Preserved Immune Function Research Articles

Immune Function After Splenic Artery Embolization for Blunt Trauma: Long-Term Assessment of CD27+ IgM B-Cell Levels

Splenic artery embolization (SAE) plays a critical role in the treatment of high-grade splenic injury not requiring emergent laparotomy. SAE preserves splenic tissue, and growing evidence demonstrates preserved short-term splenic immune function after SAE. However, long-term function is less studied. Patients who underwent SAE for blunt abdominal trauma over a 10-year period were contacted for long-term follow-up. Sixteen participants (sex: women, 10, and men, 6; age: median, 34 years, and range, 18–67 years) were followed up at a median of 7.7 years (range, 4.7–12.8 years) after embolization. Splenic lacerations were of American Association for the Surgery of Trauma grades III to V, and 14 procedures involved proximal embolization. All individuals had measurable levels of IgM memory B cells (median, 14.30 as %B cells), splenic tissue present on ultrasound (median, 122 mL), and no history of severe infection since SAE. In conclusion, this study quantitatively demonstrated that long-term immune function remains after SAE for blunt abdominal trauma based on the IgM memory B cell levels.

Persistence of Antibody Responses to the SARS-CoV-2 in Dialysis Patients and Renal Transplant Recipients Recovered from COVID-19.

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as “failure”, a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702; transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function.

Laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein (Kimura's procedure)

Authors present the case of a laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein (Kimura's procedure). A 26-year old female patient was admitted with a neoplasm of the tail of the pancreas detected by abdominal ultrasound. Pancreatic protocol CT-scan revealed a 7 cm round-shaped tumor in the tail of the pancreas. The CT features of the lesion were suggestive for mucinous cystadenoma. Spleen-preserving laparoscopic distal pancreatectomy is considered as the first choice procedure for benign lesions located at the body or tail of the pancreas and is performed very frequently worldwide. The advantages of preservation of the spleen are related to the preserved immune function of the organ. The two main surgical techniques that have been proposed and widely adopted for spleen preserving laparoscopic distal pancreatectomy are the Warshaw (splenic vessel ligation) and Kimura (splenic vessel preservation) techniques. The procedure was complicated due to the large size of the lesion and firm adhesions between the vessels and the tumor. Nevertheless the splenic vessels were successfully preserved after clipping all the branches of the splenic vein and artery. No significant bleeding occurred. The estimated blood loss was 50 ml. The operation time was 210 minutes. The postoperative course was complicated by a postoperative pancreatic fistula (POPF) grade B (according to the ISGPF classification), which was managed successfully using interventional percutaneous drainage. Final histopathological examination confirmed mucinous cystadenoma of the tail of the pancreas. The patient was discharged on postoperative day 14 with external drainage tube, which was removed in three weeks after amylase level control in an outpatient clinic. The purpose of the video is to demonstrate our experience in performing Kimura's procedure.

Mass cytometry identifies distinct CD4+ T cell clusters distinguishing HIV-1-infected patients according to antiretroviral therapy initiation.

Recent guidelines recommend antiretroviral therapy (ART) to be administered as early as possible during HIV-1 infection. Few studies addressed the immunological benefit of commencing ART during the acute phase of infection. We used mass cytometry to characterize blood CD4+ T cells from HIV-1-infected patients who initiated ART during acute or chronic phase of infection. Using this method, we analyzed a large number of markers on millions of individual immune cells. The results revealed that CD4+ T cell clusters with high expression of CD27, CD28, CD127, and CD44, whose function involves T cell migration to inflamed tissues and survival, are more abundant in healthy controls and patients initiating ART during the acute phase; on the contrary, CD4+ T cell clusters in patients initiating ART during the chronic phase had reduced expression of these markers. The results are suggestive of a better preserved immune function in HIV-1-infected patients initiating ART during acute infection.

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort

The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH). We reviewed archived transthoracic echocardiograms (TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15% with diabetes). Among those with usable images, LVH was detected in 174 of 473 persons (37%) according to LV mass criteria and in 99 of 322 persons (31%) according to American Society of Echocardiography LV mass index criteria. Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH with a CD4 count ≤ 200 cells/mm3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08-2.62), CD4 nadir ≤ 200 cells/mm3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4 nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with DD. Persons with a history of advanced human immunodeficiency virus-associated immune suppression are at higher risk of LVH and DD than infected persons with preserved immune function.

