Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice.

Cachexia is a systemic wasting syndrome that increases cancer-associated mortality. How cachexia progressively and differentially impacts distinct tissues is largely unknown. Here, we find that the heart and skeletal muscle undergo wasting at early stages and are the tissues transcriptionally most impacted by cachexia. We also identify general and organ-specific transcriptional changes that indicate functional derangement by cachexia even in tissues that do not undergo wasting, such as the brain. Secreted factors constitute a top category of cancer-regulated genes in host tissues, and these changes include upregulation of the angiotensin-converting enzyme (ACE). ACE inhibition with the drug lisinopril improves muscle force and partially impedes cachexia-induced transcriptional changes, although wasting is not prevented, suggesting that cancer-induced host-secreted factors can regulate tissue function during cachexia. Altogether, by defining prevalent and temporal and tissue-specific responses to cachexia, this resource highlights biomarkers and possible targets for general and tissue-tailored anti-cachexia therapies.

A Prospective, Cohort Study of the Effect of Acute and Chronic Malnutrition on Length of Stay in Children Having Surgery in Rwanda.

BACKGROUND: Malnutrition is common in pediatric surgical patients, but there are little data from low-income countries that estimate the association of malnutrition with surgical outcomes. We aimed to determine the prevalence of malnutrition and its association with length of stay (LOS) among pediatric surgical patients in Kigali, Rwanda. METHODS: We conducted a prospective observational cohort study. We enrolled surgical patients between 1 month and 15 years of age. We measured the association of acute malnutrition (wasting) and chronic malnutrition (stunting) with postoperative LOS using log-gamma regression to account for the skewed LOS distribution. Adjustment was made for sex, age, elective versus emergency surgery, household income, and American Society of Anesthesiologists (ASA) classification. RESULTS: Of 593 children, 124 children (21.2%) had acute malnutrition (wasting) with 39 (6.6%) severely wasted. A total of 160 (26.9%) children had chronic malnutrition (stunting), with 81 (13.7%) severely stunted. Median (interquartile range [IQR]) LOS after surgery was 2 (1-5) days for children with mild/no wasting, 6 (2.5-12.5) days for children with moderate wasting, and 6 (2-15) days with severe wasting. Median (IQR) LOS after surgery was 2 (1-6) days for children with mild/no stunting, 3 (1-3) days for children with moderate stunting, and 5 (2.3-11.8) days with severe stunting malnutrition. After adjustment for confounders, the moderate wasting was associated with increased LOS, with ratio of means (RoM), 1.6; 95% confidence interval [CI], 1.3-2.0; P < .0001. Severe wasting was not associated with increased LOS (RoM, 1.3; 95% CI, 0.9-1.7; P = .12). Severe, but not moderate, stunting was associated with increased LOS (RoM, 1.9; 1.5-2.4; P < .0001). CONCLUSIONS: Malnutrition is prevalent in >20% of children presenting for surgery and associated with increased LOS after surgery, even after accounting for individual and family-level confounders. Although some aspects of malnutrition may relate to the surgical condition, severe malnutrition may represent a modifiable social risk factor that could be targeted to improve postoperative outcomes and resource use. Severely stunted children should be identified as at risk of having delayed recovery after surgery.

Carboplatin-induced renal salt-wasting syndrome in pediatric patients with intracranial germ cell tumors and concomitant diabetes insipidus.

We report a case series of 14 children with intracranial germ cell tumor and concomitant central diabetes insipidus, who developed hyponatremia secondary to renal salt-wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatremia can be asymptomatic until it is severe.

