Retiform Purpura as a Complication of Microsphere Emboli Following Transarterial Chemoembolization for Primary Hepatocellular Carcinoma: A Case Report and Literature Review.

We report an elderly man with hepatocellular carcinoma who developed a rash after undergoing transarterial chemoembolization (TACE). On examination, there was a reticulated macular pigmentation over the chest and upper abdomen. Skin biopsy revealed foreign material that occluded the small dermal cutaneous vessels. These structures were perfectly spherical, homogeneously eosinophilic, and were also nonrefractile. They had a maximum diameter of 40 µm, consistent with the size of the microspheres used in TACE. TACE is a palliative measure used to treat hepatocellular carcinoma in patients who are not surgical candidates. Vaso-occlusive manifestations of the skin are rare occurrences, with only 8 reported cases. Seven cases attributed this to nontarget embolization of the hepatic falciform artery and 1 case postulated that collateral supply of the targeted area allowed for hematogenous migration of the occluding beads via the microcirculation. Pertaining to treatment, all patients were treated with oral nonsteroidal anti-inflammatory agents to good effect, with 1 patient receiving additional laser treatment and another having local steroid injections. Prognosis is excellent, because the skin lesions tend to resolve within a year. Several methods have been suggested to prevent these vaso-occlusive skin complications, including prophylactic application of ice or placing the tip of the microcatheter distal to the origin of the hepatic falciform artery and falciform artery.

NKT Cell Hyporesponsiveness Leads to Unrestrained Accumulation of Marginal Zone B Cells in Hypercholesterolemic Apolipoprotein E-Deficient Mice.

Recently, the role of B cells in atherosclerosis has gained more attention but studies have mainly focused on B1 and follicular B cell subsets. Therefore, the contribution of marginal zone (MZ) B cells in experimental atherosclerosis remains elusive. In the current study, we examined the MZ B cell compartment in atherosclerotic apoE-deficient (apoE-/-) mice and found that hypercholesterolemia in these mice was associated with an increased number and percentage of MZ B cells. This aberrant accumulation of MZ B cells was not associated with alterations in their development or increased proliferation but was due to decreased apoptotic cell death. This decrease in MZ B cell death in apoE-/- mice was associated with the reduced capacity of invariant NKT (iNKT) cells to produce IFN-γ and IL-4 after activation. Lowering cholesterol plasma levels with ezetimibe in apoE-/- mice reversed iNKT function and MZ B cell accumulation. To elucidate the mechanism whereby iNKT cells control MZ B cell accumulation in apoE-/- mice, we performed an adoptive transfer of iNKT cells and found that only wild-type iNKT cells but not IFN-γ-/- iNKT cells reversed MZ B cell accumulation in apoE-/- recipient mice. Our findings reveal that lipid changes associated with atherosclerotic disease induce decreased production of IFN-γ by iNKT, which in turn leads to aberrant accumulation of MZ B cells. This study further extends the importance of iNKT cells in regulating MZ B cell compartment.

Splenic extrafollicular reactions and BM plasma cells sustain IgM response associated with hypercholesterolemia.

Hypercholesterolemia associated with atherosclerotic disease is known to be associated with increased total and oxidized (ox) low-density lipoprotein (LDL)-specific IgM antibodies in circulation. However, the B-cell responses accounting for this increase remain to be elucidated. Here, we observed an association between total IgM and oxLDL-specific IgM autoantibodies with cholesterol in the plasma of hypercholesterolemic apolipoprotein E deficient (apoE(-/-)) mice. Our findings also indicated that oxLDL-specific IgM autoantibodies production was restricted to the spleen, but not the lymph nodes. Further examination of the spleen revealed that the extrafollicular responses, but not germinal center reactions, were the dominant antibody-producing pathway. A quiescent population of IgM(+) plasma cells including oxLDL-specific IgM antibody secreting cells in BM also sustained the elevated IgM antibodies response in circulation. We determined that IgM(+) plasma cells in the BM were, at least in part, splenic derived by depleting CD11c(+) DCs and plasmablasts to disrupt the humoral responses. In addition, lowering hypercholesterolemia reduced IgM response by interfering with extrafollicular and BM responses. By elucidating the mechanism underlying the elevated IgM response observed in hypercholesterolemia, this study provides insight into novel immunotherapeutic avenues.

