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Anon Paichitrojjana, Thep Chalermchai School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok, ThailandCorrespondence: Thep Chalermchai, School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, 36/87-88 PS Tower 25Fl, Asoke Road, Sukhumvit 21, Klong Toey Nua, Wattana, Bangkok, 10110, Thailand, Tel +66-2-6644360, Email thep_chalermchai@hotmail.comBackground: There is no single effective treatment for demodicosis; successful treatment requires a multimodal approach. Relapse or recurrence of demodicosis is relatively high, making the therapy challenging. Several reports have documented the successful treatment of demodicosis with acaricidal agents, which aimed at reducing the excessive number of Demodex mites and improving the patients’ symptoms. Reports of irritation and resistance to topical acaricidal agents have led to the search for effective alternative treatments.Materials and Methods: A total of 100 standardized skin surface biopsy (SSSB) biopsy slides from 100 patients with demodicosis were randomly divided into five groups, each with 20 slides exposed to immersion oil, N, N-diethyl-meta-toluamide (DEET) 5%, 10%, 20%, and permethrin 1%, respectively. The microscopic evaluation started immediately after the test agents exposed the mites. The survival time (ST) was defined as the interval between the first exposure of Demodex folliculorum to the test agents to the time the movements ceased.Results: The differences between the median ST of DEET 5% (44 min), 10% (22 min), and 20% (14 min) were significant when compared to the negative control group (240 min) with p< 0.001, < 0.001, < 0.001, respectively. While the median ST of permethrin 1% (42 min) was not significantly different from the median ST of DEET 5% (p=0.7395).Conclusion: This study demonstrated the dose-related acaricidal effect of DEET on D. folliculorum. The survival times of DEET 5%, 10%, and 20% were significantly shorter than the negative control (immersion oil). DEET 5% had a comparable in vitro killing effect as permethrin 1%. Further in vivo studies are necessary to determine the clinical efficacy in patients with demodicosis.Keywords: Demodex mites, demodicosis, N, N-diethyl-meta-toluamide, DEET, permethrin, in vitro killing effect

Anon Paichitrojjana, Thep Chalermchai School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok, ThailandCorrespondence: Thep Chalermchai, School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, 36/87-88 PS Tower 25fl, Asoke Road, Sukhumvit 21, Klong Toey Nua, Wattana, Bangkok, 10110, Thailand, Tel +66-2-6644360, Email thep_chalermchai@hotmail.comBackground: The clinical presentation of Malassezia folliculitis (MF) can imitate acne vulgaris (AV), making it difficult to distinguish between the two conditions. Moreover, MF can coexist with AV in the same patient. The incidence of MF in patients clinically diagnosed with AV may be underestimated. This study aimed to determine the prevalence, associated factors, and clinical characterization of MF patients diagnosed with AV.Materials and Methods: Three hundred twenty new acne patients were questioned regarding general information, including age, sex, itchy symptoms, and past treatment history with antibiotics and steroids within four weeks. Clinical presentations of AV (location and severity), dandruff, and seborrheic dermatitis were examined by a dermatologist. Cytologic studies to determine the abnormal proliferation of Malassezia yeasts were performed from pustules or, in the absence of pustules, comedo-like papules, and comedones. The smears were stained with methylene blue and evaluated under a light microscope by the researcher.Results: The prevalence of MF in patients clinically diagnosed with AV was 28.8% (95% Confidence interval: CI = 23.8% - 33.7%), which can be classified as 24.7% were AV with MF and the remaining 4.1% were MF only. This study revealed that patients diagnosed with MF were 7.38 times more likely to have itchy symptoms than patients diagnosed with AV. MF patients had 8.89 times and 9.17 times higher risk of acneiform lesions on the scalp/ hairline and upper back than those who did not have MF, respectively.Conclusion: This present study revealed a high prevalence of MF in patients clinically diagnosed with AV. Dermatologists should be aware of MF when encountering AV patients with acneiform lesions on the scalp/ hairline and upper back with pruritus. Diagnosis based on clinical presentations alone may lead to misdiagnosis. Methylene blue staining is easy to perform and beneficial to diagnose MF.Keywords: Malassezia folliculitis, Pityrosporum folliculitis, acne vulgaris, methylene blue, yeast

OBJECTIVE Mechanisms underlying immune activation and HIV-associated neurocognitive disorders (HAND) in untreated chronic infection remain unclear. The objective of this study was to identify phenotypic and transcriptional changes in blood monocytes and CD4 T cells in HIV-1-infected and uninfected individuals and elucidate processes associated with neurocognitive impairment. DESIGN A group of chronically HIV-1-infected Thai individuals (n = 19) were selected for comparison with healthy donor controls (n = 10). Infected participants were further classified as cognitively normal (n = 10) or with HAND (n = 9). Peripheral monocytes and CD4 T cells were phenotyped by flow cytometry and simultaneously isolated for multiplex qPCR-targeted gene expression profiling directly ex vivo. The frequency of HIV-1 RNA-positive cells was estimated by limiting dilution cell sorting. RESULTS Expression of genes and proteins involved in cellular activation and proinflammatory immune responses was increased in monocytes and CD4 T cells from HIV-1-infected relative to uninfected individuals. Gene expression profiles of both CD4 T cells and monocytes correlated with soluble markers of inflammation in the periphery (P

