This study examined the prevalence of and factors associated with post-traumatic stress disorder in recently diagnosed HIV/AIDS patients in South Africa. One hundred and forty-nine (44 male, 105 ...female) recently diagnosed HIV/AIDS patients (mean duration since diagnosis = 5.8 months, SD = 4.1) were evaluated. Subjects were assessed using the MINI International Neuropsychiatric Interview (MINI), the Carver Brief COPE coping scale and the Sheehan Disability Scale. In addition, previous exposures to trauma and past risk behaviours were assessed. Twenty-two patients (14.8%) met criteria for PTSD. Current psychiatric conditions more likely to be associated with PTSD included major depressive disorder (29% in PTSD patients versus 7% in non-PTSD patients, p=0.004), suicidality (54% versus 11%, p=0.001) and social anxiety disorder (40% versus 13%, p=0.04). Further patients with PTSD reported significantly more work impairment and demonstrated a trend towards higher usage of alcohol as a means of coping. Discriminant function analysis indicated that female gender and a history of sexual violation in the past year were significantly associated with a diagnosis of PTSD. Patients whose PTSD was a direct result of an HIV/AIDS diagnosis (8/22) did not differ from other patients with PTSD on demographic or clinical features. In the South African context, PTSD is not an uncommon disorder in patients with HIV/AIDS. In some cases, PTSD is secondary to the diagnosis of HIV/AIDS but in most cases it is seen after other traumas, with sexual violation and intimate partner violence in women being particularly important.
: Advances in surgical techniques and immunosuppression (IS) have led to an appreciable reduction in postoperative complications following transplantation. However, wound complications as probably ...the most common type of post‐transplantation surgical complication can still limit these improved outcomes and result in prolonged hospitalization, hospital readmission, and reoperation, consequently increasing overall transplant cost. Our aim was to review the literature to delineate the evidence‐based risk factors for wound complications following kidney and liver transplantation (KTx, LTx), and to present the preventive and therapeutic modalities for this bothersome morbidity. Generally, wound complications are categorized as superficial and deep wound dehiscences, perigraft fluid collections and seroma, superficial and deep wound infections, cellulitis, lymphocele and wound drainage. The results of several studies showed that the most important risk factors for wound complications are IS and obesity. Additionally, there are surgical and/or technical factors, including type of incision, reoperation, and surgeon's expertise, as well as comorbidities such as advanced age, diabetes mellitus, malnutrition, and uremia. Preventive management of wound complications necessitates defining their etiological factors so that their detrimental effects on healing processes can be addressed and reduced. IS modalities and agents, especially sirolimus (SRL), and steroids (ST) should be adjusted according to the patient's co‐existing risk factors. SRL should be administered three months after transplantation and ST should be tapered as soon as possible. A body mass index (BMI) lower than 30 kg/m2 is advisable for inclusion in a transplantation program, but higher BMIs do not exclude recipients. Surgical risk factors can be prevented by applying precise surgical techniques. Therapeutic modalities must focus on the most efficient and cost‐effective medications and/or interventions to facilitate and improve wound healing.
STUDY QUESTION
Are there differences in composition of the total regulatory T cell (Treg) pool and distinct Treg subsets (naïve CD45RA+-Tregs, HLA-DR–- and HLA-DR+-memory Tregs) between successfully ...and non-successfully IVF/ICSI-treated women?
SUMMARY ANSWER
Non-successfully IVF/ICSI-treated women have a decreased percentage of naïve CD45RA+-Tregs and an increased percentage of HLA-DR–-memory Tregs within the total Treg pool.
WHAT IS KNOWN ALREADY
Immunosuppressive Tregs play a significant role in human reproduction and studies have shown that their number and function are reduced in reproductive failure and complications of pregnancy such as pre-eclampsia and preterm labor. However, no data exist concerning the importance of Tregs for a successful outcome following assisted reproduction technologies.
