Where to Draw the Line in Surgical Obesity for Renal Transplant Recipients: An Outcome Analysis Based on Body Mass Index.

OBJECTIVES: Renal transplant is the criterion standard treatment for patients with end-stage renal disease. Because obesity rates are increasing in the global population, international standards on renal transplant in obese patients remain a gray area. The aim of this study was to determine whether renal transplant remains the treatment of choice in an obese patient with end-stage renal disease. MATERIALS AND METHODS: We performed a retrospective analysis on all patients who underwent renal transplant in our transplant unit between January 2008 and December 2013. Patients were divided into 3 cohorts based on body mass index (cohort A was < 25 kg/m2, cohort B was 25-29.99 kg/m2, and cohort C was ≥ 30 kg/m2). Postoperative complications within 90 days after transplant were assessed using one-way analysis of variance and chi-square distribution. Patient and graft survival rates over 3 years were assessed with Kaplan-Meier analyses. RESULTS: Of 610 total patients, 92 patients (15%) were classified as "obese" (≥ 30 kg/m2) in cohort C, with 294 patients in cohort A and 224 patients in cohort B (24 patients were excluded). Regarding short-term complications during the 90-day posttransplant period, obese individuals were at increased risk of a higher number of complications (P = .039 for cohort A vs cohort C). Lymphocele in particular was associated with obesity (P = .004); fortunately, this condition had no direct impact on the graft itself and was relatively easy to monitor and treat. The long-term outlook (3 years) appeared positive, with both graft survival (92% in cohort A, 91% in cohort B, and 94% in cohort C) and patient survival (97% in cohort A, 99% in cohort B, and 97% in cohort C) being independent of patient obesity. CONCLUSIONS: Increased body mass index up to 37.5 kg/m2 was not associated with increased risk of serious postoperative morbidity or mortality after renal transplant. Surgery should be considered as the criterion standard treatment for obese patients with end-stage renal disease if they are otherwise medically fit with few or well-controlled comorbidities.

Functional role of SETD2, BAP1, PARP-3 and PBRM1 candidate genes on the regulation of hTERT gene expression.

Narrowing the search for the critical hTERT repressor sequence(s) has identified three regions on chromosome 3p (3p12-p21.1, 3p21.2 and 3p21.3-p22). However, the precise location and identity of the sequence(s) responsible for hTERT transcriptional repression remains elusive. In order to identify critical hTERT repressor sequences located within human chromosome 3p12-p22, we investigated hTERT transcriptional activity within 21NT microcell hybrid clones containing chromosome 3 fragments. Mapping of chromosome 3 structure in a single hTERT-repressed 21NT-#3fragment hybrid clone, revealed a 490kb region of deletion localised to 3p21.3 and encompassing the histone H3, lysine 36 (H3K36) trimethyltransferase enzyme SETD2; a putative tumour suppressor gene in breast cancer. Three additional genes, BAP1, PARP-3 and PBRM1, were also selected for further investigation based on their location within the 3p21.1-p21.3 region, together with their documented role in the epigenetic regulation of target gene expression or hTERT regulation. All four genes (SETD2, BAP1, PARP-3 and PBRM1) were found to be expressed at low levels in 21NT. Gene copy number variation (CNV) analysis of SETD2, BAP1, PARP-3 and PBRM1 within a panel of nine breast cancer cell lines demonstrated single copy number loss of all candidate genes within five (56%) cell lines (including 21NT cells). Stable, forced overexpression of BAP1, but not PARP2, SETD2 or PBRM1, within 21NT cells was associated with a significant reduction in hTERT expression levels relative to wild-type controls. We propose that at least two sequences exist on human chromosome 3p, that function to regulate hTERT transcription within human breast cancer cells.

Does a nurse-led mental health liaison service for older people reduce psychiatric morbidity in acute general medical wards? A randomised controlled trial.

OBJECTIVE: To determine the clinical effectiveness of a nurse-led mental health liaison service in managing mental health problems in older physically ill inpatients. DESIGN: Randomised controlled trial. SETTING: Four general medical wards in a district general hospital in a northern UK town. PARTICIPANTS: 153 medically ill older people (aged 65 or over) who scored above the threshold for depression and/or cognitive impairment on a brief screening instrument (4-item geriatric depression scale and 6-item orientation-memory-concentration test): 77 were randomised to a nurse-led intervention and 76 to usual care. Included in the analysis were 120 participants who completed 6-8 week follow-up assessments. INTERVENTION: Multi-faceted intervention led by a mental health liaison nurse. MAIN OUTCOME MEASURES: Scores on the Health of the Nation Outcome Scale 65+, the geriatric depression scale, and the Standardised Mini-Mental State Examination. RESULTS: No significant differences were found between groups on the total Health of the Nation Outcome Scale 65+ scores (11.5 versus 11.5, adjusted mean difference -0.04, 95% CI-1.4 to 1.3, P = 0.96) nor on the Standardised Mini-Mental State Examination (20.3 versus 21.8, adjusted mean difference -0.4, 95% CI-2.1 to 1.3, P = 0.63). Subjects randomised to the intervention arm had significantly lower Geriatric Depression Scale scores at 6-8 week follow-up than those receiving usual care (12.2 versus 14.0, adjusted mean difference -2.0, 95% CI-4.0 to -0.1, P = 0.043). CONCLUSIONS: Nurse-led mental health liaison services which accept all screened cases from acute medical wards are unlikely to be effective in reducing general psychiatric morbidity. Services which focus on the prevention of delirium and target particular patient groups or disorders such as depression are more likely to be effective.

Validation of short screening tests for depression and cognitive impairment in older medically ill inpatients.

OBJECTIVE: To investigate the criterion validity of the four-item Geriatric Depression Scale (GDS4) and the six-item Orientation-Memory-Concentration-test (OMC) against longer widely used screening instruments. METHOD: Participants were 153 patients (aged 65 or over) admitted to four acute medical wards of a northern UK town. The validity of the GDS4 was determined using the 30-item geriatric depression scale (GDS30) as the comparator; the validity of the OMC was determined using the standardised mini-mental state examination (MMSE) as the comparator. For both screens, the area under receiver operating characteristic (ROC) curve was calculated in addition to the number of true and false positives and the sensitivity and specificity for various cut-off points. RESULTS: The area under ROC curve was 0.80 for the GDS4 and 0.90 for the OMC. Using a cut-off of 0/1, the GDS4 correctly classified 78.2% of participants, using the GDS30 as the standard. This cut-off gave a sensitivity of 90.1% and specificity of 55.3%. With a cut-off of 1/2 the GDS4 correctly classified 76.8% of participants and had sensitivity and specificity of 78% and 74.5% respectively. The GDS4 and GDS30 were highly correlated (rho=0.63, p < 0.0005). A cut-off of 10/11 on the OMC gave optimum performance. With this cut-off, it correctly classified 85.9% of participants, and had 85.6% sensitivity and 86.8% specificity. There was a significant correlation between the OMC and the SMMSE (rho = -0.827, p < 0.0005). CONCLUSION: The GDS4 and OMC appear to be useful instruments for screening for depression and cognitive impairment among older medical inpatients.