BACKGROUND The current international guideline recommended 200 mg/day of hydrocortisone intravenously to treat septic shock. However, a subsequent study on cortisol metabolism actually showed an increase in cortisol level during sepsis. Hence, the smaller hydrocortisone dose of 100 mg/day might be sufficient and reduce steroid-associated complications. We aimed to compare the clinical outcomes of minimized hydrocortisone dose of 100 mg to the currently recommended dose in the treatment of septic shock patients. METHODS A double-blinded randomized controlled trial included 80 septic shock patients with hemodynamic instability despite fluid and vasopressive therapy. Participants were divided equally into two groups to treat with 100 mg/day or 200 mg/day of hydrocortisone, then stepwise down titrated and discontinued on day 8. The outcome of interest was the hyperglycemic rate. Vital status, time to shock reversal, superinfection and gastrointestinal bleeding rates were also compared. RESULTS Patients with 100 mg hydrocortisone had significantly lower hyperglycemic rate compared with 200 mg, 63.9% versus 86.5% (the adjusted hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02-0.41, P = 0.002). Time to shock reversal was shorter in patients with 100 mg hydrocortisone, 2 days vs. 4 days, P = 0.031. The 28-day mortality rate when adjusted for Simplified Acute Physiology Score II showed no significant difference (HR, 0.68; 95% CI, 0.37-1.24, P = 0.209). The reinfection and gastrointestinal bleeding rates were comparable between groups. CONCLUSION Minimized daily hydrocortisone dosage of 100 mg could lower the occurrence of hyperglycemia without increasing mortality in septic shock, compared with the currently recommended dosage of 200 mg/day.

Whereas human immunodeficiency virus (HIV) persists in tissue macrophages during antiretroviral therapy (ART), the role of circulating monocytes as HIV reservoirs remains controversial. Three magnetic bead selection methods and flow cytometry cell sorting were compared for their capacity to yield pure CD14(+) monocyte populations. Cell sorting by flow cytometry provided the purest population of monocytes (median CD4(+) T-cell contamination, 0.06%), and the levels of CD4(+) T-cell contamination were positively correlated with the levels of integrated HIV DNA in the monocyte populations. Using cell sorting by flow cytometry, we assessed longitudinally the infection of monocytes and other cell subsets in a cohort of 29 Thai HIV-infected individuals. Low levels of HIV DNA were detected in a minority of monocyte fractions obtained before and after 1 year of ART (27% and 33%, respectively), whereas HIV DNA was readily detected in CD4(+) T cells from all samples. Additional samples (2 to 5 years of ART) were obtained from 5 individuals in whom monocyte infection was previously detected. Whereas CD4(+) T cells were infected at high levels at all time points, monocyte infection was inconsistent and absent in at least one longitudinal sample from 4/5 individuals. Our results indicate that infection of monocytes is infrequent and highlight the importance of using flow cytometry cell sorting to minimize contamination by CD4(+) T cells. IMPORTANCE The role of circulating monocytes as persistent HIV reservoirs during ART is still controversial. Several studies have reported persistent infection of monocytes in virally suppressed individuals; however, others failed to detect HIV in this subset. These discrepancies are likely explained by the diversity of the methods used to isolate monocytes and to detect HIV infection. In this study, we show that only flow cytometry cell sorting yields a highly pure population of monocytes largely devoid of CD4 contaminants. Using this approach in a longitudinal cohort of HIV-infected individuals before and during ART, we demonstrate that HIV is rarely found in monocytes from untreated and treated HIV-infected individuals. This study highlights the importance of using methods that yield highly pure populations of cells as flow cytometry cell sorting to minimize and control for CD4(+) T-cell contamination.

BACKGROUND Nitrogen plasma skin regeneration is a novel device that produces heat to the skin, resulting in the production of new collagen. Because of lower energy with safer skin damage and lesser adverse effects who have high Fitzpatrick's skin type especially Thais, this technique is very interesting for clinical application for skin esthetic treatment. However, this treatment has yet been empirically studied as the treatment for mild-to-moderate periorbital wrinkles. OBJECTIVES This study aimed to evaluate clinical efficacy of nitrogen plasma for the treatment of mild-to-moderate periorbital wrinkles. METHODS Eighteen volunteers were enrolled. Each volunteer was randomized to receive nitrogen plasma treatment on one side of periorbital wrinkles with three sessions at a three-week interval and compared with contralateral side without treatment. Photographic examination, skin wrinkle (SEw) score, melanin index, patients' satisfaction score, side effect, and pain score were reported. RESULTS At over fourteen weeks, all volunteers completed the study. Treatment with nitrogen plasma group had significantly better improvement for periorbital wrinkles score by Lemperle scale, skin wrinkle (SEw) score by Visioscan® VC 98, and the melanin index by Mexameter® than the control groups (P = 0.004, P

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development.