The perioperative dynamics of IL-7 following robot-assisted and open colorectal surgery

Interleukin-7 is critical for T-cell development and displays antimicrobial and antitumor properties. It is referred to as a “critical enhancer of protective immunity”. However, there is no information on interleukin-7 dynamics following colorectal surgery. Moreover, although robot-assisted surgery is gaining popularity, data on the immune response to it is almost non-existent. In this prospective non-randomized case-control study we found interleukin-7 dynamics to differ following robot-assisted and open approach and to affect postoperative immunity. Linear increases were seen in the robotic group while a cubic pattern with a maximum at 8 h in the open one. Low preoperative interleukin-7 was associated with developing surgical site infection. In turn, higher preoperative interleukin-7 was associated with preserved immune function: less pronounced drop in lymphocyte count and higher Δlymphocyte/Δneutrophil ratio in patients undergoing robotic surgery. The changes in other cytokines, namely, interleukin-12(p70), TNFα, interferon-γ, and interleukin-10 were independently associated with interleukin-7 dynamics. In turn, relative changes in interleukin-7 were independent predictors of changes in interferon-γ, key cytokine of favourable Th1 immune response. Taken together, we demonstrated different perioperative dynamics of interleukin-7, which may contribute to favourable outcomes following robotic colorectal surgery including lower incidence of surgical site infections, milder surgery-induced lymphopenia, and beneficial interferon-γ dynamics.

Combination antiretroviral therapy improves cognitive performance and functional connectivity in treatment-na\xefve HIV-infected individuals

Our study aimed to investigate the short-term effect of combination antiretroviral therapy (cART) on cognitive performance and functional and structural connectivity and their relationship to plasma levels of antiretroviral (ARV) drugs. Seventeen ARV treatment-naïve HIV-infected individuals (baseline mean CD4 cell count, 479 ± 48 cells/mm3) were age matched with 17 HIV-uninfected individuals. All subjects underwent a detailed neurocognitive and functional assessment and magnetic resonance imaging. HIV-infected subjects were scanned before starting cART and 12 weeks after initiation of treatment. Uninfected subjects were assessed once at baseline. Functional connectivity (FC) was assessed within the default mode network while structural connectivity was assessed by voxel-wise analysis using tract-based spatial statistics (TBSS) and probabilistic tractography within the DMN. Tenofovir and emtricitabine blood concentration were measured at week 12 of cART. Prior to cART, HIV-infected individuals had significantly lower cognitive performance than control subjects as measured by the total Z-score from the neuropsychological tests assessing six cognitive domains (p = 0.020). After 12 weeks of cART treatment, there remained only a weak cognitive difference between HIV-infected and HIV-uninfected subjects (p = 0.057). Mean FC was lower in HIV-infected individuals compared with those uninfected (p = 0.008), but FC differences became non-significant after treatment (p = 0.197). There were no differences in DTI metrics between HIV-infected and HIV-uninfected individuals using the TBSS approach and limited evidence of decreased structural connectivity within the DMN in HIV-infected individuals. Tenofovir and emtricitabine plasma concentrations did not correlate with either cognitive performance or imaging metrics. Conclusions: Twelve weeks of cART improves cognitive performance and functional connectivity in ARV treatment-naïve HIV-infected individuals with relatively preserved immune function. Longer periods of observation are necessary to assess whether this effect is maintained.

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort.

Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings.Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis.Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated.Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

Bladder cancer in HIV-infected adults: an emerging concern?

IntroductionAs HIV-infected patients get older more non-AIDS-related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV-infected patients [1]. Albeit bladder cancer is one of the most common malignancy worldwide [2], only 13 cases of bladder cancer in HIV-infected patients have been reported in the literature so far [3].Materials and MethodsWe conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013) in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV-infected patients in our hospital. ResultsBased on our administrative HIV database (6353 patients), we found 15 patients (0.2%) with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV-infection and the occurrence of bladder cancer, although in patients much younger (median age 56) than those developing bladder cancer without HIV infection (71.1 years) [4]. Haematuria was the most frequent diagnosis circumstance in HIV-infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC) tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV) co-infection. Death rate was high in this population.ConclusionsBladder cancers in HIV-infected patients remain rare but occur in relatively young HIV-infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with severe outcomes.

