JAKinhibs for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKinhibs that appear to be effective and safe over placebo for the treatment of PsA.     

Characterization of human H1N1 influenza virus variants selected in vitro with zanamivir in the presence of sialic acid-containing molecules

Understanding the molecular mechanisms of influenza virus resistance to neuraminidase inhibitors is a main concern for their clinical use. In an attempt to reproduce in vivo selective conditions where influenza virus resistance to neuraminidase inhibitors can occur the zanamivir selection of an A/H1N1 influenza virus strain was carried out in Madin-Darby canine kidney cells performed in the presence or absence of sialic acid-containing inhibitor analogues that act as virus decoy receptors. The zanamivir-selected variants passaged in the presence of sialic acid-containing molecules resembling the human-like virus receptor lost the ability to bind red blood cells. Furthermore, whereas all zanamivir-selected variants exhibited a robust reduction in susceptibility to zanamivir in plaque assays only those obtained after extensive passages acquired a powerful neuraminidase enzyme resistance to zanamivir and oseltamivir. Evidence that balanced neuraminidase and hemagglutinin activities mediated by mutations induced during selection could play a role in the decrease of virus replication susceptibility to zanamivir is reported.     

Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients

Monocyte differentiation into dendritic cells (DCs) depends on microenvironmental conditions. In this study, the capacity of human monocytes to differentiate into mature DCs and their ability to induce an antiviral immune response was investigated in HIV-infected patients. In healthy subjects, monocytes differentiate into CD1a+ DCs in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 and matured in the presence of lipopolysaccharide. Here, we found that in 30% and 45% of HIV-infected white and African subjects, respectively, monocytes gave rise to a homogeneous CD1a* DC population. In the patients who gave rise only to the CD1a* DCs, this population spontaneously produced IL-10 but not IL-12, and induced a T helper 2-like immune response when cultured with human T cells isolated from cord blood mononuclear cells. In patients with monocytes differentiated into CD1a* DCs, a high percentage of HIV-specific CD4 T cells producing IL-4 were seen in the peripheral blood. Furthermore, differentiation of monocytes into DCs with CD1a* phenotype correlated with low CD4 T-cell counts and high viral loads in HIV-infected subjects. These results suggest that the differentiation of monocytes into CD1a* DCs may be a phenotypic marker associated with progression of the disease.     

Intestinal permeability and systemic endotoxemia after laparotomic or laparoscopic cholecystectomy

OBJECTIVE: Because laparoscopic cholecystectomy (LC) is widely recognized as a "mild" or "mini-invasive" kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach. SUMMARY BACKGROUND DATA: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. METHODS: Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. RESULTS: Intestinal permeability was significantly increased at day 1 [0.106 +/- 0.005 (mean +/- SEM)] in the laparotomic group compared with the preoperative level (0.019 +/- 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 +/- 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (r(s) = 0.958; P = 0.001). CONCLUSIONS: An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.     

The institution of a Multi‐disciplinary Italian Breast Unit: Reflections of the first psychosocial research study results on distress and quality of life

Breast cancer affects patients both emotionally and physically. It is time to consider distress as the sixth vital sign in breast cancer patients in Europe. Between 2012 and 2015, our EUSOMA‐certified multi‐disciplinary group conducted a study on emotional distress and quality‐of‐life in breast cancer patients at diagnosis, and observed their trend over the first 8 months of treatment. One hundred and forty‐nine patients concluded the program. The psycho‐oncologist and the breast nurses gave out SF36, Hospital Anxiety and Depression Scale and Distress Thermometer. Our Italian data go along with the reported literature on distress and quality‐of‐life. Despite modern advances, experiencing breast cancer impacts on overall quality‐of‐life.     

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies

Purpose

Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation.

Methods

This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records.

Results

Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p?= 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p?= 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p?= 0.976.

Conclusions

Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

     

Evaluation with breast scintigraphy of breast lesions of indeterminate significance after conventional triple diagnostic approach

The role of breast scintigraphy in the evaluation of 30 women with an uncertain diagnosis following triple assessment was investigated. Scintigraphy was positive in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and 2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether dubious lesions were designated as positive or negative. This study shows that breast scintigraphy is not sufficiently sensitive or specific to use in the evaluation of lesions of uncertain diagnosis following triple assessment.