BACKGROUND: Myeloid activation contributes to cognitive impairment in chronic human immunodeficiency virus (HIV) infection. We explored whether combination antiretroviral therapy (cART) initiation during acute HIV infection impacts CD163 shedding, a myeloid activation marker, and in turn, implications on the central nervous system (CNS). METHODS: We measured soluble CD163 (sCD163) levels in plasma and cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay in Thais who initiated cART during acute HIV infection (Fiebig stages I–IV). Examination of CNS involvement included neuropsychological testing and analysis of brain metabolites by magnetic resonance spectroscopy. Chronic HIV-infected or uninfected Thais served as controls. RESULTS: We examined 51 adults with acute HIV infection (Fiebig stages I–III; male sex, >90%; age, 31 years). sCD163 levels before and after cART in Fiebig stage I/II were comparable to those in uninfected controls (plasma levels, 97.9 and 93.6 ng/mL, respectively, vs 99.5 ng/mL; CSF levels, 6.7 and 6.4 ng/mL, respectively, vs 7.1 ng/mL). In Fiebig stage III, sCD163 levels were elevated before cART as compared to those in uninfected controls (plasma levels, 135 ng/mL; CSF levels, 10 ng/mL; P < .01 for both comparisons) before normalization after cART (plasma levels, 90.1 ng/mL; CSF levels, 6.5 ng/mL). Before cART, higher sCD163 levels during Fiebig stage III correlated with poor CNS measures (eg, decreased N-acetylaspartate levels), but paradoxically, during Fiebig stage I/II, this association was linked with favorable CNS outcomes (eg, higher neuropsychological test scores). After cART initiation, higher sCD163 levels during Fiebig stage III were associated with negative CNS indices (eg, worse neuropsychological test scores). CONCLUSION: Initiation of cART early during acute HIV infection (ie, during Fiebig stage I/II) may decrease inflammation, preventing shedding of CD163, which in turn might lower the risk of brain injury.

Monocytes play a vital role in HIV-associated neurocognitive disorder (HAND), postulated to transport HIV into the brain and secrete pro-inflammatory cytokines. We analyzed cytokines released by cultured peripheral blood mononuclear cells enriched with the CD14 marker isolated from HIV-infected individuals with HAND and normal cognition (NC) in combination antiretroviral therapy naive and after 1 year on treatment. Interleukin-8 and monocyte chemoattractant protein-1 levels were higher in HAND compared with NC at baseline (P = 0.002 and P < 0.0001). These cytokines remained higher in HAND patients 1 year after combination antiretroviral therapy and were significant when NC patients who were initially HAND were excluded (P = 0.012 and P = 0.002). Both correlated with baseline CD14 peripheral blood mononuclear cell HIV DNA levels supporting the role of HIV DNA reservoir size and monocyte cytokines in HAND persistence.

Microneedle radiofrequency (FMR) for the treatment of primary axillary hyperhidrosis radiofrequency (RF) technology is a new modality that applied deep heat energy directly affecting the epidermis and dermis. Limiting data about FMR for axillary hyperhidrosis is concerning. To compare clinical efficacy between fractional microneedle radiofrequency and intradermal botulinum toxin type A injection. This study was a randomized, intraindividual split-side comparative study. Twenty female subjects clinically diagnosed of primary axillary hyperhidrosis were enrolled. All subjects randomly assigned to receive either FMR device on one side of axilla or 50 units of intradermal botulinum toxin A on contralateral side of axilla. Treatment with FMR device was scheduled for 2 sessions for 4 weeks apart. After treatment, mean Hyperhidrosis Disease Severity Score (HDSS) of both groups revealed remarkably better reduction from the baseline (p

Background Clinical inertia is a failure to intensify treatment according to evidence-based guidelines, and can have both short- and long-term adverse effects for type 2 diabetes (T2D). The aim of the present study was to demonstrate the effects of clinical inertia on glycemic control and diabetes-related complications. Methods A retrospective cohort study was conducted at a university-based hospital in Thailand. Medical records were evaluated retrospectively from January 2010 to December 2014. Patients were classified into two groups: clinical inertia and non-inertia. Clinical inertia was defined as failure to initiate insulin within 3 months in patients with HbA1c ≥9 % who were already taking two oral antidiabetic agents. Results From 1206 records, 98 patients with mean HbA1c of 10.3 % were identified and enrolled in the study. The median follow-up time of these patients was 29.5 months and 68.4 % were classified into the clinical inertia group. The mean (± SD) HbA1c decrement in the clinical inertia and non-inertia groups was 0.82 ± 1.50 % and 3.02 ± 1.80 %, respectively, at 6 months (P

HIV DNA in monocytes has been linked to HIV-associated neurocognitive disorders (HAND), however, characterization of monocyte subsets associated with HAND remains unclear. We completed a prospective study of antiretroviral therapy-naïve, HIV-infected Thais, with varying degrees of cognitive impairment, compared to HIV-uninfected controls. Monocyte subsets' CCR2, CCR5 and CD163 expression were profiled and inflammatory markers in plasma and cerebrospinal fluid (CSF), measured. Lower numbers of CCR2(+)non-classical monocytes were associated with worse neuropsychological test performance (r=0.43, p=0.024). CCR2(+)non-classical monocyte count inversely correlated with CSF neopterin (r=-0.43, p=0.035) and plasma TNF-α levels (r=-0.40, p=0.041). These data benchmark CCR2(+)non-classical monocytes as an independent index of cognitive impairment.