Incidence and predictors of reoccurrence of opportunistic infection among adult HIV/AIDS patients attending ART clinic at public health facilities in Arba Minch town, southern Ethiopia: A retrospective cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infected individuals are prone to opportunistic infections (OIs) due to HIV mediated immune suppression. When opportunistic infections occur in the form of relapse or reinfection, it is said to be reoccurrence. This study was aimed to assess Incidence and predictors of reoccurrence of opportunistic infections among adult people living with HIV (PLHIV) attending ART clinics in Arba Minch Town, Southern Ethiopia. METHODS: This retrospective cohort study was conducted on 450 HIV/AIDS patients attending anti-retro viral therapy (ART) clinics in Arba Minch town, southern Ethiopia. Simple random sampling technique was used. Kaplan-Meier graph and log rank test were used for group wise comparison. Bivariate and multivariable Cox Proportional Hazard Regression model were used to identify independent predictors of reoccurrence of opportunistic infection. RESULT: One hundred nineteen HIV/AIDS patient had reoccurrence of opportunistic infection. The incidence rate was 11.5 per 1000 person months. The mean time of reoccurrence was 56 months. One of the most reoccurred OIs was pulmonary tuberculosis (PTB). Predictors that were associated significantly were recent cell differentiation 4 (CD4) count, recent body mass index (BMI), recent functional status, and duration on anti-retroviral therapy (ART). CONCLUSION: Though the incidence rate of OIs decreased from previous findings, attention should be given to HIV patients with low CD4 count, low BMI and for those bedridden patients.

Differential Effects of 25-Hydroxyvitamin D3 versus 1α 25-Dihydroxyvitamin D3 on Adipose Tissue Browning in CKD-Associated Cachexia.

Patients with chronic kidney disease (CKD) often have low serum concentrations of 25(OH)D3 and 1,25(OH)2D3. We investigated the differential effects of 25(OH)D3 versus 1,25(OH)2D3 repletion in mice with surgically induced CKD. Intraperitoneal supplementation of 25(OH)D3 (75 µg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) for 6 weeks normalized serum 25(OH)D3 or 1,25(OH)2D3 concentrations in CKD mice, respectively. Repletion of 25(OH)D3 normalized appetite, significantly improved weight gain, increased fat and lean mass content and in vivo muscle function, as well as attenuated elevated resting metabolic rate relative to repletion of 1,25(OH)2D3 in CKD mice. Repletion of 25(OH)D3 in CKD mice attenuated adipose tissue browning as well as ameliorated perturbations of energy homeostasis in adipose tissue and skeletal muscle, whereas repletion of 1,25(OH)2D3 did not. Significant improvement of muscle fiber size and normalization of fat infiltration of gastrocnemius was apparent with repletion of 25(OH)D3 but not with 1,25(OH)2D3 in CKD mice. This was accompanied by attenuation of the aberrant gene expression of muscle mass regulatory signaling, molecular pathways related to muscle fibrosis as well as muscle expression profile associated with skeletal muscle wasting in CKD mice. Our findings provide evidence that repletion of 25(OH)D3 exerts metabolic advantages over repletion of 1,25(OH)2D3 by attenuating adipose tissue browning and muscle wasting in CKD mice.

Nutritional status and dietary diversity of school-age children living with HIV: a cross-sectional study in Phnom Penh, Cambodia.

BACKGROUND: HIV/AIDS continues to be a major public health concern for children. Each day, worldwide, approximately 440 children became newly infected with HIV, and 270 children died from AIDS-related causes in 2018. Poor nutrition has been associated with accelerated disease progression, and sufficient dietary diversity is considered a key to improve children's nutritional status. Therefore, this study aims to 1) examine nutritional status of school-age children living with HIV in Phnom Penh, Cambodia, and 2) identify factors associated with their nutritional status, especially taking their dietary diversity into consideration. METHODS: This cross-sectional study was conducted in May 2018 within the catchment area of the National Pediatric Hospital, Cambodia. Data from 298 children and their caregivers were included in the analyses. Using semi-structured questionnaires, face-to-face interviews were conducted to collect data regarding sociodemographic characteristics, quality of life, and dietary diversity. To assess children's nutritional status, body weight and height were measured. Viral load and duration of antiretroviral therapy (ART) were collected from clinical records. Multiple logistic regression analyses were performed to identify factors associated with stunting and wasting. RESULTS: Of 298 children, nearly half (46.6%) were stunted, and 13.1% were wasted. The mean number of food groups consumed by the children in the past 24 h was 4.6 out of 7 groups. Factors associated with children's stunting were age (adjusted odds ratio [AOR] 2.166, 95% confidence interval [CI]: 1.151, 4.077), household wealth (AOR 0.543, 95%CI: 0.299, 0.986), duration of receiving ART (AOR 0.510, 95%CI: 0.267, 0.974), and having disease symptoms during the past 1 year (AOR 1.871, 95%CI: 1.005, 3.480). The only factor associated with wasting was being male (AOR 5.304, 95%CI: 2.210, 12.728). CONCLUSIONS: Prevalence of stunting was more than double that of non-infected school-age children living in urban areas in Cambodia. This highlights the importance of conducting nutritional intervention programs, especially tailored for children living with HIV in the country. Although dietary diversity was not significantly associated with children's nutritional status in this study, the findings will contribute to implementing future nutritional interventions more efficiently by indicating children who are most in need of such interventions in Cambodia.