STUDY DESIGN, SIZE, DURATION
Blood samples were obtained from 210 women undergoing IVF/ICSI treatment, where 14 patients were excluded due to biochemical pregnancy or missed abortion. Age control blood samples were collected from 20 neonates and 176 healthy female volunteers. The study was performed between October 2010 and March 2012.
PARTICIPANTS/MATERIALS, SETTING, METHODS
In this study, we determined prospectively the quantity and composition of the total CD4+CD127low+/–CD25+FoxP3+-Treg pool and three different Treg subsets (naïve CD45RA+-Tregs, HLA-DR−- and HLA-DR+-memory Tregs) in all women undergoing IVF/ICSI treatment. We examined whether there were differences between those who became pregnant (n = 36) and those who did not (n = 160). The blood samples were collected within 1 h before the embryo transfer and analyzed by six-color flow cytometry. In order to evaluate these results with regard to the normal age-related changes in composition of the total Treg pool, the same analysis was performed using samples of umbilical cord blood and from healthy female volunteers aged between 17 and 76 years. The composition of the total Treg pool was documented for successfully IVF/ICSI-treated women (n = 5) throughout their pregnancy and we assessed the suppressive activity of each Treg subset in pregnant (n = 10) compared with non-pregnant women (n = 10) using suppression assays.
MAIN RESULTS AND ROLE OF CHANCE
The percentage of CD4+CD127low+/−CD25+FoxP3+-Tregs within the total CD4+-T cell pool did not change with age and did not differ between IVF/ICSI-treated women who did or did not become pregnant. For the total Treg pool, the percentage of the naïve CD45RA+-Tregs decreased continuously, while the percentage of HLA-DR−- and HLA-DR+-memory Tregs increased with aging. From the age of about 40 years, the increase in HLA-DR+-memory Tregs in particular became less pronounced, indicating that conversion of naïve CD45RA+Tregs into HLA-DR+-memory Tregs decreases with age. Women who did not achieve a pregnancy with IVF/ICSI were older than those who did (P < 0.01). However, multiple logistic regression analysis revealed that irrespective of age, the percentage of naïve CD45RA+-Tregs within the total Treg pool was decreased (P < 0.05), while the percentage of HLA-DR−-memory Tregs was increased (P < 0.01) in women who did not become pregnant compared with those who did. At the beginning of pregnancy, naïve CD45RA+-Tregs showed a major decrease but increased again during pregnancy and these cells showed a higher suppressive activity (P < 0.0001) in pregnant compared with non-pregnant women.
LIMITATIONS, REASONS FOR CAUTION
There was a large variation in the percentages of the Treg subsets within the total Treg pool between successfully and non-successfully IVF/ICSI-treated women. Therefore, their determination would not allow us to predict the IVF/ICSI outcome with sufficient specificity and sensitivity. We did not examine the antigen specificity of the Treg subsets and therefore could not discern whether the naïve CD45RA+-Tregs recognized maternal or paternal antigens.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings suggest that Tregs, especially the naïve CD45RA+-Treg subset, may play a role in determining the probability of both becoming pregnant and maintenance of the pregnancy.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the German Research Council (DFG) grant STE 885/3-2 (to A.S.). All authors declare to have no conflict of interest.
There is a paucity of data on the mortality of patients admitted to the intensive care unit (ICU), despite the fact that human immunodeficiency virus (HIV)-related diseases represent a significant ...burden to health care resources particularly in sub-Saharan Africa.
To describe the outcome and prognostic factors of HIV-infected patients requiring mechanical ventilation in an ICU.
Prospective observational study.
All 54 patients (34.8 ± 10.4 years, 38 females) admitted with confirmed HIV from October 2012 until May 2013 were enrolled. Disease severity was graded according to APACHEII score. Admission diagnoses, clinical features and laboratory investigations, complications and outcomes were recorded.