Treatments of acne vulgaris commonly use antimicrobials and comedolytic agents. Considering bacterial resistance to topical antibiotics, the alternative treatment such as silver manufactured into nanoparticle receives an attention. Silver nanoparticle has an antibacterial effect against Propionibacterium acnes and anti-inflammation. Clinical study of silver nanoparticle gel for the treatment of acne vulgaris is limited.To compare the efficacy and safety between silver nanoparticle gel and 1% clindamycin gel both combine with 2.5% benzoyl peroxide for the treatment of moderate severity of acne vulgaris.This was an experimental, double-blinded, randomized-controlled study. Sixty-four moderately severe acne patients were enrolled. They were randomized to receive either silver nanoparticle gel with 2.5% benzoyl peroxide or clindamycin gel with 2.5% benzoyl peroxide (32 patients each). The clinical outcomes were evaluated for inflammatory and non-inflammatory acne count, acne redness, the patients’ satisfaction and patients’ Dermatology Life Quality Index (DLQI) at the baseline, 2, 4, 6 and 8-week visit.After 8 weeks of follow-up period, the average mean percent change from the baseline of non-inflammatory and inflammatory acne counts were gradually declined in both silver nanoparticle and clindamycin group. At the study endpoint (8-week visit), average mean percent change from the baseline of inflammatory acne count was slightly better reduction in silver nanoparticle group (79.7%) than clindamycin group (72.6%) with no significant difference (p = 0.18). The average mean percent change from the baseline of non-inflammatory acne count reduction was also no difference from silver nanoparticle and clindamycin group (61.1% and 66.8% respectively, p = 0.22). For clinical erythema score and Mexameter erythema index to evaluate acne redness were no statistical difference between the 2 groups. Moreover, the patients’ satisfaction to study medication and their quality of life of patients (DLQI score) were reported with better improvement from the baseline in both groups but there was no statistical significant difference. Except for average mean, patients’ satisfaction to acne severity at 6-week visit showed that silver nanoparticle group had better satisfaction score than clindamycin group (4.6±0.6 vs. 4.2±0.6) with statistical significance (p = 0.01). Common adverse effects were skin dryness (28.1%) and skin irritation (4.7%) which might be caused by 2.5% benzoyl peroxide. There was no adverse effect for silver nanoparticle gel from the present study.Silver nanoparticle gel is effective with good safety profile for the treatment of acne vulgaris. The present study demonstrated that there were no clinical significant differences between silver nanoparticle gel and clindamycin gel for the treatment of moderate severity of acne vulgaris when use in combination with 2.5% benzoyl peroxide. The clinical application as alternative treatment for acne is advised.

Picosecond laser is a novel modality for pigmented skin disorders with extremely short pulse duration. Little is known about the effects of the picosecond laser in melasma.This study aimed to investigate the efficacy of fractional picosecond 1,064 nm laser in melasma treatment.A prospective, randomized, assessor-blinded, intra-individual split face comparative study.Female subjects with melasma were enrolled and received fractional picosecond 1,064 nm laser plus 4% hydroquinone cream on one randomly assigned side of the face; the results were compared to the use of hydroquinone cream only on the contralateral side. The modified melasma area severity index (mMASI) score, melanin index by Mexameter MX18®, participant satisfaction score by quartile rating scale, and the quality of life by the dermatology life quality index (DLQI) were evaluated over 12 weeks.Thirty female subjects completed the protocol. The mean (± standard deviation, SD) mMASI score at the 12-week visit was significantly reduced in the picosecond laser-treated areas compared to controls (3.52 ± 1.4 and 4.18 ± 2.03 respectively; p = 0.035). No differences were observed in the mean Mexameter melanin index, participant satisfaction score, and DLQI score. The observed adverse effects included transient mild erythema and mild skin desquamation.The addition of fractional picosecond 1,064 nm laser to 4% hydroquinone was effective and significantly better than 4% hydroquinone alone for the treatment of melasma.