Instrumental Role of Helicobacter pylori γ-Glutamyl Transpeptidase in VacA-Dependent Vacuolation in Gastric Epithelial Cells.

Helicobacter pylori causes cellular vacuolation in host cells, a cytotoxic event attributed to vacuolating cytotoxin (VacA) and the presence of permeant weak bases such as ammonia. We report here the role of γ-glutamyl transpeptidase (GGT), a constitutively expressed secretory enzyme of H. pylori, in potentiating VacA-dependent vacuolation formation in H. pylori-infected AGS and primary gastric cells. The enhancement is brought about by GGT hydrolysing glutamine present in the extracellular medium, thereby releasing ammonia which accentuates the VacA-induced vacuolation. The events of vacuolation in H. pylori wild type (WT)- and Δggt-infected AGS cells were first captured and visualized by real-time phase-contrast microscopy where WT was observed to induce more vacuoles than Δggt. By using semi-quantitative neutral red uptake assay, we next showed that Δggt induced significantly less vacuolation in AGS and primary gastric epithelial cells as compared to the parental strain (P<0.05) indicating that GGT potentiates the vacuolating effect of VacA. Notably, vacuolation induced by WT was significantly reduced in the absence of GGT substrate, glutamine (P<0.05) or in the presence of a competitive GGT inhibitor, serine-borate complex. Furthermore, the vacuolating ability of Δggt was markedly restored when co-incubated with purified recombinant GGT (rGGT), although rGGT itself did not induce vacuolation independently. Similarly, the addition of exogenous ammonium chloride as a source of ammonia also rescued the ability of Δggt to induce vacuolation. Additionally, we also show that monoclonal antibodies against GGT effectively inhibited GGT activity and successfully suppressed H. pylori-induced vacuolation. Collectively, our results clearly demonstrate that generation of ammonia by GGT through glutamine hydrolysis is responsible for enhancing VacA-dependent vacuolation. Our findings provide a new perspective on GGT as an important virulence factor and a promising target in the management of H. pylori-associated gastric diseases.

Nonablative infrared skin tightening in Type IV to V Asian skin: a prospective clinical study.

BACKGROUND: Nonablative skin tightening devices have been developed to treat facial and neck skin laxity without damage to the epidermis. There are at present two main approaches: the pioneer method by monopolar radiofrequency and the second by infrared light. OBJECTIVE: This study aims to determine the clinical efficacy and safety of nonablative infrared light in the treatment of facial and neck skin laxity in Type IV to V Asian skin. METHODS: This is a prospective noncomparative open study. Adult patients with facial and neck skin laxity were recruited for the study. Three treatment sessions spaced 4 weeks apart were performed. Photographic documentation was performed serially during the study period. Final clinical assessment was performed 6 months after the last treatment. Response parameters included patient self-assessment as well as doctor's assessment. RESULTS: Twenty-one patients were evaluated. All patients were of Fitzpatrick skin types IV and V. Patient assessments of response at 6 months after treatment were as follows: 19% reported mild improvement, 38% reported moderate improvement, and 43% reported good improvement. Doctor's assessments of photographs before and 6 months after treatment showed observable lifting of sagging skin folds in 86% of patients. Of these, 28% were assessed as significant-mild, 38% as significant-moderate, and 19% as significant-excellent. The treatments were associated with minimal pain and edema. The main side effect was isolated superficial blistering in 7 episodes of 63 treatments performed, which resolved without scarring in all patients. CONCLUSION: Direct application of infrared light with epidermal cooling is effective in achieving mild to moderate gradual clinical improvement in the treatment of facial and neck skin laxity. The procedure is associated with minimal downtime and is safe for use in darker skin, Types IV and V.

Treatment of acquired bilateral nevus of ota-like macules (Hori's nevus) with a combination of the 532 nm Q-Switched Nd:YAG laser followed by the 1,064 nm Q-switched Nd:YAG is more effective: prospective study.