The mean length of ICU stay was 11.0 days (range: 1-49 days), and 33 patients survived (ICU mortality: 38.9%). The in-hospital mortality at 30 days was 48.1%. ICU mortality was associated with an AIDS-defining diagnosis (OR = 7.97, P = 0.003). Non-survivors had higher APACHEII scores (25.8 vs. 18.6, P = 0.001) and lower mean admission CD4 counts (102.5 vs. 225.2, P = 0.014). Multiple logistical regression analysis confirmed the independent predictive value of WHO stage 4 disease (P = 0.008), lower mean CD4 count on admission (P = 0.057) and higher APACHEII score (P = 0.010) on ICU mortality, and WHO stage 4 (P = 0.007) and higher APACHE II score (P = 0.003) on 30-day mortality.
The ICU mortality of mechanically ventilated HIV-positive patients was high. WHO stage 4 disease and a higher APACHEII score were predictive of both ICU and 30-day mortality, whereas a low CD4 count on admission was associated with ICU mortality.
Background
Hemodialysis (HD), especially when first initiated, can cause neurological deterioration. Presumably this is due to transient cerebral edema, which has been observed using diffusion ...weighted magnetic resonance imaging (MRI) in experimental and human studies; however, this has not been investigated under maintenance hemodialysis (mHD). Moreover, there are no studies to date investigating regional effects of mHD on grey and white matter volumes.
Methods
In this study eight patients with end stage renal disease (ESRD) were examined immediately before and after mHD sessions with multimodal MRI, including diffusion tensor imaging (DTI) and high-resolution structural imaging. Additionally, eight healthy, age-matched and sex-matched controls were examined for comparison. Data were analyzed using tract-based spatial statistics and voxel-based morphometry.
Results
At baseline, ESRD patients had significantly reduced values of fractional anisotropy (FA) and axial diffusivity as well as bilaterally reduced grey matter volume in the insula, compared with controls. After the mHD session, FA further decreased while axial, radial, and mean diffusivity significantly increased ubiquitously throughout the white matter. Voxel-based morphometry revealed a corresponding significant increase in white matter volume in the central right hemisphere and splenium, as well as in cortical grey matter in the anterior medial frontal and cingulate cortex. None of the patients showed neurological deterioration.
Conclusion
In this study ESRD patients showed white matter changes indicative of chronic microstructural damage when compared with healthy controls, as previously reported. In addition, patients showed signs of a transient extracellular cerebral edema, which has not yet been observed in the absence of neurological symptoms.
: According to the Banff classification of renal allograft pathology, the category borderline changes defines changes insufficient for a diagnosis of acute rejection. The relationship between ...borderline changes and acute renal allograft rejection still remains unclear. The appropriate clinical management for patients showing such changes is controversial. One possible interpretation of the high incidence of subacute tubulitis is that these changes in the absence of graft dysfunction are of no consequence and that treatment with intensified immunosuppression is unnecessary and perhaps harmful. Another view, consistent with the high incidence of CAN in late protocol biopsy studies, is that immunosuppression has become so powerful, that rejection may not even be manifested by a rising serum creatinine. Borderline changes should be used as part of an algorithm, but not as the only criterion, for therapeutic decision making. Based on the weak evidence of existing studies, in our patients with clinical borderline rejection, we have to weigh the individual immunological risk against the potential side effects of increased immunosuppression. Even in the knowledge that a majority of patients with borderline infiltrates will not progress into rejection, in many transplant centers, borderline rejection is treated with additional steroids or augmentation of maintenance immunosuppression.
Background In dialysis patients, cardiac troponin T (cTNT) is often elevated despite the absence of acute myocardial ischaemia, and amino‐terminal pro‐B‐natriuretic peptide (NT‐proBNP) is markedly ...higher compared to non‐haemodialysis patients. In a longitudinal observation, we evaluated the association of cTNT and NT‐proBNP on cardiovascular morbidity and mortality in haemodialysis patients with and without fluid overload.