Background It is unclear whether intensification of standard highly active antiretroviral therapy (HAART) with entry and integrase inhibitors during acute HIV infection (AHI) could yield greater benefits in reducing markers for HIV reservoir size and immune activation. Methods Thai patients with Fiebig I–IV AHI were prospectively enrolled and offered treatment. They were randomised 1 : 1 to HAART (tenofovir/emtricitabine/efavirenz, n=31) or megaHAART, a standard regimen intensified by raltegravir/maraviroc (n=31), during the first 24 weeks of therapy. Participants were monitored at weeks 0, 2, 4, 8 and 12, then every 12 weeks. Frequencies of peripheral blood mononuclear cells (PBMCs) carrying HIV DNA (total, integrated and 2-LTR episomes), plasma C-reactive protein (CRP) concentrations, and frequencies of activated T cells were measured. Flexible sigmoidoscopy was performed in willing participants (n=25) at baseline, weeks 24 and 96, and proviral DNA and RNA were determined. Results Baseline characteristics were similar in the HAART and megaHAART arms. Median age was 28 years and 95% were men. Median CD4 cell count was 388 cells/mm3. HIV RNA was 5.6 log10 copies/mL. HIV RNA declined more rapidly in the first 4 weeks with megaHAART (median –3.3 log10) than HAART (–2.6 log10). Time to achieve HIV RNA

BACKGROUND: Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection (AHI) is unknown. METHODS: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). RESULTS: CSF CD8+ T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+ T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+ T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+ T cells in AHI exhibited increased functional gene expression profiles associated with CD8+ T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+ T cells directed to unique HIV epitopes compared with the periphery. CONCLUSIONS: These results suggest that CSF CD8+ T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.

OBJECTIVE: To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. DESIGN: A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. METHODS: AHI (n = 33) and CHI (n = 34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n = 24), 1 year in CHI participants (n = 10)]. Measured parameters were analyzed at each timepoint. Analyses employed Mann–Whitney tests and Spearman correlations. RESULTS: Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/l; P = 0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/l; P = 0.003). In untreated CHI, YKL-40 correlated with neopterin (r = 0.51, P = 0.0025), chemokine (CXC-motif) ligand-10 (r = 0.44, P = 0.011), and neurofilament light chain (r = 0.56, P = 0.0008) in CSF. CONCLUSIONS: This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.

SummaryBackground Striae distensae (SD) is a form of dermal scar. A number of treatments have been proposed, but they usually have unsatisfactory result especially in striae alba. Recently, nanofractional RF has been developed. Its mechanism of action is to stimulate dermal remodeling and epidermal re-epithelization. Aim To evaluate the efficacy and safety of nanofractional RF in the treatment of striae alba. Patients/Methods This is an experimental, assessor-blinded, before–after study. Thirty-three subjects, with striae alba on their thighs, abdomen, or buttocks (11 subjects each) were enrolled. Treatments with nanofractional RF were undergone for a total of three sessions at 4-week intervals. Clinical outcomes were assessed, by comparing pre- and post-treatment measurement of total lesional surface area (using digital Pictzar™ software), and length and width of lesions. Histopathological evaluation was also performed. Results At 4 weeks after the last treatment, the total surface area, and the width and the length of striae alba significantly decreased from the baseline (P < 0.001). Postinflammatory hyperpigmentation was reported in six subjects. Regarding histopathology, the average mean number of collagen and elastin bundles was significantly increased (P = 0.005 and 0.012, respectively). Conclusion Nanofractional RF is highly effective with a good safety profile for the treatment of striae alba.

ObjectiveTo evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment.DesignSoluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naïve individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks.MethodsPlasma and CSF levels of 19 soluble biomarkers (IFN-γ, TNFα, TNF-RII, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFNα, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay.ResultsPrior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNFα, TNF-RII, IFNα, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls.ConclusionWe provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy.

CD8+ T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8+ T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8+ T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8+ T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8+ T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8+ T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8+ T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8+ T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.

Clinical inertia is a failure to intensify treatment according to evidence-based guidelines, and can have both short- and long-term adverse effects for type 2 diabetes (T2D). The aim of the present study was to demonstrate the effects of clinical inertia on glycemic control and diabetes-related complications.A retrospective cohort study was conducted at a university-based hospital in Thailand. Medical records were evaluated retrospectively from January 2010 to December 2014. Patients were classified into two groups: clinical inertia and non-inertia. Clinical inertia was defined as failure to initiate insulin within 3 months in patients with HbA1c ≥9 % who were already taking two oral antidiabetic agents.From 1206 records, 98 patients with mean HbA1c of 10.3 % were identified and enrolled in the study. The median follow-up time of these patients was 29.5 months and 68.4 % were classified into the clinical inertia group. The mean (± SD) HbA1c decrement in the clinical inertia and non-inertia groups was 0.82 ± 1.50 % and 3.02 ± 1.80 %, respectively, at 6 months (P 0.001) and 1.46 ± 1.85 % and 3.04 ± 1.76 %, respectively, at the end of study (P 0.001). Clinical inertia was associated with a significantly shorter median time to progression of diabetic retinopathy (DR); log rank test, P = 0.02 and a higher incidence of DR progression (10 vs 2.2 cases per 1000 person-months; P = 0.003). The adjusted incidence rate ratio for DR progression in the clinical inertia group was 4.92 (95 % confidence interval 1.11-21.77; P = 0.036). Being treated by general practitioners was the strongest risk factor associated with clinical inertia.Clinical inertia can cause persistently poor glycemic control and speed up the progression of DR in T2D.

