Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34+-selected hematopoietic stem cell transplant for acute lymphoblastic leukemia

We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones. Antiviral treatment with foscarnet and ganciclovir was successful but prolonged treatment was required to prevent relapses. We hypothesize that this complication was more related to an immune reconstitution process than to an immune-deficient state post-grafting. We conclude that CMV retinitis is a late complication of HSCT that can occur despite satisfactory immune reconstitution. Usually, it is responsive to antiviral therapy. Dilated fundoscopic examination is essential both for examining patients with reduced visual acuity and for screening asymptomatic patients.     

Improvement of prognosis in idiopathic dilated cardiomyopathy: role of early diagnosis and optimized medical treatment. Study Group on Heart Muscle Diseases

BACKGROUND: The aim of this study was to assess the extent to which a more widespread use of new effective treatments for heart failure associated with earlier detection of the disease may have contributed to enhancing the prognosis of idiopathic dilated cardiomyopathy (IDC) patients over the past 20 years. METHODS: Heart transplant-free survival curves were analyzed in 343 IDC patients, prospectively enrolled from January 1, 1978 to June 30, 1997 in the Heart Muscle Disease Registry of the Cardiology Department in Trieste (94 enrolled between 1978 and 1987, Group 1; 249 between 1988 and 1997, Group 2). At enrollment, 91 patients had no heart failure symptoms (NoHF), whereas the remaining 252 showed HF of recent (HF < or = 6 months, n = 132) or non-recent (HF > 6 months, n = 120) onset. RESULTS: In comparison to Group 1, Group 2 was treated more frequently with ACE-inhibitors and beta-blockers (p < 0.0001) and showed a better long-term survival (p = 0.0034), resulting from a reduction of death for refractory HF or need for heart transplant (p = 0.011). Conversely, the risk of sudden death did not significantly differ between the two groups. NoHF, HF > 6 months and HF < or = 6 months groups were similarly treated with ACE-inhibitors and beta-blockers. Long-term survival was better in patients without HF than in those with overt HF (p = 0.0015). As compared to Group HF > 6 months, Group HF < or = 6 months had a poorer one-year prognosis (p = 0.045), related to the presence of a subgroup of patients with refractory HF and need for heart transplant, but showed a better survival rate over the following years (p = 0.015). Over the two subsequent decades of enrollment, a significant improvement in patient survival was observed within Groups NoHF (p = 0.03) and HF > 6 months (p = 0.01), but not in Group HF < or = 6 months. CONCLUSIONS: Over the past 20 years, the increasing use of ACE-inhibitors and beta-blockers in IDC was associated with a significant improvement in long-term survival, resulting from a reduction in mortality for refractory heart failure or need for heart transplant. In addition, early diagnosis may have contributed significantly to enhancing the prognosis of IDC, since the benefits of medical therapy were lower in patients identified and treated in advanced stages of the disease. Moreover, early diagnosis was shown to be useful in recognizing patients with recent onset of heart failure who are not responders to aggressive medical treatments and urgently need heart transplant.     

2D shear wave elastography in evaluation of prognostic factors in breast cancer

Purpose

To evaluate the reproducibility of the 2D shear wave elastography (2D-SWE) method and to identify the prognostic factors of breast lesions.

Methods

In this prospective study, 44 female patients were consecutively included from January 2020 to September 2021. All patients showing visible masses at B-mode ultrasound underwent to clinical evaluation, followed by qualitative and quantitative 2D-SWE by two different operators with over 15-year and 2-year experience, respectively. Subsequently, patients underwent to surgical treatment after core needle biopsy. Reproducibility of qualitative and quantitative 2D-SWE was evaluated by Cohen’s kappa and intraclass correlation coefficient (ICC). Clinical, imaging, and histopathological data and 2D-SWE evaluations were analysed with Spearman's rank correlation test.

Results

The mean age of the patients was 55 years?±?12. The mean histological and ultrasound tumour size of were 23.1 mm?±?13.2 and 17.2 mm?±?10.2, respectively. The interobserver agreement showed a good reproducibility limited to the qualitative evaluation colour maps (Cohen’s kappa?=?0.603) and to the quantitative evaluation E ratio (ICC?=?0.771). Correlation analysis between the ultrasound and 2D-SWE values and the clinical-pathological parameters showed a significant relationship between E ratio and Elston–Ellis grading (P?<?0.030) and between tumour size and Elston–Ellis grading (P?<?0.041).

Conclusion

The 2D-SWE has shown good reproducibility among operators with different experience. It could be a promising tool in the evaluation of some prognostic factors in ultrasound visible breast cancer.

     

Inhibition of influenza A virus replication by resveratrol

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.     

Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the "shell" as compared with the "core" of the rat nucleus accumbens.

The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine on extracellular dopamine concentrations in the nucleus accumbens shell and core by means of microdialysis with vertically implanted concentric probes. Doses selected were in the range of those known to sustain drug self-administration in rats. Morphine, at 0.2 and 0.4 mg/kg, and cocaine, at 0.5 mg/kg, increased extracellular dopamine selectivity in the shell. Higher doses of cocaine (1.0 mg/kg) and the lowest dose of amphetamine tested (0.125 mg/kg) increased extracellular dopamine both in the shell and in the core, but the effect was significantly more pronounced in the shell compared with the core. Only the highest dose of amphetamine (0.250 mg/kg) increased extracellular dopamine in the shell and in the core to a similar extent. The present results provide in vivo neurochemical evidence for a functional compartmentation within the nucleus accumbens and for a preferential effect of psychostimulants and morphine in the shell of the nucleus accumbens at doses known to sustain intravenous drug self-administration.     

Clinical and diagnostic aspects of cystic insulinoma

Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.