Varicella Zoster Virus-Specific Hyperimmunoglobulin in the Adjuvant Treatment of Immunocompromised Herpes Zoster Patients: A Case Series.

INTRODUCTION: Immunocompromised patients are at increased risk for herpes zoster (HZ)-associated complications. Despite standard therapy with systemic antiviral drugs and analgesics, complications are frequently encountered, including generalization of lesions or persistent neuropathic pain, so-called post-herpetic neuralgia (PHN). Given the scarcity of literature and awareness of therapeutic options to improve patient outcomes, especially for vulnerable patient groups, here we describe a strategy based on early intensification of treatment with a varicella zoster virus-specific hyperimmunoglobulin (VZV-IgG), which is approved in the adjuvant treatment of HZ. METHODS: For this case series, we selected four cases of HZ in patients with impaired immunity due to hemato-oncologic disease or immunosuppressive treatment who presented with either existing generalized lesions and/or severe pain or with other risk factors for a complicated HZ course such as PHN. They were considered to be representative examples of different patient profiles eligible for intensification of treatment by the addition of VZV-IgG to virostatic therapy. CASE REPORT: All patients showed a rapid response to combined treatment with VZV-IgG and a virostatic agent. In two patients who had generalized lesions, the formation of new lesions ceased 1 day after VZV-IgG infusion. One patient, with mantle cell lymphoma, achieved complete healing of the lesions 9 days after diagnosis of HZ, a rare occurrence compared to similar cases or cohorts. A patient with HZ in the cervical region showed a good response after a single dose of VZV-IgG. None of the patients developed post-zoster-related complications. Combination therapy of a virostatic agent and VZV-IgG was well tolerated in these four cases. CONCLUSION: This case series demonstrates highly satisfactory treatment effectiveness and tolerability for VZV-IgG in the adjuvant treatment of immunocompromised HZ patients and supports early intensification of HZ therapy in patients at high risk of severe disease progression.

[Successful therapy of retronychia]. / Erfolgreiche Therapie einer Retronychie.

ANAMNESIS: We report on a 66-year-old patient who had had painful swelling of his left big toe for about 9 months with subjectively stopped growth. EXAMINATION: Previously, bacteriological, and mycological smears and an MRI examination had not provided any groundbreaking findings, and previous antibiotic, antiseptic and anti-inflammatory therapies had not contributed to alleviating the symptoms. DIAGNOSIS AND THERAPY: Based on the clinical findings with a reddened, piston-like distended distal phalanx with a raised proximal nail wall, we made the diagnosis of retronychia and performed a nail plate extraction. CLINICAL COURSE: In the follow-up checks, which lasted more than two years, the patient was symptom-free with recovered nail growth. CONCLUSION: As in the case presented, retronychia is often misdiagnosed. The knowledge of groundbreaking clinical and anamnestic parameters and the correct therapy options allows a quick, inexpensive, and long-term successful treatment.

Pathophysiology and clinical manifestations of immune complex vasculitides.

Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass systemic and skin-limited variants of IgA vasculitis (IgAV), cryoglobulinemic vasculitis (CV), rheumatoid, lupus, and hypocomplementemic vasculitides, serum sickness cutaneous IgM/IgG (non-IgA) vasculitis, and recurrent macular (hypergammaglobulinemic or exertion-induced) vasculitis. Serum sickness and CV fulfill the criteria of a type III hypersensitivity immune reaction as large lattices of the IC precipitate at vessel walls and activate polymorphonuclear neutrophils (PMNs). Immunoglobulin-A vasculitis differs with regard to the causes of perivascular deposition of ICs since here many IgA1 molecules are hypoglycosylated (Gd-IgA1), which appears to facilitate their perivascular deposition in skin and mesangium (via e.g. CD71). The reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wall via Fcy or Fcα receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is associated with increased serum levels of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA.