An increase in Staphylococcus aureus skin colonization in atopic dermatitis patients resulted from the reduction of cathelicidin production in these patients. Recently, an in vivo study demonstrated that vitamin D could stimulate cathelicidin production. Oral supplements of vitamin D might be beneficial in atopic dermatitis.To determine the effects of oral vitamin D supplements on clinical impact including Staphylococcus aureus skin colonization evaluation in atopic dermatitis patients.Twenty-four atopic dermatitis patients were included in this double-blind, placebo-controlled study. They were randomly assigned into 2 groups for oral 2,000 IUs/day of vitamin D, supplement and placebo. The lesional swab culture for S. aureus was done at week 0, 2 and 4. Clinical outcomes were assessed by SCORAD score, mexameter for erythema index and konometer for conductance were done at week 0, 2 and 4. Serum vitamin D levels were also determined at week 0 and 4.Twenty patients completed the protocol. S. aureus skin colonization, SCORAD score and erythema index were significantly reduced from baseline to week 4for vitamin D treated group comparing with placebo (p = 0.022, 0.028 and 0.014, respectively). There was an inverse correlation between serum vitamin D levels with S. aureus skin colonization and SCORAD score (r = -1.0, p0.001).Oral vitamin D supplement could reduce skin colonization of S. aureus and demonstrated the clinical improvement of patients with atopic dermatitis.

Journal of Medicine and Health Sciences, 23, 3

Prior to widespread availability of combination antiretroviral therapy (cART), the most severe form of human immunodeficiency virus type 1 (HIV) encephalopathy, previously termed “AIDS dementia complex,” occurred almost exclusively in late disease, often when circulating CD4+ lymphocyte counts were

To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART).Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART.Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 12 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test.Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART.Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals.

Aim: The aim of the present study was to compare the efficacy of 200 mg versus 400 mg daily of pyridoxine in preventing or delaying the onset of palmar-plantar erythrodysesthesia (PPE) in capecitabine-treated patients. Methods: Patients with histologically confirmed breast cancer or colorectal cancer receiving single agent capecitabine started at 2000 to 2500 mg/m2 daily from day 1 to 14 every 3 weeks were randomly assigned to receive 200 mg or 400 mg daily of pyridoxine for PPE prophylaxis. The primary endpoint was the reduction of incidence of grade 2 or greater PPE. Secondary endpoints were reduction of severe PPE and prolongation of time to development of grade 2 or greater PPE. Results: There were 56 patients in this study. The baseline characteristics were generally similar in both groups. The high dose arm had less PPE than the low dose arm (11 of 28 or 39% vs 20 of 28 or 71%, relative risk = 0.26 [0.08, 0.79], P = 0.031). Grade III PPE developed in 3 of 28 (10.7%) versus none in patients receiving 200 mg versus 400 mg pyridoxine, respectively (relative risk 2.12 [1.594, 2.819], P = 0.24). High dose pyridoxine had a longer time to development of grade 2 or greater PPE compared to the low dose arm, 87 days versus 62 days. The 400 mg pyridoxine group had, however, a worsened tumor response and tended to have greater tumor treatment failure and shorter time to treatment failure. Conclusion: With the limitation of sample size in this study, there was a trend to improve PPE incidence and time to event with a higher dose of pyridoxine. Further validation of these results in a larger population is warranted.

Objective: The aim of this study was to review cases of extra-pulmonary small cell carcinoma (EPSCC), including their clinical manifestations and treatment outcomes. Methods: We retrospectively reviewed the medical records and pathological reports of patients who were diagnosed with EPSCC from 1998 to 2005. Results: Overall 21 EPSCC patients were eligible for this study. The most common primary sites were the gastrointestinal organs and the nasal cavity. Eleven patients (52.3%) had limited disease (LD) and 10 patients (47.7%) had extensive disease (ED). Nine patients underwent radical surgery alone, four received only radical radiation and two received only palliative chemotherapy. Two patients received adjuvant radiation or chemotherapy following surgical resection and one received a combination of all three treatment modalities. Three patients declined specific treatment and were treated with best supportive care. The median overall survival in the ED group was only 3 months (range 1–16 months), compared to 30 months (range 20–61 months) for LD. EPSCC of pancreas demonstrated a favorable clinical outcome with treatment, whereas primary EPSCC of the liver, esophagus and rectum had an aggressive natural history and a poor response to treatment. Conclusion: Our report suggests that EPSCC may have a different biology from that of pulmonary small cell carcinoma. When detected at an early stage, EPSCC may have an excellent prognosis with treatment. Additional studies involving more patients with EPSCC are warranted to further define the optimal roles of each treatment modality.