Materials and methods Plasma cTNT levels of 134 haemodialysis patients were measured before and after a dialysis session by 3rd generation electro‐chemoluminiscence immunoassay. NT‐proBNP was determined using a polyclonal antibody recognizing the N‐terminal fragment of BNP (Elecsys autoanalyzer 2010, Roche Diagnostics, Mannheim, Germany). Volume status was determined by a clinical score system. Cardiovascular morbidity and mortality were assessed over a follow‐up period of 36 months.
Results Plasma cTNT > 0·03 ng mL−1 was found in 39·6% of all patients. Patients with hypervolaemia had significantly higher cTNT levels compared to euvolaemic patients (median 0·054 ng mL−1, interquartile range 0·019–0·153 vs. 0·005 ng mL−1, < 0·001–0·034; P < 0·001). All haemodialysis patients had excessively high levels of NT‐proBNP (median 4524; interquartile range 2000–10 250 pg mL−1), and NT‐proBNP was significantly higher in hypervolaemic haemodialysis patients (11 988, 5307–19 242) compared to euvolaemic haemodialysis patients (3247, 1619–5574); P < 0·001. Receiver operator curves showed a threshold of cTNT > 0·026 ng mL−1 and NT‐proBNP > 5300 pg mL−1 as predictors of hypervolaemia. Asymptomatic chronic haemodialysis patients with cTNT > 0·026 ng mL−1 and NT‐proBNP > 5300 pg mL−1 were more likely to die due to cardiac events in the follow‐up period. Multivariate analysis documented that elevated cTNT and NT‐proBNP levels were highly predictive for cardiovascular events.
Conclusions Plasma levels of cTNT are elevated in approximately 40% and NT‐proBNP levels in 100% of asymptomatic chronic haemodialysis patients. Both parameters depend on volume status. Increased NT‐proBNP and cTNT are strongly associated with adverse outcome in end‐stage renal disease patients undergoing haemodialysis, and are a useful tool for risk stratification in chronic haemodialysis patients.
High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, ...particularly with regard to prophylactic HPV vaccines for skin cancer prevention.
High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically.
The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P<0.001) and basal cell cancers (P=0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P=0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P=0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence.
High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions.
Real‐time contrast‐enhanced sonography (RT‐CES) can assess microvascular tissue perfusion using gas‐filled microbubbles. The study was performed to evaluate the feasibility of RT‐CES in detecting ...chronic allograft nephropathy (CAN) in comparison to color Doppler ultrasonography (CDUS). A total of 26 consecutive renal transplant recipients were prospectively studied using RT‐CES and conventional CDUS. Transplant tissue perfusion imaging was performed by low‐power imaging during i.v. administration of the sonocontrast Optison™. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow A *β (A = peak signal intensity, β= slope of signal intensity rise). In contrast to conventional CDUS resistance and pulsatility indices, renal blood flow estimated by CES was highly significant related to S‐creatinine (r =–0.62, p = 0.0004). Determination of renal blood flow by CES reached a higher sensitivity (91% vs. 82%, p < 0.05), specificity (82% vs. 64%, p < 0.05) and accuracy (85% vs. 73%, p < 0.05) for the diagnosis of CAN as compared to conventional CDUS resistance indices. Perfusion parameters derived from RT‐CES significantly improve the early detection of CAN compared to conventional CDUS. RT‐CES using low‐power real‐time perfusion imaging is a feasible method to evaluate microvascular perfusion in renal allograft recipients.
The (2)H(e,e'p)n cross section at a momentum transfer of 3.5 (GeV/c)(2) was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a ...function of the neutron recoil angle θ(nq) and to extract missing momentum distributions for fixed values of θ(nq) up to 0.55 GeV/c. In the region of 35°≤θ(nq)≤45° recent calculations, which predict that final-state interactions are small, agree reasonably well with the experimental data. Therefore, these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electrodisintegration.
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