[Nutritional Support for Patients with Pancreatic Cancer].

Pancreatic cancer is the ninth common malignancy in South Korea. It has a dismal prognosis with a 5-year overall survival rate of less than 10%, and pancreatic cancer is associated with cancer cachexia, which is defined as the loss of muscle mass that is not reversible by conventional nutritional support. Cachexia is noted in over 85% of all pancreatic cancer patients and it is strongly related with the disease's mortality. Nearly 30% of pancreatic cancer deaths are due to cachexia rather than being due to the tumor burden. Therefore, it is crucial to discover the mechanisms behind the development of muscle wasting in pancreatic cancer patients and find novel therapeutics for targeting cachexia. This review deals with the current understanding about the development of cachexia and nutritional support in those patients suffering with pancreatic cancer.

Autophagy Exacerbates Muscle Wasting in Cancer Cachexia and Impairs Mitochondrial Function.

Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective ß2-agonist, muscle sparing was paralleled by reduced static autophagy markers, although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting.

Improving screening for malnourished children at high risk of death: a study of children aged 6-59 months in rural Senegal.

OBJECTIVE: To investigate whether children with concurrent wasting and stunting require therapeutic feeding and to better understand whether multiple diagnostic criteria are needed to identify children with a high risk of death and in need of treatment. DESIGN: Community-based cohort study, following 5751 children through time. Each child was visited up to four times at 6-month intervals. Anthropometric measurements were taken at each visit. Survival was monitored using a demographic surveillance system operating in the study villages. SETTING: Niakhar, a rural area of the Fatick region of central Senegal.ParticipantsChildren aged 6-59 months living in thirty villages in the study area. RESULTS: Weight-for-age Z-score (WAZ) and mid-upper arm circumference (MUAC) were independently associated with near-term mortality. The lowest WAZ threshold that, in combination with MUAC, detected all deaths associated with severe wasting or concurrent wasting and stunting was WAZ <-2·8. Performance for detecting deaths was best when only WAZ and MUAC were used. Additional criteria did not improve performance. Risk ratios for near-term death in children identified using WAZ and MUAC suggest that children identified by WAZ <-2·8 but with MUAC≥115 mm may require lower-intensity treatment than children identified using MUAC <115 mm. CONCLUSIONS: A combination of MUAC and WAZ detected all near-term deaths associated with severe anthropometric deficits including concurrent wasting and stunting. Therapeutic feeding programmes may achieve higher impact if WAZ and MUAC admission criteria are used.

Muscle wasting in young patients with dilated cardiomyopathy.

BACKGROUND: Muscle wasting can be accelerated by chronic diseases such as heart failure and is one of the major causes of disability, morbidity, and mortality in this population. We aimed to investigate the incidence of muscle wasting and its associated factors in dilated cardiomyopathy patients younger than 55 years of age. METHODS: Between April 2014 and December 2015, all symptomatic patients with a diagnosis of non-ischaemic dilated cardiomyopathy who were referred to heart failure clinic were included in our study. Dual energy X-ray absorptiometry was used to evaluate body composition and identify muscle wasting. Muscle mass was calculated as the ratio of an individual's total lean mass of legs and arms (also called appendicular skeletal muscle) to their squared height (kg/m2 ). The muscle mass values of less than 5.45 kg/m2 for women and 7.26 kg/m2 for men were considered low. RESULTS: A total of 55 patients (32 male) were included. The mean (standard deviation) of age was 37.3 (10.1) years, and the mean of left ventricular ejection fraction was 21.4%. Most of the patients were in the New York Heart Association classes of II and II-III. Twenty-six patients (47.3%) met criteria for muscle wasting. Patients with muscle wasting had lower left ventricular ejection fraction, lower 6-min walk distance, and higher New York Heart Association function class and hospitalization rate. CONCLUSIONS: We concluded that muscle wasting might be present in younger patients with heart failure, particularly in those who are in worse clinical condition.

HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition.

Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome.

Malnutrition and Cachexia in Heart Failure.

Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients.

Distinct behaviour of sorafenib in experimental cachexia-inducing tumours: the role of STAT3.

The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways.

Angiotensin II inhibits satellite cell proliferation and prevents skeletal muscle regeneration.

Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Although patients with advanced CHF or CKD often have increased angiotensin II (Ang II) levels and cachexia and Ang II causes skeletal muscle wasting in rodents, the potential effects of Ang II on muscle regeneration are unknown. Muscle regeneration is highly dependent on the ability of a pool of muscle stem cells (satellite cells) to proliferate and to repair damaged myofibers or form new myofibers. Here we show that Ang II reduced skeletal muscle regeneration via inhibition of satellite cell (SC) proliferation. Ang II reduced the number of regenerating myofibers and decreased expression of SC proliferation/differentiation markers (MyoD, myogenin, and active-Notch) after cardiotoxin-induced muscle injury in vivo and in SCs cultured in vitro. Ang II depleted the basal pool of SCs, as detected in Myf5(nLacZ/+) mice and by FACS sorting, and this effect was inhibited by Ang II AT1 receptor (AT1R) blockade and in AT1aR-null mice. AT1R was highly expressed in SCs, and Notch activation abrogated the AT1R-mediated antiproliferative effect of Ang II in cultured SCs. In mice that developed CHF postmyocardial infarction, there was skeletal muscle wasting and reduced SC numbers that were inhibited by AT1R blockade. Ang II inhibition of skeletal muscle regeneration via AT1 receptor-dependent suppression of SC Notch and MyoD signaling and proliferation is likely to play an important role in mechanisms leading to cachexia in chronic disease states such as CHF and CKD.

Autophagic degradation contributes to muscle wasting in cancer cachexia.

Muscle protein wasting in cancer cachexia is a critical problem. The underlying mechanisms are still unclear, although the ubiquitin-proteasome system has been involved in the degradation of bulk myofibrillar proteins. The present work has been aimed to investigate whether autophagic degradation also plays a role in the onset of muscle depletion in cancer-bearing animals and in glucocorticoid-induced atrophy and sarcopenia of aging. The results show that autophagy is induced in muscle in three different models of cancer cachexia and in glucocorticoid-treated mice. In contrast, autophagic degradation in the muscle of sarcopenic animals is impaired but can be reactivated by calorie restriction. These results further demonstrate that different mechanisms are involved in pathologic muscle wasting and that autophagy, either excessive or defective, contributes to the complicated network that leads to muscle atrophy. In this regard, particularly intriguing is the observation that in cancer hosts and tumor necrosis factor α-treated C2C12 myotubes, insulin can only partially blunt autophagy induction. This finding suggests that autophagy is triggered through mechanisms that cannot be circumvented by using classic upstream modulators, prompting us to identify more effective approaches to target this proteolytic system.

High prevalence of anemia with lack of iron deficiency among women in rural Bangladesh: a role for thalassemia and iron in groundwater.

Iron deficiency was absent in a recent population assessment of rural Bangladeshi women exhibiting anemia (57%), suggesting other causes of low hemoglobin. We assessed the relative influence on anemia of thalassemia, groundwater arsenic and iron, and diet among women of reproductive age living in rural Bangladesh. Women (n=207) sampled from a previous antenatal nutrient intervention trial in rural Bangladesh were visited during two seasons in 2008. Collected data included 7-day dietary and 24-hour drinking water intake recalls, 7-day morbidity recall, anthropometry, and drinking water arsenic and iron concentrations. Capillary blood was analyzed for iron (plasma ferritin, soluble transferrin receptor), inflammation (C-reactive protein) and thalassemia (ß thalassemia and Hb E) status. In stratified, adjusted analyses, only parity was associated with anemia (odds ratio, OR (95% CI): 11.34 (1.94, 66.15)) for those with thalassemia (28% prevalent). In contrast, groundwater iron intake (>30 mg/d, 0.48 (0.24, 0.96)) and wasting (2.32 (1.17, 4.62)) were associated with anemia among those without thalassemia. Elevated groundwater arsenic (>50 µg/L, 12% of tubewells) and a diverse diet were unrelated to anemia regardless of thalassemia diagnosis (p>0.70 and >0.47, respectively). Among women in this typical rural Bangladeshi area, the prevalence of thalassemia was high and, unlike iron deficiency which was absent most likely due to high iron intake from groundwater, contributed to the risk of anemia. In such settings, the influence of environmental sources of iron and the role of thalassemias in contributing to anemia at the population level may be underappreciated.