In search for putative tumor suppressor genes critical of nasopharyngeal carcinoma (NPC), we analyzed the available information from the expression profiling in conjunction with the comprehensive alleotyping published data relevant to this malignancy. Integration of this information suggested eight potential candidate tumor suppressor genes, CCNA1, HRASLS3, RARRES1, CLMN, EML1, TSC22, LOH11CR2A and MCC. However, to confirm the above observations, we chose to investigate if promoter hypermethylation of these candidate genes would be one of the mechanisms responsible for the de-regulation of gene expression in NPC in addition to the loss of genetic materials. In this study, we detected consistent hypermethylation of the 5' element of CCNA1, RARRES1, and HRASLS in NPC tissues with prevalence of 48%, 51%, and 17%, respectively. Moreover, we found a similar profile of promoter hypermethylation in primary cultured NPC cells but none in normal nasopharyngeal epithelium or leukocytes, which further substantiate our hypothesis. Our data indicate that CCNA1, RARRES1, and HRASLS3 may be the putative tumor suppressor genes in NPC.

Objective Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. Methods We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART. Results At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013). Conclusions cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.

Background. It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Methods. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Results. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = −0.40; P = .03), frontal white matter (r = −0.46; P = .01), and parietal gray matter (r = −0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = −0.51; P = .02) and parietal gray matter (r = −0.46; P = .04). Conclusions. CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

Recent reports have suggested influences of racial difference on the frequency of mutation of EGFR in lung cancer. We therefore sought to characterize the frequency and pattern of mutation of EGFR in lung adenocarcinoma in Thai patients. Overall, EGFR catalytic domain mutations were detected in 35/61 (57.4%). We found 29/60 (48.3%) of exon 19 deletions, 5/54 (9.3%) of exon 21 point mutations, and 1/54 (1.9%) of double-mutation of both exons. The presence of these mutations was significantly associated with non-smoking habit. In summary, we report a strikingly high prevalence of mutation of EGFR in Thai lung adenocarcinoma, which may explain the high response rate to the treatment with TKI among Asian populations.

Author(s): Kallianpur, Kalpana J; Valcour, Victor G; Lerdlum, Sukalaya; Busovaca, Edgar; Agsalda, Melissa; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James LK; Tipsuk, Somporn; Shikuma, Cecilia M; Shiramizu, Bruce T; Ananworanich, Jintanat; SEARCH 011 study group | Abstract: ObjectiveTo examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART).DesignA prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion.MethodsCD14 cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA).ResultsWe studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/μl and log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells for this cohort, a threshold value above which CD14 HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14 HIV DNA ≥ 45 copies/10 cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4 cell count and intracranial volume.ConclusionHIV DNA burden in CD14 monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells.

A longitudinal cohort study was conducted in Bangkok, Thailand between 2008 and 2013 in order to determine the practice effect of serial neuropsychological testing and establish normative data among normal (HIV-uninfected) Thai volunteers.The authors enrolled 511 cognitively healthy individuals (HIV-uninfected, no drug abuse or other previous/current neurological or psychological conditions) to assess baseline performance on a HIV-specific neuropsychological testing battery. Ninety-nine subjects were re-assessed at 6 and 12 months to evaluate practice effects.The mean age of the 99 subjects completing longitudinal visits was 49.2 years and 53 were male. The authors identified improved mean raw scores on most neuropsychological tests with repeated measurements; however only change in WHO Auditory Verbal Learning Test (AVLT) scores (learning, attention, immediate and delayed recall tasks) met statistical significance, with larger differences seen between baseline and 6-month compared to 6 and 12 months follow-up. Older age correlated with poorer baseline raw score, and was a predictor of worse performance at 6 months and 12 months on several tasks. Level of education was associated with practice effects on several tests. No similar effects were observed with gender.The authors identified improved performance after repeated measurements revealing a significant practice effect on an HIV-specific neuropsychological testing battery employed in Bangkok, Thailand. Main predictors were age and educational attainment.

There were errors in multiple affiliations for multiple authors. Please see the following correct list of authors and affiliations: Victor G. Valcour 1,2*,Jintanat Ananworanich, 3,4,5,6, Melissa Agsalda 6, Napapon Sailasuta 7, Thep Chalermchai 3, Alexandra Schuetz 8, Cecilia Shikuma 6, Chin-Yuan Liang 6, Supunee Jirajariyavej 9, Pasiri Sithinamsuwan 10, Somporn Tipsuk 3, David B. Clifford 11, Robert Paul 12, James L. K. Fletcher 3, Mary A. Marovich 13, Bonnie M. Slike 14, Victor DeGruttola 15, Bruce Shiramizu 6 1. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA USA 2. Division of Geriatric Medicine, Department of Medicine, University of California, San Francisco CA, USA 3. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 4. HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand 5. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 6. Hawaii Center for AIDS, University of Hawaii, Honolulu HI USA 7. Huntington Medical Research Institutes, Pasadena CA USA 8. Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 9. Taksin Hospital, Bangkok, Thailand 10. Division of Neurology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand 11. Department of Neurology, Washington University, St. Louis MO USA 12. Department of Psychology, University of Missouri, St. Louis MO, USA 13. Division of AIDS, National Institute of Allergy and Infection Diseases of the National Institutes of Health, Bethesda MD, USA 14. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring MD, USA 15. Department of Biostatistics, Harvard School of Public Health, Boston MA, USA

Objectives:Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14+ enriched monocytes predicted cognitive impairment and brain injury.Methods:We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).Results:The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.Interpretation:Reservoir burden of HIV DNA in monocyte-enriched (CD14+) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS. © 2013 Valcour et al.