Short-Term and Long-Term Clinical and Immunological Consequences of Stopping Antiretroviral Therapy in HIV-Infected Patients with Preserved Immune Function

The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function. This was a randomized 144-week follow-up CD4⁺ T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA<50 copies/ml, CD4⁺ T-cell count >500 cells/μl and nadir CD4⁺ T-cell count >100 cells/μl were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4⁺ T-cell count decreased to <350 cells/μl. The primary end points were AIDS-defining illnesses, death, CD4⁺ T-cell count <200 cells/μl, or virological failure after restarting ART. A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4⁺ T-cell count significantly decreased in the TI group (even in patients with persistently high CD4⁺ T-cell counts and no clinical events) versus the CT group (median change -408 cells/μl versus -21.5 cells/μl; P<0.001), whereas a significant increase in CD8⁺ T-cell count was observed (256 cells/μl versus -59 cells/μl; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4⁺ T-cell counts. Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4⁺ T-cell count.

Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study

HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤ 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.

Salvage Therapy for Refractory Aids-Related Primary Central Nervous System Lymphoma

A 27-year-old male patient presented with speech disorders and multiple brain masses on MRI evaluation. He tested positive for HIV. A sterotactic biopsy diagnosed primary central nervous system lymphoma (diffuse large B-cell lymphoma). After two cycles of high-dose metotrexate (HD-MTX-)-based chemotherapy, the tumor progressed. He underwent whole brain radiotherapy achieving complete response. Six cycles of consolidating immunochemotherapy with rituximab-temozolomide were administered after radiation. Forty-three months after remission, he has not recurred and his neurological status is optimal. Younger HIV patients with refractory PCNSL and preserved immune function can face salvage therapy successfully achieving long term remissions with no remarkable neurotoxicity.

A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult.

Respiratory syncytial virus (RSV) is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

Vitamin D insufficiency is common in children infected with HIV

Kakalia et al in Toronto conducted a well-conceived, well-implemented, and well-analyzed prospective randomized 6-month study of vitamin D status and effect of supplementation in children infected with HIV. In this group of clinically stable, average-aged 10-year-old children, with relatively preserved immune function, normal CD4, who were receiving predominantly antiretroviral therapy, a striking 85% had vitamin D insufficiency or deficiency (serum 25[OH]D level <75 nmol/L).Compared with the group randomized to no supplementation, groups who were given 800 IU/day or 1600 IU/day (in once a week doses) had significant increases in serum levels of 25(OH)D. Children given 1600 IU/day achieved higher mean increase in 25(OH)D than those treated with the lower dose, yet only 67% of these highly supplemented children achieved vitamin D sufficiency within 6 months of therapy. Even supplementation that achieved vitamin D sufficiency was not associated with an increase in CD4 count or percentage in the patients studied in this trial whose CD4 levels were in the normal range at baseline. Despite failure to document an immunologic effect, the implications of vitamin D supplementation for maintenance of bone health are clear. The Institute of Medicine's recommended daily vitamin D requirement of 600 IU would likely be inadequate in children infected with HIV, regardless of cutoff level used to define vitamin D sufficiency.Further research is needed in children infected with HIV, including study of optimal dosing of vitamin D supplementation (both for bone health and immunologic benefit), the impact of antiretroviral therapy on vitamin D homeostasis and the importance of serum and intracellular 1,25(OH)D levels on CD4 counts.Article page 951▶ Kakalia et al in Toronto conducted a well-conceived, well-implemented, and well-analyzed prospective randomized 6-month study of vitamin D status and effect of supplementation in children infected with HIV. In this group of clinically stable, average-aged 10-year-old children, with relatively preserved immune function, normal CD4, who were receiving predominantly antiretroviral therapy, a striking 85% had vitamin D insufficiency or deficiency (serum 25[OH]D level <75 nmol/L). Compared with the group randomized to no supplementation, groups who were given 800 IU/day or 1600 IU/day (in once a week doses) had significant increases in serum levels of 25(OH)D. Children given 1600 IU/day achieved higher mean increase in 25(OH)D than those treated with the lower dose, yet only 67% of these highly supplemented children achieved vitamin D sufficiency within 6 months of therapy. Even supplementation that achieved vitamin D sufficiency was not associated with an increase in CD4 count or percentage in the patients studied in this trial whose CD4 levels were in the normal range at baseline. Despite failure to document an immunologic effect, the implications of vitamin D supplementation for maintenance of bone health are clear. The Institute of Medicine's recommended daily vitamin D requirement of 600 IU would likely be inadequate in children infected with HIV, regardless of cutoff level used to define vitamin D sufficiency. Further research is needed in children infected with HIV, including study of optimal dosing of vitamin D supplementation (both for bone health and immunologic benefit), the impact of antiretroviral therapy on vitamin D homeostasis and the importance of serum and intracellular 1,25(OH)D levels on CD4 counts. Article page 951▶ Vitamin D Supplementation and CD4 Count in Children Infected with Human Immunodeficiency VirusThe Journal of PediatricsVol. 159Issue 6PreviewTo evaluate, in a randomized fashion, the impact of vitamin D supplementation on CD4 count and measures of vitamin D homeostasis in children infected with human immunodeficiency virus (HIV). Full-Text PDF