Hepatocyte IKK2 protects Mdr2-/- mice from chronic liver failure.

UNLABELLED: Mice lacking the Abc4 protein encoded by the multidrug resistance-2 gene (Mdr2(-/-)) develop chronic periductular inflammation and cholestatic liver disease resulting in the development of hepatocellular carcinoma (HCC). Inhibition of NF-κB by expression of an IκBα super-repressor (IκBαSR) transgene in hepatocytes was shown to prevent HCC development in Mdr2(-/-) mice, suggesting that NF-κB acts as a tumour promoter in this model of inflammation-associated carcinogenesis. On the other hand, inhibition of NF-κB by hepatocyte specific ablation of IKK2 resulted in increased liver tumour development induced by the chemical carcinogen DEN. To address the role of IKK2-mediated NF-κB activation in hepatocytes in the pathogenesis of liver disease and HCC in Mdr2(-/-) mice, we generated Mdr2-deficient animals lacking IKK2 specifically in hepatocytes using the Cre-loxP system. Mdr2(-/-) mice lacking IKK2 in hepatocytes developed spontaneously a severe liver disease characterized by cholestasis, major hyperbilirubinemia and severe to end-stage fibrosis, which caused muscle wasting, loss of body weight, lethargy and early spontaneous death. Cell culture experiments showed that primary hepatocytes lacking IKK2 were more sensitive to bile acid induced death, suggesting that hepatocyte-specific IKK2 deficiency sensitized hepatocytes to the toxicity of bile acids under conditions of cholestasis resulting in greatly exacerbated liver damage. Mdr2(-/-)IKK2(Hep-KO) mice remarkably recapitulate chronic liver failure in humans and might be of special importance for the study of the mechanisms contributing to the pathogenesis of end-stage chronic liver disease or its implications on other organs. CONCLUSION: IKK2-mediated signaling in hepatocytes protects the liver from damage under conditions of chronic inflammatory cholestasis and prevents the development of severe fibrosis and liver failure.

Anti-inflammatory therapies in cancer cachexia.

Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. Indeed, both the tumor and the patient produce cytokines that act on multiple target sites such as bone marrow, myocytes, hepatocytes, adipocytes, endothelial cells and neurons, where they produce a complex cascade of biological responses leading to the wasting associated with cachexia. The cytokines that have been involved in this cachectic response are TNF-alpha, IL-1, IL-6 and interferon-gamma. Interestingly, these cytokines share the same metabolic effects and their activities are closely interrelated. In many cases these cytokines exhibit synergic effects when administered together. Therefore, therapeutic strategies - either nutritional or pharmacological - have been based on either blocking their synthesis or their action.

Soluble human leukocyte antigen-G serum levels in patients with acquired immune deficiency syndrome affected by different disease-defining conditions before and after antiretroviral treatment.

We have previously reported that the serum levels of soluble human leukocyte antigen (HLA)-A, -B, -C, and -G antigens are elevated in human immunodeficiency virus (HIV)-infected subjects and decrease after antiretroviral therapy. In this study, we measured soluble HLA-G serum levels in patients with acquired immune deficiency syndrome (AIDS) affected by different AIDS-defining conditions before and during antiretroviral therapy and correlated them with virologic and immunologic parameters of response to treatment. Soluble HLA-G levels were significantly higher in AIDS patients before treatment as compared with healthy controls and significantly decreased after 36 months of therapy. The decrease of soluble HLA-G correlated with the decrease of plasma HIV-RNA level and CD8(+) T-lymphocytes number and with the increase of CD4(+) T-lymphocytes number. Soluble HLA-G levels were significantly higher in patients with opportunistic infections and Kaposi's sarcoma compared with patients with the wasting syndrome. These data suggest that infections and neoplasms may trigger the shedding of soluble HLA-G molecules, and confirm that the level of soluble HLA-G in serum might represent a surrogate marker to monitor virologic response and immune reconstitution in HIV-positive individuals.