Background Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection. Methods A nested case–control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT ≥ 40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection. Results A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0 ± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level > 5 log 10 copies/ml, metabolic syndrome at baseline visit, high BMI > 23 kg/m2, abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value 2 was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8, p = 0.01). Conclusions Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health care problem. Male sex and high BMI ≥ 23 kg/m2 carry higher risks for developing chronic hepatitis in this study. Therefore, these patients should be closely monitored for long-term hepatotoxicity.

Although HIV-Associated Dementia (HAD) occurs in less than 5% of individuals with access to combination antiretroviral therapy (cART), rates of milder forms of HIV-Associated Neurocognitive Disorder (HAND) are much higher. We sought to define an optimal cut-point for the International HIV-Dementia Scale (IHDS) in Thailand for the identification of symptomatic HAND, defined as both HAD and Mild Neurocognitive Disorder (MND). We then sought to determine if adding a simple test from a larger neuropsychological battery could improve the performance characteristics for identifying symptomatic HAND. In this study 75 seropositive adults in Bangkok, Thailand, subjects completed neuropsychological tests and underwent a full neurological assessment. HAND diagnoses were determined by consensus conference using the 2007 Frascati criteria, blinded to the IHDS results. The optimal IHDS cut-point was determined by Receiver Operating Characteristic analysis with cross-validation. Individual neuropsychological tests were then evaluated and combined with the IHDS to test performance characteristics. The IHDS was poor at detecting symptomatic HAND at the optimized cut-point of ≤10 (sensitivity: 53.3%, specificity: 89.8%). The Trail Making Test A was most effective in improving performance characteristics when combined with the IHDS, with net sensitivity of 86% and specificity of 79%. In this setting, the IHDS performed poorly in identifying symptomatic HAND, but was substantially improved by the addition of Trail Making Test A, which typically requires less than two minutes to complete. This combination should be validated in a larger setting since it may address the critical need for HAND screening instruments in international settings.

International studies of HIV-associated neurocognitive disorder (HAND) are needed to determine the viral and host factors associated with cognitive impairment particularly as more than 80% of HIV+ subjects reside in resource-limited settings. Recent diagnostic nomenclature of HAND requires comparison of cognitive performance specifically to local normative data. To evaluate this need for local norms, we compared normative data obtained locally in Thailand to Western norms. The current study examined cognitive performance in 477 seronegative Thai participants (male = 211, female = 266) who completed a battery of tests sensitive to cognitive changes in HIV. The cohort was divided into three age brackets (20-34; 35-49; 50-65 years) and four educational levels (no education or primary education, less than secondary certificate, high-school/associates degree, bachelor's degree or greater). The Thai cohort was compared (using analysis of covariance, ANCOVA) on a number of measures to a seronegative US cohort (n = 236; male = 198, female = 38) to examine cultural differences in performance. Normative data are provided with age and education stratification. The Thai and US groups performed significantly differently on all neuropsychological measures with the exception of verbal fluency. The Thai group performed better on measures of verbal learning (p < .001) and memory (p < .001) and measures of psychomotor speed (p < .001). Education was a more powerful predictor of performance in the Thai cohort than in the US group. These results highlight the continued need for the development of normative data within local populations. The use of Western norms as a comparison group could lead to inaccurate identification of HAND in culturally distinct groups.

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

The aim of this study was to review cases of extra-pulmonary small cell carcinoma (EPSCC), including their clinical manifestations and treatment outcomes.We retrospectively reviewed the medical records and pathological reports of patients who were diagnosed with EPSCC from 1998 to 2005.Overall 21 EPSCC patients were eligible for this study. The most common primary sites were the gastrointestinal organs and the nasal cavity. Eleven patients (52.3%) had limited disease (LD) and 10 patients (47.7%) had extensive disease (ED). Nine patients underwent radical surgery alone, four received only radical radiation and two received only palliative chemotherapy. Two patients received adjuvant radiation or chemotherapy following surgical resection and one received a combination of all three treatment modalities. Three patients declined specific treatment and were treated with best supportive care. The median overall survival in the ED group was only 3 months (range 1-16 months), compared to 30 months (range 20-61 months) for LD. EPSCC of pancreas demonstrated a favorable clinical outcome with treatment, whereas primary EPSCC of the liver, esophagus and rectum had an aggressive natural history and a poor response to treatment.Our report suggests that EPSCC may have a different biology from that of pulmonary small cell carcinoma. When detected at an early stage, EPSCC may have an excellent prognosis with treatment. Additional studies involving more patients with EPSCC are warranted to further define the optimal roles of each treatment modality.