Development of a locally sustainable functional food for people living with HIV in Sub-Saharan Africa: laboratory testing and sensory evaluation

The use of Lactobacillus rhamnosus GR-1 and micronutrients has been associated with a preserved immune function among people living with HIV. However, use of these products in the developing world remains limited due to the lack of facilities for production. We describe the development of a yogurt with L. rhamnosus GR-1 at >7×10(7) colony forming units fortified with locally grown Moringa oleifera leaves at 20% of the recommended daily allowance of vitamin A. The product was made by preparing a thin paste of Moringa which was then incubated with 4% probiotic and 2% yogurt mother culture in milk for 6 hours. The addition of M. oleifera enhanced the survival of probiotic bacteria in yogurt during the shelf life period at 5 °C (P=0.02), but had no effect on probiotic survival at 21 °C. While the sensory characteristics of probiotic and non-probiotic supplemented Moringa yogurts were indistinguishable, the addition of Moringa reduced consumer acceptance compared to regular yogurt.

Vitamin D Supplementation and CD4 Count in Children Infected with Human Immunodeficiency Virus

To evaluate, in a randomized fashion, the impact of vitamin D supplementation on CD4 count and measures of vitamin D homeostasis in children infected with human immunodeficiency virus (HIV). Children infected with HIV (n = 54) were randomized to receive no supplementation (group 1), vitamin D 5600 IU/week (group 2), or vitamin D 11 200 IU/week (group 3) for 6 months. Viral load, CD4 percent, CD4 count, 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D, and other measures of vitamin D metabolism were measured at baseline and 6 months later. A total of 53 participants completed the study. The mean age, CD4 percent, CD4 count, and log(10) viral load at baseline were 10.3 ± 3.9 years, 33% ± 10%, 927 ± 468 cells/μL, and 1.63 (95% CI, 0.76-2.50), respectively. The mean baseline 25(OH)D level was 53.1 ± 24.8 nmol/L; 85% of participants were vitamin D insufficient or deficient (<75 nmol/L). Serum levels of 25(OH)D increased significantly in participants who received supplementation with vitamin D (P = .0002 and P < .001 for participants receiving 800 IU/day and 1600 IU/day, respectively), but not in participants who did not receive supplementation (P = .27). Participants treated with 1600 IU/day of vitamin D achieved a higher mean increase in 25(OH)D than participants treated with 800 IU/day (P = .02). However, only 67% of the group supplemented with higher dose achieved vitamin D sufficiency. Vitamin D supplementation did not lead to an increase in CD4 percent or CD4 count. In children infected with HIV with relatively preserved immune function, vitamin D supplementation in doses as high as 1600 IU/day does not impact CD4 count. Vitamin D insufficiency is common in this population, and achieving vitamin D serum levels of >75 nmol/L may require a daily intake ≥1600 IU.