Comprehensive Analyses of miRNAs Revealed miR-92b-3p, miR-182-5p and miR-183-5p as Potential Novel Biomarkers in Melanoma-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are important mediators in the intercellular communication, influencing the function and phenotype of different cell types within the tumor micro-milieu and thus promote tumor progression. Since EVs safely transport packages of proteins, lipids and also nucleic acids such as miRNAs, EVs and their cargo can serve as diagnostic and prognostic markers. Therefore, the aim of this study was to investigate EV embedded miRNAs specific for melanoma, which could serve as potential biomarkers. In contrast to previous studies, we not only analysed miRNAs from EVs, but also included the miRNA profiles from the EV-secreting cells to identify candidates as suitable biomarkers. While the characterization of EVs derived from normal melanocytes and melanoma cells showed largely comparable properties with regard to size distribution and expression of protein markers, the NGS analyses yielded marked differences for several miRNAs. While miRNA load of EVs derived from normal human epidermal melanocytes (NHEMs) and melanoma cells were very similar, they were highly different from their secreting cells. By comprehensive analyses, six miRNAs were identified to be enriched in both melanoma cells and melanoma cell-derived EVs. Of those, the accumulation of miR-92b-3p, miR-182-5p and miR-183-5p in EVs could be validated in vitro. By functional network generation and pathway enrichment analysis we revealed an association with different tumor entities and signaling pathways contributing melanoma progression. Furthermore, we found that miR-92b-3p, miR-182-5p and miR-183-5p were also enriched in EVs derived from serum of melanoma patients. Our results support the hypothesis that miRNAs derived from EVs can serve as prognostic or diagnostic liquid biopsy markers in melanoma. We identified EV-derived miRNAs and showed that those miRNAs, which were enriched in melanoma cells and EVs, are also found elevated in serum-derived EVs of patients with metastatic melanoma, but not in healthy subjects.

Prevalence of Incretin-Mimetic and Sodium-Glucose-Transporter-2-Inhibitor Therapy in German Hospitalized Type-2 Diabetics Following Myocardial Revascularization: An Observational Study.

INTRODUCTION: Real-world data indicate that sodium glucose transporter-2-inhibitor therapy and/or incretin mimetics are not widely prescribed in type-2 diabetics with atherosclerotic vascular disease. We hypothesized that incretin-mimetic therapy is associated with better overall survival and 1-year mortality in type-2 diabetics following myocardial revascularization. METHODS: Hospitalized type-2 diabetics of the Departments of Cardiology and Cardiothoracic Surgery (University Hospital Halle) who needed myocardial revascularization (PCI or CABG) in 2016 were included in this observational study: group 1 (incretin-mimetic therapy), group 2 (insulin therapy without incretin mimetics) and group 3 (oral diabetes medication without incretins or insulin). They were asked to mail in a questionnaire on medical therapy and outcomes 1.9 years following discharge. In non-responders, vital status was obtained by local registration offices 2.4 years after discharge. RESULTS: Two hundred four patients were recruited in this study. At discharge, only 4.4% of all type-2 diabetics were on incretin mimetic, 39.7% on insulin and 55.9% on oral diabetes medication. At the time of follow-up (response rate: 44.1%), there was no change in terms of prevalence of incretin-mimetic therapy (5.6% of responders). Prevalence of sodium glucose transporter-2-inhibitor therapy increased from 6.9% to 15.6% in responders. In-hospital mortality (group 1: 0%, group 2: 0%, group 3: 5.2%; p = 0.092), survival after discharge (group 1: 88.9%, group 2: 86.4%, group 3: 88.0%; p = 0.942) and number of rehospitalizations within 12 months after discharge (group 1: 1.0 per capita, group 2: 1.0, group 3: 1.1; p = 0.697) were similar among prespecified groups and between group 2 and 3. By 1.9-year follow-up, hypoglycemic events were more frequent in group 2 (1.5 ± 2.9) than in group 3 (0.02 ± 0.1; p = 0.0001). CONCLUSION: The prevalence of incretin mimetics and sodium-glucose-transporter-2 inhibitors was low both during the index hospitalization and at a 1.9-year follow-up. When comparing group 2 and group 3 patients, survival and rehospitalizations were similar; hypoglycemic events occurred more often in insulin-treated diabetics than in the those without.