BACKGROUND: Acquired bilateral nevus of Ota-like macules (Hori's nevus) is a common dyschromatosis among Asian women. Q-switched lasers have been used successfully as a treatment modality. OBJECTIVE: The purpose of this study was to compare the efficacy of using the Q-switched 532 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser followed by the 1,064 nm laser versus the Q-switched 1,064 nm Nd:YAG laser alone in the treatment of Hori's nevus. METHODS: This is a prospective left-right comparative study. Ten women with bilateral Hori's nevus were recruited and treated with a combination of the Q-switched 532 and 1,064 nm Nd:YAG lasers on the right cheek and the Q-switched 1,064 nm Nd:YAG laser alone on the left cheek. Only one laser treatment session was performed. The degree of pigmentation was objectively recorded with a mexameter. Subjective assessment was made by both patients and two blinded, nontreating dermatologists. RESULTS: At 6 months, there was a statistically significant difference (p = .009) of 35.10 points using objective mexameter measurements between the two sides, favoring the side treated with a combination of 532 and 1,064 nm laser treatment. Subjective grading by the patients and blinded dermatologists also confirmed that combination therapy was more successful after one treatment. Although combination treatment had a higher incidence of mild postinflammatory changes, this disappeared within 2 months. CONCLUSIONS: Concurrent use of the Q-switched 532 nm Nd:YAG laser in combination with the 1,064 nm laser is more effective in pigment clearance than the Q-switched 1,064 nm Nd:YAG laser alone for Hori's nevi.

The psoriasis disability index in Chinese patients: contribution of clinical and psychological variables.

OBJECTIVES: To provide a description of medical and psychological aspects of Chinese psoriasis patients, and to examine the specific contribution of demographic, medical and psychological variables to the Psoriasis Disability Index. METHODS: Ninety-three Chinese psoriasis patients underwent a clinical assessment using the Psoriasis Area and Severity Index (PASI) and completed a questionnaire that included questions on demographic and medical data, the Hospital Anxiety and Depression Scale (HADS) and the Psoriasis Disability Index (PDI). RESULTS: Psoriasis patients with cosmetic involvement had higher levels of anxiety and depression and higher disability scores than those without cosmetic involvement. Thirty-four per cent of the patients reported a significant level of anxiety (HADS-anx. > 11). The clinical severity of psoriasis was not associated with psychological and PDI scores. Multiple regression analysis indicated that psychological variables were associated with PDI scores, and explained 30% of the variance. However, demographic and psoriasis severity variables explained only 6% of the variance. CONCLUSION: Psoriasis patients suffer from anxiety and depression. Psychological factors are much stronger determinants of the PDI than demographic, disease related variables. Clinical management of the disease should consider both clinical and psychological factors.

Nonablative 1450-nm diode laser in the treatment of facial atrophic acne scars in type IV to V Asian skin: a prospective clinical study.

BACKGROUND: There is presently little published data on the clinical effectiveness of nonablative lasers in the treatment of atrophic acne scars and the safety of their use in patients with darker skin types. OBJECTIVE: This study aims to determine the clinical effectiveness and safety of the nonablative 1450 nm diode laser with cryogen cooling spray in the treatment of facial atrophic acne scars in Type IV-V Asian skin. METHODS: This is a prospective non-comparative open study. 4 to 6 laser treatment sessions were performed on patients with atrophic acne scars. Final clinical assessment was performed 6 months after the last treatment. RESULTS: 57 patients were evaluated. Patient's self-assessment of scar improvement as compared with doctor's assessment was as follows: patients who completed 4 treatments (15.7% vs 6.6%), patients who completed 5 treatments (20% vs 7.9%) and patients those who completed 6 treatments (17.3% vs 5.0%). Main side effects were mild to moderate pain during the procedure, transient erythema, and hyperpigmentation which occurred in 39% of treated patients. CONCLUSION: The nonablative 1450 nm diode laser may be effective in achieving mild to moderate gradual clinical improvement in the treatment of facial atrophic acne scars. The procedure is associated with minimal downtime and is safe for use in darker skin types IV and V.