Cardiopulmonary and immunologic effects of transvaginal natural-orifice transluminal endoscopic surgery cholecystectomy compared with laparoscopic cholecystectomy in a porcine survival model

A few studies have addressed the physiology related to a basic natural-orifice transluminal endoscopy surgery (NOTES) procedure, such as transgastric peritoneoscopy, but the physiologic impact of more complex NOTES procedures has not been previously examined. To evaluate the cardiopulmonary and immunologic effects of transvaginal NOTES cholecystectomy compared with laparoscopic cholecystectomy. Survival experiments in 10 40-kg female pigs assigned to transvaginal cholecystectomy and laparoscopic cholecystectomy groups. Transvaginal cholecystectomy was performed with the assistance of a needlescopic device, and laparoscopic cholecystectomy was performed in the standard manner. Cardiopulmonary and immunologic parameters in the transvaginal cholecystectomy group were compared with those in the laparoscopic cholecystectomy group. Cardiopulmonary parameters included heart rate, blood pressure, saturation pulse oximetry, intratracheal pressure, and arterial blood gases. Immunologic parameters included white blood cell count, tumor necrosis factor-α, interleukin-1β, and interleukin-6. All procedures were performed successfully without complications. Although operation times were longer for transvaginal cholecystectomy than for laparoscopic surgery, cardiopulmonary changes were similar and stable in both groups. White blood cell count, interleukin-1β, and interleukin-6 did not differ between the 2 groups, and the increase in tumor necrosis factor α after transvaginal cholecystectomy was significantly smaller on postoperative day 1 than after laparoscopic cholecystectomy (133.4 pg/mL vs 200.4 pg/mL; P < .05). Animal model and small sample size. Transvaginal cholecystectomy resulted in cardiopulmonary stability and well preserved immune function similar to those of laparoscopic cholecystectomy, suggesting that NOTES may be less invasive than laparoscopic surgery.

Correlation of transient elastography with APRI and FIB‐4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection

Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono- or human immunodeficiency virus (HIV)/HCV coinfection. Non-invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono- or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV-positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase-to-platelet ratio index (APRI) and a simple index called FIB-4 were calculated and results were correlated with TE. A total number of 174 patients were included (23% HCV, 36% HIV/HCV coinfected, 33% with cleared HCV and 8% with ongoing HIV but cleared HCV). TE correlated significantly with APRI and FIB-4 (r = 0.60; P < 0.001 and r = 0.54; P < 0.001 respectively). This correlation was pronounced in patients with ongoing HCV infection (r = 0.67; P < 0.001 and r = 0.60; P < 0.001). Prediction of advanced fibrosis resulted in concordance rates >80% with combinations of TE plus APRI and APRI plus FIB-4. HIV/HCV coinfected patients did not present with advanced fibrosis stages when compared with HCV-monoinfected patients. Combinations of two non-invasive markers may significantly reduce the number of liver biopsies in patients with bleeding disorders and advanced liver fibrosis. Furthermore, our data support previous studies that observed a favourable outcome in patients with HIV/HCV and a preserved immune function in times of highly active antiretroviral therapy.

Preserved Immune Functions and Controlled Leukocyte Oxidative Stress in Naturally Long-lived Mice: Possible Role of Nuclear Factor Kappa B

In order to verify the survival biomarker role of several immune functions, and to determine the oxidation and inflammation mechanisms underlying variability in the aging process, we have investigated a variety of immune functions and oxidative stress parameters as well as activation of the nuclear factor kappa B (NF kappaB) in peritoneal leukocytes from four different age groups of mice, including natural extreme longevity. Immune cells from naturally long-lived animals showed preservation of immune function in response to stimuli and controlled oxidative stress as well as nuclear factor kappa B activation in resting conditions. Moreover, leukocytes from extreme long-lived animals showed increased catalase activity when compared with the adults. In contrast, the old and very old animal groups showed impaired immune function and increased oxidation as well as NF kappaB activation. Our results support preserved immune function as a biomarker of extended survival and point to controlled regulation of NF kappaB activity as a key mechanism restraining oxidative stress in immune cells and contributing to reach longevity.

Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort

Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function. Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count >350 cells/mm(3), had HIV RNA viral load <55,000 cp/mL, and were on ART (>or=2 drugs) for >or=6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination. A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm(3) and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p < 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. Subjects with preserved immune function found that neurocognition improved significantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration. This study provides Class III evidence that discontinuing ART is associated with an improvement in 2 neuropsychological tests (Trail-Making Test A & B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) for up to 96 weeks. Resuming ART was not associated with a decline in these scores for up to 45 weeks.