Immunogenicity and safety of a live herpes zoster vaccine in hematopoietic stem cell transplant recipients.

BACKGROUND: Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination. METHODS: Live HZ vaccine was administered to patients 2-5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored. RESULTS: Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2-5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96-5.07] vs 5.05, 95% CI [2.50-10.20] vs 2.97, 95% CI [2.30-3.83] vs 1.42, 95% CI [1.08-1.86]). The GMFR of cellular immune responses was highest in the HSCT 2-5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period. CONCLUSION: Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Recovery of Tenofovir-induced Nephrotoxicity following Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Human Immunodeficiency Virus-Positive Patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity is related to high plasma tenofovir concentrations. Tenofovir alafenamide (TAF) is a tenofovir prodrug with 90% lower plasma tenofovir concentrations. The aim of this study was to evaluate changes in tenofovir-induced nephrotoxicity in Human Immunodeficiency Virus (HIV)-positive patients who switched from TDF to TAF. MATERIALS AND METHODS: We identified all HIV-positive patients who switched from elvitegravir/cobicistat/emtricitabine/TDF to elvitegravir/cobicistat/emtricitabine/TAF at a tertiary hospital. We assessed tubulopathy and renal dysfunction before TDF administration, at the time TAF was used following at least 3 months of TDF use, and 3 months after TAF administration. Tubulopathy was defined by the presence of at least three abnormalities in fractional excretion of phosphate, fractional excretion of uric acid, urinary ß2-microglobulin, urinary N-acetyl-ß-D-glucosaminidase, glucosuria or proteinuria. Renal dysfunction was defined as decreased by more than 25% in the estimated glomerular filtration rate (eGFR) relative to baseline. RESULTS: In 80 patients, the mean eGFR was 96.8 mL/min/1.73 m² before administration of TDF, 81.2 (P <0.001) at the time of change to TAF, 90.9 (P <0.001) after TAF administration. Renal dysfunction occurred in 19 patients (23.8%) after TDF use for a median 15 months, 11 (57.9%) of these patients recovered from renal dysfunction after TAF administration. Six patients (7.5%) had tubulopathy before TDF administration, 36 (45.0%) after TDF administration (P <0.001), 12 (15.0%) after TAF administration (P = 0.002). CONCLUSION: Tenofovir-induced nephrotoxicity in HIV-positive patients receiving TDF was mostly reversible after changing to TAF. Thus, TAF-containing regimens can be administered safely to HIV-positive patients with tenofovir-induced nephrotoxicity.

Factors associated with recurrent fifth metatarsal stress fracture.

BACKGROUND: Many surgeons agree that fifth metatarsal stress fractures have a tendency toward delayed union, nonunion, and possibly refracture. Difficulty healing seems to be correlated with fracture classification. However, refracture sometimes occurs after low-grade fracture, even long after apparent resolution. METHODS: The records of 168 consecutive cases of fifth metatarsal stress fracture (163 patients) treated by modified tension band wiring from March 2002 to June 2011 were evaluated retrospectively. Mean length of follow-up was 23.6 months (range, 10-112 months). Forty-nine cases classified as Torg III were bone grafted initially also. All enrolled patients were elite athletes. Eleven patients experienced nonunion and 18 refracture. The 11 nonunion cases were bone grafted. The 157 patients (excluding nonunion cases) were allocated to either a refracture group or a union group. Clinical features, such as age, weight, fracture classification, time to union, and reinjury history, were compared. Radiological parameters representing cavus deformity and fifth metatarsal head protrusion were compared to evaluate the influence of structural abnormalities. RESULTS: Mean group weights were significantly different (P = .041), but mean ages (P = .879), fracture grades (P = .216, P = .962), and time from surgery to rehabilitation (P = .539) were similar. No significant intergroup differences were found for talocalcaneal (TC) angle (P = .470), calcaneal pitch (CP) angle (P = .847), or talo-first metatarsal (T-MT1) angle (P = .407) on lateral radiographs; for fifth metatarsal lateral deviation (MT5-LD) angle (P = .623) on anteroposterior (AP) radiographs; or for MT5-LD angle (P = .065) on the 30-degree medial oblique radiographs. However, the mean fourth-fifth intermetatarsal (IMA4-5) angle on AP radiographs was significantly greater in the refracture group, and for Torg II cases, mean weight (P = .042), IMA4-5 angle on AP radiographs (P = .014), and MT5-LD angle (P = .043) on 30-degree medial oblique radiographs were significantly greater in the refracture group. For B2 cases (incomplete fracture and a plantar gap of 1 mm or larger), mean weight (P = .046), IMA4-5 angle on AP radiographs (P = .019), and MT5-LD angle (P = .045) on 30-degree medial oblique radiographs were significantly greater in the refracture group. All cases of refracture had a traumatic history after bone union. Refracture developed within 6 months of starting rehabilitation in 13 cases and within 3 months in 8 cases. CONCLUSION: The development of refracture after the surgical treatment of fifth metatarsal stress fractures was found to be associated with higher body mass index (BMI) and with radiological parameters (IMA4-5 on AP radiographs, MT5-LD on oblique radiographs) associated with protrusion of the fifth metatarsal head. The study indicates that patients with a protruding fifth metatarsal head and a high BMI should approach rehabilitation with care before considering a return to previous sporting activity levels. LEVEL OF EVIDENCE: Level III, retrospective comparative series.